Dissimilar effects of chronic treatment with aspirin, flubiprofen and indomethacin on renal prostaglandins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quilley, C.P.; McGiff, J.C.; Quilley, J.

Inhibition of prostaglandin (PG) excretion is not sustained during long-term aspirin administration. The authors compared the effects of 9d treatment of SHR rats with aspirin (A), 200 mg/kg/d s.c., flubiprofen (F), 2.5 mg/kg/12h s.c., and indomethacin (I), 2.5 mg/kg/12 s.c. on excretion of radioimmunoassayable PGE/sub 2/ and PGF/sub 2..cap alpha../. Conversion of 1-(/sup 14/C) arachidonic acid (AA) by renal papillae was also examined. In vehicle-treated control rats (C) PGF/sub 2..cap alpha../ excretion varied from 32.2 +/- 6.2 (mean +/- SEM) to 41.6 +.- 7.3 ng/6h, 3-fold higher than that of PGE/sub 2/. Within 6h of administration all 3 drugs reducedmore » excretion of PGF/sub 2..cap alpha../ and PGE/sub 2/ to less than 20% and 35% of C rats. Although urinary concentrations of PGF/sub 2..cap alpha../ and PGE/sub 2/ in A-treated rats remained depressed, a 2-fold increase in urine volume resulted in excretion rates similar to C rats. In contrast, urine volume in I- and F-treated rats was unaffected while PGF/sub 2..cap alpha../ and PGE/sub 2/ excretion rates in I-treated rats were 50''% of C rats and were also lower than control in F-treated rats. Paradoxically, metabolism of AA to PGs by by renal papillae dissected on day 10, 2-4h after the last drug dose, was markedly inhibited by A (PGF/sub 2..cap alpha../ by 62% and PGE/sub 2/ by 82%), but unaffected by I and F. As the effects of cyclooxygenase inhibitors differ on in vivo and indices of PG production, their intended action should be verified by measuring PG levels in biological fluids.« less

Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery.

PubMed

Knock, Greg A; Shaifta, Yasin; Snetkov, Vladimir A; Vowles, Benjamin; Drndarski, Svetlana; Ward, Jeremy P T; Aaronson, Philip I

2008-02-01

We investigated the role of src family kinases (srcFK) in agonist-mediated Ca2+-sensitization in pulmonary artery and whether this involves interaction with the rho/rho-kinase pathway. Intra-pulmonary arteries (IPAs) and cultured pulmonary artery smooth muscle cells (PASMC) were obtained from rat. Expression of srcFK was determined at the mRNA and protein levels. Ca2+-sensitization was induced by prostaglandin F(2 alpha) (PGF(2 alpha)) in alpha-toxin-permeabilized IPAs. Phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light-chain-20 (MLC20) and translocation of rho-kinase in response to PGF(2 alpha) were also determined. Nine srcFK were expressed at the mRNA level, including src, fyn, and yes, and PGF(2 alpha) enhanced phosphorylation of three srcFK proteins at tyr-416. In alpha-toxin-permeabilized IPAs, PGF(2 alpha) enhanced the Ca2+-induced contraction (pCa 6.9) approximately three-fold. This enhancement was inhibited by the srcFK blockers SU6656 and PP2 and by the rho-kinase inhibitor Y27632. Y27632, but not SU6656 or PP2, also inhibited the underlying pCa 6.9 contraction. PGF(2 alpha) enhanced phosphorylation of MYPT-1 at thr-697 and thr-855 and of MLC20 at ser-19. This enhancement, but not the underlying basal phosphorylation, was inhibited by SU6656. Y27632 suppressed both basal and PGF(2 alpha)-mediated phosphorylation. The effects of SU6656 and Y27632, on both contraction and MYPT-1 and MLC20 phosphorylation, were not additive. PGF(2 alpha) triggered translocation of rho-kinase in PASMC, and this was inhibited by SU6656. srcFK are activated by PGF(2 alpha) in the rat pulmonary artery and may contribute to Ca2+-sensitization and contraction via rho-kinase translocation and phosphorylation of MYPT-1.

Effects of prostaglandin F2alpha and latanoprost on phosphoinositide turnover, myosin light chain phosphorylation and contraction in cat iris sphincter.

PubMed

Ansari, Habib R; Davis, Angela M; Kaddour-Djebbar, Ismail; Abdel-Latif, Ata A

2003-06-01

The effects of the ocular hypotensive agents prostaglandin F(2alpha) (PGF(2alpha)) and its analog latanoprost on intraocular pressure (IOP) in both animals and human have been investigated extensively in the last two decades. While there is general agreement that application of these PGs to the eye alters IOP by altering the aqueous humor outflow of the eye via the uveoscleral and trabecular meshwork pathways, the mechanism of action of these agents on IOP lowering remains unclear. There is evidence which suggests that myosin light kinase (MLC kinase) may be involved in the IOP-lowering effects of these agents. Thus, the purpose of the present work was to investigate in cat iris sphincter the effects of these PGs on the MLC kinase signaling pathway, inositol phosphates production, MLC phosphorylation and contraction, in order to gain more information about the mechanism through which these agents modulate smooth muscle function and lower IOP. [(3)H]myo-inositol phosphates production was measured by ion-exchange chromatography, MLC kinase activity was measured by incorporation of (32)Pi into MLC, and changes in muscle tension were recorded isometrically. PGF(2alpha) and latanoprost induced contraction in a concentration-dependent manner with EC(50) values of 18.6 and 29.9 nM, respectively, and increased inositol phosphates production in a concentration-dependent manner. At 1 microM, PGF(2alpha) and latanoprost increased inositol phosphates formation by 125 and 102% over basal, respectively. PGF(2alpha) and latanoprost increased MLC phosphorylation in a concentration- and time-dependent manner, at 1 microM and 5 min incubation, the PGs increased the MLC response by 181 and 176% over basal, respectively. In general, PGF(2alpha) was slightly more potent in inducing the biochemical and pharmacological responses. Wortmannin, ML-7 and ML-9, selective inhibitors of MLC kinase, inhibited significantly PGF(2alpha)- and latanoprost-induced MLC phosphorylation and contraction. These results demonstrate for the first time involvement of the MLC kinase pathway in the FP receptor function of this ocular tissue. Contraction-relaxation of smooth muscle alters the shape and stiffness of smooth muscle cells and MLC kinase, through myosin phosphorylation and dephosphorylation, has been shown to be involved in cytoskeletal remodeling, cytoskeletal alterations, and IOP lowering. In light of these reports and the findings presented here we suggest that alterations in the MLC kinase signaling pathway and its derived second messengers, which leads to changes in contraction-relaxation of the smooth muscles of the anterior segment, could facilitate aqueous humor outflow and thus contribute to the IOP-lowering effects of the FP-class PGs.

Continuous extraovular administration of prostaglandin F2alpha for midtrimester abortion.

PubMed

Lauersen, N H; Wilson, K H

1974-09-15

Midtrimester abortion was successfully induced in 74 of 76 patients by a continuous extraovular administration of (PGF2alpha) prostaglandin F2alpha via a constant-infusion pump. 2 patients in the 13th-14th weeks of gestation failed to abort despite good uterine activity. The mean abortion time for successful inductions was 16.21 hours. Parous patients aborted somewhat faster than nulliparous patients, but the difference was not statistically significant. All patients were monitored throughout the abortion procedure, and uterine activity was calculated and analyzed. Uterine activity developed within 15 minutes of PGF2alpha instillation and showed the characteristic uterine response to PGs with a sharp rise in intrauterine tonus. The gastrointestinal side effects in this series were much less than those reported for intraamniotic instillation of PG, and there was good patient tolerance of the procedure. The main complication of extraovular administration of PGF2alpha for midtrimester abortion was endometritis, which occurred in 7 patients. The patients who developed endometritis had, as a group, longer abortion times (mean=28 hours). 3 patients with severe preeclampsia and intrauterine death in the third trimester also had successfully induced labor with extraovular administration of PGF2alpha. The method of PGF2alpha administration in the series was found to have a high success rate, good patient tolerance, and fewer side effects than when abortion was induced by intraamniotic instillation of PGF2alpha.

Prostaglandin F2alpha-induced estrus in ewes exhibiting estrous cycles of different duration.

PubMed

Cárdenas, Horacio; Wiley, Todd M; Pope, William F

2004-07-01

Effects of prostaglandin F(2alpha) (PGF(2alpha)), administered during the mid-luteal phase of the estrous cycle, were examined in ewes exhibiting estrous cycles classified as short (< or =16.5 days, short-cycle ewes, n = 10) or long (> or =18 days, long-cycle ewes, n = 9) based on the durations of two estrous cycles (cycles -2 and -1) before treatment. The ewes received (i.m.) 20mg of PGF(2alpha) on day 10 of the third estrous cycle (cycle 0) followed, 36 h later, by 25 microg of gonadotropin releasing hormone (GnRH) to time the events of ovulation. Duration of subsequent estrous cycles +1 and +2 were recorded, and then the ewes were treated with the same combination of PGF(2alpha) and GnRH beginning on day 10 of estrous cycle +3. Ovaries were recovered 6h after GnRH administration to assess development of pre-ovulatory follicles. The proportion of ewes that exhibited estrus after PGF(2alpha) and GnRH treatment on cycle 0 was not different (P > 0.05) between short- and long-cycle ewes. Onset of estrus occurred sooner (P < 0.05) after PGF(2alpha) injection in short-cycle ewes than in long-cycle ewes (1.9 +/- 0.1 days and 2.3 +/- 0.1 days, duration of cycle 0 was 11.9 and 12.3 days, respectively). Duration of estrous cycle +1 was 1.2 days longer (P < 0.01) than cycle -1 in short-cycle ewes. However, duration of estrous cycle +1 did not change (P > 0.05) after PGF(2alpha) and GnRH administration in ewes having long cycles. Pre-ovulatory follicles did not differ (P > 0.05) in numbers, diameter, layers of granulosa cells nor concentrations of progesterone and estradiol-17beta in follicular fluid between short- and long-cycle ewes after PGF(2alpha) and GnRH treatment. In conclusion, ewes having short or long estrous cycles responded differently to PGF(2alpha) and GnRH treatment with respect to the interval to onset of estrus and duration of the subsequent estrous cycle.

BM-520, an original TXA2 modulator, inhibits the action of thromboxane A2 and 8-iso-prostaglandin F2alphain vitro and in vivo on human and rodent platelets, and aortic vascular smooth muscles from rodents.

PubMed

Rolin, S; Hanson, J; Vastersaegher, C; Cherdon, C; Pratico, D; Masereel, B; Dogne, J M

2007-08-01

Thromboxane A(2) (TXA(2)) and 8-iso-PGF(2alpha) are two prostanoid agonists of the thromboxane A(2) receptor (TP), whose activation has been involved in platelet aggregation and atherosclerosis. Agents able to counteract the actions of these agonists are of great interest in the treatment and prevention of cardiovascular events. Here, we investigated in vitro and in vivo the pharmacological profile of BM-520, a new TP antagonist. In our experiments, this compound showed a great binding affinity for human washed platelets TP receptors, and prevented human platelet activation and aggregation induced by U-46619, arachidonic acid and 8-iso-PGF(2alpha). The TP receptor antagonist property of BM-520 was confirmed by its relaxing effect on rat aorta smooth muscle preparations precontracted with U-46619 and 8-iso-PGF(2alpha). Further, its TP antagonism was also demonstrated in vivo in guinea pig after a single intravenous injection (10 mg kg(-1)). We conclude that this novel TP antagonist could be a promising therapeutic tool in pathologies such as atherosclerosis where an increased production of TXA(2) and 8-iso-PGF(2alpha), as well as TP activation are well-established pathogenic events.

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle.

PubMed

Ulbrich, S E; Schulke, K; Groebner, A E; Reichenbach, H D; Angioni, C; Geisslinger, G; Meyer, H H D

2009-08-01

Prostaglandins (PGs) are important regulators of reproductive processes including early embryonic development. We analyzed the most relevant PG in bovine uteri at different preimplantation pregnancy stages when compared with non-pregnant controls. Additionally, endometrium and trophoblast tissues were examined regarding specific enzymes and receptors involved in PG generation and function. Simmental heifers were artificially inseminated or received seminal plasma only. At days 12, 15, or 18, post-estrus uteri were flushed for PG determination by liquid chromatography-tandem mass spectrometry. Endometrium and trophoblast tissues were sampled for RNA extraction and quantitative real-time PCR analysis. At all days and points of time examined, the concentration of 6-keto PGF(1alpha) (stable metabolite of PGI(2)) was predominant followed by PGF(2alpha)>PGE(2)>PGD(2) approximately TXB(2) (stable metabolite of TXA(2)). At days 15 and 18, PG increased from overall low levels at day 12, with a much more pronounced increase during pregnancy. The PGF(2alpha)/PGE(2) ratio was not influenced by status. The highest PG concentration was measured at day 15 with 6-keto PGF(1alpha) (6.4 ng/ml) followed by PGF(2alpha) (1.1 ng/ml) and PGE(2) (0.3 ng/ml). Minor changes in endometrial PG biosynthesis enzymes occurred due to pregnancy. Trophoblasts revealed high transcript abundance of general and specific PG synthases contributing to uterine PG. As PGI(2) and PGF(2alpha) receptors were abundantly expressed by the trophoblast, abundant amounts of PGI(2) and PGF(2alpha) in the uterine lumen point towards an essential role of PG for the developing embryo. High amounts of PG other than PGE(2) in the preimplantation uterus may be essential rather than detrimental for successful reproduction.

Arachidonic acid and prostaglandin endoperoxide metabolism in isolated rabbit and coronary microvessels and isolated and cultivated coronary microvessel endothelial cells.

PubMed Central

Gerritsen, M E; Cheli, C D

1983-01-01

Isolated microvessels and isolated and cultured microvessel endothelial cells were prepared from rabbit cardiac muscle. Pathways of arachidonic acid metabolism were determined by measurement of exogenous substrate utilization [( 1-14C]arachidonic acid incorporation and release from intact tissue and cells; [1-14C]prostaglandin H2 (PGH2) metabolism by broken cell preparations) and by quantification of endogenous products (immunoreactive 6-keto-prostaglandin F1 alpha (PGF1 alpha) and prostaglandin E (PGE) release) by selective radioimmunoassay. Rabbit coronary microvessels and derived microvascular endothelial cells (RCME cells) synthesized two major products of the cyclooxygenase pathway: 6-keto-PGF1 alpha (hydrolytic product of prostaglandin I2) and PGE2. A reduced glutathione requiring PGH-E isomerase was demonstrated in coronary microvessels and RCME cells, but not in rabbit circumflex coronary artery or aorta. In addition, a minor amount of a compound exhibiting similar characteristics to 6-keto-PGE1 was found to be produced by microvessels and RCME cells. Measurement of endogenously released prostaglandins indicated that under basal and stimulated conditions, PGE release exceeded that of 6-keto-PGF1 alpha. Microvessels and microvessel endothelial cells derived from cardiac muscle of rabbit exhibit pathways of arachidonate metabolism that are different from those of many large blood vessels and derived endothelial cells. Images PMID:6415116

Effects of prostaglandin F(2alpha)and carbachol on MAP kinases, cytosolic phospholipase A(2)and arachidonic acid release in cat iris sphincter smooth muscle cells.

PubMed

Husain, S; Abdel-Latif, A A

2001-05-01

The signal transduction pathways initiated by Ca(2+)-mobilizing agonists, such as prostaglandin F(2alpha)(PGF(2alpha)) and carbachol (CCh), leading to activation of cytosolic phospholipase A(2)(cPLA(2)) and arachidonic acid (AA) release in a wide variety of tissues remain obscure. To further define the role of protein kinases in receptor mediated stimulation of cPLA(2)and consequently AA release we have investigated the role of mitogen-activated protein (MAP) kinases and protein kinase C (PKC) in PGF(2alpha)- and CCh-induced cPLA(2)phosphorylation and AA release in cat iris sphincter smooth muscle (CISM) cells. The cells were prelabeled with [(3)H]AA for 24 hr and incubated in the absence or presence of the agonist for 5-10 min as indicated. MAP kinases activities and cPLA(2)phosphorylation were determined in immunoprecipitates obtained by using anti-p38 MAP kinase and anti-cPLA(2)antibodies. We found that: (a) PGF(2alpha)and CCh increased p38 MAP kinase activity by 197 and 215%, respectively, and increased p42/p44 MAP kinase activity by 200 and 125%, respectively. (b) SB202190, a p38 MAP kinase specific inhibitor, inhibited PGF(2alpha)- and CCh-induced cPLA(2)phosphorylation by 92 and 85%, respectively, and AA release by 62 and 78%, respectively. (c) PD98059, a p42/p44 MAP kinase inhibitor, inhibited CCh-induced cPLA(2)phosphorylation by 70% and AA release by 71%, but had no effect on that of PGF(2alpha). (d) Inhibition of PKC activity by RO 31-8220 inhibited both PGF(2alpha)- and CCh-stimulation of p38 MAP kinase, p42/p44 MAP kinases and cPLA(2)phosphorylation. We conclude from these results that in CISM cells PGF(2alpha)-induced cPLA(2)phosphorylation and AA release is mediated through p38 MAP kinase, but not through p42/p44 MAP kinases, whereas that of CCh is mediated through both p38 MAP kinase and p42/p44 MAP kinases. These effects of PGF(2alpha)and CCh are regulated by the MAP kinases in a PKC-dependent manner. Studies aimed at elucidating the role of protein kinases in the coupling mechanism between the activation of PGF(2alpha)and muscarinic receptors, and the stimulation of cPLA(2)and AA release in the smooth muscles of the iris-ciliary body will provide important information about the role of protein kinases signaling pathways in smooth muscle function, as well as about the mechanism of the intraocular pressure-lowering effects of PGF(2alpha)and its analog, latanoprost, in glaucoma therapy. Copyright 2001 Academic Press.

Prostaglandin F2alpha-F-prostanoid receptor signaling promotes neutrophil chemotaxis via chemokine (C-X-C motif) ligand 1 in endometrial adenocarcinoma.

PubMed

Wallace, Alison E; Sales, Kurt J; Catalano, Roberto D; Anderson, Richard A; Williams, Alistair R W; Wilson, Martin R; Schwarze, Jurgen; Wang, Hongwei; Rossi, Adriano G; Jabbour, Henry N

2009-07-15

The prostaglandin F(2alpha) (PGF(2alpha)) receptor (FP) is elevated in endometrial adenocarcinoma. This study found that PGF(2alpha) signaling via FP regulates expression of chemokine (C-X-C motif) ligand 1 (CXCL1) in endometrial adenocarcinoma cells. Expression of CXCL1 and its receptor, CXCR2, are elevated in cancer tissue compared with normal endometrium and localized to glandular epithelium, endothelium, and stroma. Treatment of Ishikawa cells stably transfected with the FP receptor (FPS cells) with 100 nmol/L PGF(2alpha) increased CXCL1 promoter activity, mRNA, and protein expression, and these effects were abolished by cotreatment of cells with FP antagonist or chemical inhibitors of Gq, epidermal growth factor receptor, and extracellular signal-regulated kinase. Similarly, CXCL1 was elevated in response to 100 nmol/L PGF(2alpha) in endometrial adenocarcinoma explant tissue. CXCL1 is a potent neutrophil chemoattractant. The expression of CXCR2 colocalized to neutrophils in endometrial adenocarcinoma and increased neutrophils were present in endometrial adenocarcinoma compared with normal endometrium. Conditioned media from PGF(2alpha)-treated FPS cells stimulated neutrophil chemotaxis, which could be abolished by CXCL1 protein immunoneutralization of the conditioned media or antagonism of CXCR2. Finally, xenograft tumors in nude mice arising from inoculation with FPS cells showed increased neutrophil infiltration compared with tumors arising from wild-type cells or following treatment of mice bearing FPS tumors with CXCL1-neutralizing antibody. In conclusion, our results show a novel PGF(2alpha)-FP pathway that may regulate the inflammatory microenvironment in endometrial adenocarcinoma via neutrophil chemotaxis.

Stimulation of phosphatidylcholine breakdown and diacylglycerol production by growth factors in Swiss-3T3 cells.

PubMed Central

Price, B D; Morris, J D; Hall, A

1989-01-01

The effect of a number of growth factors on phosphatidylcholine (PtdCho) turnover in Swiss-3T3 cells was studied. Phorbol 12-myristate 13-acetate (PMA), bombesin, platelet-derived growth factor (PDGF) and vasopressin rapidly stimulated PtdCho hydrolysis, diacylglycerol (DAG) production, and PtdCho synthesis. Insulin and prostaglandin F2 alpha (PGF2 alpha) stimulated PtdCho synthesis, but not its breakdown, whereas epidermal growth factor (EGF) and bradykinin were without effect. Stimulation of PtdCho hydrolysis by the above ligands resulted in increased production of phosphocholine and DAG (due to phospholipase C activity) and significant amounts of choline, suggesting activation of a phospholipase D as well. CDP-choline and glycerophosphocholine levels were unchanged. Down-regulation of protein kinase C with PMA (400 nM, 40 h) abolished the stimulation of PtdCho hydrolysis and PtdCho synthesis by PMA, bombesin, PDGF and vasopressin, but not the stimulation of PtdCho synthesis by insulin and PGF2 alpha. PtdCho hydrolysis therefore occurs predominantly by activation of protein kinase C (either by PMA or PtdIns hydrolysis) leading to elevation of DAG levels derived from non-PtdIns(4,5)P2 sources. PtdCho synthesis occurs by both a protein kinase C-dependent pathway (stimulated by PMA, PDGF, bombesin and vasopressin) and a protein kinase C-independent pathway (stimulated by insulin and PGF2 alpha). DAG production from PtdCho hydrolysis is not the primary signal to activate protein kinase C, but may contribute to long-term activation of this kinase. PMID:2690829

Defibrotide modulates prostaglandin production in the rat mesenteric vascular bed.

PubMed

Peredo, H A

2002-10-01

Defibrotide 1 microM, a polydeoxyribonucleotide extracted from mammalian organs, reduced the contractile responses to noradrenaline (NA) in the rat isolated and perfused mesenteric vascular bed, in intact as well as in de-endothelialized preparations. Defibrotide was without effect on the acetylcholine-induced relaxations of U-46619-precontracted mesenteric vascular beds. Moreover, defibrotide increased 6-keto prostaglandin (PG) F(2alpha) (stable metabolite of prostacyclin) release sixfold in the presence, but not in the absence of the endothelium, with no modification on the release of other prostanoids. Defibrotide also inhibited the NA-induced increase in PGF(2alpha) release, in both intact and de-endothelialized mesenteric vascular beds. In conclusion, the present results show that defibrotide modulates PG production in the mesenteric bed and that the observed inhibition of the contractile responses should be due to the impairment of the NA-induced increase in PGF(2alpha) release.

Urinary prostaglandin excretion in pregnancy: the effect of dietary sodium restriction.

PubMed

Delemarre, F M; Thomas, C M; van den Berg, R J; Jongsma, H W; Steegers, E A

2000-10-01

Dietary sodium restriction results in activation of the renin-angiotensin-aldosterone-system. In the non-pregnant situation renin release in response to a low sodium diet is mediated by prostaglandins. We studied the effect of dietary sodium restriction on urinary prostaglandin metabolism in pregnancy. In a randomized, longitudinal study the excretion of urinary metabolites of prostacyclin (6-keto-PGF(1 alpha)and 2,3-dinor-6-keto-PGF(1 alpha)) and thromboxane A(2)(TxB(2)and 2,3-dinor-TxB(2)) was determined throughout pregnancy and post partum in 12 women on a low sodium diet and in 12 controls. In pregnancy the excretion of all urinary prostaglandins is increased. The 6-keto-PGF(1 alpha)/ TxB(2)-ratio as well as the 2, 3-dinor-6-keto-PGF(1 alpha)/ 2,3-dinor-TxB(2)-ratio did not significantly change in pregnancy. CONCLUISION Prostacyclin and thromboxane do not seem to play an important role in sodium balance during pregnancy. Copyright 2000 Harcourt Publishers Ltd.

[Intra-amniotic administration of prostaglandin F 2 alpha, 12-methyl-prostaglandin F 2 alpha and hypertonic sodium chloride solution for induction of abortion in second-trimester pregnancy].

PubMed

Persianinov, L S; Chernukha, E A

1975-01-01

The authors had performed comperative studies of the effect of the induction of abortion in late pregnancy according to the medical indications by intra-amniotic injection of 20% hypertonic NaCl saline in 26 pregnant patients, of 25 mg prostaglandin F2alpha with 6 hours' intervals in 25 patients, a single dose injection of 40 mg PGF2alpha in 27 cases and single dose injection of 2,5 mg 15-me-PGF2alpha given to 25 patients. The highest success rate was obtained with the single dose injection of 2,5 mg 15-me-PGF2alpha and the lowest success rate was obtained with 25 mg prostaglandin F2alpha with 6 hours' intervals. Despite of rather high procentage of success rate in using the hypertonic NaCl saline, this method is more dangerous in the moment of the injection of saline and complications during the abortion (water intoxication, necrosis of tissue, coagulation defects and other). The most frequently incountered side-effects in using PGs were vomiting and diarhea. Histologic examinations of the placenta revealed massive bleedings, at frequency rate being the same for prostaglandins and the hypertonic saline. The degree of isoimmunisation was lower with prostaglandins than with hypertonic NaCl saline, despite of the late dates of pregnancy termination. The intro-amniotic injection of the small volume solution of 15-me-PGF2alpha or PGF2alpha is more simpler and easier from the technical point of view than any methodic recommended for using saline and at the same time it is more effective.

Incidence of premature estrus in lactating dairy cows and conception rates to standing estrus or fixed-time inseminations after synchronization using GnRH and PGF(2alpha).

PubMed

DeJarnette, J M; Salverson, R R; Marshall, C E

2001-07-03

Fixed-time AI (TAI) after GnRH-PGF(2alpha)-GnRH treatment is a method to achieve pregnancies in dairy herds without estrous detection. However, cows that fail to respond to the initial GnRH may have compromised TAI conception rates due to asynchronous ovarian response. This study documented the percentage of GnRH-treated Holstein cows (n=345) in two herds that displayed estrus at an inopportune time for optimum TAI conception rate (< or =48h post-PGF(2alpha); premature estrus (PE)) and compared conception rates of two TAI protocols in cows that did not display PE. At biweekly herd health exams, cows diagnosed as not pregnant to a previous AI and cows >80 days postpartum with no AI were treated with 100 microg GnRH (day -7) and 25mg PGF(2alpha) (day 0). Cows detected in PE by twice-daily visual observation from day -7 to day 2 were bred by AI 8-12h later. Cows not detected in PE were randomly assigned by parity, body condition score, and postpartum interval to receive either: (1) 100microg GnRH at 48h after PGF(2alpha) and TAI 16 to 18h later (Ovsynch); or (2) TAI at 72h post-PGF(2alpha) and a concurrent 100 microg GnRH injection to those cows not detected in estrus between 48 and 72h post-PGF(2alpha) (modified Ovsynch (MOV)). All hormone injections were im. Twenty percent (68/345) of the cows were detected in estrus before 48 after PGF(2alpha), of which 5% (17/345) were detected in estrus before PGF(2alpha) (< or =day 0). Herd influenced the percentage of cows in the PE group (herd A versus herd B; 25% versus 14%; P<0.05). Conception rates were not affected by treatment (PE versus Ovsynch versus MOV; 32% (21/65) versus 30% (37/125) versus 32% (47/145); P>0.10). However, within MOV-treated cows, conception rates were greater (P<0.05) in cows detected in estrus (46% (23/50)) compared with cows not detected in estrus (25% (24/95)). In conclusion, 20% of GnRH-treated cows displayed PE and necessitates estrous detection during this period if maximal pregnancy rates are to be achieved. Although additional estrous detection is required compared to Ovsynch, reduced cow handling and hormone usage, efficient use of expensive semen through greater conception rates in cows detected in estrus, and comparable TAI conception rates, suggests the MOV protocol may be a cost effective alternative to Ovsynch in many dairy herd reproductive management programs.

Mechanical stimulation of skeletal muscle increases prostaglandin F2(alpha) synthesis and cyclooxygenase activity by a pertussis toxin sensitive mechanism

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman H.; Shansky, Janet; Solerssi, Rosa; Chromiak, Joseph

1992-01-01

Repetitive mechanical stimulation of differentiated skeletal muscle in tissue culture increases the production of prostaglandin F(sub 2(alpha)), an anabolic stimulator of myofiber growth. Within 4 h of initiating mechanical activity, the activity of cyclooxygenase, a regulatory enzyme in prostaglandin synthesis, was increased 82% (P is less than .005), and this increase was maintained for at least 24 h. Kinetic analysis of the stretch-activated cyclooxygenase indicated a two to three-fold decrease in the enzyme's K(sub m) with no change in V(sub max). The stretch-induced increase in enzymatic activity was not inhibited by cycloheximide, was independent of cellular electrical activity (tetrodotoxin-insensitive), but was prevented by the G protein inhibitor pertussis toxin. Pertussis toxin also inhibited the stretch-induced increases in PGF(sub 2(alpha)) production, and cell growth. It is concluded that stretch of skeletal muscle increases the synthesis of the anabolic modulator PGF(sub 2(alpha)) by a G protein-dependent process which involves activation of cyclooxygenase by a posttranslational mechanism.

Altering the time of the second gonadotropin-releasing hormone injection and artificial insemination (AI) during Ovsynch affects pregnancies per AI in lactating dairy cows.

PubMed

Brusveen, D J; Cunha, A P; Silva, C D; Cunha, P M; Sterry, R A; Silva, E P B; Guenther, J N; Wiltbank, M C

2008-03-01

Based on previous research, we hypothesized that Cosynch at 72 h [GnRH-7 d-PGF(2alpha)-72 h-GnRH + artificial insemination (AI)] would result in a greater number of pregnancies per AI (P/AI) than Cosynch at 48 h. Further, we hypothesized that P/AI would be improved to a greater extent when GnRH was administered at 56 h after PGF(2alpha) before AI at 72 h due to a more optimal interval between the LH surge and AI. Nine hundred twenty-seven lactating dairy cows (n = 1,507 AI) were blocked by pen, and pens rotated through treatments. All cows received GnRH followed 7 d later by PGF(2alpha) and then received one of the following: 1) GnRH + timed AI 48 h after PGF(2alpha) (Cosynch-48); 2) GnRH 56 h after PGF(2alpha) + timed AI 72 h after PGF(2alpha) (Ovsynch-56); or 3) GnRH + timed AI 72 h after PGF(2alpha) (Cosynch-72). Pregnancy diagnoses were performed by ultrasound at 31 to 33 d post-AI and again at 52 to 54 d post-AI. Overall P/AI were similar for the Cosynch-48 (29.2%) and Cosynch-72 (25.4%) groups. The Ovsynch-56 group had a greater P/AI (38.6%) than Cosynch-48 or Cosynch-72. Presynchronized first-service animals had greater P/AI than cows at later services in Cosynch-48 (36.2 vs. 23.0%) and Ovsynch-56 (44.8 vs. 32.7%) but not in Cosynch-72 (24.6 vs. 26.2%). Similarly, primiparous cows had greater P/AI than multiparous cows in Cosynch-48 (34.1 vs. 22.9%) and Ovsynch-56 (41.3 vs. 32.6%), but not Cosynch-72 (29.8 vs. 25.3%). In conclusion, we found no advantage to Cosynch at 72 h vs. 48 h. In contrast, we found a clear advantage to treating with GnRH at 56 h, 16 h before a 72-h AI, probably because of more-optimal timing of AI before ovulation.

Mechanisms of intracellular calcium homeostasis in developing and mature bovine corpora lutea.

PubMed

Wright, Marietta F; Bowdridge, Elizabeth; McDermott, Erica L; Richardson, Samuel; Scheidler, James; Syed, Qaisar; Bush, Taylor; Inskeep, E Keith; Flores, Jorge A

2014-03-01

Although calcium (Ca(2+)) is accepted as an intracellular mediator of prostaglandin F2 alpha (PGF2alpha) actions on luteal cells, studies defining mechanisms of Ca(2+) homeostasis in bovine corpora lutea (CL) are lacking. The increase in intracellular Ca(2+) concentration ([Ca(2+)]i) induced by PGF2alpha in steroidogenic cells from mature CL is greater than in those isolated from developing CL. Our hypothesis is that differences in signal transduction associated with developing and mature CL contribute to the increased efficacy of PGF2alpha to induce a Ca(2+) signal capable of inducing regression in mature CL. To test this hypothesis, major genes participating in Ca(2+) homeostasis in the bovine CL were identified, and expression of mRNA, protein, or activity, in the case of phospholipase Cbeta (PLCbeta), in developing and mature bovine CL was compared. In addition, we examined the contribution of external and internal Ca(2+) to the PGF2alpha stimulated rise in [Ca(2+)]i in LLCs isolated from developing and mature bovine CL. Three differences were identified in mechanisms of calcium homeostasis between developing and mature CL, which could account for the lesser increase in [Ca(2+)]i in response to PGF2alpha in developing than in mature CL. First, there were lower concentrations of inositol 1,4,5-trisphosphate (IP3) after similar PGF2alpha challenge, indicating reduced phospholipase C beta (PLCbeta) activity, in developing than mature CL. Second, there was an increased expression of sorcin (SRI) in developing than in mature CL. This cytoplasmic Ca(2+) binding protein modulates the endoplasmic reticulum (ER) Ca(2+) release channel, ryanodine receptor (RyR), to be in the closed configuration. Third, there was greater expression of ATP2A2 or SERCA, which causes calcium reuptake into the ER, in developing than in mature CL. Developmental differences in expression detected in whole CL were confirmed by Western blots using protein samples from steroidogenic cells isolated from developing and mature CL. Localization of these genes in steroidogenic luteal cells was confirmed by immunohistochemistry. Therefore, it is concluded that the cellular mechanisms that allow PGF2alpha to induce a calcium signal of greater magnitude in mature than in developing CL involve 1) greater PLCbeta activity with enhanced generation of IP3, 2) an enhanced Ca(2+) release from the ER via unrestrained RYR2 due to a decrease in SRI expression, and 3) a reduction in calcium reuptake to the ER due to lower expression of ATP2A2. Accordingly, the increase in [Ca(2+)]i induced by PGF2alpha in mature large steroidogenic cells had less dependency from extracellular calcium than in those isolated from immature CL.

Termination of pregnancy by extraamniotic prostaglandins and the synergistic action of oxytocin.

PubMed

Embrey, M P; Hillier, K; Mahendran, P

1973-01-01

This study determines the efficacy of extraamniotic administration of prostaglandins E2 and F2alpha (PGE2 and PGF2alpha) in abortion induction. The method consists of introducing a Foley catheter (14 gauge) through the cervix with the aid of a speculum so that the inflated balloon lies just within the internal os. The balloon volume varies from 30 ml at 12 weeks to 40 ml at 16 weeks gestation and over. Following an initial test dose, a fully effective dose of 200 mcg PGE2 or 750 mcg PGF2alpha is instilled for diffusion into the extraovular space; this dose is repeated at 2 hourly intervals. An automatic pump may also be used to administer the PG. The pattern of uterine contractility with this method is similar to that seen with intravenous therapy. Of 163 consecutive cases analyzed, 144 (88%) achieved abortions within 36 hours, 72% aborted within 24 hours and 94% within 48 hours. Mean abortion time was 22.2 hours. No significant difference was seen in the success rate or abortion time between 21 patients in their 1st trimester of pregnancy and 142 patients in the 2nd trimester. In primigravidas, abortion (within 36 hours) was successful in 87% of the cases; mean abortion time was 24.0 hours. Multigravidas had higher success rate (90%) and shorter mean abortion time (20.4 hours). Comparison of results obtained separately with PGF2alpha and PGE2 shows the superiority of PGE2. Of 93 patients receiving PGF2alpha, 85% aborted within 36 hours (mean abortion time, 24.9 hours). Of 70 PGE2-treated patients, 93% aborted within 36 hours (p=.01) (mean abortion time, 19.4 hours). When parity was considered, PGE2 came out superior again over PGF2alpha. In primigravidas, only 84% of PGF2alpha-treated patients had abortion within 36 hours compared to 90% for PGE2-treated patients. In multigravidas, the success rates at 36 hours were 86% for PGF2alpha and 95% for PGE2. Side effects were minimal. In another trial, intravenous oxytocin was used in addition to extraamniotic PG, resulting in a very substantial decrease in mean abortion time. This method is a simple, effective abortion technique which can be carried out in most cases on a 24-hour basis.

Effects of a single administration of prostaglandin F2alpha, or a combination of prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in dairy cows 3-5 weeks post partum, a randomized, double-blind clinical trial.

PubMed

Hirsbrunner, Gaby; Burkhardt, Heinz W; Steiner, Adrian

2006-12-21

Delayed uterine involution has negative effects on the fertility of cows; use of prostaglandin F2alpha alone as a single treatment has not been shown to consistently improve fertility. Combined administration of PGF2alpha and PGE2 increased uterine pressure in healthy cows. We hypothesized, that the combination of both prostaglandins would accelerate uterine involution and have, therefore, a positive effect on fertility variables. In commercial dairy farming, the benefit of a single post partum combined prostaglandin treatment should be demonstrated. 383 cows from commercial dairy farms were included in this study. Uterine size and secretion were evaluated at treatment 21-35 days post partum and 14 days later. Cows were randomly allocated to one of three treatment groups: PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the study, the following reproduction variables were recorded: Interval from calving to first insemination, days open, number of artificial inseminations (AI) to conception; subsequent treatment of uterus, subsequent treatment of ovaries. Plasma progesterone level at time of treatment was used as a covariable. For continuous measurements, analysis of variance was performed. Fisher's exact test for categorical non-ordered data and exact Kruskal-Wallis test for ordered data were used; pairwise group comparisons with Bonferroni adjustment of significance level were performed. There was no significant difference among treatment groups in uterine size. Furthermore, there was no significant difference among treatments concerning days open, number of AI, and subsequent treatment of uterus and ovaries. Days from calving to first insemination tended to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in combination than for the placebo-group (P = 0.024). The results of this study indicate that the administration of PGF2alpha or a combination of PGF2alpha and PGE2 21 to 35 days post partum had no beneficial effect upon measured fertility variables. The exception was a tendency for a shorter interval from calving to first insemination after administration of the combination of PGF2alpha and PGE2, as compared to the placebo group. Further research should be done in herds with reduced fertility and/or an increased incidence of postpartum vaginal discharge.

Effects of a single administration of prostaglandin F2alpha, or a combination of prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in dairy cows 3–5 weeks post partum, a randomized, double-blind clinical trial

PubMed Central

Hirsbrunner, Gaby; Burkhardt, Heinz W; Steiner, Adrian

2006-01-01

Background Delayed uterine involution has negative effects on the fertility of cows; use of prostaglandin F2alpha alone as a single treatment has not been shown to consistently improve fertility. Combined administration of PGF2alpha and PGE2 increased uterine pressure in healthy cows. We hypothesized, that the combination of both prostaglandins would accelerate uterine involution and have, therefore, a positive effect on fertility variables. In commercial dairy farming, the benefit of a single post partum combined prostaglandin treatment should be demonstrated. Methods 383 cows from commercial dairy farms were included in this study. Uterine size and secretion were evaluated at treatment 21–35 days post partum and 14 days later. Cows were randomly allocated to one of three treatment groups: PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the study, the following reproduction variables were recorded: Interval from calving to first insemination, days open, number of artificial inseminations (AI) to conception; subsequent treatment of uterus, subsequent treatment of ovaries. Plasma progesterone level at time of treatment was used as a covariable. For continuous measurements, analysis of variance was performed. Fisher's exact test for categorical non-ordered data and exact Kruskal-Wallis test for ordered data were used; pairwise group comparisons with Bonferroni adjustment of significance level were performed. Results There was no significant difference among treatment groups in uterine size. Furthermore, there was no significant difference among treatments concerning days open, number of AI, and subsequent treatment of uterus and ovaries. Days from calving to first insemination tended to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in combination than for the placebo-group (P = 0.024). Conclusion The results of this study indicate that the administration of PGF2alpha or a combination of PGF2alpha and PGE2 21 to 35 days post partum had no beneficial effect upon measured fertility variables. The exception was a tendency for a shorter interval from calving to first insemination after administration of the combination of PGF2alpha and PGE2, as compared to the placebo group. Further research should be done in herds with reduced fertility and/or an increased incidence of postpartum vaginal discharge. PMID:17184541

Calcium metabolism in cows receiving an intramuscular injection of 1,25-dihydroxyvitamin D3 combined with prostaglandin F(2alpha) closely before parturition.

PubMed

Yamagishi, Norio; Ayukawa, Yu; Lee, Inhyung; Oboshi, Kenji; Naito, Yoshihisa

2005-06-01

To determine the effect of exogenous 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] combined with induced parturition on calcium (Ca) metabolism, cows received a single intramuscular injection of 1,25(OH)2D3 and prostaglandin F(2alpha) (PGF(2alpha)) closely before calving. Ten late-pregnant, multiparous Holstein cows were assigned to 1,25(OH)2D3 group (five treated with both 1,25(OH)2D3 and PGF(2alpha)) and control group (five treated with PGF(2alpha)). 1,25(OH)2D3 group showed an increase in plasma Ca concentration around parturition, whereas control group revealed a decrease in plasma Ca level. Plasma Ca concentration in 1,25(OH)2D3 group were significantly higher than that in control group during -0.5 to 3 days after parturition.

Estrus synchronization and artificial insemination of hair sheep ewes in the tropics.

PubMed

Godfrey, R W; Collins, J R; Hensley, E L; Wheaton, J E

1999-04-01

Hair sheep ewes (St. Croix White and Barbados Blackbelly) were used to evaluate 3 methods of estrus synchronization for use with transcervical artificial insemination (TAI). To synchronize estrus, ewes (n = 18) were treated with PGF2alpha (15 mg, im) 10 d apart, with controlled internal drug release (CIDR) devices containing 300 mg progesterone for 12 d (n = 18), or with intravaginal sponges containing 500 mg progesterone for 12 d (n = 18). On the day of the second PGF2alpha injection or at CIDR or sponge removal, sterile rams were placed with the ewes. Jugular blood samples were collected from the ewes at 6-h intervals until the time of ovulation, and daily for 16 d after estrus (Day 0). Plasma was harvested and stored at -20 degrees C until LH, and progesterone concentrations were determined by RIA. There was no difference (P>0.10) in time to estrus among the CIDR-, PGF2alpha- or sponge-treated ewes. All of the ewes in the CIDR group and 94.4% of the sponge treated ewes exhibited estrus by 36 h after ram introduction, while only 72.2% of PGF2alpha-treated ewes showed signs of estrus by this time (P<0.06). The time from ram introduction to ovulation was not different (P>0.10) among the CIDR-, PGF2alpha- or sponge-treated ewes. The time to the preovulatory LH surge was similar (P>0.10) among CIDR, PGF2alpha and sponge treated ewes. Progesterone levels through Day 16 after the synchronized estrus were not different (P>0.10) among treatment groups. Hair sheep ewes (n = 23) were synchronized using PGF2alpha and bred by TAI using frozen-thawed semen 48 h after the second injection. The conception rate to TAI was 2/23 (8.7%) and produced 3 ram lambs. In a subsequent trial, 17 ewes were synchronized with CIDR devices and bred by TAI using frozen-thawed semen 48 h after CIDR removal, resulting in a conception rate of 52.9% (9/17). It is possible to synchronize estrus in hair sheep using either CIDRs, sponges or PGF2alpha. Even though there were no significant differences in the timing of ovulation or the LH surge among the treatment groups, a higher conception rate was achieved in ewes synchronized with CIDR devices during the second trial. This may reflect an increase in the skill level of the TAI technician.

Modification of dyskinesias following the intrastriatal injection of prostaglandins in the rodent.

PubMed Central

Costall, B.; Holmes, S. W.; Kelly, M. E.; Naylor, R. J.

1985-01-01

The abilities of prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2 alpha to antagonize striatal dopamine function were assessed following bilateral and unilateral injections into the striata of the rat and guinea-pig. Three tests were used to assess the effects of the bilateral injections, ability to antagonize dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin (0.025 mg kg-1 s.c.), ability to antagonize stereotyped behaviour induced by apomorphine (0.5 or 2 mg kg-1 s.c.) and ability to induce catalepsy. Asymmetry/circling behaviour revealed on challenge with apomorphine (0.25 mg kg-1 s.c.) was measured following unilateral injection into the striatum. In the rat, dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin was antagonized by PGE1 (0.001-1 micrograms) and PGE2 (0.00001-1 micrograms) but not by PGD2 or PGF2 alpha (1 microgram). Stereotyped behaviour induced by apomorphine was not antagonized by any of the prostaglandins. A weak catalepsy was induced by PGE1 (1 microgram only), PGE2 (0.001-1 micrograms) and PGD2 (0.001-1 micrograms) but not by PGF2 alpha. Asymmetry and circling behaviour was only observed following the unilateral injection into the striatum of PGE1 and PGD2 (0.01-1 microgram) and challenge with apomorphine. In the guinea-pig the actions of PGE1 and E2 were compared with those of PGF2 alpha. Dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin was antagonized by bilateral injections into the striatum of PGE2 (0.001-1 microgram), but not PGE1 (0.5 micrograms) and PGF2 alpha (1 microgram) but not PGE, (0.5 micrograms) and PGF2 alpha (1 microgram).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3862460

[Effects of electro-acupuncture at Zusanli point on gastric and intestinal blood flow in rats with acute necrotizing pancreatitis].

PubMed

Bai, Lu; Zhu, Lin; Tang, Wen-Fu; Wan, Mei-Hua; Huang, Wei; Chen, Guang-Yuan

2013-11-01

To investigate the effects of electro-acupuncture (EA) at Zusanli point on gastric and intestinal blood flow and serum endothelin-1(ET-1), nitricoxide(NO), thromboxaneB2 (TXB2), 6-keto-prostaglandin F1alpha (6-K-PGF1alpha) in rats with acute necrotizing pancreatitis (ANP). Thirty-six male Sprague Dawley (SD) rats were randomly divided into sham operation (sham), ANP and EA groups (n = 12). ANP model was induced by retrograde injection of 5% sodium taurocholate into pancreaticobiliary. EA was applied to Zusanli for 30 min at 2 h and 6 h after the operation in EA group. Gastric and intestinal mucosal blood flow was measured by laser doppler flowmetry (LDF) at 12 h and 24 h after operation, while the levels of serum ET-1, NO, TXB2 and 6-K-PGF1alpha were detected. The gastric and intestinal blood flow in ANP rats were significantly lower than those in the sham group (P < 0.05), but those of EA groups were higher than those in ANP groups (P < 0.05). The serum ET-1, NO and ET-1/NO levels in ANP group were increased when compared with SO group (P < 0.05). After the electro-acupuncture treatment at Zusanli point, the levels of ET-1, NO and ET-1/N were decreased, and there were significant differences of ET-1 (at 12 h, 24 h), NO (at 12 h) and ET-1/NO (at 24 h) between EA and ANP group (P < 0.05). The levels of serum TXB2, 6-K-PGF1alpha and TXB2/6-K-PGF1alpha in ANP group were also increased (P < 0.05), but those in EA group were decreased, and there were significant differences of TXB2 (at 12 h, 24 h), 6-K-PGF1alpha (at 12 h) and TXB2/6-K-PGF1alpha (at 24 h) compared with ANP groups (P < 0.05). Electro-acupuncture at Zusanli point can significantly improve the gastric and intestinal mucosa blood flow in ANP rats, which may be related to the regulation of serum ET-1, NO, TXB2, 6-K-PGF1alpha.

Comparison of prostaglandin F2alpha, bimatoprost (prostamide), and butaprost (EP2 agonist) on Cyr61 and connective tissue growth factor gene expression.

PubMed

Liang, Yanbin; Li, Chen; Guzman, Victor M; Evinger, Albert J; Protzman, Charles E; Krauss, Achim H-P; Woodward, David F

2003-07-18

Connective tissue growth factor (CTGF) and Cyr61 (cysteine-rich angiogenic protein 61) are members of the CCN gene family that encode multifunctional, extracellular matrix-associated signaling proteins. Because the mechanism of action of certain anti-glaucoma drugs involves extracellular matrix remodeling of ocular ciliary muscle, with a resultant increase in drainage of aqueous humor from the eye, we compared the effects of three pharmacologically distinct ocular hypotensive agents on Cyr61 and CTGF gene expression. Thus, prostaglandin F2alpha (PGF2alpha) (FP receptor agonist), Butaprost (EP2 receptor agonist), and Bimatoprost (a prostamide) were compared. Using Affymetrix gene chip technology, we first identified that PGF2alpha dramatically up-regulated Cyr61 and CTGF mRNA expression in HEK 293/EBNA cells (hFP-HEK 293/EBNA). Northern blot further confirmed the Cyr61 and CTGF up-regulation is in a dose- and time-dependent manner. PGF2alpha-induced up-regulation of Cyr61 appeared to exclusively involve the Rho pathway, and up-regulation of CTGF was via multiple intracellular pathways. Because prostamide receptors are, to date, defined only at the pharmacological level, Bimatoprost effects on Cyr61 and CTGF were studied in the isolated feline iris sphincter preparation, a tissue highly responsive to prostamides. Both PGF2alpha and Bimatoprost up-regulated Cyr61 mRNA expression in the cat iris tissue. Only PGF2alpha up-regulated CTGF mRNA expression in the cat iris. Therefore, PGF2alpha and Bimatoprost appear to interact with different receptors populations in the cat iris, according to their markedly different effects on CTGF. Activation of prostaglandin EP2 receptors (Gs-coupled) also up-regulated Cyr61 but not CTGF mRNA expression in the isolated cat iris. Similar data were observed in human primary ciliary smooth muscle cells. Thus, despite quite different signal transduction pathways, FP receptor stimulation up-regulates CTGF and Cyr61. The prostamide analog Bimatoprost and an EP2-selective agonist affects only Cyr61.

The contributions of adrenal hormones, hemodynamic factors, and the endotoxin-related stress reaction to stable prostaglandin analog-induced peripheral lymphopenia and neutrophilia.

PubMed

Ulich, T R; Keys, M; Ni, R X; del Castillo, J; Dakay, E B

1988-01-01

Stable prostaglandin analogs are known to induce lymphopenia and neutrophilia in a dose-dependent fashion after subcutaneous injection in rats. The purpose of the present investigation is to determine whether the prostaglandin-induced changes in circulating leukocytes might be secondary to hypotension with the ensuing release of adrenal hormones. The adrenal medullary catecholamine epinephrine was found to induce neutrophilia in both intact and adrenalectomized rats, and the glucocorticosteroid analog dexamethasone induced a profound lymphopenia in rats as reported by previous investigators. A stable analog of PGF2 alpha (15-S-15-methyl PGF2 alpha; M-PGF2 alpha) at the dose of 1 mg/kg induced marked systemic hypotension 1 h after injection, with lymphopenia and neutrophilia 6 h after injection. The non-prostanoid hypotensive agent captopril, at a dose of 63 mg/kg, induced a hypotension of similar magnitude and kinetics to that induced by prostaglandin. Captopril also induced lymphopenia and neutrophilia at 6 h, although the neutrophilia was of lesser magnitude than that induced by prostaglandins. The prostaglandin-induced lymphopenia was found to be mediated, at least in part, by the hypotension-induced release of adrenal hormones, as evidenced by the abrogation of lymphopenia in prostaglandin-treated adrenalectomized rats. Captopril-treated adrenalectomized rats, however, did develop a significant lymphopenia, suggesting that hypotension can result in lymphopenia even in adrenalectomized rats. The M-PGF2 alpha-induced neutrophilia in adrenalectomized rats, by comparison to captopril-induced neutrophilia in adrenalectomized rats, was greater than the neutrophilia expected as the result of hypotension alone. Indeed, the M-PGF2 alpha-induced neutrophilia in adrenalectomized rats was greater than the captopril-induced neutrophilia in sham-adrenalectomized rats. Thus, a portion of the neutrophilia induced by M-PGF2 alpha in intact rats may be mediated through adrenal-independent, hemodynamic-independent mechanisms. The possibility that M-PGF2 alpha might be inducing neutrophilia via an endotoxin-like stress reaction was investigated by examining changes in circulating white blood cells in intact and adrenalectomized C3H/HeN (endotoxin-sensitive) and C3H/HeJ (endotoxin-resistant) mice after prostaglandin administration. No quantitative differences in the prostaglandin-induced neutrophilia were noted in C3H/HeJ mice as compared to the C3H/HeN mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Fertility of male rats treated with 15(S)-15-methyl prostaglandin F2 alpha methyl ester-containing silastic implants.

PubMed

Kimball, F A; Frielink, R D; Porteus, S E

1978-01-01

Male Spraque-Dawley rats receiving implants of silicone rubber discs containing 1% or 2% 15(S)-15-methyl prostaglandin F2 alpha methyl ester (15-Me-PGF 2 alpha) or no prostaglandin were tested in successive breeding trials for potency and fertility. One week after implantation, discs containing 1% 15-Me-PGF2 alpha reduced potency and fertility, which returned 2 weeks after implantation. Animals receiving implants of the 2% discs were apparently impotent the 1st week following implantation; potency returned before full fertility returned 11 weeks after implantation.

Continuous prostaglandin-F 2 infusion for middle-trimester abortion.

PubMed

Lauersen, N H; Wilson, K H

1973-05-26

Induction of midtrimester abortion with a continuous intravenous infusion of prostaglandin (PG) was described by Karim and Filshie and Roth-Brandel et al. in 1970, but the effective dose of PGF2alpha was associated with side effects severely limiting clinical usefulness. Karim and Sharma induced abortion by intravaginal PG, but again this route also seemed complicated by severe side effects. Independent reports followed of successful induction of midtrimester abortion by intraamniotic PGF2alpha and PGE2 with few side effects. Although we also successfully induced abortion in 20 patients with a single intraamniotic instillation of 40 mg PGF2alpha, there is a potential hazard in this method; i.e., PG may leak from the amniotic cavity around the catheter and pass in large quantity into the systemic circulation, resulting in undesirable, severe side effects. A more reasonable and effective method would be to inject the PGF2alpha directly at the target organ, the myometrium, by extraovular administration. Side effects could thus be minimized and effective doses of PG reduced. Such intrauterine extraovular administration of PG has been reported. The incidence of side effects was greatly reduced, although the instillation of PG was required every 1-3 hours and there were some incomplete abortions. The investigation of extraovular PGF2alpha administration for induction of abortion in gestations between 12 and 16 weeks has been especially interesting. The procedure outlined by Wiqvist and Bygdeman and Embrey and Hillier was the 1 that the authors followed initially. 250 mcg PGF2alpha was instilled initially and was followed by 750 mcg in 5 minutes and 1 mg in 30 minutes. 1 mg was then instilled at 6 hour intervals. However, the failure rate with this dosage schedule was quite high. There was a good initial uterine response, but during the administrationsat 12, 18, and 24 hours, the response diminished considerably . The frequency of administration was then increased to every 2-3 hours and the amount instilled was increased to 2-3 mg. Although somewhat more successful than the original dose schedule, this method was also unsatisfactory. It appeared from our results that the closer the injections, the higher the success rate. Thus, a brief case report is presented using continuous extraovular administration of PGF2alpha with a Harvard pump, and the results indicate it is quite satisfactory. The patients complained of very little pain and side effects have been slight. The mean abortion time for 15 patients was 14 hours. The mean time for multiparas, 11.7 hours, was faster than the 15.8 hours for primiparas.

Changes of TXA2 and PGI2 during postoperative hypertensive crisis in patients with hypertensive intracerebral hemorrhage.

PubMed

Wang, Zhi; Wang, Chao; Zhang, Weiguang; Wang, Laizang; Lei, Ting

2008-02-01

In order to explore the changes and the roles of TXA2 and PGI2 during postoperative hypertensive crisis in patients with hypertensive intracerebral hemorrhage, 31 cases subject to craniotomy were divided into three groups: group A, 9 patients with postoperative hypertensive crisis; group B, 13 patients without postoperative hypertensive crisis; and group C, 9 patients without history of hypertension and hypertensive intracerebral hemorrhage. TXA2, TXB2, 6-keto-PGF1 alpha and PGI2 were measured after operation in the three groups respectively. The postoperative blood pressure in group A, including SBP and DBP, was elevated more obviously than that in the other two groups. TXA2 and PGI2 in group A were significantly higher than those in other two groups (P<0.01). Moreover, the ratio of TXB2 to 6-keto-PGF1 alpha in group A was significantly higher than that in other two groups (P<0.05). The increase of TXA2 and the relative inadequacy of prostacyclin, especially 6-keto-PGF1 alpha, may play roles in the postoperative hypertensive crisis. And the increased value of TXB2 to 6-keto-PGF1 alpha could provide the basis for diagnosis of postoperative hypertensive crisis.

Dependence of cerebral arterial contractions on intracellularly stored Ca++.

PubMed

Sasaki, T; Kassell, N F; Zuccarello, M

1986-01-01

The purpose of the present study was to evaluate the dependence of the arterial contractions induced by different vasoactive agents upon intracellularly stored calcium in canine versus monkey cerebral arteries. The potency for inducing contractions in Ca++-free media was in the order of 9,11-epithio-11,12-metano-thromboxane A2 (STXA2) greater than prostaglandin F2 alpha (PGF2 alpha) much greater than serotonin greater than K+ in canine basilar arteries, and STXA2 greater than PGF2 alpha much greater than serotonin = K+ in monkey basilar arteries.

Effect of progesterone prior to GnRH-PGF2alpha treatment on induction of oestrus and pregnancy in anoestrous Awassi ewes.

PubMed

Husein, M Q; Kridli, R T

2003-06-01

An experiment was conducted to examine the effect of progesterone prior to a GnRH-PGF2alpha treatment on oestrus and pregnancy in seasonally anoestrous Awassi ewes. Twenty-four ewes were randomly assigned to three groups to be pre-treated with 60 mg medroxyprogesterone acetate sponges (group A), 600 mg progesterone sponges (group B) or blank sponges (group C) for 4 days. All ewes were injected with 100 microg of GnRH 24 h after sponge removal followed, 5 days later, by 20 mg PGF2alpha injection. Ewes were exposed to three fertile rams at the time of PGF2alpha injection (day 0, 0 h) and were checked for breeding marks at 6-h intervals for 5 days. Blood samples were collected from all ewes 1 day (day -10) prior to sponge insertion, at the time of sponge removal (day -6), 1 day following sponge removal (day -5, at the time of GnRH injection) and at the time of PGF2alpha injection (day 0) for analysis of progesterone. Progesterone concentrations on days -10 and -5 were basal and averaged 0.2 +/- 0.04 and 0.2 +/- 0.2 ng/ml, respectively. Progesterone concentrations on day -6 were elevated only in group B ewes and were higher (p < 0.0001) than those of groups A and C. Progesterone concentrations on day 0 were higher (p = 0.002) in groups A and B than group C. Oestrous responses occurred only in ewes of groups A and B (p > 0.05). Induced oestrus conception rate was greater (p < 0.01) in group A than groups B and C. Ewes returned to oestrus 17-20 days following day 0 were two of eight, six of eight and three of eight of groups A, B and C, respectively, all of which eventually lambed. The overall lambing rate was 82% in progesterone-primed ewes compared with only 38% non-progesterone-primed ewes (p < 0.05). Progesterone priming apparently sensitizes GnRH-PGF2alpha-treated seasonally anoestrous ewes and increases their response in oestrus and pregnancy rates.

Dietary (n-3) fatty acids reduce plasma F2-isoprostanes but not prostaglandin F2alpha in healthy humans.

PubMed

Nälsén, Cecilia; Vessby, Bengt; Berglund, Lars; Uusitupa, Matti; Hermansen, Kjeld; Riccardi, Gabrielle; Rivellese, Angela; Storlien, Len; Erkkilä, Arja; Ylä-Herttuala, Seppo; Tapsell, Linda; Basu, Samar

2006-05-01

(n-3) Fatty acids are unsaturated and are therefore easily subject to oxidization; however, they have several beneficial health effects, which include protection against cardiovascular diseases. The aim of this study was to investigate whether (n-3) fatty acids, with a controlled fat quality in the background diet, affect nonenzymatic and enzymatic lipid peroxidation and antioxidant status in humans. A total of 162 men and women in a multicenter study (The KANWU study) were randomly assigned to a diet containing a high proportion of saturated fatty acids or monounsaturated fatty acids (MUFA) for 3 mo. Within each diet group, there was a second random assignment to supplementation with fish-oil capsules [3.6 g (n-3) fatty acids/d] or placebo. Biomarkers of nonenzymatic and enzymatic lipid peroxidation in vivo were determined by measuring 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) and prostaglandin F(2alpha) (PGF(2alpha)) concentrations in plasma at baseline and after 3 mo. Antioxidant status was determined by measuring plasma antioxidant capacity with an enhanced chemiluminescence assay. The plasma 8-iso-PGF(2alpha) concentration was significantly decreased after 3 mo of supplementation with (n-3) fatty acids (P = 0.015), whereas the PGF(2alpha) concentration was not affected. The antioxidant status was not affected by supplementation of (n-3) fatty acids, but was improved by the background diet with a high proportion of MUFA. We conclude that supplementation with (n-3) fatty acids decreases nonenzymatic free radical-catalyzed isoprostane formation, but does not affect cyclooxygenase-mediated prostaglandin formation.

Environmental, genetic and social factors affecting the expression of estrus in beef cows.

PubMed

Landaeta-Hernández, Antonio J; Yelich, Joel V; Lemaster, J Willard; Fields, Michael J; Tran, Than; Chase, Chad C; Rae, D Owen; Chenoweth, Peter J

2002-03-01

Genetic, social and environmental factors affecting behavioral estrus were evaluated in Angus (n = 10), Brahman (n = 10) and Senepol (n = 10) cows during a PGF2alpha synchronized estrus and subsequent spontaneous estrus. Cows were equally stratified by breed to two groups of 15. Both groups were pre-synchronized with a modified two-injection PGF2alpha protocol. At the start of the experiment, cows were treated with 25 mg PGF2alpha followed by a second and third administration of 12.5 mg PGF2alpha, 11 and 12 days later to induce synchronized estrus. The subsequent estrus was designated as spontaneous estrus. Behavioral estrus data including the onset and end of estrus, estrous duration and the total number of mounts received for the synchronized and spontaneous estruses were collected using HeatWatch". Interval from the third PGF2alpha, treatment to the onset of a HeatWatch" estrus occurred earlier (P < 0.05) in Angus (31 +/- 5 h) than Brahman (53 +/- 7 h) or Senepol (53 +/- 4 h) cows, with dominant Senepol and Brahman cows taking longer to exhibit estrus after PGF2alpha than subordinate cows. The duration of the synchronized estrus tended to be shorter (P < 0.06) in Senepol (12 +/- 3 h) than in Angus (19 +/- 2 h) or Brahman (17 +/- 2 h) cows. Behavioral estrus data between the two periods were confounded by greater temperature-humidity index (THI) values during spontaneous estrus. The THI during spontaneous estrus appeared (P = 0.09) to affect the duration of estrus (9 +/- 1 h versus 16 +/- 1 h) and did affect (P < 0.0001) the total number of mounts received (8 +/- 4 mounts versus 34 +/- 4 mounts) during spontaneous estrus compared to synchronized estrus. Breed had no effect (P > 0.10) on the duration and total number of mounts received during synchronized and spontaneous estruses. In conclusion, type of estrus (synchronized or spontaneous), THI, social dominance and breed exerted significant effects on characteristics associated with behavioral estrus in beef cattle in subtropical environments.

Bronchodilator effects of prostacyclin (PGI2) in dogs and guinea pigs.

PubMed

Wasserman, M A; Ducharme, D W; Wendling, M G; Griffin, R L; Degraaf, G L

1980-08-22

prostacyclin (PGI2), a recently discovered unstable product in the biosynthetic conversion of prostaglandin endoperoxides, was examined for bronchopulmonary actions. in anesthetized dogs, PGI2 given i.v. (0.3-30.0 microgram/kg) and by aerosol (0.002-0.2%) inhibited significantly PGF2 alpha-induced increases in pulmonary resistance and decreases in dynamic lung compliance in a dose-related fashion. Intrinsically, PGI2 affected resting bronchopulmonary and cardiac functions minimally, but decreased peripheral and pulmonary vascular pressures. PGI2 (0.1-10 mg/kg, i.p.) afforded protection against histamine-induced asphyxial collapse in normal guinea pigs and ovalbumin-induced anaphylaxis in sensitized animals. Cumulative concentrations of PGI2 (1.0 x 10(-9)--3.0 x 10(-4) M) relaxed contractions of the isolated guine pig trachea produced by carbachol. These bronchodilator and hemodynamic effects could not be ascribed to the stable metabolic product of PGI2, because 6-keto-PGF1 alpha was inactive or markedly less active than PGI2 in these test systems. The results of this investigation suggest that PGI2 possesses considerable bronchodilator and vasodilator activity in experimental animal systems.

Prostaglandin production by melanocytic cells and the effect of alpha-melanocyte stimulating hormone.

PubMed

Nicolaou, Anna; Estdale, Sian E; Tsatmali, Marina; Herrero, Daniel Pascual; Thody, Anthony J

2004-07-16

Prostaglandins are potent mediators of the inflammatory response and are also involved in cancer development. In this study, we show that human melanocytes and FM55 melanoma cells express cyclooxygenase-1 and -2 (COX-1 and -2) and thus have the capability to produce prostaglandins. The FM55 cells produced predominantly PGE2 and PGF2alpha, whereas the HaCaT keratinocyte cell line produced mainly PGE2. The anti-inflammatory peptide, alpha-melanocyte stimulating hormone (alpha-MSH), reduced prostaglandin production in FM55 and HaCaT cells and reversed the effect of the pro-inflammatory cytokine TNF-alpha in the former. These results indicate that melanocytes produce prostaglandins and that alpha-MSH, by inhibiting this response, may play an important role in regulating inflammatory responses in the skin.

[Determination of prostaglandin F2alpha release in the rat spinal cord upon hydroxyl free radical damage by high performance liquid chromatography].

PubMed

Li, L

1997-05-01

As prostaglandin F2alpha is present in biological materials, and plays an important physiological role at trace level in the living body, then, highly sensitive determination of PGs is required. Various fluorescence derivatization reagents have been proposed for the determination of PGs. The 3-bromomethyl-6,7-methylenedioxyl-1-methyl-2(1H)-quinoxalinone was found to be a highly sensitive fluorescence derivatization reagent for PGF2alpha in HPLC with a detectable limit of 10-15 fmol for PGF2alpha. In this work we optimized its reaction conditions. Thus the PGF2alpha was extracted from the microdialysates with ethyl acetate at pH 3.0-3.5 following which the extracts were evaporated to dryness. The residue was derivatized by adding acetonitrile, KHCO3, Br-DMEQ and 18-crown-6-ether at 50 degrees C for 30min in the dark. The corresponding fluorescent derivatives produced were separated on a C8 column (Phase-Sep Ltd.), 5microm, 4.6mm x 150mm. Stepwise elution with different ratios of A and B was carried out. 30:10:60 of CHsCN:CH3OH:H2O constituted A solution and 35:30:35 made B solution. The A/B (97/3) was first run for 25 min and A/B (50/50) for the next 15min. Then the column was equilibrated with A/B (97/3) for 20min before the next sample injected. Fluorescence detector was used at lambdaEX 370nm and lambdaEM 455nm, and flow-rate of 2.0mL/min. Because the most evidence for a role of free radicals in tissue damage is indirect, we attempt to determine whether OH causes release of arachidonic acid products in vivo. We did this by (1) generating OH radical in vivo in rat spinal cord by administering H2O2 and FeCl2/EDTA through two parallel microdialysis fibers so they mixed in the cord, and (2) analyzing PGF2alpha in microdialysates in response to OH generation by HPLC. We utilized dialysis fibers of < or = 220microm external diameter including their coating except for a 2mm dialysis zone which was coated with a thin layer of silicon rubber. When the animal was clamped, two microdialysis fibers glued together were inserted through the cord until the dialysis zone just placed in the gray matters of the cord. The time course of changes in levels of PGF2alpha during OH generation by Fe/H2O2 is given. Typical chromatogram of the dialysate collected from one animal is illustrated. Prostaglandin F2alpha dramatically increased in response to hydroxyl radical generation from undetectable (basal level) to about 333 +/- 166nmol/L (SD, n = 5) in 90min, Prostaglandin F2alpha was undetectable when either H2O2 or FeCl2/EDTA was administered alone in control experiments, demonstrating that its formation was caused by generated hydroxyl radical.

Factors affecting synchronization and conception rate after the Ovsynch protocol in lactating Holstein cows.

PubMed

Galvão, K N; Santos, J E P

2010-06-01

Objectives were to evaluate risk factors affecting ovulatory responses and conception rate to the Ovsynch protocol. Holstein cows, 466, were submitted to the Ovsynch protocol [day 0, GnRH-1; day 7, prostaglandin (PG) F(2alpha); day 9, GnRH-2] and 103 cows were inseminated 12 h after GnRH-2. Information on parity, days in milk at GnRH-1, body condition, milk yield, exposure to heat stress, pre-synchronization with PGF(2alpha) and the use of progesterone insert from GnRH-1 to PGF(2alpha) was collected. Ovaries were scanned to determine responses to treatments. Overall, 54.7%, 10.6%, 2.2%, 81.1%, 9.0%, 91.5% and 36.9% of the cows ovulated to GnRH-1, multiple ovulated to GnRH-1, ovulated before GnRH-2, ovulated to GnRH-2, multiple ovulated to GnRH-2, experienced corpus luteum (CL) regression and conceived, respectively. Ovulation to GnRH-1 was greater in cows without a CL at GnRH-1, cows with follicles >19 mm and cows not pre-synchronized with PGF(2alpha) 14 days before GnRH-1. Multiple ovulations to GnRH-1 increased in cows without CL at GnRH-1 and cows with follicles < or =19 mm at GnRH-1. Ovulation before GnRH-2 was greater in cows without CL at PGF(2alpha). Ovulation to GnRH-2 increased in cows that received a progesterone insert, cows with a CL at GnRH-1, cows with follicles not regressing from the PGF(2alpha) to GnRH-2, cows with larger follicles at GnRH-2, cows that ovulated to GnRH-1 and cows not pre-synchronized. Multiple ovulations after GnRH-2 increased in cows with no CL at GnRH-1, multiparous cows and cows that multiple ovulated to GnRH-1. Conception rate at 42 days after AI increased in cows with body condition score > 2.75 and cows that ovulated to GnRH-2. Strategies that optimize ovulation to GnRH-2, such as increased ovulation to GnRH-1, should improve response to the Ovsynch protocol.

Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs.

PubMed

Brainard, Benjamin M; Meredith, Craig P; Callan, Mary Beth; Budsberg, Steven C; Shofer, Francis S; Driessen, Bernd; Otto, Cynthia M

2007-03-01

To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs. 8 client-owned dogs with clinical signs of osteoarthritis. Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E(2), platelet thromboxane B(2) (TXB(2)), and free serum TXB(2) and 6-keto-prostaglandin F (PGF)-1alpha concentrations. Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and alpha-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E(2) decreased after treatment with carprofen or deracoxib, and platelet TXB(2) production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1alpha did not change significantly after treatment with any of the drugs, although the ratio of free TXB(2) to 6-keto-PGF-1alpha decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib. At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.

Oxidant damage during and after spaceflight

NASA Technical Reports Server (NTRS)

Stein, T. P.; Leskiw, M. J.

2000-01-01

The objectives of this study were to assess oxidant damage during and after spaceflight and to compare the results against bed rest with 6 degrees head-down tilt. We measured the urinary excretion of the F(2) isoprostane, 8-iso-prostaglandin (PG) F(2alpha), and 8-oxo-7,8-dihydro-2 deoxyguanosine (8-OH DG) before, during, and after long-duration spaceflight (4-9 mo) on the Russian space station MIR, short-duration spaceflight on the shuttle, and 17 days of bed rest. Sample collections on MIR were obtained between 88 and 186 days in orbit. 8-iso-PGF(2alpha) and 8-OH DG are markers for oxidative damage to membrane lipids and DNA, respectively. Data are mean +/- SE. On MIR, isoprostane levels were decreased inflight (96. 9 +/- 11.6 vs. 76.7 +/- 14.9 ng. kg(-1). day(-1), P < 0.05, n = 6) due to decreased dietary intake secondary to impaired thermoregulation. Isoprostane excretion was increased postflight (245.7 +/- 55.8 ng. kg(-1). day(-1), P < 0.01). 8-OH DG excretion was unchanged with spaceflight and increased postflight (269 +/- 84 vs 442 +/- 180 ng. kg(-1). day(-1), P < 0.05). On the shuttle, 8-OH DG excretion was unchanged in- and postflight, but 8-iso-PGF(2alpha) excretion was decreased inflight (15.6 +/- 4.3 vs 8.0 +/- 2.7 ng. kg(-1). day(-1), P < 0.05). No changes were found with bed rest, but 8-iso-PGF(2alpha) was increased during the recovery phase (48.9 +/- 23.0 vs 65.4 +/- 28.3 ng. kg(-1). day(-1), P < 0.05). The changes in isoprostane production were attributed to decreased production of oxygen radicals from the electron transport chain due to the reduced energy intake inflight. The postflight increases in the excretion of the products of oxidative damage were attributed to a combination of an increase in metabolic activity and the loss of some host antioxidant defenses inflight. We conclude that 1) oxidative damage was decreased inflight, and 2) oxidative damage was increased postflight.

/sup 45/Ca efflux for myometrial cells: comparison of the effects of prostaglandin F/sub 2/. cap alpha. (PGF/sub 2/), oxytocin (OT) and arachidonate (A)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katona, G.; Molnar, M.; Toth, M.

1986-03-01

The aim of this study was to measure PGF/sub 2..cap alpha../-induced Ca/sup 2 +/ release from uterine cells and to compare this to the actions of OT and A. Smooth muscle cells isolated from the uterus (shell gland) of laying hens were cultured for 7 days in M199 plus 10% fetal calf serum. The cells were treated with digitonin (20..mu..M) and preloaded with /sup 45/Ca for 40 min. Addition of PGF/sub 2..cap alpha../ caused a biphasic /sup 45/Ca-efflux. There was a small but significant /sup 45/Ca-release within 30 sec (rapid phase) followed by a larger one within 7 min (slowmore » phase). In comparison, both OT and A stimulated /sup 45/Ca efflux during a single, slow phase. The maximal effect of A was observed at < 7 min, whereas that of OT was slower, peaking after 7 min. Mepacrin, an inhibitor of A release, attenuated the action of OT without having any effect on A promoted /sup 45/Ca-efflux. Indomethacin, an inhibitor of PG synthase, failed to suppress the Ca-releasing effect of A suggesting the A itself or a lipoxygenase product may have been responsible for the observed effects. Moreover, these results provide suggestive evidence that A release is an important step in the action of various uterotonic agents converging on the mobilization of intracellular Ca.« less

Oxidative stress and its association with coronary artery disease and different atherogenic risk factors.

PubMed

Vassalle, C; Petrozzi, L; Botto, N; Andreassi, M G; Zucchelli, G C

2004-10-01

It is well known that free radicals contribute to endothelial dysfunction and are involved in the pathogenesis and development of cardiovascular diseases, such as atherosclerosis. The aim of this study was to provide evidence for enhanced oxidative stress in coronary artery disease (CAD). Plasma levels of 8-isoprostane (8-epiPGF(2alpha)), marker of lipid peroxidation, were measured in 68 subjects (age: 60 +/- 2 years, mean +/- SEM). Subjects included 30 healthy control subjects and 38 patients with angiographically proven CAD. In addition, the total antioxidant power (PAO) was evaluated in a subgroup (40 subjects, 12 healthy and 28 CAD). Levels of 8-epiPGF(2alpha) increased with the number of affected vessels (one- and multi-vessel disease versus control subjects, P < 0.001) and considering different risk determinants for atherosclerosis (i.e. hypertension, gender, hypercholesterolaemia, P < 0.01). In multivariate regression models the number of affected vessels was independently correlated with 8-epiPGF(2alpha) (P < 0.05). PAO values significantly decreased with increased number of affected vessels (P < 0.05) and in hypertensive patients when compared with those without hypertension (P < 0.05). In multivariate regression models the number of affected vessels resulted an independent determinant for PAO (P < 0.05). Concentration of 8-epiPGF(2alpha) and PAO also correlated with the number of cardiovascular risk factors (P < 0.01 and P = 0.07, respectively). These findings indicate that elevated levels of plasma 8-epiPGF(2alpha) and reduced antioxidant capacity are associated with the extent and the severity of CAD and with the occurrence and number of different atherogenic risk factors. This observation may assist in providing more information as to how oxidative stress may predispose to atherogenesis and suggest attractive therapeutic strategies in the prevention and treatment of cardiovascular disease.

Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins.

PubMed

Morimoto, A; Nakamori, T; Watanabe, T; Ono, T; Murakami, N

1988-04-01

To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.

Inhibition of prostaglandin production in the inflammatory tissue by loxoprofen-Na, an anti-inflammatory prodrug.

PubMed

Sugimoto, M; Kojima, T; Asami, M; Iizuka, Y; Matsuda, K

1991-11-27

The effect of loxoprofen-Na, a novel non-steroidal anti-inflammatory drug with a prodrug property, on prostaglandin (PG) levels in the inflammatory tissue was investigated with a carrageenin-induced pleurisy model in rats. The intrapleural injection of carrageenin caused a marked increase in the levels of PGE2 and 6-keto-PGF1 alpha in the pleural exudate up to 3 hr after the injection. When [14C]PGE2 was injected into the cavity 2 hr after the carrageenin injection, the PG rapidly disappeared from the cavity (T 1/2 = 5 min). Thus, the PG level determined in the inflammatory exudate represents PG produced in the inflammatory tissue. Loxoprofen-Na, administered orally 2 hr after the carrageenin injection, dose-dependently inhibited the increase in the levels of PGs in the exudate 1 hr after administration (ID50 = 0.07 mg/kg for PGE2 and 0.10 mg/kg for 6-keto-PGF1 alpha). Indomethacin also inhibited PG production, but was less effective (ID50 = 0.24 mg/kg for PGE2 and 0.47 mg/kg for 6-keto-PGF1 alpha). Similar results were obtained 3 hr after the administration of these drugs (ID50 of PGE2 production = 0.14 mg/kg for loxoprofen-Na and 0.28 mg/kg for indomethacin). The time-course analysis of the effect of loxoprofen-Na showed that this drug had more immediate and stronger inhibitory activity than indomethacin. The relative potencies of suppression of protein leakage and leukocyte infiltration correlated well with the inhibition of PG production, but higher doses were needed for an obvious anti-inflammatory effect. The active metabolite (SRS trans-OH) of loxoprofen-Na determined in the inflammatory exudate 1 hr after oral administration of 0.2 and 2 mg/kg of loxoprofen-Na was 0.05 and 0.25 micrograms/mL, respectively. The concentration was sufficient to suppress PG production in the exudate, because the IC50 of the SRS trans-OH for PG production in vitro with leukocytes was 0.02 microgram/mL (0.01 microM). The potency of the SRS trans-OH metabolite to inhibit PGE2 production in leukocytes was about 20 times stronger than that of the parent compound and 3 times stronger than that of indomethacin.

Effect of Mailuoning injection on 8-iso-prostaglandin F2 alpha and superoxide dismutase in rabbits with extremity ischemia-reperfusion injury.

PubMed

Wang, Dai-Jun; Tian, Hua

2014-12-01

To date, there are no effective treatments for extremity ischemia-reperfusion (IR) injury. The objective of the present study was to explore the protective effect of Mailuoning on IR injury by investigating the plasma levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF2α) and the activity of superoxide dismutase (SOD) in rabbits. The experimental models of posterior limb IR injury were established in thirty rabbits that were divided into three groups: the sham, IR, and IR + Mailuoning groups. At the end of ischemia, Mailuoning was injected intravenously into the rabbits in the IR + Mailuoning group, and normal saline solution was administered to the rabbits in the sham and IR groups. Venous blood samples were collected to measure the levels of 8-iso-PGF2α and the activity of SOD in the plasma at the following time points: at the onset of ischemia, the end of ischemia, and 2, 4, 8, 12, and 24 h after reperfusion. The skeletal muscles were harvested to examine the ultrastructure. The levels of 8-iso-PGF2α increased significantly and SOD activity decreased in the IR group at every time point after reperfusion (P <0.01 or P <0.05). In contrast, the levels of 8-iso-PGF2α and SOD activity were not significantly different after reperfusion in the IR + Mailuoning group (P >0.05) but were significantly different compared with the IR group (P <0.01). Using electron microscopy, the skeletal muscle injury was shown to be milder in the IR+ Mailuoning group after reperfusion compared with the IR group. The Mailuoning is capable of decreasing the excessive production of 8-iso-PGF2α and protecting SOD activity, thereby exhibiting a protective effect on extremity IR injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Existence of compensatory defense mechanisms against oxidative stress and hypertension in preeclampsia.

PubMed

Roland, L; Gagné, A; Bélanger, M-C; Boutet, M; Berthiaume, L; Fraser, W D; Julien, P; Bilodeau, J-F

2010-01-01

Preeclampsia is a complex obstetrical syndrome characterized by hypertension and proteinuria. This syndrome is associated with oxidative stress, antioxidant imbalance and impaired production of vasoactive eicosanoids such as thromboxane A(2) (TXA(2)), a potent vasoconstrictor, and prostacyclin (PGI(2)), a well-known vasodilator. We hypothesized that there was a relationship between antioxidant vitamins, such as vitamin E and coenzyme Q(10) (CoQ(10)), and the production of vasoactive eicosanoids- PGI(2) and TXA(2)-potentially regulated by pro-oxidants and antioxidants in preeclampsia. Therefore, the plasma levels of vitamin E, CoQ(10), TXA(2) and PGI(2) in normotensive (n = 30) and preeclamptic (n = 29) pregnancies were evaluated. Reduced and oxidized forms of vitamin E and CoQ(10) in blood were measured using a HPLC coupled to electrochemical detection. The levels of TXB(2) and 6-keto-PGF(1alpha), stable metabolites of TXA(2) and PGI(2) respectively, were measured by ELISA. The CoQ(10) oxidized/reduced ratio was significantly higher in preeclamptic compared to normotensive pregnancies (p = 0.04). A strong correlation between plasma levels of reduced vitamin E and CoQ(10), corrected for apolipoprotein B, was observed only in preeclampsia (r = 0.69, p < 0.0001). The 6-keto-PGF(1alpha)/TXB(2) ratio was higher in preeclampsia than in controls (p = 0.02), and this ratio was correlated to the oxidized/reduced ratio of both, vitamin E and CoQ(10) in all pregnancies (p <0.023). The data indicated that CoQ(10) is a sensitive marker of oxidative stress in preeclampsia. The correlation between vitamin E and CoQ(10) suggested a coordinated defense mechanism against oxidation. Furthermore, the higher 6-keto-PGF(1alpha)/TXB(2) ratio that strongly correlated with oxidative stress markers, suggests a mechanism developed by the maternal cardiovascular system to counteract hypertension during preeclampsia.

Rapid quantitative analysis of 8-iso-prostaglandin-F(2alpha) using liquid chromatography-tandem mass spectrometry and comparison with an enzyme immunoassay method.

PubMed

Dahl, Jeffrey H; van Breemen, Richard B

2010-09-15

A rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed for the measurement of urinary 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)), a biomarker of lipid peroxidation. Because urine contains numerous F(2) prostaglandin isomers, each with identical mass and similar mass spectrometric fragmentation patterns, chromatographic separation of 8-iso-PGF(2alpha) from its isomers is necessary for its quantitative analysis using MS/MS. We were able to achieve this separation using an isocratic LC method with a run time of less than 9min, which is at least threefold faster than previous methods, while maintaining sensitivity, accuracy, precision, and reliability. The limits of detection and quantitation were 53 and 178pg/ml urine, respectively. We compared our method with a commercially available affinity purification and enzyme immunoassay kit and found both assays to be in agreement. Despite the high sensitivity of the enzyme immunoassay method, it is more expensive and has a narrower dynamic range than LC-MS/MS. Our method was optimized for rapid measurement of 8-iso-PGF(2alpha) in urine, and it is ideally suited for clinical sample analysis. 2010 Elsevier Inc. All rights reserved.

Effect of breeding protocols and reproductive tract score on reproductive performance of dairy heifers and economic outcome of breeding programs.

PubMed

Stevenson, J L; Rodrigues, J A; Braga, F A; Bitente, S; Dalton, J C; Santos, J E P; Chebel, R C

2008-09-01

The objectives of this study were to evaluate the effect of reproductive protocols and reproductive tract score on reproductive performance of dairy heifers and economic outcomes of breeding programs. Holstein heifers (n = 534), 13 +/- 1 mo of age, were randomly assigned to 1 of 4 reproductive protocols. On the day of enrollment (d 0), heifers were palpated per rectum and received a score according to the maturity of their reproductive tract (1 = prepubertal; 2 = peripubertal; and 3 = puber-tal). Estrous detection-control heifers (CON, n = 146) received no treatment and were inseminated on detection of estrus for 28 d. Prostaglandin F(2alpha)-treated heifers (PGED, n = 137) received 1 injection of PGF(2alpha) on d 0 and were inseminated on detection of estrus; heifers not in-seminated by d 14 received a second injection of PGF(2alpha) and were observed for estrus and artificial insemination (AI) for an additional 14 d. Heifers enrolled in the estrous detection-timed AI (EDTAI, n = 140) treatment received a controlled internal drug-release (CIDR) insert on d 0, and 7 d later, the CIDR was removed and all heifers received an injection of PGF(2alpha), heifers received AI on detection of estrus, and those not inseminated by 72 h after PGF(2alpha) received an injection of GnRH concurrent with AI. Heifers in the GnRH-timed AI (GTAI, n = 111) treatment received 1 injection of GnRH on d 0, on d 6 heifers received a CIDR insert and injections of GnRH and PGF(2alpha), on d 13 the CIDR was removed and heifers received an injection of PGF(2alpha), and 48 h later all heifers received an injection of GnRH and AI. Pregnancy was diagnosed at 32 +/- 3 and 62 +/- 3 d after AI. Cost of reproductive protocols and their economic outcomes were calculated for a 28 d period beginning at enrollment. Heifers in the PGED treatment were inseminated at a faster rate than CON heifers. A smaller proportion of prepubertal and peripubertal heifers were inseminated within 14 d of enrollment compared with pubertal heifers. Pregnancy per AI of CON and PGED heifers was greater compared with EDTAI and GTAI heifers. Proportion of GTAI heifers pregnant at the end of the 28-d breeding program was or tended to be smaller compared with PGED and CON heifers, respectively. Heifers in the CON and PGED treatments had the smallest cost per pregnancy followed by heifers in the EDTAI and GTAI treatments, respectively. When different scenarios were evaluated, however, the mean cost per pregnancy was smallest for PGED heifers. Cost per pregnancy generated was greatest for prepubertal heifers, whereas pubertal heifers had the smallest cost per pregnancy generated. Treatment of dairy heifers with PGF(2alpha) every 14 d until insemination and pregnancy results in the best economic outcomes, and screening heifers according to RTS may prove beneficial to identify heifers that may not be pubertal and would have compromised reproductive and economic performance in a breeding program.

Relationship of oestrus synchronization method, circulating hormones, luteinizing hormone and prostaglandin F-2 alpha receptors and luteal progesterone concentration to premature luteal regression in superovulated sheep.

PubMed

Schiewe, M C; Fitz, T A; Brown, J L; Stuart, L D; Wildt, D E

1991-09-01

Ewes were treated with exogenous follicle-stimulating hormone (FSH) and oestrus was synchronized using either a dual prostaglandin F-2 alpha (PGF-2 alpha) injection regimen or pessaries impregnated with medroxy progesterone acetate (MAP). Natural cycling ewes served as controls. After oestrus or AI (Day 0), corpora lutea (CL) were enucleated surgically from the left and right ovaries on Days 3 and 6, respectively. The incidence of premature luteolysis was related (P less than 0.05) to PGF-2 alpha treatment and occurred in 7 of 8 ewes compared with 0 of 4 controls and 1 of 8 MAP-exposed females. Sheep with regressing CL had lower circulating and intraluteal progesterone concentrations and fewer total and small dissociated luteal cells on Day 3 than gonadotrophin-treated counterparts with normal CL. Progesterone concentration in the serum and luteal tissue was higher (P less than 0.05) in gonadotrophin-treated ewes with normal CL than in the controls; but luteinizing hormone (LH) receptors/cell were not different on Days 3 and 6. There were no apparent differences in the temporal patterns of circulating oestradiol-17 beta, FSH and LH. High progesterone in gonadotrophin-treated ewes with normal CL coincided with an increase in total luteal mass and numbers of cells, which were primarily reflected in more small luteal cells than in control ewes. Gonadotrophin-treated ewes with regressing CL on Day 3 tended (P less than 0.10) to have fewer small luteal cells and fewer (P less than 0.05) low-affinity PGF-2 alpha binding sites than sheep with normal CL. By Day 6, luteal integrity and cell viability was absent in ewes with prematurely regressed CL. These data demonstrate that (i) the incidence of premature luteal regression is highly correlated with the use of PGF-2 alpha; (ii) this abnormal luteal tissue is functionally competent for 2-3 days after ovulation, but deteriorates rapidly thereafter and (iii) luteal-dysfunctioning ewes experience a reduction in numbers of small luteal cells without a significant change in luteal mass by Day 3 and, overall, have fewer low-affinity PGF-2 alpha binding sites.

Mechanism whereby nitric oxide (NO) infused chronically intrauterine in ewes is antiluteolytic rather than being luteolytic.

PubMed

Weems, Y S; Lennon, E; Uchima, T; Raney, A; Goto, K; Ong, A; Zaleski, H; Weems, C W

2008-02-01

Nitric oxide (NO) has been reported to be luteolytic in vitro and in vivo in cows. However, an NO donor reversed PGF2alpha-induced inhibition of rat luteal progesterone secretion in vitro and an NO donor or endothelin-1 stimulated bovine luteal tissue secretion of prostaglandins E (PGE; PGE1, PGE2) in vitro without affecting progesterone or PGF2alpha secretion. In addition, chronic infusion of an NO donor into the interstitial tissue of the ovarian vascular pedicle adjacent the luteal-containing ovary prevented the decline in circulating progesterone, while a nitric oxide synthase (NOS) inhibitor did not affect luteolysis. The objective of this experiment was to determine whether an NO donor or NOS inhibitor infused chronically intrauterine adjacent to the luteal-containing ovary during the ovine estrous cycle was luteolytic or antiluteolytic. Ewes were treated either with vehicle (N=5), diethylenetriamine (DETA-control for DETANONOate; N=5), (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETANONOate-long acting NO donor; N=6), l-arginine (N=5), l-nitro-arginine methyl ester (l-NAME-NOS inhibitor; N=6), or NG-monomethyl-l-arginine acetate (l-NMMA; NOS inhibitor; N=5) every 6h from 2400h (0h) on day 8 through 1800h on day 18 of the estrous cycle. Jugular venous blood and inferior vena cava plasma via a saphenous vein cathether 5cm anterior to the juncture of the ovarian vein and inferior vena cava were collected every 6h for analysis for progesterone and PGF2alpha and PGE, respectively, by RIA. Corpora lutea were collected at 1800h on day 18 and weighed. Weights of corpora lutea were heavier (P< or =0.05) in DETANONOate-treated ewes when compared to vehicle, DETA, l-arginine, l-NAME, or l-NMMA-treated ewes, l-arginine luteal weights were heavier than vehicle, DETA, l-arginine, l-NAME, or l-NMMA-treated ewes, and luteal weights of vehicle, DETA, l-NAME, or l-NMMA-treated ewes did not differ amongst each other (P> or =0.05). Profiles of progesterone in jugular venous blood on days 8-18 differed (P< or =0.05) in DETANONOate-treated ewes when compared to vehicle, DETA, l-arginine, l-NMMA or l-NAME-treated ewes, which did not differ (P> or =0.05) amongst each other. The PGE:PGF2alpha ratio profile in inferior vena cava plasma of DETANONOate-treated ewes was increased (P< or =0.05) when compared to all other treatment groups. In a second experiment, conversion of [3H PGE2] to [3H PGF2alpha] by day 15 ovine caruncular endometrium in vitro was determined in vehicle, DETA, or DETANONOate-treatment groups. Conversion of [3H PGE2] to [3H PGF2alpha] was decreased (P< or =0.05) only by DETANONOate. It is concluded that NO is not luteolytic during the ovine estrous cycle, but may instead be antiluteolytic and prevent luteolysis by altering the PGE:PGF2alpha ratio secreted by the uterus.

Isoprostane 8-epi-PGF2alpha is frequently increased in patients with muscle pain and/or CK-elevation after HMG-Co-enzyme-A-reductase inhibitor therapy.

PubMed

Sinzinger, H; Lupattelli, G; Chehne, F; Oguogho, A; Furberg, C D

2001-08-01

Muscle pains with or without CK-elevation are among the most frequently observed side-effects in patients with hyperlipoproteinemia on various statins. The pathophysiological background, however, remains obscure. We examined isoprostane 8-epi-PGF2alpha, a marker of in-vivo oxidation injury, in plasma, serum and urine in these patients at baseline, when muscle problems manifested and different time intervals after withdrawing the respective statin. A healthy control group and a group of untreated patients with hyperlipoproteinemia were run as controls. The majority of patients with muscular side-effects show elevated 8-epi-PGF2alpha in plasma and urine, whereas serum values were elevated only to a lesser extent. Stopping statin therapy or successfully changing to another member of this family of compounds resulted in a normalization of the values in all patients. These findings indicate a significant involvement of oxidative injury in the muscular side-effects of statins in patients suffering from hyperlipoproteinemia.

Prostaglandin release from in vitro guinea-pig gallbladder.

PubMed

Booker, M L; LaMorte, W W

1983-02-01

In order to study prostaglandin release from guinea pig gallbladder, full thickness tissue sections were incubated for one hour in Krebs solution. Extraction and two dimensional chromatography of incubation media obtained in the presence of radio-labelled arachidonic acid demonstrated the presence of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane B2. These results were supported by radioimmunoassay of incubations conducted in the absence of exogenous arachidonate and in the presence of varying concentrations of unlabelled exogenous arachidonate. The previously reported predominance of PGE2 was only seen at high concentrations of exogenous arachidonate.

Efficacy of different doses of aspirin in decreasing blood levels of inflammatory markers in patients with cardiovascular metabolic syndrome.

PubMed

Gao, Xiu-Ren; Adhikari, Chandar M; Peng, Long-Yun; Guo, Xiao-Gang; Zhai, Yuan-Sheng; He, Xu-Yu; Zhang, Li-Yuan; Lin, Jun; Zuo, Zhi-Yi

2009-11-01

Inflammation and platelet aggregation and activation are key processes in the initiation of a cardiovascular event. Patients with metabolic syndrome have a high risk of cardiovascular events. This study determined whether small and medium doses of aspirin have anti-inflammation and antiplatelet aggregation effects in patients with metabolic syndrome. One hundred and twenty-one consecutive patients with metabolic syndrome were randomized into three groups, receiving 100 mg/day of aspirin, 300 mg/day of aspirin or a placebo, respectively, for 2 weeks. The blood levels of thromboxane B2 (TXB2), a stable product of the platelet aggregation mediator TXA2, 6-keto-prostaglandin F1-alpha (6-keto-PGF1-alpha), a stable product of the endogenous cyclooxygenase metabolite prostaglandin I2, and inflammatory mediators including high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), were determined by ELISA and radioimmunoassay. The blood levels of hs-CRP, TNF-alpha, IL-6 and TXB2 were significantly decreased after 2 weeks of treatment with 300 mg/day of aspirin. Patients who received 100 mg/day of aspirin had decreased blood levels of hs-CRP and TXB2. The blood level of IL-6 in the 300 mg/day aspirin group was significantly lower than that in the other two groups after 2 weeks of therapy. Aspirin at either dose did not affect the blood level of 6-keto-PGF1-alpha. Aspirin at all doses suppresses the blood levels of inflammatory markers and the platelet aggregation mediator TXA2 in Chinese patients with metabolic syndrome. Since the suppression induced by 300 mg/day of aspirin was greater than that induced by 100 mg/day of aspirin, these data suggest that 300 mg/day of aspirin may be beneficial in decreasing the risk of cardiovascular events in Chinese patients with metabolic syndrome.

F-prostanoid receptor regulation of fibroblast growth factor 2 signaling in endometrial adenocarcinoma cells.

PubMed

Sales, Kurt J; Boddy, Sheila C; Williams, Alistair R W; Anderson, Richard A; Jabbour, Henry N

2007-08-01

Prostaglandin (PG) F(2alpha) is a potent bioactive lipid in the female reproductive tract, and exerts its function after coupling with its heptahelical G-protein-coupled receptor [F-series-prostanoid (FP) receptor] to initiate cell signaling and target gene transcription. In the present study, we found elevated expression of fibroblast growth factor (FGF) 2, FGF receptor 1 (FGFR1), and FP receptor, colocalized within the neoplastic epithelial cells of endometrial adenocarcinomas. We investigated a role for PGF(2alpha)-FP receptor interaction in modulating FGF2 expression and signaling using an endometrial adenocarcinoma cell line stably expressing the FP receptor to the levels detected in endometrial adenocarcinomas (FPS cells) and endometrial adenocarcinoma tissue explants. PGF(2alpha)-FP receptor activation rapidly induced FGF2 mRNA expression, and elevated FGF2 protein expression and secretion into the culture medium in FPS cells and endometrial adenocarcinoma explants. The effect of PGF(2alpha) on the expression and secretion of FGF2 could be abolished by treatment of FPS cells and endometrial tissues with an FP receptor antagonist (AL8810) and inhibitor of ERK (PD98059). Furthermore, we have shown that FGF2 can promote the expression of FGF2 and cyclooxygenase-2, and enhance proliferation of endometrial adenocarcinoma cells via the FGFR1 and ERK pathways, thereby establishing a positive feedback loop to regulate neoplastic epithelial cell function in endometrial adenocarcinomas.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nadel, G.L.; Malik, K.U.; Lew, D.B.

The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ({sup 14}C)AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ({sup 14}C)AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2{alpha}. Trace amounts of PGD2 and 6-keto-PGF1{alpha}more » but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10{sup {minus}7}, 10{sup {minus}7}M respectively). In contrast, dobutamine, norepinephrine, phenylnephrine and xylazine (up to 10{sup {minus}6}M) did not significantly increase PGE2 production. Isoproterenol-induced iPGE2 production was inhibited by a selective {beta}2 antagonist, butoxamine (70%: 10{sup {minus}7}M, 91%: 10{sup {minus}6}M) and somewhat reduced by {beta}1 antagonists practolol and metoprolol (30-64%:10{sup {minus}6}M). These data suggest that isoproterenol induced iPGE2 synthesis is primarily mediated via activation of {beta}2 adrenergic receptor.« less

Early transcriptome responses of the bovine midcycle corpus luteum to prostaglandin F2a includes cytokine signaling

USDA-ARS?s Scientific Manuscript database

In ruminants, prostaglandin F2alpha (PGF2a)-mediated luteolysis is essential prior to estrous cycle resumption, and is a target for improving fertility. To deduce early PGF2a-provoked changes in the corpus luteum a short time-course (0.5–4 h) was performed on cows at midcycle. A microarray-determin...

Tilmicosin and tylosin have anti-inflammatory properties via modulation of COX-2 and iNOS gene expression and production of cytokines in LPS-induced macrophages and monocytes.

PubMed

Cao, Xing-Yuan; Dong, Mei; Shen, Jian-Zhong; Wu, Bei-Bei; Wu, Cong-Ming; Du, Xiang-Dang; Wang, Zhuo; Qi, Yi-Tao; Li, Bing-Yu

2006-05-01

Macrolides have been reported to modify the host immune and inflammatory responses both in vivo and in vitro. We examined the in vitro effect of the macrolides tilmicosin and tylosin, which are only used in the veterinary clinic, on the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and cytokines by lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and mouse peripheral blood mononuclear cells (PBMCs). Compared with 5 microg/mL, tilmicosin and tylosin concentrations of 10 microg/mL and 20 microg/mL significantly decreased the production of 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), PGE(2), NO, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6, and increased IL-10 production. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) gene expression were also significantly reduced. These results support the opinion that macrolides may exert an anti-inflammatory effect through modulating the synthesis of several mediators and cytokines involved in the inflammatory process.

Reproductive performance of ewes after 5-day treatment with intravaginal inserts containing progesterone in combination with injection of prostaglandin f2alpha.

PubMed

Dixon, A B; Knights, M; Pate, J L; Lewis, P E; Inskeep, E K

2006-04-01

Three experiments were conducted with a total of 1579 ewes to examine reproductive performance in response to synchronization of oestrus during the breeding season, using controlled internal drug releasing (CIDR-G) inserts in regimens designed to provide high concentrations of circulating progesterone. In experiment 1, treatment with two CIDR-G inserts for 12 days produced conception rate (79%) and prolificacy (1.9) to first service equivalent to breeding at natural oestrus (56% and 2.0, respectively). Pregnancy rates to two service periods were 90 and 79%, respectively. In experiments 2 and 3, progesterone was delivered by a single CIDR-G insert for 5 days in combination with prostaglandin F2alpha (PGF2alpha; 5 mg i.m., twice, 3 h apart) the day before (experiment 2), or at insert removal (experiment 3). The combined treatments improved rates of synchronization of oestrus (p<0.01) by 23 and 20% points, respectively, and pregnancy rates to the first service period by 19 (p<0.05) and 13 (p<0.01) percentage points, respectively, compared to treatment with PGF2alpha alone. It is concluded that the combination of treatment for 5 days with a CIDR-G insert and two injections of 5 mg PGF2alpha, the day before, or the day of insert removal, were effective treatments to obtain high fertility at synchronized oestrus in ewes during the breeding season.

Uterine, ovarian, and production responses of lactating dairy cows to increasing dietary concentrations of menhaden fish meal.

PubMed

Mattos, R; Staples, C R; Williams, J; Amorocho, A; McGuire, M A; Thatcher, W W

2002-04-01

The primary objective was to determine whether the dietary polyunsaturated fatty acids, eicosapentaenoic (EPA, C20:5, n-3) and docosahexaenoic (DHA, C22:6, n-3), present in fish meal (FM) can attenuate uterine secretion of PGF2alpha in response to a challenge with estradiol and oxytocin in lactating dairy cows. Cycling multiparous cows (n = 32) were fed diets containing 0 (OFM), 2.6 (2.6FM), 5.2 (5.2FM), or 7.8% menhaden FM (7.8FM). The diet consisting of 7.8FM also contained fish oil (0.28% of dietary dry matter) to increase intake of EPA and DHA. Average dry matter intake was 24.9 kg/d and unaffected by diet. Combined intakes of EPA and DHA averaged 0, 12.8, 24.1, and 54.0 g/d from the OFM, 2.6FM, 5.2FM, and 7.8FM diets, respectively. At 30 to 34 d after initiation of dietary treatments, cows received an i.m. injection of 100 microg of GnRH followed by i.m. administration of 25 and 15 mg of PGF2alpha after 7 and 8 d, respectively. Synchronous ovulation was induced by an injection of 3000 IU of human chorionic gonadotropin (hCG) given 24 h later on d 9. Subsequent luteal phase increases in plasma progesterone concentrations did not differ (0.88 ng/ml per day). At 15 d after hCG injection, cows were injected with estradiol-17beta (3 mg, i.v.) at 0900 h and oxytocin (100 IU, i.v.) at 1300 h. Plasma PGF2alpha metabolite concentrations after oxytocin injection were reduced in cows fed diets containing FM compared with those fed OFM. Milk production (39.1 kg/d) and concentrations of fat, protein, or urea nitrogen in milk were not affected by diet. Feeding fish meal and fish oil containing eicosapentaenoic acid and docosahexaenoic acid reduced the proportion of n-6 fatty acids and increased that of n-3 fatty acids in milk in a dose-responsive manner.

Species differences in the effects of prostaglandins on inositol trisphosphate accumulation, phosphatidic acid formation, myosin light chain phosphorylation and contraction in iris sphincter of the mammalian eye: interaction with the cyclic AMP system.

PubMed

Yousufzai, S Y; Chen, A L; Abdel-Latif, A A

1988-12-01

Comparative studies on the effects of prostaglandins (PGs) on 1,2-diacylglycerol, measured as phosphatidic acid (PA), and inositol trisphosphate (IP3) production, cyclic AMP (cAMP) formation, myosin light chain (MLC) phosphorylation and contraction in the iris sphincter smooth muscle of rabbit, bovine and other mammalian species were undertaken and functional and biochemical relationships between the IP3-Ca++ and cAMP second messenger systems were demonstrated. The findings obtained from these studies can be summarized as follows: 1) all PGs investigated, including PGE2, PGF2 alpha, PGF2 alpha-ester, PGE1 and PGA2 increased IP3 accumulation and PA formation, and the extent of stimulation was dependent on the animal species. Thus, PGF2 alpha-ester (1 microM), the most potent of the PGs, increased IP3 accumulation in rabbit and bovine sphincters by 33 and 58%, respectively, and increased PA formation by 67 and 56%, respectively. The PG increased IP3 accumulation in both rabbit and bovine sphincters very rapidly (T1/2 values about 26 sec) and in a dose-dependent manner. 2) The PG had no effect on MLC phosphorylation in the rabbit sphincter, but it increased that of the bovine by 36%. 3) The PG increased cAMP formation by 75% in the rabbit sphincter but it had no effect on that of the bovine. 4) The PG induced a maximal contractile response in the bovine sphincter but it had no effect on that of the rabbit. 5) In the bovine, PGA2 induced IP3 accumulation and contraction, without an effect on cAMP formation; however, in the rabbit, cat and dog it increased cAMP formation and had no effect on IP3 accumulation and contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

He-Ne laser treatment on menorrhagia

NASA Astrophysics Data System (ADS)

Ding, Ai-Hua

1993-03-01

By using He-Ne laser treatment, 84.7 - 91.1% of patients with menorrhagia, a common symptom of multiple gynecological diseases, are treated effectively. After laser irradiation, the amount of vaginal bleeding was reduced 47.1% on average. It has been proven that low-energy laser is an effective non-traumatic, painless, and easily acceptable new physical method in patients with menorrhagia. To study the mechanisms of efficiency, the quantitative determination of PGE2, PGF2(alpha ), 6-Keto-PGF1(alpha ), TXB2 in endometrium and blood flow before and after treatment were carried out. The results suggest that the effectiveness may be due to the recovery regulation of local uterine PGS level.

Activation of p42/p44 mitogen-activated protein kinase and contraction by prostaglandin F2alpha, ionomycin, and thapsigargin in cat iris sphincter smooth muscle: inhibition by PD98059, KN-93, and isoproterenol.

PubMed

Ansari, H R; Husain, S; Abdel-Latif, A A

2001-10-01

In the present study we investigated the cross talk between the Ca2+ mobilization pathway and the mitogen-activated protein (MAP) kinase pathway and contraction in the cat iris sphincter smooth muscle. Three Ca2+-mobilizing agonists, namely, prostaglandin F2alpha (PGF2alpha), ionomycin, and thapsigargin, and three specific inhibitors, PD98059, a p42/p44 MAP kinase inhibitor; KN-93, a Ca2+-calmodulin-dependent protein kinase II (CaMKII) blocker; and isoproterenol, a cAMP-elevating agent, were used. Changes in tension in response to the agonists were recorded isometrically and MAP kinase phosphorylation and activation were monitored by Western blotting and by in situ myelin basic protein phosphorylation, respectively. We found that 1) stimulation of the sphincter muscle with PGF2alpha, ionomycin, or thapsigargin resulted in rapid phosphorylation and activation of p42/p44 MAP kinase and contraction; and 2) treatment of the muscles with PD98059, KN-93, or isoproterenol resulted in inhibition of the Ca2+-mobilizing agonist-induced responses. The contractile responses induced by PGF2alpha, ionomycin, and thapsigargin were (mg of tension/mg of wet weight tissue) 15.2, 15.4, and 16.2, respectively; the increases in MAP kinase phosphorylation by these agonists were 228, 203, and 190%, respectively; and the increases in MAP kinase activation by the agonists were 212, 191, and 162%, respectively. The stimulatory effects of the agonists on contraction and on MAP kinase phosphorylation and activation were blocked by preincubation of the muscle with PD98059, KN-93, or isoproterenol. These data demonstrate that in the iris sphincter phosphorylation and activation of p42/p44 MAP kinases by PGF2alpha, ionomycin, or thapsigargin require intracellular Ca2+ either from extracellular sources or from internal stores, that CaMKII plays an important role in the regulation of contraction, that CaMKII acts upstream of MAP kinase to control its activation, and that the MAP kinase signaling pathway can play a significant role in mediating the cellular effects of these Ca2+-mobilizing agonists.

[Prostaglandins in gynecology and obstetrics].

PubMed

Klausch, B; Kyank, H

1972-06-03

A review of early research (up through 1970) on prostaglandins (PGs) is presented. Their chemical structure and classification based on their ring-structure is detailed as well as various analytic methods of mammalian tissues and body fluids. For clinical use PGE1 and 2, PGF2alpha and PGA1 are the most significant ones because of their properties. PGs have many physiological activities encompassing many organ systems. Their pharmacological actions include: 1) stimulation of nonvascular smooth muscle; 2) peripheral vasodilation (excluding PGFs which cause vasoconstriction); 3) inhibition of lipolysis; 4) inhibition of platelet aggregation; 5) inhibition of gastric peristalsis and gastric juice secretion; 6) bronchodilation; and 7) inhibition of spontaneous CNS activity. The level of PGEs in semen is closely related to the degree of fertility; normally fertile men have 55 mcg PGE/ml and never less than 11 mcg/ml. Current studies are under way on the effect of PGE in artificial insemination of sperm of subfertile men. PGF2alpha and PGE2 stimulate menstruation and uterine contraction; other PGs inhibit uterine contraction. PGs from semen have a role in sperm transport and possibly act on fallopian tube motility aiding sperm capacitation, and ovum retention and transport. Early trials with PGs point to a possible action as an abortifacient, as a once-a-month contraceptive, or a postconception contraceptive agent. PGF2alpha is found in variable concentrations in maternal blood during contraction of the pregnant uterus; levels increase as labor progresses. PGs have been used for labor induction, for induction of abortion and in mole pregnancy. Given as a constant intravenous infusion they produce regular contractions leading to natural expulsion of the fetus and causing very few side effects in the woman with no adverse effects on the fetus. PGs' action compares favorably with that of oxytocin and is preferable for labor induction in certain pregnancy complications. PGE1 and 2 have a stronger effect than PGF2alpha, hence can be used in smaller dosage and cause fewer adverse effects.

Postpartum levels of 8-iso-prostaglandin F2α in plasma and milk phospholipid fractions as biomarker of oxidative stress in first-lactating dairy cows.

PubMed

Vernunft, A; Viergutz, T; Plinski, C; Weitzel, J M

2014-08-01

F2-isoprostanes such as 8-iso-prostaglandin F2 (8-iso-PGF2α) are formed by free radical-catalyzed mechanisms from membrane phospholipids and from low density lipoproteins through peroxidation of arachidonic acid. Esterified 8-iso-PGF2α is cleaved by phospholipases, circulates in blood and is excreted as putatively harmful oxidatively modified lipid via the kidney into urine. In this study we demonstrate that 8-iso-PGF2α concentrations in plasma samples from heifers are higher (p<0.005) compared to those from first-lactating dairy cows at 71 days postpartum. Furthermore, plasma 8-iso-PGF2α concentrations vary with ovarian activity and differ in response to luteolytic initiation as well as activation of the hypothalamic-pituitary-gonadal axis between heifers and first-lactating cows. Sustainable concentrations of 8-iso-PGF2α (50-150 pg/ml) are detectable in the phospholipid fraction of milk, suggesting milk as an additional excretion route for 8-isoprostanes. Plasma levels largely paralleled levels in milk (p<0.001). Plasma phospholipid 8-iso-PGF2α concentrations in cyclic cows decreased (p<0.05) from day 38 to day 71 postpartum, whereas milk phospholipid 8-iso-PGF2α rather increased (p<0.05). Cyclic cows tend to have higher 8-isoprostane levels compared to acyclic animals. In contrast to lipohydroperoxides, concentration of 8-iso-PGF2α were not correlated with milk yield (p>0.05). Our data indicate 8-iso-PGF2α may be a novel biomarker of oxidative stress in dairy cow, which is detectable in blood as well as in milk. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationship between platelet and urinary 8-Iso-PGF2α levels in subjects with different degrees of NOX2 regulation.

PubMed

Carnevale, Roberto; Iuliano, Luigi; Nocella, Cristina; Bartimoccia, Simona; Trapè, Stefano; Russo, Roberta; Gentile, Maria Cristina; Cangemi, Roberto; Loffredo, Lorenzo; Pignatelli, Pasquale; Violi, Francesco

2013-06-14

Urinary 8-iso-PGF2α, a marker of oxidative stress, is influenced by the activation of NOX2. It is unclear if platelets 8-iso-PGF2α contribute to urinary 8-iso-PGF2α. In a cross-sectional study, platelet, urinary, and serum 8-iso-PGF2α were determined in subjects with downregulation (X-linked chronic granulomatous disease [X-CGD], n=25) and upregulation (type II diabetic patients [T2D], n=121) of NOX2 and 153 controls matched for sex and age. In diabetic patients (n=18), the above variables were repeated before and after 7 days treatment with 100 mg/day aspirin or 100 mg/day aspirin plus 40 mg/day atorvastatin. In vitro study was performed to see the contribution of blood cells to serum 8-iso-PGF2α. Compared with controls, X-CGD patients had lower platelet, serum, and urinary 8-iso-PGF2α values; conversely, diabetic patients had higher values of 8-iso-PGF2α compared with controls. Urinary 8-iso-PGF2α significantly correlated with both platelet and serum 8-iso-PGF2α in the 2 cohorts. A parallel increase of platelet, serum, and urinary 8-iso-PGF2α by aspirin and a parallel decrease by aspirin plus atorvastatin were detected in the interventional study. In vitro study demonstrated that platelets contribute to 37% of serum 8-iso-PGF2α and that only 13% of it is of extravascular origin. The study suggests that NOX2 contributes to the formation of 8-iso-PGF2α in both platelets and urine. The direct correlation between platelet and urinary 8-iso-PGF2α suggests that, at least partly, urinary 8-iso-PGF2α reflects platelet 8-iso-PGF2α production. Analysis of serum 8-iso-PGF2α may represent a novel tool to investigate the production of 8-iso-PGF2α by blood cells including platelets. URL: ClinicalTrials.gov. Unique Identifier: NCT01250340.

Tromboxane B2 inhibits the pulmonary inactivation of prostaglandin E2 in the dog.

PubMed Central

Fitzpatrick, T. M.; Friedman, L. S.; Kot, P. A.; Ramwell, P. W.

1980-01-01

1 The systemic vasodepressor response to intravenously administered prostaglandin E2 (PGE2, 0.3, 1.0 and 3.0 micrograms/kg) is potentiated during intravenous infusion of thromboxane B2 (TXB2, 1.0 micrograms kg-1 min-1) in the anaesthetized dog. 2 The augmented haemodynamic response returns toward control values following cessation of the TXB2 infusion. 3 The systemic haemodynamic responses to intra-arterially administered PGE2, PGF2 alpha and PGI2 as well as intravenously administered PGF2 alpha and PGI2 are not altered by TXB2 infusion. 4. This study suggests that TXB2 inhibits the pulmonary inactivation of PGE2. 5 Arachidonic acid metabolites may interact, producing haemodynamic responses differing from their individual effects. PMID:7000216

[Differential action of non-steroidal antiinflammatory drugs on human gallbladder cyclooxygenase and lipoxygenase].

PubMed

Franchi, A; Di Girolamo, G; Farina, M; de los Santos, A R; Martí, M L; Gimeno, M A

2000-01-01

Lysine clonixinate (LC) is a non-steroidal antiinflammatory agent (NSAID) with only few adverse effects. This characteristic has prompted us to suggest that its administration, at levels equivalent to those found in human plasma following therapeutic doses, slightly inhibits cyclooxygenase I (COX I). Three experiments were performed. Experiment 1: to study the in vitro effect of LC at concentrations of 4 and 6 micrograms/ml, comparable with those found in plasma following an oral therapeutic dose of 125 mg. Gallbladder tissue segments were incubated with 0.25 microCi of 14C-arachidonic acid and the production of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was measured. LC did not affect basal production of any of the 3 prostaglandins (PGs) but at 6 micrograms/ml slightly reduced the levels of 5-hidroxyeicosatetraenoic acid (5-HETE). Experiment 2: LC was administered preoperatively to 6 patients by continuous perfusion, to achieve a steady-state concentration between 4 and 6 micrograms/ml. Gallbladder segments from the 6 treated and another 6 control patients were incubated in 14C-arachidonic acid. Gallbladder segments treated with LC did not show a decreased production of any of the three PGs whereas 5-HETE released to the medium was significantly lower. Experiment 3: 18 patients received an i.v. bolus of LC 100 mg (n1 = 6) or LC 200 mg (n2 = 6) or indomethacin (INDO) 50 mg (n3 = 6). Unlike the administration of INDO bolus, LC in the above doses did not inhibit PG synthesis. Both NSAIDs showed different effects when the production of 5-HETE synthesis was assessed. Treatment with INDO did not alter the production of 5-HETE while LC elicited significant inhibition. The three studies conducted, namely in vitro and in vivo continuous perfusion and i.v. bolus, revealed that LC had no effect on prostaglandin synthesis while reducing significantly the levels of 5-HETE.

[Pharmacological profiles of latanoprost (Xalatan), a novel anti-glaucoma drug].

PubMed

Nomura, S; Hashimoto, M

2000-05-01

Latanoprost is a novel prostaglandin F2 alpha (PGF2 alpha) derivative. Topically applied latanoprost into the glaucomatous monkey eyes lowered intraocular pressure (IOP). Latanoprost, however, failed to produce the hypotensive effect in either rabbit or cat eyes. This species difference may be attributed to its high selectivity for the FP receptor and differences in prostaglandin receptor subtypes existed in the eye amongst these species. In ligand binding studies with bovine corpus luteum cell membranes, the Kd value for the FP receptor of latanoprost was the same as that for PGF2 alpha, 2.8 nM. Latanoprost augmented uveoscleral outflow (Uv) in monkeys without affecting trabecular outflow or outflow facility like PGF2 alpha. Although the precise mechanism of the increase in Uv is not fully understood, it is suggested that a decrease in extracellular matrix components in ciliary muscle may contribute to the increase in Uv. On the other hand, an increase in blood flow at the optic nerve head and neuroprotective action in addition to the IOP lowering effect may contribute to the efficacy of latanoprost in glaucoma therapy. Only tolerable conjunctival hyperemia was seen in rabbits. A phase III clinical trial revealed latanoprost (0.005%) once daily produced sustained reduction of IOP in ocular hypertension or primary open-angle glaucoma patients to a greater extent than timolol did. Furthermore, the effects of latanoprost on aqueous humor dynamics in normal human volunteers were similar to those in monkeys, indicating that latanoprost lowers IOP by the increase in Uv in humans.

Effect of infused prostaglandin F 2 on hormonal levels during early pregnancy.

PubMed

Wentz, A C; Jones, G S; Graeber, J

1972-12-01

In light of the theory of prostaglandin (PG) mechanism of action as removal of a progesterone block mediating myometrial stimulation, the effect of PGF2alpha on hormonal patterns was analyzed in 8 patients between 11.5 and 18.5 weeks of gestation. PGF2 alpha was administered intravenously by pump and blood samples were drawn hourly during the first 12 hours and every 2 hours thereafter until abortion occurred. Serum estradiol (2) and estriol (E3) were assayed by radioimmunassay, as was plasma progesteronep. 2 patients had missed abortions; 5 of the 6 remaining patients aborted successfully. The remaining patient of 12 weeks gestation failed to abort. Missed abortion patients had absence of detectible E3 in serum, and E2 and P values were decreased 50%. 3 of 5 successful terminations showed decreases in E3 within first 4 infusion hours and aborted in 17 hours. A 4th patient showed a precipitous E3 drop at 16 infusion hours and aborted at 26 hours. 1 patient showed little E3 change until after abortion, and then it was a 50% decrease. Serum P declined in all 5 successful terminations. E2 values reduced within 4-8 hours before abortion and after infusion. The authors suggest that these findins show a direct effect of PGF2 alpha on steroidogenesis.

Acceleration of lipid peroxidation in alpha-tocopherol transfer protein-knockout mice following the consumption of drinking water containing a radical initiator.

PubMed

Yoshida, Yasukazu; Hayakawa, Mieko; Cynshi, Osamu; Jishage, Kou-ichi; Niki, Etsuo

2008-01-01

To assess the antioxidative role of vitamin E (VE) in a mouse model of severe VE deficiency by using biomarkers, alpha-tocopherol transfer protein (alpha-TTP(-/-))-knockout mice were maintained on a VE-deficient diet for 28 weeks [KO group, n = 6]. Wild-type C57BL/6 mice were maintained on a diet containing 0.002% alpha-tocopherol [WT group, n = 6]. The animals were housed individually in a metabolic cage from the age of 9 weeks (Week 0) to 27 weeks. Urine was collected every week, and the levels of total hydroxyoctadecadienoic acid (tHODE), 7-hydroxycholesterol (t7-OHCh), and 8-iso-prostaglandin F(2alpha)(t8-isoPGF(2alpha)), which are biomarkers for lipid peroxidation, were measured by gas chromatography (GC)-mass spectrometry. From the age of 21 weeks (Week 12), three mice in each group were provided drinking water containing the water-soluble radical initiator 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) until the end of the study (Week 19). Blood and tissue samples were collected, and the levels of the abovementioned biomarkers therein were assessed. AIPH consumption clearly elevated the plasma and erythrocyte levels of tHODE and t8-isoPGF(2alpha) in both the WT and KO groups except for the erythrocyte level of tHODE in the WT group. Furthermore, this elevation was more prominent in the KO group than in the WT group. Interestingly, AIPH consumption reduced the stereoisomer ratio of HODE (ZE/EE), which is reflective of the efficacy of a compound as an antioxidant in vivo; this suggests that free radical-mediated oxidation reduces the antioxidant capacity in vivo. The urine levels of tHODE, t7-OHCh, and t8-isoPGF(2alpha) tended to increase with AIPH consumption, but these individual levels fluctuated. It was clearly demonstrated by the proposed biomarkers that maintaining alpha-TTP(-/-) mice on a VE-deficient diet results in a severe VE deficiency and promotes lipid peroxidation.

Relationship Between Platelet and Urinary 8‐Iso‐PGF2α Levels in Subjects With Different Degrees of NOX2 Regulation

PubMed Central

Carnevale, Roberto; Iuliano, Luigi; Nocella, Cristina; Bartimoccia, Simona; Trapè, Stefano; Russo, Roberta; Gentile, Maria Cristina; Cangemi, Roberto; Loffredo, Lorenzo; Pignatelli, Pasquale; Violi, Francesco

2013-01-01

Background Urinary 8‐iso‐PGF2α, a marker of oxidative stress, is influenced by the activation of NOX2. It is unclear if platelets 8‐iso‐PGF2α contribute to urinary 8‐iso‐PGF2α. Methods and Results In a cross‐sectional study, platelet, urinary, and serum 8‐iso‐PGF2α were determined in subjects with downregulation (X‐linked chronic granulomatous disease [X‐CGD], n=25) and upregulation (type II diabetic patients [T2D], n=121) of NOX2 and 153 controls matched for sex and age. In diabetic patients (n=18), the above variables were repeated before and after 7 days treatment with 100 mg/day aspirin or 100 mg/day aspirin plus 40 mg/day atorvastatin. In vitro study was performed to see the contribution of blood cells to serum 8‐iso‐PGF2α. Compared with controls, X‐CGD patients had lower platelet, serum, and urinary 8‐iso‐PGF2α values; conversely, diabetic patients had higher values of 8‐iso‐PGF2α compared with controls. Urinary 8‐iso‐PGF2α significantly correlated with both platelet and serum 8‐iso‐PGF2α in the 2 cohorts. A parallel increase of platelet, serum, and urinary 8‐iso‐PGF2α by aspirin and a parallel decrease by aspirin plus atorvastatin were detected in the interventional study. In vitro study demonstrated that platelets contribute to 37% of serum 8‐iso‐PGF2α and that only 13% of it is of extravascular origin. Conclusions The study suggests that NOX2 contributes to the formation of 8‐iso‐PGF2α in both platelets and urine. The direct correlation between platelet and urinary 8‐iso‐PGF2α suggests that, at least partly, urinary 8‐iso‐PGF2α reflects platelet 8‐iso‐PGF2α production. Analysis of serum 8‐iso‐PGF2α may represent a novel tool to investigate the production of 8‐iso‐PGF2α by blood cells including platelets. Clinical Trial Registration URL: ClinicalTrials.gov. Unique Identifier: NCT01250340. PMID:23770972

The effect of leg hyperthermia using far infrared rays in bedridden subjects with type 2 diabetes mellitus.

PubMed

Kawaura, Akihiko; Tanida, Noritoshi; Kamitani, Masato; Akiyama, Junichi; Mizutani, Masatoshi; Tsugawa, Naoko; Okano, Toshio; Takeda, Eiji

2010-04-01

We examined the effect of leg hyperthermia on oxidative stress in bedridden subjects with type 2 diabetes mellitus using 15-min sessions of far infrared rays over a two-week period. Four subjects (male 1, female 3) incapacitated by a stroke were recruited for this study. All patients were admitted to Takahashi Central Hospital and ate the same hospital meals. Fasting plasma glucose, HbA1c, tumor necrosis factor (TNF)alpha, free fatty acid, leptin, adiponectin and plasma 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) levels as a marker of oxidative stress were measured on admission, just before and 2 weeks after local heating of the leg. Results showed that plasma total 8-epi-PGF2alpha levels were decreased significantly while TNFalpha levels were increased significantly. On the other hand, glucose, HbA1c, free fatty acid, leptin and adiponectin levels were not changed during the study period. These results suggest that repeated leg hyperthermia may protect against oxidative stress.

Effect of number of cows in estrus and confinement area on estrous behavior of beef cows.

PubMed

Floyd, L N; Lents, C A; White, F J; Wettemann, R P

2009-06-01

Mature Angus and Angus x Hereford cows were used to determine the effects of confinement area and number of cows in estrus on estrous behavior. During each of 2 replicates, 32 nonpregnant, nonlactating cows were maintained in a drylot (60 x 100 m) or in a pasture (12 ha). Estrous cycles were synchronized with 2 injections of PGF(2alpha) 10 to 14 d apart at the initiation of the experiment. Thereafter, PGF(2alpha) was administered between d 6 and 18 of the estrous cycle so that 1, 2 to 3, 4 to 6, or > or = 7 cows were in estrus at the same time. Concentrations of progesterone were quantified in plasma at treatment to ensure cows had a normal response to PGF(2alpha). Duration of estrus and the number of mounts received during estrus were recorded by HeatWatch. If any part of estrus for a cow occurred at the same time as estrus for another cow, the cow was considered to have concurrent estrus with the other cow. Cows in the drylot had a shorter (P < 0.02; 61.8 +/- 3.1 h) interval to estrus after PGF(2alpha) compared with cows on pasture (72.8 +/- 3.3 h). The interval to estrus was longer (P < 0.07) when cows were treated with PGF(2alpha) on d 10 to 13 (76.7 +/- 3.3 h) of the estrous cycle than when treated on d 6 to 9 (62.3 +/- 4.7 h) or d 14 to 18 (62.9 +/- 3.6 h). Increasing the number of cows concurrently in estrus increased the number of mounts each cow received per estrus (P < 0.001) and the duration of estrus (P < 0.01). When only 1 cow was in estrus, she received 11.0 +/- 6.2 mounts during 11.6 +/- 1.5 h. When > or = 7 cows were in estrus at the same time, each cow received 50.4 +/- 3.2 mounts during 17.3 +/- 0.8 h. Cows in drylot were in estrus longer (P < 0.04; 16.4 +/- 0.8 h) than cows on pasture (14.2 +/- 0.7 h). Duration of the longest interval between mounts received decreased (P < 0.002) as the number of cows in estrus at one time increased (5.3 +/- 0.7 h for 1 estrous cow; 2.6 +/- 0.3 h when > or = 7 cows were in estrus). We conclude that increasing the number of beef cows in estrus at the same time will increase the number of times a cow is mounted and the duration of estrus. The increase in estrous behavior associated with more cows in estrus could increase the number of estrous cows detected with infrequent visual observation.

Induction of estrus during the non-breeding season in Egyptian Baladi goats.

PubMed

Medan, Mohamed; Shalaby, Abdel-Hamid; Sharawy, Sayed; Watanabe, Gen; Taya, Kazuyoshi

2002-01-01

The induction of estrus during the non-breeding season was investigated in 100 Egyptian Baladi goats (Capra hircus). All animals assigned to treatments had low progesterone concentrations (<0.5 ng/ml) tested 2 times 10 days apart to confirm anestrous condition. Animals were assigned to three experimental groups. A group of animals received subcutaneous norgestomet ear implant for 11 days and a single i.m. injection of PGF2alpha 24 hr before implant removal (group I; n=40). Second group of animals received subcutaneous norgestomet ear implant for 11 days and a single i.m. injection of PGF2alpha 24 hr before implant removal and gonadotropin releasing hormone 24 hr after implant removal (group II; n=40). Third group of animals received no treatment (control group; n=20). The percentage of goats that showed estrous behavior during the first 72 hr after implant removal was 77.5, 85.0% and 10.0% in group I, group II and control group, respectively. The fertility rate was 57.5, 70.0% and 10.0% in group I, group II and control group, respectively. In conclusion, estrus can be induced in seasonally anestrous Egyptian Baladi goats using norgestomet and PGF2alpha and the injection of GnRH 24 hr after norgestomet implant removal synchronized ovulation in a higher percentage of goats.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellis, L.C.; James, L.F.; McMullen, R.W.

Feeding 300 or 400 g of dried spotted locoweed, Astragalus lentiginosus per day to 11 pregnant Columbia ewes from the 20th to the 50th days of their gestations resulted in dead and edematous fetuses. Aspartate aminotransferase values were increased, whereas serum progesterone values were significantly diminished in a dose-dependent manner by locoweed ingestion. Cotyledonary 6-keto-prostaglandin (PG)F1 alpha (400 g/day only) and PGF2 alpha (300 and 400 g/day) values were significantly increased, whereas PGE values were not affected by the treatment. Alterations in PG values in these sheep may be a mechanism for altering corpus luteum function and inducing fetal death,more » which would ultimately result in abortion.« less

Do high progesterone concentrations decrease pregnancy rates in embryo recipients synchronized with PGF2alpha and eCG?

PubMed

Nogueira, Marcelo F Gouveia; Melo, Danilas S; Carvalho, Luciano M; Fuck, Egon J; Trinca, Luzia A; Barros, Ciro Moraes

2004-05-01

The objective of this study was to evaluate the effects of equine chorionic gonadotropin (eCG) treatment on the number of induced accessory corpora lutea (CL), plasma progesterone concentrations and pregnancy rate in cross-bred heifers after transfer of frozen-thawed (1.5M ethylene glycol) embryos. All recipients received 500 microg PGF2alpha (dl-cloprostenol, i.m.) at random stages of the estrous cycle (Day 0) and were observed for estrus for 7 days. On Day 14, heifers detected in estrus between 2 and 7 days after PGF2alpha treatment were randomly allocated to four groups ( n=83 per group) and given 0 (control), 200, 400, or 600 IU of eCG. Two days later (Day 16), these recipients were given PGF2alpha and observed for estrus. Six to eight days after detection of estrus, plasma samples were collected to determine progesterone concentration and ultrasonography was performed to observe ovarian structures. Heifers with multiple CL or a single CL >15 mm in diameter received an embryo by direct transfer. Embryos of excellent and good quality were thawed and transferred to the recipients by the same veterinarian. Pregnancy was diagnosed by ultrasonography and confirmed by transrectal palpation 21 and 83 days after embryo transfer (ET), respectively. Plasma progesterone concentrations on the day of transfer (Day 7 of the estrous cycle) were 3.9+/-0.7, 4.2+/-0.4,6.0+/-0.4 and 7.8+/-0.6 ng/ml for groups Control, 200, 400, and 600, respectively (Control versus treated groups P=0.009; 200 versus 400 and 600 groups P=0.0001; and 400 versus 600 P=0.012 ). Conception rates 83 days after ET were 41.9, 50.0, 25.0, and 20.9% for groups Control, 200, 400, and 600, respectively (200 versus 400 and 600 groups P=0.0036 ). In conclusion, an increase in progesterone concentration, induced by eCG treatment, did not improve pregnancy rates in ET recipients. Conversely, there was a decline in conception rates in the animals with the highest plasma progesterone concentrations.

Nafazatrom (Bay g-6575), an antithrombotic and antimetastatic agent, inhibits 15-hydroxyprostaglandin dehydrogenase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, P.Y.; Chao, P.H.; McGiff, J.C.

1982-12-01

Nafazatrom (Bay g-6575) is a potent antithrombotic agent which has been suggested to stimulate prostacyclin (PGI2) release from the vascular wall. This study demonstrates that nafazatrom inhibits 15-hydroxyprostaglandin dehydrogenase (15-OH PGDH) of bovine lung and vascular wall. As 15-OH PGDH, the key prostaglandin (PG) catabolizing enzyme, inactivates PGI2 as well as PGE2 and PGF2 alpha, inhibition of this enzyme can result in increased levels of PGI2. Nafazatrom, in the micromolar range, inhibits the metabolism of PGs by 15-OH PGDH in a dose-dependent manner. The IC50 for inhibition of 15-OH PGDH was estimated to be 18.5 microM when (/sup 3/H)PGF2 alphamore » was used as substrate. We also estimated nafazatrom-induced changes in PGI2 degradation by lung 15-OH PGDH using the more stable methyl ester (ME) of PGI2 (PGI2-ME) which resists spontaneous degradation. Nafazatrom also inhibited catabolism by 15-OH PGDH of (/sup 3/H)PGI2-ME to (/sup 3/H)6,15-diketo-PGF1 alpha ME. These results suggest that the inhibitory action of nafazatrom on 15-OH PGDH contributes to its antithrombotic effect by prolonging the biological half-life of PGI2.« less

Species differences in the effects of prostanoids on MAP kinase phosphorylation, myosin light chain phosphorylation and contraction in bovine and cat iris sphincter smooth muscle.

PubMed

Kaddour-Djebbar, I; Ansari, H R; Akhtar, R A; Abdel-Latif, A A

2005-01-01

There is evidence from our own laboratory and that of others that EP-receptor ligands are strong contractile agonists in bovine iris sphincter and that FP-receptor agonists are strong contractile agonists in cat iris sphincter. Here, we have investigated the effects of prostaglandin (PG) receptor agonists of the FP-, EP-, TP- and DP-class on myosin light chain (MLC) phosphorylation, p42/p44 MAP kinase phosphorylation and contraction in the iris sphincter of bovine and cat. Using three signal transduction mechanism assays, namely MLC phosphorylation, MAP kinase phosphorylation and contraction, we demonstrated that in bovine iris sphincter the rank order of potency of the PG agonists in the contractile and MLC phosphorylation assays is as follows: E2>U46619>F2alpha>D2, and in cat F2alpha>D2>E2>U46619. In the MAP kinase assay, in bovine iris sphincter the rank order of potency is E2>F2alpha and in cat F2alpha>E2. These conclusions are supported by the following findings: (1) In the contractile assay, in the bovine sphincter the EC50s for PGF2alpha, PGE2, U46619 and PGD2 were found to be 1.4x10(-7), 5.0x10(-9), 9.0x10(-9) and 1.3x10(-6)M, respectively, and the corresponding values in the cat were 1.9x10(-8), 2.3x10(-7), 1.5x10(-6) and 6.9x10(-8)M, respectively. (2) In the MLC phophorylation assay, in the bovine sphincter PGF2alpha, PGE2, U46619 and PGD2 increased MLC phophorylation by 118%, 165%, 153% and 72%, respectively, and the corresponding values in cat were 175%, 99%, 90% and 95%, respectively. (3) In the MAP kinase assay, in the bovine iris sphincter PGF2alpha and PGE2, increased MAP kinase phosphorylation by 276% and 328%, respectively, and the corresponding values in cat were 308% and 245%, respectively. The data presented demonstrate pronounced species differences in the effects of the prostanoids on the MLC kinase signaling pathway in bovine and cat irides and furthermore confirm the existence of FP-receptors in that of the bovine.

Regulation of vascular prostaglandin synthesis by metabolites of arachidonic acid in perfused rabbit aorta.

PubMed Central

Kent, R S; Diedrich, S L; Whorton, A R

1983-01-01

To address the hypothesis that metabolites of arachidonic acid are important regulators of prostaglandin (PG) synthesis in intact vascular tissue, we studied arachidonate metabolism in rabbit aortas in response to a continuous infusion of arachidonic acid, 10 micrograms/ml. Prostacyclin (PGI2; measured as 6-keto-PGF1 alpha) production rate accelerated during the first 2 min, reached peak velocity at 2 min, and then progressively decelerated. The velocity profile of PGI2 production was similar to that previously reported for cyclooxygenase holoenzyme assayed in vitro, and was consistent with progressive inactivation of the enzymes leading to PGI2 synthesis. We determined the specific inhibition of cyclooxygenase and prostacyclin synthetase by measuring PGI2 and PGE2 production rates and by infusing cyclic endoperoxides. Our results indicate preferential inactivation of cyclooxygenase during arachidonate metabolism, most likely due to cyclooxygenase-derived oxidative intermediates. This was a dose-dependent response and resulted in a progressive decrease in the 6-keto-PGF1 alpha/PGE2 ratio. Exogenously added 15-hydroperoxy eicosatetraenoic acid, on the other hand, actually stimulated cyclooxygenase activity at low doses, while markedly inhibiting prostacyclin synthetase. This finding, along with the accelerating nature of arachidonate metabolism, is consistent with the concept of "peroxide tone" as a mediator of cyclooxygenase activity in this system. These results demonstrate that arachidonate metabolites regulate PG synthesis in intact blood vessels. The progressive enzymatic inhibition intrinsic to arachidonate metabolism may be a model for similar changes occurring in states of enhanced lipid peroxidation. These metabolic alterations might greatly influence the numerous vascular functions known to involve arachidonic acid metabolism. PMID:6409932

Stretch-induced prostaglandins and protein turnover in cultured skeletal muscle

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman H.; Hatfaludy, Sophia; Sohar, Istvan; Shansky, Janet

1990-01-01

The purpose of the study is to determine whether mechanical stimulation of cultured muscle cells influences prostaglandin efflux rates and whether they are related to stretch-induced alterations in protein turnover rates. The materials and methods of the experiment, including cell cultures, mechanical stimulation, protein synthesis, and degradation assays are outlined, and emphasis is placed on the effect of short-term mechanical stimulation in basal medium prostaglandin efflux from cultured skeletal muscle and stretch-induced alterations in prostaglandins efflux in complete medium. The major finding of the study is that mechanical stimulation of tissue-cultured skeletal-muscle cells under conditions inducing skeletal-muscle hypertropy increases the efflux of PGE(2) and PGE(2-alpha) but not 6-keto-PGF(1-alpha), the prostacyclin product.

Failure of Ibuprofen to prevent progressive dermal ischemia after burning in guinea pigs.

PubMed

Tan, Qian; Lin, Zihao; Ma, Wenxi; Chen, Huairen; Wang, Lei; Ning, Guansen; Zhou, Xu

2002-08-01

It is controversial whether the use of prostaglandin inhibitors could prevent progressive dermal ischemia in the postburn stasis zone. This study evaluated the effect of Ibuprofen on preventing postburn dermal ischemia using an animal model of India ink perfusion and skin transparent preparation techniques. The closely clipped backs of the guinea pigs were bathed in 75 degrees C water for 10s. Ibuprofen-treated groups were fed intragastrically with Ibuprofen (12.5mg/kg) every 6h. All animals were perfused with 70% India ink via a cervical artery cannula at 16 kPa constant pressure at 0, 8, 16, 24h postburn. Skin transparent preparations were made, and 6-keto-PGF(1 alpha) and T x B(2) levels in skin tissue were assessed. India ink filling rates in skin capillary plexuses decreased gradually with postburn time elapsing (P<0.01). 6-keto-PGF(1 alpha) and T x B(2) levels in two groups increased. The increase of T x B(2) was dominant, which was related to postburn dermal ischemia (r=0.742, P<0.01). Though levels of 6-keto-PGF(1 alpha) and T x B(2) decreased in Ibuprofen-treated groups, India ink filling rates showed no significant difference between controls and experimental groups (P>0.05). The results were also confirmed by observation of skin transparent preparations. This study suggests that Ibuprofen has no preventive effect on progressive dermal ischemia after burning.

Caspase 3 Activity and Lipoperoxidative Status in Raw Semen Predict the Outcome of Cryopreservation of Stallion Spermatozoa.

PubMed

Muñoz, Patricia Martín; Ferrusola, Cristina Ortega; Lopez, Luis Anel; Del Petre, Chiara; Garcia, Mercedes Alvarez; de Paz Cabello, Paulino; Anel, Luis; Peña, Fernando J

2016-09-01

Stallion-to-stallion variability in the quality of cryopreserved ejaculates postthaw affects the commercial acceptability of frozen semen and thus is a major constraint for the equine industry. In recent years, the molecular mechanisms associated with sperm damage during cryopreservation have become better understood. Identification of the freezability of the ejaculates before the freezing process is initiated will have a major impact on the equine industry. We studied three markers of oxidative stress in sperm, including 8-iso-PGF2alpha, 8-OH guanosine, and 4-hydroxynonenal (4-HNE); the presence of active caspase 3; and their changes after sperm cryopreservation. Although 4-HNE levels increased after cryopreservation (from 7% to 33%, P < 0.001), 8OH-guanosine and 8-ISO-PGF2alpha levels decreased after cryopreservation (from 130 to 35 arbitrary fluorescence units, P < 0.01, and from 1280 to 1233, P < 0.01, respectively). Postthaw sperm quality was classified as poor, average, or good using the 25th and 75th percentiles of all assays of sperm quality studied (motility, velocity, membrane functionality, and thiol content) as thresholds. Using these values, a sperm postthaw quality index was proposed. Receiver operating characteristic curves and the Youden J statistic were used to investigate the value of the measured parameters in fresh sperm as predictors of potential freezability. Using these techniques, we identified markers of bad freezers (percentages of caspase 3-positive dead sperm [area under the curve (AUC) = 0.820, P < 0.05] and percentages of caspase 3- and 4-HNE-positive sperm [AUC = 0.872, P < 0.05]) and good freezers (percentages of caspase 3-negative live sperm [AUC = 0.815, P < 0.05], percentages of live sperm with high thiol content [AUC = 0.907, P < 0.01], and percentages of 8-ISO-PGF2alpha-positive sperm [AUC = 0.900, P < 0.01]. Moreover, we described for the first time the presence of 8-ISO-PGF2alpha in stallion spermatozoa and revealed the importance of considering different markers of oxidative stress. © 2016 by the Society for the Study of Reproduction, Inc.

Prostaglandins in the kidney: developments since Y2K.

PubMed

Nasrallah, Rania; Clark, Jordan; Hébert, Richard L

2007-10-01

There are five major PGs (prostaglandins/prostanoids) produced from arachidonic acid via the COX (cyclo-oxygenase) pathway: PGE(2), PGI(2) (prostacyclin), PGD(2), PGF(2alpha) and TXA(2) (thromboxane A(2)). They exert many biological effects through specific G-protein-coupled membrane receptors, namely EP (PGE(2) receptor), IP (PGI(2) receptor), DP (PGD(2) receptor), FP (PGF(2alpha) receptor) and TP (TXA(2) receptor) respectively. PGs are implicated in physiological and pathological processes in all major organ systems, including cardiovascular function, gastrointestinal responses, reproductive processes, renal effects etc. This review highlights recent insights into the role of each prostanoid in regulating various aspects of renal function, including haemodynamics, renin secretion, growth responses, tubular transport processes and cell fate. A thorough review of the literature since Y2K (year 2000) is provided, with a general overview of PGs and their synthesis enzymes, and then specific considerations of each PG/prostanoid receptor system in the kidney.

Pollen-mediated gene flow from transgenic cotton is constrained by physical isolation measures.

PubMed

Yan, Shuo; Zhu, Weilong; Zhang, Boyu; Zhang, Xinmi; Zhu, Jialin; Shi, Jizhe; Wu, Pengxiang; Wu, Fengming; Li, Xiangrui; Zhang, Qingwen; Liu, Xiaoxia

2018-02-12

The public concern about pollen-mediated gene flow (PGF) from genetically modified (GM) crops to non-GM crops heats up in recent years over China. In the current study, we conducted greenhouse and field experiments to measure PGF with various physical isolation measures, including 90, 80, 60 and 40 holes/cm 2 separation nets and Sorghum bicolor, Zea mays and Lycopersicon esculentum separation crops between GM cotton and non-GM line (Shiyuan321) by seed DNA test during 2013 to 2015, and pollen grain dyeing was also conducted to assess the pollen flow in greenhouse during 2013. Our results revealed that (1) PGF varied depending on the physical isolation measures. PGF was the lowest with 90 holes/cm 2 separation net and S. bicolor separation crop, and the highest with 40 holes/cm 2 separation net and no isolation measure. (2) Similar to PGF results, 90 holes/cm 2 separation net and S. bicolor separation crop could minimize the pollen dispersal. (3) PGF declined exponentially with increasing distance between GM cotton and Shiyuan321. Because of the production mode of farm household (limited cultivated area) in China, our study is particularly important, which is not only benefit for constraining PGF, but also has potential application value in practical production and the scientific researches.

Association of oxidative stress, insulin resistance, and diabetes risk phenotypes: the Framingham Offspring Study.

PubMed

Meigs, James B; Larson, Martin G; Fox, Caroline S; Keaney, John F; Vasan, Ramachandran S; Benjamin, Emelia J

2007-10-01

Systemic oxidative stress causes insulin resistance in rodents. We tested the hypothesis that oxidative stress and insulin resistance are associated in humans. We used cross-sectional data from 2,002 nondiabetic subjects of the community-based Framingham Offspring Study. We measured insulin resistance with the homeostasis model and defined categorical insulin resistance as homeostasis model assessment of insulin resistance (HOMA-IR) > 75th percentile. We measured oxidative stress using the ratio of urine 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) to creatinine and used age- and sex-adjusted regression models to test the association of oxidative stress with insulin resistance in individuals without diabetes and among subgroups at elevated risk of diabetes. Across 8-epi-PGF2alpha/creatinine tertiles, the prevalence of insulin resistance increased (18.0, 27.5, and 29.4% for the first, second, and third tertiles, respectively; P < 0.0001), as did mean levels of HOMA-IR (3.28, 3.83, and 4.06 units; P < 0.0001). The insulin resistance-oxidative stress association was attenuated by additional adjustment for BMI (P = 0.06 across tertiles for insulin resistance prevalence; P = 0.004 for mean HOMA-IR). Twenty-six percent of participants were obese (BMI > or = 30 kg/m2), 39% had metabolic syndrome (according to the Adult Treatment Panel III definition), and 37% had impaired fasting glucose (IFG) (fasting glucose 5.6-6.9 mmol/l). Among 528 obese participants, respectively, insulin resistance prevalence was 41.3, 60.6, and 54.2% across 8-epi-PGF2alpha/creatinine tertiles (P = 0.005); among 781 subjects with metabolic syndrome, insulin resistance prevalence was 41.3, 56.7, and 51.7% (P = 0.0025); and among 749 subjects with IFG, insulin resistance prevalence was 39.6, 47.2, and 51.6% (P = 0.04). Systemic oxidative stress is associated with insulin resistance in individuals at average or elevated risk of diabetes even after accounting for BMI.

Serum tryptase level is a better predictor of systemic side effects than prostaglandin D2 metabolites during venom immunotherapy in children.

PubMed

Cichocka-Jarosz, E; Sanak, M; Szczeklik, A; Brzyski, P; Gielicz, A; Pietrzyk, J J

2011-01-01

We performed a prospective study to analyze mast cell mediators as predictors of systemic adverse reactions during rush venom-specific immunotherapy (VIT) in children. Nineteen children aged 5-17 years received VIT with Venomenhal (HALAllergy). We analyzed serum tryptase (CAP, Phadia), plasma prostaglandin (PG) D2 metabolites (9alpha, 11beta-PGF2), and urine PGD2 metabolites (9alpha, 11beta-PGF2, tetranor-PGD-M) using gas chromatography mass spectrometry before and after the rush protocol. Three boys with high baseline serum tryptase values (>7.76 g/L) (P < .001) and low 9alpha, 11beta-PGF2 concentrations developed grade III systemic adverse reactions during VIT. Baseline serum tryptase was lowest in children who had a Mueller grade II reaction (1.93 [0.36]) before VIT and highest in children with a Mueller grade III reaction (6.31 [4.80]) (P = .029). Repeated measures analysis of variance confirmed that, in children who developed systemic adverse reactions during VIT, serum tryptase was higher both before and after desensitization and increased significantly following the procedure. Analysis of PGD2 metabolites in the prediction of systemic adverse reactions during VIT was inadequate (sensitivity 67% and specificity 0.53%), whilst prediction based on serum tryptase was accurate. In children with severe systemic adverse reactions to Hymenoptera sting, the evaluation of baseline tryptase levels should be a standard procedure. Children with Apis mellifera venom allergy and baseline tryptase levels higher than 7.75 g/L are at risk of anaphylaxis during buildup. Lower baseline values of plasma and urinary PGD2 metabolite concentration in patients with systemic adverse reaction during VIT suggest that prostaglandin catabolism is altered.

Vasomodulatory effects of the angiotensin II type 1 receptor antagonist losartan on experimentally induced cerebral vasospasm after subarachnoid haemorrhage.

PubMed

Wanderer, Stefan; Mrosek, Jan; Gessler, Florian; Seifert, Volker; Konczalla, Juergen

2018-02-01

Cerebral vasospasm following subarachnoid haemorrhage (SAH) remains one of the major factors contributing to poor overall patient outcome. Prostaglandin F2-alpha (PGF2a) induces vasoconstriction. After SAH, PGF2a leads to cerebral inflammation and enhanced vasoconstriction, resulting in cerebral vasospasm. Losartan is already known to have beneficial effects in stroke models and also on several cerebral inflammatory processes. Therefore, the aim of the study was to analyse the effect of losartan on PGF2a-enhanced vasoconstriction after SAH. To investigate the effect of losartan on PGF2a-enhanced vasoconstriction after SAH, cerebral vasospasm was induced by a double-haemorrhage model. Rats were killed on day 3 and 5 after SAH followed by measurement of the isometric force of basilar artery ring segments in an organ bath. PGF2a induced a dose-dependent contraction. After pre-incubation with losartan, the maximum contraction (E max ) for sham-operated animals was significantly lowered [E max 6% in losartan 3 × 10 -4  molar (M) vs. 56% without losartan]. Also, after induced SAH, PGF2a induced no vasoconstriction in pre-incubated vessels with losartan 3 × 10 -4  M on day 3 (d3) as well as on day 5 (d5). For the vasorelaxative investigations, vessel segments were pre-incubated with PFG2a. Cumulative application of losartan completely resolved the pre-contraction in sham-operated animals (non SAH: 95% relaxation). After SAH, losartan not only resolved the pre-contraction (d5: 103%), but also exceeded the pre-contraction (d3: 119%). Therefore, a statistically significantly increased and earlier relaxation was calculated for all losartan concentrations [E max (d3/d5) and pD 2 (d3/d5)] compared with the solvent control group. In a physiological and pathophysiological setup, losartan reduces a PGF2-induced vasoconstriction and reverses a PGF2a-precontraction completely. This fact can be integrated in pushing forward further concepts trying to antagonise/prevent cerebral vasospasm after SAH.

Effects of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs.

PubMed

Blois, Shauna L; Allen, Dana G; Wood, R Darren; Conlon, Peter D

2010-03-01

To determine effects of therapeutic dosages of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs. 10 hound-crossbred dogs. Aspirin (10 mg/kg, PO, q 12 h), carprofen (4.4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), meloxicam (0.1 mg/kg, PO, q 24 h), and a placebo were administered for 7 days in a random order to each of 10 healthy dogs; there was a 21-day washout period between subsequent treatments. One-stage prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and plasma concentrations of thromboxane (TX)B(2) and 6-keto prostaglandin (PG)F(1alpha) were measured before and after treatment administration. Platelet function was assessed by use of a platelet-function analyzer and aggregation. Aspirin, carprofen, and meloxicam did not significantly affect platelet function. Deracoxib caused a mild decrease in platelet aggregation induced by 50microM ADP. Platelet number, Hct, PT, aPTT, and plasma TXB(2) and 6-keto PGF(1alpha) concentrations were unchanged after NSAID administration. Meloxicam administration resulted in a significant decrease in fibrinogen concentration, but results remained within the laboratory reference interval. Oral administration of commonly used NSAIDs at therapeutic dosages in healthy dogs did not alter plasma TXB(2) and 6-keto PGF(1alpha) concentrations. Deracoxib administration resulted in a minor abnormality in platelet aggregation. Anti-inflammatory doses of aspirin did not affect platelet function as measured by use of optical aggregometry and a platelet-function analyzer. Further evaluation of the effects of aspirin and cyclooxygenase-2-selective inhibitors on hemostasis should be performed.

Reinterpreting the best biomarker of oxidative stress: The 8-iso-prostaglandin F2α/prostaglandin F2α ratio shows complex origins of lipid peroxidation biomarkers in animal models.

PubMed

Van't Erve, Thomas J; Lih, Fred B; Jelsema, Casey; Deterding, Leesa J; Eling, Thomas E; Mason, Ronald P; Kadiiska, Maria B

2016-06-01

Oxidative stress is elevated in numerous environmental exposures and diseases. Millions of dollars have been spent to try to ameliorate this damaging process using anti-oxidant therapies. Currently, the best accepted biomarker of oxidative stress is the lipid oxidation product 8-iso-prostaglandin F2α (8-iso-PGF2α), which has been measured in over a thousand human and animal studies. 8-iso-PGF2α generation has been exclusively attributed to nonenzymatic chemical lipid peroxidation (CLP). However, 8-iso-PGF2α can also be produced enzymatically by prostaglandin-endoperoxide synthases (PGHS) in vivo. When failing to account for PGHS-dependent generation, 8-iso-PGF2α cannot be interpreted as a selective biomarker of oxidative stress. We investigated the formation of 8-iso-PGF2α in rats exposed to carbon tetrachloride (CCl4) or lipopolysaccharide (LPS) using the 8-iso-PGF2α/PGF2α ratio to quantitatively determine the source(s) of 8-iso-PGF2α. Upon exposure to a 120mg/kg dose of CCl4, the contribution of CLP accounted for only 55.6±19.4% of measured 8-iso-PGF2α, whereas in the 1200mg/kg dose, CLP was the predominant source of 8-iso-PGF2α (86.6±8.0% of total). In contrast to CCl4, exposure to 0.5mg/kg LPS was characterized by a significant increase in both the contribution of PGHS (59.5±7.0) and CLP (40.5±14.0%). In conclusion, significant generation of 8-iso-PGF2α occurs through enzymatic as well as chemical lipid peroxidation. The distribution of the contribution is dependent on the exposure agent as well as the dose. The 8-iso-PGF2α/PGF2α ratio accurately determines the source of 8-iso-PGF2α and provides an absolute measure of oxidative stress in vivo. Copyright © 2016. Published by Elsevier Inc.

Oxytocin induces prostaglandin F2 alpha release in pregnant cows: influence of gestational age and oxytocin receptor concentrations.

PubMed

Fuchs, A R; Rollyson, M K; Meyer, M; Fields, M J; Minix, J M; Randel, R D

1996-03-01

Brahman cows with known breeding dates received i.v. injections of either 10 or 100 IU oxytocin (OT) on Days 50, 150, 250, or 280 of gestation (n = 6 for each stage). Concentrations of the prostaglandin (PG) F2 alpha metabolite, 13,14-dihydro-15-keto-prostaglandin (PGFM), and OT were measured in samples of peripheral plasma collected at 15-min intervals for 1 h before and 1 h after treatment and then at 30-min intervals for 3 h. Plasma progesterone was measured daily for 14 days after OT injections on Days 50 and 250 of gestation. The increase in plasma OT after injection was dose-dependent (p = 0.001) but not affected by stage of gestation. Plasma PGFM increased after OT in a dose- and stage-dependent manner (p = 0.0001). At Day 280, the increase in plasma PGFM after 100 IU OT was sevenfold greater than at Day 50. Plasma progesterone declined significantly during the 7th to 12th days postinjection and returned to normal pregnancy values by the 14th day (4.4 +/- 0.3 ng/ml) except in two cows treated on Day 50 of gestation that later aborted. In these, plasma progesterone was significantly lower, 2.6 +/- 0.1 ng/ml. In a second experiment, the concentration of OT receptors was determined in endometrium collected from purebred Angus or Hereford cows slaughtered on Days 50, 150, 250, and 280 of gestation (n = 3 or 4 at each stage). Endometrial concentrations of OT receptor changed as a function of gestational age, increasing sixfold from Day 50 to Day 280, which was parallel to the increase by OT of plasma PGFM. Thus, endometrial OT receptors are functionally coupled to PGF2 alpha release during pregnancy, and their concentration determines the magnitude of OT-induced PGF2 alpha release during gestation. Consequently, endogenous OT is a factor in the regulation of PGF2 alpha release from the bovine uterus during pregnancy and parturition.

Effects of prostaglandins and thromboxane analogues on bullock and dog iris sphincter preparations.

PubMed Central

Dong, Y. J.; Jones, R. L.

1982-01-01

1 The bullock iris sphincter was contracted by low concentrations of prostaglandin E2 (PGE2), 16, 16-dimethyl PGE2 and 17,18,19,20-tetranor-16-p-chlorophenoxy PGE2. Other compounds with thromboxane-like actions, for example 11,9-epoxymethano PGH2, were also potent spasmogens, ZK 36374, a stable carbacyclin, was a partial agonist on the PGE-sensitive system of this tissue. 2 The thromboxane antagonist, EP 045, had little effect on the action of PGE2 and 16,16-dimethyl PGE2 on the bullock iris. 3 The dog iris sphincter was sensitive to PGF2 alpha but not to PGE2 and 11,9-epoxymethano PGH2. 4 16,16-dimethyl PGE2 had very low activity on the dog iris in contrast to its high activity on the bullock iris. The reverse was found with the 17,18,19,20-tetranor-16-m-trifluoromethylphenoxy analogue of PGF2 alpha (ICI 81008). This indicates a considerable selectivity of action of the two analogues. 5 The results are discussed in relation to the existing knowledge of prostanoid receptors. PMID:6177369

The effects of progesterone priming on reproductive performance of GnRH-PGF2alpha-treated anestrous goats.

PubMed

Husein, Mustafa Q; Ababneh, Mohammed M; Haddad, Serhan G

2005-01-01

The objective of this experiment was to determine the effect of a 5-day progesterone priming prior to a GnRH-PGF2alpha treatment on reproductive performance of anestrous goats. Thirty-six Mountain Black goats were randomly assigned in a 2 x 2 factorial arrangement and were administered intravaginally on day -12, either with 300 mg progesterone inserts (CGPE and CGP) or with 0 mg progesterone (GPE and GP) for 5 days. On day -6, the goats were injected with 100 microg GnRH, followed 6 days later by 15 mg PGF2alpha (day 0), the time at which the goats in the CGPE and GPE groups were administered 300 IU eCG injections and those in CGP and GP groups were administered the control solution. The goats were exposed to four fertile bucks at 0 h and were checked for breeding marks at 6-h intervals for 72 h. Blood samples were collected from all goats for progesterone analysis. Progesterone concentrations increased only in CGPE and CGP during the period of device insertion but remained low in GPE and GP groups (P < 0.001). Progesterone levels at the time of GnRH injection on day -6 were basal (0.2 +/- 0.04 ng.mL-1) among the groups and began to increase starting on day -2. Day 0 progesterone concentrations differed (P < 0.05) among groups and were significantly influenced by CIDR-G (P < 0.001). A similar proportion of goats expressed estrus and intervals to detected estrus were shorter (P < 0.05) in the CGPE and GPE groups than in GP with no difference between the CGPE, CGP and GPE or between CGP and GP groups. The number of goats ovulating based upon elevated progesterone levels on day 0 was significantly greater (P = 0.002) in CGPE (9/9) and CGP (9/9) than GPE (6/9) and GP (5/9) groups and was significantly influenced by CIDR-G (P = 0.03). All pregnant goats had elevated progesterone concentration on day 0 and none of the goats with basal progesterone levels became pregnant. Pregnancy and kidding rates, twinning percentage and the number of kids born per goat exposed were greater (P < 0.05) among goats treated with progesterone and eCG. In conclusion, progesterone priming and eCG are essential for producing higher rates of pregnancy and kidding in GnRH-PGF2alpha-treated anestrous goats.

Identification of an antagonist that selectively blocks the activity of prostamides (prostaglandin-ethanolamides) in the feline iris.

PubMed

Woodward, D F; Krauss, A H; Wang, J W; Protzman, C E; Nieves, A L; Liang, Y; Donde, Y; Burk, R M; Landsverk, K; Struble, C

2007-02-01

The prostamides (prostaglandin-ethanolamides) and prostaglandin (PG) glyceryl esters are biosynthesized by COX-2 from the respective endocannabinoids anandamide and 2-arachidonyl glycerol. Agonist studies suggest that their pharmacologies are unique and unrelated to prostanoid receptors. This concept was further investigated using antagonists. The isolated feline iris was used as a key preparation, where prostanoid FP receptors and prostamide activity co-exist. Activity at human recombinant FP and other prostanoid receptors was determined using stable transfectants. In the feline iris, AGN 204396 produced a rightward shift of the dose-response curves for prostamide F2alpha and the prostamide F2alpha analog bimatoprost but did not block the effects of PGF2alpha and synthetic FP receptor agonists. Studies on human recombinant prostanoid receptors confirmed that AGN 204396 did not behave as a prostanoid FP receptor antagonist. AGN 204396 exhibited no antagonism at DP and EP1-4, but was a highly effective TP receptor antagonist. Contrary to expectation, the FP receptor antagonist AL-8810 efficaciously contracted the cat iris. AGN 204396 did not affect AL-8810 induced contractions, demonstrating that AL-8810 and AGN 204396 are pharmacologically distinct. Unlike AL-8810, the ethylamide derivate of AL-8810 was not an agonist. Al-8810 did not block prostamide F2alpha activity. Finally, AGN 204396 did not block PGE2-glyceryl ester activity. The ability of AGN 204396 to selectively block prostamide responses suggests the existence of prostamide sensitive receptors as entities distinct from receptors recognizing PGF2alpha and PGE2-glyceryl ester.

Placental dysfunction in Suramin-treated rats: impact of maternal diabetes and effects of antioxidative treatment.

PubMed

Nash, Peppi; Olovsson, Matts; Eriksson, Ulf J

2005-04-01

The aim of the present study was to evaluate a rat model of placental dysfunction/preeclampsia in pregnancies complicated by maternal diabetes. A second objective was to evaluate the effects of vitamin E treatment in this model. Normal and streptozotocin-induced diabetic rats of two different strains (U and H) were given intraperitoneal (IP) injections of the angiogenesis inhibitor Suramin (Sigma Chemical Co, St Louis, MO) or saline in early pregnancy, and fed standard or vitamin E-enriched food. The outcome of pregnancy was evaluated on gestational day 20. In both rat strains Suramin caused fetal growth retardation, decreased placental blood flow, and increased placental concentration of the isoprostane 8-iso-PGF(2alpha). In the U rats Suramin also caused increased fetal resorption rate, increased maternal blood pressure, decreased renal blood flow, and diminished maternal growth. Diabetes caused severe maternal and fetal growth retardation, increased resorption rate, and increased placental 8-iso-PGF(2alpha) concentration independent of Suramin administration. The maternal and fetal effects of Suramin and diabetes were more pronounced in the U strain than in the H strain. Vitamin E treatment improved the status of Suramin-injected diabetic rats: in U rats the blood pressure increase was normalized; and in both U and H rats the decreased placental blood flow was marginally enhanced, and the increase in placental 8-iso-PGF(2alpha) was partly normalized by vitamin E. Suramin injections to pregnant rats cause a state of placental insufficiency, which in U rats resembles human preeclampsia. The induction of this condition is at least partly mediated by oxidative stress, and antagonized by antioxidative treatment. Maternal diabetes involves increased oxidative stress, and causes both maternal and fetal morbidity, which are only marginally affected by additional Suramin treatment.

THG113.31, a specific PGF2alpha receptor antagonist, induces human myometrial relaxation and BKCa channel activation

PubMed Central

Doheny, Helen C; O'Reilly, Michael J; Sexton, Donal J; Morrison, John J

2007-01-01

Background PGF2alpha exerts a significant contractile effect on myometrium and is central to human labour. THG113.31, a specific non-competitive PGF2alpha receptor (FP) antagonist, exerts an inhibitory effect on myometrial contractility. The BKCa channel is ubiquitously encountered in human uterine tissue and plays a significant role in modulating myometrial cell membrane potential and excitability. The objective of this study was to investigate potential BKCa channel involvement in the response of human myometrium to THG113.31. Methods Single and whole-cell electrophysiological BKCa channel recordings from freshly dispersed myocytes, were investigated in the presence and absence of THG113.31. Functional studies investigated the effects of THG113.31 on isolated spontaneous myometrial contractions, in the presence and absence of the BKCa channel blocker, iberiotoxin. Results Single channel recordings identified the BKCa channel as a target of THG113.31. THG113.31 significantly increased the open state probability of these channels [control 0.023+/-0.006; 10 microM THG113.31 0.087+/-0.012 (P = 0.009); and 50 microM THG113.31 0.1356+/-0.018 (P = 0.001)]. In addition, THG113.31 increased whole-cell BKCa currents over a range of membrane potentials, and this effect was reversed by 100 nanoM IbTX. Isometric tension studies demonstrated that THG113.31 exerted a significant concentration-dependent relaxant effect on human myometrial tissue and pre-incubation of strips with IbTX abolished this effect on spontaneously occurring contractions. Conclusion These data suggests that activation of the BKCa channel may contribute, at least partially, to the uterorelaxant effect of THG113.31. PMID:17367527

Modulators of Bufo arenarum ovulation.

PubMed

Ramos, Inés; Cisint, Susana B; Crespo, Claudia A; Medina, Marcela F; Fernández, Silvia N

2008-02-01

In this study we investigated ovulation in vitro using ovary samples from Bufo arenarum with respect to their response to stimulation with homologous pituitary homogenate (HPH) or with progesterone and prostaglandins (PGF2alpha and PGE1) as intermediates of pituitary action. Ovary samples were obtained from animals captured during the breeding period. Our results demonstrate that the ovulatory response to all different inducers was dose dependent, the highest percentage of ovulated oocytes being obtained with HPH treatment. An important increase in the ovulatory response was obtained by the association of PGF2alpha with either HPH or progesterone at suboptimal doses, indicating that this prostaglandin induced a synergistic potentiating effect. Incubation with cyclooxygenase inhibitors (indomethacin or diclofenac sodium) produced a significant decrease in the ovulation induced by HPH, demonstrating that prostaglandins are involved in the action of the pituitary gland in this process. According to our results, PGE1 not only had no participation in the ovulatory process, but also produced an inhibitory effect on ovulation induced by HPH treatment.

Effects of single oral doses of lysine clonixinate and acetylsalicylic acid on platelet functions in man.

PubMed

Pallapies, D; Muhs, A; Bertram, L; Rohleder, G; Nagyiványi, P; Peskar, B A

1996-01-01

Lysine clonixinate is an analgesic drug with a so far unknown mechanism of action. We have determined its effect on platelet cyclooxygenase in man. Biosynthesis of thromboxane (TX)B2 and prostaglandin (PG)F2 alpha in clotting whole blood ex vivo as well as collagen-induced platelet aggregation measured before and at various time points after oral administration of 125 mg lysine clonixinate were compared to results obtained with 500 mg acetylsalicylic acid (ASA). While biosynthesis of both TXB2 and PGF2 alpha measured radioimmunologically was inhibited significantly 2.5 h, but not 6 h, after administration of lysine clonixinate, inhibition by ASA was much greater and still highly significant after 48 h. Similarly, collagen-induced aggregation of platelet-rich plasma was inhibited for a longer period and to a greater extent after administration of ASA than after lysine clonixinate. Our results indicate that lysine clonixinate is a cyclooxygenase inhibitor of moderate potency. It remains to be investigated whether mechanisms other than inhibition of cyclooxygenase contribute to the analgesic activity of lysine clonixinate.

Placental Growth Factor Contributes to Micro-Vascular Abnormalization and Blood-Retinal Barrier Breakdown in Diabetic Retinopathy

PubMed Central

Kowalczuk, Laura; Touchard, Elodie; Omri, Samy; Jonet, Laurent; Klein, Christophe; Valamanes, Fatemeh; Berdugo, Marianne; Bigey, Pascal; Massin, Pascale; Jeanny, Jean-Claude; Behar-Cohen, Francine

2011-01-01

Objective There are controversies regarding the pro-angiogenic activity of placental growth factor (PGF) in diabetic retinopathy (DR). For a better understanding of its role on the retina, we have evaluated the effect of a sustained PGF over-expression in rat ocular media, using ciliary muscle electrotransfer (ET) of a plasmid encoding rat PGF-1 (pVAX2-rPGF-1). Materials and Methods pVAX2-rPGF-1 ET in the ciliary muscle (200 V/cm) was achieved in non diabetic and diabetic rat eyes. Control eyes received saline or naked plasmid ET. Clinical follow up was carried out over three months using slit lamp examination and fluorescein angiography. After the control of rPGF-1 expression, PGF-induced effects on retinal vasculature and on the blood-external barrier were evaluated respectively by lectin and occludin staining on flat-mounts. Ocular structures were visualized through histological analysis. Results After fifteen days of rPGF-1 over-expression in normal eyes, tortuous and dilated capillaries were observed. At one month, microaneurysms and moderate vascular sprouts were detected in mid retinal periphery in vivo and on retinal flat-mounts. At later stages, retinal pigmented epithelial cells demonstrated morphological abnormalities and junction ruptures. In diabetic retinas, PGF expression rose between 2 and 5 months, and, one month after ET, rPGF-1 over-expression induced glial activation and proliferation. Conclusion This is the first demonstration that sustained intraocular PGF production induces vascular and retinal changes similar to those observed in the early stages of diabetic retinopathy. PGF and its receptor Flt-1 may therefore be looked upon as a potential regulatory target at this stage of the disease. PMID:21408222

Ion transport regulation by prostaglandins in mouse macrophages.

PubMed

Braquet, P; Diez, J; Garay, R

1985-01-01

Although the prostaglandins PGE1, PGE2 and PGF2 alpha had no effect on ion transport in isolated human erythrocytes, they modulated ion transport in isolated mouse macrophages, apparently through the mediation of cAMP, by inhibiting the NA+, K+ cotransport system, stimulating the Na+, K+ pump, and stimulating the Na+: Ca++ exchange mechanism.

Synthesis and preliminary pharmacological evaluation of asymmetric chloroquine analogues.

PubMed

Witiak, D T; Grattan, D A; Heaslip, R J; Rahwan, R G

1981-06-01

Asymmetric chloroquine analogues (1-4) were prepared of known absolute configuration in order to assess stereochemical influences on selected biological activities. Since chloroquine has been shown to possess spasmolytic properties, analogues 1-4 were tested for similar pharmacological effects on smooth-muscle contraction. The (S)- and (R)-chlorochloroquine enantiomers (1 and 2, respectively) were more potent antispasmodics than the less lipophilic (S)- and (R)-hydroxychloroquines (3 and 4, respectively) when tested against KCl- or acetylcholine-induced contractions of the isolated mouse ileum. A membrane stabilizing mechanism of action for the chloroquine analogues is proposed since neither cellular toxicity nor calcium antagonism plays a role in the spasmolytic action of these compounds. Although compounds 1-4 also inhibited PGF2 alpha-induced contractions of the ileum, 1 was significantly more potent than 2; the latter in turn was equipotent to 3 and 4. It is tentatively proposed that 1 may possess stereoselective affinity for the PGF2 alpha receptor in the ileum. This observation may be further exploited to obtain more selective profiles of biological activity through molecular manipulation.

Cat iris sphincter smooth-muscle contraction: comparison of FP-class prostaglandin analog agonist activities.

PubMed

Sharif, Najam A; Kaddour-Djebbar, Ismail; Abdel-Latif, Ata A

2008-04-01

The pharmacologic characteristics of a number of FP-class prostaglandin (PG) analogs were determined by using the cat iris sphincter smooth-muscle-contraction assay. Cumulative concentration-response curves were generated for each compound. The relative agonist potencies (EC(50)) of the compounds were: cloprostenol (0.0012 +/- 0.0004 nM) > travoprost acid (0.46 +/- 0.13 nM) = bimatoprost acid (0.99 +/- 0.19 nM) > (+/-)-fluprostenol (15.8 +/- 2.6 nM) = PGF(2alpha) (18.6 +/- 1.8 nM) > latanoprost acid (29.9 +/- 1.6 nM) > bimatoprost (140 +/- 45 nM) > S-1033 (588 +/- 39 nM) > unoprostone (UF-021; 1280 +/- 50 nM; n = 4-14). The maximum response induced by travoprost acid (122% +/- 2.3% maximum response relative to PGF(2alpha)) was significantly greater than that induced by all the other PG compounds (P < 0.001 - P < 0.02). Interestingly, the FP-receptor antagonist, AL-8810, behaved as a moderate efficacy partial agonist (EC(50) = 2140 +/- 190 nM; 63 +/- 4.3% maximum response relative to PGF(2alpha)), indicating that the cat iris contains an extremely well-coupled FP-receptor population, and/or the tissue contains an extremely high density of the FP-receptor and/or spare receptors. The cat iris contraction data were well correlated with other FP-receptor-mediated signal-transduction processes, including FP-receptor binding in bovine corpus luteum (r = 0.86), FP-receptor binding in human iris (r = 0.61), phosphoinositide (PI) hydrolysis in human ciliary muscle and trabecular meshwork cells (r = 0.77 - 0.86), PI turnover in rat and mouse cells (r = 0.73 - 0.76) and via cloned human FP-receptor (r = 0.9), and rat uterus contraction (r = 0.84). These data confirm the presence of functional FP-receptors in the cat iris sphincter, which are exquisitely well coupled and which respond to a variety of FP-class PG analogs with differing potencies.

JSAR Innovative Technology Award. Development of ovulation synchronization and fixed time artificial insemination in dairy cows.

PubMed

Yamada, Kyoji

2005-04-01

Recently, reproductive management has become more difficult as a result of increased herd size. Problems with missing estrous signs and decrease in conception rate by artificial insemination (AI) performed at wrong timing have caused low AI conception rates. In 1995, ovulation synchronization and fixed-time AI (Ovsynch/TAI) was developed in the USA as a new reproductive technology, which was accepted as an useful reproductive management tool in many countries. However, no information on the use of Ovsynch/TAI was available in Japan. It was, therefore, warranted to show the ovulation rate and conception rate after Ovsynch/TAI using gonadotropin releasing hormone analogue (GnRH-A, fertirelin acetate) and prostaglandin F2alpha (PGF2alpha)-THAM, both were commercially available in this country. The conception rate after Ovsynch/TAI has been known to vary among different herds and individuals. Investigation and analysis of factors affecting the conception rate was also warranted to improve the conception rate. A series of experiments were carried out to establish Ovsynch/TAI using domestically produced GnRH-A and PGF2alpha and to study factors affecting conception rate after Ovsynch protocol. Ovsynch using 100 microg GnRH-A and 25 mg PGF2alpha were observed using ultrasonography. As a result, a high synchronization rate of ovulation at 16 to 20 h after the second GnRH injection was confirmed. The conception rate after Ovsynch/TAI was compared in 87 cows with the conception rate after AI at estrus induced by PGF2alpha (139 cows). Conception rate after Ovsynch/TAI was higher than the figure after AI at induced estrus (59.1% vs 20.9%, P<0.05). The dose of GnRH-A was also studied and a practical dose of GnRH-A was found to be 50 microg per cow. To clarify some factors affecting the conception rate after Ovsynch/TAI, 1,558 cows were investigated for the state of their ovaries, days after calving, parity, season, ovarian cyclicity postpartum and nutritional state at the day of Ovsynch. The overall conception rate after Ovsynch/TAI was 51.5%. Fifty-six cows (3.6%) showed estrus at 6 to 7 d after the first injection of GnRH-A. The conception rate after Ovsynch/TAI was low in cows that were 40 to 60 d postpartum, those in their 5th lactation or more, those bred in July to August, and those recovering ovarian cyclicity later than 56 d postpartum. The conception rate after Ovsynch/TAI was high in cows in which body condition score (BCS) was 3.75 at dry period and 3.0 at the day of Ovsynch. In conclusion, Ovsynch/TAI is an effective tool for the reproductive management of dairy cows. A steady and sufficient conception rate after Ovsynch/TAI could be expected by taking the factors affecting the conception rate into the consideration.

Effect of Ocimum basilicum L. on cyclo-oxygenase isoforms and prostaglandins involved in thrombosis.

PubMed

Umar, Anwar; Zhou, Wenting; Abdusalam, Elzira; Tursun, Arzigul; Reyim, Nadira; Tohti, Ibadet; Moore, Nicholas

2014-02-27

Ocimum basilicum L. (OBL) is a plant used in traditional Uyghur medicine for the treatment and prevention of cardiovascular disease. In previous studies we had found an antihypertensive and antithrombotic effect suggestive of an effect on prostaglandins, which we attempt to document here. 6-keto-PGF1α, the metabolite of prostacyclin, and PGE2 were measured in the supernatant of human umbilical vein endothelial cells (HUVEC) and basal or LPS-stimulated mouse coeliac macrophage cultures exposed to OBL ethanol (OBL-E) extracts and petroleum ether, chloroform, ethylacetate and butanol (PE, C, EA, B) fractions. In addition, 6-keto-PGF1α and thromboxane B2 (TXB2) were measured in a rat model of thromboangiitis obliterans exposed or not to OBL. Short-term exposure to OBL-E dose-dependently increased 6-keto-PGF1α from HUVEC, and long-term (24h) exposure decreased it. OBL-C and OBL-B increased 6-keto-PGF1α, whereas the other fractions tended to decrease it after 24h exposure. The extract and all fractions decreased basal and stimulated PGE2 production, but only OBL-EA and OBL-B reduced PGE2 in stimulated cultures to concentrations below the unstimulated values (P<0.05). In vivo OBL increased 6-keto-PGF1α and decreased TXB2. OBL and its extracts increased 6-keto-PGF1α and reduced PGE2 and TXB2 production in a dose and time-related manner. This could indicate simultaneous inhibition of COX-2 and stimulation of endothelial COX-1. The butanol fraction seemed most promising in this respect. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Role of arachidonic acid cascade in Rhinella arenarum oocyte maturation.

PubMed

Ortiz, Maria Eugenia; Arias-Torres, Ana Josefina; Zelarayán, Liliana Isabel

2015-08-01

There are no studies that document the production of prostaglandins (PGs) or their role in Rhinella arenarum oocyte maturation. In this study, we analysed the effect of arachidonic acid (AA) and prostaglandins (PGs) on maturation, activation and pronuclear formation in R. arenarum oocytes. Our results demonstrated that AA was capable of inducing maturation in time-dependent and dose-dependent manner. Arachidonic acid-induced maturation was inhibited by indomethacin. PGs from AA hydrolysis, such as prostaglandin F2α (PGF2α) and, to a lesser extent, PGE2, induced meiosis resumption. Oocyte maturation in response to PGF2α was similar to that produced by progesterone (P4). Oocyte response to PGE1 was scarce. Rhinella arenarum oocyte PGF2α-induced maturation showed seasonal variation. From February to June, oocytes presented low sensitivity to PGF2α. In following periods, this response increased until a maximum was reached during October to January, a close temporal correlation with oocyte response to P4 being observed. The effect of PGF2α on maturation was verified by analysing the capacity of oocytes to activate and form pronuclei after being injected with homologous sperm. The cytological analysis of activated oocytes demonstrated the absence of cortical granules in oocytes, suggesting that PGF2α induces germinal vesicle breakdown (GVBD) and meiosis resumption up to metaphase II. In turn, oocytes matured by the action of PGF2α were able to form pronuclei after fertilization in a similar way to oocyte maturated by P4. In microinjection of mature cytoplasm experiments, the transformation of pre-maturation promoting factor (pre-MPF) to MPF was observed when oocytes were treated with PGF2α. In summary, our results illustrated the participation of the AA cascade and its metabolites in maturation, activation and pronuclei formation in R. arenarum.

Effects of IL8 and Immune Cells on the Regulation of Luteal Progesterone Secretion‡

PubMed Central

Talbott, Heather; Delaney, Abigail; Zhang, Pan; Yu, Yangsheng; Cushman, Robert A.; Cupp, Andrea; Hou, Xiaoying; Davis, John S.

2015-01-01

Recent studies suggest that chemokines may mediate the luteolytic action of PGF2α (PGF). Our objective was to identify chemokines induced by PGF in vivo and to determine the effects of IL8 on specific luteal cell types in vitro. Midcycle cows were injected with saline or PGF, ovaries were removed after 0.5 – 4 h and chemokine expression was analyzed by qPCR. In vitro expression of IL8 was analyzed after PGF administration and with cell signaling inhibitors to determine the mechanism of PGF-induced chemokine expression. Purified neutrophils were analyzed for migration and activation in response to IL8 and PGF. Purified luteal cell types (steroidogenic, endothelial and fibroblast cells) were used to identify which cells respond to chemokines. Neutrophils and peripheral blood mononuclear cells (PBMCs) were co-cultured with steroidogenic cells to determine their effect on progesterone production. IL8, CXCL2, CCL2, and CCL8 transcripts were rapidly increased following PGF treatment in vivo and. The stimulatory action of PGF on IL8 mRNA expression in vitro was prevented by inhibition of p38 and JNK signaling. IL8, but not PGF, TNF, or TGFB1, stimulated neutrophil migration. IL8 had no apparent action in purified luteal steroidogenic, endothelial, or fibroblast cells, but IL8 stimulated ERK phosphorylation in neutrophils. In co-culture experiments neither IL8 nor activated neutrophils altered basal or LH-stimulated luteal cell progesterone synthesis. In contrast, activated PBMCs inhibited LH-stimulated progesterone synthesis from cultured luteal cells. These data implicate a complex cascade of events during luteolysis involving chemokine signaling, neutrophil recruitment, and immune cell action within the corpus luteum. PMID:24686456

Vascular trauma and prostacyclin release.

PubMed

Jeremy, J Y; Mikhailidis, D P; Dandona, P

1984-10-01

The effect of trauma on prostacyclin (PGI2) secretion by rat aorta was examined. Whereas cutting and puncturing markedly increased PGI2 secretion, sonication and stretch had no effect. Cutting and puncturing were also effective in stimulating further endogenous secretion of PGI2 from 'exhausted' aortic segments in whom PGI2 production had dwindled to a negligible rate. These experiments show that trauma is an important stimulator of PGI2 secretion, the exhaustion of PGI2 secretion by vascular segments is not due to the depletion of substrate (arachidonic acid) and that an unusually traumatic venepuncture may invalidate the subsequent assays of PGI2 and its stable metabolite, 6-oxo-PGF1 alpha, in plasma. The close relationship of vascular trauma to PGI2 release also suggests a possible cytoprotective effect of this prostanoid on vascular endothelium.

Endothelial cell markers in vascular neoplasms: an immunohistochemical study comparing factor VIII-related antigen, blood group specific antigens, 6-keto-PGF1 alpha, and Ulex europaeus 1 lectin.

PubMed

Little, D; Said, J W; Siegel, R J; Fealy, M; Fishbein, M C

1986-06-01

Markers for endothelial cells including Ulex europaeus 1 lectin, blood group A, B, and H, and the prostaglandin metabolite 6-keto-PGF1 alpha were evaluated in paraffin secretions from formalin-fixed benign and malignant vascular neoplasms using a variety of immunohistochemical techniques, and results compared with staining for factor VIII-related antigen. Staining for Ulex appeared more sensitive than factor VIII-related antigen in identifying poorly differentiated neoplasms including haemangiosarcomas and spindle cell proliferations in Kaposi's sarcoma. Staining for blood group related antigens correlated with blood group in all cases. Ulex europaeus 1 lectin was the only marker for endothelial cells in lymphangiomas.

Protocols for the measurement of the F2-isoprostane, 15(S)-8-iso-prostaglandin F2α, in biological samples by GC-MS or GC-MS/MS coupled with immunoaffinity column chromatography.

PubMed

Tsikas, Dimitrios; Suchy, Maria-Theresia

2016-04-15

Arachidonic acid, the origin of the eicosanoids family, occurs in biological samples as free acid and as ester in lipids. Free arachidonic acid is oxidized to numerous metabolites by means of enzymes including cyclooxygenase (COX). Arachidonic acid esterified to lipids is attacked by reactive oxygen species (ROS) to generate numerous oxidized arachidonic acid derivatives. Generally, it is assumed that ROS-derived arachidonic acid derivatives are distinct from those generated by enzymes such as COX. Therefore, ROS-generated eicosanoids are considered specific biomarkers of oxidative stress. However, there are serious doubts concerning a strict distinction between the enzyme-derived eicosanoids and the ROS-derived iso-eicosanoids. Prominent examples are prostaglandin F2α (PGF2α) and 15(S)-8-iso-prostaglandin F2α (15(S)-8-iso-PGF2α) which have been originally considered to exclusively derive from COX and ROS, respectively. There is convincing evidence that both COX and ROS can oxidize arachidonic acid to PGF2α and 15(S)-8-iso-PGF2α. Thus, many results previously reported for 15(S)-8-iso-PGF2α as exclusive ROS-dependent reaction product, and consequently as a specific biomarker of oxidative stress, require a careful re-examination which should also consider the analytical methods used to measure 15(S)-8-iso-PGF2α. This prominent but certainly not the only example underlines more than ever the importance of the analytical chemistry in basic and clinical research areas of oxidative stress. In the present work, we report analytical protocols for the reliable quantitative determination of 15(S)-8-iso-PGF2α in human biological samples including plasma and urine by mass spectrometry coupled to gas chromatography (GC-MS, GC-MS/MS) after specific isolation of endogenous 15(S)-8-iso-PGF2α and the externally added internal standard [3,3',4,4'-(2)H4]-15(S)-8-iso-PGF2α by immunoaffinity column chromatography (IAC). 15(S)-8-iso-PGF2α esterified to plasma lipids is hydrolysed by KOH. 15(S)-8-iso-PGF2α and [3,3',4,4'-(2)H4]-15(S)-8-iso-PGF2α are analyzed as pentafluorobenzyl ester trimethylsilyl ether derivatives in the electron-capture negative-ion chemical ionization mode. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of calcitonin gene-related peptide on canine cerebral artery strips and the in-vivo vertebral blood flow in dogs.

PubMed

Ikegaki, I; Suzuki, Y; Satoh, S; Asano, T; Shibuya, M; Sugita, K

1989-10-01

The effects of calcitonin gene-related peptide (CGRP) on canine cerebral arteries and on vertebral blood flow were investigated in-vivo and in-vitro and the findings compared with the effects of vasoactive intestinal peptide (VIP) and substance P. Administration of CGRP into the vertebral artery caused a dose-dependent and long-lasting increase in blood flow. The in-vivo vasodilatory effects of substance P and VIP were short-lasting. CGRP (0.1 to 100 nmol/l) elicited a concentration-dependent relaxation of the isolated middle cerebral and basilar arteries when the tissues were precontracted by exposure to prostaglandin F2 alpha (PGF2 alpha). This effect was not antagonized by propranolol, atropine, tetrodotoxin, (N-Ac-Tyr1, D-Phe2)-growth hormone-releasing factor(1-29)-NH2 or (D-Pro2, D-Trp7,9) substance P. CGRP also reduced concentration-dependently the contraction of cerebral arteries induced by KCl or 9,11-epithio-11,12-metano-thromboxane A2 (STXA2). Mechanical removal of the endothelium did not abolish the vasodilatory response to CGRP. In PGF2 alpha-contracted canine cerebral arteries, VIP (0.1 to 100 nmol/l) was less potent a vasodilator than CGRP. At low concentrations (0.01 to 1 nmol/l) substance P elicited a rapid and short-lasting relaxation, and in the absence of endothelium this relaxation disappeared. These findings are clear evidence that CGRP modulates vascular tone.

Social and breed effects on the expression of a PGF2alpha induced oestrus in beef cows.

PubMed

Landaeta-Hernández, A J; Palomares-Naveda, R; Soto-Castillo, G; Atencio, A; Chase, C C; Chenoweth, P J

2004-10-01

Social organization and breed effects following PGF2alpha were studied in mature Angus, Brahman and Senepol cows allocated into two groups (each A = 5, B = 5 and S = 5). Variables including interval to oestrus onset (IEO), oestrous duration (DE), total mounts received (TMR), and oestrous intensity (IE) were derived via HeatWatch. Breed-type influenced IEO (B = 42.6 +/- 6.7 h; S = 54.6 +/- 6.0 h; and A = 27.8 +/- 5.8 h; p < 0.003). Within breeds, dominant B (69.4 +/- 13.3 h) and S (65.5 +/- 7.4 h) cows were slower (p < 0.05) to be detected in oestrus than subordinate (38.1 +/- 4.4 h) and intermediate (40.6 +/- 6.0 h). However, within A, dominant cows (16.4 +/- 12.5 h) were detected in oestrus earlier (p < 0.05) than intermediate (44.3 +/- 9.2 h) and subordinates (32.7 +/- 5.1 h). Angus (21.5 +/- 2.4 h) and B (22.1 +/- 3.0 h) cows had longer (p < 0.01) DE than S (9.1 +/- 2.8 h). Dominants (20.4 +/- 3.0) and intermediates (20.2 +/- 2.3 h) cows had longer DE (p < 0.04) than subordinates (12.1 +/- 2.1 h) although the interaction breed x social order showed that dominant S had shorter DE than dominant A and B (10.1 +/- 3.3; 34.8 +/- 6.0 h; and 20.0 +/- 6.4 h, respectively; p < 0.001). Angus cows had less TMR than B (p < 0.02) and tended to be less than S cows (p < 0.06). Overall, greatest (p < 0.008) IE occurred in the first 9 h after onset of oestrus with no breed effect (p > 0.05). Dominant cows tended (p < 0.10) to have less TMR (3.2 +/- 0.7 mounts) than subordinate (4.1 +/- 0.4 mounts) and intermediate (4.7 +/- 0.6 mounts) throughout, especially 3-6 h after oestrus onset (p < 0.07). Breed and social order both influence PGF2alpha-induced oestrus behaviour.

Enhancement of scleral macromolecular permeability with prostaglandins.

PubMed Central

Weinreb, R N

2001-01-01

PURPOSE: It is proposed that the sclera is a metabolically active and pharmacologically responsive tissue. These studies were undertaken to determine whether prostaglandin exposure can enhance scleral permeability to high-molecular-weight substances. METHODS: Topical prostaglandin F2 alpha (PGF2 alpha) was administered to monkeys to determine if this altered the amount of scleral matrix metalloproteinases (MMPs). Experiments also were performed to determine whether the prostaglandin F (FP) receptor and gene transcripts are expressed in normal human sclera. Permeability of organ-cultured human sclera following prostaglandin exposure then was studied and the amount of MMP released into the medium measured. Finally, the permeability of human sclera to basic fibroblast growth factor (FGF-2) was determined following prostaglandin exposure. RESULTS: Topical prostaglandin administration that reduced scleral collagen also increased scleral MMP-1, MMP-2, and MMP-3 by 63 +/- 35%, 267 +/- 210%, and 729 +/- 500%, respectively. FP receptor protein was localized in scleral fibroblasts, and FP receptor gene transcript was identified in sclera. Exposure to prostaglandin F2 alpha, 17-phenyltrinor, PGF2 alpha, or latanoprost acid increased scleral permeability by up to 124%, 183%, or 213%, respectively. In these cultures, MMP-1, MMP-2, and MMP-3 were increased by up to 37%, 267%, and 96%, respectively. Finally, transscleral absorption of FGF-2 was increased by up to 126% with scleral exposure to latanoprost. CONCLUSIONS: These studies demonstrate that the sclera is metabolically active and pharmacologically responsive to prostaglandins. Further, they demonstrate the feasibility of cotreatment with prostaglandin to enhance transscleral delivery of peptides, such as growth factors and high-molecular-weight substances, to the posterior segment of the eye. PMID:11797317

Role of calcium in the constriction of isolated cerebral arteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wendling, W.W.

1987-01-01

Calcium entry blockers (CEB) have been used in the experimental treatment or prevention of many cerebrovascular disorders including stroke, post-ischemic hypoperfusion after cardiac arrest, cerebral vasospasm after subarachnoid hemorrhage, and migraine headache. However, the mechanism of action of these drugs on the cerebral circulation is poorly understood. This study examined the effects of calcium antagonists, Ca/sup 2 +/-deficient solutions, and vasocostrictors on cerebrovascular tone and /sup 45/Ca fluxes, to determine the role of calcium in cerebral arterial constriction. A Scatchard plot of /sup 45/Ca binding to BMCA showed that Ca/sup 2 +/ was bound at either low or high affinitymore » binding sties. The four vasoconstrictors (potassium, serotonin, PGF/sub 2 ..cap alpha../, or SQ-26,655) each increased low affinity /sup 45/Ca uptake into BMCA. The results demonstrate that: (1) Potassium and serotonin constrict BMCA mainly by promoting Ca/sup 2 +/ influx through CEB-sensitive channels; (2) PGF/sub 2 ..cap alpha../ and SQ-26,655 constrict BMCA in part by promoting Ca/sup 2 +/ influx through CEB-sensitive channels, and in part by releasing Ca/sup 2 +/ from depletable internal stores; (3) The major action of CEB on BMCA is to block vasoconstrictor-induced Ca/sup 2 +/ uptake through both potential-operated (K/sup +/-stimulated) and receptor-operated channels.« less

Excitotoxicity-induced prostaglandin D2 production induces sustained microglial activation and delayed neuronal death.

PubMed

Iwasa, Kensuke; Yamamoto, Shinji; Yagishita, Sosuke; Maruyama, Kei; Yoshikawa, Keisuke

2017-04-01

Excitotoxicity is the pivotal mechanism of neuronal death. Prostaglandins (PGs) produced during excitotoxicity play important roles in neurodegenerative conditions. Previously, we demonstrated that initial burst productions of PGD 2 , PGE 2 , and PGF 2α are produced by cyclooxygenase-2 (COX-2) in the hippocampus following a single systemic kainic acid (KA) administration. In addition, we showed that blocking of all PG productions ameliorated hippocampal delayed neuronal death at 30 days after KA administration. To investigate the role of individual PGs in the delayed neuronal death, we performed intracerebroventricular injection of PGD 2 , PGE 2 , or PGF 2α in rats whose hippocampal PG productions were entirely blocked by pretreatment of NS398, a COX-2 selective inhibitor. Administration of PGD 2 and PGF 2α had a latent contribution to the delayed neuronal death, sustained over 30 days after a single KA treatment. Furthermore, PGD 2 enhanced microglial activation, which may be involved in the delayed neuronal death in the hippocampus. These findings suggest that excitotoxic delayed neuronal death is mediated through microglia activated by PGD 2 . Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Regional expression of prostaglandin E2 and F2alpha receptors in human myometrium, amnion, and choriodecidua with advancing gestation and labor.

PubMed

Grigsby, Peta L; Sooranna, Suren R; Adu-Amankwa, Bernice; Pitzer, Brad; Brockman, Diane E; Johnson, Mark R; Myatt, Leslie

2006-08-01

The change from uterine quiescence to enhanced contractile activity may be due to the differential expression of prostaglandin receptors within the myometrium and fetal membranes, in a temporal and topographically distinct manner. To address this question, we determined the localization and expression of the PGE2 receptor subtypes (PTGER1-4) and the PGF2alpha receptor (PTGFR) in paired upper and lower segment myometrium, amnion, and choriodecidual samples throughout human pregnancy, with and without labor. All receptor subtypes were found throughout the muscle layers in both the upper and lower uterine segments, colocalizing with alpha smooth muscle actin. A change in intracellular localization was observed at term labor, where PTGER1 and PTGER4 were predominately associated with the nucleus. Minimal changes in the expression of the PGE2 and PGF2alpha receptor subtypes were observed with gestational age, labor, or between the upper and lower myometrial segments. Receptor expression in maternal and fetal tissues differed between the receptor subtypes; PTGER1 and PTGER4 were predominately expressed in the fetal membranes, PTGER2 was greatest in the myometrium, whereas PTGER3 and PTGFR were similarly expressed in the myometrium and fetal membranes. Myometrial activation through the prostaglandin receptors is perhaps more subtle and may be mediated by a balance between one or several of the prostaglandin receptor subtypes together with other known contraction associated proteins. Lack of coordination in receptor expression between the myometrium and fetal membranes may indicate different regulatory mechanisms between these tissues, or it may suggest a function for these receptors in the amnion and choriodecidua that is independent of that seen in the myometrium.

[A study on the effects of a Mg-deficient diet on blood pressure and various hormonal systems in Wistar rats and spontaneously hypertensive rats].

PubMed

Honda, M; Izumi, Y; Hatano, M

1988-08-20

The influence of a Mg-deficient diet on blood pressure and various hormonal systems was examined in Wistar rats (WR) and spontaneously hypertensive rats (SHR). The WR and SHR were individually divided into 2 groups. The Mg-deficient diet was given to one group, and a Mg-containing diet was given to the other group for 3 weeks. During this experimental period, the body weight, blood pressure, urine volume, blood and urinary electrolytes, plasma steroid hormones, plasma renin activity (PRA), and urinary hormones [kinin, prostaglandin E2 (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and noradrenaline] were examined. Although no significant difference in body weight was observed between the Mg-deficient and Mg-containing diet groups in either the WR or SHR (because the experiments were performed in a pair-fed fashion in both kinds of rat), the blood pressure was increased in the Mg-containing diet group but was unchanged in the Mg-deficient diet group. As regards changes in electrolytes, a decreased urinary excretion of Mg and significantly increased urinary excretion of P were observed in the Mg-deficient diet group in both the WR and SHR. Furthermore, decreased levels of serum Mg and P and increased levels of serum Ca were also noted. In the WR group, the urinary excretion of noradrenaline was significantly increased in the Mg-deficient diet group as compared to the Mg-containing diet group. However, the change was reversed in the SHR group. The plasma steroid hormones and PRA were both significantly low in the Mg-deficient diet group in both the WR and SHR. The urinary excretions of PGE2, 6-keto-PGF1 alpha, and kinin showed no significant differences between the two diet groups. The above results indicate that blood pressure is not affected by the Mg-deficient diet in either the WR or SHR, and the possible participation of the sympathetic nervous system in the mechanism of control of blood pressure may differ somewhat between the WR and SHR. In addition, Mg ion was found to play an important role in the biosynthesis of renin and steroid hormones but to have no such significant role in the urinary excretions of kinin, PGE2, and 6-keto-PGF1 alpha.

Control of the estrous cycle in guinea-pig (Cavia porcellus).

PubMed

Grégoire, A; Allard, A; Huamán, E; León, S; Silva, R M; Buff, S; Berard, M; Joly, T

2012-09-01

The aim of this work was to look for a simple method to obtain synchronized ovulation in guinea pigs under farming conditions while respecting animal welfare. The luteolytic activity of three different prostaglandins F2alpha (PGF2α) analogs (D-cloprostenol, D,L-cloprostenol and luprostiol) and a daily treatment with oral progestagen (altrenogest) was tested successively at different stages of the estrous cycle on the same group of females during a period of 8 mo. The estrous cycle length was not modified by the administration of PGF2α analogs, whatever the stage of the estrous cycle when the treatment was initiated. Our results led us to reject the use of PGF2α analog to induce practical synchronization of the estrus in this species. In females (n = 29), given 15 days with altrenogest (0.1 mL po once a day), ovulation occurred 4.43 ± 0.13 days after the end of the treatment. Altrenogest treatment was followed by mating. No negative impacts of the treatment on the pregnancy rates, delivery rates and litter sizes were observed. This standard method of guinea-pig estrus synchronization is less stressful for the animals compared to techniques using progesterone tubing. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of a Novel Prostaglandin F2α Synthase in Trypanosoma brucei

PubMed Central

Kubata, Bruno Kilunga; Duszenko, Michael; Kabututu, Zakayi; Rawer, Marc; Szallies, Alexander; Fujimori, Ko; Inui, Takashi; Nozaki, Tomoyoshi; Yamashita, Kouwa; Horii, Toshihiro; Urade, Yoshihiro; Hayaishi, Osamu

2000-01-01

Members of the genus Trypanosoma cause African trypanosomiasis in humans and animals in Africa. Infection of mammals by African trypanosomes is characterized by an upregulation of prostaglandin (PG) production in the plasma and cerebrospinal fluid. These metabolites of arachidonic acid (AA) may, in part, be responsible for symptoms such as fever, headache, immunosuppression, deep muscle hyperaesthesia, miscarriage, ovarian dysfunction, sleepiness, and other symptoms observed in patients with chronic African trypanosomiasis. Here, we show that the protozoan parasite T. brucei is involved in PG production and that it produces PGs enzymatically from AA and its metabolite, PGH2. Among all PGs synthesized, PGF2α was the major prostanoid produced by trypanosome lysates. We have purified a novel T. brucei PGF2α synthase (TbPGFS) and cloned its cDNA. Phylogenetic analysis and molecular properties revealed that TbPGFS is completely distinct from mammalian PGF synthases. We also found that TbPGFS mRNA expression and TbPGFS activity were high in the early logarithmic growth phase and low during the stationary phase. The characterization of TbPGFS and its gene in T. brucei provides a basis for the molecular analysis of the role of parasite-derived PGF2α in the physiology of the parasite and the pathogenesis of African trypanosomiasis. PMID:11067881

Control of the estrous cycle to improve fertility for fixed-time artificial insemination in beef cattle: a review.

PubMed

Lamb, G C; Dahlen, C R; Larson, J E; Marquezini, G; Stevenson, J S

2010-04-01

Early estrus-synchronization protocols focused on regressing the corpus luteum (CL) with an injection of PGF(2alpha) followed by detection of estrus or involved the use of exogenous progestins that prevent estrus from occurring. Later, protocols combining the use of PGF(2alpha) and exogenous progestins were developed. Gonadotropin-releasing hormone was utilized to control follicular waves, synchronize ovulation, or to luteinize large dominant follicles. Our research aimed to develop reliable protocols that 1) relied solely on fixed-timed AI (TAI); 2) required a maximum of 3 animal handlings, and 3) were successful in estrous-cycling and noncycling females. In cows, insertion of an intravaginal progesterone insert during the 7-d interval between the initial GnRH and PGF(2alpha) injections enhanced pregnancy rates by 9 to 10%. In a multi-location study, a TAI protocol yielded pregnancy rates similar to a protocol involving detection of estrus plus a fixed-time clean-up AI for females not detected in estrus (54 vs. 58%, respectively, for cows and 53 vs. 57%, respectively, for heifers). Initiation of estrous cycles in noncycling cows is likely the primary manner in which beef producers may improve fertility in response to estrus synchronization and TAI protocols. Treatment of noncycling females with progesterone and GnRH increases the percentage of cycling females and improves fertility to a TAI, but inducing cyclicity with hCG failed to enhance fertility in TAI protocols. Supplementing progesterone after TAI failed to increase pregnancy rates in beef cattle. In contrast, administration of hCG 7 d after TAI induced an accessory CL, increased progesterone, and tended to enhance pregnancy rates. Development of TAI protocols that reduce the hassle factors associated with ovulation synchronization and AI provide cattle producers efficient and effective tools for capturing selective genetic traits of economic consequences. Location variables, however, which may include differences in pasture and diet, breed composition, body condition, postpartum interval, climate, and geographic location, affect the success of TAI protocols.

The effect of inhibition of prostaglandin F2 alpha synthesis on placental expulsion in the ewe.

PubMed

Chassagne, M; Barnouin, J

1993-04-01

Five ewes were injected with two doses of a nonsteroidal anti-inflammatory drug (NSAI), lysine acetyl salicylate, at birth of their first lamb and one hour later, and five others were injected once only, at birth of their first lamb. A control group of six animals was constituted. The times needed for fetal expulsion and placental release were recorded. The peripheral plasma PgF2 alpha (as PGFM) levels were measured prepartum during the seven last days of gestation, at parturition, then 1 h, 2 h and 12 h after lambing. The results were compared among and within treatment groups. They indicate that the physiological increase in peripheral PGFM levels starts two days before lambing and that the level peaks at lambing. The normal decrease after parturition is emphasized by NSAI injections as detected 1 h and 2 h posttreatment (p < 0.01). The NSAI drug is short-acting as revealed by the lower PGFM levels in twice-treated animals 2 h after birth compared to once treated animals and the similar low levels in all three groups 12 h after birth. The fetal membranes were expelled normally in all treated and nontreated animals, but the time needed for placental expulsion in ewes injected with two doses of NSAI was longer than in controls (p < 0.05). A negative correlation (p < 0.05) was found between plasma PGFM levels measured two hours after lambing and the time needed for fetal membrane expulsion. PgF2 alpha appears to have a role in placental release in the ewe.

The effect of inhibition of prostaglandin F2 alpha synthesis on placental expulsion in the ewe.

PubMed Central

Chassagne, M; Barnouin, J

1993-01-01

Five ewes were injected with two doses of a nonsteroidal anti-inflammatory drug (NSAI), lysine acetyl salicylate, at birth of their first lamb and one hour later, and five others were injected once only, at birth of their first lamb. A control group of six animals was constituted. The times needed for fetal expulsion and placental release were recorded. The peripheral plasma PgF2 alpha (as PGFM) levels were measured prepartum during the seven last days of gestation, at parturition, then 1 h, 2 h and 12 h after lambing. The results were compared among and within treatment groups. They indicate that the physiological increase in peripheral PGFM levels starts two days before lambing and that the level peaks at lambing. The normal decrease after parturition is emphasized by NSAI injections as detected 1 h and 2 h posttreatment (p < 0.01). The NSAI drug is short-acting as revealed by the lower PGFM levels in twice-treated animals 2 h after birth compared to once treated animals and the similar low levels in all three groups 12 h after birth. The fetal membranes were expelled normally in all treated and nontreated animals, but the time needed for placental expulsion in ewes injected with two doses of NSAI was longer than in controls (p < 0.05). A negative correlation (p < 0.05) was found between plasma PGFM levels measured two hours after lambing and the time needed for fetal membrane expulsion. PgF2 alpha appears to have a role in placental release in the ewe. PMID:8490813

Pharmacologic properties of KT2-962 (6-isopropyl-3-[4-(p- chlorobenzenesulfonylamino)-butyl]-azulene-1-sulfonic acid sodium salt); a new TXA2/prostaglandin endoperoxide receptor antagonist.

PubMed

Kosakai, K; Wakabayashi, S; Sato, T; Mochizuki, S; Tomiyama, A; Zhou, Q; Satake, N; Shibata, S

1993-03-01

Pharmacologic properties of KT2-962 (6-isopropyl-3-[4-(p-chlorobenzenesulfonylamino)butyl]-azulene+ ++-1-sulfonic acid sodium salt, KT) were studied in isolated rat aorta, rat tail artery, rabbit aorta, rabbit renal artery, and pig coronary artery. KT competitively inhibited the contractions induced by thromboxane A2 (TXA2) mimetic, U46619 (pA2 values 9.95, 8.85, 7.87, 8.49, and 9.12, respectively). KT also inhibited the contraction of rabbit aorta induced by prostaglandin2 alpha (PGF2 alpha, pA2 value 7.85) and the contraction of guinea pig ileum induced by LTD4 (pA2 value 5.48) but did not alter the contractions induced by norepinephrine (NE), Ca2+, serotonin, and histamine. KT did not alter the contractions of guinea pig ileum, which did not contract with U46619, induced by PGE2 and PGF2 alpha. KT inhibited the aggregations of rabbit platelets induced by U46619, arachidonic acid, and collagen (IC50 values 7.9, 140, and 16 microM, respectively) but not those induced by ADP. It also inhibited the specific binding of TXA2/PGH2 receptor antagonist, [3H]SQ29,548, to rabbit gel-filtered platelets with an IC50 value of 1.5 x 10(-8) M. In in vivo experiments with mice, oral administration of KT protected the U46619-induced sudden death with the minimum effective dose of 0.3 mg/kg and provided such protection for > 8 h at 1.0 mg/kg. These results indicate that KT is a new nonprostanoid type TXA2/PGH2 receptor antagonist that is orally effective and long acting.

Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF(2α)/PGF(2α) ratio distinguishes chemical from enzymatic lipid peroxidation.

PubMed

van 't Erve, Thomas J; Lih, Fred B; Kadiiska, Maria B; Deterding, Leesa J; Eling, Thomas E; Mason, Ronald P

2015-06-01

The biomarker 8-iso-prostaglandin F2α (8-iso-PGF2α) is regarded as the gold standard for detection of excessive chemical lipid peroxidation in humans. However, biosynthesis of 8-iso-PGF2α via enzymatic lipid peroxidation by prostaglandin-endoperoxide synthases (PGHSs), which are significantly induced in inflammation, could lead to incorrect biomarker interpretation. To resolve the ambiguity with this biomarker, the ratio of 8-iso-PGF2α to prostaglandin F2α (PGF2α) is established as a quantitative measure to distinguish enzymatic from chemical lipid peroxidation in vitro, in animal models, and in humans. Using this method, we find that chemical lipid peroxidation contributes only 3% to the total 8-iso-PGF2α in the plasma of rats. In contrast, the 8-iso-PGF2α levels in plasma of human males are generated >99% by chemical lipid peroxidation. This establishes the potential for an alternate pathway of biomarker synthesis, and draws into question the source of increases in 8-iso-PGF2α seen in many human diseases. In conclusion, increases in 8-iso-PGF2α do not necessarily reflect increases in oxidative stress; therefore, past studies using 8-iso-PGF2α as a marker of oxidative stress may have been misinterpreted. The 8-iso-PGF2α/PGF2α ratio can be used to distinguish biomarker synthesis pathways and thus confirm the potential change in oxidative stress in the myriad of disease and chemical exposures known to induce 8-iso-PGF2α. Published by Elsevier Inc.

Developmental changes in endothelium-dependent pulmonary vasodilatation in pigs.

PubMed Central

Liu, S. F.; Hislop, A. A.; Haworth, S. G.; Barnes, P. J.

1992-01-01

1. We compared in vitro endothelium-dependent vasorelaxant responses to acetylcholine (ACh) and the endothelium-independent vasodilator response to sodium nitroprusside (SNP) in prostaglandin F2 alpha (PGF2 alpha)-precontracted muscular pulmonary arteries (PA) from pigs aged 5 min to 2 h (neonatal), 3-10 days, 3-8 weeks and adults. 2. In the pulmonary artery (PA) rings from neonatal animals, the vasodilator response to ACh was negligible. However, responses to ACh were present in all PA rings from older animals, being greatest at 3-10 days and then decreasing with age (P less than 0.001, ANOVA). ACh (30 microM) induced a 1 +/- 1%, 92 +/- 9%, 62 +/- 5% and 51 +/- 6% reduction of the PGF2 alpha-generated tension in neonatal, 3-10 days, 3-8 weeks and adult groups, respectively. 3. The relaxant response to SNP was present in the PA rings from all age groups and increased with age (P less than 0.001, ANOVA). SNP (1 microM)-induced relaxation was 55 +/- 9%, 73 +/- 7%, 97 +/- 5% and 93 +/- 6% in neonatal, 3-10 days, 3-8 week and adult groups, respectively. 4. Removal of the vascular endothelium abolished the relaxant response to ACh but had no effect on the response to SNP in any groups. 5. NG-monomethyl-L-arginine (30 microM), a nitric oxide synthesis inhibitor, inhibited the response to ACh but not to SNP. The lipoxygenase inhibitor, nordihydroguaiaretic acid, had no significant effect on responses to ACh or SNP in any group.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 PMID:1393265

Prostaglandins and prognosis in human breast cancer.

PubMed Central

Watson, D. M.; Kelly, R. W.; Miller, W. R.

1987-01-01

Prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) were measured by gas liquid chromatography--mass spectrometry (glc-ms) in extracts of primary tumours from 78 patients with early breast cancer. These levels have been related to factors of established prognostic value and the patients disease-free interval. Although there was a wide variation in amounts of both prostaglandins extracted from different tumours, no significant relationship was observed between levels of prostaglandins and oestrogen receptors (ER), tumour size, presence of lymph node involvement and disease-free interval following primary treatment. It therefore seems unlikely that the level of these particular prostaglandins within breast carcinomas plays a fundamental role in the prognosis of the disease. PMID:3478073

Plasma concentrations of 15-keto-13,14-dihydro-PGF-2 alpha, oestrone sulphate, oestradiol-17 beta and progesterone in pregnant guinea-pigs treated with polychlorinated biphenyls.

PubMed

Lundkvist, U; Kindahl, H

1989-09-01

Guinea-pigs treated by gavage with a total dose of 100 mg polychlorinated biphenyls (PCB: Clophen A50) during Days 17-61 of gestation had higher plasma concentrations of 15-keto-13,14-dihydroprostaglandin F-2 alpha, oestrone sulphate and oestradiol-17 beta during the later stages of gestation than did vehicle-treated guinea-pigs. No changes were observed in plasma progesterone concentrations. Our results provide no support for the hypothesis that an enzyme-induced decrease in progesterone concentrations is the main cause of the fetal death observed in PCB-treated guinea-pigs.

[Glycemic variability and oxidative stress in children, with type 1 diabetes attending a summer camp].

PubMed

Colomo, N; Tapia, M J; Vallejo, M R; García-Torres, F; Rubio-Martín, E; Caballero, F F; Jiménez, J M; Pelaez, M J; Gómez, A M; Sánchez, I; López-Siguero, J P; Soriguer, F; Ruiz de Adana, M S

2014-09-01

To assess glycemic variability, oxidative stress and their relationship in children and adolescents with type 1 diabetes (T1DM) attending a summer camp. Cross-sectional study that included 54 children and adolescents with T1DM aged 7-16, attending a 7 day summer camp. Sociodemographic information, clinical data, and blood glucose values measured using an Accu-Chek Nano® glucose meter were recorded. Glucose variability markers (standard deviation [SD], low blood glucose index [LBGI], high blood glucose index [HBGI], mean amplitude of glycemic excursions [MAGE] and mean of daily differences [MODD]) were calculated. Oxidative stress was assessed by the measurement of 8-iso-prostaglandin F2 alpha (PGF2α) in a 24-hour urine sample collected at the end of the camp in 14 children. The Median SD, MAGE and MODD indexes were in the high range (61, 131 and 58 mg/dl, respectively), LBGI in the moderate range (3.3), and HBGI in the low range (4.5). The mean HbA1c was 7.6% and the median urinary excretion rate of 8-iso-PGF2α was 864.39 pg/mg creatinine. The Spearman correlation coefficients between markers of glycemic variability (SD, HBGI, MAGE, MODD) were significant. Non-significant correlations were found between markers of glycemic variability and urinary 8-iso-PGF2α. High glycemic variability was observed in children and adolescents attending a summer camp. However, no correlations were found between markers of glycemic variability and oxidative stress measured by urinary 8-iso-PGF2α. Further studies are needed to address the relationship between oxidative stress and glycemic variability in children with T1DM. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Endogenous opioids: role in prostaglandin-dependent and -independent fever.

PubMed

Fraga, Daniel; Machado, Renes R; Fernandes, Luíz C; Souza, Glória E P; Zampronio, Aleksander R

2008-02-01

This study evaluated the participation of mu-opioid-receptor activation in body temperature (T(b)) during normal and febrile conditions (including activation of heat conservation mechanisms) and in different pathways of LPS-induced fever. The intracerebroventricular treatment of male Wistar rats with the selective opioid mu-receptor-antagonist cyclic d-Phe-Cys-Try-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP; 0.1-1.0 microg) reduced fever induced by LPS (5.0 microg/kg) but did not change T(b) at ambient temperatures of either 20 degrees C or 28 degrees C. The subcutaneous, intracerebroventricular, and intrahypothalamic injection of morphine (1.0-10.0 mg/kg, 3.0-30.0 microg, and 1-100 ng, respectively) produced a dose-dependent increase in T(b). Intracerebroventricular morphine also produced a peripheral vasoconstriction. Both effects were abolished by CTAP. CTAP (1.0 microg icv) reduced the fever induced by intracerebroventricular administration of TNF-alpha (250 ng), IL-6 (300 ng), CRF (2.5 microg), endothelin-1 (1.0 pmol), and macrophage inflammatory protein (500 pg) and the first phase of the fever induced by PGF(2alpha) (500.0 ng) but not the fever induced by IL-1beta (3.12 ng) or PGE(2) (125.0 ng) or the second phase of the fever induced by PGF(2alpha). Morphine-induced fever was not modified by the cyclooxygenase (COX) inhibitor indomethacin (2.0 mg/kg). In addition, morphine injection did not induce the expression of COX-2 in the hypothalamus, and CTAP did not modify PGE(2) levels in cerebrospinal fluid or COX-2 expression in the hypothalamus after LPS injection. In conclusion, our results suggest that LPS and endogenous pyrogens (except IL-1beta and prostaglandins) recruit the opioid system to cause a mu-receptor-mediated fever.

Prostaglandin action on transmitter release of adrenergic neuroeffector junctions.

PubMed

Hedqvist, P

1976-01-01

The results presented here indicate that 1. The inhibitory action of the endoperoxides on NE release can be at least partly explained in terms of formation of degradation products, presumably mainly PGE2. 2. PGA2 is less active and the PG analogue 16,16-dimethyl-PGE2 more active than PGEs on transmitter release from adrenergic nerves. 3. PGF2alpha seems to enhance vascular responses to renal nerve activity solely by a postjunctional action. 4. PG synthesis inhibition augments NE turnover in a number of rat organs, thereby increasing the probability of PGs being involved in the control of adrenergic neurotransmission in vivo. 5. Prolongation of the duration of the impulse and action potential counteracts the effect of PGE on NE release, thereby strengthening the view that PGs operate on NE release from adrenergic nerve terminals by interfering with Ca2+ influx.

Indomethacin inhibits the effects of oestrogen in the anterior pituitary gland of the rat.

PubMed

Rosental, D G; Machiavelli, G A; Cherñavsky, A C; Speziale, N S; Burdman, J A

1989-06-01

Two inhibitors of prostaglandin synthesis, indomethacin and aspirin, blocked the increase of oestrogen-binding sites in the nuclear subcellular fraction, an increase which occurs after the administration of oestradiol. Consequently the biological effects of oestrogens in the anterior pituitary gland of the rat (prolactin synthesis, concentration of progesterone-binding sites and cell proliferation) are diminished. The anterior pituitary gland synthesized prostaglandin F2 alpha (PGF2 alpha), PGE2 and PGD2 from arachidonic acid. This synthesis was blocked when indomethacin was added to the culture media. Oestrogen increased the concentration of PGE2: an increase that was partially prevented by indomethacin. Prostaglandins may have an important role on the effects of oestrogen in the anterior pituitary gland of the rat.

Elevated plasma 8-iso-prostaglandin F2α levels in human smokers originate primarily from enzymatic instead of non-enzymatic lipid peroxidation.

PubMed

van 't Erve, Thomas J; Lih, Fred B; Kadiiska, Maria B; Deterding, Leesa J; Mason, Ronald P

2018-02-01

It is widely accepted that free radicals in tobacco smoke lead to oxidative stress and generate the popular lipid peroxidation biomarker 8-iso-prostaglandin F 2α (8-iso-PGF 2α ). However, 8-iso-PGF 2α can simultaneously be produced in vivo by the prostaglandin-endoperoxide synthases (PGHS) induced by inflammation. This inflammation-dependent mechanism has never been considered as a source of elevated 8-iso-PGF 2α in tobacco smokers. The goal of this study is to quantify the distribution of chemical- and PGHS-dependent 8-iso-PGF 2α formation in the plasma of tobacco smokers and non-smokers. The influences of gender and hormonal contraceptive use were accounted for. The distribution was determined by measuring the 8-iso-PGF 2α /prostaglandin F 2α (PGF 2α ) ratio. When comparing smokers (n = 28) against non-smokers (n = 30), there was a statistically significant increase in the 8-iso-PGF 2α concentration. The source of this increased 8-iso-PGF 2α was primarily from PGHS. When stratifying for gender, the increase in 8-iso-PGF 2α in male smokers (n = 9) was primarily from PGHS. Interestingly, female smokers on hormonal contraceptives had increased 8-iso-PGF 2α in both pathways, whereas those not on hormonal contraceptives did not have increased 8-iso-PGF 2α . In conclusion, increased plasma 8-iso-PGF 2α in tobacco smokers has complex origins, with PGHS-dependent formation as the primary source. Accounting for both pathways provides a definitive measurement of both oxidative stress and inflammation. Published by Elsevier Inc.

Impact of cooked functional meat enriched with omega-3 fatty acids and rosemary extract on inflammatory and oxidative status; a randomised, double-blind, crossover study.

PubMed

Bermejo, L M; López-Plaza, B; Weber, T K; Palma-Milla, S; Iglesias, C; Reglero, G; Gómez-Candela, C

2014-11-01

n-3 fatty acid intake has been associated with inflammatory benefits in cardiovascular disease (CVD). Functionalising meat may be of great interest. The aim of the present study was to assess the effect of functional meat containing n-3 and rosemary extract on inflammatory and oxidative status markers in subjects with risk for CVD. A randomised, double-blind, cross-over study was undertaken to compare the effects on the above markers of consuming functional or control meat products. 43 volunteers with at least two lipid profile variables showing risk for CVD were randomly assigned to receive functional meat (FM) or control meat (CM) over 12-weeks with a 4-week wash-out interval before crossover. Functional effects were assessed by examining lipid profile, CRP, PAI-1, TNF-alpha, IL-6, fibrinogen (inflammatory markers), and TBARS, FRAP and 8-iso-PGF2 (oxidative status markers). 33 subjects (24 women) aged 50.7±8.8 years completed the study. In FM treatment, PAI-1, fibrinogen and 8-iso-PGF2 decreased significantly after 12 weeks, while FRAP significantly increased. In contrast, in CM treatment, a significant increase was seen in PAI-1, while FRAP significantly declined. Significant differences were also seen between the FM and CM treatments after 12 weeks in terms of the change observed in PAI-1, FRAP and 8-iso-PGF2 values. No significant differences were seen in anthropometric variables nor were adverse effects reported. The consumption of FM containing n-3 and rosemary extract improved oxidative and inflammatory status of people with at least two lipid profile variables showing risk for CVD. The inclusion of such functional meat in a balanced diet might be a healthy lifestyle option. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Urinary 11-dehydro-thromboxane B₂ and 2,3-dinor-6-keto-prostaglandin-F₁α in healthy post-menopausal and pre-menopausal women receiving aspirin 100 mg.

PubMed

Hartanto, Marcia Dewi; Arieselia, Zita; Setiabudy, Rianto; Setiawati, Arini; Baziad, Ali

2012-07-01

The prevalence of cardiovascular diseases in women increases sharply after menopause. In postmenopausal women, thromboxane production increases while prostacyclin decreases. Low dose aspirin reduces the production of both thromboxane and prostacyclin. The present study was an open-label clinical trial with two parallel groups of 15 premenopausal women and 15 postmenopausal women. Twenty-four hours urine was collected from each subject before and after aspirin 100 mg daily for 7 days. The concentration of thromboxane and prostacyclin was measured as their metabolites (11-dehydro-thromboxane B(2) and 2,3-dinor-6-keto-prostaglandin-F(1α)) in urine using enzyme immunoassay methods. This study showed that aspirin significantly reduced thromboxane in both groups with significantly larger percentage reduction in postmenopausal women compared to premenopausal women (73.32 vs. 61.13%, p = 0.021). This study also showed that aspirin reduced prostacyclin significantly in both groups, but the percentage reduction between the groups was not significantly different. The decrease in the ratio of 11-dTXB(2)/2,3-dinor-6-keto-PGF(1α) should be compared to assess aspirin efficacy as an antithrombotic. Calculation of the ratio of 11-dTXB(2)/2,3-dinor-6-keto-PGF(1α) before aspirin consumption was higher in postmenopausal women than in premenopausal women. The decrease in 11-dTXB(2)/2,3-dinor-6-keto-PGF(1α) ratio by aspirin was greater in postmenopausal women than in premenopausal women (1.91 vs. 0.17; p = 0.022). It was concluded that aspirin reduced thromboxane and prostacyclin significantly in each group with significant 11-dTXB(2) percentage reduction between groups and non-significant 2,3-dinor-6-keto-PGF(1α) percentage reduction between groups, but reduced the 11-dTXB(2)/2,3-dinor-6-keto-PGF(1α) ratio much larger in postmenopausal women compared to that in premenopausal women.

Factors associated with first service conception in artificially inseminated nulliparous Holstein heifers.

PubMed

Donovan, G Arthur; Bennett, Fred L; Springer, Frederick S

2003-06-01

Animal and management factors associated with first service conception in nulliparous dairy heifers were determined in 601 Holstein heifers from a dairy farm in north central Florida. Animal data collected included body weight, height at the withers and tail head, body condition score at 6 months of age and just prior to first artificial insemination (AI), and pelvimetry measurements taken just prior to first AI. Management data included season of first AI, inseminator, service sire, method of estrus detection, whether the estrus of first insemination was induced using prostaglandin F(2alpha) (PGF(2alpha)), and whether the heifer received a modified live virus (MLV) vaccine within 21 days of first insemination. Data were analyzed using multivariable logistic regression. Heifers inseminated in the summer were more than four times less likely to become pregnant to first insemination than heifers bred during the rest of the year (odds ratio (OR)=0.24; 95% CI=0.14, 0.41). Using secondary signs for estrus detection instead of standing estrus resulted in significantly reduced odds of conception to first service (OR=0.37; 95% CI 0.13, 1.02). Also, heifers inseminated at estrus induced by PGF(2alpha) were approximately one-third less likely to conceive than those heifers inseminated to a naturally occurring estrus (OR=0.66; 95% CI 0.46, 0.95). An interaction between pelvic size and breeding season was found indicating that large pelvic size had a significant positive effect on fertility in the summer, but was not associated with conception to first service in the winter.

Low-dose natural prostaglandin F2α (dinoprost) at timed insemination improves conception rate in dairy cattle.

PubMed

Ambrose, Divakar J; Gobikrushanth, Mohanathas; Zuidhof, Sjoert; Kastelic, John P

2015-03-01

The primary objective was to determine if low doses of PGF2α (dinoprost) given intramuscularly (im) concurrent with timed artificial insemination (TAI) would improve conception rates in dairy cattle. A secondary objective was to determine if body condition score (BCS) and parity would influence conception rates, either independently or in interaction with PGF2α treatment. In experiment I, 307 lactating Holstein cows were randomly assigned to receive either 5-mg PGF2α im (PGF2α treated, n = 154) or 0-mg PGF2α (control, n = 153) at TAI (Day 0). Blood samples were obtained on Days -10, -3, 0, and 7 to determine plasma progesterone (P4) concentrations. Pregnancy was confirmed 30 to 32 days after insemination by transrectal ultrasonography. In experiment II, 451 cows were randomly assigned to receive either 10-mg PGF2α im (PGF2α treated, n = 226) or 0-mg PGF2α (control, n = 225) at TAI, and pregnancy was confirmed 45 to 50 days after TAI by palpation per rectum. Pregnancy data were analyzed by CATMOD (SAS). In experiment I, PGF2α treatment, BCS, and parity did not affect conception rate (35.7% vs. 37.0% for PGF2α treated vs. control; P > 0.05). However, in experiment II, conception rates were higher in cows given 10-mg PGF2α than those in control cows (45.8% vs. 36.0%; P < 0.05), in cows with high BCS than in cows with low BCS (52.1% vs. 30.4%; P < 0.01), and in primiparous than in multiparous cows (47.6% vs. 34.4%; P < 0.01), but their interaction with PGF2α treatment did not affect conception rates. In summary, 5 mg of PGF2α given im concurrent with TAI failed to enhance conception rate in lactating dairy cows, whereas 10 mg of PGF2α significantly increased conception rate. Copyright © 2015 Elsevier Inc. All rights reserved.

Luteinizing hormone induces ovulation via tumor necrosis factor α-dependent increases in prostaglandin F2α in a nonmammalian vertebrate

PubMed Central

Crespo, Diego; Goetz, Frederick W.; Planas, Josep V.

2015-01-01

Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. The pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin (PG) F2α (PGF2α) are involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH is not well established. Here we show that Lh induces PGF2α synthesis through its stimulation of Tnfα production in trout, a primitive teleost fish. Recombinant trout Tnfα (rTnfα) and PGF2α recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfα secretion or PG synthesis and all actions of rTnfα are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfα–dependent increase in PGF2α production is necessary for the pro-ovulatory actions of Lh. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility. PMID:26374476

Effects of carnitine and its congeners on eicosanoid discharge from rat cells: implications for release of TNFα

PubMed Central

Elliott, Graham R.; Pruimboom, Wanda M.; Zijlstra, Freek J.; Bonta, Iván L.

1993-01-01

THE acyl carrier coenzyme A (CoA) is involved in fatty acid metabolism. The carnitine/CoA ratio is of particular importance in regulating the transport of long-chain fatty acids into mitochondria for oxidation. Also CoA has a role in the formation and breakdown of products from both the cyclooxygenase and lipoxygenase pathways of the precursor arachidonic acid. In the present study the effect of 4 days feeding of 300 mg/kg/day of L-carnitine, acetyl Lcarnitine and propionyl L-carnitine on the basal and calcium ionophore (A23187) stimulated release of arachidonic acid metabolites from rat carrageenin elicited peritoneal cells was investigated. There were two series of experiments carried out. In the first, the harvested peritoneal cell population consisted of less than 90% macrophages and additional polymorphonuclear (PMN) leucocytes. The basal release of prostaglandin E2 (PGE2), 6-ketoprostaglandin F1α (6-keto-PGF1α) and leukotriene B4 (LTB4) was stimulated by all treatments. The A23187 stimulated release of 6-keto-PGF1α and LTB4 was increased by all three compounds. The 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 ratios were increased by carnitine treatment. These results suggested that carnitine could modify the macrophage component of an inflammatory site in vivo. In the second series of experiments the harvested cell population was highly purified (>95% macrophages) and none of the compounds fed to the rats caused a change of either eicosanoid or TNFα formation. Moreover the 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 ratios were not enhanced by any of the compounds tested. It is conceivable that in the first series the increased ratios 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 reflected the effect of carnitine or its congeners on PMN leucocytes rather than on macrophages. PMID:18475573

Sodium molybdate prevents hypertension and vascular prostanoid imbalance in fructose-overloaded rats.

PubMed

Peredo, H A; Andrade, V; Donoso, A S; Lee, H J; Puyó, A M

2013-10-01

(1) Fructose (F) overload produces elevated blood pressure (BP), hyperglycaemia, hypertriglyceridemia and insulin resistance, resembling human metabolic syndrome. Previously, we found altered vascular prostanoid (PR) production in this model. (2) Sodium molybdate (Mo), as well as sodium tungstate, causes insulin-like effects and normalizes plasma glucose levels in streptozotocin-treated diabetic rats. We studied the effects of Mo on BP, metabolic parameters and release of PR from the mesenteric vascular bed (MVB) in F-overloaded rats. (3) Four groups of male Sprague-Dawley rats were analysed: Control, tap water to drink; F, F solution 10% W/V to drink; CMo, Mo 100 mg kg day(-1) and FMo, both treatments. After 9 weeks, the animals were killed and MVBs removed and the released PRs measured. (4) F increased BP, glycemia, triglyceridemia and insulinemia. Mo treatment prevented the increases in BP and glycemia, but did not modify triglyceridemia or insulinemia. In addition, Mo decreased BP in controls. (5) Prostaglandins (PG) F2 alpha and E2, PG 6-ketoF1 alpha and thromboxane (TX) B2 , as well as inactive metabolites of prostacyclin (PGI2 ) and TXA2 were detected. F decreased the production of vasodilator PRs PGI2 and PGE2 in MVB. Mo prevented these alterations and increased PGE2 in controls. Vasoconstrict or PRs PGF2 alpha and TXA2 release was not modified. (6) Mo treatment, beyond its known lowering effect on glycemia, prevents the reduction in the vascular release of vasodilator PR observed in this model. This could be one of the mechanisms by which Mo avoids the increase in BP caused by F overload in the rat. © 2013 John Wiley & Sons Ltd.

Synergistic suppression of early phase of adipogenesis by microsomal PGE synthase-1 (PTGES1)-produced PGE2 and aldo-keto reductase 1B3-produced PGF2α.

PubMed

Fujimori, Ko; Yano, Mutsumi; Ueno, Toshiyuki

2012-01-01

We recently reported that aldo-keto reductase 1B3-produced prostaglandin (PG) F(2α) suppressed the early phase of adipogenesis. PGE(2) is also known to suppress adipogenesis. In this study, we found that microsomal PGE(2) synthase (PGES)-1 (mPGES-1; PTGES1) acted as the PGES in adipocytes and that PGE(2) and PGF(2α) synergistically suppressed the early phase of adipogenesis. PGE(2) production was detected in preadipocytes and transiently enhanced at 3 h after the initiation of adipogenesis of mouse adipocytic 3T3-L1 cells, followed by a quick decrease; and its production profile was similar to the expression of the cyclooxygenase-2 (PTGS2) gene. When 3T3-L1 cells were transfected with siRNAs for any one of the three major PTGESs, i.e., PTGES1, PTGES2 (mPGES-2), and PTGES3 (cytosolic PGES), only PTGES1 siRNA suppressed PGE(2) production and enhanced the expression of adipogenic genes. AE1-329, a PTGER4 (EP4) receptor agonist, increased the expression of the Ptgs2 gene with a peak at 1 h after the initiation of adipogenesis. PGE(2)-mediated enhancement of the PTGS2 expression was suppressed by the co-treatment with L-161982, a PTGER4 receptor antagonist. Moreover, AE1-329 enhanced the expression of the Ptgs2 gene by binding of the cyclic AMP response element (CRE)-binding protein to the CRE of the Ptgs2 promoter; and its binding was suppressed by co-treatment with L-161982, which was demonstrated by promoter luciferase and chromatin immunoprecipitation assays. Furthermore, when 3T3-L1 cells were caused to differentiate into adipocytes in medium containing both PGE(2) and PGF(2α), the expression of the adipogenic genes and the intracellular triglyceride level were decreased to a greater extent than in medium containing either of them, revealing that PGE(2) and PGF(2α) independently suppressed adipogenesis. These results indicate that PGE(2) was synthesized by PTGES1 in adipocytes and synergistically suppressed the early phase of adipogenesis of 3T3-L1 cells in cooperation with PGF(2α) through receptor-mediated activation of PTGS2 expression.

Synergistic Suppression of Early Phase of Adipogenesis by Microsomal PGE Synthase-1 (PTGES1)-Produced PGE2 and Aldo-Keto Reductase 1B3-Produced PGF2α

PubMed Central

Fujimori, Ko; Yano, Mutsumi; Ueno, Toshiyuki

2012-01-01

We recently reported that aldo-keto reductase 1B3-produced prostaglandin (PG) F2α suppressed the early phase of adipogenesis. PGE2 is also known to suppress adipogenesis. In this study, we found that microsomal PGE2 synthase (PGES)-1 (mPGES-1; PTGES1) acted as the PGES in adipocytes and that PGE2 and PGF2α synergistically suppressed the early phase of adipogenesis. PGE2 production was detected in preadipocytes and transiently enhanced at 3 h after the initiation of adipogenesis of mouse adipocytic 3T3-L1 cells, followed by a quick decrease; and its production profile was similar to the expression of the cyclooxygenase-2 (PTGS2) gene. When 3T3-L1 cells were transfected with siRNAs for any one of the three major PTGESs, i.e., PTGES1, PTGES2 (mPGES-2), and PTGES3 (cytosolic PGES), only PTGES1 siRNA suppressed PGE2 production and enhanced the expression of adipogenic genes. AE1-329, a PTGER4 (EP4) receptor agonist, increased the expression of the Ptgs2 gene with a peak at 1 h after the initiation of adipogenesis. PGE2-mediated enhancement of the PTGS2 expression was suppressed by the co-treatment with L-161982, a PTGER4 receptor antagonist. Moreover, AE1-329 enhanced the expression of the Ptgs2 gene by binding of the cyclic AMP response element (CRE)-binding protein to the CRE of the Ptgs2 promoter; and its binding was suppressed by co-treatment with L-161982, which was demonstrated by promoter luciferase and chromatin immunoprecipitation assays. Furthermore, when 3T3-L1 cells were caused to differentiate into adipocytes in medium containing both PGE2 and PGF2α, the expression of the adipogenic genes and the intracellular triglyceride level were decreased to a greater extent than in medium containing either of them, revealing that PGE2 and PGF2α independently suppressed adipogenesis. These results indicate that PGE2 was synthesized by PTGES1 in adipocytes and synergistically suppressed the early phase of adipogenesis of 3T3-L1 cells in cooperation with PGF2α through receptor-mediated activation of PTGS2 expression. PMID:22970288

Generation of human endometrial knockout cell lines with the CRISPR/Cas9 system confirms the prostaglandin F2α synthase activity of aldo-ketoreductase 1B1.

PubMed

Lacroix Pépin, Nicolas; Chapdelaine, Pierre; Rodriguez, Yoima; Tremblay, Jacques-P; Fortier, Michel A

2014-07-01

Prostaglandins (PGs) are important regulators of female reproductive function. The primary PGs produced in the endometrium are PGE2 and PGF2α. Relatively little is known about the biosynthetic pathways leading to the formation of PGF2α. We have described the role of aldo-ketoreductase (AKR)1B1 in increased PGF2α production by human endometrial cells following stimulation with interleukin-1β (IL-1β). However, alternate PGF synthases are expressed concurrently in endometrial cells. A definite proof of the role of AKR1B1 would require gene knockout; unfortunately, this gene has no direct equivalent in the mouse. Recently, an efficient genome-editing technology using RNA-guided DNase Cas9 and the clustered regularly interspaced short palindromic repeats (CRISPR) system has been developed. We have adapted this approach to knockout AKR1B1 gene expression in human endometrial cell lines. One clone (16-2) of stromal origin generated by the CRISPR/Cas9 system exhibited a complete loss of AKR1B1 protein and mRNA expression, whereas other clones presented with partial edition. The present report focuses on the characterization of clone 16-2 exhibiting deletion of 68 and 2 nucleotides, respectively, on each of the alleles. Cells from this clone lost their ability to produce PGF2α but maintained their original stromal cell (human endometrial stromal cells-2) phenotype including the capacity to decidualize in the presence of progesterone (medroxyprogesterone acetate) and 8-bromo-cAMP. Knockout cells also maintained their ability to increase PGE2 production in response to IL-1β. In summary, we demonstrate that the new genome editing CRISPR/Cas9 system can be used in human cells to generate stable knockout cell line models. Our results suggest that genome editing of human cell lines can be used to complement mouse KO models to validate the function of genes in differentiated tissues and cells. Our results also confirm that AKR1B1 is involved in the synthesis of PGF2α. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characterization of endocrine events during the periestrous period in sheep after estrous synchronization with controlled internal drug release (CIDR) device.

PubMed

Van Cleeff, J; Karsch, F J; Padmanabhan, V

1998-01-01

The Controlled Internal Drug Releasing (CIDR) device is an intravaginal pessary containing progesterone (P4) designed for synchronizing estrus in ruminants. To date, there has been little information available on the timing, duration, and quality of the follicular phase after CIDR removal and how those characteristics compare with natural periovulatory endocrine events. The present communication relates the results of methods we used to characterize the endocrine events that followed CIDR synchronization. Breeding-season ewes were given an injection (10 mg) of Lutalyse (PGF2 alpha), and then studied during three consecutive estrous cycles, beginning in the luteal phase after the estrus induced by PGF2 alpha. Cycle 1 estrus was synchronized with 1 CIDR (Type G) inserted for 8 d beginning 10 d after PGF2 alpha. Cycles 2 and 3 were synchronized with two CIDRs for 8 d beginning 10 d after previous CIDR removal. Cycle 1 estrous behavior and serum gonadotropins showed a follicular phase (the interval from CIDR withdrawal to gonadotropin surge [surge] peak) of 38.2 +/- 1.5 hr. Two CIDRs lengthened the interval to 46.2 +/- 1.5 hr (P < 0.0001). At CIDR removal, circulating P4 concentrations were higher in ewes treated with two CIDRs (5.1 +/- 0.3 and 6.4 +/- 0.4 ng/mL in Cycles 2 and 3 vs. 2.7 +/- 0.3 ng/mL in Cycle 1), whereas estradiol concentrations were higher in the 1 CIDR cycle (3.3 +/- 0.5 pg/mL in Cycle 1 vs. 0.5 +/- 0.1, and 0.7 +/- 0.2 pg/mL in Cycles 2 and 3), suggesting that the lower levels of P4 achieved with one CIDR was not sufficient to arrest follicular development. There were no differences in any other endocrine variable. Both one and two CIDR synchronization concentrated surges within a 24-hr period in 92% of the ewes in Cycles 1 and 2. Cycles 3 ewes were euthanized at estimated luteal, early follicular, late follicular, LH surge, and secondary FSH rise timepoints. Endocrine data and ovaries showed that 88% of the ewes synchronized with two CIDRs were in the predicted stage of the estrous cycle. These data demonstrate that the CIDR device applied during the luteal phase effectively synchronizes estrus and results in a CIDR removal-to-surge interval of similar length to a natural follicular phase.

Modulation of JB6 Mouse Epidermal Cell Transformation Response by the Prostaglandin F2 Alpha Receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, Thomas J.; Markillie, Lye MENG.; Chrisler, William B.

2002-12-01

Prostaglandin F2a (PGF2a) has been associated with the modulation of clonal selection processes in the mouse skin model of carcinogenesis. We have investigated whether JB6 mouse epidermal cells express a functional PGF2a receptor (FP) coupled to the regulation of anchorage-dependent and -independent growth. Treatment of JB6 cells with a FP receptor ligand (fluprostenol) potently (pM-nM) increased anchorage-dependent and -independent growth, as determined by a battery of in vitro assays. Treatment of JB6 cells with PGF2a and fluprostenol increased inositol phospholipid accumulation and extracellular signal regulated kinase (ERK) activity, consistent with FP receptor-related signaling. FP receptor mRNA was detected by reversemore » transcription-polymerase chain reaction and a radiolabel binding assay determined the average specific [3H]PGF2a binding to be 8.25 + 0.95 fmol/mg protein. Treatment of cells with fluprostenol as a single exposure resulted in a significant increase in anchorage-dependent and -independent growth in media containing low (0.1-0.5%), but not high (5%) concentrations of fetal bovine serum (FBS). In contrast, treatment of cells with fluprostenol at two day intervals resulted in a more robust growth response under anchorage-dependent conditions only in media containing low FBS concentrations; and under anchorage-independent conditions only in media containing high FBS concentrations. ERK activation and colony size were increased by cotreatment of JB6 cells with EGF and fluprostenol to a greater extent than either treatment alone, while the cotreatment effect on colony number appeared to be simply additive. In summary, FBS concentration and signal oscillation exert pronounced effects on the biological response to a FP receptor agonist. The data raise the possibility that the FP receptor may independently contribute to clonal selection processes, but may play a more important role as a response modifier.« less

Circulating progesterone dynamics after intravaginal instillation of prostaglandin-F2α to lactating dairy cows.

PubMed

Wijma, R; Stangaferro, M L; Giordano, J O

2016-06-01

Our objectives were to evaluate circulating progesterone (P4) concentration dynamics and test the feasibility of inducing luteal regression after intravaginal (IVG) instillation of the PGF2α analogue dinoprost (PGF) in lactating dairy cows. In two experiments, cows were synchronized using the Ovsynch protocol to induce the formation of a corpus luteum (CL). Cows with at least one functional (P4 ≥1 ng/mL) CL ≥15 mm 7.5 days after Ovsynch remained in the studies. In experiment 1, cows (n = 31) were stratified by parity group and received 5 mL of saline IVG (SAL-IVG, n = 6), 25 mg of PGF intramuscular (IM) (PGF25-IM, n = 7), 25 mg of PGF IVG (PGF25-IVG, n = 6), 50 mg of PGF IVG (PGF50-IVG, n = 6), and 125 mg of PGF IVG (PGF125-IVG, n = 6). Experiment 2 was conducted to test the hypothesis that IVG instillation of two 25 mg doses of PGF 12 hours apart would be more effective than a 25- or 50-mg dose in a single application. Cows (n = 32) were stratified by parity and received SAL-IVG (n = 7), PGF25-IM (n = 7), PGF25-IVG (n = 6), and PGF50-IVG (n = 6) as in experiment 1, whereas another group received two IVG instillations of 25 mg of PGF 12 hours apart (PGF25-2X-IVG, n = 6). Blood was collected at -1 hour, every 6 hours from 0 hour to 24 hours, and every 12 hours up to 96 hours after treatment (trt). In experiment 1, there was an effect of trt (P < 0.01), time (P < 0.001), and an interaction between trt and time on P4 concentrations (P < 0.001). All PGF-treated groups had lower (P < 0.05) concentrations of P4 than cows in the SAL-IVG group from 12 to 96 hours after trt. Although an initial decline in P4 concentrations was induced in all PGF-treated cows, some cows in the IVG-treated groups presented a rebound in plasma P4, indicating CL recovery. More cows in the PGF25-IVG and PGF125-IVG groups than in the PGF50-IVG and PGF25-IM groups presented CL recovery, suggesting that greater doses of PGF may not necessarily improve CL regression. In experiment 2, there was an effect of trt (P < 0.001), time (P < 0.001), and an interaction between trt and time on P4 concentrations (P < 0.001). All PGF-treated groups had lower (P < 0.05) P4 than the SAL-IVG group from 12 to 96 hours after trt. Cows in the PGF25-2X-IVG group had a P4 profile that was similar to that of cows in the PGF25-IM group and the lowest P4 concentrations after treatment among the IVG-treated groups, and all cows presented complete CL regression (defined as P4 <0.4 ng/mL). We conclude that CL regression can be induced through IVG instillation of PGF in lactating dairy cows and that instillation of two IVG doses of 25 mg of PGF 12 hours apart was the most effective strategy. Copyright © 2016 Elsevier Inc. All rights reserved.

Plasma 8-iso-Prostaglandin F2α, a possible prognostic marker in aneurysmal subarachnoid hemorrhage.

PubMed

Pan, De-Sheng; Yan, Min; Hassan, Muhammad; Fang, Ze-Bin; Chen, Man-Tao

2017-06-01

8-iso-Prostaglandin F2α (8-iso-PGF2α) is a potential biomarker of oxidative stress. This study clarified whether plasma 8-iso-PGF2α concentrations were affected and its underlying relevance to prognosis in aneurysmal subarachnoid hemorrhage (aSAH). In this prospective, observational study, a total of 170 controls and 170 aSAH patients were enrolled. Plasma 8-iso-PGF2α concentrations were detected using an ELISA. Severity was assessed by World Federation of Neurological Surgeons (WFNS) scale and modified Fisher grading scale. Clinical outcomes included 6-month mortality and poor outcome referred to as Glasgow outcome scale score of 1-3. As compared to controls, admission plasma 8-iso-PGF2α concentrations were significantly enhanced. Increased concentrations of plasma 8-iso-PGF2α correlated with WFNS scores and modified Fisher scores. 8-iso-PGF2α in plasma was an independent predictor for clinical outcomes. Under ROC curve, the predictive values of 8-iso-PGF2α concentrations resembled those of WFNS scores and modified Fisher scores for clinical outcomes. An elevation in plasma 8-iso-PGF2α concentrations is associated with the severity and poor outcome after aSAH, substantializing 8-iso-PGF2α as a potential prognostic biomarker of aSAH. Copyright © 2017. Published by Elsevier B.V.

Blood and urine 8-iso-PGF2α levels in babies of different gestational ages.

PubMed

Li, Sitao; Hao, Hu; Zhou, Ping; Gao, Ping Ming; Xiao, Xin

2014-01-01

We measured cord blood and urine 8-iso-prostaglandin F2α (8-iso-PGF2α) levels in babies of different gestational ages to determine lipid peroxidation status. Babies at gestational ages of 28-43 weeks were divided into group A (28-32 weeks), group B (33-36 weeks), group C (37-41 weeks), and group D (42-43 weeks). 8-iso-PGF2α in umbilical cord blood (UCB) at birth and urine at 6 hours after birth was and tested by ELISA. UCB and urine 8-iso-PGF2α levels in group C were 130.09 ± 31.73 pg/ml and 27.14 ± 6.73 pg/ml, respectively. UCB 8-iso-PGF2α levels in group A and B were 188.42 ± 59.34 pg/ml and 189.37 ± 68.46 pg/ml, and urine 8-iso-PGF2α were 32.14 ± 7.32 pg/ml and 30.46 ± 8.83 pg/ml, respectively. Blood and urine 8-iso-PGF2α levels in group D (post-term) were 252.01 ± 46.42 pg/ml and 44.00 ± 8.50 pg/ml. For all babies, UCB and urine iso-PGF2α levels were significantly correlated (r = 0.65, P < 0.01). We established blood and urine iso-PGF2α levels in normal full-term babies. Urine 8-iso-PGF2α levels may reflect the extent of lipid peroxidation in babies. In pre-term and post-term babies, there was evidence for increased lipid peroxidation.

Canine placenta: a source of prepartal prostaglandins during normal and antiprogestin-induced parturition.

PubMed

Kowalewski, Mariusz Pawel; Beceriklisoy, Hakki Bülent; Pfarrer, Christiane; Aslan, Selim; Kindahl, Hans; Kücükaslan, Ibrahim; Hoffmann, Bernd

2010-03-01

Expression of cyclooxygenase 2 (COX2, now known as PTGS2), prostaglandin E2 synthase (PTGES, PGES), and prostaglandin F2alpha synthase (PGFS), of the respective receptors PTGFR (FP), PTGER2 (EP2), and PTGER4 (EP4) and of the progesterone receptor (PGR, PR) was assessed by real-time PCR, immunohistochemistry (IHC), or in situ hybridization (ISH) in utero/placental tissue samples collected from three to five bitches on days 8-12 (pre-implantation), 18-25 (post-implantation), and 35-40 (mid-gestation) of pregnancy and during the prepartal luteolysis. Additionally, ten mid-pregnant bitches were treated with the antiprogestin aglepristone (10 mg/kg bw (2x/24 h)); ovariohysterectomy was 24 and 72 h after the second treatment. Plasma progesterone and 15-ketodihydro-PGF2alpha (PGFM) concentrations were determined by RIA. Expression of the PGR was highest before implantation and primarily located to the endometrium; expression in the placenta was restricted to the decidual cells. PTGS2 was constantly low expressed until mid-gestation; a strong upregulation occurred at prepartal luteolysis concomitant with an increase in PGFM. PGFS was upregulated after implantation and significantly elevated through early and mid-gestation. PTGES showed a gradual increase and a strong prepartal upregulation. PTGFR, PTGER2, and PTGER4 were downregulated after implantation; a gradual upregulation of PTGFR and PTGER2 occurred towards parturition. ISH and IHC co-localized PGFS, PTGFR, PTGES, and PTGS2 in the trophoblast and endometrium. The changes following application of aglepristone were in the same direction as those observed from mid-gestation to prepartal luteolysis. These data suggest that the prepartal increase of PGF2alpha results from a strong upregulation of PTGS2 in the fetal trophoblast with the withdrawal of progesterone having a signalling function and the decidual cells playing a key role in the underlying cell-to-cell crosstalk.

Contribution of vasoactive eicosanoids and nitric oxide production to the effect of selective cyclooxygenase-2 inhibitor, NS-398, on endotoxin-induced hypotension in rats.

PubMed

Tunctan, Bahar; Korkmaz, Belma; Cuez, Tuba; Kemal Buharalioglu, C; Sahan-Firat, Seyhan; Falck, John; Malik, Kafait U

2010-11-01

Our previous studies with the use of non-selective cyclooxygenase (COX) inhibitor, indomethacin, demonstrated that prostanoids produced during endotoxaemia increase inducible nitric oxide synthase (iNOS) protein expression and nitric oxide synthesis, and decrease cyctochrome P450 (CYP) 4A1 protein expression and CYP 4A activity. The results suggest that dual inhibition of iNOS and COX by indomethacin restores blood pressure presumably due to increased production of 20-hydroxyeicosatetraenoic acid (20-HETE) derived from CYP 4A in endotoxaemic rats. The present study examined whether increased levels of vasoconstrictor eicosanoids, 20-HETE, prostaglandin F(2α) (PGF(2α) )and thromboxane A(2) (TxA(2) ), would contribute to the effect of selective COX-2 inhibition to prevent endotoxin (ET)-induced fall in blood pressure associated with an increase in the production of vasodilator prostanoids, prostaglandin I(2) (PGI(2) ) and prostaglandin E(2) (PGE(2) ) and nitric oxide synthesis. Mean arterial blood pressure fell by 31 mmHg and heart rate (HR) rose by 90 beats/min. in male Wistar rats treated with ET (10 mg/kg, i.p.). The fall in mean arterial pressure and increase in HR were associated with increased levels of 6-keto-prostaglandin F(1α) (6-keto-PGF(1α) ), PGE(2) , TxB(2) , and nitrite in the serum, kidney, heart, thoracic aorta and/or superior mesenteric artery. Systemic and renal 20-HETE and PGF(2α) levels were also decreased in endotoxaemic rats. These effects of ET were prevented by a selective COX-2 inhibitor, N-(2-cyclohexyloxy-4-nitrophenyl)methansulphonamide (10 mg/kg, i.p.), given 1 hr after injection of ET. These data suggest that an increase in 20-HETE and PGF(2α) levels associated with decreased production of PGI(2) , PGE(2) , and TxA(2) , and nitric oxide synthesis contributes to the effect of selective COX-2 inhibitor to prevent the hypotension during rat endotoxaemia. © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.

Influence of puberty and antral follicle count on calving day in crossbred beef heifers.

PubMed

McNeel, Anthony K; Cushman, Robert A

2015-10-15

Lifetime productivity and longevity are greater in beef cows that give birth early in their first calving season. The ability of heifers to conceive early in the breeding season is traditionally thought to be a function of pubertal status; however, recent evidence suggests that antral follicle count is positively associated with calving day in pubertal beef heifers. Additionally, there is evidence to suggest that the total number of ovarian follicles may alter response to hormonal synchronization protocols. The objectives of this study were to confirm the beneficial influence of antral follicle count on calving day in beef heifers and to determine whether response to PGF2α is associated with differences in antral follicle counts. A 2 × 2 factorial experiment was designed to investigate the interaction between calving period (early vs. late) and PGF2α (control vs. PGF) on calving day and antral follicle count in yearling beef heifers (n = 95). As intended, calving day was less in the early calving period compared to the late calving period (P < 0.01). There were no differences in calving day in response to treatment with PGF2α (P > 0.05). There was a significant interaction between calving period and PGF2α on age at first calving (P < 0.01), such that heifers treated with PGF2α that gave birth early were younger than heifers treated with saline that gave birth early. Calf weaning weights were greater in the early calving group than in the late calving group (P < 0.01). Heifers that gave birth in the early calving group possessed more antral follicles at prebreeding ultrasonographic examination than heifers that gave birth in the late calving group (P = 0.05). These findings confirm that antral follicle counts are associated with calving day in pubertal beef heifers. The use of antral follicle counts as a prebreeding phenotype provides additional utility to reproductive tract scoring for commercial production because of its association with calving day. As a prebreeding ovarian phenotype, antral follicle counts may hold additional applicability for organic beef producers looking to reduce the length of their calving season without increasing the total number of replacement heifers retained. Published by Elsevier Inc.

Independent and combined influence of AGTR1 variants and aerobic exercise on oxidative stress in hypertensives.

PubMed

Fenty-Stewart, Nicola; Park, Joon-Young; Roth, Stephen M; Hagberg, James M; Basu, Samar; Ferrell, Robert E; Brown, Michael D

2009-01-01

Abstract Angiotensin II (AngII), via the AngII type 1 receptor (AT(1)R), contributes to oxidative stress. Aerobic exercise training (AEXT) reduces the risk of cardiovascular (CV) disease, presumably by reducing the grade of oxidative stress. We investigated the independent and combined influence of the AGTR1 A1166C and -825 T/A polymorphisms on oxidative stress and plasma AngII responses to AEXT in pre- and stage 1 hypertensives. Urinary 8-iso-PGF(2alpha) significantly increased with AEXT (p=0.002); however, there were no significant changes in superoxide dismutase activity or AngII levels. There was a significant difference in the change in AngII levels with AEXT between A1166C genotype groups (p=0.04) resulting in a significant interactive effect of the A1166C polymorphism and AEXT on the change in AngII (p<0.05). Only the TT genotype group of the -825 T/A polymorphism had a significant reduction in plasma AngII (p=0.02). Risk allele analysis revealed a significant reduction in plasma AngII (p=0.04) and a significant increase in urinary 8-iso-PGF(2alpha) (p=0.01) with AEXT in individuals with two risk alleles only. Our findings suggest that variation in the AGTR1 gene is associated with differential changes in plasma AngII but not oxidative stress.

Peroxiredoxin 2 regulates PGF2α-induced corpus luteum regression in mice by inhibiting ROS-dependent JNK activation.

PubMed

Park, Sun-Ji; Kim, Jung-Hak; Kim, Tae-Shin; Lee, Sang-Rae; Park, Jeen-Woo; Lee, Seunghoon; Kim, Jin-Man; Lee, Dong-Seok

2017-07-01

Luteal regression is a natural and necessary event to regulate the reproductive process in all mammals. Prostaglandin F2α (PGF2α) is the main factor that causes functional and structural regression of the corpus luteum (CL). It is well known that PGF2α-mediated ROS generation is closely involved in luteal regression. Peroxiredoxin 2 (Prx2) as an antioxidant enzyme plays a protective role against oxidative stress-induced cell death. However, the effect of Prx2 on PGF2α-induced luteal regression has not been reported. Here, we investigated the role of Prx2 in functional and structural CL regression induced by PGF2α-mediated ROS using Prx2-deficient (-/-) mice. We found that PGF2α-induced ROS generation was significantly higher in Prx2-/- MEF cells compared with that in wild-type (WT) cells, which induced apoptosis by activating JNK-mediated apoptotic signaling pathway. Also, PGF2α treatment in the CL derived from Prx2-/- mice promoted the reduction of steroidogenic enzyme expression and the activation of JNK and caspase3. Compared to WT mice, serum progesterone levels and luteal expression of steroidogenic enzymes decreased more rapidly whereas JNK and caspase3 activations were significantly increased in Prx2-/- mice injected with PGF2α. However, the impaired steroidogenesis and PGF2α-induced JNK-dependent apoptosis were rescued by the addition of the antioxidant N-acetyl-L-cysteine (NAC). This is the first study to demonstrate that Prx2 deficiency ultimately accelerated the PGF2α-induced luteal regression through activation of the ROS-dependent JNK pathway. These findings suggest that Prx2 plays a crucial role in preventing accelerated luteal regression via inhibition of the ROS/JNK pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Boron deprivation alters rat behaviour and brain mineral composition differently when fish oil instead of safflower oil is the diet fat source.

PubMed

Nielsen, Forrest H; Penland, James G

2006-01-01

To determine whether boron deprivation affects rat behaviour and whether behavioural responses to boron deprivation are modified by differing amounts of dietary long-chain omega-3 fatty acids. Female rats were fed diets containing 0.1 mg (9 micromol)/kg boron in a factorial arrangement with dietary variables of supplemental boron at 0 and 3mg (278 micromol)/kg and fat sources of 75 g/kg safflower oil or 65 g/kg fish (menhaden) oil plus 10 g/kg linoleic acid. After 6 weeks, six females per treatment were bred. Dams and pups continued on their respective diets through gestation, lactation and after weaning. Between ages 6 and 20 weeks, behavioural tests were performed on 13-15 male offspring from three dams in each dietary treatment. The rats were euthanized at age 21 weeks for the collection of tissues and blood. At ages 6 and 19 weeks, auditory startle was evaluated with an acoustic startle system and avoidance behaviour was evaluated by using an elevated plus maze. At ages 7 and 20 weeks, spontaneous behaviour activity was evaluated with a photobeam activity system. A brightness discrimination test was performed on the rats between age 15 and 16 weeks. Brain mineral composition was determined by coupled argon plasma atomic emission spectroscopy. Plasma total glutathione was determined by HPLC and total cholesterol and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) were determined by using commercially available kits. Boron-deficient rats were less active than boron-adequate rats when fed safflower oil based on reduced number, distance and time of horizontal movements, front entries, margin distance and vertical breaks and jumps in the spontaneous activity evaluation. Feeding fish oil instead of safflower oil attenuated the activity response to boron deprivation. In the plus maze evaluation, the behavioural reactivity of the boron-deficient rats fed fish oil was noticeably different than the other three treatments. They made more entries into both open and closed arms and the center area and thus visited more locations. The boron-deficient rats fed fish oil also exhibited the lowest copper and zinc and highest boron concentrations in brain and the highest plasma glutathione concentration. Both boron deprivation and safflower oil increased plasma 8-iso-PGF2alpha. Both dietary boron and long-chain omega-3 fatty acids influence rat behaviour and brain composition and the influence of one these bioactive substances can be altered by changing the intake of the other. Brain mineral and plasma cholesterol, glutathione and 8-iso-PGF2alpha findings suggest that rat behaviour is affected by an interaction between boron and fish oil because both affect oxidative metabolism and act the cellular membrane level.

Estrous synchronization strategies to optimize beef heifer reproductive performance after reproductive tract scoring.

PubMed

Kasimanickam, Ramanathan K; Whittier, William D; Hall, John B; Kastelic, John P

2016-08-01

Three experiments comparing four estrous synchronization protocols were conducted to determine estrous expression rate and artificial insemination pregnancy rate (AI-PR) in heifers with a range (1-5) of reproductive tract scores (RTSs). At enrollment (Day 0), 1783 Angus cross beef heifers from six locations were given body condition score and RTS. The four protocols were: (1) HRTS-DPGF group-heifers with RTS 5 received prostaglandin F2α (PGF; Dinoprost 25 mg; im) on Days 0 and 14; (2) HRTS-CIDR-PGF group-heifers with RTS 5 received a CIDR (1.3-g progesterone) insert on Day 7, followed by CIDR removal and PGF on Day 14; (3) LRTS-CIDR-PGF group-heifers with RTS 4 or less received a CIDR insert on Day 7, followed by CIDR removal and PGF on Day 14; and (4) HRTS-Select-Synch group-heifers with RTS 5 received 100 μg of gonadorelin diacetate tetrahydrate (gonadotropin releasing homone; im) on Day 7 and PGF on Day 14. In all groups, heifers observed in estrus were artificially inseminated (within 120 hours after PGF) using the AM-PM rule. In Experiment 1, estrus expression rates were 82.2% (282/343) and 88.5% (184/208) for HRTS-DPGF and LRTS-CIDR-PGF, respectively (P < 0.05), whereas AI-PR were 51.3% (176/343) and 59.1% (123/208; P < 0.1). In Experiment 2, estrus expression rates were 79.6 (168/211), 86.9 (186/214) and 84.2% (176/209) for HRTS-DPGF, HRTS-CIDR-PGF, and LRTS-CIDR-PGF groups (P > 0.1) and AI-PR were 52.1 (110/211), 60.3 (129/214), and 58.4% (122/209; P > 0.05). In Experiment 3, estrus expression rates were 77.5 (131/169), 85.5 (142/166), and 83.3% (219/263) for HRTS-DPGF, HRTS-Select-Synch and LRTS-CIDR-PGF (P > 0.05) and AI-PR were 53.3 (90/169), 60.2 (100/166), and 58.6% (154/263; P > 0.1). Overall, estrus expression rates for HRTS-DPGF, HRTS-Select-Synch, LRTS-CIDR-PGF, and HRTS-CIDR-PGF groups were 80.4 (581/723), 85.5 (142/166), 85.1 (579/680), and 86.9% (186/214), respectively; higher for heifers in LRTS-CIDR-PGF and HRTS-CIDR-PGF groups compared to heifers in HRTS-DPGF group (P < 0.05). The AI-PR for heifers in HRTS-DPGF was lower (52.0 [376/723]) compared with HRTS-Select-Synch (60.2 [100/166]), LRTS-CIDR-PGF (58.7 [399/680]), and HRTS-CIDR-PGF (60.3 [129/214]); P < 0.05). In conclusion, heifers achieved greater AI-PR after CIDR-PGF or HRTS-Select-Synch estrous synchronization protocols. Even though acceptable AI-PRs achieved in heifers with RTS 5 that were subjected to a double PGF protocol, the reproductive performance was reduced compared with other protocols used in this study. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of polyunsaturated fatty acids and prostaglandins on oocyte maturation in a marine teleost, the European sea bass (Dicentrarchus labrax).

PubMed

Sorbera, L A; Asturiano, J F; Carrillo, M; Zanuy, S

2001-01-01

The effects of the polyunsaturated fatty acids (PUFAs), arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and prostaglandins (PGs) on oocyte maturation were investigated in a marine teleost, the sea bass (Dicentrarchus labrax). Follicle-enclosed postvitellogenic, preovulatory oocytes were cultured in vitro and maturation was verified by assessing volume increase, lipid droplet coalescence, yolk clarification, and germinal vesicle migration and breakdown. Human chorionic gonadotropin was administered as the maturation-inducing gonadotropin (GTH) and was capable of inducing maturation in a time- and dose-dependent manner. Free AA induced maturation in a dose- and time-dependent manner and enhanced GTH-induced maturation, while EPA, DHA, and oleic acid were ineffective. Maturation induced by GTH was significantly suppressed by a phospholipase A(2) blocker, suggesting that mobilization of AA was involved in GTH-induced maturation. Moreover, EPA and DHA exhibited a significant, dose-dependent attenuation of GTH-induced maturation. Maturation induced by GTH was inhibited in the presence of a cyclooxygenase inhibitor, indomethacin, and this inhibition was reversed by addition of AA, PGE(2), or PGF(2alpha). PGE(2) and PGF(2alpha) alone were both effective stimulators of maturation, while PGE(1) and PGE(3) were ineffective. The effect of PUFAs on oocyte maturation in vitro were corroborated with studies in vivo. Oocytes were obtained from females fed a commercial, PUFA-enriched diet (RD) and maturational behavior was compared with oocytes from females fed a natural diet (ND) with a higher EPA content and n-3:n-6 ratio. Although no significant difference was observed in the rate of spontaneous oocyte maturation, a higher percentage of GTH-induced maturation and lower percentage of atresia were observed in RD oocytes. Moreover, while basal PGE production from oocytes from both groups was the same, RD oocytes produced significantly higher levels of PGE in the presence of hCG. The results from this study provide evidence for the participation of AA metabolism in GTH-induced oocyte maturation, and suggest that other PUFAs and PGs may play important roles in the induction of maturation in a marine teleost.

Postoperative plasma 8-iso-prostaglandin F2α levels are associated with delirium and cognitive dysfunction in elderly patients after hip fracture surgery.

PubMed

Zheng, Yuan-Bo; Ruan, Guo-Mo; Fu, Jia-Xing; Su, Zhong-Liang; Cheng, Peng; Lu, Jian-Zuo

2016-04-01

Oxidative stress may be involved in occurrence of postoperative delirium (POD) and cognitive dysfunction (POCD). 8-iso-Prostaglandin F2α (8-iso-PGF2α), an isoprostane derived from arachidonic acid via lipid peroxidation, is considered a gold standard for measuring oxidative stress. The present study aimed to investigate the ability of postoperative plasma 8-iso-PGF2α levels to predict POD and POCD in elderly patients undergoing hip fracture surgery. Postoperative plasma 8-iso-PGF2α levels of 182 patients were measured by an enzyme-linked immunosorbent assay. We assessed the relationships between plasma 8-iso-PGF2α levels and the risk of POD and POCD using a multivariate analysis. Plasma 8-iso-PGF2α levels and age were identified as the independent predictors for POD and POCD. Based on areas under receiver operating characteristic curve, the predictive values of 8-iso-PGF2α were obviously higher than those of age for POD and POCD. In a combined logistic-regression model, 8-iso-PGF2α significantly enhanced the areas under curve of age for prediction of POD and POCD. Postoperative plasma 8-iso-PGF2α levels may have the potential to predict POD and POCD in elder patients undergoing hip fracture surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

Oestrus synchronisation and superovulation alter the production and biochemical constituents of ovine cervicovaginal mucus.

PubMed

Maddison, Jessie W; Rickard, Jessica P; Mooney, Ethan; Bernecic, Naomi C; Soleilhavoup, Clement; Tsikis, Guillaume; Druart, Xavier; Leahy, Tamara; de Graaf, Simon P

2016-09-01

Controlled breeding programmes utilising exogenous hormones are common in the Australian sheep industry, however the effects of such programmes on cervicovaginal mucus properties are lacking. As such, the aim of this study was to investigate cervicovaginal (CV) mucus from naturally cycling (NAT), progesterone synchronised (P4), prostaglandin synchronised (PGF2α), and superovulated (SOV) Merino ewes. Experiment 1; volume, colour, spinnbarkeit, chemical profile and protein concentration of mucus (NAT, P4, PGF2α and SOV; n=5 ewes/treatment) during the follicular (5 d) and luteal phases (8 d) was investigated. Experiment 2; in vivo mucus pH and in vitro mucus penetration by frozen-thawed spermatozoa (NAT, P4 and SOV; n=11 ewes/treatment) was investigated over oestrus (2 d) and the mid-luteal phase (pH only, 2 d). Oestrus mucus was more abundant, clearer in colour and less proteinaceous than luteal phase mucus (p<0.05). SOV increased mucus production and protein concentration (p<0.05) while PGF2α reduced mucus volume (p<0.05). Mucus pH (oestrus 6.2-6.5), chemical profile and mucus penetration by sperm were unchanged (p>0.05). Results indicate that exogenous hormones used for controlled breeding affect cervicovaginal mucus production, but few other tested characteristics. Further research is required to explain fertility differences between synchronised and naturally cycling animals following cervical AI. Copyright © 2016 Elsevier B.V. All rights reserved.

Modifications of the G6G timed-AI protocol improved pregnancy per AI and reduced pregnancy loss in lactating dairy cows.

PubMed

Heidari, F; Dirandeh, E; Ansari Pirsaraei, Z; Colazo, M G

2017-11-01

In dairy cows, subjected to a G6G protocol, objectives were to determine effects of (1) extending the interval from prostaglandin F2α (PGF2α) to gonadotropin-releasing hormone (GnRH) during presynchronization; and (2) adding a second PGF2α treatment before artificial insemination (AI), on ovarian response, plasma progesterone (P4) concentrations and pregnancy per AI (P/AI). In a 2×2 factorial design, lactating cows were randomly assigned to one of four timed AI (TAI) protocols: (1) G6G (n=149), one injection of PGF2α, GnRH 2 days later and a 7-day Ovsynch (GnRH, 7 days, PGF2α, 56 h, GnRH, 16 h, TAI) was initiated 6 days later; (2) G6GP (n=144), an additional PGF2α treatment (24 h after the first) during Ovsynch of the G6G protocol; (3) MG6G, one injection of PGF2α, GnRH 4 days later before initiation of the G6G protocol; and (4) MG6GP, an additional PGF2α treatment (24 h after the first) during Ovsynch of the MG6G protocol. Blood samples were collected (subset of 200 cows) at first GnRH and PGF2α of the Ovsynch, and at TAI to measure P4. Ultrasound examinations were performed in a subset of 406 cows to evaluate ovarian response at various times of Ovsynch, and in all cattle to determine pregnancy status at 32 and 60 days after TAI. Extending the interval by 2 days between PGF2α and GnRH during presynchronization increased (P<0.01) ovulatory response to first GnRH of Ovsynch, circulating P4 during Ovsynch, and P/AI at 32 and 60 days after TAI. Adding a second PGF2α treatment before AI increased the proportion of cows with luteal regression (P=0.04), improved P/AI at 60 days after TAI (P=0.05), and reduced pregnancy loss between 30 and 60 days after TAI (P=0.04). In summary, extending the interval from PGF2α to GnRH during presynchronization increased response to first GnRH of Ovsynch and P4 concentrations during Ovsynch, whereas adding a second PGF2α treatment before AI enhanced luteal regression. Both modifications of the G6G protocol improved fertility in lactating dairy cows.

Luteal function, largest follicle, and fertility in postpartum dairy cows treated with 14dCIDR-PGF2α versus 2xPGF2α-Ovsynch for timed AI.

PubMed

Escalante, Rebecca C; Poock, Scott E; Lucy, Matthew C

2013-11-01

A method for timed artificial insemination (AI) that is used for beef cows, beef heifers, and dairy heifers employs progesterone-releasing inserts, such as the controlled internal drug release (CIDR; Zoetis, New York, NY, USA) that are left in place for 14 days. The 14-day CIDR treatment is a method of presynchronization that ensures that cattle are in the late luteal phase of the estrous cycle when PGF2α is administered before timed AI. The objective of this study was to test the effectiveness of the 14dCIDR-PGF2α program in postpartum dairy cows by comparing it with the traditional "Presynch-Ovsynch" (2xPGF2α-Ovsynch) program. The 14dCIDR-PGF2α cows (n = 132) were treated with a CIDR insert on Day 0 for 14 days. At 19 days after CIDR removal (Day 33), the cows were treated with a luteolytic dose of PGF2α, 56 hours later were treated with an ovulatory dose of GnRH (Day 35), and 16 hours later were inseminated. The 2xPGF2α-Ovsynch cows were treated with a luteolytic dose of PGF2α on Day 0 and again on Day 14. At 12 days after the second PGF2α treatment (Day 26), the cows were treated with GnRH. At 7 days after GnRH, the cows were treated with PGF2α (Day 33), then 56 hours later treated with GnRH (Day 35), and then 16 hours later were inseminated. There was no effect of treatment or treatment by parity interaction on pregnancies per AI (P/AI) when pregnancy diagnosis was performed on Day 32 (115/263; 43.7%) or Days 60 to 90 (99/263; 37.6%) after insemination. There was an effect of parity (P < 0.05) on P/AI because primiparous cows had lesser P/AI (35/98; 35.7%) than multiparous cows (80/165; 48.5%) on Day 32. Cows observed in estrus after the presynchronization step (within 5 days after CIDR removal or within 5 days after the second PGF2α treatment) had greater P/AI than those not observed in estrus (55/103; 53.4% vs. 60/160; 37.5%; observed vs. not observed; P < 0.01; d 32 pregnancy diagnosis). When progesterone data were examined in a subset of cows (n = 208), 55.3% of cows had a "prototypical" response to treatment (i.e., the cow had an estrous cycle that was synchronized by the presynchronization treatment and then the cow responded appropriately to the subsequent PGF2α and GnRH treatments before timed AI). Collectively, cows with a prototypical response to either treatment had 52.2% P/AI that was greater (P < 0.001) than the P/AI for cows that had a nonprototypical response (19%) (P/AI determined at 60-90 days of pregnancy). In conclusion, we did not detect a difference in P/AI when postpartum dairy cows were treated with 14dCIDR-PGF2α or 2xPGF2α-Ovsynch before timed AI. The primary limitation to the success of either program was the failure of the cow to respond appropriately to the sequence of treatments. Copyright © 2013 Elsevier Inc. All rights reserved.

Estradiol-17beta, prostaglandin E2 (PGE2), and the PGE2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium.

PubMed

Waclawik, Agnieszka; Jabbour, Henry N; Blitek, Agnieszka; Ziecik, Adam J

2009-08-01

Before implantation, the porcine endometrium and trophoblast synthesize elevated amounts of luteoprotective prostaglandin estradiol-17beta (E(2)) (PGE(2)). We hypothesized that embryo signal, E(2), and PGE(2) modulate expression of key enzymes in PG synthesis: PG-endoperoxide synthase-2 (PTGS2), microsomal PGE synthase (mPGES-1), PGF synthase (PGFS), and PG 9-ketoreductase (CBR1) as well as PGE(2) receptor (PTGER2 and -4) expression and signaling within the endometrium. We determined the site of action of PGE(2) in endometrium during the estrous cycle and pregnancy. Endometrial tissue explants obtained from gilts (n = 6) on d 11-12 of the estrous cycle were treated with vehicle (control), PGE(2) (100 nM), E(2) (1-100 nm), or phorbol 12-myristate 13-acetate (100 nm, positive control). E(2) increased PGE(2) secretion through elevating expression of mPGES-1 mRNA and PTGS2 and mPGES-1 protein in endometrial explants. By contrast, E(2) decreased PGFS and CBR1 protein expression. E(2) also stimulated PTGER2 but not PTGER4 protein content. PGE(2) enhanced mPGES-1 and PTGER2 mRNA as well as PTGS2, mPGES-1, and PTGER2 protein expression. PGE(2) had no effect on PGFS, CBR1, and PTGER4 expression and PGF(2alpha) release. Treatment of endometrial tissue with PGE(2) increased cAMP production. Cotreatment with PTGER2 antagonist (AH6809) but not PTGER4 antagonist (GW 627368X) inhibited significantly PGE(2)-mediated cAMP production. PTGER2 protein was localized in luminal and glandular epithelium and blood vessels of endometrium and was significantly up-regulated on d 11-12 of pregnancy. Our results suggest that E(2) prevents luteolysis through enzymatic modification of PG synthesis and that E(2), PGE(2), and endometrial PTGER2 are involved in a PGE(2) positive feedback loop in porcine endometrium.

The use of hormonal treatments to improve reproductive performance of anestrous beef cattle in tropical climates.

PubMed

Baruselli, P S; Reis, E L; Marques, M O; Nasser, L F; Bó, G A

2004-07-01

Most of the world's bovine herd is found in tropical regions. Bos indicus predominates, due to their adaptation to the climate and management conditions. Anestrous is the main factor that negatively affects reproductive performance of animals bred in these regions of the globe. Several factors affect postpartum anestrous, including suckling and maternal-offspring bond, and pre- and postpartum nutritional status. The short duration of estrus and the tendency to show estrus during the night, greatly affect the efficiency of artificial insemination (AI) programs in B. indicus cattle managed in tropical areas. Several restricted suckling or weaning procedures (temporary or permanent), and hormonal treatments have been used to induce ovulation and cyclicity in postpartum cows. Most hormonal treatments are based on progesterone/progestogen (P4) releasing devices associated with estradiol benzoate (EB), or a combination of GnRH/PGF(2alpha)/GnRH (Ovsynch). Treatments with GnRH/PGF(2alpha)/GnRH has presented inconsistent results, probably due to the variable number of cows in anestrous. Treatments using P4 devices and EB have resulted in apparently more consistent results than Ovsynch programs in B. indicus cattle; however, pregnancy rates are low in herds presenting high anestrous rates and moderate to low body condition. The addition of an eCG treatment at the time of device removal, which increased plasma progesterone concentrations and pregnancy rates in anestrous postpartum suckled B. indicus cows, may be useful to improve reproductive performance of beef cattle in tropical climates.

Nature of extracellular signal that triggers RhoA/ROCK activation for the basal internal anal sphincter tone in humans

PubMed Central

Singh, Jagmohan; Kumar, Sumit; Phillips, Benjamin

2015-01-01

The extracellular signal that triggers activation of rho-associated kinase (RhoA/ROCK), the major molecular determinant of basal internal anal sphincter (IAS) smooth muscle tone, is not known. Using human IAS tissues, we identified the presence of the biosynthetic machineries for angiotensin II (ANG II), thromboxane A2 (TXA2), and prostaglandin F2α (PGF2α). These end products of the renin-angiotensin system (RAS) (ANG II) and arachidonic acid (TXA2 and PGF2α) pathways and their effects in human IAS vs. rectal smooth muscle (RSM) were studied. A multipronged approach utilizing immunocytochemistry, Western blot analyses, and force measurements was implemented. Additionally, in a systematic analysis of the effects of respective inhibitors along different steps of biosynthesis and those of antagonists, their end products were evaluated either individually or in combination. To further describe the molecular mechanism for the IAS tone via these pathways, we monitored RhoA/ROCK activation and its signal transduction cascade. Data showed characteristically higher expression of biosynthetic machineries of RAS and AA pathways in the IAS compared with the RSM. Additionally, specific inhibition of the arachidonic acid (AA) pathway caused ∼80% decrease in the IAS tone, whereas that of RAS lead to ∼20% decrease. Signal transduction studies revealed that the end products of both AA and RAS pathways cause increase in the IAS tone via activation of RhoA/ROCK. Both AA and RAS (via the release of their end products TXA2, PGF2α, and ANG II, respectively), provide extracellular signals which activate RhoA/ROCK for the maintenance of the basal tone in human IAS. PMID:25882611

Simultaneous Analysis of Seven Biomarkers of Oxidative Damage to Lipids, Proteins, and DNA in Urine.

PubMed

Martinez, Maria P; Kannan, Kurunthachalam

2018-06-05

The determination of oxidative stress biomarkers (OSBs) is useful for the assessment of health status and progress of diseases in humans. Whereas previous methods for the determination of OSBs in urine were focused on a single marker, in this study, we present a method for simultaneous determination of biomarkers of oxidative damage to lipids, proteins, and DNA. 2,4-Dinitrophenylhydrazine (DNPH) derivatization followed by solid phase extraction (SPE) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) allowed the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG), o- o'-dityrosine (diY), malondialdehyde (MDA), and four F 2 -isoprostane isomers: 8-iso-prostaglandinF 2α (8-PGF 2α ), 11β-prostaglandinF 2α (11-PGF 2α ), 15( R)-prostaglandinF 2α (15-PGF 2α ), and 8-iso,15( R)-prostaglandinF 2α (8,15-PGF 2α ) in urine. Derivatization with DNPH and SPE was optimized to yield greater sensitivity and selectivity for the analysis of target chemicals. The limits of detection of target analytes in urine were below 30 pg mL -1 . The assay intra- and interday variability was below 16% of the relative standard deviation, and the recoveries of target chemicals spiked into synthetic urine were near 100%. The method was applied to the analysis of 21 real urine samples, and the analytes were found at a detection frequency of 85% for 8-PGF 2α and 15-PGF 2α , 71% for 11-PGF 2α , 81% for 8,15-PGF 2α , and 100% for diY, 8-OHdG, and MDA. This method offers simultaneous determination of multiple OSBs of different molecular origin in urine samples selectively with high accuracy and precision.

Vegetable production facility as a part of a closed life support system in a Russian Martian space flight scenario

NASA Astrophysics Data System (ADS)

Berkovich, Yu. A.; Smolyanina, S. O.; Krivobok, N. M.; Erokhin, A. N.; Agureev, A. N.; Shanturin, N. A.

2009-07-01

A Manned Mars Mission scenario had been developed in frame of the Project 1172 supported International Science & Technology Center in Moscow. The Mars transit vehicle (MTV) supposed to have a crew of 4-6 with Pilot Laboratory compartment volume of 185 m 3 and with inner diameter of 4.1 m. A vegetable production facility with power consumption up to 10 kW is being considered as a component of the life support system to supply crew members by fresh vegetables during the mission. Proposed design of conveyor-type plant growth facility (PGF) comprised of 4-modules. Each module has a cylindrical planting surface and spiral cylindrical LED assembly to provide a high specific productivity relative to utilized onboard resources. Each module has a growth chamber that will be from 0.7 m to 1.5 m in length, and a crop illuminated area from 1.7 m 2 to 4.0 m 2. Leafy crops (cabbage, lettuce, spinach, chard, etc.) have been selected for module 1, primarily because of the highest specific productivity per consumed resources. Dietitians have recommended also carrot crop for module 2, pepper for module 3 and tomato for module 4. The maximal total PGF light energy estimated as 1.16 kW and total power consumption as about 7 kW. The module 1 characteristics have been calculated using own experimental data, information from the best on ground plant growth experiments with artificial light were used to predict crop productivity and biomass composition in the another modules. 4-module PGF could produce nearly 0.32 kg per crew member per day of fresh edible biomass, which would be about 50% of recommended daily vegetable supplement. An average crop harvest index is estimated as 0.75. The MTV food system could be entirely closed in terms of vitamins C and A with help of the PGF. In addition the system could provide 10-25% of essential minerals and vitamins of group B, and about 20% of food fibers. The present state of plant growth technology allows formulating of requirements specification for the flight-qualified modules.

Effects of the estrous cycle, pregnancy and interferon tau on expression of cyclooxygenase two (COX-2) in ovine endometrium

PubMed Central

Kim, Seokwoon; Choi, Youngsok; Spencer, Thomas E; Bazer, Fuller W

2003-01-01

In sheep, the uterus produces luteolytic pulses of prostaglandin F2α (PGF) on Days 15 to 16 of estrous cycle to regress the corpus luteum (CL). These PGF pulses are produced by the endometrial lumenal epithelium (LE) and superficial ductal glandular epithelium (sGE) in response to binding of pituitary and/or luteal oxytocin to oxytocin receptors (OTR) and liberation of arachidonic acid, the precursor of PGF. Cyclooxygenase-one (COX-1) and COX-2 are rate-limiting enzymes in PGF synthesis, and COX-2 is the major form expressed in ovine endometrium. During pregnancy recognition, interferon tau (IFNτ), produced by the conceptus trophectoderm, acts in a paracrine manner to suppress development of the endometrial epithelial luteolytic mechanism by inhibiting transcription of estrogen receptor α (ERα) (directly) and OTR (indirectly) genes. Conflicting studies indicate that IFNτ increases, decreases or has no effect on COX-2 expression in bovine and ovine endometrial cells. In Study One, COX-2 mRNA and protein were detected solely in endometrial LE and sGE of both cyclic and pregnant ewes. During the estrous cycle, COX-2 expression increased from Days 10 to 12 and then decreased to Day 16. During early pregnancy, COX-2 expression increased from Days 10 to 12 and remained higher than in cyclic ewes. In Study Two, intrauterine infusion of recombinant ovine IFNτ in cyclic ewes from Days 11 to 16 post-estrus did not affect COX-2 expression in the endometrial epithelium. These results clearly indicate that IFNτ has no effect on expression of the COX-2 gene in the ovine endometrium. Therefore, antiluteolytic effects of IFNτ are to inhibit ERα and OTR gene transcription, thereby preventing endometrial production of luteolytic pulses of PGF. Indeed, expression of COX-2 in the endometrial epithelia as well as conceptus is likely to have a beneficial regulatory role in implantation and development of the conceptus. PMID:12956885

Effects of IL8 and immune cells on the regulation of luteal progesterone secretion

USDA-ARS?s Scientific Manuscript database

Recent studies suggest that chemokines may mediate the luteolytic action of PGF2a (PGF). Our objective was to identify chemokines induced by PGF in vivo and to determine the effects of IL8 on specific luteal cell types in vitro. Midcycle cows were injected with saline or PGF, ovaries were removed ...

[The most effective dosage in the administration of PGF2-alpha for interruption of pregnancy during the 2d trimester].

PubMed

Herczeg, J; Szontágh, F

1974-06-23

Artificial interruption of pregnancy contains too many risks from the 12th week of pregnancy. The authors have been working at finding the most suitable and effective dosage of prostaglandin for the interruption of pregnancy during the 2nd trimester. The new dosage experimented was 25 mg of prostaglandin F2alpha, followed by another 25 mg 6 hours later. The clinical efficiency of this dosage was tested. This procedures was used in 45 cases. The efficiency of the method was compared to the efficiency of the previously used dosage, which was 25 mg of prostaglandin F2alpha, followed by 25 mg 24 hours later. The new dosage was evaluated 91% efficient, while the previous dosage was found to be 75% efficient. The side effects were rated as acceptable by the patients. There was no case of infection. Two undeniable advantages were found with this new dosage: the duration of the actual procedure is considerably reduced, and the method appears to be much safer. The authors conclude that this new procedure offers numerous clinical advantages.

Fertility after two doses of PGF2α concurrently or at 6-hour interval on the day of CIDR removal in 5-day CO-Synch progesterone-based synchronization protocols in beef heifers.

PubMed

White, Stephanie S; Kasimanickam, Ramanathan K; Kasimanickam, Vanmathy R

2016-08-01

Timed artificial insemination protocols in beef cattle are designed to synchronize ovulation in a greater proportion of females while simultaneously achieving acceptable pregnancy rates and a concise calving season. Protocols achieving such goals reduce time and labor associated with estrus detection and make advanced reproductive technologies implementable for beef producers. The objective of the study was to determine the effect of three different PGF2α (PGF) dosage schemes on artificial insemination (AI) pregnancy rates in beef heifers. We hypothesized that two doses of PGF administered concurrently at the time of controlled internal drug release (CIDR) removal would attain similar pregnancy rates compared with two doses given 6-hours apart-one at CIDR removal and the next 6 hours later in the 5-day CO-Synch progesterone-based synchronization protocol. Angus heifers (n = 875) at six locations in Washington, Idaho, and Oregon states were included in this study. Heifers within locations were assigned a body condition score (BCS). All heifers received a CIDR (1.38 g of progesterone) and 100 μg IM of GnRH on Day 0. The CIDRs were removed on Day 5, heifers were randomly allocated to one of three protocol groups: 1PGF (n = 291), received 25 mg IM of dinoprost (PGF); 2CO-PGF (n = 291), received 50 mg IM of dinoprost at CIDR removal, 2PGF (n = 293), received 25 mg IM of dinoprost at CIDR removal, and an additional 25 mg IM of dinoprost 6 hours later. Each heifer was given GnRH (100 μg, IM) and artificially inseminated at 56 hours after CIDR removal. Heifers were examined for pregnancy status between 50 and 70 days after AI to determine time of conception. A mixed-model procedure (PROC GLIMMIX of SAS) was used to evaluate the effect of treatments (1PGF, 2CO-PGF, and 2PGF) on AI pregnancy rates. Models included were treatments, BCS categories (≤5 and >5), and treatment by BCS category interaction. Location (state), handling facilities, handlers, inseminators, and AI sires were included as a random effect in the model. The 2PGF group had greater AI pregnancy rate of 63.6% (185/291), compared with the 2CO-PGF group at 51.9% (151/291) and 1PGF group at 54.9% (161/293; P < 0.001). An AI pregnancy rate of 50% (104/208) was observed for heifers with BCS less than or equal to 5 versus 58.9% (393/667) for heifers with BCS greater than 5 (P < 0.05). Location did not influence the AI pregnancy rate (P > 0.1). In conclusion, beef heifers received two 25-mg doses of PGF at 6-hour interval on Day 5 at CIDR insert removal in a 5-day CO-Synch + CIDR synchronization protocols achieved greater pregnancy compared with heifers received 50 mg of PGF concurrently at CIDR removal. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of flutamide on prostaglandin F2α synthase and prostaglandin F2α receptor expression, and prostaglandin F2α concentration in the porcine corpus luteum of pregnancy.

PubMed

Grzesiak, M; Knapczyk-Stwora, K; Slomczynska, M

2017-04-01

Recently, we have indicated that flutamide-induced androgen deficiency diminished progesterone production in the porcine corpus luteum (CL) during late pregnancy and before parturition, as a sign of functional luteolysis. In pigs, the main luteolytic factor is prostaglandin F 2α (PGF 2α ), which acts via specific receptors (PTGFRs), and its biosynthesis is catalyzed by prostaglandin F 2α synthase (PGFS). The present study investigated the impact of flutamide on luteal PGFS and PTGFR expression, as well as intraluteal PGF 2α content during pregnancy in pigs. Flutamide (50 mg/kg BW per day, for 7 d) or corn oil (control groups) were administered subcutaneously into pregnant gilts (n = 3 per group) between 83 and 89 (GD90) or 101-107 (GD108) days of gestation (GD). On GD90 and GD108 ovaries were collected and CLs were obtained. Real-time PCR and Western blot analyses were conducted to quantify PGFS and PTGFR mRNA and protein expression, respectively. In addition, immunohistochemical localization of both proteins was performed and the concentration of PGF 2α was analyzed by enzyme immunoassay method. Flutamide caused upregulation of PGFS mRNA and protein in GD90F (P = 0.008; P = 0.008, respectively) and GD108F (P = 0.041; P = 0.009, respectively) groups. The level of PTGFR mRNA increased only in the GD90F (P = 0.007) group, whereas PTGFR protein expression was greater in both gestational periods (P = 0.035; P = 0.038, respectively). On GD90 PGFS was immunolocalized in the cytoplasm of large luteal cells only, whereas on GD108, sparse small luteal cells also displayed positive staining. PTGFR showed membranous localization within large luteal cells on both days of pregnancy. In luteal tissue, PGF 2α concentration was greater after flutamide exposure on both days (P = 0.041; P = 0.038, respectively), when compared with control groups. Overall, the enhanced luteal PGF 2α content due to increased PGFS expression after flutamide administration might contribute to premature CL regression. Moreover, higher PTGFR protein levels indicate enhanced sensitivity of luteal cells to PGF 2α under androgen deficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

Relaxant effects of butylidenephthalide in isolated dog blood vessels.

PubMed

Ko, Wun Chang; Liao, Chao-Chiun; Shih, Chih-Hsien; Lei, Chien-Bang; Chen, Chi-Ming

2002-11-01

We investigated the reason why butylidenephthalide (Bdph) can have an antianginal effect without changing blood pressure in conscious rats. Isolated dog coronary artery (CA), femoral vein (FV), femoral artery (FA), and mesenteric artery (MA) were used to evaluate the relaxant effects of Bdph. Bdph concentration-dependently relaxed isolated CA, FV, FA, and MA precontracted by KCl (60 mM) and phenylephrine (phe, 5 microM) with the exception that CA was precontracted by prostaglandin F 2 alpha (PGF 2 alpha, 2 microM) instead of phe. The potency order of Bdph to these blood vessels was FV > CA > FA > or = MA. Bdph also concentration-dependently and non-competitively inhibited cumulative KCl (5 - 120 mM)- and phe (0.1 - 100 microM)-induced contractions in normal, and inhibited cumulative Ca 2+-induced contractions in depolarized blood vessels. The potency order of Bdph to these blood vessels was FV congruent with CA > FA congruent with MA. Bdph (0.02 - 0.04 mM) concentration-dependently and leftward-shifted the log concentration-response curves in parallel and significantly increased the pD 2 value of forskolin, but not nitroprusside in FV. Bdph (0.1 mM) did both in CA. Bdph (0.225 - 0.45 mM) did the opposite to that of nitroprusside, but not forskolin, in FA. Bdph (0.45 - 0.9 mM) did neither in MA. Bdph (0.1 - 1 mM) significantly inhibited cAMP- but not cGMP-PDE activities in these four blood vessels, suggesting that Bdph more selectively inhibited the former in these tissues. The above results suggest that the higher potencies of Bdph on FV and CA than on FA and MA, may be interpreted as the reason why Bdph is useful in the treatment of angina pectoris without changing blood pressure, after Bdph administration in vivo, because the venoreturn may be reduced and the coronary flow may be increased without affecting the arterioles, such as MA, the main determinant of blood pressure. Abbreviations. Bdph:butylidenephthalide Phe:phenylephrine PGF 2alpha :prostaglandin F 2alpha CA:coronary artery FV:femoral vein FA:femoral artery MA:mesenteric artery cAMP:adenosine 3',5'-cyclic monophosphate cGMP:guanosine 3',5'-cyclic monophosphate PDE:phosphodiesterase

Areca nut extract up-regulates prostaglandin production, cyclooxygenase-2 mRNA and protein expression of human oral keratinocytes.

PubMed

Jeng, J H; Ho, Y S; Chan, C P; Wang, Y J; Hahn, L J; Lei, D; Hsu, C C; Chang, M C

2000-07-01

There are about 600 million betel quid (BQ) chewers in the world. BQ chewing is associated with increased incidence of oral cancer and submucous fibrosis. In this study, areca nut (AN) extract (200-800 microg/ml) induced the prostaglandin E(2) (PGE(2)) production by 1. 4-3.4-fold and 6-keto-PGF(1 alpha) production by 1.1-1.7-fold of gingival keratinocytes (GK), respectively, following 24 h of exposure. Exposure of GK to AN extract (>400 microg/ml) led to cell retraction and intracellular vacuoles formation. At concentrations of 800 and 1200 microg/ml, AN extract induced cell death at 21-24 and 32-52% as detected by MTT assay and cellular lactate dehydrogenase release, respectively. Interestingly, AN-induced morphological changes of GK are reversible. GK can still proliferate following exposure to AN extract. Cytotoxicity of AN extract cannot be inhibited by indomethacin (1 microM) and aspirin (50 microM), indicating that prostaglandin (PG) production is not the major factor responsible for AN cytotoxicity. PGE(2) exhibited little effect on the growth of GK at concentrations ranging from 100-1000 pg/ml. Stimulating GK production of PGs by AN extract could be due to induction of cyclooxygenase-2 (COX-2) mRNA expression and protein production. These results suggest that AN ingredients are critical in the pathogenesis of oral submucous fibrosis and oral cancer via their stimulatory effects on the PGs, COX-2 production and associated tissue inflammatory responses. AN cytotoxicity to GK is not directly mediated by COX-2 stimulation and PG production.

Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery

PubMed Central

Knock, Greg A.; Shaifta, Yasin; Snetkov, Vladimir A.; Vowles, Benjamin; Drndarski, Svetlana; Ward, Jeremy P.T.; Aaronson, Philip I.

2008-01-01

Abstract Aims We investigated the role of src family kinases (srcFK) in agonist-mediated Ca2+-sensitization in pulmonary artery and whether this involves interaction with the rho/rho-kinase pathway. Methods and results Intra-pulmonary arteries (IPAs) and cultured pulmonary artery smooth muscle cells (PASMC) were obtained from rat. Expression of srcFK was determined at the mRNA and protein levels. Ca2+-sensitization was induced by prostaglandin F2α (PGF2α) in α-toxin-permeabilized IPAs. Phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light-chain-20 (MLC20) and translocation of rho-kinase in response to PGF2α were also determined. Nine srcFK were expressed at the mRNA level, including src, fyn, and yes, and PGF2α enhanced phosphorylation of three srcFK proteins at tyr-416. In α-toxin-permeabilized IPAs, PGF2α enhanced the Ca2+-induced contraction (pCa 6.9) approximately three-fold. This enhancement was inhibited by the srcFK blockers SU6656 and PP2 and by the rho-kinase inhibitor Y27632. Y27632, but not SU6656 or PP2, also inhibited the underlying pCa 6.9 contraction. PGF2α enhanced phosphorylation of MYPT-1 at thr-697 and thr-855 and of MLC20 at ser-19. This enhancement, but not the underlying basal phosphorylation, was inhibited by SU6656. Y27632 suppressed both basal and PGF2α-mediated phosphorylation. The effects of SU6656 and Y27632, on both contraction and MYPT-1 and MLC20 phosphorylation, were not additive. PGF2α triggered translocation of rho-kinase in PASMC, and this was inhibited by SU6656. Conclusions srcFK are activated by PGF2α in the rat pulmonary artery and may contribute to Ca2+-sensitization and contraction via rho-kinase translocation and phosphorylation of MYPT-1. PMID:18032393

Elevated urinary levels of 8-oxo-2'-deoxyguanosine, (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines, and 8-iso-prostaglandin F2α as potential biomarkers of oxidative stress in patients with prediabetes.

PubMed

Kant, Melis; Akış, Merve; Çalan, Mehmet; Arkan, Tuğba; Bayraktar, Fırat; Dizdaroglu, Miral; İşlekel, Hüray

2016-12-01

Prediabetes is the preclinical stage of type 2 diabetes mellitus (T2DM) with intermediate state of hyperglycemia. Hyperglycemia results in a state of oxidative stress, which may contribute to the production of insulin resistance, β-cell dysfunction and long-term complications of diabetes. Novel approaches are required for prevention and treatment of diabetes. New biomarkers that can be used in risk stratification and therapy control as supplementary to current parameters are needed. These biomarkers may facilitate a more individualized and sufficient treatment of diabetes. Therefore, the aim of this study was to investigate the levels of oxidatively induced DNA damage products, 8-oxo-2'-deoxyguanosine (8-oxo-dG) (also known as 8-OH-dG), (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines (R-cdA and S-cdA), and the lipid peroxidation product 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) as reliable oxidative stress markers in patients with prediabetes or T2DM in comparison with healthy volunteers. Urine samples were collected from these subjects. Absolute quantification of 8-oxo-dG, R-cdA, S-cdA and 8-iso-PGF 2α was achieved by liquid chromatography-isotope dilution tandem mass spectrometry. The levels of 8-oxo-dG, S-cdA and 8-iso-PGF 2α were significantly greater in prediabetes patients than those in healthy volunteers. T2DM patients also had higher levels of 8-oxo-dG than healthy volunteers. No statistically significant difference was observed for R-cdA levels. 8-Oxo-dG levels positively correlated with R-cdA and S-cdA levels for prediabetes and newly diagnosed T2DM. S-cdA levels and HbA1c were found negatively correlated in prediabetes patients. Also 8-iso-PGF 2α levels and HbA1c were found negatively correlated in prediabetes patients. These results indicate that oxidatively induced macromolecular damage appears before the establishment of T2DM. Thus, our data suggest that oxidatively induced DNA damage and lipid peroxidation products that were found to be elevated in prediabetic stage may be used as early disease markers in patients at risk for T2DM. Copyright © 2016 Elsevier B.V. All rights reserved.

Asymmetric dimethylarginine (ADMA) levels are increased in patients with fibromyalgia: correlation with tumor necrosis factor-α (TNF-α) and 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)).

PubMed

Topal, G; Donmez, A; Doğan, B S Uydes; Kucur, M; Cengiz, D Taspinar; Berkoz, F B; Erdogan, N

2011-04-01

The aim of the study was to investigate serum levels of asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and plasma levels of 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)) in patients with fibromyalgia. Twenty-seven patients with fibromyalgia and twenty healthy controls were enrolled in this study. ADMA, TNF-α, IL-6 and 8-iso-PGF(2α) levels were measured by enzyme-linked immunosorbent assay (ELISA). Serum levels of ADMA and TNF-α and plasma levels 8-iso-PGF(2α) were significantly increased in patients with fibromyalgia compared to controls. However, no significant difference was observed in IL-6 levels between the two groups. ADMA concentrations were positively correlated with TNF-α and 8-iso-PGF(2α) levels in patients with fibromyalgia. This is the first study reporting that ADMA levels are significantly elevated in patients with fibromyalgia in association with increased 8-iso-PGF(2α) and TNF-α concentrations. Thereby, ADMA could be suggested as a reliable marker of endothelial dysfunction in patients with fibromyalgia. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Induced ovulation and conception in locating sows.

PubMed

Hausler, C L; Hodson, H H; Kuo, D C; Kinney, T J; Rauwolf, V A; Strack, L E

1980-05-01

Fifty lactating sows were injected with 1,500 IU pregnant mare serum gonadotrophin (PMSG) at an average of 25 days postpartum. Twenty-four of these sows received prostaglandin F2 alpha (PGF2 alpha) 24 hr prior to PMSG. Ninety-six hours after the PMSG injection, 1,000 IU of human chorionic gonadotrophin (HCG) were injected. Artificial insemination was performed at 24 and 36 to 42 hr post-HCG. The PMSG/HCG treatment resulted in pregnancy in 17 of 20 sows slaughtered from 34 to 43 days postbreeding and in 23 of 30 sows allowed to complete gestation. Mean numbers of corpora lutea (33) and viable embryos (15) were counted at slaughter. Litter sizes were averaged (11) for those sows allowed to farrow. Treatment with PGF2 alpha prior to PMSG injection had no effect on conception rates, number of corpora lutea, number of embryos or litter size in the lactating sows. In a second experiment, the same hormone treatments were administered to lactating sows beginning on day 5, 10, 15 or 20 postpartum. Pregnancy rates were 0/10, 2/10, 8/10 and 6/10, respectively (P less than .05, chi-square). At slaughter (30 to 40 days postbreeding), corpora lutea and embryo numbers recorded from pregnant sows were 23.0, 9.5; 31.5, 15.3, and 28.0, 18.8, respectively, for the sows in the day 10, day 15 and day 20 groups. In a third experiment, sows were given PMSG-HCG as previously described on either day 5 (five sows) or day 10 (14 sows) postpartum. Laparotomy of these sows 2 to 5 days postbreeding revealed minimal ovarian responsiveness at day 5, but 43% of the animals responded with multiple ovulations at day 10. The low pregnancy rate seen at day 10 in Exp. 2 may reflect embryonic mortality due to unfavorable uterine environment. We conclude that the PMSG/HCG treatment followed by timed artificial insemination of lactating sows will induce ovulation and coneption as early as 15 days postfarrowing. Pregnancy is thus concurrent with lactation, eliminating the need for early weaning and reducing the interval between successive farrowings.

Urinary 8-iso-prostaglandin F2α as a marker of metabolic risks in the general Japanese population: The ROAD study.

PubMed

Mure, Kanae; Yoshimura, Noriko; Hashimoto, Marowa; Muraki, Shigeyuki; Oka, Hiroyuki; Tanaka, Sakae; Kawaguchi, Hiroshi; Nakamura, Kozo; Akune, Toru; Takeshita, Tatsuya

2015-07-01

To determine whether 8-iso-prostaglandin F2α (8-iso-PGF2α) is a reliable biomarker of the accumulation of metabolic risks [e.g., overweight, hypertension, impaired glucose tolerance (IGT), and dyslipidemia]. This was a cross-sectional study of the baseline characteristics of a Japanese general population cohort study: Research on Osteoarthritis/Osteoporosis Against Disability (ROAD). Of 1,690 participants, 1,527 fulfilled all questionnaires and examinations. Free and conjugated urinary 8-iso-PGF2α levels and metabolic syndrome (MetS) components including blood pressure, HbA1c, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and non-HDL-C were analyzed. The data were analyzed by ANCOVA, multiple regression analysis, and multinomial logistic analysis. 8-iso-PGF2α was significantly associated with HbA1c and significantly inversely associated with total cholesterol and non-HDL-C. Notably, IGT with an HbA1c cut-off of 5.5% was significantly associated with 8-iso-PGF2α level in participants aged ≤50 years. Multinomial logistic regression analysis revealed 8-iso-PGF2α level was significantly associated with a greater number of MetS risks present; this association was stronger in younger participants. In participants aged ≥71 years, 8-iso-PGF2α was significantly associated with a greater number of MetS risks with higher IGT cut-offs. Urinary 8-iso-PGF2α can be a reliable marker of IGT and the accumulation of MetS risks, especially in younger people. © 2015 The Obesity Society.

Evidence for differential activation of arachidonic acid metabolism in formylpeptide- and macrophage-activation-factor-stimulated guinea-pig macrophages.

PubMed Central

Homma, Y; Hashimoto, T; Nagai, Y; Takenawa, T

1985-01-01

Alterations of phospholipid and arachidonic acid metabolism were studied by treatment of guinea-pig peritoneal-exudate macrophages with chemotactic peptide, formylmethionyl-leucylphenylalanine (fMet-Leu-Phe) and macrophage activation factor (MAF). The chemotactic peptide caused a rapid rearrangement in inositol phospholipids, including a breakdown of polyphosphoinositides within 30s, followed by a resultant formation of phosphatidylinositol (PI), diacylglycerol, phosphatidic acid and non-esterified arachidonic acid within 5 min. In addition to these sequential alterations, arachidonic acid was released mainly from PI. On the other hand, MAF induced a slow liberation of arachidonic acid, mainly from phosphatidylethanolamine (PE) and phosphatidylcholine (PC) by phospholipase A2 after the incubation period of 30 min, but not any rapid changes in phospholipids. Treatment of macrophages for 15 min with fMet-Leu-Phe produced the leukotrienes (LTs) B4, C4 and D4, prostaglandins (PG) E2 and F2 alpha and thromboxane (TX) B2. In contrast, MAF could not stimulate the production of arachidonic acid metabolites during the incubation period of 15 min, but could enhance that of PGE2, PGF2 alpha, TXB2 and hydroxyeicosatetraenoic acids at 6 h. However, the stimulated formation of LTs was not detected at any time. These results indicate that the effects of fMet-Leu-Phe on both phospholipid and arachidonic acid metabolism are very different from those mediated by MAF. PMID:3931627

Prostanoids-induced dispersion in the melanophores of a carp Labeo rohita (Ham.).

PubMed

Ovais, M; Ahmed, Fraz; Mubashshir, Md; Sumoona, Safia

2014-02-01

Effects of three prostaglandins (i.e., prostanoids) and one of its precursors, arachidonic acid, were examined on the melanophores of the fish Labeo rohita (Ham.). PGE₁, PGE₂, PGF(2α) and arachidonic acid elicit a concentration-related dispersion in the fish melanophores. In vitro analysis of melanophores was performed through incubation of the isolated fish scales in different agonists and antagonists solutions. Dispersal effect of prostanoids may be mediated directly through the typical receptors or indirectly through release of neurotransmitter substance(s) from the melanophore nerve endings. Denervation of fish melanophores rendered them insensitive to prostanoid (PGF(2α)). Propranolol and verapamil completely inhibited the dispersal effects of PGF(2α); theophylline and indomethacine blocked the effects of higher concentrations of PGF(2α). During dispersing influence of PGF(2α), a free flux of Ca²⁺ ions was required and the indirectly released substance(s) from melanophore nerve endings would be the catecholamines of adrenergic and purinergic in nature.

Advanced nutrient root feeding system for conveyer-type cylindrical plant growth facilities developed for microgravity

NASA Astrophysics Data System (ADS)

Berkovich, Yuliy A.; Smolyanina, Svetlana O.; Krivobok, Anna; Krivobok, Nikolay

A new brand of cylindrical conveyer-type space plant growth facilities (PGF) has been created to improve of cosmonauts’ diet in the microgravity conditions. Up to date several ground prototypes of the space PGF have been made and tested: “Phytocycle”, “Vitacycle”, “Phytocycle-LED”, “Phytoconveyer”; now the space PGF “Vitacycle-T” for the Russian segment of the ISS is under developing. In the PGFs the ion-exchange salt-saturated fibrous artificial soil (AS) is used as a root medium. We have proposed the system for enrichment of irrigation water by nutrients to decrease of the AS store required for PGF working during the long space mission. The system includes root modules filled in fibrous ion-exchange AS, the enrichment column with crumble salt-saturation ion-exchange resin and the cassette with slow releasing fertilizer (SRF). Both substrates (ion-exchange resin and SRF) are necessary because of the SRF contains mostly N, P and K but another three essential elements S, Ca, Mg are provided by the ion-exchange resin. In the system water goes throw the enrichment column with ion-exchange resin fertilizing by the nutrients and comes into the mixer cell fertilize equipped with the electrical conductivity sensor. When the signal of the conductivity sensor is coming to the controller it turns on the pump directed the water flow throw the cassette with SRF until the electric conductivity of the solution in the mixer cell will reach the setpoint. The nutrient root feeding system was tested during 88 days when Chinese cabbage grew in PGF “Phytocycle-LED”. The crop has been continuously illuminated by red and blue LEDs in the PPF ratio 7 to 1; an integral PPF level has been (240 ± 10) µmol/(m2×s). There was no renewal of the used fibrous AS during the experiment. The PGF total electric power consumption was of 0,45 kW. The average fresh biomass productivity of the PGF during steady state working mode was equal 135×g/day per m2 of the illuminated crop area and specific productivity was 4,15 g per 1 g of ion-exchange resin “BIONA-312” and SRF “Osmocote 14-14-14” total mass. The solution pH in the pores of the moistened fibrous AS “BIONA-V3” persisted inside diapason of 6,0 - 6,6 which was favorable for the most greens. The data permits to hope that the nutrient root feeding system could be able to stabilize the nutrient solution in microgravity automatically and minimize the required supply of a fibrous AS.

Flurbiprofen axetil increases arterial oxygen partial pressure by decreasing intrapulmonary shunt in patients undergoing one-lung ventilation.

PubMed

Chai, Xiao-Qing; Ma, Jun; Xie, Yan-Hu; Wang, Di; Chen, Kun-Zhou

2015-12-01

In the present study, we investigated whether flurbiprofen axetil (FA) alleviates hypoxemia during one-lung ventilation (OLV) by reducing the pulmonary shunt/total perfusion (Q s/Q t) ratio, and examined the relationship between the Q s/Q t ratio and the thromboxane B2 (TXB2)/6-keto-prostaglandin F1α (6-K-PGF1α) ratio. Sixty patients undergoing esophageal resection for carcinoma were randomly assigned to groups F and C (n = 30 for each group). FA and placebo were administered i.v. 15 min before skin incision in groups F and C, respectively. The partial pressure of arterial oxygen (PaO2) was measured and the Q s/Q t ratio was calculated. Serum TXB2, 6-K-PGF1α, and endothelin (ET) were measured by radioimmunoassay. The relationship between TXB2/6-K-PGF1α and Q s/Q t was investigated. Compared with group C, PaO2 was higher and the Q s/Q t ratio was lower during OLV in group F (P < 0.05). After treatment with FA, both serum TXB2 and 6-K-PGF1α decreased significantly (P < 0.05) but the TXB2/6-K-PGF1α ratio increased significantly (P < 0.01). Increases in the TXB2/6-K-PGF1α ratio were correlated with reductions in the Q s/Q t ratio during OLV in group F (r = -0.766, P < 0.01). There was no significant difference in serum ET between groups F and C. Treatment with FA reduced the Q s/Q t ratio and further increased the PaO2 level during OLV, possibly due to upregulation of the vasoactive agent TXB2/6-K-PGF1α ratio.

Enhanced renal prostaglandin production in the dog. I. Effects on renal function.

PubMed

Tannenbaum, J; Splawinski, J A; Oates, J A; Nies, A S

1975-01-01

The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 and F2alpha.PGE2given at 0.01-0.3 mug/kg min--1 produced dose-related increases in urine flow, sodium and potassium excretion, free water clearance, and renal blood flow. The glomerular filtration rage increased only at the lowest dose and the calculated filtration fraction fell. Arachidonic acid at 1.0-30.0 mug/kg min--1 similarly produced dose-related increases in electrolyte excretion, but the increase in renal blood flow was much less than that produced by PGE2 and there were no changes in glomerular filtration rate, filtration fraction, or free water clearances. PGF2alpha had essentially no effects at infusion rates of 0.03-1.0 mug/kg min--1. All renal effects of arachidonic acid were inhibited by simultaneous infusions of an inhibitor of prostaglandin synthetase, 5, 8, 11,14-eicosatetraynoic acid (20:4). None of the effects produced by PGE2 were inhibited by 20:4. These results indicate that enhanced endogenous renal prostaglandin synthesis, which can be produced by arachidonate infusion, results in significant alterations of renal function. This finding strengthens the hypothesis that renal prostaglandins formed in vivo have physiological importance as regulators of renal function.

The 9-day CIDR-PG protocol: Incorporation of PGF2α pretreatment into a long-term progestin-based estrus synchronization protocol for postpartum beef cows.

PubMed

Thomas, Jordan M; Bishop, Brianne E; Abel, Jillian M; Ellersieck, Mark R; Smith, Michael F; Patterson, David J

2016-06-01

A pilot experiment was designed to test the hypothesis that administration of PGF2α before progestin treatment would allow for a reduced duration of progestin treatment in a long-term progestin-based estrus synchronization protocol. A modified presynchronization treatment was compared with a standard long-term controlled internal drug release (CIDR) treatment, and treatments were compared on the basis of ovarian follicular dynamics, estrous response rate, synchrony of estrus expression, and pregnancy rates resulting from timed artificial insemination (TAI) in postpartum beef cows. Estrous was synchronized for 85 cows, with cows assigned to one of two treatments based on age, days postpartum, and body condition score. Cows assigned to the 14-day CIDR-PG protocol received a CIDR insert (1.38 g progesterone) on Day 0, CIDR removal on Day 14, and administration of PGF2α (25 mg im) on Day 30. Cows assigned to the 9-day CIDR-PG protocol received PGF2α concurrent with CIDR insertion on Day 5, PGF2α concurrent with CIDR removal on Day 14, and administration of PGF2α on Day 30. In both treatments, split-time AI was performed based on estrous response. At 72 hours after PGF2α (Day 33), cows having expressed estrus received TAI; cows that failed to express estrus by 72 hours received TAI 24 hours later (96 hours after PGF2α on Day 34), with GnRH (100 μg im) administered to nonestrous cows. Estrus-detection transmitters were used from CIDR removal until AI to determine onset time of estrus expression both after CIDR removal and after PGF2α. Ovarian ultrasonography was performed at CIDR removal on Day 14, PGF2α on Day 30, and AI on Days 33 or 34. At CIDR removal on Day 14, diameter of the largest follicle present on the ovary was similar between treatments. The proportion of cows expressing estrus after CIDR removal tended to be higher (P = 0.09) among cows assigned to the 9-day CIDR-PG treatment (93%; 40 of 43) than among cows assigned to the 14-day CIDR-PG treatment (81%; 34 of 42). After PGF2α, a significantly higher proportion (P = 0.02) of cows expressed estrus after synchronization with the 9-day CIDR-PG treatment (91%; 39 of 43) than the 14-day CIDR-PG treatment (69%; 29 of 42). Consequently, pregnancy rate to TAI tended to be increased (P = 0.09) among the 9-day CIDR-PG treatment (76.7%; 33 of 43) compared with the 14-day CIDR-PG treatment (59.5%; 25 of 42). In summary, a long-term CIDR-based estrous synchronization protocol for postpartum beef cows was enhanced through administration of PGF2α at CIDR insertion and CIDR removal. Copyright © 2016 Elsevier Inc. All rights reserved.

Association between prenatal psychological stress and oxidative stress during pregnancy.

PubMed

Eick, Stephanie M; Barrett, Emily S; van 't Erve, Thomas J; Nguyen, Ruby H N; Bush, Nicole R; Milne, Ginger; Swan, Shanna H; Ferguson, Kelly K

2018-03-30

Prenatal psychological stress during pregnancy has been associated with adverse reproductive outcomes. A growing animal literature supports an association between psychological stress and oxidative stress. We assessed this relationship in pregnant women, hypothesising that psychological stress is associated with higher concentrations of oxidative stress biomarkers during pregnancy. Psychosocial status and stressful life events (SLE) were self-reported. 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) was measured as a biomarker of oxidative stress in urine samples at median 32 weeks' gestation. We examined SLEs individually (ever vs never) and in summary (any vs none) and psychosocial status as measured by individual subscales and in summary (poor vs good). Linear models estimated associations between these parameters and urinary 8-iso-PGF 2α concentrations after adjusting for covariates. The geometric mean of 8-iso-PGF 2α was significantly higher among pregnant women who were non-White, smokers, had less than a college education, higher pre-pregnancy BMI and were unmarried. Having ever had a death in the family (n = 39) during pregnancy was associated with a 22.9% increase in 8-iso-PGF 2α in unadjusted models (95% confidence interval [CI] 1.50, 48.8). Poor psychosocial status was associated with a 13.1% (95% CI 2.43, 25.0) greater mean 8-iso-PGF 2α in unadjusted analyses. Associations were attenuated, but remained suggestive, after covariate adjustment. These data suggest that 8-iso-PGF 2α is elevated in pregnant women with who are at a sociodemographic disadvantage and who have higher psychological stress in pregnancy. Previous studies have observed that 8-iso-PGF 2α levels are associated with adverse birth outcomes, oxidative stress could be a mediator in these relationships. © 2018 John Wiley & Sons Ltd.

Cyclo-oxygenase-2 contributes to constitutive prostanoid production in rat kidney and brain

PubMed Central

2005-01-01

Cyclo-oxygenases (COXs) catalyse the synthesis of PGH2 (prostaglandin H2), which serves as the common substrate for the production of PGE2, PGD2, PGF2α, prostacyclin (or PGI2) and TXs (thromboxanes). While COX-1 is the major isoform responsible for prostanoid synthesis in healthy tissues, little information is available on the contribution of constitutive COX-2 to the various prostanoid synthetic pathways under non-inflammatory conditions. To evaluate further the role of COX-2 in prostanoid biosynthesis, rats were acutely treated with the selective COX-1 inhibitor SC-560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole] or the selective COX-2 inhibitors MF tricyclic [3-(3,4-difluorophenyl)-4-(4-(methylsulphonyl)phenyl)-2-(5H)-furanone] and DFU [5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2-(5H)-furanone]. Selected tissues were then processed for a complete analysis of their prostanoid content by liquid chromatography MS. Whereas the treatment with SC-560 caused a 60–70% inhibition in the total prostanoid content of most tissues examined, a significant decrease (35–50%) in total prostanoid content following selective COX-2 inhibition was solely detected for kidney and brain tissues. Analysis of the individual prostanoids reveals significant inhibition of 6-oxo-PGF1α, PGE2, PGD2, PGF2α and TXB2 in the kidney and inhibition of all these prostanoids with the exception of PGD2 in the forebrain. These results demonstrate that constitutively expressed COX-2 contributes to the production of prostanoids in kidney and brain for each of the PGE2, PGI2 and TXB2 pathways under non-inflammatory conditions. Approaches to modulate inflammation through specific inhibition of terminal synthases, such as mPGES-1 (microsomal PGE2 synthase-1), thus have the potential to differ from COX-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs with regard to effects on constitutive prostanoid synthesis and on renal function. PMID:16008526

Major urinary metabolites of 6-keto-prostaglandin F2α in mice[S

PubMed Central

Kuklev, Dmitry V.; Hankin, Joseph A.; Uhlson, Charis L.; Hong, Yu H.; Murphy, Robert C.; Smith, William L.

2013-01-01

Western diets are enriched in omega-6 vs. omega-3 fatty acids, and a shift in this balance toward omega-3 fatty acids may have health benefits. There is limited information about the catabolism of 3-series prostaglandins (PG) formed from eicosapentaenoic acid (EPA), a fish oil omega-3 fatty acid that becomes elevated in tissues following fish oil consumption. Quantification of appropriate urinary 3-series PG metabolites could be used for noninvasive measurement of omega-3 fatty acid tone. Here we describe the preparation of tritium- and deuterium-labeled 6-keto-PGF2α and their use in identifying urinary metabolites in mice using LC-MS/MS. The major 6-keto-PGF2α urinary metabolites included dinor-6-keto-PGF2α (∼10%) and dinor-13,14-dihydro-6,15-diketo-PGF1α (∼10%). These metabolites can arise only from the enzymatic conversion of EPA to the 3-series PGH endoperoxide by cyclooxygenases, then PGI3 by prostacyclin synthase and, finally, nonenzymatic hydrolysis to 6-keto-PGF2α. The 6-keto-PGF derivatives are not formed by free radical mechanisms that generate isoprostanes, and thus, these metabolites provide an unbiased marker for utilization of EPA by cyclooxygenases. PMID:23644380

Ovarian steroids, oxytocin, and tumor necrosis factor modulate equine oviduct function.

PubMed

Pinto-Bravo, P; Galvão, A; Rebordão, M R; Amaral, A; Ramilo, D; Silva, E; Szóstek-Mioduchowska, A; Alexandre-Pires, G; Roberto da Costa, R; Skarzynski, D J; Ferreira-Dias, G

2017-10-01

The oviduct plays important roles in the early reproductive process. The aim of this study was to evaluate gene transcription and protein expression of progesterone receptor (PGR), estrogen receptors 1 (ESR1) and 2 (ESR2); oxytocin receptor (OXTR); prostaglandin F2α synthase (AKR1C3), and prostaglandin E2 synthase (Ptges) in mare oviduct in different estrous cycle stages. Estradiol (E 2 ), progesterone (P 4 ), oxytocin (OXT), and tumor necrosis factor α (TNF) effect on in vitro PGE 2 and prostaglandin F2α (PGF 2α ) secretion by equine oviduct explants or by oviductal epithelial cells (OECs) were also assessed. During the breeding season, oviduct tissue was obtained post mortem from cyclic mares. Protein of ESR1, ESR2, PGR, AKR1C3, and Ptges was present in OECs, whereas OXTR was shown in oviduct stroma. In follicular phase, protein expression of ESR1, ESR2, PGR, and OXTR increased in oviduct explants (P < 0.05), whereas no estrous cycle effect was noted for AKR1C3 or Ptges. In follicular phase, mRNA transcription was upregulated for Pgr but downregulated for Oxtr, Ptges, and Akr1c3 (P < 0.05). Nevertheless, Esr1 and Esr2 mRNA levels did not change with the estrous cycle. In the ampulla, Esr1, Esr2, and Oxtr mRNA transcription increased, but not for Pgr or Ptges. In contrast, Akr1c3 mRNA level was upregulated in the infundibulum (P < 0.05). In follicular phase, E 2 , P 4 , and OXT downregulated PGE 2 production by OEC (P < 0.05), but no difference was observed in mid-luteal phase. Explants production of PGE 2 rose when treated with OXT in follicular phase; with TNF or OXT in early luteal phase; or with TNF, OXT, or P 4 in mid-luteal phase. PGF 2α production by OEC was downregulated by all treatments in follicular phase but upregulated in mid-luteal phase (P < 0.05). Oviduct explants PGF 2α production was stimulated by TNF or OXT in all estrous cycle phases. In conclusion, this work has shown that ESR1, ESR2, OXTR, Ptges, and AKRLC3 gene transcription and/or translation is estrous cycle dependent and varies with oviduct portion (infundibulum vs ampulla) and cell type. Ovarian steroid hormones, OXT and TNF stimulation of PGF 2α and/or PGE 2 production is also estrous cycle dependent and varies in the different portions of mare oviduct. Differential transcription level and protein localization in various portions of the oviduct throughout the estrous cycle, as well as PG production, suggest coordinated physiologic actions and mechanisms of steroid hormones, OXT, and TNF in the equine oviduct. Copyright © 2017 Elsevier Inc. All rights reserved.

[Measurement of bronchoconstrictive eicosanoids in chronic obstructive pulmonary disease].

PubMed

Gross-Sondej, Iwona; Soja, Jerzy; Sładek, Krzysztof; Pulka, Grażyna; Skucha, Wojciech; Niżankowska-Mogilnicka, Ewa

2012-01-01

The aim of the study was the evaluation of the concentration of 9α11β prostaglandin F(2) - a stable metabolite of prostaglandin D(2) (PGD(2)) and leukotriene E(4) (LTE(4)) in stable and exacerbated COPD patients. 29 COPD patients aged 73 ± 8.34, mean FEV1 = 48.64 ± 15.75% of predictive value and 29 healthy controls aged 57.48 ± 10.86, mean FEV1 = 97.17 ± 13.81% of predictive value participated in this study. Samples of urine and blood were taken from COPD patients during exacerbation and in stable state of the disease; LTE(4) was determined in urine using commercial enzyme immunoassay (EIA) and 9α11β prostaglandin F(2) (9α11βPGF(2)) - stable metabolite of PGD(2) was evaluated in blood and urine using GC/MS. LTE(4) concentration in urine (677.15 vs. 436.4 pg/mg of creatinine; p = 0.035) and 9α11βPGF(2) in blood serum (5.35 vs. 3.07 pg/ml; p = 0.007) were significantly higher in exacerbated COPD patients than in control group. There was no difference in LTE(4) level in urine and 9α11βPGF2 in blood serum between exacerbated and stable COPD. The urinary 9α11βPGF(2) concentration did not differ between all studied groups. We found a positive correlation between smoking history and the urine LTE(4) level (r = 0.395; p = 0.002) as well as blood 9α11βPGF(2) concentration (r = 0.603; p = 0.001) in COPD patients. 9α11βPGF(2) and LTE(4) level in urine did not differ between the stable COPD group and the control group. We also did not find any difference between LTE4 level in urine and 9α11βPGF(2) in blood and urine between exacerbated and stable COPD. Finally, LTE(4) concentration in urine and 9α11βPGF(2) in blood occurred to be significantly higher in exacerbated COPD patients than in control group.

Effects of red ginger capsule supplementin reducing PGF2α concentrations and pain intensity in primary dysmenorrhea

NASA Astrophysics Data System (ADS)

Simarmata, M.; Halim, B.; Ardinata, D.

2018-03-01

Primary dysmenorrhea is a gynecological disorder which most commonly occurs like a pain in the initial menstruation. One ofthe attempts to handle dysmenorrhea is by using anon-pharmacological method such as herbal therapy which uses red ginger. The research was at Akbid and Akper Harapan Mama, Deli Serdang Regency, with pre-experimental design and one group pretest-posttest. The samples were 32 female students as the respondents, taken by using non-probability or consecutive sampling technique. PGF2a content measurement by ELISA, theintensity of pain by Visual Analogue Scale and analyzed by using Wilcoxon test. PGF2α content before giving red ginger capsule supplement median was 156.50 pg/ml (min-max: 57-1037 pg/ml), after giving it was 101 (min-max: 22-785), pain intensity before giving it in the mean score of 2 was 15 respondents (47%), after giving it in the mean score of 0 was 14 respondents (44%). The result of statistic test on PGF2α content before and after giving it was p-value = 0.001, and pain intensity before and after giving it was p < 0.001 which indicated that there was asignificant decrease in PGF2α and pain intensity after giving it. Red ginger capsule supplement could decrease PGF2α content during primary dysmenorrhea.

Avian reproductive anatomy, physiology and endocrinology.

PubMed

Pollock, Christal G; Orosz, Susan E

2002-09-01

Although many environmental cues influence reproductive activity, the seasonal breeder responds most strongly to long day length. THE MALE BIRD: Testicular interstitial cells secrete testosterone, which influences reproductive behavior such as territorial aggression and song. Other changes observed in seasonal breeders include testicular hypertrophy and enlargement of the ductus deferens and seminal glomus. THE FEMALE BIRD: Early changes associated with rising estrogen levels in the hen include osteomyelosclerosis and hypercalcemia. Ovulation is then induced by LH, which is followed by eggshell calcification, which is under the control of progesterone. Sources of calcium for shell production include intestinal absorption from the diet, renal control of calcium levels, and mobilization of bone calcium stores. During oviposition, PGF2 alpha and vasotocin stimulate powerful uterine contractions [32] in the presence of calcium. Incubation is associated with falling LH levels and rising prolactin levels. If the hen actually enters reproductive quiescence at this time, then molt will follow. Molt is associated with the total regression of the reproductive tract.

Endogenous circulating sympatholytic factor in orthostatic intolerance

NASA Technical Reports Server (NTRS)

Shapiro, R. E.; Winters, B.; Hales, M.; Barnett, T.; Schwinn, D. A.; Flavahan, N.; Berkowitz, D. E.

2000-01-01

Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.

Effect of engineered nanoparticles on vasomotor responses in rat intrapulmonary artery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Courtois, Arnaud, E-mail: arnaud.courtois@u-bordeaux2.f; Inserm, U885, Bordeaux, F-33076; Andujar, Pascal

2010-06-01

Pulmonary circulation could be one of the primary vascular targets of finest particles that can deeply penetrate into the lungs after inhalation. We investigated the effects of engineered nanoparticles on vasomotor responses of small intrapulmonary arteries using isometric tension measurements. Acute in vitro exposure to carbon nanoparticles (CNP) decreased, and in some case abolished, the vasomotor responses induced by several vasoactive agents, whereas acute exposure to titanium dioxide nanoparticles (TiO{sub 2}NP) did not. This could be attributed to a decrease in the activity of those vasoactive agents (including PGF{sub 2{alpha}}, serotonin, endothelin-1 and acetylcholine), as suggested when they were exposedmore » to CNP before being applied to arteries. Also, CNP decreased the contraction induced by 30 mM KCl, without decreasing its activity. After endoplasmic reticulum calcium stores depletion (by caffeine and thapsigargin), CaCl{sub 2} addition induced a contraction, dependent on Store-Operated Calcium Channels that was not modified by acute CNP exposure. Further addition of 30 mM KCl elicited a contraction, originating from activation of Voltage-Operated Calcium Channels that was diminished by CNP. Contractile responses to PGF{sub 2{alpha}} or KCl, and relaxation to acetylcholine were modified neither in pulmonary arteries exposed in vitro for prolonged time to CNP or TiO{sub 2}NP, nor in those removed from rats intratracheally instilled with CNP or TiO{sub 2}NP. In conclusion, prolonged in vitro or in vivo exposure to CNP or TiO{sub 2}NP does not affect vasomotor responses of pulmonary arteries. However, acute exposure to CNP decreases contraction mediated by activation of Voltage-Operated, but not Store-Operated, Calcium Channels. Moreover, interaction of some vasoactive agents with CNP decreases their biological activity that might lead to misinterpretation of experimental data.« less

Do alterations in prostanoid or catecholamine release influence the antiarrhythmic activity of nicergoline?

PubMed

Williams, F M; Coker, S J; Dean, H G; Kane, K A; Parratt, J R

1986-01-01

We examined the effects of nicergoline, an alpha-adrenoceptor blocking drug and an inhibitor of platelet phospholipase, on haemodynamics, blood gases, cardiac arrhythmias, and prostanoid and catecholamine release in anaesthetised greyhounds before, during, and after a 40-min occlusion of the left anterior descending coronary artery. Twenty-five minutes after commencing the intravenous infusion of nicergoline (50 micrograms kg-1 min-1) there were significant reductions in heart rate, arterial blood pressure, left ventricular dP/dtmax, and cardiac output. Nicergoline also increased the 0(2) extraction by the myocardium both before and during coronary artery occlusion. In contrast to control animals, heart rate decreased but there were no further reductions in arterial blood pressure during the occlusion period. Nicergoline improved survival (from 17 in control dogs to 50%) following the combined period of myocardial ischaemia and reperfusion and appeared to suppress the phase 1b occlusion-induced arrhythmias. The release of thromboxane B2 from the ischaemic myocardium was partially suppressed by nicergoline, and the ratio of 6-keto PGF1 alpha/thromboxane B2 (the stable breakdown products of prostacyclin and thromboxane A2, respectively) was increased. The washout of noradrenaline and adrenaline from the ischaemic myocardium following release of the occlusion was slightly enhanced by nicergoline. It is concluded that the beneficial metabolic and prostacyclin-promoting properties of nicergoline may be opposed by its action on noradrenaline washout, thus limiting its antiarrhythmic effectiveness.

Separation and simultaneous quantitation of PGF2α and its epimer 8-iso-PGF2α using modifier-assisted differential mobility spectrometry tandem mass spectrometry.

PubMed

Liang, Chunsu; Sun, Hui; Meng, Xiangjun; Yin, Lei; Fawcett, J Paul; Yu, Huaidong; Liu, Ting; Gu, Jingkai

2018-03-01

Because many therapeutic agents are contaminated by epimeric impurities or form epimers as a result of metabolism, analytical tools capable of determining epimers are increasingly in demand. This article is a proof-of-principle report of a novel DMS-MS/MS method to separate and simultaneously quantify epimers, taking PGF2 α and its 8-epimer, 8- iso -PGF2 α , as an example. Good accuracy and precision were achieved in the range of 10-500 ng/mL with a run time of only 1.5 min. Isopropanol as organic modifier facilitated a good combination of sensitivity and separation. The method is the first example of the quantitation of epimers without chromatographic separation.

Placental growth factor deficiency is associated with impaired cerebral vascular development in mice.

PubMed

Luna, Rayana Leal; Kay, Vanessa R; Rätsep, Matthew T; Khalaj, Kasra; Bidarimath, Mallikarjun; Peterson, Nichole; Carmeliet, Peter; Jin, Albert; Croy, B Anne

2016-02-01

Placental growth factor (PGF) is expressed in the developing mouse brain and contributes to vascularization and vessel patterning. PGF is dynamically expressed in fetal mouse brain, particularly forebrain, and is essential for normal cerebrovascular development. PGF rises in maternal plasma over normal human and mouse pregnancy but is low in many women with the acute onset hypertensive syndrome, pre-eclampsia (PE). Little is known about the expression of PGF in the fetus during PE. Pgf  (-/-) mice appear normal but recently cerebral vascular defects were documented in adult Pgf  (-/-) mice. Here, temporal-spatial expression of PGF is mapped in normal fetal mouse brains and cerebral vasculature development is compared between normal and congenic Pgf  (-/-) fetuses to assess the actions of PGF during cerebrovascular development. Pgf/PGF, Vegfa/VEGF, Vegf receptor (Vegfr)1 and Vegfr2 expression were examined in the brains of embryonic day (E)12.5, 14.5, 16.5 and 18.5 C57BL/6 (B6) mice using quantitative PCR and immunohistochemistry. The cerebral vasculature was compared between Pgf  (-/-) and B6 embryonic and adult brains using whole mount techniques. Vulnerability to cerebral ischemia was investigated using a left common carotid ligation assay. Pgf/PGF and Vegfr1 are highly expressed in E12.5-14.5 forebrain relative to VEGF and Vegfr2. Vegfa/VEGF is relatively more abundant in hindbrain (HB). PGF and VEGF expression were similar in midbrain. Delayed HB vascularization was seen at E10.5 and 11.5 in Pgf  (-/-) brains. At E14.5, Pgf  (-/-) circle of Willis showed unilateral hypoplasia and fewer collateral vessels, defects that persisted post-natally. Functionally, adult Pgf  (-/-) mice experienced cerebral ischemia after left common carotid arterial occlusion while B6 mice did not. Since Pgf  (-/-) mice were used, consequences of complete absence of maternal and fetal PGF were defined. Therefore, the effects of maternal versus fetal PGF deficiency on cerebrovascular development cannot be separated. However, as PGF was strongly expressed in the developing brain at all timepoints, we suggest that local PGF has a more important role than distant maternal or placental sources. Full PGF loss is not expected in PE pregnancies, predicting that the effects of PGF deficiency identified in this model will be more severe than any effects in PE-offspring. These studies provoke the question of whether PGF expression is decreased and cerebral vascular maldevelopment occurs in fetuses who experience a preeclamptic gestation. These individuals have already been reported to have elevated risk for stroke and cognitive impairments. N/A. This work was supported by awards from the Natural Sciences and Engineering Research Council, the Canada Research Chairs Program and the Canadian Foundation for Innovation to B.A.C. and by training awards from the Universidade Federal de Pernambuco and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil to R.L.L.; Queen's University to V.R.K. and the Canadian Institutes of Health Research to M.T.R. The work of P.C. is supported by the Belgian Science Policy BELSPO-IUAP7/03, Structural funding by the Flemish Government-Methusalem funding, and the Flemish Science Fund-FWO grants. There were no competing interests. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The role of GPR1 signaling in mice corpus luteum

PubMed Central

Yang, Ya-Li; Ren, Li-Rong; Sun, Li-Feng; Huang, Chen; Xiao, Tian-Xia; Wang, Bao-Bei; Chen, Jie; Zabel, Brian A

2016-01-01

Chemerin, a chemokine, plays important roles in immune responses, inflammation, adipogenesis, and carbohydrate metabolism. Our recent research has shown that chemerin has an inhibitory effect on hormone secretion from the testis and ovary. However, whether G protein-coupled receptor 1 (GPR1), the active receptor for chemerin, regulates steroidogenesis and luteolysis in the corpus luteum is still unknown. In this study, we established a pregnant mare serum gonadotropin-human chorionic gonadotropin (PMSG-hCG) superovulation model, a prostaglandin F2α (PGF2α) luteolysis model, and follicle and corpus luteum culture models to analyze the role of chemerin signaling through GPR1 in the synthesis and secretion of gonadal hormones during follicular/luteal development and luteolysis. Our results, for the first time, show that chemerin and GPR1 are both differentially expressed in the ovary over the course of the estrous cycle, with highest levels in estrus and metestrus. GPR1 has been localized to granulosa cells, cumulus cells, and the corpus luteum by immunohistochemistry (IHC). In vitro, we found that chemerin suppresses hCG-induced progesterone production in cultured follicle and corpus luteum and that this effect is attenuated significantly by anti-GPR1 MAB treatment. Furthermore, when the phosphoinositide 3-kinase (PI3K) pathway was blocked, the attenuating effect of GPR1 MAB was abrogated. Interestingly, PGF2α induces luteolysis through activation of caspase-3, leading to a reduction in progesterone secretion. Treatment with GPR1 MAB blocked the PGF2α effect on caspase-3 expression and progesterone secretion. This study indicates that chemerin/GPR1 signaling directly or indirectly regulates progesterone synthesis and secretion during the processes of follicular development, corpus luteum formation, and PGF2α-induced luteolysis. PMID:27149986

Induction of parturition with prostaglandin f2 alpha as a possible model to study impaired reproductive performance in the dairy cow.

PubMed

Kask, K; Gustafsson, H; Gunnarsson, A; Kindahl, H

2000-05-31

Parturitions were induced in five cows, 2 weeks before term using prostaglandin (PG) F(2alpha). Two i.m. injections were performed with an interval of 24 h. All cows calved within 5 days (average 2.7 days) after the first injection of PGF(2alpha). Out of five cows, four had retained fetal membranes (RFM). Each animal was sampled for bacteriological examination using uterine biopsies twice a week during 42 days postpartum (PP). Jugular vein blood samples were withdrawn for PGF(2alpha)-metabolite and progesterone analyses five times per day during the first week PP and eight times per 24 h during the 2nd and 3rd weeks PP. From the 4th week, the sampling interval was reduced back to five times per day. From the 5th week PP, the sampling was reduced to two times per day and sampling was terminated after day 46 PP. Only morning samples were used for progesterone analyses. From day 10 PP, ultrasonography (US) was performed every 3rd day until day 39 PP for detection of ovarian activity and follicular dynamics. The highest incidence of bacteriological species was found during the first 3 weeks PP. After the 5th week of collection, all animals were free from bacteria. The species of bacteria found were Arcanobacterium (Actinomyces) pyogenes, Escherichia coli, alpha-hemolytic streptococcae and Pasteurella multocida. Immediately after parturition, very high levels of the PG-metabolite were seen in all animals, with a sharp decrease to line of significance around days 9-12 PP. Small increases above the line of significance were detected up to day 27 PP in cows with RFM, and after that time the levels were considered to be at baseline. Low levels of progesterone were seen in four animals during the whole experimental time. In one animal, an increase was seen on day 43 PP, which was maintained until the end of the experimental period on day 46 PP. Based on US, follicular waves were detected in all animals during the experimental period. In three animals, three non-ovulatory follicular waves were detected and in two animals, four non-ovulatory follicular waves were detected during 39 days of ultrasound sessions. Based on progesterone levels, only one animal was considered to have ovulated around day 40 PP. Results from the present study indicate that reproductive performance of cows after PG-induced parturitions differs from those of spontaneous cases of RFM. Differences regarding the resumption of ovarian activity were also observed between previous studies of dexamethasone-induced parturitions and the present study.

Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

PubMed

Weksler, B B; Tack-Goldman, K; Subramanian, V A; Gay, W A

1985-02-01

The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI2 produced by vascular tissues of control subjects who received no aspirin preoperatively (51 +/- 10 pg 6-keto-PGF1 alpha/mg aortic wet weight [mean +/- SEM] in aspirin-treated subjects vs 130 +/- 16 pg/mg in control subjects, and 71 +/- 8 pg/mg saphenous vein wet weight vs 131 +/- 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 +/- 229 ml in aspirin-treated subjects vs 645 +/- 271 ml in control subjects), hematocrit nadir (31.2 +/- 1.9% vs 31.8 +/- 1.7%), or transfusions (2.2 +/- 1.3 units of red blood cells vs 2.2 +/- 1.7 units).(ABSTRACT TRUNCATED AT 250 WORDS)

Therapy of bovine endometritis with prostaglandin F2α: a meta-analysis.

PubMed

Haimerl, P; Heuwieser, W; Arlt, S

2013-05-01

The objective of the conducted meta-analysis was to assess the efficacy of the treatment of bovine endometritis with PGF(2α) by statistical means. Postpartum uterine infections have a high prevalence and a very negative effect on reproductive performance in dairy cattle. Because of a wide discordance between research results, a meta-analysis of the efficacy of the treatment of bovine endometritis with PGF(2α) was conducted. A comprehensive literature search was performed using online databases to reveal a total of 2,307 references. In addition, 5 articles were retrieved by reviewing citations. After applying specific exclusion criteria and evaluating specific evidence parameters, 5 publications, comprising 6 trials, were eligible for being analyzed by means of meta-analysis. Data for each trial were extracted and analyzed using meta-analysis software Review Manager (version 5.1; The Nordic Cochrane Centre, Copenhagen, Denmark). Estimated effect sizes of PGF(2α) were calculated on calving to first service and calving to conception interval. Prostaglandin F(2α) treatment of cows with chronic endometritis had a negative effect on both reproductive performance parameters. Heterogeneity was substantial for calving to first service and calving to conception interval [I(2) (measure of variation beyond chance)=100 and 87%, respectively]; therefore, random-effects models were used. Sensitivity analysis as well as subgroup analysis showed that the performance of randomization was influential in modifying effect size of PGF(2α) treatment. The funnel plot illustrated a publication bias toward smaller studies that reported a prolonged calving to conception interval after a PGF(2α) treatment. We conclude that the investigation of this subject by means of meta-analysis did not reveal an improvement of reproductive performance of cows with endometritis after treatment with PGF(2α). Furthermore, there is a shortage of comparable high quality studies investigating reproductive performance after PGF(2α) treatment of cows with chronic endometritis. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Low physiological levels of prostaglandins E2 and F2α improve human sperm functions.

PubMed

Rios, Mariana; Carreño, Daniela V; Oses, Carolina; Barrera, Nelson; Kerr, Bredford; Villalón, Manuel

2016-03-01

Prostaglandins (PGs) have been reported to be present in the seminal fluid and cervical mucus, affecting different stages of sperm maturation from spermatogenesis to the acrosome reaction. This study assessed the effects of low physiological PGE2 and PGF2α concentrations on human sperm motility and on the ability of the spermatozoa to bind to the zona pellucida (ZP). Human spermatozoa were isolated from seminal samples with normal concentration and motility parameters and incubated with 1μM PGE2, 1μM PGF2α or control solution to determine sperm motility and the ability to bind to human ZP. The effects of both PGs on intracellular calcium levels were determined. Incubation for 2 or 18h with PGE2 or PGF2α resulted in a significant (P<0.05) increase in the percentage of spermatozoa with progressive motility. In contrast with PGF2α, PGE2 alone induced an increase in sperm intracellular calcium levels; however, the percentage of sperm bound to the human ZP was doubled for both PGs. These results indicate that incubation of human spermatozoa with low physiological levels of PGE2 or PGF2α increases sperm functions and could improve conditions for assisted reproduction protocols.

The Regulation of Vascular Endothelial Growth Factor by Hypoxia and Prostaglandin F2α during Human Endometrial Repair

PubMed Central

Maybin, Jacqueline A.; Hirani, Nikhil; Brown, Pamela; Jabbour, Henry N.

2011-01-01

Context: The human endometrium has an exceptional capacity for repeated repair after menses, but its regulation remains undefined. Premenstrually, progesterone levels fall and prostaglandin (PG) F2α synthesis increases, causing spiral arteriole constriction. We hypothesized that progesterone withdrawal, PGF2α, and hypoxia increase vascular endothelial growth factor (VEGF), an endometrial repair factor. Design and Results: Endometrial biopsies were collected (n = 47) with ethical approval and consent. VEGF mRNA, quantified by quantitative RT-PCR, was increased during menstruation (P < 0.01).VEGF protein was maximally secreted from proliferative endometrial explants. Treatment of an endometrial epithelial cell line and primary human endometrial stromal cells with 100 nm PGF2α or hypoxia (0.5% O2) resulted in significant increases in VEGF mRNA and protein. VEGF was maximal when cells were cotreated with PGF2α and hypoxia simultaneously (P < 0.05–0.001). Secretory-phase endometrial explants also showed an increase in VEGF with cotreatment (P < 0.05). However, proliferative-phase explants showed no increase in VEGF on treatment with PGF2α and/or hypoxia. Proliferative tissue was induced to increase VEGF mRNA expression when exposed to progesterone and its withdrawal in vitro but only in the presence of hypoxia and PG. Hypoxia-inducible factor-1α (HIF-1α) silencing with RNA interference suppressed hypoxia-induced VEGF expression in endometrial cells but did not alter PGF2α-induced VEGF expression. Conclusions: Endometrial VEGF is increased at the time of endometrial repair. Progesterone withdrawal, PGF2α, and hypoxia are necessary for this perimenstrual VEGF expression. Hypoxia acts via HIF-1α to increase VEGF, whereas PGF2α acts in a HIF-1α-independent manner. Hence, two pathways regulate the expression of VEGF during endometrial repair. PMID:21677035

Increased levels of the oxidative stress biomarker 8-iso-prostaglandin F2α in wastewater associated with tobacco use.

PubMed

Ryu, Yeonsuk; Gracia-Lor, Emma; Bade, Richard; Baz-Lomba, J A; Bramness, Jørgen G; Castiglioni, Sara; Castrignanò, Erika; Causanilles, Ana; Covaci, Adrian; de Voogt, Pim; Hernandez, Felix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; Ort, Christoph; Plósz, Benedek G; Ramin, Pedram; Rousis, Nikolaos I; Reid, Malcolm J; Thomas, Kevin V

2016-12-15

Wastewater analysis has been demonstrated to be a complementary approach for assessing the overall patterns of drug use by a population while the full potential of wastewater-based epidemiology has yet to be explored. F 2 -isoprostanes are a prototype wastewater biomarker to study the cumulative oxidative stress at a community level. In this work, 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) was analysed in raw 24 h-composite wastewater samples collected from 4 Norwegian and 7 other European cities in 2014 and 2015. Using the same samples, biomarkers of alcohol (ethyl sulfate) and tobacco (trans-3'-hydroxycotinine) use were also analysed to investigate any possible correlation between 8-iso-PGF 2α and the consumption of the two drugs. The estimated per capita daily loads of 8-iso-PGF 2α in the 11 cities ranged between 2.5 and 9.9 mg/day/1000 inhabitants with a population-weighted mean of 4.8 mg/day/1000 inhabitants. There were no temporal trends observed in the levels of 8-iso-PGF 2α , however, spatial differences were found at the inter-city level correlating to the degree of urbanisation. The 8-iso-PGF 2α mass load was found to be strongly associated with that of trans-3'-hydroxycotinine while it showed no correlation with ethyl sulfate. The present study shows the potential for 8-iso-PGF 2α as a wastewater biomarker for the assessment of community public health.

Increased levels of the oxidative stress biomarker 8-iso-prostaglandin F2α in wastewater associated with tobacco use

NASA Astrophysics Data System (ADS)

Ryu, Yeonsuk; Gracia-Lor, Emma; Bade, Richard; Baz-Lomba, J. A.; Bramness, Jørgen G.; Castiglioni, Sara; Castrignanò, Erika; Causanilles, Ana; Covaci, Adrian; de Voogt, Pim; Hernandez, Felix; Kasprzyk-Hordern, Barbara; Kinyua, Juliet; McCall, Ann-Kathrin; Ort, Christoph; Plósz, Benedek G.; Ramin, Pedram; Rousis, Nikolaos I.; Reid, Malcolm J.; Thomas, Kevin V.

2016-12-01

Wastewater analysis has been demonstrated to be a complementary approach for assessing the overall patterns of drug use by a population while the full potential of wastewater-based epidemiology has yet to be explored. F2-isoprostanes are a prototype wastewater biomarker to study the cumulative oxidative stress at a community level. In this work, 8-iso-prostaglandin F2α (8-iso-PGF2α) was analysed in raw 24 h-composite wastewater samples collected from 4 Norwegian and 7 other European cities in 2014 and 2015. Using the same samples, biomarkers of alcohol (ethyl sulfate) and tobacco (trans-3‧-hydroxycotinine) use were also analysed to investigate any possible correlation between 8-iso-PGF2α and the consumption of the two drugs. The estimated per capita daily loads of 8-iso-PGF2α in the 11 cities ranged between 2.5 and 9.9 mg/day/1000 inhabitants with a population-weighted mean of 4.8 mg/day/1000 inhabitants. There were no temporal trends observed in the levels of 8-iso-PGF2α, however, spatial differences were found at the inter-city level correlating to the degree of urbanisation. The 8-iso-PGF2α mass load was found to be strongly associated with that of trans-3‧-hydroxycotinine while it showed no correlation with ethyl sulfate. The present study shows the potential for 8-iso-PGF2α as a wastewater biomarker for the assessment of community public health.

Involvement of cyclooxygenase-2 in carbachol-induced positive inotropic response in mouse isolated left atrium.

PubMed

Hara, Yukio; Ike, Asako; Tanida, Riyo; Okada, Muneyoshi; Yamawaki, Hideyuki

2009-12-01

The mouse heart is expected to have characteristic contractile properties. However, basic information on the function of the mouse heart has not been accumulated sufficiently. In this study, the involvement of cyclooxygenase (COX)-2 in carbachol (CCh)-induced inotropic response was investigated in mouse isolated left atrium. Influences of CCh and their mechanisms of action on developed tension elicited by electrical stimulation were examined pharmacologically. The presence of COX-2 in atrium was examined by Western blotting and immunohistochemical analysis. CCh (3 microM for 15 min) produced a biphasic inotropic response: a transient decrease in contractile force followed by a late increase. Atropine suppressed the biphasic inotropic response to CCh. A muscarinic M(3) receptor antagonist, 4-diphenyl-acetoxy-N-methlpiperidine, inhibited the late positive inotropic action. Blockade of prostaglandin (PG) E(2) or F(2alpha) receptor by 6-isopropoxy-9-oxoxanthene-2-carboxylic acid (AH6809) or 9alpha, 15R-dihydroxy-11beta-fluoro-15-(2,3-dihydro-1H-inden-2-yl)-16,17,18,19,20-pentanor-prosta 5Z, 13E-dien-1-oic acid (AL8810), respectively, significantly suppressed the positive inotropic response to CCh. A nonselective COX inhibitor, indomethacin, and a selective COX-2 inhibitor, N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) inhibited the positive response. A COX-1 inhibitor, valeroyl salicylate, did not affect the positive response. The positive response was almost completely abolished in the endocardial endothelium-deprived atria. Existence of COX-2 in endocardial endothelium was confirmed by Western blotting and immunohistochemical analysis. The present study indicated that the CCh-induced positive inotropic response was mediated by PGs, possibly PGE(2) and PGF(2alpha), released in part from endocardial endothelium. Furthermore, for the first time, we demonstrated that the production of PGs depended in part on COX-2 in endocardial endothelium through the muscarinic M(3) receptor stimulation.

An elevated amniotic fluid prostaglandin F2α concentration is associated with intra-amniotic inflammation/infection, and clinical and histologic chorioamnionitis, as well as impending preterm delivery in patients with preterm labor and intact membranes.

PubMed

Park, Jee Yoon; Romero, Roberto; Lee, JoonHo; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun

2016-01-01

To determine whether an elevated amniotic fluid concentration of prostaglandin F2α (PGF2α) is associated with intra-amniotic inflammation/infection and adverse pregnancy outcomes in patients with preterm labor and intact membranes. The retrospective cohort study included 132 patients who had singleton pregnancies with preterm labor (< 35 weeks of gestation) and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as for genital mycoplasmas. Intra-amniotic inflammation was defined by an elevated amniotic fluid matrix metalloproteinase-8 (MMP-8) concentration (>23 ng/mL). PGF2α was measured with a sensitive and specific immunoassay. The amniotic fluid PGF2α concentration was considered elevated when it was above the 95th percentile among pregnant women at 15-36 weeks of gestation who were not in labor (≥170 pg/mL). (1) The prevalence of an elevated amniotic fluid PGF2α concentration was 40.2% (53/132) in patients with preterm labor and intact membranes; (2) patients with an elevated amniotic fluid PGF2α concentration had a significantly higher rate of positive amniotic fluid culture [19% (10/53) versus 5% (4/79); p = 0.019], intra-amniotic inflammation/infection [49% (26/53) versus 20% (16/79); p = 0.001], spontaneous preterm delivery, clinical and histologic chorioamnionitis, and funisitis, as well as a higher median amniotic fluid MMP-8 concentration and amniotic fluid white blood cell count and a shorter amniocentesis-to-delivery interval than those without an elevated concentration of amniotic fluid PGF2α (p < 0.05 for each); and (3) an elevated amniotic fluid PGF2α concentration was associated with a shorter amniocentesis-to-delivery interval after adjustment for the presence of intra-amniotic inflammation/infection [hazard ratio 2.1, 95% confidence interval (CI) 1.4-3.1; p = 0.001]. The concentration of PGF2α was elevated in the amniotic fluid of 40.2% of patients with preterm labor and intact membranes and is an independent risk factor for intra-amniotic inflammation/infection, impending preterm delivery, chorioamnionitis, and funisitis.

Presynchronization of lactating dairy cows with PGF2α and GnRH simultaneously, 7 days before Ovsynch have similar outcomes compared to G6G.

PubMed

Yousuf, Muhammad Rizwan; Martins, João Paulo N; Ahmad, Nasim; Nobis, Kerry; Pursley, J Richard

2016-10-01

The overarching objective of this study was to develop an alternative strategy for first and greater services that will improve fertility in lactating dairy cows for dairy operations limited by labor or other logistical constraints that make it difficult to use Presynch-11, G6G, or Double-Ovsynch. Our overall hypothesis was that simplification of a Presynch program through the combination of PGF2α and GnRH on the same day (PG + G), 7 days before the first GnRH of Ovsynch, would allow for similar ovulation and luteolysis rate and pregnancies per AI (P/AI) compared with G6G. Lactating dairy cows 58 to 64 days in milk (first service; n = 114), and cows diagnosed not pregnant 39 days after previous AI (second + service; n = 122) were blocked by parity and service and randomly assigned to control or PG + G. Control cows received G6G (n = 116) that consisted of PGF2α, 2-day GnRH, 6-day GnRH, 7-day PGF2α, 56-hour GnRH, and 16-hour AI. Treated cows (PG + G; n = 121) received PGF2α and GnRH, 7-day GnRH, 7-day PGF2α, 56-hour GnRH, and 16-hour AI. All cows received a second PGF2α 24 hours after the PGF2α of Ovsynch. First service cows received AI between 76 and 82 days in milk and second + service received AI 57 days after previous AI. Pregnancies/AI (n = 230) were similar in controls compared with treated cows on Day 35 (57 vs. 50%; P = 0.27) and Day 49 (54 vs. 47%; P = 0.33), respectively. Percent of cows ovulating after GnRH of the presynchronization was greater (P = 0.002) for controls vs. treated (80 vs. 58%); however, ovulation after first GnRH of Ovsynch was similar (67 vs. 68%; P = 0.86). Serum concentrations of progesterone were similar (P = 0.78) at the time of first GnRH of Ovsynch for control and treated cows (2.22 vs. 2.14 ng/mL). However, serum progesterone at the time of PGF2α of Ovsynch was greater (P = 0.002) for control cows compared with treated cows (5.75 vs. 4.64 ng/mL). In summary, administering both PGF2α and GnRH on the same day, 7 days before the start of Ovsynch, appears to be a simple alternative that results in acceptable P/AI but potentially less progesterone during the growth of the ovulatory follicle. Copyright © 2016 Elsevier Inc. All rights reserved.

ATF3 Expression in the Corpus Luteum: Possible Role in Luteal Regression†

PubMed Central

Mao, Dagan; Hou, Xiaoying; Talbott, Heather; Cushman, Robert; Cupp, Andrea

2013-01-01

The present study investigated the induction and possible role of activating transcription factor 3 (ATF3) in the corpus luteum. Postpubertal cattle were treated at midcycle with prostaglandin F2α(PGF) for 0–4 hours. Luteal tissue was processed for immunohistochemistry, in situ hybridization, and isolation of protein and RNA. Ovaries were also collected from midluteal phase and first-trimester pregnant cows. Luteal cells were prepared and sorted by centrifugal elutriation to obtain purified small (SLCs) and large luteal cells (LLCs). Real-time PCR and in situ hybridization showed that ATF3 mRNA increased within 1 hour of PGF treatment in vivo. Western blot and immunohistochemistry demonstrated that ATF3 protein was expressed in the nuclei of LLC within 1 hour and was maintained for at least 4 hours. PGF treatment in vitro increased ATF3 expression only in LLC, whereas TNF induced ATF3 in both SLCs and LLCs. PGF stimulated concentration- and time-dependent increases in ATF3 and phosphorylation of MAPKs in LLCs. Combinations of MAPK inhibitors suppressed ATF3 expression in LLCs. Adenoviral-mediated expression of ATF3 inhibited LH-stimulated cAMP response element reporter luciferase activity and progesterone production in LLCs and SLCs but did not alter cell viability or change the expression or activity of key regulators of progesterone synthesis. In conclusion, the action of PGF in LLCs is associated with the rapid activation of stress-activated protein kinases and the induction of ATF3, which may contribute to the reduction in steroid synthesis during luteal regression. ATF3 appears to affect gonadotropin-stimulated progesterone secretion at a step or steps downstream of PKA signaling and before cholesterol conversion to progesterone. PMID:24196350

Restoration of On-Time Embryo Implantation Corrects the Timing of Parturition in Cytosolic Phospholipase A2 Group IVA Deficient Mice1

PubMed Central

Brown, Naoko; Morrow, Jason D.; Slaughter, James C.; Paria, Bibhash C.; Reese, Jeff

2009-01-01

Cytosolic phospholipase A2 (cPLA2, PLA2G4A) catalyzes the release of arachidonic acid for prostaglandin synthesis by cyclooxygenase 1 (PTGS1) and cyclooxygenase 2 (PTGS2). Mice with Pla2g4a deficiency have parturition delay and other reproductive deficits, including deferred onset of implantation, crowding of implantation sites, and small litters. In this study, we examined the contribution of PLA2G4A to parturition in mice. Pla2g4a mRNA and protein expression were discretely localized in the term and preterm uterine luminal epithelium and colocalized with Ptgs1, but not Ptgs2, expression. The levels of PGE2, PGF2alpha, 6-keto-PGF1alpha, and TxB2 were significantly decreased in Pla2g4a-null uterine tissues, similar to Ptgs1-null uteri, consistent with predominance of PLA2G4A-PTGS1-mediated prostaglandin synthesis in preparation for murine parturition. Litter size was strongly associated with the timing of parturition in Pla2g4a-null mice but could not fully account for the parturition delay. Pla2g4a-null females that received PGE2 + carbaprostacyclin at the time of implantation delivered earlier (20.5 ± 0.2 days vs. 21.6 ± 0.2 days, P < 0.01), although litter size was not improved (4.6 vs. 4.4 pups per litter, P = 0.6). After correction for small litter size, multivariate analysis indicated that Pla2g4a-null mice given prostaglandin treatment to improve implantation timing had gestational length that was similar to wild-type and Pla2g4a heterozygous mice. These results indicate that, despite specific Pla2g4a expression and function in term gestation uteri, the delayed parturition phenotype in Pla2g4a-null mice is primarily due to deferral of implantation. The role of PLA2G4A in timely parturition appears to be critically related to its actions in early pregnancy. PMID:19684335

Prostaglandin F2α–F-Prostanoid Receptor Signalling Promotes Neutrophil Chemotaxis via Chemokine (CXC motif) Ligand-1 in Endometrial Adenocarcinoma

PubMed Central

Wallace, Alison E; Sales, Kurt J; Catalano, Roberto D; Anderson, Richard A; Williams, Alistair RW; Wilson, Martin R; Schwarze, Jurgen; Wang, Hongwei; Rossi, Adriano G; Jabbour, Henry N

2009-01-01

The prostaglandin F2α (PGF2α) receptor (FP) is elevated in endometrial adenocarcinoma. This study found that PGF2α signalling via FP regulates expression of chemokine (C-X-C motif) ligand 1 (CXCL1) in endometrial adenocarcinoma cells. Expression of CXCL1 and its receptor, CXCR2, are elevated in cancer tissue as compared to normal endometrium and localised to glandular epithelium, endothelium and stroma. Treatment of Ishikawa cells stably transfected with the FP receptor (FPS cells) with 100nM PGF2α increased CXCL1 promoter activity, mRNA and protein expression, and these effects were abolished by co-treatment of cells with FP antagonist or chemical inhibitors of Gq, EGFR and ERK. Similarly, CXCL1 was elevated in response to 100 nM PGF2α in endometrial adenocarcinoma explant tissue. CXCL1 is a potent neutrophil chemoattractant. The expression of CXCR2 colocalised to neutrophils in endometrial adenocarcinoma and increased neutrophils were present in endometrial adenocarcinoma compared with normal endometrium. Conditioned media from PGF2α-treated FPS cells stimulated neutrophil chemotaxis which could be abolished by CXCL1 protein immunoneutralisation of the conditioned media or antagonism of CXCR2. Finally, xenograft tumours in nude mice arising from inoculation with FPS cells showed increased neutrophil infiltration compared to tumours arising from wild-type cells or following treatment of mice bearing FPS tumours with CXCL1-neutralising antibody. In conclusion, our results demonstrate a novel PGF2α-FP pathway that may regulate the inflammatory microenvironment in endometrial adenocarcinoma via neutrophil chemotaxis. PMID:19549892

Rapid modulation of gene expression profiles in the telencephalon of male goldfish following exposure to waterborne sex pheromones.

PubMed

Lado, Wudu E; Zhang, Dapeng; Mennigen, Jan A; Zamora, Jacob M; Popesku, Jason T; Trudeau, Vance L

2013-10-01

Sex pheromones rapidly affect endocrine physiology and behaviour, but little is known about their effects on gene expression in the neural tissues that mediate olfactory processing. In this study, we exposed male goldfish for 6h to waterborne 17,20βP (4.3 nM) and PGF2α (3 nM), the main pre-ovulatory and post-ovulatory pheromones, respectively. Both treatments elevated milt volume (P=0.001). Microarray analysis of male telencephalon following PGF2α treatment identified 71 unique transcripts that were differentially expressed (q<5%; 67 up, 4 down). Functional annotation of these regulated genes indicates that PGF2α pheromone exposure affects diverse biological processes including nervous system functions, energy metabolism, cholesterol/lipoprotein transport, translational regulation, transcription and chromatin remodelling, protein processing, cytoskeletal organization, and signalling. By using real-time RT-PCR, we further validated three candidate genes, ependymin-II, calmodulin-A and aldolase C, which exhibited 3-5-fold increase in expression following PGF2α exposure. Expression levels of some other genes that are thought to be important for reproduction were also determined using real-time RT-PCR. Expression of sGnRH was increased by PGF2α, but not 17,20βP, whereas cGnRH expression was increased by 17,20βP but not PGF2α. In contrast, both pheromones increase the expression of glutamate (GluR2a, NR2A) and γ-aminobutyric acid (GABAA γ2) receptor subunit mRNAs. Milt release and rapid modulation of neuronal transcription are part of the response of males to female sex pheromones. Copyright © 2013 Elsevier Inc. All rights reserved.

Lipoic acid prevents suppression of connective tissue proliferation in the rat liver induced by n-3 PUFAs. A pilot study.

PubMed

Arend, A; Zilmer, M; Vihalemm, T; Selstam, G; Sepp, E

2000-01-01

As previously shown, dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) suppress connective tissue proliferation in the rat liver wound concurrent with an elevated level of lipid peroxidation. The present study was undertaken to investigate the influence of alpha-lipoic acid (LA), a natural anti-oxidant, on these effects of n-3 PUFAs. Rats were fed with a commercial pellet diet (control group) or with diets enriched with 10% of sunflower oil (n-6 group) or 10% of fish oil (n-3 group) for 8 weeks followed by addition of LA to the same diets for 10 days. Then a liver thermic wound was induced and the administration of LA was continued for 6 days. The proliferation of the connective tissue, the level of lipid peroxidation and their peroxidizability and the content of prostaglandins E2 and F2alpha were measured in the liver wounds. LA prevented the suppression of connective tissue proliferation in the healing wound induced by n-3 PUFAs, avoided the increase in peroxidation of lipids, reduced peroxidizability of lipids and modulated the decrease in PGE2 and PGF2alpha. The results indicate that dietary LA may prevent the suppression of liver wound healing induced by n-3 PUFAs.

Replacement therapy with levothyroxine modulates platelet activation in recent-onset post-thyroidectomy subclinical hypothyroidism.

PubMed

Desideri, G; Bocale, R; D'Amore, A; Necozione, S; Boscherini, M; Carnassale, G; Barini, A; Barini, A; Bellantone, R; Lombardi, C P

2017-10-01

Subclinical hypothyroidism has been linked to increased risk of atherosclerotic disease. Soluble CD40 ligand (sCD40L), mainly derived from activated platelets, and the lipid peroxidation product 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) are known to play a relevant pathophysiological role in atherogenesis. In this study, we analyzed the relationship between thyroid hormones and circulating levels of sCD40L and 8-iso-PGF 2α in patient with recent-onset post-thyroidectomy subclinical hypothyroidism under replacement therapy. Circulating levels of thyroid hormones, sCD40L, and 8-iso-PGF 2α were assessed in 40 recently thyroidectomized patients (33 females, mean age 52.0 ± 11.7 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with levothyroxine (LT-4). At baseline, circulating levels of thyroid hormones were indicative of a subclinical hypothyroidism (TSH 7.7 ± 3.9 μU/mL, FT3 1.8 ± 0.6 pg/mL, and FT3 8.9 ± 3.0 pg/mL). Circulating levels of sCD40L and 8-iso-PGF 2α were directly correlated with each other (r = 0.360, p = 0.023) and with TSH levels (r = 0.322, p = 0.043 and r = 0.329 p = 0.038, respectively). After 2 months under the replacement therapy with LT-4 circulating levels of TSH (from 7.7 ± 3.9 to 2.7 ± 2.8 μU/mL, p < 0.0001), sCD40L (from 6.11 ± 2.41 to 2.43 ± 2.00 ng/mL, p < 0.0001) and 8-iso-PGF 2α (from 45.33 ± 6.94 to 40.36 ± 6.20, p < 0.0001) significantly decreased. Changes in circulating levels of sCD40L and 8-iso-PGF 2α were directly correlated with each other (r = 0.349 p = 0.028) and with changes in TSH levels (r = 0.367 p = 0.020 and r = 0.339 p = 0.032, respectively). Our study suggests an influential role of TSH on proatherogenic activation of platelets, probably through enhanced lipid peroxidation. These findings could partially explain the increased susceptibility of patients with subclinical hypothyroidism to develop atherosclerotic disease. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Predictors of premature gonadal failure in patients with systemic lupus erythematosus. Results from LUMINA, a multiethnic US cohort (LUMINA LVIII).

PubMed

González, L A; McGwin, G; Durán, S; Pons-Estel, G J; Apte, M; Vilá, L M; Reveille, J D; Alarcón, G S

2008-08-01

To examine the predictors of time to premature gonadal failure (PGF) in patients with systemic lupus erythematosus from LUMINA, a multiethnic US cohort. PGF was defined according to the SLICC Damage Index (SDI). Factors associated with time to PGF occurrence were examined by univariable and multivariable Cox proportional hazards regression analyses: three models according to cyclophosphamide use, at T0 (model 1), over time (model 2) and the total number of intravenous pulses (model 3). Thirty-seven of 316 women (11.7%) developed PGF (19 Texan-Hispanics, 14 African-Americans, four Caucasians and no Puerto Rican-Hispanics). By multivariable analyses, older age at T0 (hazards ratio (HR) = 1.10-1.14; 95% CI 1.02-1.05 to 1.19-1.23) and disease activity (Systemic Lupus Activity Measure-Revised) in all models (HR = 1.22-1.24; 95% CI 1.10-1.12 to 1.35-1.37), Texan-Hispanic ethnicity in models 2 and 3 (HR = 4.06-5.07; 95% CI 1.03-1.25 to 15.94-20.47) and cyclophosphamide use in models 1 and 3 (1-6 pulses) (HR = 4.01-4.65; 95% CI 1.55-1.68 to 9.56-13.94) were predictors of a shorter time to PGF. Disease activity and Texan-Hispanic ethnicity emerged as predictors of a shorter time to PGF while the associations with cyclophosphamide use and older age were confirmed. Furthermore, cyclophosphamide induction therapy emerged as an important determinant of PGF.

Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis.

PubMed

Danz, Henning; Stoyanova, Stefka; Thomet, Olivier A R; Simon, Hans-Uwe; Dannhardt, Gerd; Ulbrich, Holger; Hamburger, Matthias

2002-10-01

The indolo[2,1- b]quinazoline alkaloid tryptanthrin has previously been identified as the cyclooxygenase-2 (COX-2) inhibitory principle in the extract ZE550 prepared from the medicinal plant Isatis tinctoria (Brassicaceae). We here investigated the potential inhibitory activity of tryptanthrin and ZE550 on COX-2, COX-1 in cellular and cell-free systems. A certain degree of selectivity towards COX-2 was observed when COX-1-dependent formation of thromboxane B(2) (TxB(2)) in HEL cells and COX-2-dependent formation of 6-ketoprostaglandin F(1alpha) (6-keto-PGF(1alpha)) in Mono Mac 6 and RAW 264.7 cells were compared. Preferential inhibition of COX-2 by two orders of magnitude was found in phorbol myristate acetate (PMA) activated bovine aortic coronary endothelial cells (BAECs). Assays with purified COX isoenzymes from sheep confirmed the high selectivity towards COX-2. The leukotriene B(4) (LTB(4)) release from calcium ionophore-stimulated human granulocytes (neutrophils) was used as a model to determine 5-lipoxygenase (5-LOX) activity. Tryptanthrin and the extract ZE550 inhibited LTB(4) release in a dose dependent manner and with a potency comparable to that of the clinically used 5-LOX inhibitor zileuton.

Individuals with autism have higher 8-Iso-PGF2α levels than controls, but no correlation with quantitative assay of Paraoxonase 1 serum levels.

PubMed

Pop, Bianca; Niculae, Alexandru-Ștefan; Pop, Tudor Lucian; Răchișan, Andreea Liana

2017-12-01

Autism spectrum disorder (ASD) represents a very large set of neurodevelopmental issues with diverse clinical outcomes. Various hypotheses have been put forth for the etiology of autism spectrum disorder, including issues pertaining to oxidative stress. In this study, we conducted measurements of serum 8-Iso-Prostaglanding F2 α (8-iso-PGF2α, which is the results of non-enzimatically mediated polyunsaturated fatty acid oxidation) in a population of individuals with autism and a control group of age and sex matched controls. A quantitative assay of Paraoxonase 1 (PON1) was conducted. Data regarding comorbidities, structural MRI scans, medication, intelligence quotient (IQ) and Childhood Autism Rating Scale scores (CARS) were also included in our study. Our results show that patients diagnosed with autism have higher levels of 8-iso-PGF2α than their neurotypical counterparts. Levels of this particular metabolite, however, do not correlate with quantitative serum levels of Paraoxonase 1, which has been shown to be altered in individuals with autism. Neither 8-iso-PGF2α nor quantitative levels of PON1 provide any meaningful correlation with clinical or neuroimaging data in this study group. Future research should focus on providing data regarding PON 1 phenotype, in addition to standard quantitative measurements, in relation to 8-iso-PGF2α as well as other clinical and structural brain findings.

Performance of the dot product function in radiative transfer code SORD

NASA Astrophysics Data System (ADS)

Korkin, Sergey; Lyapustin, Alexei; Sinyuk, Aliaksandr; Holben, Brent

2016-10-01

The successive orders of scattering radiative transfer (RT) codes frequently call the scalar (dot) product function. In this paper, we study performance of some implementations of the dot product in the RT code SORD using 50 scenarios for light scattering in the atmosphere-surface system. In the dot product function, we use the unrolled loops technique with different unrolling factor. We also considered the intrinsic Fortran functions. We show results for two machines: ifort compiler under Windows, and pgf90 under Linux. Intrinsic DOT_PRODUCT function showed best performance for the ifort. For the pgf90, the dot product implemented with unrolling factor 4 was the fastest. The RT code SORD together with the interface that runs all the mentioned tests are publicly available from ftp://maiac.gsfc.nasa.gov/pub/skorkin/SORD_IP_16B (current release) or by email request from the corresponding (first) author.

Technical report. The application of probability-generating functions to linear-quadratic radiation survival curves.

PubMed

Kendal, W S

2000-04-01

To illustrate how probability-generating functions (PGFs) can be employed to derive a simple probabilistic model for clonogenic survival after exposure to ionizing irradiation. Both repairable and irreparable radiation damage to DNA were assumed to occur by independent (Poisson) processes, at intensities proportional to the irradiation dose. Also, repairable damage was assumed to be either repaired or further (lethally) injured according to a third (Bernoulli) process, with the probability of lethal conversion being directly proportional to dose. Using the algebra of PGFs, these three processes were combined to yield a composite PGF that described the distribution of lethal DNA lesions in irradiated cells. The composite PGF characterized a Poisson distribution with mean, chiD+betaD2, where D was dose and alpha and beta were radiobiological constants. This distribution yielded the conventional linear-quadratic survival equation. To test the composite model, the derived distribution was used to predict the frequencies of multiple chromosomal aberrations in irradiated human lymphocytes. The predictions agreed well with observation. This probabilistic model was consistent with single-hit mechanisms, but it was not consistent with binary misrepair mechanisms. A stochastic model for radiation survival has been constructed from elementary PGFs that exactly yields the linear-quadratic relationship. This approach can be used to investigate other simple probabilistic survival models.

Classifying oxidative stress by F2-isoprostane levels across human diseases: A meta-analysis.

PubMed

van 't Erve, Thomas J; Kadiiska, Maria B; London, Stephanie J; Mason, Ronald P

2017-08-01

The notion that oxidative stress plays a role in virtually every human disease and environmental exposure has become ingrained in everyday knowledge. However, mounting evidence regarding the lack of specificity of biomarkers traditionally used as indicators of oxidative stress in human disease and exposures now necessitates re-evaluation. To prioritize these re-evaluations, published literature was comprehensively analyzed in a meta-analysis to quantitatively classify the levels of systemic oxidative damage across human disease and in response to environmental exposures. In this meta-analysis, the F 2 -isoprostane, 8-iso-PGF 2α , was specifically chosen as the representative marker of oxidative damage. To combine published values across measurement methods and specimens, the standardized mean differences (Hedges' g) in 8-iso-PGF 2α levels between affected and control populations were calculated. The meta-analysis resulted in a classification of oxidative damage levels as measured by 8-iso-PGF 2α across 50 human health outcomes and exposures from 242 distinct publications. Relatively small increases in 8-iso-PGF 2α levels (g<0.8) were found in the following conditions: hypertension (g=0.4), metabolic syndrome (g=0.5), asthma (g=0.4), and tobacco smoking (g=0.7). In contrast, large increases in 8-iso-PGF 2α levels were observed in pathologies of the kidney, e.g., chronic renal insufficiency (g=1.9), obstructive sleep apnoea (g=1.1), and pre-eclampsia (g=1.1), as well as respiratory tract disorders, e.g., cystic fibrosis (g=2.3). In conclusion, we have established a quantitative classification for the level of 8-iso-PGF 2α generation in different human pathologies and exposures based on a comprehensive meta-analysis of published data. This analysis provides knowledge on the true involvement of oxidative damage across human health outcomes as well as utilizes past research to prioritize those conditions requiring further scrutiny on the mechanisms of biomarker generation. Copyright © 2017. Published by Elsevier B.V.

Pollen-mediated gene flow from transgenic cotton under greenhouse conditions is dependent on different pollinators

PubMed Central

Yan, Shuo; Zhu, Jialin; Zhu, Weilong; Li, Zhen; Shelton, Anthony M.; Luo, Junyu; Cui, Jinjie; Zhang, Qingwen; Liu, Xiaoxia

2015-01-01

With the large-scale release of genetically modified (GM) crops, there are ecological concerns on transgene movement from GM crops to non-GM counterparts and wild relatives. In this research, we conducted greenhouse experiments to measure pollen-mediated gene flow (PGF) in the absence and presence of pollinators (Bombus ignitus, Apis mellifera and Pieris rapae) in one GM cotton (resistant to the insect Helicoverpa armigera and the herbicide glyphosate) and two non-GM lines (Shiyuan321 and Hai7124) during 2012 and 2013. Our results revealed that: (1) PGF varied depending on the pollinator species, and was highest with B. ignitus (10.83%) and lowest with P. rapae (2.71%); (2) PGF with B. ignitus depended on the distance between GM and non-GM cottons; (3) total PGF to Shiyuan321 (8.61%) was higher than to Hai7124 (4.10%). To confirm gene flow, we tested hybrids carrying transgenes for their resistance to glyphosate and H. armigera, and most hybrids showed strong resistance to the herbicide and insect. Our research confirmed that PGF depended on pollinator species, distance between plants and the receptor plant. PMID:26525573

Evaluation of local trace element status and 8-Iso-prostaglandin F2α concentrations in patients with Tinea pedis.

PubMed

Miraloglu, Meral; Kurutas, Ergul Belge; Ozturk, Perihan; Arican, Ozer

2016-01-01

Tinea pedis (TP) is an infection of the feet caused by fungi. The infectious diseases caused by dermatophytes are mainly related to the enzymes produced by these fungi. Up to the now, the local 8-iso-prostaglandin F2α (8-iso-PGF2α), concentration as oxidative stress biomarker and trace elements status have not been published in patients with TP. The aim of this study is to evaluate the relationship between oxidative stress and trace elements (Cu, Zn, Se), and to evaluate the ratios of Cu/Zn and Cu/Se in this disorder. Forty-three consecutive patients with a diagnosis of unilateral interdigital TP were enrolled in this study. The samples were obtained by scraping the skin surface. 8-iso-PGF2α concentrations in scraping samples were determined by ELISA. In addition, the levels of Se, Zn and Cu in scraping samples were determined on flame and furnace atomic absorption spectrophotometer using Zeeman background correction. Oxidative stress was confirmed by the significant elevation in 8-iso-PGF2α concentrations (p < 0.05). When compared to non-lesional area, Zn and Se levels were significantly lower on lesional area, whereas Cu levels was higher on the lesional area than the non-lesional area (p < 0.05). In addition, the correlation results of this study were firstly shown that there were significant and positive correlations between Cu and 8-iso-PGF2α parameters, but negative correlations between Se-Cu; Se-8-iso-PGF2α parameters in lesional area. Furthermore, the ratios of Cu/Zn and Cu/Se were significantly higher on the lesional area than the non-lesional area (p < 0.05). According to sex and fungal subtypes, there was no significant difference in the concentrations of 8-iso-PGF2α and trace elements in patients with TP (p > 0.05). Our results showed that there is a possible link between oxidative stress (increased 8-iso-PGF2α concentrations) and imbalanced of trace elements status in lesional area of TP patients. The use of antifungal agents together with both Zn and Se drugs could be helpful in the both regression of disease and in shortening the duration of disease.

The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation.

PubMed

Sun, Yu-Qian; He, Gan-Lin; Chang, Ying-Jun; Xu, Lan-Ping; Zhang, Xiao-Hui; Han, Wei; Chen, Huan; Chen, Yu-Hong; Wang, Yu; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

2015-10-01

Primary poor graft function (PGF) is a severe complication after allogeneic stem cell transplantation (SCT). The incidence, risk factors, and outcomes of PGF have not been well described, especially in the haploidentical SCT setting. We retrospectively reviewed patients who received haploidentical SCT at Peking University Institute of Hematology between January 1, 2011, and December 31, 2012. PGF was defined as persistent neutropenia (≤0.5 × 10(9) L(-1)), thrombocytopenia (platelets ≤20 × 10(9) L(-1)), and/or hemoglobin ≤70 g L(-1) after engraftment with hypocellular bone marrow and full donor chimerism, without concurrent graft-versus-host disease or disease relapse. Incidence was calculated from all patients. Of the 464 total patients, 26 (5.6 %) developed primary PGF. The risk factors were analyzed and compared with control patients with good graft function who were selected using the case-pair method. Finally, 104 patients were selected as a control group according to the matching conditions: (1) the type (acute leukemia, myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML)) and status (standard risk, high risk) of underlying disease, (2) sex, (3) year in which the transplantation was received, and (4) a 1:4 ratio of case-control. No factors were found to be associated with primary PGF. Compared to cases with good graft function, patients with primary PGF experienced poor overall survival (34.6 vs. 82.7 %, p < 0.001). Of the 26 primary PGF patients, only nine achieved hematopoietic recovery and survived. In conclusion, primary PGF is a rare but life-threatening complication after haploidentical SCT, and effective therapies need to be explored.

Insights into the Prostanoid Pathway in the Ovary Development of the Penaeid Shrimp Penaeus monodon

PubMed Central

Wimuttisuk, Wananit; Tobwor, Punsa; Deenarn, Pacharawan; Danwisetkanjana, Kannawat; Pinkaew, Decha; Kirtikara, Kanyawim; Vichai, Vanicha

2013-01-01

The prostanoid pathway converts polyunsaturated fatty acids (PUFAs) into bioactive lipid mediators, including prostaglandins, thromboxanes and prostacyclins, all of which play vital roles in the immune and reproductive systems in most animal phyla. In crustaceans, PUFAs and prostaglandins have been detected and often associated with female reproductive maturation. However, the presence of prostanoid biosynthesis genes remained in question in these species. In this study, we outlined the prostanoid pathway in the black tiger shrimp Penaeus monodon based on the amplification of nine prostanoid biosynthesis genes: cytosolic phospholipase A2, hematopoietic prostaglandin D synthase, glutathione-dependent prostaglandin D synthase, prostaglandin E synthase 1, prostaglandin E synthase 2, prostaglandin E synthase 3, prostaglandin F synthase, thromboxane A synthase and cyclooxygenase. TBLASTX analysis confirmed the identities of these genes with 51-99% sequence identities to their closest homologs. In addition, prostaglandin F2α (PGF2α), which is a product of the prostaglandin F synthase enzyme, was detected for the first time in P. monodon ovaries along with the previously identified PUFAs and prostaglandin E2 (PGE2) using RP-HPLC and mass-spectrometry. The prostaglandin synthase activity was also observed in shrimp ovary homogenates using in vitro activity assay. When prostaglandin biosynthesis was examined in different stages of shrimp ovaries, we found that the amounts of prostaglandin F synthase gene transcripts and PGF2α decreased as the ovaries matured. These findings not only indicate the presence of a functional prostanoid pathway in penaeid shrimp, but also suggest a possible role of the PGF2α biosynthesis in shrimp ovarian development. PMID:24116186

Plasma oxidative stress biomarkers and progesterone profiles in a dairy cow diagnosed with an ovarian follicular cyst.

PubMed

Talukder, S; Ingenhoff, L; Kerrisk, K L; Celi, P

2014-01-01

This study was conducted to examine the oxidative stress biomarkers in a cow diagnosed with a follicular cyst in her left ovary. Progesterone (P4) and plasma oxidative stress status was measured in 13 Holstein cows after synchronization of oestrus with controlled internal drug release (CIDR) and prostaglandinF2α (PGF2α) protocol. The presence and size of ovarian structures were monitored by transrectal ultrasound at 4 hourly intervals. Of the 13 cows, 12 were monitored until ovulation was detected and recorded, whereas one cow failed to ovulate and developed a follicular cyst. Oxidative stress biomarkers; reactive oxygen metabolites (ROMs), biological antioxidant potential (BAP), oxidative stress index (OSI), glutathione (GSH), ceruloplasmin and advanced oxidation protein products (AOPP) were measured in the cystic cow and compared to those of the 12 ovulated cows and are referred to as higher or lower if they are outside the mean ± standard error of mean of those of ovulated cows. The cystic cow had lower ROMs and OSI between 36 and 84 h after PGF2α injection and at 9 h, from 36 to 60 h after PGF2α injection respectively. On the other hand, antioxidant (BAP and GSH) was higher in the cystic cow compared to her ovulated herd mates. The observed imbalance between oxidant and antioxidant might have disrupted the physiological events for ovulation to occur, leading to cystic ovarian disease.

Increased leukotriene E4 excretion in systemic mastocytosis.

PubMed

Butterfield, Joseph H

2010-06-01

Cysteinyl leukotrienes such as LTE(4) are produced by mast cells, neutrophils, eosinophils, and macrophages. LTE(4) levels have not been reported in systemic mastocytosis, a disorder with a large increase in mast cell numbers. Urinary LTE(4) from patients referred for symptoms potentially due to mast cell degranulation or systemic mastocytosis was measured by a commercial cysteinyl leukotriene enzyme immunoassay kit. The diagnosis of systemic mastocytosis was established using current World Health Organization criteria. Compared with a control group of patients with various potential mast cell-related symptoms (e.g., "spells"), patients with systemic mastocytosis had a significant (P=.01) increase in urinary LTE(4) excretion, whether expressed as LTE(4) ng/g creatinine or as LTE(4) ng/24h. There was a moderate correlation of LTE(4) ng/24h with excretion of N-methyl histamine and serum tryptase but not with urinary 11beta-prostaglandin F(2alpha) (11beta-PGF(2alpha)) excretion. LTE(4) excretion is increased in patients with systemic mastocytosis and potentially contributes to clinical symptoms. Copyright 2010 Elsevier Inc. All rights reserved.

Improvement of physiological parameters of rats subjected to hypercaloric diet, with the use of Pereskia grandifolia (Cactaceae) leaf flour.

PubMed

de Almeida, Martha Elisa Ferreira; Simão, Anderson Assaid; Corrêa, Angelita Duarte; de Barros Fernandes, Regiane Victória

The aim of the present study was to investigate the anti-obesity effects of Pereskia grandifolia leaf flour on rats fed a hypercaloric diet. After a hypercaloric diet for 10 weeks, 21 animals were divided into the following groups and were fed the following diets for 4 weeks: control (CH), hypercaloric diet with P. grandifolia flour (PGF) 5%, and hypercaloric diet with PGF 10%. Several measurements were performed including body weight, food consumption, body mass index, Lee index, liver weight, liver and body moisture content, and body and hepatic lipid level. Data were analyzed by Tukey's test at 5% probability. Rats fed PGF diet had decreased food consumption and body weight and showed lower body mass and Lee indices compared to control group. At week 2, weight of the PGF 10% group was statistically lower than the control group (CH). At week 4, the PGF 10% group demonstrated the highest body weight loss compared to the other two groups. There were no significant difference in total lipids and moisture level between the groups; however, rats fed PGF diet had lower hepatic lipids levels than control group and reduced liver weight. This suggests that PGF induced weight loss and decreased hepatic lipid level and may be effective in treating obesity and related metabolic diseases. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Mechanically induced alterations in cultured skeletal muscle growth

NASA Technical Reports Server (NTRS)

Vandenburgh, H. H.; Hatfaludy, S.; Karlisch, P.; Shansky, J.

1991-01-01

Model systems are available for mechanically stimulating cultured skeletal muscle cells by passive tensile forces which simulate those found in vivo. When applied to embryonic muscle cells in vitro these forces induce tissue organogenesis, metabolic adaptations, and muscle cell growth. The mechanical stimulation of muscle cell growth correlates with stretch-induced increases in the efflux of prostaglandins PGE2 and PGF2(alpha) in a time and frequency dependent manner. These prostaglandins act as mechanical 'second messengers' regulating skeletal muscle protein turnover rates. Since they also effect bone remodelling in response to tissue loading and unloading, secreted prostaglandins may serve as paracrine growth factors, coordinating the growth rates of muscle and bone in response to external mechanical forces. Cell culture model systems will supplement other models in understanding mechanical transduction processes at the molecular level.

Merging Station Observations with Large-Scale Gridded Data to Improve Hydrological Predictions over Chile

NASA Astrophysics Data System (ADS)

Peng, L.; Sheffield, J.; Verbist, K. M. J.

2016-12-01

Hydrological predictions at regional-to-global scales are often hampered by the lack of meteorological forcing data. The use of large-scale gridded meteorological data is able to overcome this limitation, but these data are subject to regional biases and unrealistic values at local scale. This is especially challenging in regions such as Chile, where climate exhibits high spatial heterogeneity as a result of long latitude span and dramatic elevation changes. However, regional station-based observational datasets are not fully exploited and have the potential of constraining biases and spatial patterns. This study aims at adjusting precipitation and temperature estimates from the Princeton University global meteorological forcing (PGF) gridded dataset to improve hydrological simulations over Chile, by assimilating 982 gauges from the Dirección General de Aguas (DGA). To merge station data with the gridded dataset, we use a state-space estimation method to produce optimal gridded estimates, considering both the error of the station measurements and the gridded PGF product. The PGF daily precipitation, maximum and minimum temperature at 0.25° spatial resolution are adjusted for the period of 1979-2010. Precipitation and temperature gauges with long and continuous records (>70% temporal coverage) are selected, while the remaining stations are used for validation. The leave-one-out cross validation verifies the robustness of this data assimilation approach. The merged dataset is then used to force the Variable Infiltration Capacity (VIC) hydrological model over Chile at daily time step which are compared to the observations of streamflow. Our initial results show that the station-merged PGF precipitation effectively captures drizzle and the spatial pattern of storms. Overall the merged dataset has significant improvements compared to the original PGF with reduced biases and stronger inter-annual variability. The invariant spatial pattern of errors between the station data and the gridded product opens up the possibility of merging real-time satellite and intermittent gauge observations to produce more accurate real-time hydrological predictions.

Evaluation of the role of 8-iso-PGF levels at multiple sites during intracranial hemorrhage in pediatric patients.

PubMed

Qi, B-X; Yao, H; Shang, L; Sheng, L-P; Wang, X-C; Zhu, L; Zhang, X-X; Wang, J-P; Fang, D-H

2017-09-01

The present study was planned to explore the role of 8-isomeric-prostaglandinF2α (8-iso-PGF2α) levels at the multiple sites of cerebrospinal fluid in children with intracranial hemorrhage. 90 children with intracranial hemorrhage were admitted to Surgery Intensive Care Unit (SICU) of our hospital from January to December 2013 and were selected as study subjects. They were divided into group A (n=30), group B (n=30) and group C (n=30). The group A was given conventional treatment, the group B was treated with minimally invasive puncture and the group C was treated with cerebrospinal fluid decompression. After 1 d, 2 d, 3 d, and 7 d of hospitalization, enzyme-linked immunosorbent assay (ELISA) was used to detect the 8-iso-PGF2α levels in peripheral blood of children in all groups. On the day of admission and 10 d after treatment, 3 groups of children were implemented with brain nuclear magnetic resonance spectroscopy for metabolite analyses. On the day of admission there were no significant differences in the 8-iso-PGF2α levels among group A, B and C. Further, after 1 d, 3 d, 7 d of hospital stay, the 8-iso-PGF2α levels in peripheral blood showed a gradual downward trend, and decline range of the group C was greater than that of group A and B (p < 0.05). After 10 days of treatment, there were significant differences in the bilateral temporal lobe and hippocampal NAA/Creatinine (Cr), Cho/Cr, mI/Cr and NAA/mI among group A, B, and C. The survival rate of group C was higher than that of group A and B (p < 0.05). On the other hand, the prevalence of sequelae was significantly lower than that of group A and B (p < 0.05). The amount of blood loss in children with intracranial hemorrhage was positively correlated with the levels of 8-iso-PGF2α in peripheral blood (r = 0.546, p < 0.05) as observed by Spearman correlation analysis. 8-iso-PGF2α plays an important role in the pathogenesis of intracranial hemorrhage, and could be utilized as a biomarker of oxidative stress in children with intracranial hemorrhage. Further, cerebrospinal fluid decompression is a better method of treatment for intracranial hemorrhage.

Prostaglandins mediate the stimulatory effects of endothelin-1 on cAMP accumulation and inositol-1,4,5-trisphosphate production and contraction in cat iris sphincter.

PubMed

Yousufzai, S Y; Ye, Z; Abdel-Latif, A A

1995-12-01

We previously reported that in the iris sphincter smooth muscle, endothelin-1 (ET-1) activates both adenylyl cyclase and the phosphoinositide cascade and that the changes in the levels of cAMP and inositol-1,4,5-trisphosphate (IP3) produced are species specific. In the present study, we examined the mechanism of the ET-1 effects in cat iris sphincter. In general, we found that ET-1 (0.1 microM) increased prostaglandin E2 (PGE2) release by 156%, cAMP accumulation by 310%, IP3 production by 88% and induced contraction; that PGE2 increased cAMP accumulation, IP3 production and contraction; and that the effects of ET-1 are inhibited by indomethacin (Indo), suggesting that arachidonic acid metabolites may mediate the responses to the peptide. Kinetic studies revealed the following: (1) The effect of ET-1 on cAMP accumulation is rapid (within 30 sec), dose dependent (EC50 = 5.8 nM) and completely abolished by Indo (Ki = 0.16 microM), a cyclooxygenase inhibitor, but not by nordihydroguairetic acid, a lipoxygenase inhibitor, implying the involvement of PGs. (2) ET-1 dose-dependently evoked PGe2 release (EC50 = 1.8 nM), IP3 production (EC50 = 4.5 nM) and contraction (EC50 = 5 nM) and that all of these responses were inhibited by Indo. (3) PGE2 increased cAMP accumulation in a dose-dependent manner with an EC50 of 1.5 x 10(-7) M, and PGD2 and PGF2 alpha had little effect on the cyclic nucleotide. (4) PGE2 (1 microM), increased IP3 production by 55% and induced muscle contraction in a dose-dependent manner (EC50 = 40 nM). We conclude from these data that in cat iris sphincter PGs may mediate ET-1-induced cAMP accumulation, IP3 production and smooth muscle contraction.

The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases.

PubMed

Rhodes, Lesley E; Gledhill, Karl; Masoodi, Mojgan; Haylett, Ann K; Brownrigg, Margaret; Thody, Anthony J; Tobin, Desmond J; Nicolaou, Anna

2009-11-01

Sunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids, and their subsequent metabolism by cyclooxygenases (COXs) and lipoxygenases (LOXs) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course. We exposed skin of healthy humans (n=32) to UVB and, for 72 h, examined expression of proinflammatory and anti-inflammatory eicosanoids using LC/ESI-MS/MS, and examined immunohistochemical expression of COX-2, 12-LOX, 15-LOX, and leukocyte markers, while quantifying clinical erythema. We show that vasodilatory prostaglandins (PGs) PGE(2), PGF(2alpha), and PGE(3) accompany the erythema in the first 24-48 h, associated with increased COX-2 expression at 24 h. Novel, potent leukocyte chemoattractants 11-, 12-, and 8-monohydroxy-eicosatetraenoic acid (HETE) are elevated from 4 to 72 h, in association with peak dermal neutrophil influx at 24 h, and increased dermal CD3(+) lymphocytes and 12- and 15-LOX expression from 24 to 72 h. Anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72 h. Sunburn is characterized by overlapping sequential profiles of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution.

Depressed levels of prostaglandin F2α in mice lacking Akr1b7 increase basal adiposity and predispose to diet-induced obesity.

PubMed

Volat, Fanny E; Pointud, Jean-Christophe; Pastel, Emilie; Morio, Béatrice; Sion, Benoit; Hamard, Ghislaine; Guichardant, Michel; Colas, Romain; Lefrançois-Martinez, Anne-Marie; Martinez, Antoine

2012-11-01

Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prostaglandin F(2α) (PGF(2α)) is a potent antiadipogenic factor in cultured preadipocytes, but evidence for its involvement in physiological context is lacking. We previously reported that Akr1b7, an aldo-keto reductase enriched in adipose stromal vascular fraction but absent from mature adipocytes, has antiadipogenic properties possibly supported by PGF(2α) synthase activity. To test whether lack of Akr1b7 could influence WAT homeostasis in vivo, we generated Akr1b7(-/-) mice in 129/Sv background. Akr1b7(-/-) mice displayed excessive basal adiposity resulting from adipocyte hyperplasia/hypertrophy and exhibited greater sensitivity to diet-induced obesity. Following adipose enlargement and irrespective of the diet, they developed liver steatosis and progressive insulin resistance. Akr1b7 loss was associated with decreased PGF(2α) WAT contents. Cloprostenol (PGF(2α) agonist) administration to Akr1b7(-/-) mice normalized WAT expansion by affecting both de novo adipocyte differentiation and size. Treatment of 3T3-L1 adipocytes and Akr1b7(-/-) mice with cloprostenol suggested that decreased adipocyte size resulted from inhibition of lipogenic gene expression. Hence, Akr1b7 is a major regulator of WAT development through at least two PGF(2α)-dependent mechanisms: inhibition of adipogenesis and lipogenesis. These findings provide molecular rationale to explore the status of aldo-keto reductases in dysregulations of adipose tissue homeostasis.

Comparison of 2 protocols to increase circulating progesterone concentration before timed artificial insemination in lactating dairy cows with or without elevated body temperature.

PubMed

Pereira, M H C; Wiltbank, M C; Guida, T G; Lopes, F R; Vasconcelos, J L M

2017-10-01

Two treatments designed to increase circulating progesterone concentration (P4) during preovulatory follicle development were compared. One treatment used 2 intravaginal P4 implants (controlled internal drug-releasing inserts; CIDR) and the other used a GnRH treatment at beginning of the protocol. Lactating Holstein cows that had been diagnosed as nonpregnant were randomly assigned to receive timed artificial insemination (TAI) following 1 of 2 treatments (n = 1,638 breedings): (1) GnRH: CIDR+ 2 mg of estradiol (E2) benzoate + 100 µg of GnRH on d -11, PGF 2α on d -4, CIDR withdrawal + 1.0 mg of E2-cypionate + PGF 2α ) on d -2, and TAI on d 0; or (2) 2CIDR: 2 CIDR + 2 mg of E2-benzoate on d -11, 1 CIDR withdrawn + PGF 2α on d -4, second CIDR withdrawn + 1.0 mg of E2-cypionate + PGF 2α on d -2, and TAI on d 0. Milk yield was measured daily between d 0 and d 7. Rectal temperature was measured using a digital thermometer at d 0 and 7, and elevated body temperature was defined as an average rectal temperature ≥39.1°C. Pregnancy diagnoses were performed on d 32 and 60 after TAI. We detected no effect of treatments on pregnancy per AI or pregnancy loss regardless of elevated body temperature, body condition score, parity, milk yield, or presence or absence of a corpus luteum (CL) on d -11 or d -4. Pregnancy per AI at 60 d was reduced [elevated body temperature = 22.8% (162/709), no elevated body temperature 34.1% (279/817)] and pregnancy loss tended to increase [elevated body temperature = 20.2% (41/203), no elevated body temperature 14.4% (47/326)] in cows with elevated body temperature. Various physiological measurements associated with greater fertility were also reduced in cows with elevated body temperature, such as percentage of cows with a CL at PGF 2α (decreased 7.9%), ovulatory follicle diameter (decreased 0.51 mm), expression of estrus (decreased 5.1%), and ovulation near TAI (decreased 2.8%) compared with cows without elevated body temperature. A greater proportion of cows (30.2%) had a CL at PGF 2α in the GnRH treatment [74.1% (570/763)] than in the 2CIDR treatment [56.9% (434/763)]; however, circulating P4 concentration was greater at the time of PGF 2α treatment (d -4) for cows 2CIDR (4.26 ± 0.13 ng/mL) than in cows in GnRH (3.99 ± 0.14 ng/mL). Thus, these 2 protocols yield similar fertility results that might be due to somewhat different physiological alterations. Treatment with GnRH increased the proportion of cows with a CL at PGF 2α ; however, the 2CIDR protocol increased circulating P4 under all circumstances. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Plerocercoid growth factor (PGF), a human growth hormone (hGH) analogue produced by the tapeworm Spirometra mansonoides, has direct insulin-like action in adipose tissue of normal rats in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salem, M.A.M.; Phares, C.K.

1986-03-01

The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate (U-/sup 14/C)glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity.more » To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10/sup 5/ cells/ml) were incubated with either (/sup 125/I)insulin or (/sup 125/I)hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and /sup 14/C-incorporation into lipids. Insulin, hGH and PGF inhibited lipolysis (33%, 29% and 34%, respectively). Adipose tissue was very sensitive to the lipolytic effect of hGH but PGF was neither lipolytic nor did it confer refractoriness to its insulin-like action. PGF bound to GH but not to insulin receptors. Therefore, PGF had direct insulin-like effects but did not stimulate lipolysis in tissue from normal rats in vitro.« less

A longitudinal study of atrazine and 2,4-D exposure and oxidative stress markers among Iowa corn farmers

PubMed Central

Lerro, Catherine C.; Beane Freeman, Laura E.; Portengen, Lützen; Kang, Daehee; Lee, Kyoungho; Blair, Aaron; Lynch, Charles F.; Bakke, Berit; De Roos, Anneclaire J.; Vermeulen, Roel C.H.

2018-01-01

Reactive oxygen species, potentially formed through environmental exposures, can overwhelm an organism’s antioxidant capabilities resulting in oxidative stress. Long-term oxidative stress is linked with chronic diseases. Pesticide exposures have been shown to cause oxidative stress in vivo. We utilized a longitudinal study of corn farmers and non-farming controls in Iowa to examine the impact of exposure to the widely used herbicides atrazine and 2,4-dichlorophenoxyacetic acid (2,4-D) on markers of oxidative stress. 225 urine samples were collected during five agricultural time periods (pre-planting, planting, growing, harvest, off-season) for 30 farmers who applied pesticides occupationally and 10 controls who did not; all were non-smoking men ages 40–60. Atrazine mercapturate (atrazine metabolite), 2,4-D, and oxidative stress markers (malondialdehyde [MDA], 8-hydroxy-2′-deoxyguanosine [8-OHdG], and 8-isoprostaglandin-F2α [8-isoPGF]) were measured in urine. We calculated β estimates and 95% confidence intervals (95%CI) for each pesticide-oxidative stress marker combination using multivariate linear mixed-effect models for repeated measures. Farmers had higher urinary atrazine mercapturate and 2,4-D levels compared to controls. In regression models, after natural log transformation, 2,4-D was associated with elevated levels of 8-OHdG (β=0.066, 95%CI=0.008–0.124) and 8-isoPGF (β=0.088, 95%CI=0.004–0.172). 2,4-D may be associated with oxidative stress because of modest increases in 8-OHdG, a marker of oxidative DNA damage, and 8-isoPGF, a product of lipoprotein peroxidation, with recent 2,4-D exposure. Future studies should investigate the role of 2,4-D-induced oxidative stress in the pathogenesis of human diseases. PMID:28116766

Increased prostaglandin response to oxytocin in ewes fed a diet high in omega-6 polyunsaturated fatty acids.

PubMed

Gulliver, Catherine E; Friend, Michael A; King, Belinda J; Robertson, Susan M; Wilkins, John F; Clayton, Edward H

2013-02-01

Diets high in omega-6 polyunsaturated fatty acids (n-6) are associated with increased prostaglandin F(2α) (PGF(2α)) synthesis in cattle, however, the specific effects on the potential prostaglandin response to an oxytocin challenge in sheep have not been reported. The aim of the current study was to determine whether oxytocin-stimulated PGF(2α) was significantly increased when ewes were fed a diet high in n-6 compared with a control diet low in n-6. Merino x Border Leicester ewes (n = 30) received one of two dietary treatments, either high in n-6 (70 % oat grain) or low in n-6 (control diet, 100 % cereal/legume silage). Ewes consumed the diets for 44 days prior to two consecutive oxytocin challenges. Plasma n-6 and PGF(2α) metabolite (PGFM) concentrations following oxytocin challenge were greater (P < 0.05) when ewes were fed a diet high in n-6 compared with the control diet. A higher availability of n-6 may have lead to an increased in vivo synthesis of PGF(2α), however, further research is required to determine the exact mechanisms involved.

A unique mechanism of successful fertilization in a domestic bird.

PubMed

Sasanami, Tomohiro; Izumi, Shunsuke; Sakurai, Naoki; Hirata, Toshifumi; Mizushima, Shusei; Matsuzaki, Mei; Hiyama, Gen; Yorinaga, Eriko; Yoshimura, Takashi; Ukena, Kazuyoshi; Tsutsui, Kazuyoshi

2015-01-09

Fertilization is an indispensable step for formation of a zygote in sexual reproduction, leading to species survival. When mating occurs, sperm is transported to the female reproductive tracts via the seminal plasma (SP). SP is derived from male accessory sex glands and it plays pivotal roles for fertilization in animals. However, molecular mechanisms of SP or a fluid derived from male accessory sex glands for successful fertilization remain unclear. Here, we report that in male quail the cloacal gland (CG) produces prostaglandin F2α (PGF2α) that contributes to successful fertilization. PGF2α, as well as the secretion of CG (CGS), induced vaginal contractions and caused the opening of the entrance of the sperm storage tubules, the structures responsible for the long-term sperm storage and fertilization. The removal of CGS from the male before mating reduced the fertility, but the supplementation of CGS or PGF2α rescued the subfertility. We further showed that male CG contains glucose that is utilized as energy source for the intrinsic sperm mobility after transportation to female vagina. This mechanism, in concert with the excitatory effects of PGF2α enables successful fertilization in the domestic bird.

Oxidative Stress Assessment in Response to Ultraendurance Exercise: Thiols Redox Status and ROS Production according to Duration of a Competitive Race

PubMed Central

Vezzoli, Alessandra; Dellanoce, Cinzia; Montorsi, Michela; Tonini, Annamaria; Accinni, Roberto

2016-01-01

Purpose. Response to an ultraendurance competitive race on thiols redox status, reactive oxygen species (ROS) production, and oxidative stress (OxS) was investigated according to duration. Methods. Twenty-four elite runners were examined: six completed 50 km and eighteen 100 km. Blood and urine samples were collected before and immediately after the race. Erythrocytes and plasma aminothiols by high-performance liquid chromatography, total antioxidant capacity (TAC), and OxS biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive substances (TBARS), 8-isoprostane (8-iso-PGF2α), and 8-OH-2-deoxyguanosine (8-OH-dG)) by immunoenzymatic assays and ROS production by Electron Paramagnetic Resonance were assessed. Results. Significant increases (P between <0.05 and <0.0001) were recorded in plasma total and oxidized aminothiols concentration and TAC (P < 0.0001) only after 100 km: plasmatic (ROS production (+12 versus +29%), PC (+54 versus +115%), and TBARS (+28 versus +55%)) and urinary (8-OH-dG.creatinine−1 (+71 versus +158%) and 8-iso-PGF2α.creatinine−1 (+43 versus +135%)) concentrations for 50 and 100 km (duration 4 h 3′ versus 8 h 42′), respectively. Conclusion. Very prolonged ultraendurance exercise causes an increase in ROS production and OxS depending on specific biomarker examined but always linearly and directly related to exercise duration. Redox status of erythrocytes was preserved. A relationship between running performance and both prerace ROS production and antioxidant-redox status was found in 100 km race. PMID:27504148

Simultaneous quantification of PGI2 and TXA2 metabolites in plasma and urine in NO-deficient mice by a novel UHPLC/MS/MS method.

PubMed

Kij, Agnieszka; Mateuszuk, Lukasz; Sitek, Barbara; Przyborowski, Kamil; Zakrzewska, Agnieszka; Wandzel, Krystyna; Walczak, Maria; Chlopicki, Stefan

2016-09-10

The balance between vascular prostacyclin (PGI2) generated mainly via cyclooxygenase-2 (COX-2) and its physiological antagonist platelet-derived thromboxane A2 (TXA2) formed by cyclooxygenase-1 (COX-1) determines cardiovascular homeostasis. In the present work, a novel bioanalytical method for simultaneous quantification of stable plasma and urinary metabolites of PGI2 (6-keto-PGF1α, 2,3-dinor-6-keto-PGF1α) and TXA2 (TXB2, 2,3-dinor-TXB2) using ultra high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC/MS/MS) was developed. The method was validated using artificial plasma and urine and linearity range, intra- and inter-day precision and accuracy, recovery of analytes, relative and absolute matrix effect and stability of analytes were determined. The use of artificial biofluids improved the method sensitivity as it eliminated the contribution of endogenous metabolites present in mice plasma and urine to validation procedure. The newly developed and validated method allowed to quantify 6-keto-PGF1α and TXB2 in mice plasma as well as 2,3-dinor-6-keto-PGF1α and 2,3-dinor-TXB2 in urine samples with high sensitivity and accuracy. The calibration range was established from 0.1 to 100ng/mL for all analytes using artificial biofluids and the recoveries were greater than 89.9%. All validated parameters met the criteria of acceptance specified in FDA and EMA guidance. This method was successfully employed for profiling of the changes in PGI2 and TXA2 generation in NO-deficient mice. This work demonstrated that NO-deficiency induced by L-NAME, evidenced by a fall in nitrite in plasma and urine, was associated with platelet activation, robust increase in TXB2 and mild increase in 6-keto-PGF1α concentration in plasma. Changes in 2,3-dinor-6-keto-PGF1α and 2,3-dinor-TXB2 concentration in urine were less evident suggesting that the measurements in plasma better reflect modest changes in PGI2/TXA2 homeostasis than measurements in urine. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of concanavalin A on the progesterone production by bovine steroidogenic luteal cells in vitro.

PubMed

Destro, F C; Martin, I; Landim-Alvarenga, Fdc; Ferreira, Jcp; Pate, J L

2016-10-01

The aim of this study was to evaluate the effects of concanavalin A (CONA) on the progesterone (P4) production by bovine steroidogenic luteal cells (LCs) in vitro. Luteal cells were collected during the mid-luteal stage (at 10-12 days following ovulation) and processed in the laboratory. Luteal cells were grown for 7 days in a humid atmosphere with 5% CO2 , with or without 10% foetal bovine serum, and were subjected to the following treatments: control: no treatment; CONA (10 μg/ml); LH (100 μg/ml); CONA + LH; LH (100 μg/ml) + prostaglandin F2α (PGF2α) (10 ng/ml); CONA + LH + PGF2α. Samples of the culture media were collected on days 1 (D1) and 7 (D7) for P4 quantification. The cells were counted on D7 of culture. Differences between treatments were considered statistically significant at p < .05. Culture in the presence of CONA decreased the P4-secreting capacity of LCs on D7 of culture, particularly in the absence of serum. The cell numbers did not change between treatments. © 2016 Blackwell Verlag GmbH.

Effect of oxytocin and PGF2α on chlortetracycline absorption from the uterus of early postpartum camels (Camelus dromedarius).

PubMed

Ghoneim, I M; Abdelghany, A M; Waheed, M M; Elmoslemany, A M; Alhaider, A K; Al-Eknah, M M

2015-09-01

Fifteen parturient camels given chlortetracycline (CTC) as intrauterine pessaries (3 g/head) were divided into the control group (n = 5), which remained untreated, oxytocin-treated group (50 IU, intramuscular; n = 5), and cloprostenol-treated group (Estrumate, 500 μg, intramuscular; n = 5). Serum samples were collected at 0, 1, 2, 4, 8, 24, 48, and 72 hours after treatment and CTC was determined. The CTC appeared in blood within 1 hour. The maximum concentration of CTC was detected in blood after 72 (543.58 ± 117.85 μg/L), 8 (520.48 ± 13.65 μg/L), and 1 hour (831.98 ± 111.01 μg/L) of administration in control, oxytocin-, and PGF2α-treated camels, respectively. There was a high significant effect of time (P < 0.001) and treatment-by-time interaction (P < 0.001) on serum CTC concentration. In the control group, there was a significant (P < 0.05) increase in CTC concentrations at 72 hours compared to the other times. In the oxytocin group, there was a significant (P < 0.05) decrease in CTC concentrations at 24, 48, and 72 hours compared to its level after 1 or 8 hours. In PGF2α, there was a significant (P < 0.001) decrease in CTC concentrations at 2, 4, 8, 24, 48, and 72 hours compared to its level after 1 hour. Treatment contrast at different time points showed a significant (P < 0.001) increase in CTC concentration after 1 hour in the PGF2α-treated group compared to oxytocin and control groups. By 72 hours, CTC concentrations were significantly (P < 0.05) lower in PGF2α and oxytocin groups than in the control group. In conclusion, serum CTC concentration in dromedary camels increases within 1 hour after intrauterine administration and remains elevated for at least 72 hours in control, oxytocin-, and PGF2α-treated animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Recent advances in PC-Linux systems for electronic structure computations by optimized compilers and numerical libraries.

PubMed

Yu, Jen-Shiang K; Yu, Chin-Hui

2002-01-01

One of the most frequently used packages for electronic structure research, GAUSSIAN 98, is compiled on Linux systems with various hardware configurations, including AMD Athlon (with the "Thunderbird" core), AthlonMP, and AthlonXP (with the "Palomino" core) systems as well as the Intel Pentium 4 (with the "Willamette" core) machines. The default PGI FORTRAN compiler (pgf77) and the Intel FORTRAN compiler (ifc) are respectively employed with different architectural optimization options to compile GAUSSIAN 98 and test the performance improvement. In addition to the BLAS library included in revision A.11 of this package, the Automatically Tuned Linear Algebra Software (ATLAS) library is linked against the binary executables to improve the performance. Various Hartree-Fock, density-functional theories, and the MP2 calculations are done for benchmarking purposes. It is found that the combination of ifc with ATLAS library gives the best performance for GAUSSIAN 98 on all of these PC-Linux computers, including AMD and Intel CPUs. Even on AMD systems, the Intel FORTRAN compiler invariably produces binaries with better performance than pgf77. The enhancement provided by the ATLAS library is more significant for post-Hartree-Fock calculations. The performance on one single CPU is potentially as good as that on an Alpha 21264A workstation or an SGI supercomputer. The floating-point marks by SpecFP2000 have similar trends to the results of GAUSSIAN 98 package.

Depressed Levels of Prostaglandin F2α in Mice Lacking Akr1b7 Increase Basal Adiposity and Predispose to Diet-Induced Obesity

PubMed Central

Volat, Fanny E.; Pointud, Jean-Christophe; Pastel, Emilie; Morio, Béatrice; Sion, Benoit; Hamard, Ghislaine; Guichardant, Michel; Colas, Romain; Lefrançois-Martinez, Anne-Marie; Martinez, Antoine

2012-01-01

Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prostaglandin F2α (PGF2α) is a potent antiadipogenic factor in cultured preadipocytes, but evidence for its involvement in physiological context is lacking. We previously reported that Akr1b7, an aldo-keto reductase enriched in adipose stromal vascular fraction but absent from mature adipocytes, has antiadipogenic properties possibly supported by PGF2α synthase activity. To test whether lack of Akr1b7 could influence WAT homeostasis in vivo, we generated Akr1b7−/− mice in 129/Sv background. Akr1b7−/− mice displayed excessive basal adiposity resulting from adipocyte hyperplasia/hypertrophy and exhibited greater sensitivity to diet-induced obesity. Following adipose enlargement and irrespective of the diet, they developed liver steatosis and progressive insulin resistance. Akr1b7 loss was associated with decreased PGF2α WAT contents. Cloprostenol (PGF2α agonist) administration to Akr1b7−/− mice normalized WAT expansion by affecting both de novo adipocyte differentiation and size. Treatment of 3T3-L1 adipocytes and Akr1b7−/− mice with cloprostenol suggested that decreased adipocyte size resulted from inhibition of lipogenic gene expression. Hence, Akr1b7 is a major regulator of WAT development through at least two PGF2α-dependent mechanisms: inhibition of adipogenesis and lipogenesis. These findings provide molecular rationale to explore the status of aldo-keto reductases in dysregulations of adipose tissue homeostasis. PMID:22851578

Protectant activity of defibrotide in cardioplegia followed by ischemia/reperfusion injury in the isolated rat heart.

PubMed

Rossoni, G; Pompilio, G; Biglioli, P; Alamanni, F; Tartara, P; Rona, P; Porqueddu, M; Berti, F

1999-01-01

Previous studies have shown that defibrotide, a polydeoxyribonucleotide obtained by depolymerization of DNA from porcine tissues, has important protective effects on myocardial ischemia, which may be associated with a prostacyclin-related mechanism. The purpose of this study was to investigate the direct effects of defibrotide (given in cardioplegia or after ischemia) on a model of rat heart recovery after cardioplegia followed by ischemia/reperfusion injury. Isolated rat hearts, undergoing 5 minutes of warm cardioplegic arrest followed by 20 minutes of global ischemia and 30 minutes of reperfusion, were studied using the modified Langendorff model. The cardioplegia consisted of St. Thomas' Hospital solution augmented with defibrotide (50, 100, and 200 microg/mL) or without defibrotide (controls). Left ventricular mechanical function and the levels of creatine kinase, lactate dehydrogenase, and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha; the stable metabolite of prostacyclin) were measured during preischemic and reperfusion periods. After global ischemia, hearts receiving defibrotide in the cardioplegic solution (n = 8) manifested in a concentration-dependent fashion lower left ventricular end-diastolic pressure (p < 0.001), higher left ventricular developed pressure (p < 0.01), and lower coronary perfusion pressure (p < 0.001) compared to the control group. After reperfusion, hearts receiving defibrotide in the cardioplegic solution also had, in a dose-dependent way, lower levels of creatine-kinase (p < 0.01), lactate dehydrogenase (p < 0.001), and higher levels of 6-keto-PGF1alpha (p < 0.001) compared to the control group. Furthermore, when defibrotide was given alone to the hearts at the beginning of reperfusion (n = 7), the recovery of postischemic left ventricular function was inferior (p < 0.05) to that obtained when defibrotide was given in cardioplegia. Defibrotide confers to conventional crystalloid cardioplegia a potent concentration-dependent protective effect on the recovery of isolated rat heart undergoing ischemia/reperfusion injury. The low cost and the absence of contraindications (cardiac toxicity and hemodynamic effects) make defibrotide a promising augmentation to cardioplegia.

Effect of post-mating GnRH analogue (buserelin) treatment on PGF2alpha release in ewes and ewe lambs.

PubMed

Khan, T H; Beck, N F G; Mann, G E; Khalid, M

2006-09-01

The objectives of this study were to determine the effects of buserelin or saline treatment on ovarian function (Experiment 1), plasma PGFM concentrations and oxytocin stimulated prostaglandin F(2alpha) (PGF(2alpha)) release (Experiment 2) in ewe lambs and ewes. Welsh Halfbred ewes (n=26) and ewe lambs (n=24) were mated to vasectomised rams at synchronised oestrus and on Day 12 post-mating each animal was injected intramuscularly either normal saline or 4 microg buserelin. In Experiment 1, plasma progesterone and oestradiol concentrations were determined in samples collected by jugular venepuncture 1h before and at 0, 2, 4, 6, 8, 24, 48 and 72 h after treatment (n=7 per treatment group). Progesterone concentrations increased (P<0.05) from 2 to 8h after buserelin treatment and returned to basal levels after 72 h, whereas oestradiol concentrations were maximal at 2h post-treatment and returned to basal levels after 24h (P<0.05). Oestradiol concentrations were lower (P<0.05) in buserelin-treated animals than controls at 72 h post-treatment. Basal and post-treatment progesterone concentrations were greater (P<0.05) in ewes than in ewe lambs but oestradiol levels were similar for both age groups. Ovulation rate, determined by laparoscopy on Day 14, was similar for both age groups (ewes 1.1; ewe lambs 1.0). Buserelin treatment induced accessory corpora lutea in ewes (4/7; 57%) but not in ewe lambs (0/7; 0%). In the Experiment 2, plasma PGFM concentrations were determined in samples collected at 20-min intervals for 6h on Day 14 and at 20-min intervals for 1h before and at 10-min intervals for 1h and then at 20-min intervals for a further 3h period after an intravenous injection of oxytocin (1IU/kg body weight) on Day 15 post-oestrus. In this experiment there were five ewe lambs and six ewes per treatment group. There was no effect of buserelin treatment or age on basal PGFM concentrations on either Day 14 or 15. Although peak PGFM concentrations tended to be lower in buserelin-treated animals, the difference was not significant (P>0.05). However, peak duration following oxytocin challenge on Day 15 post-mating was shorter (P<0.05) in control ewes compared with control ewe lambs. In conclusion, buserelin treatment given on Day 12 post-oestrus enhances luteal function more in ewes than ewe lambs and after a transitory increase, reduces oestradiol concentrations in both ewes and ewe lambs. However, buserelin treatment does not significantly attenuate the luteolytic signal.

Growth hormone-like factor produced by the tapeworm, Spirometra mansonoides, displaces human growth hormone (hGH) from its receptors on cultured human lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watts, D.J.; Phares, C.K.

1986-03-01

An analogue of hGH isolated from plerocercoids of the tapeworm Spirometra mansonoides displaces (/sup 125/I)hGH from its receptors in rabbit, rat, and hamster liver membranes. Biologically, plerocercoid growth factor (PGF) is more similar to hGH than to other mammalian GH's but has not been shown to bond human cells. Receptors specific for hGH have been described on cultured human lymphocytes (IM-9). In this study, the authors compared the binding of PGF and hGH in IM-9 cells and in rabbit hepatic membranes. IM-9 lymphocytes (12 x 10/sup 6/ cells/tube) were incubated with (/sup 125/I)hGH and increasing concentrations of hGH (ng/ml) ormore » PGF (serial dilutions) for 90 min at 30/sup 0/ C. Specific binding (B/sub 0/ - NSB) was determined for each dose of hGH or PGF and the binding curves were analyzed by logit-log regression. The results show that PGF displaced (/sup 125/I)hGH from human cells in a dose dependent manner (r = 0.98). Based on the IM-9 assay, 1 ml of the PGF had an activity equivalent to 625 ng of the hGH standard (ngE). However, the binding activity of the PGF in the rabbit liver RRA was 1653 ngE/ml, indicating that the binding potency of PGF in IM-9 cells was only 38% of that in the rabbit liver. These results clearly demonstrate that PGF binds hGH receptors in cells of human origin, suggesting that PGF will be effective in humans.« less

Endocrine alterations around the time of abortion in mares impregnated with donkey or horse semen.

PubMed

Boeta, M; Zarco, L

2010-08-01

The objective of this study was to monitor and compare the concentrations of equine chorionic gonadotropin (eCG), progesterone and estrone sulphate during normal and failed pregnancies of mares impregnated with donkey or horse semen, relating their individual endocrine profiles to the time of pregnancy loss, and to the histopathologic findings in the aborted fetuses and placenta. Mares (n=54) were used, 32 of them impregnated with donkey semen and 22 impregnated with horse semen. Blood samples were taken twice a week from Day 35 to 120 of pregnancy. Ultrasonographic observations of the fetus were carried out twice a week. The incidence of abortion in mares impregnated with donkey semen (30%) was greater (P<0.05) than the 5% observed in mares impregnated with horse semen. From Week 8 to the end of the sampling period, the mean progesterone concentrations of mares with normal mule pregnancies were less (P<0.05) than those of mares with normal pregnancies with equine fetuses. The concentrations of eCG were less (P<0.05) in mule pregnancies from Week 6. Estrone sulphate concentrations were only different (P<0.05) between types of pregnancy on Weeks 13 and 14, being in this case greater with the mule pregnancies. Most of the abortions of mule fetuses were associated with lesser progesterone concentrations than the average for mares with successful mule pregnancies. Four of the abortions of mule fetuses and the only abortion of horse fetus occurred in mares with lesser progesterone and very low eCG concentrations, and were classified as caused by luteal impairment secondary to eCG deficiency; estrone sulphate concentrations were less than normal or absent before these abortions. Two mares aborted after several weeks of low progesterone concentrations in the presence of eCG concentrations that were normal for mule pregnancies, suggesting primary luteal deficiency. In three mares carrying a mule fetus, the concentrations of progesterone and estrone sulphate decreased abruptly immediately before fetal death, suggesting luteolysis due to active prostaglandin F2 alpha (PGF2alpha) secretion. It is concluded that the greater incidence of abortion in mares impregnated by donkeys is associated with different kinds of luteal malfunction. Deficiency of eCG may be a primary cause of many of these cases, either by failing to stimulate enough luteal progesterone secretion and/or by failing to protect the corpora lutea (CL) of pregnancy from endogenous PGF2alpha secretion. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Redirection of arachidonic acid metabolism by ICI D1542: effects on thrombus formation in the coronary artery of the anaesthetized dog.

PubMed Central

McAuliffe, S. J.; Moors, J. A.; Snow, H. M.; Wayne, M.; Jessup, R.

1993-01-01

1. The effects of simultaneous redirection of arachidonic acid metabolism, by inhibition of thromboxane A2 (TXA2) synthase and blockade of the platelet thromboxane A2 receptor (TP-receptor), was examined on the rate of thrombus formation in a stenosed coronary artery with damaged endothelium in an anaesthetized dog. 2. Redirection of arachidonic acid metabolism was achieved by intravenous doses of ICI D1542, a selective and potent inhibitor of TXA2 synthase and the TP-receptor. 3. Redirection of arachidonic acid metabolism was demonstrated in whole blood, stimulated ex vivo by collagen. The ED50 for inhibition of TXB2 production was 7.1 micrograms kg-1, i.v.; there were corresponding increases in the production of the eicosanoids prostaglandin D2 (PGD2), PGE2 and PGF2 alpha. 4. Thrombus formation was inhibited by D1542 (ED50 0.55 micrograms kg-1, i.v.), but could be restarted by an intravenous infusion of adrenaline (0.2-38 micrograms kg-1 min-1, i.v.). In the presence of the maximum effective dose of D1542 (1 mg kg-1, i.v.) a 190 fold increase in the infusion rate of adrenaline was required to restore thrombus formation. 5. In the presence of D1542, removal of endoperoxide metabolites by inhibition of cyclo-oxygenase with aspirin (5 mg kg-1, i.v.) caused thrombus formation to restart, indicating the ability of the endoperoxide metabolites to inhibit thrombus formation in vivo. 6. These results indicate that, in the stenosed and damaged coronary artery of the dog, redirection of arachidonic acid metabolism by D1542 is more effective at preventing thrombus formation than inhibition of cyclo-oxygenase by aspirin. PMID:8485629

Effects of vasoactive intestinal polypeptide on antigen-induced bronchoconstriction and thromboxane release in guinea-pig lung.

PubMed Central

Ciabattoni, G.; Montuschi, P.; Currò, D.; Togna, G.; Preziosi, P.

1993-01-01

1. Exogenous vasoactive intestinal polypeptide (VIP) infused into the pulmonary artery of isolated and ventilated lungs of guinea-pigs decreased, in a dose-dependent fashion (1.0-10.0 nmol), airway resistance and thromboxane B2 (TXB2, the stable hydrolysis product of TXA2) release in the perfusion medium. Prostacyclin (PGI2) synthesis, as reflected by the release of its stable hydrolysis product 6-oxo-PGF1 alpha, was unaffected. Pretreatment with the 5-lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) did not modify the bronchodilatory effect of VIP or its inhibitory action on TXB2 release. 2. Basal release of immunoreactive VIP from perfused lungs decreased from an initial value of 0.96 +/- 0.10 ng min-1 (mean +/- s.e.mean) in the first 2 min to an average of 0.58 +/- 0.10 ng min-1 in the following 15-20 min. 3. Antigen challenge with ovalbumin (0.1%) in sensitized lungs caused an anaphylactic reaction in 45% of tested lungs, concomitant with a 5 fold increase in both VIP and TXB2 release. Tetrodotoxin pretreatment (10(-6) M) reduced basal VIP release by > 80% and abolished the VIP increase observed during anaphylaxis, without modifying TXB2 release or the bronchoconstrictor response. 4. Indomethacin (10(-6) M) inhibited TXB2 synthesis and release by > 90%, delayed the bronchoconstrictor response and blunted the increased VIP release during lung anaphylaxis, without influencing basal VIP release. 5. The 5-lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) blunted the increase of TXB2 and VIP release from guinea-pig lung and attenuated the bronchoconstrictor response following ovalbumin challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8495242

Therapeutic effects of flurbiprofen axetil on mesenteric traction syndrome: randomized clinical trial.

PubMed

Takahashi, Hidemasa; Shida, Dai; Tagawa, Kyoko; Iwamoto, Ryo; Arita, Makoto; Arai, Hiroyuki; Suzuki, Takeo

2017-08-11

This study aimed to reveal the appropriate timing for the intravenous administration of flurbiprofen axetil for preventing mesenteric traction syndrome (MTS), caused by prostacyclin release. In this prospective, randomized, clinical study, forty-five patients who were undergoing elective surgery for colorectal cancer via laparotomy were enrolled. Patients were randomly divided into 3 groups: a preoperative group (n = 16) receiving flurbiprofen axetil directly before surgery; a post-MTS group (n = 14) receiving following MTS onset; and a control group (n = 15) who were not administered flurbiprofen axetil. 6-keto-PGF1α, a stable metabolite of prostacyclin, levels were measured and mean blood pressures were recorded. In the preoperative group, 6-keto-PGF1α levels did not increase, blood pressure levels did not decrease, and no facial flushing was observed. In both the post-MTS and control groups, 6-keto-PGF1α levels increased markedly after mesenteric traction and blood pressure decreased significantly. The post-MTS group exhibited a faster decreasing trend in 6-keto-PGF1α levels and quick restore of the mean blood pressure, and the use of vasopressors and phenylephrine were lower than that in the control group. Even therapeutic administration of flurbiprofen axetil after the onset of MTS has also effects on MTS by suppressing prostacyclin production. Clinical trial number: UMIN000009111 . (Registered 14 October 2012).

UVB light upregulates prostaglandin synthases and prostaglandin receptors in mouse keratinocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Black, Adrienne T.; Gray, Joshua P.; Shakarjian, Michael P.

Prostaglandins belong to a class of cyclic lipid-derived mediators synthesized from arachidonic acid via COX-1, COX-2 and various prostaglandin synthases. Members of this family include prostaglandins such as PGE{sub 2}, PGF{sub 2{alpha}}, PGD{sub 2} and PGI{sub 2} (prostacyclin) as well as thromboxane. In the present studies we analyzed the effects of UVB on prostaglandin production and prostaglandin synthase expression in primary cultures of undifferentiated and calcium-differentiated mouse keratinocytes. Both cell types were found to constitutively synthesize PGE{sub 2}, PGD{sub 2} and the PGD{sub 2} metabolite PGJ{sub 2}. Twenty-four hours after treatment with UVB (25 mJ/cm{sup 2}), production of PGE{sub 2}more » and PGJ{sub 2} increased, while PGD{sub 2} production decreased. This was associated with increased expression of COX-2 mRNA and protein. UVB (2.5-25 mJ/cm{sup 2}) also caused marked increases in mRNA expression for the prostanoid synthases PGDS, mPGES-1, mPGES-2, PGFS and PGIS, as well as expression of receptors for PGE{sub 2} (EP1 and EP2), PGD{sub 2} (DP and CRTH2) and prostacyclin (IP). UVB was more effective in inducing COX-2 and DP in differentiated cells and EP1 and IP in undifferentiated cells. UVB readily activated keratinocyte PI-3-kinase (PI3K)/Akt, JNK and p38 MAP signaling pathways which are known to regulate COX-2 expression. While inhibition of PI3K suppressed UVB-induced mPGES-1 and CRTH2 expression, JNK inhibition suppressed mPGES-1, PGIS, EP2 and CRTH2, and p38 kinase inhibition only suppressed EP1 and EP2. These data indicate that UVB modulates expression of prostaglandin synthases and receptors by distinct mechanisms. Moreover, both the capacity of keratinocytes to generate prostaglandins and their ability to respond to these lipid mediators are stimulated by exposure to UVB.« less

Strategies to decrease oxidative stress biomarker levels in human medical conditions: A meta-analysis on 8-iso-prostaglandin F2α.

PubMed

van 't Erve, Thomas J

2018-05-09

The widespread detection of elevated oxidative stress levels in many medical conditions has led to numerous efforts to design interventions to reduce its effects. Efforts have been wide-ranging, from dietary changes to administration of antioxidants, supplements, e.g., omega-3-fatty acids, and many medications. However, there is still no systemic assessment of the efficacy of treatments for oxidative stress reduction across a variety of medical conditions. The goal of this meta-analysis is, by combining multiple studies, to quantitate the change in the levels of the popular oxidative stress biomarker 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) after a variety of treatment strategies in human populations. Nearly 350 unique publications with 180 distinct strategies were included in the analysis. For each strategy, the difference between pre- or placebo and post-treatment levels calculated using Hedges' g value of effect. In general, administration of antibiotics, antihyperlipidemic agents, or changes in lifestyle (g = - 0.63, - 0.54, and 0.56) had the largest effect. Administration of supplements, antioxidants, or changes in diet (g = - 0.09, - 0.28, - 0.12) had small quantitative effects. To fully interpret the effectiveness of these treatments, comparisons to the increase in g value for each medical condition is required. For example, antioxidants in populations with coronary artery disease (CAD) reduce the 8-iso-PGF 2α levels by g = - 0.34 ± 0.1, which is quantitatively considered a small effect. However, CAD populations, in comparison to healthy populations, have an increase in 8-iso-PGF 2α levels by g = 0.38 ± 0.04; therefore, the overall reduction of 8-iso-PGF 2α levels is ≈ 90% by this treatment in this specific medical condition. In conclusion, 8-iso-PGF 2α levels can be reduced not only by antioxidants but by many other strategies. Not all strategies are equally effective at reducing 8-iso-PGF 2α levels. In addition, the effectiveness of any strategy can be assessed only in relation to the medical condition investigated. Copyright © 2018. Published by Elsevier B.V.

Vascular Nitric Oxide-Superoxide Balance and Thrombus Formation after Acute Exercise.

PubMed

Przyborowski, Kamil; Proniewski, Bartosz; Czarny, Joanna; Smeda, Marta; Sitek, Barbara; Zakrzewska, Agnieszka; Zoladz, Jerzy A; Chlopicki, Stefan

2018-02-21

An acute bout of strenuous exercise in humans results in transient impairment of NO-dependent function, but it remains unknown whether this phenomenon is associated with increased risk of post-exercise thrombotic events. This study aimed to evaluate effects of a single bout of exhaustive running in mice on the balance of vascular nitric oxide (NO)/reactive oxygen species (ROS) production, and on thrombogenicity. At different time-points (0h, 2h and 4h) after exercise and in sedentary C57BL/6 mice the production of NO and superoxide (O2) in aorta was measured by electron paramagnetic resonance (EPR) spin trapping and by dihydroethidium (DHE)/HPLC-based method, respectively, while collagen-induced thrombus formation was analyzed in a microchip-based flow-chamber system (T-TAS). We also measured pre- and post-exercise plasma concentration of nitrite/nitrate and 6-keto-PGF1α. An acute bout of exhaustive running in mice resulted in decreased production of NO and increased production of O2 in aorta, with maximum changes 2h after completion of exercise when compared to sedentary mice. However, platelet thrombus formation was not changed by exercise as evidenced by unaltered time to start of thrombus formation (T10) and capillary occlusion (OT), and total thrombogenicity (AUC) as measured in a flow-chamber system. Strenuous exercise increased the plasma concentration of nitrite but did not affect nitrate and 6-keto-PGF1α concentrations. An acute bout of strenuous exercise in mice reduced NO and in parallel increased O2 production in aorta. This response was most pronounced 2h after exercise. Surprisingly, the reduced NO and increased O2 production did not result in increased post-exercise platelet-dependent thrombogenicity. These results show that transient reduction in NO bioavailability, caused by exercise-induced oxidative stress, does not modify post-exercise thromboresistance in healthy mice.

Acceleration of atherogenesis by COX-1-dependent prostanoid formation in low density lipoprotein receptor knockout mice.

PubMed

Praticò, D; Tillmann, C; Zhang, Z B; Li, H; FitzGerald, G A

2001-03-13

The cyclooxygenase (COX) product, prostacyclin (PGI(2)), inhibits platelet activation and vascular smooth-muscle cell migration and proliferation. Biochemically selective inhibition of COX-2 reduces PGI(2) biosynthesis substantially in humans. Because deletion of the PGI(2) receptor accelerates atherogenesis in the fat-fed low density lipoprotein receptor knockout mouse, we wished to determine whether selective inhibition of COX-2 would accelerate atherogenesis in this model. To address this hypothesis, we used dosing with nimesulide, which inhibited COX-2 ex vivo, depressed urinary 2,3 dinor 6-keto PGF(1alpha) by approximately 60% but had no effect on thromboxane formation by platelets, which only express COX-1. By contrast, the isoform nonspecific inhibitor, indomethacin, suppressed platelet function and thromboxane formation ex vivo and in vivo, coincident with effects on PGI(2) biosynthesis indistinguishable from nimesulide. Indomethacin reduced the extent of atherosclerosis by 55 +/- 4%, whereas nimesulide failed to increase the rate of atherogenesis. Despite their divergent effects on atherogenesis, both drugs depressed two indices of systemic inflammation, soluble intracellular adhesion molecule-1, and monocyte chemoattractant protein-1 to a similar but incomplete degree. Neither drug altered serum lipids and the marked increase in vascular expression of COX-2 during atherogenesis. Accelerated progression of atherosclerosis is unlikely during chronic intake of specific COX-2 inhibitors. Furthermore, evidence that COX-1-derived prostanoids contribute to atherogenesis suggests that controlled evaluation of the effects of nonsteroidal anti-inflammatory drugs and/or aspirin on plaque progression in humans is timely.

The effects of heavy metals and their interactions with polycyclic aromatic hydrocarbons on the oxidative stress among coke-oven workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Tian; Feng, Wei; Kuang, Dan

Heavy metals and polycyclic aromatic hydrocarbons (PAHs) are predominate toxic constituents of particulate air pollution that may be related to the increased risk of cardiopulmonary events. We aim to investigate the effects of the toxic heavy metals (arsenic, As; cadmium, Cd; chromium, Cr; nickel, Ni; and lead, Pb), and their interactions with PAHs on oxidative stress among coke-oven workers. A total of 1333 male workers were recruited in this study. We determined their urinary levels of As, Cd, Cr, Ni, Pb, twelve PAH metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso-prostaglandin-F2α (8-iso-PGF2α). Multivariate linear regression models were used to analyze the effects ofmore » these metals and their interactions with PAHs on 8-OHdG and 8-iso-PGF2α levels. It was found that only urinary As and Ni showed marginal or significant positive linear dose-dependent effects on 8-OHdG in this study population, especially among smokers (β=0.103, P=0.073 and β=0.110, P=0.002, respectively). After stratifying all participants by the quartiles of ΣOH-PAH, all five metals showed linear association with 8-OHdG in the highest quartile subgroup (Q4) of ΣOH-PAHs. However, these five urinary metals showed significantly consistent linear associations with 8-iso-PGF2α in all subjects and each stratum. Urinary ΣOH-PAHs can significant modify the effects of heavy metals on oxidative stress, while co-exposure to both high levels of ΣOH-PAHs and heavy metals render the workers with highest 8-OHdG and 8-iso-PGF2α (all P{sub interaction}≤0.005). This study showed evidence on the interaction effects of heavy metals and PAHs on increasing the oxidative stress, and these results warrant further investigation in more longitudinal studies. - Highlights: • Heavy metals and PAHs are predominate toxic constituents of particulate matters. • Urinary As and Ni showed linear dose-dependent effects on 8-OHdG and 8-iso-PGF2α. • PAHs significant interact with toxic metal in increasing 8-OHdG and 8-iso-PGF2α. • Co-exposure to high PAHs and toxic metals contribute to highest oxidative stress.« less

Pregnancy Recognition and Implantation of the Conceptus in the Mare.

PubMed

Klein, Claudia

2015-01-01

Few, if any, biological processes are as diverse among domestic species as establishment of early pregnancy, in particular maternal recognition of pregnancy. Following fertilization and initial development in the mare oviduct, selective transport of the embryo through the uterotubal junction driven by embryo-derived PGE2 occurs. Upon arrival in the uterus, an acellular glycoprotein capsule is formed that covers the embryo, blastocyst, and conceptus (embryo and associated extraembryonic membranes) between the second and third weeks of pregnancy. Between Days 9 and 15/16 of pregnancy, the conceptus undergoes an extended phase of mobility. Conceptus mobility is driven by conceptus-derived PGF2α and PGE2 that stimulate uterine contractions which in turn propel migration of the conceptus within the uterine lumen. Cessation of conceptus mobility is referred to as fixation and appears to be attributable to increasing size of the conceptus, preferential thickening of the endometrium near the mesometrial attachment referred to as encroachment, and a reduction in sialic acid content of the capsule. During maternal recognition of pregnancy, endometrial PGF2α release is attenuated, a consequence of reduced expression of key enzymes involved in prostaglandin production. Oxytocin responsiveness is altered during early pregnancy, and reduced expression of the oxytocin receptor appears to be regulated at the posttranscriptional level rather than the transcriptional level. Prostaglandin release is attenuated temporarily only during early pregnancy; during the third week of pregnancy, the endometrium resumes the ability to secrete PGF2α. The equine conceptus initiates steroidogenesis as early as Day 6 and synthesizes estrogens, androgens, and progesterone. Estrogens are metabolized locally, presumably regulating their bioavailability and actions. Results of experiments attempting to prove that conceptus-derived estrogens are responsible for extension of corpus luteum function have been inconclusive. By the fourth week of pregnancy, the chorionic girdle becomes visible on the trophoblast. Subsequent invasion of chorionic girdle cells leads to formation of endometrial cups which secrete equine chorionic gonadotropin. Equine chorionic gonadotropin has luteinizing hormone functions in the mare, causing luteinization of follicles resulting in the formation of secondary corpora lutea essential to production of progesterone and maintenance of pregnancy.

Steroid hormones, prostanoids, and angiogenic systems during rescue of the corpus luteum in pigs.

PubMed

Przygrodzka, E; Kaczmarek, M M; Kaczynski, P; Ziecik, A J

2016-02-01

In order to characterize the transition of the corpora lutea (CL) from acquisition of luteolytic sensitivity to rescue of luteal function: i) the expression of 38 factors associated with steroids, prostanoids, and angiogenic systems and ii) concentrations of the main hormones responsible for maintenance of CL function in cyclic and pregnant pigs were examined. Additionally, the effect of prostaglandin (PG) E2 and F2 α on luteal function during the estrous cycle and pregnancy was evaluated in vitro. Significantly up-regulated gene expression was revealed in CL collected on day 14 of the estrous cycle (CYP19A1, ESR2, PTGS2, HIF1A, and EDN1) and on days 12-14 of pregnancy (SCARB1, PGRMC1, STAR, HSD3B1, NR5A1, PTGFR, PTGER4, and VEGFA). Elevated concentrations of estradiol-17β and PGE2 occurred in CL on days 12 and 14 of pregnancy respectively, while an increased intraluteal PGF2 α content was noted on day 14 of the estrous cycle. Both PGs increased the synthesis of progesterone by cultured luteal slices obtained on day 14 of pregnancy, in contrast to the action of PGF2 α on the corresponding day of the estrous cycle. PGE2 stimulated cAMP production via PTGER2 and PTGER4, while PGF2 α elevated the content of CREB in cultured luteal slices from CL of pregnant pigs. In silico analysis showed that infiltration of lymphocytes and apoptosis of microvascular endothelium were activated in CL on day 12 of the estrous cycle vs pregnancy. Summarizing, an abundance of E2 and PGE2 during pregnancy regulates specific pathways responsible for steroidogenesis, the prostanoid signaling system and angiogenesis during rescue from luteolysis in porcine CL. © 2016 Society for Reproduction and Fertility.

Clofibric acid, a peroxisome proliferator-activated receptor alpha ligand, inhibits growth of human ovarian cancer.

PubMed

Yokoyama, Yoshihito; Xin, Bing; Shigeto, Tatsuhiko; Umemoto, Mika; Kasai-Sakamoto, Akiko; Futagami, Masayuki; Tsuchida, Shigeki; Al-Mulla, Fahd; Mizunuma, Hideki

2007-04-01

Recent reports have shown that peroxisome proliferator-activated receptor (PPAR)alpha ligands reduce growth of some types of malignant tumors and prevent carcinogenesis. In this study, we investigated the inhibitory effect of clofibric acid (CA), a ligand for PPARalpha on growth of ovarian malignancy, in in vivo and in vitro experiments using OVCAR-3 and DISS cells derived from human ovarian cancer and aimed to elucidate the molecular mechanism of its antitumor effect. CA treatment significantly suppressed the growth of OVCAR-3 tumors xenotransplanted s.c. and significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared with control. CA also dose-dependently inhibited cell proliferation of cultured cell lines. CA treatment increased the expression of carbonyl reductase (CR), which promotes the conversion of prostaglandin E(2) (PGE(2)) to PGF(2alpha), in implanted OVCAR-3 tumors as well as cultured cells. CA treatment decreased PGE(2) level as well as vascular endothelial growth factor (VEGF) amount in both of OVCAR-3-tumor and DISS-derived ascites. Reduced microvessel density and induced apoptosis were found in solid OVCAR-3 tumors treated by CA. Transfection of CR expression vector into mouse ovarian cancer cells showed significant reduction of PGE(2) level as well as VEGF expression. These results indicate that CA produces potent antitumor effects against ovarian cancer in conjunction with a reduction of angiogenesis and induction of apoptosis. We conclude that CA could be an effective agent in ovarian cancer and should be tested alone and in combination with other anticancer drugs.

Oxytocin and tumor necrosis factor alpha stimulate expression of prostaglandin E2 synthase and secretion of prostaglandin E2 by luminal epithelial cells of the porcine endometrium during early pregnancy.

PubMed

Waclawik, Agnieszka; Blitek, Agnieszka; Ziecik, Adam J

2010-10-01

Oxytocin (OXT) and tumor necrosis factor α (TNF) have been implicated in the control of luteolysis by stimulating endometrial secretion of luteolytic prostaglandin F(2α) (PGF(2α)). Nevertheless, OXT concentration in porcine uterine lumen increases markedly on days 11-12 of pregnancy, and TNF is expressed in endometrium during pregnancy. The objective of the study was to determine the effect of OXT and TNF on expression of the enzymes involved in PG synthesis: PG-endoperoxide synthase 2 (PTGS2), PGE(2) synthase (mPGES-1) and PGF synthase, and PGE(2) receptor (PTGER2), as well as on PG secretion by endometrial luminal epithelial cells (LECs) on days 11-12 of the estrous cycle and pregnancy. LECs isolated from gilts on days 11-12 of the estrous cycle (n=8) and pregnancy (n=7) were treated with OXT (100  nmol/l) and TNF (0.6  nmol/l) for 24  h. OXT increased PTGS2 mRNA and mPGES-1 protein contents, as well as PGE(2) secretion but only on days 11-12 of pregnancy. TNF stimulated PTGS2 and mPGES-1 mRNA, as well as mPGES-1 protein expression and PGE(2) release on days 11-12 of pregnancy and the estrous cycle. In addition, expressions of PTGER2 and PTGER4 were determined in corpus luteum (CL). Abundance of PTGER2 mRNA and PTGER4 protein in CL was upregulated on day 14 of pregnancy versus day 14 of the estrous cycle. This study indicates that TNF and OXT regulate PGE(2) synthesis in LECs during early pregnancy. PGE(2) secreted by LECs, after reaching ovaries, could have a luteoprotective effect through luteal PTGER2 and PTGER4, or may directly promote uterine function and conceptus development.

Modification of Streptococcus mutans Cnm by PgfS Contributes to Adhesion, Endothelial Cell Invasion, and Virulence

PubMed Central

Avilés-Reyes, Alejandro; Miller, James H.; Simpson-Haidaris, Patricia J.; Hagen, Fred K.

2014-01-01

Expression of the surface protein Cnm has been directly implicated in the ability of certain strains of Streptococcus mutans to bind to collagen and to invade human coronary artery endothelial cells (HCAEC) and in the killing of Galleria mellonella. Sequencing analysis of Cnm+ strains revealed that cnm is located between the core genes SMU.2067 and SMU.2069. Reverse transcription-PCR (RT-PCR) analysis showed that cnm is cotranscribed with SMU.2067, encoding a putative glycosyltransferase referred to here as PgfS (protein glycosyltransferase of streptococci). Notably, Cnm contains a threonine-rich domain predicted to undergo O-linked glycosylation. The previously shown abnormal migration pattern of Cnm, the presence of the threonine-rich domain, and the molecular linkage of cnm with pgfS lead us to hypothesize that PgfS modifies Cnm. A ΔpgfS strain showed defects in several traits associated with Cnm expression, including collagen binding, HCAEC invasion, and killing of G. mellonella. Western blot analysis revealed that Cnm from the ΔpgfS mutant migrated at a lower molecular weight than that from the parent strain. In addition, Cnm produced by ΔpgfS was highly susceptible to proteinase K degradation, in contrast to the high-molecular-weight Cnm version found in the parent strain. Lectin-binding analyses confirmed the glycosylated nature of Cnm and strongly suggested the presence of N-acetylglucosamine residues attached to Cnm. Based on these findings, the phenotypes observed in ΔpgfS are most likely associated with defects in Cnm glycosylation that affects protein function, stability, or both. In conclusion, this study demonstrates that Cnm is a glycoprotein and that posttranslational modification mediated by PgfS contributes to the virulence-associated phenotypes linked to Cnm. PMID:24837294

Effects of propylene glycol drenching before and after luteolysis on blood glucose, ovarian steroids and follicular dynamics in heifers.

PubMed

Umeki, A; Tanaka, T; Kamomae, H

2012-02-01

The effect of propylene glycol drenching on ovarian and hormonal dynamics was studied in heifers. Five cycling heifers were used twice (as control and treatment) with crossover design. After the confirmation of ovulation (day 0), the heifers in the treatment group received propylene glycol on days 6, 7 and 8 as an oral drench (250 ml of 90% propylene glycol). On day 10, prostaglandin F2α (PGF2α), 15 mg per head of dinoprost, was administered intramuscularly to induce luteal regression followed by the follicular phase and then propylene glycol was again administered twice daily (500 ml/day) on days 10, 11 and 12. Palpation per rectum and ovarian ultrasonography were performed every other day from days 0 to 10, and daily after PGF2α administration until the subsequent ovulation (second ovulation) for analysis of follicular and luteal dynamics. Blood samples were also collected every other day from days 0 to 10, and then at 6 h intervals after PGF2α administration until the second ovulation. For the samples taken at 6-h intervals after PGF2α administration, the concentrations of glucose showed clear daily fluctuations in both groups. Changes in the plasma concentration of glucose in the treatment group were significantly (P < 0.05) higher than those of the control groups during the period between 0 and 72 h after PGF2α administration. No significant difference was detected in the growth of dominant follicles, maximum diameter of the ovulatory follicles and the changes in oestradiol and progesterone during the follicular phase between treatment and control groups. This study showed the clear daily fluctuations and stimulatory changes in the blood glucose concentrations at 24-h intervals during the short-term treatment of propylene glycol drenching in heifers. However, no significant changes in ovarian and hormonal dynamics were found under such metabolic conditions.

The effect of the interval from PGF treatment to ovulation on embryo recovery and pregnancy rate in the mare.

PubMed

Cuervo-Arango, J; Mateu-Sánchez, S; Aguilar, J J; Nielsen, J M; Etcharren, V; Vettorazzi, M L; Newcombe, J R

2015-05-01

The objective of this study was to determine the effect of the interval from induced luteolysis to ovulation on fertility of mares from two different farms. At farm 1, 215 mares were inseminated with frozen/thawed semen during 513 estrous cycles over seven consecutive breeding seasons. Estrus was induced with analogues of PGF2α in 179 cycles. At farm 2, 375 embryo flushings were performed in 65 donor mares inseminated with fresh semen; of which, 327 were performed following artificial insemination after PGF-induced luteolysis. In both farms, the intervals from PGF treatment to ovulation (ITO) data were divided into three interval groups: less than 6 days, 6 to 8 days, and greater than 8 days. A mixed regression model was created to determine the effect of different factors on the pregnancy rate (PR) and embryo recovery rate (ERR). Of all factors analyzed, the ITO was the only one that significantly influenced the PR and ERR (P < 0.05). In farm 1, the PR of mares with an ITO of less than 6 days, 6 to 8 days, and greater than 8 days was 26.6%, 39.4%, and 55.9%, respectively (P = 0.01). The PR for mares inseminated after spontaneous luteolysis (without PGF) was 42.5%. In farm 2, the ERR of donor mares for the same ITO groups was 55.0%, 62.6%, and 73.7%, respectively (P = 0.02). The ERR for mares flushed after a previous spontaneous estrus was 75.0%. In conclusion, the ITO had a significant effect on the PR and ERR in the mare. Fertility was reduced as the ITO became shorter. Copyright © 2015 Elsevier Inc. All rights reserved.

Irradiation of human skin by short wavelength ultraviolet radiation (100--290 nm) (u.v.C): increased concentrations of arachidonic acid and prostaglandines E2 and F2alpha.

PubMed Central

Camp, R D; Greaves, M W; Hensby, C N; Plummer, N A; Warin, A P

1978-01-01

1. Human abdominal skin was irradiated with six times the minimal erythema dose of ultraviolet C (100--290 nm) radiation. Erythema appeared at 3 h, was of moderate degree by 6 h and was maximal at 12--24 h. It was reduced at 48 h and by 72 h had disappeared. 2. A suction bulla technique was used for the recovery of exudate from normal and inflamed skin at 6, 18, 24 and 48 h after irradiation. 3. Prostaglandin-like activity, estimated by bioassay, showed maximum increase at 18 h, when erythema was also maximum. PGF 2alpha, measured by both radioimmunoassay and by combined gas-liquid chromatography--gas spectrometry, followed a similar time course then fell to normal, or near normal, levels at 48 h. 4. Prostaglandin E2 and arachidonic acid concentrations, measured by gas chromatography--mass spectrometry, were maximally raised at 18--24 h. At 48 h, when some erythema was still present, though reduced, prostaglandin E2 concentrations were still raised above control values. 5. The results provide direct evidence in support of the view that the erythma following irradiation of human skin by u.v.C involves activation of arachidonic acid metabolism. However, the relationship between the erythema and increased prostaglandin activity is not fully understood. PMID:678391

Effect of exogenous progesterone administration on luteal sensitivity to PGF during the early development of the corpus luteum in mares and cows.

PubMed

Garcia-Muñoz, A; Valldecabres-Torres, X; Newcombe, J R; Cuervo-Arango, J; Garcia-Rosello, E

2017-12-01

The objective of this study was to determine the effect of exogenous progesterone administration at ovulation and during the early development of the CL, on its future sensitivity to a single administration of PGF2a in mares and cows. Horse Retrospective reproductive data from an equine clinic in the UK during three breeding seasons were used. Mares were divided into: control group, cycles with single ovulations; double ovulation group cycles with asynchronous double ovulations; and PRID group: cycles with single ovulations and treatment with intravaginal progesterone device (CIDR) immediately after the ovulation. All mares were treated with d-cloprostenol (PGF) at either: (i) 88 hr; (ii) 96 hr; (iii) 104 hr; or (iv) 112 hr after the last ovulation. Cattle A total of nine non-lactating Holstein cows were used. All cows were administered PGF14 d apart and allocated to one of two groups control group GnRH was administered 56 hr after the second PGF administration. CIDR group CIDR was inserted at the same time of GnRH administration. All cows were administered PGF at 120 hr post-ovulation. The complete luteolysis rate of mares with double ovulation (66.7%) and those treated with exogenous progesterone (68.4%) was significantly higher than the rate of mares with single ovulation (35.6%) at 104 hr. In the cow, however, the treatment with CIDR did not increase the luteolytic response in cows treated at 120 hr post-ovulation. In conclusion, the degree of complete luteolysis can be influenced by increasing the concentration of progesterone during the early luteal development in mares. © 2017 Blackwell Verlag GmbH.

Marker of lipid peroxidation related to diabetic nephropathy in Indonesian type 2 diabetes mellitus patients.

PubMed

Sauriasari, R; Andrajati, R; Azizahwati; Dharmeizar; Saputri, D A; Muris, R U; Manfaatun, A; Amanda, O F; Setiawan, H; Sakano, N; Wang, D H; Ogino, K

2015-04-01

Even though diabetes patients exhibit an increased oxidative stress, its correlation with diabetic nephropathy is not fully understood. The purpose of this study was to determine whether lipid peroxidation marker correlates well with eGFR and UACR in type 2 diabetes mellitus patients. We collected urine and serum samples of Indonesian type 2 diabetes mellitus outpatients with normo- and microalbuminuria at a Local Government Clinic (from ages: 39-74 years). Urinary 8-iso-PGF2α was measured by ELISA, the serum malondialdehyde by TBARS assay, and urinary albumin by BCG albumin assay. eGFR was calculated using the corrected-Cockcroft-Gault (CG), MDRD, and CKD-EPI equation. Other necessary data were obtained through questionnaires. The results showed that the increasing level of malondialdehyde was mildly correlated with the decline in eGFR (MDRD). In contrary, there was a significant positive correlation between 8-iso-PGF2α concentration and eGFR based on the corrected-CG, MDRD study, and CKD-EPI equation (r=0.457, p<0.001; r=0.424, p<0.001; r=0.443, p<0.001). This relationship still persisted in the normoalbuminuric subjects (n=43) (r=0.491, p=0.001; r=0.461, p=0.002; r=0.455, p=0.002). The multivariate analysis showed that 8-iso-PGF2α together with fasting plasma glucose was the most predictive factor for the high 2-quantile eGFR (adjusted OR 1.001, (95% CI, 1.000-1.001)). However, there was no significant correlation between UACR with malondialdehyde (r=0.268, p=0.050) and 8-iso-PGF2α(r=-0.030, p=0.808). UACR itself was inversely correlated with eGFR based on the corrected-CG, the MDRD, and CKD-EPI (r=-0.232, p<0.05; r=-0.228, p<0.05; r=-0.232, p<0.05). Increased 8-iso-PGF2α and malondialdehyde in type 2 diabetes mellitus patients may play a role in the pathophysiologic significance of diabetic nephropathy, even while considering the effect of potential confounders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

In vitro study of antiadipogenic profile of latanoprost, travoprost, bimatoprost, and tafluprost in human orbital preadiopocytes.

PubMed

Choi, Hee Young; Lee, Ji Eun; Lee, Ji Woong; Park, Hyun Jun; Lee, Ji Eun; Jung, Jae Ho

2012-04-01

To investigate the effect of prostaglandin F2α (PGF2α), latanoprost, travoprost, bimatoprost, and tafluprost on human orbital preadipocyte differentiation and intracellular lipid storage, and to reveal the potential mechanisms by which topical prostaglandin analogs induce orbital fat volume reduction and cause deep superior sulcus syndrome. Human orbital adipose precursors were treated in vitro for 24 h (day 1) with PGF2α, latanoprost, travoprost, bimatoprost, and tafluprost in their commercial formulations (1:100 dilution). Expressions of adipogenic transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ), and CCAAT-enhancer-binding protein α (C/EBPα) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) at day 7. At 14 days, cells were stained with oil red O, intracellular lipid accumulation was evaluated by lipid absorbance, and adipocyte expression marker [Lipoprotein lipase (LPL)] was determined by real-time RT-PCR. Our results showed that PGF2α and topical prostaglandin analogs down-regulated the expression of PPARγ and C/EBPα, and inhibited accumulation of intra-cytoplasmic lipid droplets and expression of LPL compared with the untreated control. Comparison between the 4 drugs showed that latanoprost had the weakest antiadipogenic effect, and bimatoprost induced the most significant reduction of adipogenesis. Latanoprost, travoprost, bimatoprost, and tafluprost inhibited human preadipocyte differentiation and intracellular lipid accumulation. Morphologic and metabolic changes in orbital adipocytes caused by PGF2α analogs are a possible pathophysiologic explanation of superior eyelid deepening in patients with glaucoma.

Amniotic Fluid Eicosanoids in Preterm and Term Births: Effects of Risk Factors for Spontaneous Preterm Labor

PubMed Central

Menon, Ramkumar; Fortunato, Stephen J.; Milne, Ginger L.; Brou, Lina; Carnevale, Claudine; Sanchez, Stephanie C.; Hubbard, Leah; Lappas, Martha; Drobek, Cayce Owens; Taylor, Robert N.

2012-01-01

OBJECTIVE To evaluate amniotic fluid (AF) arachidonic acid metabolites using enzymatic and nonenzymatic (lipid peroxidation) pathways in spontaneous preterm birth and term births, and to estimate whether prostanoid concentrations correlate with risk factors (race, cigarette smoking, and microbial invasion of amniotic cavity) associated with preterm birth. METHODS In a case-control study, AF was collected at the time of labor or during cesarean delivery. AF samples were subjected to gas chromatography, negative ion chemical ionization, and mass spectrometry for prostaglandin (PG)E2, PGF2α, and PGD2, 6-keto-PGF1α (6-KPGF1α, thromboxane (TXB2), and F2-isoprostane (F2-IsoP). Primary analysis examined differences between prostanoid concentrations in preterm birth (n=133) compared with term births (n=189). Secondary stratified analyses (by race, cigarette smoking and microbial invasion of amniotic cavity) compared eicosanoid concentrations in three epidemiological risk factors. RESULTS AF F2-IsoP, PGE2, and PGD2 were significantly higher at term than in PTB, whereas PGF2 α was higher in PTB 6-KPGF1α and TXB2 concentrations were not different. Data stratified by race (African American or Caucasian) showed no significant disparity among prostanoid concentrations. Regardless of gestational age status, F2-IsoP was threefold higher in smokers, and other eicosanoids were also higher in smokers compared to non-smokers. Preterm birth with microbial invasion of amniotic cavity had significantly higher F2-IsoP compared to preterm birth without microbial invasion of amniotic cavity. CONCLUSIONS Most AF eicosanoid concentrations (F2-isoP PGE2 and PGD2), are higher at term than in preterm birth. The only AF eicosanoid that is not higher at term is PGF2α. PMID:21691170

Reciprocal Cross Talk between Gonadotropin-Releasing Hormone (GnRH) and Prostaglandin Receptors Regulates GnRH Receptor Expression and Differential Gonadotropin Secretion

PubMed Central

Naor, Zvi; Jabbour, Henry N.; Naidich, Michal; Pawson, Adam J.; Morgan, Kevin; Battersby, Sharon; Millar, Michael R.; Brown, Pamela; Millar, Robert P.

2007-01-01

The asynchronous secretion of gonadotrope LH and FSH under the control of GnRH is crucial for ovarian cyclicity but the underlying mechanism is not fully resolved. Because prostaglandins (PG) are autocrine regulators in many tissues, we determined whether they have this role in gonadotropes. We first demonstrated that GnRH stimulates PG synthesis by induction of cyclooxygenase-2, via the protein kinase C/c-Src/phosphatidylinositol 3′-kinase/MAPK pathway in the LβT2 gonadotrope cell line. We then demonstrated that PGF2α and PGI2, but not PGE2 inhibited GnRH receptor expression by inhibition of phosphoinositide turnover. PGF2α, but not PGI2 or PGE2, reduced GnRH-induction of LHβ gene expression, but not the α-gonadotropin subunit or the FSHβ subunit genes. The prostanoid receptors EP1, EP2, FP, and IP were expressed in rat gonadotropes. Incubations of rat pituitaries with PGF2α, but not PGI2 or PGE2, inhibited GnRH-induced LH secretion, whereas the cyclooxygenase inhibitor, indomethacin, stimulated GnRH-induced LH secretion. None of these treatments had any effect on GnRH-induced FSH secretion. The findings have thus elaborated a novel GnRH signaling pathway mediated by PGF2α-FP and PGI2-IP, which acts through an autocrine/paracrine modality to limit autoregulation of the GnRH receptor and differentially inhibit LH and FSH release. These findings provide a mechanism for asynchronous LH and FSH secretions and suggest the use of combination therapies of GnRH and prostanoid analogs to treat infertility, diseases with unbalanced LH and FSH secretion and in hormone-dependent diseases such as prostatic cancer. PMID:17138645

Microflora inside closed modules with plant growth facility

NASA Astrophysics Data System (ADS)

Zyablova, Natalya V.; Berkovich, Yuliy A.; Shanturin, Nikolai; Deshevaya, Elena; Smolyanina, Svetlana O.

Currently, plant growth facility (PGF) is included in the LSS in many scenarios of Martian expedition. A number of investigators assume growing of crops can accelerate microflora re-production in closed ecological system. To estimate experimentally the change of density of microbiological community in the isolated module, Chinese cabbage Brassica hinensis L., cv. Vesnyanka, has been grown in the closed climatic chambers in volume 0.07 m3, 3 m3 and 250 m3 under continuous illumination in the range of values of temperature and relative humidity of air 23 -270 and 30 -60%, respectively. There were no differences in growth and develop-ment of plants grown during 30 days on the test-beds in the laboratory room (control) and in the closed chamber by 0.07 m3 volume (test). The microbiological analysis of root zone has revealed the presence of exclusively saprophytic species -the typical representatives of the soil microbiota. Then the plants were growing during 45 days in the prototype of the conveyor space PGF "Phytocycle LED" placed inside the chamber of 3 m3 volume. Every 3 days 50 -60 cm3 of liquid imitator of air condensate (IAC) from inhabited module had been injected to the chamber to simulate air pollution. The content of colony-forming units of the micromycetes in the air of the chamber, on the inner surfaces of the climate chamber, internal and external surfaces of the PGF and the leaves did not exceed the permissible values. When the PGF has been installed during 14 days inside the inhabited module with volume of 250 m3, the representatives of saprophytic and conditioned-pathogenic species of micromycetes (Trichethe-cium rozeum, Trichoderma sp., Fuzarrium sp., Mucor sp., Penicillium sp.) have been found out exclusively on the open surfaces of artificial soil and water-saturated porous passage. The obtained data shows that PGF inside closed modules can assure microbiological safety when all wet surfaces are isolated from the gas environment.

Increased Oxidative Stress in Healthy Children Following an Exercise Program: A Pilot Study

PubMed Central

Nasca, Melita M.; Zhang, Renliang; Super, Dennis M.; Hazen, Stanley L.; Hall, Howard R.

2010-01-01

Exercise can induce oxidative stress or an imbalance between reactive oxygen species and cellular antioxidant defenses. Objective We investigated the effect of a real-life exercise program on systemic oxidative stress measured by urinary concentrations of 8-isoprostaglandin F2α (8-iso-PGF2α), a noninvasive index of lipid peroxidation, in a well-characterized pediatric group. Methods Healthy but primarily sedentary, 8- to 10-year-old children (n = 6, mean age 8.8 ± 0.9 years) of equally distributed healthy weight, overweight, and obese categories, participated in a 5-week exercise program (track and field summer camp, 2 hours/day, 1–2 days/week). Results By using high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS), we found a significant (p = .028) increase in group mean urinary 8-iso-PGF2α concentration from 8.163 ± 6.919 ng/mg creatinine pre-exercise program to 32.320 ± 16.970 ng/mg creatinine post-exercise program. The increase was also measured at each individual level. We found preliminary evidence that pre- and post-exercise program urinary 8-iso-PGF2α concentrations selectively correlated with children’s cardiometabolic characteristics and mood. Conclusion Our results warrant further exploration of the relationships between pre/post-exercise oxidative stress marker 8-iso-PGF2α and cardiometabolic characteristics, exercise habits, eating habits, and mood to determine whether increased post-exercise oxidative stress in healthy children is part of their normal adaptation to exercise or mediator of oxidative injury. PMID:20495476

Postglacial seismic activity along the Isovaara-Riikonkumpu fault complex

NASA Astrophysics Data System (ADS)

Ojala, Antti E. K.; Mattila, Jussi; Ruskeeniemi, Timo; Palmu, Jukka-Pekka; Lindberg, Antero; Hänninen, Pekka; Sutinen, Raimo

2017-10-01

Analysis of airborne LiDAR-based digital elevation models (DEMs), trenching of Quaternary deposits, and diamond drilling through faulted bedrock was conducted to characterize the geological structure and full slip profiles of the Isovaara-Riikonkumpu postglacial fault (PGF) complex in northern Finland. The PGF systems are recognized from LiDAR DEMs as a complex of surface ruptures striking SW-NE, cutting through late-Weichselian till, and associated with several postglacial landslides within 10 km. Evidence from the terrain rupture characteristics, the deformed and folded structure of late-Weichselian till, and the 14C age of 11,300 cal BP from buried organic matter underneath the Sotka landslide indicates a postglacial origin of the Riikonkumpu fault (PGF). The fracture frequency and lithology of drill cores and fault geometry in the trench log indicate that the Riikonkumpu PGF dips to WNW with a dip angle of 40-45° at the Riikonkumpu site and close to 60° at the Riikonvaara site. A fault length of 19 km and the mean and maximum cumulative vertical displacement of 1.3 m and 4.1 m, respectively, of the Riikonkumpu PGF system indicate that the fault potentially hosted an earthquake with a moment magnitude MW ≈ 6.7-7.3 assuming that slip was accumulated in one seismic event. Our interpretation further suggests that the Riikonkumpu PGF system is linked to the Isovaara PGF system and that, together, they form a larger Isovaara-Riikonkumpu fault complex. Relationships between the 38-km-long rupture of the Isovaara-Riikonkumpu complex and the fault offset parameters, with cumulative displacement of 1.5 and 8.3 m, respectively, indicate that the earthquake(s) contributing to the PGF complex potentially had a moment magnitude of MW ≈ 6.9-7.5. In order to adequately sample the uncertainty space, the moment magnitude was also estimated for each major segment within the Isovaara-Riikonkumpu PGF complex. These estimates vary roughly between MW ≈ 5-8 for the individual segments.

Efficacy of various locally applied chemicals as contragestational agents in rats.

PubMed

Conner, E A; Blake, D A; Parmley, T H; Burnett, L S; King, T M

1976-05-01

Test agents were selected because of previous evidence of contragestationaal activity when administered systemically or because of known local effects which would be likely to cause endometrial changes having an adverse effect on pregnancy. A group of virgin female Sprague-Dawley rats were treated on Day 3 of pregnancy (preimplantation) and another group on Day 7 of pregnancy (postimplantation). Injections of .05 ml were made directly into the lumen of each uterine horn. Sodium chloride .9% was used on 1 side and the test agent on the other side. Implantation sites were counted before injections on Day 7. The number of corpora lutea indicated the expected number of conceptions of those injected on Day 3. On Day 15 rats were sacrificed and corpora lutea, viable conceptuses, and absorption sites were counted. Ethanol at 100, 80, 70, and 63% was a highly effective contragestational agent when given on Day 3. Formaldehyde 7-.5% was also highly effective when given on Day 3 but higher concentrations produced maternal toxicity and death. Silver nitrate, iodine, rivanol, cyclizine, urea, and 17beta-bromoacetoxy-19-nortestosterone produced no maternal toxicity but were all effective in reducing the number of viable fetuses. Prostaglandin (PGF2alpha), indomethacin, and ergonovine had no observable effect on preimplantation embryos. Methotrexate reduced survival when injected on Day 3 and more so when given on Day 7 but a systemic toxic effect was also noted. When injected on Day 7 all of the compounds except methotrexate were markedly less effective. Survival of fetuses in the control horns varied from 50% to 100%. Ethanol produced sloughing and necrosis but the endometrium appeared to be normal after 96 hours. Fecundity had not returned after 4-5 estrous cycles. The other compounds produced no histologically evident long-lasting effects. Superficial endometrial damage seemed to be the mechanism of action of compounds that were effective on Day 3. The discrepancies noted between results obtained and the documented efficiency of PGF2alpha and of urea as abortifacients in humans raises the question of the suitability of the rat as a model for predicting abortifacient activity in humans. However, the action of these 2 substances may be different in later gestational phases.

Synthesis and reception of prostaglandins in corpora lutea of domestic cat and lynx.

PubMed

Zschockelt, Lina; Amelkina, Olga; Siemieniuch, Marta J; Kowalewski, Mariusz P; Dehnhard, Martin; Jewgenow, Katarina; Braun, Beate C

2016-08-01

Felids show different reproductive strategies related to the luteal phase. Domestic cats exhibit a seasonal polyoestrus and ovulation is followed by formation of corpora lutea (CL). Pregnant and non-pregnant cycles are reflected by diverging plasma progesterone (P4) profiles. Eurasian and Iberian lynxes show a seasonal monooestrus, in which physiologically persistent CL (perCL) support constantly elevated plasma P4 levels. Prostaglandins (PGs) represent key regulators of reproduction, and we aimed to characterise PG synthesis in feline CL to identify their contribution to the luteal lifespan. We assessed mRNA and protein expression of PG synthases (PTGS2/COX2, PTGES, PGFS/AKR1C3) and PG receptors (PTGER2, PTGER4, PTGFR), and intra-luteal levels of PGE2 and PGF2α Therefore, CL of pregnant (pre-implantation, post-implantation, regression stages) and non-pregnant (formation, development/maintenance, early regression, late regression stages) domestic cats, and prooestrous Eurasian (perCL, pre-mating) and metoestrous Iberian (perCL, freshCL, post-mating) lynxes were investigated. Expression of PTGS2/COX2, PTGES and PTGER4 was independent of the luteal stage in the investigated species. High levels of luteotrophic PGE2 in perCL might be associated with persistence of luteal function in lynxes. Signals for PGFS/AKR1C3 expression were weak in mid and late luteal stages of cats but were absent in lynxes, concomitant with low PGF2α levels in these species. Thus, regulation of CL regression by luteal PGF2α seems negligible. In contrast, expression of PTGFR was evident in nearly all investigated CL of cat and lynxes, implying that luteal regression, e.g. at the end of pregnancy, is triggered by extra-luteal PGF2α. © 2016 Society for Reproduction and Fertility.

Systemic inflammatory response after endoscopic (TEP) vs Shouldice groin hernia repair.

PubMed

Schwab, R; Eissele, S; Brückner, U B; Gebhard, F; Becker, H P

2004-08-01

Endoscopic techniques are commonly used for many different types of surgery. It is claimed that videoendoscopic procedures have the advantage of being less traumatic and of offering higher postoperative patient comfort than conventional open techniques. The extent of tissue trauma can be evaluated on the basis of the inflammatory response observed in the wake of surgery. Available studies that have compared endoscopic and conventional techniques suggest that endoscopic cholecystectomy, laparoscopic colorectal resection, and thoracoscopic pulmonary resection have immunologic advantages over conventional approaches. The objective of this prospective study was to determine whether endoscopic hernia repair techniques are also preferable to conventional procedures and to what extent the anesthetic technique (local or general anesthesia) influences the postoperative inflammatory response. For this purpose, biochemical monitoring of cytokine activity [C-reactive protein (CRP), prostaglandin F1alpha (PGF1alpha), neopterin, interleukin-6 (IL-6)] was done prospectively in 101 patients [totally extraperitoneal approach (TEP) n=32, unilateral n=12, bilateral n=20; Shouldice n=69, local anesthesia (LA) n=23, general anesthesia (GA) n=46] before and until 3 days after surgery. The parameters IL-6 and PGF1alpha suggested that the immune trauma immediately after surgery was significantly higher in the group of patients with endoscopic hernia repair than in the group of patients who received a Shouldice repair. No significant differences were observed after the first postoperative day. A comparison between the TEP group and the patients who received conventional surgery under local anesthesia showed that the TEP approach was also associated with a higher postoperative neopterin level. Within the first 3 days after surgical intervention, bilateral endoscopic hernia repair induced no significantly higher inflammatory response than the surgical treatment of unilateral conditions. The anesthetic procedure that was used in the Shouldice operation had no significant effect on inflammatory response. Unlike other types of endoscopic surgery, the repair of groin hernias using an endoscopic technique cannot be regarded as a minimally invasive procedure that is less traumatic than conventional approaches. Instead, the conventional Shouldice procedure appears to cause the lowest inflammatory response and to be the least traumatic approach to hernia repair, especially when it is performed under local anesthesia.

[Synchronization of ovulation (OVSYNCH) in high-producing dairy cattle herds. I. Fertility parameters, body condition score and plama progesterone contration].

PubMed

Klindworth, H P; Hoedemaker, M; Burfeindt, D; Heilkenbrinker, T

2001-01-01

A method for synchronization of ovulation (OVSYNCH) was evaluated for its practical use in seven North German dairy cattle herds. The original procedure of PURSLEY et al. (1995) was applied, i.e. cows were injected Gonadotropin Releasing Hormone (GnRH) at a random stage of the estrous cycle, followed by an injection of a prostaglandin F2 alpha (PGF2 alpha)-analogon seven days later and another injection of GnRH two days after PGF2 alpha. Cows were inseminated 24 h after the last injection by artificial insemination. Control animals were assigned by corresponding lactation number and stage of lactation (month of partus). Cows from the OVSYNCH group returned to the conventional reproductive management after the OVSYNCH treatment, which was the same management as that for the control group. The average milk yield in 1997 and 1998 was 8128.6 +/- 637.0 kg and 8688.3 +/- 665.0 kg per year, respectively. First service conception rate (FSC) in the OVSYNCH group (n = 187) (39.77%) was lower than in the controls (n = 175) (54.34%; P < 0.01). In 1997, FSC for the OVSYNCH group did not differ from controls (48.94% vs. 55.45%; P > 0.05), whereas in 1998, FSC for the OVSYNCH group (29.27%) was significantly lower than in the control group (29.27% vs. 52.78%) and the OVSYNCH group in 1997 (each time P < 0.01). First service conception rate of first lactation cows in the OVSYNCH group was significantly lower than in the control group (37.84% vs. 71.05%; P < 0.01), whereas no difference was found for the other lactation groups. The mean interval calving to first service was shortened in the OVSYNCH group by about 14 d as compared with the controls (P < 0.01). However, mean days open only differed by 2.92 d (P > 0.05). Proportion of cows in each class of lactation number (1., 2. and > 2. lactation number) with days open < or = 115 d in the OVSYNCH group were similar to controls (P > 0.05). There was a great influence of body condition on the success of OVSYNCH. Cows with a body condition score (BCS) of 3.00 had a significant better FSC than cows with a BCS < 3.00 (P < 0.05). First service conception rate was lower for cows with a BCS > 3.25 and < 2.75 (cows in good and poor condition taken together) than for cows with a BCS of 3.00 (P < 0.05). A positive effect of OVSYNCH was found in acyclic cows as determined by progesterone concentration in blood plasma. Nine out of eleven cows reacted with the resumption of ovarian activity. Two cows became pregnant after first insemination.

Efficacy of four synchronization protocols on the estrus behavior and conception in native Korean cattle (Hanwoo).

PubMed

Lee, Myeung-Sik; Rahman, Md Saidur; Kwon, Woo-Sung; Chung, Hak-Jae; Yang, Boh-Suk; Pang, Myung-Geol

2013-11-01

Ineffective estrus detection is the foremost limiting factor in the fertility of farmed cattle worldwide. Failure to detect estrus or erroneous diagnosis of estrus results in great economic losses in Korea each year. This study was carried out in order to comprehensively describe the estrus behaviors and conception rates of different estrus synchronization protocols applied to 40 cycling native Korean cattle (Hanwoo). The cows were grouped into four (n = 10) and treated with the following protocols: (1) Day -15: controlled intravaginal drug-releasing device (CIDR) for 12 days; Day -5: prostaglandin F2α (PGF2α), (2) ovulation synchronization (OVS): Day -15: GnRH; Day -6: PGF2α; Day -4: GnRH, (3) Day -15: progesterone-releasing intravaginal device for 12 days; Day -5: PGF2α; and (4) Day -15: PGF2α; Day -4: PGF2α. Artificial insemination was performed 12 hours after the detection of estrus using frozen-thawed semen. Estrus signs were compared using a charge-coupled device camera (CCDC) and a control method (direct visual observation). The pregnancy of the cows was determined by transrectal ultrasonography at Days 25 to 30 postinsemination. The results indicated that the day of estrus return was significantly earlier using the CCDC method compared with direct visualization (P < 0.05). Mounting of other cows was the most predominant sign of estrus among the flock (P < 0.05), as analyzed using the CCDC. In the OVS group, a lower rate of mounting was observed than in the other three groups. Moreover, significantly fewer estrus behaviors were noticed in the OVS protocol group (P < 0.05). Both first service conception and overall conception rates were significantly higher (P < 0.05) in the CIDR and OVS treatment groups. In conclusion, the CIDR and OVS protocols appear to be the best practice for the synchronization of estrus for reproductive competence through the CCDC in Hanwoo cows. However, CIDR has a practical advantage over OVS with respect to estrus detection. Copyright © 2013 Elsevier Inc. All rights reserved.

Short-Term Exposure to Air Pollution and Biomarkers of Oxidative Stress: The Framingham Heart Study.

PubMed

Li, Wenyuan; Wilker, Elissa H; Dorans, Kirsten S; Rice, Mary B; Schwartz, Joel; Coull, Brent A; Koutrakis, Petros; Gold, Diane R; Keaney, John F; Lin, Honghuang; Vasan, Ramachandran S; Benjamin, Emelia J; Mittleman, Murray A

2016-04-28

Short-term exposure to elevated air pollution has been associated with higher risk of acute cardiovascular diseases, with systemic oxidative stress induced by air pollution hypothesized as an important underlying mechanism. However, few community-based studies have assessed this association. Two thousand thirty-five Framingham Offspring Cohort participants living within 50 km of the Harvard Boston Supersite who were not current smokers were included. We assessed circulating biomarkers of oxidative stress including blood myeloperoxidase at the seventh examination (1998-2001) and urinary creatinine-indexed 8-epi-prostaglandin F2α (8-epi-PGF2α) at the seventh and eighth (2005-2008) examinations. We measured fine particulate matter (PM2.5), black carbon, sulfate, nitrogen oxides, and ozone at the Supersite and calculated 1-, 2-, 3-, 5-, and 7-day moving averages of each pollutant. Measured myeloperoxidase and 8-epi-PGF2α were loge transformed. We used linear regression models and linear mixed-effects models with random intercepts for myeloperoxidase and indexed 8-epi-PGF2α, respectively. Models were adjusted for demographic variables, individual- and area-level measures of socioeconomic position, clinical and lifestyle factors, weather, and temporal trend. We found positive associations of PM2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2- to 7-day moving averages of PM2.5 and sulfate were consistently positively associated with 8-epi-PGF2α. Stronger positive associations of black carbon and sulfate with myeloperoxidase were observed among participants with diabetes than in those without. Our community-based investigation supports an association of select markers of ambient air pollution with circulating biomarkers of oxidative stress. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Estrus synchronization in microminipig using estradiol dipropionate and prostaglandin F2α

PubMed Central

NOGUCHI, Michiko; IKEDO, Tomonobu; KAWAGUCHI, Hiroaki; TANIMOTO, Akihide

2016-01-01

The induction of pseudopregnancy by the exogenous administration of estradiol dipropionate (EDP) was investigated in cyclic Microminipigs (MMpigs) and the effects of exogenous administration of prostaglandin (PG) F2α on estrus exhibition were assessed in pseudopregnant MMpigs. In experiment 1, ovariectomized MMpigs were given a single intramuscular injection of 0.5, 1.5, or 2.5 mg of EDP. The estradiol-17β level at each of these doses was significantly higher 1 to 3 days after EDP administration than on the day of the injection. In experiment 2, animals were given 1.5 mg of EDP once at 9 to 12 days after the end of estrus (D0) and then no (1.5 mg × 1 group), one (D0 and D4; 1.5 mg × 2 group), or two (D0, D4 and D7; 1.5 mg × 3 group) additional treatments. The pseudopregnancy rate was significantly higher in the 1.5 mg × 3 than in the 1.5 mg × 1 group. In experiment 3, PGF2α was administered twice between 26 and 28 days after EDP treatment to five pseudopregnant gilts with a 24-h interval between the two injections. Estrus after PGF2α treatment and LH surge were observed in 100% and 80% pseudopregnant MMpigs, respectively. The interval from the day of the first PGF2α treatment to the onset of estrus was 6.5 ± 0.2 days. These results indicate that multiple EDP treatments are required for induction of pseudopregnancy in MMpigs and estrus exhibition can be controlled in MMpigs by treatment with EDP and PGF2α. PMID:27151362

Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases.

PubMed

Nguyen, Quan Dong; De Falco, Sandro; Behar-Cohen, Francine; Lam, Wai-Ching; Li, Xuri; Reichhart, Nadine; Ricci, Federico; Pluim, Jennifer; Li, William W

2018-02-01

The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research. © 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation and European Association for Vision & Eye Research.

Activation of Gq/11 in the Mouse Corpus Luteum Is Required for Parturition

PubMed Central

Mejia, Rachel; Waite, Courtney

2015-01-01

Mice with a deletion of Gαq/11 in granulosa cells were previously shown to be subfertile. They also have a reduced ovulatory response due to a deficiency in the ability of the activated LH receptor to fully induce the granulosa cell progesterone receptor. Because this conditional deletion of Gαq/11 will interfere with the actions of any G protein-coupled receptor that activates Gq/11 in granulosa or luteal cells, we sought to determine whether the actions of other hormones that contribute to fertility were also impaired. We focused our attention on prostaglandin F2 (PGF2)α, because this hormone is known to activate phospholipase C (a prominent Gαq/11 effector) in luteal cells and because the action of PGF2α on luteal cells is the first step in the murine parturition pathway. Our data show that the conditional deletion of Gαq/11 from granulosa cells prevents the ability of PGF2α to induce Akr1c18 in luteal cells. Akr1c18 codes for 20α-hydroxysteroid dehydrogenase, an enzyme that inactivates progesterone. The PGF2α-mediated induction of this enzyme towards the end of pregnancy increases the inactivation of progesterone and precipitates parturition in mice. Thus, the conditional deletion of Gαq/11 from granulosa/luteal cells prevents the progesterone withdrawal that occurs at the end of pregnancy and impairs parturition. This novel molecular defect contributes to the subfertile phenotype of the mice with a deletion of Gαq/11 from granulosa cells. PMID:25495873

Activation of Gq/11 in the mouse corpus luteum is required for parturition.

PubMed

Mejia, Rachel; Waite, Courtney; Ascoli, Mario

2015-02-01

Mice with a deletion of Gα(q/11) in granulosa cells were previously shown to be subfertile. They also have a reduced ovulatory response due to a deficiency in the ability of the activated LH receptor to fully induce the granulosa cell progesterone receptor. Because this conditional deletion of Gα(q/11) will interfere with the actions of any G protein-coupled receptor that activates G(q/11) in granulosa or luteal cells, we sought to determine whether the actions of other hormones that contribute to fertility were also impaired. We focused our attention on prostaglandin F2 (PGF2)α, because this hormone is known to activate phospholipase C (a prominent Gα(q/11) effector) in luteal cells and because the action of PGF2α on luteal cells is the first step in the murine parturition pathway. Our data show that the conditional deletion of Gα(q/11) from granulosa cells prevents the ability of PGF2α to induce Akr1c18 in luteal cells. Akr1c18 codes for 20α-hydroxysteroid dehydrogenase, an enzyme that inactivates progesterone. The PGF2α-mediated induction of this enzyme towards the end of pregnancy increases the inactivation of progesterone and precipitates parturition in mice. Thus, the conditional deletion of Gαq/11 from granulosa/luteal cells prevents the progesterone withdrawal that occurs at the end of pregnancy and impairs parturition. This novel molecular defect contributes to the subfertile phenotype of the mice with a deletion of Gα(q/11) from granulosa cells.

Electric Field-Assisted Orientation of Short Phosphate Glass Fibers on Stainless Steel for Biomedical Applications.

PubMed

Chen, Qiang; Jing, Jiajia; Qi, Hongfei; Ahmed, Ifty; Yang, Haiou; Liu, Xianhu; Lu, T L; Boccaccini, Aldo R

2018-04-11

Structural and compositional modifications of metallic implant surfaces are being actively investigated to achieve improved bone-to-implant bonding. In this study, a strategy to modify bulk metallic surfaces by electrophoretic deposition (EPD) of short phosphate glass fibers (sPGF) is presented. Random and aligned orientation of sPGF embedded in a poly(acrylic acid) matrix is achieved by vertical and horizontal EPD, respectively. The influence of EPD parameters on the degree of alignment is investigated to pave the way for the fabrication of highly aligned sPGF structures in large areas. Importantly, the oriented sPGF structure in the coating, owing to the synergistic effects of bioactive composition and fiber orientation, plays an important role in directional cell migration and enhanced proliferation. Moreover, gene expression of MC3T3-E1 cells cultured with different concentrations of sPGF is thoroughly assessed to elucidate the potential stimulating effect of sPGF on osteogenic differentiation. This study represents an innovative exploitation of EPD to develop textured surfaces by orientation of fibers in the macroscale, which shows great potential for directional functionalization of metallic implants.

Effects of differential supplementation of fatty acids during the peripartum and breeding periods of Holstein cows: I. Uterine and metabolic responses, reproduction, and lactation.

PubMed

Silvestre, F T; Carvalho, T S M; Francisco, N; Santos, J E P; Staples, C R; Jenkins, T C; Thatcher, W W

2011-01-01

The objectives were to evaluate the effects of differential timing of supplementation of different Ca salts (CS) of fatty acids (FA) on FA profiles of cotyledonary-caruncular tissues, metabolic status, uterine health, pregnancy, pregnancy losses after 2 artificial inseminations (AI), and milk yield. Holstein cows (n=1,380) were assigned randomly to be fed either CS of palm oil (PO) or safflower oil (SO) from 30 d prepartum until 30 d postpartum (dpp) and further randomized to receive either CS of PO or fish oil (FO) from 30 to 160 dpp. Supplementation of CS of FA was at 1.5% of dietary dry matter. Tissues (n=23) and blood (n=32) were collected from a subsample of cows. Blood was collected daily from parturition to 10 dpp and three times weekly thereafter until 30 dpp for analyses of PGF2α metabolite, nonesterified FA, β-hydroxybutyric acid, blood urea nitrogen, and glucose. Cows were evaluated once between 8 to 10 dpp for cervical discharge type. At 43 dpp, cows received 2 injections of PGF2α 14 d apart, followed 14 d later by injections of GnRH at 7 d before and 56 h after an injection of PGF2α with AI at 16 h after the second GnRH injection. All cows received intravaginally a controlled internal drug-releasing device, containing 1.38 g of progesterone, at 18 d after the first AI followed 7 d later by removal of the device and injection of GnRH. Nonpregnant cows at 32 d after AI were injected with PGF2α, followed 56 h later with a GnRH injection and second AI 16 h thereafter. Cows diagnosed pregnant after both AI were re-examined at 60 d of pregnancy to determine pregnancy losses. Milk weights were recorded monthly for all cows. Caruncular n-6:n-3 FA ratio was greater in cows fed SO. Plasma concentrations of metabolites and frequency of cervical discharge type did not differ between PO- and SO-fed cows. Plasma PGF2α metabolite was greater in SO-fed cows at 4 and 7 dpp. Pregnancy per AI at 32 and 60 d post first AI was not affected by diets, but pregnancy loss was less in FO-fed cows. At second AI, pregnancy was greater in FO-fed cows at 32 d and in SO-FO-fed cows at 60 d post AI. Pregnancy loss after second AI was not affected by diets. Overall pregnancy per AI was greater in cows fed SO followed by FO at 60 d of pregnancy and pregnancy loss was reduced in FO-fed cows. Monthly milk yield was greater (0.7 kg/d) in SO-fed cows. In conclusion, strategic feeding of CS of FA during transition and breeding periods can benefit fertility and milk production of lactating dairy cows. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Heterotypic contact reveals a COX-2-mediated suppression of osteoblast differentiation by endothelial cells: A negative modulatory role for prostanoids in VEGF-mediated cell: cell communication?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clarkin, Claire E.; Garonna, Elena; Pitsillides, Andrew A.

In bone, angiogenesis must be initiated appropriately, but limited once remodelling or repair is complete. Our recent findings have supported a role for prostaglandins (PG), known modulators of osteoblast (OB) and endothelial cell (EC) behaviour, in facilitating VEGF-mediated paracrine communication from OBs to 'remotely located' ECs, but the mechanism(s) regulating OB:EC crosstalk when these cells are closely opposed are undefined. In this study we have examined: (i) the effects of exogenous PGE{sub 2} on VEGF-driven events in ECs, and (ii) the role of endogenous COX-2-derived prostanoids in mediating communication between intimately opposed OBs and ECs in direct contact. Exposure ofmore » ECs to PGE{sub 2} increased ERK1/2 phosphorylation, COX-2 induction, 6-keto-PGF{sub 1{alpha}} release and EC proliferation. In contrast, PGE{sub 2} attenuated VEGF{sub 165}-induced VEGFR2/Flk1 phosphorylation, ERK1/2 activation and proliferation of ECs, suggesting that exogenous PGE{sub 2} restricts the actions of VEGF. However, the COX-2-selective inhibitor, NS398, also attenuated VEGF-induced proliferation, implying a distinct role for endogenous COX-2 activity in regulating EC behaviour. To examine the effect of OB:EC proximity and the role of COX-2 products further, we used a confrontational co-culture model. These studies showed that COX-2 blockade with NS398 enhanced EC-dependent increases in OB differentiation, that this effect was reversed by exogenous PGH{sub 2} (immediate COX-2 product), and that exogenous VEGF did not influence EC-dependent OB differentiation under these conditions. Our findings indicate that locally produced prostanoids may serve distinct roles depending on OB:EC proximity and negatively modulate VEGF-mediated changes in EC behaviour when these cells are closely opposed to control angiogenesis during bone (re)modelling.« less

Arterial stiffness and sedentary lifestyle: Role of oxidative stress.

PubMed

Lessiani, Gianfranco; Santilli, Francesca; Boccatonda, Andrea; Iodice, Pierpaolo; Liani, Rossella; Tripaldi, Romina; Saggini, Raoul; Davì, Giovanni

2016-04-01

Sedentary lifestyle is a risk factor for the development of cardiovascular disease, and leads to a quantifiable impairment in vascular function and arterial wall stiffening. We tested the hypothesis of oxidative stress as a determinant of arterial stiffness (AS) in physically inactive subjects, and challenged the reversibility of these processes after the completion of an eight-week, high-intensity exercise training (ET). AS was assessed before and after ET, measuring carotid to femoral pulse wave velocity (PWV) with a Vicorder device. At baseline and after ET, participants performed urine collection and underwent fasting blood sampling. Urinary 8-iso-PGF2α, an in vivo marker of lipid peroxidation, total, HDL and LDL cholesterol, and triglyceride concentrations were measured. ET was associated with significantly reduced urinary 8-iso-PGF2α(p<0.0001) levels. PWV was significantly reduced after ET completion (p<0.0001), and was directly related to urinary 8-iso-PGF2α(Rho=0.383, p=0.021). After ET, cardiovascular fitness improved [peak oxygen consumption (p<0.0001), peak heart rate (p<0.0001)]. However, no improvement in lipid profile was observed, apart from a significant reduction of triglycerides (p=0.022). PWV and triglycerides were significantly related (Rho=0.466, p=0.005) throughout the study period. PWV levels were also related to urinary 8-iso-PGF2α in our previously sedentary subjects. We conclude that regular physical exercise may be a natural antioxidant strategy, lowering oxidant stress and thereby the AS degree. Copyright © 2015 Elsevier Inc. All rights reserved.

The prostaglandin E2 receptor PTGER2 and prostaglandin F2α receptor PTGFR mediate oviductal glycoprotein 1 expression in bovine oviductal epithelial cells.

PubMed

Zhang, Nan; Mao, Wei; Zhang, Ying; Huang, Na; Liu, Bo; Gao, Long; Zhang, Shuangyi; Cao, Jinshan

2018-04-13

Oviductal glycoprotein 1 (OVGP1), an oviductin, is involved in the maintenance of sperm viability and motility and contributes to sperm capacitation in the oviduct. In this study, the regulatory effects exerted by prostaglandin E 2 (PGE 2 ) and F 2α (PGF 2α ) on OVGP1 expression via their corresponding receptors in bovine oviductal epithelial cells (BOECs) were investigated. BOECs were cultured in vitro, and their expression of receptors of PGE 2 (PTGER1, PTGER2, PTGER3, and PTGER4) and PGF 2α (PTGFR) was measured using RT-qPCR. Ca 2+ concentration was determined with a fluorescence-based method and cAMP was quantified by enzyme-linked immunosorbent assays to verify activation of PTGER2 and PTGFR by their corresponding agonists in these cells. OVGP1 mRNA and protein expression was measured using RT-qPCR and western blotting, respectively, following PTGER2 and PTGFR agonist-induced activation. PTGER1, PTGER2, PTGER4, and PTGFR were found to be present in BOECs; however, PTGER3 expression was not detected. OVGP1 expression was significantly promoted by 10 -6 M butaprost (a PTGER2 agonist) and decreased by 10 -6 M fluprostenol (a PTGFR agonist). In addition, 3 μM H-89 (a PKA inhibitor) and 3 μM U0126 (an ERK inhibitor) effectively inhibited PGE 2 -induced upregulation of OVGP1, and 5 μM chelerythrine chloride (a PKC inhibitor) and 3 μM U0126 negated OVGP1 downregulation by PGF 2α . In conclusion, this study demonstrates that OVGP1 expression in BOECs is enhanced by PGE 2 via PTGER2-cAMP-PKA signaling, and reduced by PGF 2α through the PTGFR-Ca 2+ -PKC pathway.

Virgin olive oil, palm olein and coconut oil diets do not raise cell adhesion molecules and thrombogenicity indices in healthy Malaysian adults.

PubMed

Voon, P T; Ng, T K W; Lee, V K M; Nesaretnam, K

2015-06-01

Effects of high-protein diets that are rich in saturated fats on cell adhesion molecules, thrombogenicity and other nonlipid markers of atherosclerosis in humans have not been firmly established. We aim to investigate the effects of high-protein Malaysian diets prepared separately with virgin olive oil (OO), palm olein (PO) and coconut oil (CO) on cell adhesion molecules, lipid inflammatory mediators and thromobogenicity indices in healthy adults. A randomized cross-over intervention with three dietary sequences, using virgin OO, PO and CO as test fats, was carried out for 5 weeks on each group consisting of 45 men and women. These test fats were incorporated separately at two-thirds of 30% fat calories into high-protein Malaysian diets. For fasting and nonfasting blood samples, no significant differences were observed on the effects of the three test-fat diets on thrombaxane B2 (TXB2), TXB2/PGF1α ratios and soluble intracellular and vascular cell adhesion molecules. The OO diet induced significantly lower (P<0.05) plasma leukotriene B4 (LTB4) compared with the other two test diets, whereas PGF1α concentrations were significantly higher (P<0.05) at the end of the PO diet compared with the OO diet. Diets rich in saturated fatty acids from either PO or CO and high in monounsaturated oleic acid from virgin OO do not alter the thrombogenicity indices-cellular adhesion molecules, thromboxane B2 (TXB2) and TXB2/prostacyclin (PGF1α) ratios. However, the OO diet lowered plasma proinflammatory LTB4, whereas the PO diet raised the antiaggregatory plasma PGF1α in healthy Malaysian adults. This trial was registered at clinicaltrials.gov as NCT 00941837.

The Expression and Regulation of Adrenomedullin in the Human Endometrium: A Candidate for Endometrial Repair

PubMed Central

Maybin, Jacqueline A.; Battersby, Sharon; Hirani, Nikhil; Nikitenko, Leonid L.; Critchley, Hilary O. D.

2011-01-01

After menstruation, the endometrium has a remarkable capacity for repair, but the factors involved remain undefined. We hypothesize adrenomedullin (AM) plays a role in this process. Premenstrually progesterone levels decline, stimulating prostaglandin (PG) synthesis, vasoconstriction, and hypoxia. This study aimed to determine 1) AM expression throughout the menstrual (M) cycle and 2) its regulation by PG and hypoxia. Human endometrial biopsies (n = 51) were collected with ethical approval and consent. AM mRNA expression was examined by quantitative RT-PCR and was found to be selectively elevated in endometrium from the menstrual (M) phase (P < 0.001). AM immunohistochemical staining was maximal in M and proliferative (P) endometrium. Culture of secretory, but not P, explants with 100 nm PGF2α or hypoxia (0.5% O2) increased AM mRNA (P < 0.05). P explants were induced to increase AM expression using in vitro progesterone withdrawal but required the presence of hypoxia (P < 0.05). Short hairpin sequences against hypoxia-inducible factor-1α (HIF-1α) inhibited AM hypoxic up-regulation but did not alter PGF2α-induced expression. The AM receptor was immunolocalized to endothelial cells in both lymphatic and blood vessels. Conditioned medium from PGF2α-treated cells increased endothelial cell proliferation and branching (P < 0.05). This was abolished by AM receptor antagonists. In conclusion, AM is elevated at the time of endometrial repair and induces both angiogenesis and lymphangiogenesis by stimulating endothelial cell proliferation and tube formation. In the human endometrium, AM expression is up-regulated by two mechanisms: a HIF-1α-mediated hypoxic induction and a HIF-1α-independent PGF2α pathway. These physiological mechanisms may provide novel therapeutic targets for disorders such as heavy menstrual bleeding. PMID:21558311

Use of gonadotropin releasing hormone to improve reproductive responses of ewes introduced to rams during seasonal anestrus.

PubMed

Jordan, K M; Inskeep, E K; Knights, M

2009-12-01

Three experiments were conducted on anestrous ewes of Suffolk, Dorset, and Katahdin breeding to examine the potential value of GnRH to improve ovulation and pregnancy in response to introduction of rams. In Experiment 1, treatment with GnRH 2d after treatment with progesterone (P(4); 25mg i.m.) at introduction of rams was compared to treatment with P(4) alone at the time of introduction of rams. Treatment with GnRH did not increase percentages of ewes with a corpus luteum (CL) 14d after introduction of rams, pregnant 32d after treatment with PGF(2)alpha 14d after introduction of rams, or percent of treated ewes lambing to all services. In Experiment 2, treatments with GnRH on day 2, 7, or both after introduction of rams were compared. Treatments did not differ in mean estrous response, percentages of ewes with a detectable CL or number of CL present on day 11, or mean pregnancy and lambing rates. Therefore, neither one nor two injections of GnRH at these times appeared to be effective to induce anestrous ewes to breed. In Experiment 3, treatments compared included GnRH 4d before introduction of rams, GnRH 4d before and 1d after introduction of rams, ram introduction alone, and treatment with P(4) (25mg i.m.) at the time of introduction of rams. Percentages of ewes with concentrations of P(4) greater than 1ng/mL (indicating formation of CL had occurred) 7d after ram introduction tended to be greater (P<0.07) in ewes treated with GnRH or P(4) than in control ewes treated with ram introduction alone. However, there was no difference in P(4) concentrations between groups by day 11 or 12 after introduction of rams. Estrous response rates and percentages of ewes pregnant 95d after PGF(2)alpha was administered (on day 12 after introduction of rams) tended to be greater (P=0.08 and 0.06, respectively) in ewes treated with GnRH or P(4) than in ewes exposed to rams only. There was no difference in response variables between ewes treated with GnRH 4d before introduction of rams and ewes treated with GnRH 4d before and 1d after introduction of rams. In conclusion, treatment with GnRH 4d before ram introduction showed promise as an alternative to treatment with P(4) to improve the ovulatory response and reproductive performance of ewes introduced to rams during seasonal anestrus.

Time course of defense mechanisms in bovine endometrium in response to lipopolysaccharide.

PubMed

Swangchan-Uthai, Theerawat; Lavender, Chloe R M; Cheng, Zhangrui; Fouladi-Nashta, Ali A; Wathes, D Claire

2012-06-01

Endometritis caused by uterine infection after calving reduces fertility and causes major economic losses to the dairy industry. This study investigated the time course of an inflammatory response in bovine endometrium triggered by exposure to bacterial endotoxin lipopolysaccharide (LPS). Mixed endometrial epithelial and stromal cells (9:1 ratio) were grown to confluence as a model system and treated with an optimized dose of 100 ng/ml LPS in vitro. Gene expression responses were measured using quantitative PCR, and gene products were investigated using assays of culture medium and Western blotting. Of 17 candidate genes tested initially, LPS treatment for 24 h up-regulated mRNA expression of TLR4 signaling (TLR4, CD14), cytokines (IL1B, TNF), chemokines (IL8, CXCL5), antimicrobial peptides (LAP, S100A8, S100A9, S100A12), and matrix metalloproteinases (MMP1, MMP13). A 48 h, LPS time course study showed that TNF increased first at 1 h, followed by peak expression of IL1B at 6 h, and those of S100A8, S100A12, and LAP at 12 h. The intracellular S100A8 protein content doubled at 12-24 h but with little excretion into the medium. Regarding prostaglandin biosynthesis, PTGES mRNA was slightly higher after LPS exposure, whereas expression of the PGF synthase AKR1B1 was inhibited. Despite this, LPS treatment stimulated the secretion of both PGE₂ and PGF₂(alpha) to a similar extent. These results suggest that the family of S100 Ca²⁺ binding proteins are released from damaged endometrial cells and may play a major antimicrobial role. Prostaglandin synthesis increased during the uterine infection, but we found no evidence that this was associated with a change in the PGE:PGF ratio.

Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lingappan, Krithika, E-mail: lingappa@bcm.edu; Jiang, Weiwu; Wang, Lihua

Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expressionmore » in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.« less

Evaluation of two progestogen-based estrous synchronization protocols in yearling heifers of Bos indicus × Bos taurus breeding.

PubMed

McKinniss, E N; Esterman, R D; Woodall, S A; Austin, B R; Hersom, M J; Thatcher, W W; Yelich, J V

2011-06-01

Yearling Bos indicus × Bos taurus heifers (n = 410) from three locations, were synchronized with either the Select Synch/CIDR+timed-AI (SSC+TAI) or 7-11+timed-AI (7-11+TAI) treatments. On Day 0 of the experiment, within each location, heifers were equally distributed to treatments by reproductive tract score (RTS; Scale 1-5: 1 = immature, 5 = estrous cycling) and body condition score. The 7-11+TAI treatment consisted of melengestrol acetate (0.5 mg/head/d) from Days 0 to 7, with PGF(2α) (25 mg im) on Day 7, GnRH (100 μg im) on Day 11, and PGF(2α) (25 mg im) on Day 18. The SSC+TAI heifers received the same carrier supplement (without MGA) from Days 0 to 7, and on Day 11 they were given 100 μg GnRH and an intravaginal CIDR (containing 1.38 g progesterone). The CIDR were removed on Day 18, concurrent with 25 mg PGF(2α) im For both treatments, estrus was visually detected for 1 h twice daily (0700 and 1600 h) for 72 h after PGF(2α), with AI done 6 to 12 h after a detected estrus. Non-responders were timed-AI and received GnRH (100 μg im) 72 to 76 h post PGF(2α). The 7-11+TAI heifers had a greater (P < 0.05) estrous response (55.2 vs 41.9%), conception rate (47.0 vs 31.3%), and synchronized pregnancy rate (33.5 vs 24.8%) compared to SSC+TAI heifers, respectively. Heifers exhibiting estrus at 60 h (61.7%) had a greater (P < 0.05) conception rate compared to heifers that exhibited estrus at ≤ 36 (35.3%), 48 (31.6%), and 72 h (36.2%), which were similar (P > 0.05) to each other. As RTS increased from ≤ 2 to ≥ 3, estrous response, conception rate, synchronized pregnancy rate, and 30 d pregnancy rate all increased (P < 0.05), irrespective of synchronization treatment. In conclusion, the 7-11+TAI treatment yielded greater synchronized pregnancy rates compared to SSC+TAI treatment in yearling Bos indicus × Bos taurus heifers. Copyright © 2011 Elsevier Inc. All rights reserved.

Fertility of Angus cross beef heifers after GnRH treatment on day 23 and timing of insemination in 14-day CIDR protocol.

PubMed

Kasimanickam, R K; Hall, J B; Whittier, W D

2017-02-01

This study compared artificial insemination pregnancy rate (AI-PR) between 14-day CIDR-GnRH-PGF2α-GnRH and CIDR-PGF2α-GnRH synchronization protocol with two fixed AI times (56 or 72 hr after PGF2α). On day 0, heifers (n = 1311) from nine locations assigned body condition score (BCS: 1, emaciated; 9, obese), reproductive tract score (RTS: 1, immature, acyclic; 5, mature, cyclic) and temperament score (0, calm; and 1, excited) and fitted with a controlled internal drug release (CIDR, 1.38 g of progesterone) insert for 14 days. Within herd, heifers were randomly assigned either to no-GnRH group (n = 635) or to GnRH group (n = 676), and heifers in GnRH group received 100 μg of GnRH (gonadorelin hydrochloride, IM) on day 23. All heifers received 25 mg of PGF2α (dinoprost, IM) on day 30 and oestrous detection aids at the same time. Heifers were observed for oestrus thrice daily until AI. Within GnRH groups, heifers were randomly assigned to either AI-56 or AI-72 groups. Heifers in AI-56 group (n = 667) were inseminated at 56 hr (day 32 PM), and heifers in AI-72 group (n = 644) were inseminated at 72 hr (day 33 AM) after PGF2α administration. All heifers were given 100 μg of GnRH concurrently at the time AI. Controlling for BCS (p < .05), RTS (p < .05), oestrous expression (p < .001), temperament (p < .001) and GnRH treatment by time of insemination (p < .001), the AI-PR differed between GnRH treatment [GnRH (Yes - 60.9% (412/676) vs. No - 55.1% (350/635); p < .05)] and insemination time [AI-56 - 54.6% (364/667) vs. AI-72 - 61.8% (398/644); (p < .01)] groups. The GnRH treatment by AI time interaction influenced AI-PR (GnRH56 - 61.0% (208/341); GnRH72 - 60.9% (204/335); No-GnRH56 - 47.9% (156/326); No-GnRH72 - 62.8% (194/309); p < .001). In conclusion, 14-day CIDR synchronization protocol for FTAI required inclusion of GnRH on day 23 if inseminations were to be performed at 56 hr after PGF2α in order to achieve greater AI-PR. © 2016 Blackwell Verlag GmbH.

Dipetalodipin, a Novel Multifunctional Salivary Lipocalin That Inhibits Platelet Aggregation, Vasoconstriction, and Angiogenesis through Unique Binding Specificity for TXA2, PGF2α, and 15(S)-HETE*

PubMed Central

Assumpção, Teresa C. F.; Alvarenga, Patricia H.; Ribeiro, José M. C.; Andersen, John F.; Francischetti, Ivo M. B.

2010-01-01

Dipetalodipin (DPTL) is an 18 kDa protein cloned from salivary glands of the triatomine Dipetalogaster maxima. DPTL belongs to the lipocalin superfamily and has strong sequence similarity to pallidipin, a salivary inhibitor of collagen-induced platelet aggregation. DPTL expressed in Escherichia coli was found to inhibit platelet aggregation by collagen, U-46619, or arachidonic acid without affecting aggregation induced by ADP, convulxin, PMA, and ristocetin. An assay based on incubation of DPTL with small molecules (e.g. prostanoids, leukotrienes, lipids, biogenic amines) followed by chromatography, mass spectrometry, and isothermal titration calorimetry showed that DPTL binds with high affinity to carbocyclic TXA2, TXA2 mimetic (U-46619), TXB2, PGH2 mimetic (U-51605), PGD2, PGJ2, and PGF2α. It also interacts with 15(S)-HETE, being the first lipocalin described to date to bind to a derivative of 15-lipoxygenase. Binding was not observed to other prostaglandins (e.g. PGE1, PGE2, 8-iso-PGF2α, prostacyclin), leukotrienes (e.g,. LTB4, LTC4, LTD4, LTE4), HETEs (e.g. 5(S)-HETE, 12(S)-HETE, 20-HETE), lipids (e.g. arachidonic acid, PAF), and biogenic amines (e.g. ADP, serotonin, epinephrine, norepinephrine, histamine). Consistent with its binding specificity, DPTL prevents contraction of rat uterus stimulated by PGF2α and induces relaxation of aorta previously contracted with U-46619. Moreover, it inhibits angiogenesis mediated by 15(S)-HETE and did not enhance inhibition of collagen-induced platelet aggregation by SQ29548 (TXA2 antagonist) and indomethacin. A 3-D model for DPTL and pallidipin is presented that indicates the presence of a conserved Arg39 and Gln135 in the binding pocket of both lipocalins. Results suggest that DPTL blocks platelet aggregation, vasoconstriction, and angiogenesis through binding to distinct eicosanoids involved in inflammation. PMID:20889972

Supercapacitors based on graphene-supported iron nanosheets as negative electrode materials.

PubMed

Long, Conglai; Wei, Tong; Yan, Jun; Jiang, Lili; Fan, Zhuangjun

2013-12-23

We report a facile strategy to prepare iron nanosheets directly grown on graphene sheets nanocomposite (C-PGF) through the carbonization of iron ions adsorbed onto polyaniline nanosheet/graphene oxide hybrid material. Because of the synergistic effect of iron nanosheets and graphene sheets, the as-obtained C-PGF exhibits an ultrahigh capacitance of ca. 720 F g(-1) in 6 M KOH aqueous solution. Additionally, the assembled asymmetric supercapacitor (C-PGF//Ni(OH)2/CNTs) delivers a remarkable high power density and a noticeable ultrahigh energy density of ca. 140 Wh kg(-1) (based on the total mass of active materials) and an acceptable cycling performance of 78% retention after 2000 cycles. Therefore, the designed supercapacitors with high energy density, comparable to rechargeable lithium-ion batteries (LIBs), offer an important guideline for future design of advanced next-generation supercapacitors for both industrial and consumer applications.

Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages.

PubMed

Lara-Guzmán, Oscar J; Gil-Izquierdo, Ángel; Medina, Sonia; Osorio, Edison; Álvarez-Quintero, Rafael; Zuluaga, Natalia; Oger, Camille; Galano, Jean-Marie; Durand, Thierry; Muñoz-Durango, Katalina

2018-05-01

Oxidized low-density lipoprotein (oxLDL) is a well-recognized proatherogenic particle that functions in atherosclerosis. In this study, we established conditions to generate human oxLDL, characterized according to the grade of lipid and protein oxidation, particle size and oxylipin content. The induction effect of the cellular proatherogenic response was assessed in foam cells by using an oxLDL-macrophage interaction model. Uptake of oxLDL, reactive oxygen species production and expression of oxLDL receptors (CD36, SR-A and LOX-1) were significantly increased in THP-1 macrophages. Analyses of 35 oxylipins revealed that isoprostanes (IsoP) and prostaglandins (PGs) derived from the oxidation of arachidonic, dihomo gamma-linolenic and eicosapentaenoic acids were strongly and significantly induced in macrophages stimulated with oxLDL. Importantly, the main metabolites responsible for the THP1-macrophage response to oxLDL exposure were the oxidative stress markers 5-epi-5-F 2t -IsoP, 15-E 1t -IsoP, 8-F 3t -IsoP and 15-keto-15-F 2t -IsoP as well as inflammatory markers PGDM, 17-trans-PGF 3α , and 11β-PGF 2α , all of which are reported here, for the first time, to function in the interaction of oxLDL with THP-1 macrophages. By contrast, a salvage pathway mediated by anti-inflammatory PGs (PGE 1 and 17-trans-PGF 3α ) was also identified, suggesting a response to oxLDL-induced injury. In conclusion, when THP-1 macrophages were treated with oxLDL, a specific induction of biomarkers related to oxidative stress and inflammation was triggered. This work contributes to our understanding of initial atherogenic events mediated by oxLDL-macrophage interactions and helps to generate new approaches for their modulation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Conception rates to fixed-time artificial insemination of two oestrus synchronisation programmes in dairy heifers.

PubMed

Sahu, S K; Parkinson, T J; Laven, R A

2015-05-01

To evaluate the conception rate to fixed-time artificial insemination (FTAI) of two oestrus synchronisation programmes in dairy heifers on eight farms over 2 years. The study was conducted in 2008 and 2010 on eight farms near Palmerston North, New Zealand. Nulliparous Friesian and Friesian×Jersey heifers (13-15 months of age) were randomly allocated to one of two oestrus synchronisation programmes. Group 1 (GPG+P4; n=330), received gonadotrophin-releasing hormone (GnRH) I/M on Day 0, a progesterone (P4)-releasing intravaginal device from Days 0-7, prostaglandin F2α (PGF) I/M on Day 7 and a second dose of GnRH at the time of FTAI on Day 9. The second group (P4+PGF; n=343) received a P4-releasing intravaginal device from Days 0-7, PGF on Day 6 and FTAI on Day 9. Pregnancy was diagnosed from Days 42-52 by transrectal ultrasonography. The overall conception rate was 52.4% and 54.8% for the GPG+P4 and P4+PGF groups, respectively. The odds of conception for the two treatments were not different (OR=0.90; 95% CI=0.67-1.23), nor was there any difference between groups in different years (p=0.58). Farm affected conception rate (p=0.002), but there was no interaction with treatment (p=0.92) . This study has shown that an alternative synchronisation programme can produce similar results in terms of conception rate to the GPG+P4 treatment, currently commonly used in heifers. More research is required to establish whether other modifications to the GPG+P4 programme can produce similar results at lower costs, and to identify and quantify farm factors which affect the economic benefit of heifer synchronisation. This study indicated that synchronising heifers with P4 and PGF resulted in conception rates equivalent to those resulting from a GPG+P4 treatment, but with reduced drug costs. However, because heifers in the GPG+P4 group received the second GnRH injection at the time of AI, they needed only three yardings as opposed to the four required for the heifers treated with P4 and PGF. Thus, the choice of programme for an individual farm will depend on that farm's circumstances, in particular the cost of yarding the heifers.

Effects of breed, age, season, and multiple ovulations on cyclic, PGF2α-induced, and postpartum estrus characteristics in Spanish jennies.

PubMed

Perez-Marin, C C; Galisteo, I; Perez-Rico, A; Galisteo, J

2016-04-01

This retrospective, population-based, cross-sectional study analyzed data for a total of 104 jennies reared in southern Spain over the period 1995 to 2014. Intervals to ovulation and incidence of multiple ovulation and pregnancy were charted for spontaneous, PGF2α-induced, and postpartum estrous cycles. In spontaneous estrous cycles, the interovulatory interval varied as a function of breed (P < 0.03) and month of ovulation (P < 0.01), and duration of estrus signs was longer in older jennies (0.04). Spontaneous cycles were also associated with higher ovulation rates from September to January (P < 0.006). When PGF2α was used to induce the estrus, not only did estrus signs last longer in old (P < 0.004) and in polyovular (0.02) jennies but old jennies also displayed significantly higher ovulation rates (P < 0.03). In postpartum jennies, no variations were observed as a function of any of the independent variables analyzed. Comparison of ovulation rates between different types of cycle revealed that postpartum jennies exhibited significantly lower ovulation rates (1.32 ± 0.07) and a lower incidence of multiple ovulation (30.4%) than spontaneous (1.62 ± 0.04, 55.0%) and PGF2α-induced (1.74 ± 0.08, 65.5%) groups. No differences were observed in the incidence of ovulation or pregnancy depending on the location of ovulation in polyovular cycles, and ovulation occurred at similar rates in the right and left ovaries. These findings shed further light on reproductive physiology in jennies and may be of value in improving animal management. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence for CB2 receptor involvement in LPS-induced reduction of cAMP intracellular levels in uterine explants from pregnant mice: pathophysiological implications.

PubMed

Salazar, Ana Inés; Carozzo, Alejandro; Correa, Fernando; Davio, Carlos; Franchi, Ana María

2017-07-01

What is the role of the endocannabinoid system (eCS) on the lipopolysaccharide (LPS) effects on uterine explants from 7-day pregnant mice in a murine model of endotoxin-induced miscarriage? We found evidence for cannabinoid receptor type2 (CB2) involvement in LPS-induced increased prostaglandin-F2α (PGF2α) synthesis and diminished cyclic adenosine monophosphate (cAMP) intracellular content in uterine explants from early pregnant mice. Genital tract infections by Gram-negative bacteria are a common complication of human pregnancy that results in an increased risk of pregnancy loss. LPS, the main component of the Gram-negative bacterial wall, elicits a strong maternal inflammatory response that results in embryotoxicity and embryo resorption in a murine model endotoxin-induced early pregnancy loss. We have previously shown that the eCS mediates the embryotoxic effects of LPS, mainly via CB1 receptor activation. An in vitro study of mice uterine explants was performed to investigate the eCS in mediating the effects of LPS on PGF2α production and cAMP intracellular content. Eight to 12-week-old virgin female BALB/c or CD1 (wild-type [WT] or CB1-knockout [CB1-KO]) mice were paired with 8- to 12-week-old BALB/c or CD1 (WT or CB1-KO) males, respectively. On day 7 of pregnancy, BALB/c, CD1 WT or CD1 CB1-KO mice were euthanized, the uteri were excised, implantation sites were removed and the uterine tissues were separated from decidual and embryo tissues. Uterine explants were cultured and exposed for an appropriate amount of time to different pharmacological treatments. The tissues were then collected for cAMP assay and PGF2α content determination by radioimmunoassay. In vitro treatment of uteri explants from 7-day pregnant BALB/c or CD1 (WT or CB1-KO) mice with LPS induced an increased production of PGF2α (P < 0.05) and a reduction of the tissue content of cAMP (P < 0.05). These effects were mediated by CB2 receptors since exposure to AM630 (a specific CB2 receptor antagonist) prevented these LPS-induced effects (P < 0.05). Collectively, our results suggest a role for the eCS mediating LPS-induced deleterious effects on reproductive tissues. Since our experimental design involves in vitro experiments of uterine explants, the extrapolation of the results presented here to humans is limited. Our findings provide evidence for the role of CB2 receptors in reproductive events as well as their participation as a mediator of LPS deleterious effects on reproductive tissues. None. Dr Ana María Franchi was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2010/0813 and PICT 2013/0097) and by Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Carlos Davio was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013/2050). The authors have no competing interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Oestradiol and prostaglandin F2α regulate sexual displays in females of a sex-role reversed fish

PubMed Central

Gonçalves, David; Costa, Silvia Santos; Teles, Magda C.; Silva, Helena; Inglês, Mafalda; Oliveira, Rui F.

2014-01-01

The mechanisms regulating sexual behaviours in female vertebrates are still poorly understood, mainly because in most species sexual displays in females are more subtle and less frequent than displays in males. In a sex-role reversed population of a teleost fish, the peacock blenny Salaria pavo, an external fertilizer, females are the courting sex and their sexual displays are conspicuous and unambiguous. We took advantage of this to investigate the role of ovarian-synthesized hormones in the induction of sexual displays in females. In particular, the effects of the sex steroids oestradiol (E2) and testosterone (T) and of the prostaglandin F2α (PGF2α) were tested. Females were ovariectomized and their sexual behaviour tested 7 days (sex steroids and PGF2α) and 14 days (sex steroids) after ovariectomy by presenting females to an established nesting male. Ovariectomy reduced the expression of sexual behaviours, although a significant proportion of females still courted the male 14 days after the ovary removal. Administration of PGF2α to ovariectomized females recovered the frequency of approaches to the male's nest and of courtship displays towards the nesting male. However, E2 also had a positive effect on sexual behaviour, particularly on the frequency of approaches to the male's nest. T administration failed to recover sexual behaviours in ovariectomized females. These results suggest that the increase in E2 levels postulated to occur during the breeding season facilitates female mate-searching and assessment behaviours, whereas PGF2α acts as a short-latency endogenous signal informing the brain that oocytes are mature and ready to be spawned. In the light of these results, the classical view for female fishes, that sex steroids maintain sexual behaviour in internal fertilizers and that prostaglandins activate spawning behaviours in external fertilizers, needs to be reviewed. PMID:24452030

Loss of luteotropic prostaglandin E plays an important role in the regulation of luteolysis in women.

PubMed

Nio-Kobayashi, Junko; Kudo, Masataka; Sakuragi, Noriaki; Iwanaga, Toshihiko; Duncan, W Colin

2017-05-01

Do intraluteal prostaglandins (PG) contribute to luteal regulation in women? Prostaglandin E (PGE), which is produced in human granulosa-lutein cells stimulated with luteotropic hCG, exerts similar luteotropic effects to hCG, and the expression of PG synthetic and metabolic enzymes in the human CL is driven toward less PGE but more prostaglandin F (PGF) during luteolysis. Uterine PGF is a major luteolysin in many non-primate species but not in women. Increases in the PGF synthase, aldo-ketoreductase family one member C3 (AKR1C3), have been observed in the CL of marmoset monkeys during luteolysis. PGE prevents spontaneous or induced luteolysis in domestic animals. Human CL tissues staged as the early-luteal (n = 6), mid-luteal (n = 6), late-luteal (n = 5) and menstrual (n = 3) phases were obtained at the time of hysterectomy for benign gynecological conditions. Luteinized granulosa cells (LGCs) were purified from follicular fluids obtained from patients undergoing assisted conception. Upon collection, one half of the CL was snap-frozen and the other was fixed with formalin and processed for immunohistochemical analysis of a PGE synthase (PTGES). Quantitative RT-PCR was employed to examine changes in the mRNA abundance of PG synthetic and metabolic enzymes, steroidogenic enzymes, and luteolytic molecules in the staged human CL and in human LGCs in vitro treated with hCG, PGE and PGF. A PGE withdrawal experiment was also conducted in order to reveal the effects of the loss of PGE in LGCs. Progesterone concentrations in the culture medium were measured. The key enzyme for PGE synthesis, PTGES mRNA was abundant in the functional CL during the mid-luteal phase (P < 0.01), while mRNA abundance for genes involved in PGF synthesis (AKR1B1 and AKR1C1-3) increased in the CL during the late-luteal phase and menstruation (P < 0.05-0.001). PTGES mRNA expression positively correlated with that of 3β-hydroxysteroid dehydrogenase (HSD3B1; r = 0.7836, P < 0.001), while AKR1C3 expression inversely correlated with that of HSD3B1 (r = -0.7514, P = 0.0012) and PTGES (r = -0.6923, P = 0.0042). PGE exerted similar effects to hCG-promoting genes, such as steroidogenic acute regulatory protein (STAR) and HSD3B1, to produce progesterone and luteotropic PGE, suppress PGF synthetic enzymes and down-regulate luteolytic molecules such as βA- and βB-inhibin subunits (INHBA and INHBB) and bone morphogenetic proteins (BMP2, BMP4 and BMP6). PGE withdrawal resulted in reductions in the enzymes that produce progesterone (STAR; P < 0.001) and PGE (PTGES; P < 0.001), and the capacity to produce PGE decreased, while the capacity to produce PGF increased during the culture. The addition of PGF did not recapitulate the luteolytic effects of PGE withdrawal. None. Changes in mRNA expression of PG synthetic and metabolic enzymes may not represent actual increases in PGF during luteolysis in the CL. The effects of PGF on luteal cells currently remain unclear and the mechanisms responsible for decreases in the synthesis of PGE in vitro and at luteolysis have not been elucidated in detail. The results obtained strongly support a luteotropic function of PGE in regulation of the human CL. They suggest that the main PG produced in human luteal tissue changes from PGE to PGF during the maturation and regression of the CL, and the loss of PGE is more important than the effects of PGF during luteolysis in women. This may be accompanied by reduced effects of LH/hCG in luteal cells, particularly decreased activation of cAMP/protein kinase A; however, the underlying mechanisms remain unknown. This study was supported by the Cunningham Trust to WCD, a Postdoctoral Fellowship for Research Abroad from the Japan Society for the Promotion of Science and the Suntory Foundation for Life Sciences to J.N.-K.; W.C.D. is supported by an MRC Centre Grant G1002033 and a Scottish Senior Clinical Fellowship. The authors have nothing to disclose. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Cord blood biomarkers of vascular endothelial growth (VEGF and sFlt-1) and postnatal growth: a preterm birth cohort study

PubMed Central

Voller, Stephannie Baehl; Chock, Susanne; Ernst, Linda M.; Su, Emily; Liu, Xin; Farrow, Kathryn N.; Mestan, Karen K.

2014-01-01

Background Preterm infants are at risk for postnatal growth failure (PGF). Identification of biomarkers that are associated with neonatal growth may help reduce PGF and associated long-term morbidity. Objective To investigate the associations between cord blood vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1) with birth weight (BW) and postnatal growth in premature infants. Study Design and Methods From an ongoing birth cohort, 123 premature infants from 23 to 36 weeks gestational age (GA) were studied. Cord blood plasma VEGF and sFlt-1 were measured via enzyme-linked immunoassay. Growth parameters and nutritional information were evaluated. Multivariate logistic regression models were constructed to evaluate the associations of VEGF and sFlt-1 on PGF, defined as weight < 10th percentile at 36 weeks corrected age or discharge. Results VEGF was positively correlated, and sFlt-1 was negatively correlated with BW and BW-for-GA percentiles. Higher cord blood VEGF levels were associated with reduced risk of PGF (OR=0.7; 95% CI=0.5–0.9), while higher sFlt-1 levels appeared to increase the risk of PGF (OR=1.6; 95% CI=1.1–2.4). The above biomarker associations were attenuated after adjustment for maternal preeclampsia, fetal growth restriction and related neonatal characteristics, and when taking into account placental vascular pathologies. Longitudinal growth patterns by mean weight and length percentiles were consistently lower among infants with low VEGF/sFlt-1 ratios. Conclusions Our data support that intrauterine regulation of angiogenesis is an important mechanism of fetal and postnatal growth. Cord blood VEGF and sFlt-1 are useful in elucidating how intrauterine processes may have long-standing effects on developing premature infants. PMID:24480606

Oxidative stress in drug-naïve first episode patients with schizophrenia and major depression: effects of disease acuity and potential confounders.

PubMed

Jordan, Wolfgang; Dobrowolny, Henrik; Bahn, Sabine; Bernstein, Hans-Gert; Brigadski, Tanja; Frodl, Thomas; Isermann, Berend; Lessmann, Volkmar; Pilz, Jürgen; Rodenbeck, Andrea; Schiltz, Kolja; Schwedhelm, Edzard; Tumani, Hayrettin; Wiltfang, Jens; Guest, Paul C; Steiner, Johann

2018-03-01

Oxidative stress and immune dysregulation have been linked to schizophrenia and depression. However, it is unknown whether these factors are related to the pathophysiology or whether they are an epiphenomenon. Inconsistent oxidative stress-related findings in previous studies may have resulted from the use of different biomarkers which show disparate aspects of oxidative stress. Additionally, disease severity, medication, smoking, endocrine stress axis activation and obesity are potential confounders. In order to address some of these shortcomings, we have analyzed a broader set of oxidative stress biomarkers in our exploratory study, including urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), 8-OH-2-deoyxguanosine (8-OH-2-dG), and blood levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione S-transferase (GST) in acutely ill drug-naïve first episode patients with schizophrenia (n = 22), major depression (n = 18), and controls (n = 43). Possible confounding factors were considered, and patients were followed-up after 6 weeks of treatment. No differences were observed regarding 8-OH-2-dG, MDA and GST. At baseline, 8-iso-PGF2α levels were higher in patients with schizophrenia (p = 0.004) and major depression (p = 0.037), with a trend toward higher SOD concentrations in schizophrenia (p = 0.053). After treatment, schizophrenia patients showed a further increase in 8-iso-PGF2α (p = 0.016). These results were not related to age, sex, disease severity, medication or adipose tissue mass. However, 8-iso-PGF2α was associated with smoking, endocrine stress axis activation, C-reactive protein levels and low plasma concentrations of brain-derived neurotrophic factor. This study suggests a role of lipid peroxidation particularly in drug-naïve acutely ill schizophrenia patients and highlights the importance of taking into account other confounding factors in biomarker studies.

Generation of reactive oxygen species in the reaction catalyzed by alpha-ketoglutarate dehydrogenase.

PubMed

Tretter, Laszlo; Adam-Vizi, Vera

2004-09-08

Alpha-ketoglutarate dehydrogenase (alpha-KGDH), a key enzyme in the Krebs' cycle, is a crucial early target of oxidative stress (Tretter and Adam-Vizi, 2000). The present study demonstrates that alpha-KGDH is able to generate H(2)O(2) and, thus, could also be a source of reactive oxygen species (ROS) in mitochondria. Isolated alpha-KGDH with coenzyme A (HS-CoA) and thiamine pyrophosphate started to produce H(2)O(2) after addition of alpha-ketoglutarate in the absence of nicotinamide adenine dinucleotide-oxidized (NAD(+)). NAD(+), which proved to be a powerful inhibitor of alpha-KGDH-mediated H(2)O(2) formation, switched the H(2)O(2) forming mode of the enzyme to the catalytic [nicotinamide adenine dinucleotide-reduced (NADH) forming] mode. In contrast, NADH stimulated H(2)O(2) formation by alpha-KGDH, and for this, neither alpha-ketoglutarate nor HS-CoA were required. When all of the substrates and cofactors of the enzyme were present, the NADH/NAD(+) ratio determined the rate of H(2)O(2) production. The higher the NADH/NAD(+) ratio the higher the rate of H(2)O(2) production. H(2)O(2) production as well as the catalytic function of the enzyme was activated by Ca(2+). In synaptosomes, using alpha-ketoglutarate as respiratory substrate, the rate of H(2)O(2) production increased by 2.5-fold, and aconitase activity decreased, indicating that alpha-KGDH can generate H(2)O(2) in in situ mitochondria. Given the NADH/NAD(+) ratio as a key regulator of H(2)O(2) production by alpha-KGDH, it is suggested that production of ROS could be significant not only in the respiratory chain but also in the Krebs' cycle when oxidation of NADH is impaired. Thus alpha-KGDH is not only a target of ROS but could significantly contribute to generation of oxidative stress in the mitochondria.

N-acetylcysteine reduces oxidative stress, nuclear factor-κB activity and cardiomyocyte apoptosis in heart failure

PubMed Central

WU, XIAO-YAN; LUO, AN-YU; ZHOU, YI-RONG; REN, JIANG-HUA

2014-01-01

The roles of oxidative stress on nuclear factor (NF)-κB activity and cardiomyocyte apoptosis during heart failure were examined using the antioxidant N-acetylcysteine (NAC). Heart failure was established in Japanese white rabbits with intravenous injections of doxorubicin, with ten rabbits serving as a control group. Of the rabbits with heart failure, 12 were not treated (HF group) and 13 received NAC (NAC group). Cardiac function was assessed using echocardiography and hemodynamic analysis. Myocardial cell apoptosis, apoptosis-related protein expression, NF-κBp65 expression and activity, total anti-oxidative capacity (tAOC), 8-iso-prostaglandin F2α (8-iso-PGF2α) expression and glutathione (GSH) expression levels were determined. In the HF group, reduced tAOC, GSH levels and Bcl-2/Bax ratios as well as increased 8-iso-PGF2α levels and apoptosis were observed (all P<0.05), which were effects that were attenuated by the treatment with NAC. NF-κBp65 and iNOS levels were significantly higher and the P-IκB-α levels were significantly lower in the HF group; expression of all three proteins returned to pre-HF levels following treatment with NAC. Myocardial cell apoptosis was positively correlated with left ventricular end-diastolic pressure (LVEDP), NF-κBp65 expression and 8-iso-PGF2α levels, but negatively correlated with the maximal and minimal rates of increase in left ventricular pressure (+dp/dtmax and −dp/dtmin, respectively) and the Bcl-2/Bax ratio (all P<0.001). The 8-iso-PGF2α levels were positively correlated with LVEDP and negatively correlated with +dp/dtmax and −dp/dtmin (all P<0.001). The present study demonstrated that NAC increased the antioxidant capacity, decreased the NF-κB activation and reduced myocardial cell apoptosis in an in vivo heart failure model. PMID:24889421

Gastric cancer in Zambian adults: a prospective case-control study that assessed dietary intake and antioxidant status by using urinary isoprostane excretion.

PubMed

Asombang, Akwi W; Kayamba, Violet; Mwanza-Lisulo, Mpala; Colditz, Graham; Mudenda, Victor; Yarasheski, Kevin; Chott, Robert; Rubin, Deborah C; Gyawali, C Prakash; Sinkala, Edford; Mwanamakondo, Stayner; Anderson-Spearie, Catherine; Kelly, Paul

2013-05-01

Gastric cancer is increasingly recognized in Zambia. Although nutritional factors contribute to gastric cancer risk, their effect in Zambia is unknown. The objective was to investigate the association between intake of dietary antioxidants, urinary 8-iso prostaglandin F2α (8-iso PGF2α) as a marker of oxidative stress, and gastric cancer. This was a case-control study at the University Teaching Hospital in Zambia. Gastric cancer cases were compared with age- and sex-matched controls. Urine 8-iso PGF2α was measured primarily by ELISA, and by gas chromatography-mass spectrometry in a subset, expressed as a ratio to creatinine. Blood was collected for Helicobacter pylori, HIV serology, gastrin-17, and pepsinogen 1 and 2 concentrations. Clinical and dietary data were collected by using questionnaires. Food items were broadly classified into 7 major categories (fruit, vegetables, fish, meat, insects, cereals, and starches). Fifty cases with gastric cancer (mean age: 61 y; n = 31 males) and 90 controls (mean age: 54 y; n = 41 males) were enrolled. Median urinary 8-iso PGF2α excretion was higher in cases (0.014; IQR: 0.008-0.021) than in controls (0.011; IQR: 0.006-0.018; P = 0.039). On univariate analysis, habitual fruit intake was lower in cases than in controls during the dry season (P = 0.02). On multivariate analysis, smoking (OR: 7.22; IQR: 1.38-37.9) and gastric atrophy (OR: 2.43; IQR: 1.12-5.13) were independently associated with cancer, and higher fruit intake was protective (OR: 0.44; IQR: 0.20-0.95). Isoprostane excretion was inversely correlated with total fruit intake (ρ = -0.23; n = 140; P = 0.006). Urinary 8-iso PGF2α excretion was associated with the risk of gastric cancer, as were smoking and gastric atrophy, but increased fruit intake conferred protection. This trial was registered at www.pactr.org as ISRCTN52971746.

Effects of chronic nitric oxide synthase inhibition on V'O2max and exercise capacity in mice.

PubMed

Wojewoda, M; Przyborowski, K; Sitek, B; Zakrzewska, A; Mateuszuk, L; Zoladz, J A; Chlopicki, S

2017-03-01

Acute inhibition of NOS by L-NAME (N ω -nitro-L-arginine methyl ester) is known to decrease maximal oxygen consumption (V'O 2max ) and impair maximal exercise capacity, whereas the effects of chronic L-NAME treatment on V'O 2max and exercise performance have not been studied so far. In this study, we analysed the effect of L-NAME treatment, (LN2 and LN12, respectively) on V'O 2max and exercise capacity (in maximal incremental running and prolonged sub-maximal incremental running tests), systemic NO bioavailability (plasma nitrite (NO 2 - ) and nitrate (NO 3 - )) and prostacyclin (PGI 2 ) production in C57BL6/J mice. Mice treated with L-NAME for 2 weeks (LN2) displayed higher V'O 2max and better running capacity than age-matched control mice. In LN2 mice, NO bioavailability was preserved, as evidenced by maintained NO 2 - plasma concentration. PGI 2 production was activated (increased 6-keto-PGF 1α plasma concentration) and the number of circulating erythrocytes (RBC) and haemoglobin concentration were increased. In mice treated with L-NAME for 12 weeks (LN12), NO bioavailability was decreased (lower NO 2 - plasma concentration), and 6-keto-PGF 1α plasma concentration and RBC number were not elevated compared to age-matched control mice. However, LN12 mice still performed better during the maximal incremental running test despite having lower V'O 2max . Interestingly, the LN12 mice showed poorer running capacity during the prolonged sub-maximal incremental running test. To conclude, short-term (2 weeks) but not long-term (12 weeks) treatment with L-NAME activated robust compensatory mechanisms involving preservation of NO2- plasma concentration, overproduction of PGI 2 and increased number of RBCs, which might explain the fully preserved exercise capacity despite the inhibition of NOS.

Parturition failure in mice lacking Mamld1

PubMed Central

Miyado, Mami; Miyado, Kenji; Katsumi, Momori; Saito, Kazuki; Nakamura, Akihiro; Shihara, Daizou; Ogata, Tsutomu; Fukami, Maki

2015-01-01

In mice, the onset of parturition is triggered by a rapid decline in circulating progesterone. Progesterone withdrawal occurs as a result of functional luteolysis, which is characterized by an increase in the enzymatic activity of 20α-hydroxysteroid dehydrogenase (20α-HSD) in the corpus luteum and is mediated by the prostaglandin F2α (PGF2α) signaling. Here, we report that the genetic knockout (KO) of Mamld1, which encodes a putative non-DNA-binding regulator of testicular steroidogenesis, caused defective functional luteolysis and subsequent parturition failure and neonatal deaths. Progesterone receptor inhibition induced the onset of parturition in pregnant KO mice, and MAMLD1 regulated the expression of Akr1c18, the gene encoding 20α-HSD, in cultured cells. Ovaries of KO mice at late gestation were morphologically unremarkable; however, Akr1c18 expression was reduced and expression of its suppressor Stat5b was markedly increased. Several other genes including Prlr, Cyp19a1, Oxtr, and Lgals3 were also dysregulated in the KO ovaries, whereas PGF2α signaling genes remained unaffected. These results highlight the role of MAMLD1 in labour initiation. MAMLD1 likely participates in functional luteolysis by regulating Stat5b and other genes, independent of the PGF2α signaling pathway. PMID:26435405

Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis.

PubMed

Huang, Xiao X; McCaughan, Geoffrey W; Shackel, Nicholas A; Gorrell, Mark D

2007-09-01

Cirrhosis can lead to hepatocellular carcinoma (HCC). Non-diseased liver and hepatitis C virus (HCV)-associated cirrhosis with or without HCC were compared. Proliferation pathway genes, immune response genes and oncogenes were analysed by a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining. Real-time RT-PCR showed up-regulation of genes in HCV cirrhosis including the proliferation-associated genes bone morphogenetic protein 3 (BMP3), placental growth factor 3 (PGF3), vascular endothelial growth factor receptor 1 (VEGFR1) and soluble VEGFR1, the oncogene FYN, and the immune response-associated genes toll-like receptor 9 (TLR9) and natural killer cell transcript 4 (NK4). Expressions of TLR2 and the oncogenes B-cell CLL/lymphoma 9 (BCL9) and PIM2 were decreased in HCV cirrhosis. In addition, PIM2 and TLR2 were increased in HCV cirrhosis with HCC compared with HCV cirrhosis. The ligand/receptor pair PGF and VEGFR1 was intensely expressed by the portal tract vascular endothelium. VEGFR1 was expressed in reactive biliary epithelial structures in fibrotic septum and in some stellate cells and macrophages. PGF and VEGFR1 may have an important role in the pathogenesis of the neovascular response in cirrhosis.

Models for the action of barley alpha-amylase isozymes on linear substrates.

PubMed

MacGregor, E A; MacGregor, A W; Macri, L J; Morgan, J E

1994-05-05

The formation of maltodextrins, G1 to G12, during the hydrolysis of amylose by alpha-amylases 1 and 2 from barley malt was followed by HPLC. Similar, but not identical, distributions of products were obtained with the two alpha-amylase components. Maltose, G6, and G7 were major products, but G7 was degraded as hydrolysis proceeded. alpha-Amylase 1 produced more G1 and G3 than did alpha-amylase 2 at all stages of hydrolysis. Products formed during the hydrolysis of G9, G10, G11, and G12 by the two alpha-amylases were also determined. A different spectrum of products was observed with each substrate and small differences were observed in the action pattern of the two alpha-amylases, e.g., G3 and G7 were the major products formed during the hydrolysis of G10 by alpha-amylase 1, whereas G2 and G8 were the major products formed by alpha-amylase 2 on the same substrate. These results were used to develop a model of the active site of barley malt alpha-amylases. This site contains ten contiguous subsites with the catalytic site situated between subsites 7 and 8. The model can be used to predict hydrolysis patterns of amylose and maltodextrins by cereal alpha-amylases.

The effect of follicle age on pregnancy rate in beef cows.

PubMed

Abreu, F M; Geary, T W; Cruppe, L H; Madsen, C A; Jinks, E M; Pohler, K G; Vasconcelos, J L M; Day, M L

2014-03-01

The effect of the age of the ovulatory follicle on fertility in beef cows was investigated. Multiparous (n = 171) and primiparous (n = 129) postpartum beef cows in 2 groups (G1 and G2) received estradiol benzoate (EB; 1 mg/500 kg BW, intramuscular [i.m.]) 5.5 d (G1; n = 162) and 6.5 d (G2; n = 138) after the final GnRH of a synchronization program (5d CO-Synch + CIDR) to induce emergence of a new follicular wave (NFW), followed by prostaglandin F2α (PGF(2α); 25 mg, i.m.) administration either 5.5 d ("young" follicle, YF; n = 155) or 9.5 d ("mature" follicle, MF; n = 145) after EB. Estrous detection coupled with AI 12 h later (estrus-AI) was performed for 60 h (MF) and 84 h (YF) after PGF(2α); cows not detected in estrus within this period received timed AI (TAI) coupled with GnRH at 72 and 96 h, respectively. Within the first 72 h after PGF(2α), more (P < 0.01) cows in the MF (76.3%) than YF treatment (47.7%) exhibited estrus, but through 96 h, the proportion detected in estrus (P < 0.05) and interval from PGF(2α) to estrus (P < 0.01) were greater in the YF than MF treatment (88.6% vs. 76.3%, 78.9 ± 0.8 vs. 57.5 ± 1.6 h, respectively). Age of the ovulatory follicle at AI was greater (P < 0.01) in the MF (9.32 ± 0.04 d) than YF (6.26 ± 0.02 d) treatment, but follicle diameter at AI and pregnancy rates did not differ between MF (13.1 ± 0.2 mm; 72.0%) and YF (12.9 ± 0.1 mm; 67.1%) treatments. Regardless of treatment, the diameter of the ovulatory follicle at AI and pregnancy rate were greater (P < 0.01) with estrus-AI (13.1 ± 0.1 mm; 75.0%) than TAI (12.6 ± 0.2 mm; 55.4%). Cows in the MF treatment that initiated a second NFW after EB but before PGF(2α) (MF2; n = 47) were induced to ovulate with GnRH and TAI at 72h, when ovulatory follicles were 4 d old and 10.2 ± 0.2 mm in diameter. Pregnancy rate for TAI (51.1%) in MF2 did not differ from TAI pregnancy rate (55.4%) across the MF and YF treatments. In summary, the age of the ovulatory follicle affected interval to estrus and AI but did not influence pregnancy rate in suckled beef cows.

Positive Association between Urinary Concentration of Phthalate Metabolites and Oxidation of DNA and Lipid in Adolescents and Young Adults

NASA Astrophysics Data System (ADS)

Lin, Chien-Yu; Chen, Pau-Chung; Hsieh, Chia-Jung; Chen, Chao-Yu; Hu, Anren; Sung, Fung-Chang; Lee, Hui-Ling; Su, Ta-Chen

2017-03-01

Phthalate has been used worldwide in various products for years. Little is known about the association between phthalate exposure and biomarkers of oxidative stress in adolescents and young adults. Among 886 subjects recruited from a population-based cohort during 2006 to 2008, 751 subjects (12-30 years) with complete phthalate metabolites and oxidation stress measurement were enrolled in this study. Nine urine phthalate metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso prostaglandin F2α (8-isoPGF2α) were measured in urine to assess exposure and oxidative stress to DNA and lipid, respectively. Multiple linear regression analysis revealed that an ln-unit increase in mono-methyl phthalate (MMP) concentration in urine was positively associated with an increase in urine biomarkers of oxidative stress (in μg/g creatinine of 0.098 ± 0.028 in 8-OHdG; and 0.253 ± 0.051 in 8-isoPGF2α). There was no association between other eight phthalate metabolite concentrations and oxidative stress. In conclusion, a higher MMP concentration in urine was associated with an increase in markers of oxidative stress to DNA and lipid in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between exposure to phthalate and oxidative stress.

The effects of heavy metals and their interactions with polycyclic aromatic hydrocarbons on the oxidative stress among coke-oven workers.

PubMed

Wang, Tian; Feng, Wei; Kuang, Dan; Deng, Qifei; Zhang, Wangzhen; Wang, Suhan; He, Meian; Zhang, Xiaomin; Wu, Tangchun; Guo, Huan

2015-07-01

Heavy metals and polycyclic aromatic hydrocarbons (PAHs) are predominate toxic constituents of particulate air pollution that may be related to the increased risk of cardiopulmonary events. We aim to investigate the effects of the toxic heavy metals (arsenic, As; cadmium, Cd; chromium, Cr; nickel, Ni; and lead, Pb), and their interactions with PAHs on oxidative stress among coke-oven workers. A total of 1333 male workers were recruited in this study. We determined their urinary levels of As, Cd, Cr, Ni, Pb, twelve PAH metabolites, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso-prostaglandin-F2α (8-iso-PGF2α). Multivariate linear regression models were used to analyze the effects of these metals and their interactions with PAHs on 8-OHdG and 8-iso-PGF2α levels. It was found that only urinary As and Ni showed marginal or significant positive linear dose-dependent effects on 8-OHdG in this study population, especially among smokers (β=0.103, P=0.073 and β=0.110, P=0.002, respectively). After stratifying all participants by the quartiles of ΣOH-PAH, all five metals showed linear association with 8-OHdG in the highest quartile subgroup (Q4) of ΣOH-PAHs. However, these five urinary metals showed significantly consistent linear associations with 8-iso-PGF2α in all subjects and each stratum. Urinary ΣOH-PAHs can significant modify the effects of heavy metals on oxidative stress, while co-exposure to both high levels of ΣOH-PAHs and heavy metals render the workers with highest 8-OHdG and 8-iso-PGF2α (all P(interaction)≤0.005). This study showed evidence on the interaction effects of heavy metals and PAHs on increasing the oxidative stress, and these results warrant further investigation in more longitudinal studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Anti-ischemic activity and endothelium-dependent vasorelaxant effect of hydrolysable tannins from the leaves of Rhus coriaria (Sumac) in isolated rabbit heart and thoracic aorta.

PubMed

Beretta, Giangiacomo; Rossoni, Giuseppe; Santagati, Natale Alfredo; Facino, Roberto Maffei

2009-11-01

The aim of this work was to investigate the cardioprotective activity of hydrolysable gallotannins from Rhus coriaria L. leaves extract (RCLE) in isolated rabbit heart preparations, submitted to low-flow ischemia/reperfusion damage. RCLE induces a dose-dependent normalization of coronary perfusion pressure (CPP), reducing left ventricular contracture during ischemia, and improving left ventricular developed pressure and the maximum rate of rise and fall of left ventricular pressure at reperfusion. Creatinine kinase (CK) and lactate dehydrogenase (LDH) outflow were significantly reduced during reperfusion. In parallel there was a rise in the release of the cytoprotective 6-ketoprostaglandin F (1alpha) (6-keto-PGF (1alpha)) and a decrease of tumor necrosis factor-alpha (TNF-alpha), both significant only at the highest RCLE concentrations (150-500 microg/mL). The vasorelaxant activity of RCLE was studied in isolated rabbit aorta rings precontracted with norepinephrine (NE) with and without endothelium. The vasorelaxation induced by RCLE was predominantly endothelium-dependent as demonstrated by the loss of RCLE vasorelaxant ability in i) de-endothelized rings and ii) in intact aortic rings after pretreatment with NG-monomethyl- L-arginine (L-NMMA) and 1 H-[1.2.4]oxadiazolo[4.3- A]quinoxalin-1-one (ODQ). The inhibition of vasorelaxation in intact rings by indomethacin (INDO) demonstrates the ability of RCLE to modulate the coronary endothelium cyclooxygenase (COX) pathway. The K-ATP channel antagonist glibenclamide (GLIB) was ineffective. The antioxidant activity of RCLE, investigated in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) model and in living cell systems (rat erythrocytes), was stronger than that of gallic acid, ascorbic acid and trolox. The structure of its main bioactive constituents, profiled by HPLC-ESI-HR-S, comprised a mixture of polygalloylated D-glucopyranose with different degrees of galloylation and 3- O-methylgallic acid. The cardiovascular protective effect of RCLE seems to be due to an interplay of different factors: COX pathway activation, TNF-alpha inhibition, endothelial nitric oxide synthase (eNOS) activation, and free radical and ROS scavenging. Georg Thieme Verlag KG Stuttgart, New York.

Enhanced external counterpulsation (EECP) decreases advanced glycation end products and proinflammatory cytokines in patients with non-insulin-dependent type II diabetes mellitus for up to 6 months following treatment.

PubMed

Sardina, Paloma D; Martin, Jeffrey S; Dzieza, Wojciech K; Braith, Randy W

2016-10-01

Enhanced external counterpulsation (EECP) is a noninvasive, non-pharmacologic intervention proven to increase nitric oxide bioavailability in patients with coronary artery disease. The purpose of the present study was to evaluate the potential clinical benefits of EECP on advanced glycation end products (AGEs) and proinflammatory cytokine concentrations in patients with a clinical diagnosis of type II diabetes mellitus (T2DM). Thirty subjects (60.7 ± 1.9 years) with T2DM were randomly assigned (2:1 ratio) to receive either 35 1-h sessions of EECP (n = 20) or time-matched standard care (n = 10). AGEs, receptors for AGEs (RAGEs), soluble vascular cell adhesion molecules-1 (sVCAM-1), and 8-iso-prostaglandin 2α (8-iso-PGF2α) were evaluated before and at 48 h, 2 weeks, 3, and 6 months following EECP treatment or time-matched control. EECP significantly decreased AGEs and RAGEs at all follow-up measurement time points. AGEs and RAGEs were decreased at 48 h (-75 and -16 %), 2 weeks (-87 and -28 %), 3 months (-89 and -29 %), and 6 months (-92 and -20 %) following EECP treatment, respectively. sVCAM-1 and 8-iso-PGF2α were significantly decreased at 48 h (-30 and -49 %) and 2 weeks (-22 and -27 %) following EECP, respectively. sVCAM-1 (-27 %) remained significantly reduced at 3 months following EECP. Nitrite/nitrate (NOx) was significantly increased at 48 h (+48.4 %) and 2 weeks (+51.9 %) following EECP treatment. Our findings provide novel evidence that EECP decreases AGE/RAGE concentrations, inflammation, and oxidative stress in patients with T2DM that persist for up to 6 months following treatment.

[Effects of silkworm pupa oil on serum lipids level and platelet function in rats].

PubMed

Yang, Xuefeng; Huang, Lianzhen; Hu, Jianping; Li, Tao

2002-08-01

To observe the effects of silkworm pupa oil on serum lipids level and platelet function in rats, according to serum TG, TC level, 40 male Wistar rats are divided into four groups (normal control group, high fat control group, silkworm pupa oil group and silkworm pupa oil + VE group). The rats are fed different diets and six weeks later, serum lipids level and platelet function are measured. The results show that (1) Compared with high fat control group, serum TC, TG, LDL-C level, AI value, Platelet aggregability, plasma TXB2 level and T/P ratio decrease significantly while HDL-C level and 6-k-PGF1 level increase in silkworm pupa oil group; (2) Serum TC, LDL-C level, T/P ratio and platelet aggregability are significantly lower in silkworm pupa oil + VE group than in silkworm pupa oil group. It is suggested that silkworm pupa oil rich in alpha-linolenic acid can reduce serum lipids level and inhibit platelet aggregation, which is more effective with the supplementation with VE.

A comparison of the effects of progesterone sponges and ear implants, PGF2alpha, and their combination on efficacy of estrus synchronization and fertility of Mashona goat does.

PubMed

Kusina, N T; Tarwirei; Hamudikuwanda, H; Agumba, G; Mukwena, J

2000-05-01

Efficacy of estrus synchronization and fertility after synchronization of 60 multiparous Mashona goat does using intravaginal progesterone (P4) sponges (Group 1), norgestomet ear implants (Group 2), cloprostenol (Group 3), or a combination of P4 sponges and cloprostenol (Group 4) was compared with untreated does (Group 5). At the end of treatments, all does were mated to intact fertile bucks for 21 d. The number of does bred within 11 to 96 h was significantly higher (P < 0.05) in the treated groups than the untreated control, with rates of 80, 80, 64, 67 and 30% for Groups 1 to 5, respectively. There were no differences (P > 0.05) among treated does. Kidding rates ranged from 64 to 83% but were not different (P > 0.05) between groups. Prolificacy and overall fecundity were similar (P > 0.05) among the groups. The results indicate that all 4 treatment methods were effective in synchronizing estrus and that none of the methods affected overall fertility of the does.

Endocrine relationships during human spaceflight

NASA Technical Reports Server (NTRS)

Stein, T. P.; Schluter, M. D.; Moldawer, L. L.

1999-01-01

Human spaceflight is associated with a chronic loss of protein from muscle. The objective of this study was to determine whether changes in urinary hormone excretion could identify a hormonal role for this loss. Urine samples were collected from the crews of two Life Sciences Space Shuttle missions before and during spaceflight. Data are means +/- SE with the number of subjects in parentheses. The first value is the mean preflight measurement, and the second value is the mean inflight measurement. Adrenocorticotropic hormone (ACTH) [27.7 +/- 4.4 (9) vs. 25.1 +/- 3.4 (9) ng/day], growth hormone [724 +/- 251 (9) vs. 710 +/- 206 (9) ng/day], insulin-like growth factor I [6.81 +/- 0.62 vs. 6.04 +/- 0.51 (8) nM/day], and C-peptide [44.9 +/- 8.3 (9) vs. 50.7 +/- 10.3 (9) micrograms/day] were unchanged with spaceflight. In contrast, free 3,5,3'-triiodothyronine [791 +/- 159 (9) vs. 371 +/- 41 (9) pg/day, P < 0.05], prostaglandin E2 (PGE2) [1, 064 +/- 391 (8) vs. 465 +/- 146 (8) ng/day, P < 0.05], and its metabolite PGE-M [1,015 +/- 98 (9) vs. 678 +/- 105 (9) ng/day, P < 0. 05] were decreased inflight. The urinary excretion of most hormones returned to their preflight levels during the postflight period, with the exception of ACTH [47.5 +/- 10.3 (9) ng/day], PGE2 [1,433 +/- 327 (8) ng/day], PGF2alpha, [2,786 +/- 313 (8) ng/day], and its metabolite PGF-M [4,814 +/- 402 (9) ng/day], which were all increased compared with the preflight measurement (P < 0.05). There was a trend for urinary cortisol to be elevated inflight [55.3 +/- 5. 9 (9) vs. 72.5 +/- 11.1 micrograms/day, P = 0.27] and postflight [82.7 +/- 8.6 (8) micrograms/day, P = 0.13]. The inflight human data support ground-based in vitro work showing that prostaglandins have a major role in modulating the changes in muscle protein content in response to tension or the lack thereof.

Progesterone concentration and lambing rate of Karakul ewes treated with prostaglandin and GnRH combined with the ram effect during breeding and non-breeding seasons.

PubMed

Mirzaei, A; Mohebbi-Fani, M; Omidi, A; Boostani, A; Nazifi, S; Mahmoodian-Fard, H R; Chahardahcherik, M

2017-09-15

The combination of ram effect with two injections of PGF 2α 10-days apart and the same protocol plus an additional injection of GnRH prior to the first injection of PGF 2α were examined in Karakul ewes during breeding and non-breeding seasons, respectively. Plasma progesterone (P 4 ) concentrations (to detect the presence of active corpus luteum), twin lambing, litter size and synchronization of lambing were evaluated. In each study 70 ewes (2-4 years old) were divided to a treatment (n = 40) and a control (n = 30) group. During the breeding season, on days -10 and 0 before ram release, the treatment group was injected intramuscularly with PGF 2α (D-Cloprostenol; 0.15 mg). During the non-breeding season, on day -15 before ram release the treatment group was injected with GnRH (buserelin; 4.2 μg) intramuscularly followed by two injections of PGF 2α on days -10 and 0. In both studies, the rams were released into the ewe flock after the second prostaglandin injection (day 0). Blood samples of ewes were collected on days -10, 0, 20 and 70 of the study in breeding season and on days -15, -10, 0, 20 and 70 during non-breeding season. The treatment group had higher P 4 concentrations compared to the control ewes on day 0 in the breeding season (5.80 ± 0.61 vs. 5.0 ± 0.93 ng/mL) and day -10 in the non-breeding season (3.50 ± 0.33 vs. 2.70 ± 0.35 ng/mL) though the differences were not significant (P > 0.05). Based on plasma P 4 concentrations (>1 ng/mL) on day 70, in the breeding season all control ewes (100%) and 91.9% of the treatment ewes were detected to have active corpus luteum (P = 0.09). An almost inverse result (90% vs. 97.5%; P = 0.2) was detected in the non-breeding season. The lambing rate was higher (P = 0.03) in the treatment group compared to the control ewes during the non-breeding season (90% vs. 70%), but tended to be lower (P = 0.07) in the breeding season (73% vs. 90%). Twin lambing rate was higher in the treatment group compared to the control ewes in the breeding (40.7% vs. 0.0%; P < 0.05) and non-breeding (22.2% vs. 0.0%; P < 0.05) seasons. The litter size of the control and treated ewes were 1.0 ± 0.0 vs. 1.40 ± 0.10 in the breeding and 1.0 ± 0.0 vs. 1.22 ± 0.10 in the non-breeding season (P < 0.05). No effect was observed regard to synchronization of the treated ewes. In the breeding season two injections of PGF 2α ten days apart combined with ram effect, may lower the lambing rate, but may enhance twin pregnancies and litter size in Karakul ewes. In the non-breeding season, however, the GnRH-PGF 2α treatment plus ram effect may enhance the lambing rate, twin pregnancies and litter size. Copyright © 2017. Published by Elsevier Inc.

Bioreactor perfusion system for the long-term maintenance of tissue-engineered skeletal muscle organoids

NASA Technical Reports Server (NTRS)

Chromiak, J. A.; Shansky, J.; Perrone, C.; Vandenburgh, H. H.

1998-01-01

Three-dimensional skeletal muscle organ-like structures (organoids) formed in tissue culture by fusion of proliferating myoblasts into parallel networks of long, unbranched myofibers provide an in vivo-like model for examining the effects of growth factors, tension, and space flight on muscle cell growth and metabolism. To determine the feasibility of maintaining either avian or mammalian muscle organoids in a commercial perfusion bioreactor system, we measured metabolism, protein turnover. and autocrine/paracrine growth factor release rates. Medium glucose was metabolized at a constant rate in both low-serum- and serum-free media for up to 30 d. Total organoid noncollagenous protein and DNA content decreased approximately 22-28% (P < 0.05) over a 13-d period. Total protein synthesis rates could be determined accurately in the bioreactors for up to 30 h and total protein degradation rates could be measured for up to 3 wk. Special fixation and storage conditions necessary for space flight studies were validated as part of the studies. For example, the anabolic autocrine/paracrine skeletal muscle growth factors prostaglandin F2alpha (PGF2alpha) and insulin-like growth factor-1 (IGF-1) could be measured accurately in collected media fractions, even after storage at 37 degrees C for up to 10 d. In contrast, creatine kinase activity (a marker of cell damage) in collected media fractions was unreliable. These results provide initial benchmarks for long-term ex vivo studies of tissue-engineered skeletal muscle.

Relation between biomarkers in exhaled breath condensate and internal exposure to metals from gas metal arc welding.

PubMed

Hoffmeyer, Frank; Raulf-Heimsoth, Monika; Weiss, Tobias; Lehnert, Martin; Gawrych, Katarzyna; Kendzia, Benjamin; Harth, Volker; Henry, Jana; Pesch, Beate; Brüning, Thomas

2012-06-01

Concerning possible harmful components of welding fumes, besides gases and quantitative aspects of the respirable welding fumes, particle-inherent metal toxicity has to be considered.The objective of this study was to investigate the effect markers leukotriene B4 (LTB4),prostaglandin E2 (PGE2) and 8-isoprostane (8-Iso PGF2α) as well as the acid–base balance(pH) in exhaled breath condensate (EBC) of 43 full-time gas metal arc welders (20 smokers) in relation to welding fume exposure. We observed different patterns of iron, chromium and nickel in respirable welding fumes and EBC. Welders with undetectable chromium in EBC(group A, n = 24) presented high iron and nickel concentrations. In this group, higher 8-isoPGF2α and LTB4 concentrations could be revealed compared to welders with detectable chromium and low levels of both iron and nickel in EBC (group B): 8-iso PGF2α443.3 pg mL−1 versus 247.2 pg mL−1; p = 0.001 and LTB4 30.5 pg mL−1 versus 17.3 pgmL−1; p = 0.016. EBC-pH was more acid in samples of group B (6.52 versus 6.82; p = 0.011).Overall, effect markers in welders were associated with iron concentrations in EBC according to smoking habits--non-smokers/smokers: LTB4 (rs = 0.48; p = 0.02/rs = 0.21; p = 0.37),PGE2 (rs = 0.15; p = 0.59/rs = 0.47; p = 0.07), 8-iso PGF2α (rs = 0.18; p = 0.54/rs = 0.59;p = 0.06). Sampling of EBC in occupational research provides a matrix for the simultaneous monitoring of metal exposure and effects on target level. Our results suggest irritative effects in the airways of healthy welders. Further studies are necessary to assess whether these individual results might be used to identify welders at elevated risk for developing a respiratory disease.

Stimultion by angiotensin of prostacyclin biosynthesis in rats and dogs.

PubMed

Dusting, G J; Mullins, E M

1980-01-01

1. Stimulation of prostanoid release by angiotensins (AI and AII) in rat isolated mesenteric vasculature and in the circulation of anaesthetized dogs has been investigated by bioassay. 2. AI and AII released a PGI2-like substance into rat mesenteric effluent and arterial blood of dogs; PGE2, PGF2 alpha, or TXA2 were not detected. 3. AI stimulated PGI2 release in both systems largely as a result of its conversion to AII, since PGI2 release was much reduced after treatment with captorpril. 3. AI stimulated PGI2 release in both systems largely as a result of its conversion to AII, since PGI2 release was much reduced after treatment with captopril. 4. Intravenous AII (0.02-1.0 microgram kg-1min-1) in dogs released PGI2 mainly from the lungs since right atrial blood contained much less than arterial blood. 5. Indomethacin (1 microgram/ml) abolished AII-induced PGI2 release from the memestery preparation, but intravenous idomethacin (10 mg/kg), meclofenamate (2 mg/kg) or aspirin (100 mg/kg) did not eliminate the pulmonary source of PGI2 in dogs. These findings highlight the dangers of assuming in vivo treatment with cyclo-oxygenase inhibitors abolished biosynthesis of all prostanoids.

Expression of alpha-AR subtypes in T lymphocytes and role of the alpha-ARs in mediating modulation of T cell function.

PubMed

Bao, Jing-Yin; Huang, Yan; Wang, Feng; Peng, Yu-Ping; Qiu, Yi-Hua

2007-01-01

Previous work in our laboratory has shown that alpha-adrenoreceptors (alpha-ARs) and beta-ARs exist on lymphocytes from functional profile, and that the receptors mediate the regulation of lymphocyte function by catecholamines. In the present study, we directly examined the expression of alpha-AR subtypes, alpha(1)-AR and alpha(2)-AR mRNAs, in T lymphocytes and explored the roles of the alpha-AR subtypes and intracellular signal transduction mechanisms linked to the receptors in mediating the modulation of T lymphocyte function. T lymphocytes from mesenteric lymph nodes of rats were purified by using a nylon wool column. Reverse transcription polymerase chain reaction was used to detect the expression of alpha(1)-AR and alpha(2)-AR mRNAs in the freshly isolated T cells and the mitogen concanavalin A (Con A)-activated lymphocytes. Colorimetric methylthiazoletetrazolium assay was employed to measure lymphocyte proliferation induced by Con A. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels in the Con A-stimulated lymphocyte culture supernatants were examined by enzyme-linked immunosorbent assay. T cells expressed both alpha(1)-AR and alpha(2)-AR mRNAs. The expression of both alpha(1)-AR and alpha(2)-AR mRNAs was significantly higher in the Con A-activated lymphocytes than in the resting lymphocytes. Phenylephrine, a selective alpha(1)-AR agonist, had no evident effect on lymphocyte proliferation nor on IFN-gamma and IL-4 production induced by Con A. However, the selective alpha(2)-AR agonist clonidine attenuated Con A-induced lymphocyte proliferation as well as IFN-gamma and IL-4 production. The inhibited lymphocyte proliferation and IFN-gamma and IL-4 production by clonidine were blocked by yohimbine, an alpha(2)-AR antagonist. Either phospholipase C inhibitor U-73122 or protein kinase C inhibitor chelerythrine partially prevented the suppressive effect of clonidine on Con A-stimulated lymphocyte proliferation and IL-4 production. T lymphocytes express both alpha(1)-ARs and alpha(2)-ARs, but only the alpha(2)-ARs participate in the suppressive modulation of lymphocyte proliferation and cytokine production in vitro. The inhibitory effect of alpha(2)-AR stimulation on lymphocyte function is partially mediated via the phospholipase C-protein kinase C pathway. (c) 2008 S. Karger AG, Basel.

Effects of 1 or 2 treatments with prostaglandin F₂α on subclinical endometritis and fertility in lactating dairy cows inseminated by timed artificial insemination.

PubMed

Lima, F S; Bisinotto, R S; Ribeiro, E S; Greco, L F; Ayres, H; Favoreto, M G; Carvalho, M R; Galvão, K N; Santos, J E P

2013-10-01

The objectives of the current study were to investigate the efficacy of PGF₂α as a therapy to reduce the prevalence of subclinical endometritis and improve pregnancy per artificial insemination (P/AI) in cows subjected to a timed artificial insemination (AI) program. A total of 1,342 lactating Holstein dairy cows were allocated randomly at 25 ± 3 d in milk (DIM) to remain as untreated controls (control, n=454) or to receive a single PGF₂α treatment at 39 ± 3 DIM (1PGF, n=474) or 2 treatments with PGF(α at 25 ± 3 and 39 ± 3 DIM (2PGF, n=414). All cows were enrolled in the double Ovsynch program at 48 ± 3 DIM and were inseminated at 75 ± 3 DIM. A subset of 357 cows had uterine samples collected for cytological examination at 25 ± 3, 32 ± 3, and 46 ± 3 DIM to determine the percentage of polymorphonuclear leukocytes (PMNL). Subclinical endometritis was defined by the presence of ≥ 5% PMNL. Vaginal discharge score was evaluated at 25 ± 3 DIM and used to define the prevalence of purulent vaginal discharge. Body condition score was assessed at 25 ± 3 DIM. Pregnancy was diagnosed 32 d after AI and reconfirmed 28 d later. At 32 ± 3 DIM, the prevalence of subclinical endometritis was reduced by treatment with PGF₂α at 25 ± 3 DIM in 2PGF (control=23.5% vs. 1PGF=28.3% vs. 2PGF=16.7%); however, this benefit disappeared at 46 ± 3 DIM, and 14% of the cows remained with subclinical endometritis. One or 2 treatments with PGF₂α did not influence P/AI on d 32 or 60 after timed AI, which averaged 39.9 and 35.2%. Similarly, treatment with PGF₂α had no effect on pregnancy loss between 32 and 60 d of gestation (11.9%). Cows diagnosed with both purulent vaginal discharge and subclinical endometritis had the lowest P/AI and the highest pregnancy loss compared with those diagnosed with only 1 of the 2 diseases or compared with cows having no diagnosis of uterine diseases. Interestingly, subclinical endometritis depressed P/AI and increased pregnancy loss only when it persisted until 46 DIM. On d 32 after AI, cows not diagnosed with subclinical endometritis and those that resolved subclinical endometritis by 46 DIM had greater P/AI than those that remained with subclinical endometritis at 46 DIM (45.4 and 40.0 vs. 25.0%, respectively). Similar to P/AI, cows not diagnosed with subclinical endometritis and those that resolved subclinical endometritis by 46 DIM had less pregnancy loss than those with subclinical endometritis at 46 DIM (9.6 and 13.5 vs. 43.9%, respectively). One or 2 treatments with PGF₂α before initiation of the timed AI program were unable to improve uterine health, P/AI, and maintenance of pregnancy in lactating dairy cows. Cows diagnosed with both purulent vaginal discharge and subclinical endometritis had the greatest depressions in measures of fertility at first AI, particularly when subclinical endometritis persisted in the early postpartum period. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Physicochemistry and cardiovascular toxicity of metal fume PM2.5: a study of human coronary artery endothelial cells and welding workers

PubMed Central

Lai, Chane-Yu; Lai, Ching-Huang; Chuang, Hsiao-Chi; Pan, Chih-Hong; Yen, Cheng-Chieh; Lin, Wen-Yi; Chen, Jen-Kun; Lin, Lian-Yu; Chuang, Kai-Jen

2016-01-01

Occupational exposure to welding fumes causes a higher incidence of cardiovascular disease; however, the association remains unclear. To clarify the possible association, exposure assessment of metal fumes with an aerodynamic diameter of <2.5 μm (PM2.5) in welding and office areas was characterized in a shipyard in Taiwan. Cardiovascular toxicity caused by PM2.5 was determined in workers (in both the welding and office areas). Significant amounts of bimodal metal fume particles with count median diameters (CMDs) of 14.1~15.1 and 126.3~135.8 nm were produced in the shipyard. Metal fume PM2.5 resulted in decreased cell viability and increased levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), interleukin (IL)-6, and nitric oxide (NO) in human coronary artery epithelial cells (HCAECs). We recruited 118 welding workers and 45 office workers for a personal PM2.5 exposure assessment and determination of urinary levels of 8-OHdG, 8-iso-prostaglandin F2α (8-iso-PGF2α), and various metals. We observed that a 10-μg/m3 increase in the mean PM2.5 concentration was associated with a 2.15% increase in 8-OHdG and an 8.43% increase in 8-iso-PGF2α in welding workers. Both 8-OHdG and 8-iso-PGF2α were associated with Fe and Zn in the urine. In conclusion, metal fume PM2.5 could increase the risk of cardiovascular toxicity after inhalation. PMID:27641436

Physicochemistry and cardiovascular toxicity of metal fume PM2.5: a study of human coronary artery endothelial cells and welding workers.

PubMed

Lai, Chane-Yu; Lai, Ching-Huang; Chuang, Hsiao-Chi; Pan, Chih-Hong; Yen, Cheng-Chieh; Lin, Wen-Yi; Chen, Jen-Kun; Lin, Lian-Yu; Chuang, Kai-Jen

2016-09-19

Occupational exposure to welding fumes causes a higher incidence of cardiovascular disease; however, the association remains unclear. To clarify the possible association, exposure assessment of metal fumes with an aerodynamic diameter of <2.5 μm (PM2.5) in welding and office areas was characterized in a shipyard in Taiwan. Cardiovascular toxicity caused by PM2.5 was determined in workers (in both the welding and office areas). Significant amounts of bimodal metal fume particles with count median diameters (CMDs) of 14.1~15.1 and 126.3~135.8 nm were produced in the shipyard. Metal fume PM2.5 resulted in decreased cell viability and increased levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), interleukin (IL)-6, and nitric oxide (NO) in human coronary artery epithelial cells (HCAECs). We recruited 118 welding workers and 45 office workers for a personal PM2.5 exposure assessment and determination of urinary levels of 8-OHdG, 8-iso-prostaglandin F2α (8-iso-PGF2α), and various metals. We observed that a 10-μg/m(3) increase in the mean PM2.5 concentration was associated with a 2.15% increase in 8-OHdG and an 8.43% increase in 8-iso-PGF2α in welding workers. Both 8-OHdG and 8-iso-PGF2α were associated with Fe and Zn in the urine. In conclusion, metal fume PM2.5 could increase the risk of cardiovascular toxicity after inhalation.

Physicochemistry and cardiovascular toxicity of metal fume PM2.5: a study of human coronary artery endothelial cells and welding workers

NASA Astrophysics Data System (ADS)

Lai, Chane-Yu; Lai, Ching-Huang; Chuang, Hsiao-Chi; Pan, Chih-Hong; Yen, Cheng-Chieh; Lin, Wen-Yi; Chen, Jen-Kun; Lin, Lian-Yu; Chuang, Kai-Jen

2016-09-01

Occupational exposure to welding fumes causes a higher incidence of cardiovascular disease; however, the association remains unclear. To clarify the possible association, exposure assessment of metal fumes with an aerodynamic diameter of <2.5 μm (PM2.5) in welding and office areas was characterized in a shipyard in Taiwan. Cardiovascular toxicity caused by PM2.5 was determined in workers (in both the welding and office areas). Significant amounts of bimodal metal fume particles with count median diameters (CMDs) of 14.1~15.1 and 126.3~135.8 nm were produced in the shipyard. Metal fume PM2.5 resulted in decreased cell viability and increased levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), interleukin (IL)-6, and nitric oxide (NO) in human coronary artery epithelial cells (HCAECs). We recruited 118 welding workers and 45 office workers for a personal PM2.5 exposure assessment and determination of urinary levels of 8-OHdG, 8-iso-prostaglandin F2α (8-iso-PGF2α), and various metals. We observed that a 10-μg/m3 increase in the mean PM2.5 concentration was associated with a 2.15% increase in 8-OHdG and an 8.43% increase in 8-iso-PGF2α in welding workers. Both 8-OHdG and 8-iso-PGF2α were associated with Fe and Zn in the urine. In conclusion, metal fume PM2.5 could increase the risk of cardiovascular toxicity after inhalation.

Gastric cancer in Zambian adults: a prospective case-control study that assessed dietary intake and antioxidant status by using urinary isoprostane excretion123

PubMed Central

Asombang, Akwi W; Kayamba, Violet; Mwanza-Lisulo, Mpala; Colditz, Graham; Mudenda, Victor; Yarasheski, Kevin; Chott, Robert; Rubin, Deborah C; Gyawali, C Prakash; Sinkala, Edford; Mwanamakondo, Stayner; Anderson-Spearie, Catherine; Kelly, Paul

2013-01-01

Background: Gastric cancer is increasingly recognized in Zambia. Although nutritional factors contribute to gastric cancer risk, their effect in Zambia is unknown. Objective: The objective was to investigate the association between intake of dietary antioxidants, urinary 8-iso prostaglandin F2α (8-iso PGF2α) as a marker of oxidative stress, and gastric cancer. Design: This was a case-control study at the University Teaching Hospital in Zambia. Gastric cancer cases were compared with age- and sex-matched controls. Urine 8-iso PGF2α was measured primarily by ELISA, and by gas chromatography–mass spectrometry in a subset, expressed as a ratio to creatinine. Blood was collected for Helicobacter pylori, HIV serology, gastrin-17, and pepsinogen 1 and 2 concentrations. Clinical and dietary data were collected by using questionnaires. Food items were broadly classified into 7 major categories (fruit, vegetables, fish, meat, insects, cereals, and starches). Results: Fifty cases with gastric cancer (mean age: 61 y; n = 31 males) and 90 controls (mean age: 54 y; n = 41 males) were enrolled. Median urinary 8-iso PGF2α excretion was higher in cases (0.014; IQR: 0.008–0.021) than in controls (0.011; IQR: 0.006–0.018; P = 0.039). On univariate analysis, habitual fruit intake was lower in cases than in controls during the dry season (P = 0.02). On multivariate analysis, smoking (OR: 7.22; IQR: 1.38–37.9) and gastric atrophy (OR: 2.43; IQR: 1.12–5.13) were independently associated with cancer, and higher fruit intake was protective (OR: 0.44; IQR: 0.20–0.95). Isoprostane excretion was inversely correlated with total fruit intake (ρ = −0.23; n = 140; P = 0.006). Conclusion: Urinary 8-iso PGF2α excretion was associated with the risk of gastric cancer, as were smoking and gastric atrophy, but increased fruit intake conferred protection. This trial was registered at www.pactr.org as ISRCTN52971746. PMID:23535107

Exercise Training, NADPH Oxidase p22phox Gene Polymorphisms, and Hypertension

PubMed Central

FEAIRHELLER, DEBORAH L.; BROWN, MICHAEL D.; PARK, JOON-YOUNG; BRINKLEY, TINA E.; BASU, SAMAR; HAGBERG, JAMES M.; FERRELL, ROBERT E.; FENTY-STEWART, NICOLA M.

2010-01-01

Introduction Oxidative stress that is mediated through NADPH oxidase activity plays a role in the pathology of hypertension, and aerobic exercise training reduces NADPH oxidase activity. The involvement of genetic variation in the p22phox (CYBA) subunit genes in individual oxidative stress responses to aerobic exercise training has yet to be examined in Pre and Stage 1 hypertensives. Methods Ninety-four sedentary Pre and Stage 1 hypertensive adults underwent 6 months of aerobic exercise training at a level of 70% V̇O2max to determine whether the CYBA polymorphisms, C242T and A640G, were associated with changes in urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), urinary nitric oxide metabolites (NOx), and plasma total antioxidant capacity (TAC). Results Demographic and subject characteristics were similar among genotype groups for both polymorphisms. At baseline, a significant (P = 0.03) difference among the C2424T genotype groups in 8-iso-PGF2α levels was detected, with the TT homozygotes having the lowest levels and the CC homozygotes having the highest levels. However, no differences were found at baseline between the A640G genotype groups. After 6 months of aerobic exercise training, there was a significant increase in V̇O2max (P < 0.0001) in the entire study population. In addition, there were significant increases in both urinary 8-iso-PGF2α (P = 0.002) and plasma TAC (P = 0.03) levels and a significant decrease in endogenous urinary NOx (P < 0.0001). Overall, aerobic exercise training elicited no significant differences among genotype groups in either CYBA variant for any of the oxidative stress variables. Conclusions We found that compared with CYBA polymorphisms C242T and A640G, it was aerobic exercise training that had the greatest influence on the selected biomarkers; furthermore, our results suggest that the C242T CYBA variant influences baseline levels of urinary 8-iso-PGF2α but not the aerobic exercise-induced responses. PMID:19516159

Induction of successive follicular waves by gonadotropin-releasing hormone and prostaglandin F(2α) to improve fertility of high-producing cows during the summer and autumn.

PubMed

Friedman, E; Voet, H; Reznikov, D; Dagoni, I; Roth, Z

2011-05-01

Reduced conception rate during the hot summer and subsequent autumn is a well-documented phenomenon. Evaporative cooling systems greatly increase milk production but only slightly improve reproductive performance; hence, additional approaches to improving fertility during the hot season are required. The purpose of the present study was to examine whether the combination of an efficient cooling system and hormonal manipulation (GnRH+PGF(2α)) might improve fertility during the summer and autumn. The experiment was conducted from July to December in 2 commercial herds in Israel and included 382 healthy Holstein cows. Cows (50 to 60 d in milk) were hormonally treated to induce 3 consecutive 9-d follicular waves, with GnRH administration followed by PGF(2α) injection 7 d later. Both control (n=187) and treated (n=195) cows were inseminated following estrus, and pregnancy was determined by palpation 45 d post-insemination. Data revealed an interaction between treatment and primiparous cows, reflected by a 16% increase in conception rate [odds ratio (OR) 2.32, 95% confidence interval (CI): 0.96-5.61] and 14% increase in pregnancy rate at 120 d in milk (OR 3.16, 95% CI: 0.93-10.47). Interaction between treatment and high body condition score was reflected by a 14% increase in pregnancy rate at 90 d in milk (OR 3.02, 95% CI: 1.14-7.96). About 60% of the treated cows expressed estrus at the expected time (normal response within 5 d following the third PGF(2α) injection); the remaining 40% that manifested estrus later (late response) had higher milk yield and lower body condition score. Additional analyses indicated that treatment interacted with normal response to raise conception rates and pregnancy rates of primiparous cows and cows with high body condition score. On the other hand, treatment by late-response interaction lowered conception rate during the summer. Implementation of such hormonal treatment in combination with an efficient cooling system may improve reproductive performance of dairy cows during the summer and subsequent autumn. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Potential for control of detrusor smooth muscle spontaneous rhythmic contraction by cyclooxygenase products released by interstitial cells of Cajal

PubMed Central

Collins, Clinton; Klausner, Adam P; Herrick, Benjamin; Koo, Harry P; Miner, Amy S; Henderson, Scott C; Ratz, Paul H

2009-01-01

Interstitial cells of Cajal (ICCs) have been identified as pacemaker cells in the upper urinary tract and urethra, but the role of ICCs in the bladder remains to be determined. We tested the hypotheses that ICCs express cyclooxygenase (COX), and that COX products (prostaglandins), are the cause of spontaneous rhythmic contraction (SRC) of isolated strips of rabbit bladder free of urothelium. SRC was abolished by 10 μM indomethacin and ibuprofen (non-selective COX inhibitors). SRC was concentration-dependently inhibited by selective COX-1 (SC-560 and FR-122047) and COX-2 inhibitors (NS-398 and LM-1685), and by SC-51089, a selective antagonist for the PGE-2 receptor (EP) and ICI-192,605 and SQ-29,548, selective antagonists for thromboxane receptors (TP). The partial agonist/antagonist of the PGF-2α receptor (FP), AL-8810, inhibited SRC by ∼50%. Maximum inhibition was ∼90% by SC-51089, ∼80–85% by the COX inhibitors and ∼70% by TP receptor antagonists. In the presence of ibuprofen to abolish SRC, PGE-2, sulprostone, misoprostol, PGF-2α and U-46619 (thromboxane mimetic) caused rhythmic contractions that mimicked SRC. Fluorescence immunohistochemistry coupled with confocal laser scanning microscopy revealed that c-Kit and vimentin co-localized to interstitial cells surrounding detrusor smooth muscle bundles, indicating the presence of extensive ICCs in rabbit bladder. Co-localization of COX-1 and vimentin, and COX-2 and vimentin by ICCs supports the hypothesis that ICCs were the predominant cell type in rabbit bladder expressing both COX isoforms. These data together suggest that ICCs appear to be an important source of prostaglandins that likely play a role in regulation of SRC. Additional studies on prostaglandin-dependent SRC may generate opportunities for the application of novel treatments for disorders leading to overactive bladder. PMID:19243470

Factors for consideration in the interpretation of the adverse effects of elevated environmental temperatures on reproduction in the male rat

NASA Astrophysics Data System (ADS)

Bedrak, E.; Chap, Z.; Fried, K.

1980-06-01

Continuous exposure of male rats to an elevated environmental temperature (33 35° C) for 3 weeks led to heat-acclimatized (HA) rats whose serum testosterone concentratrion was significantly lower (P<0.01) than that of control (C) rats (20 22° C). The decrease in the androgen level was independent of major changes in serum FSH and LH concentrations, as well as hypothalamic content of thyrotropin-releasing hormone (THR), gonadotropin-releasing hormone (GnRH) and prostaglandin E2 (PGE2). However, the prostaglandin F2α(PGF2α) content of the hypothalamus of HA rats was significantly lower (P < 0.05) than that of C. The number of receptors for human chorionic gonadotropin (hCG) was significantly lower in testicular tissue of HA rats as compared to C males. Histological examination of the testis disclosed that exposure to heat adversely affected the sperm production and integrity of the Sertoli cells. Activity of enzymes associated with testosterone biosynthesis in testicular tissue of rats incubated at temperatures similar to those prevailing in the scrotum of HA rats resembled the activity of these enzymes observed in HA animals. Catabolism of testosterone was enhanced when kidney and liver of C rats were incubated at temperatures similar to the deep-body temperatures of HA rats, supporting the thesis that acclimatization to heat is coupled, inter alin, with increase androgen catabolism and excretion. It is suggested that the lower reproductive performance of HA rats is associated with several phenomena: a low number of receptors for hCG in the testes, decreased testoster one production rate by the Leydig cells, increased cata bolism and excretion of androgen, and partial atrophy of seminiferous tubules and Sertoli cells. These changes appear to be independent of either alteration in serum gonadotropin concentration or hypothalamic contents of TRH, GnR H and PGE2. The physiological significance in the response of PGF2α awaits further clarification.

Estradiol-17β, prostaglandin E2 (PGE2) and the prostaglandin E2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium

PubMed Central

Waclawik, Agnieszka; Jabbour, Henry N.; Blitek, Agnieszka; Ziecik, Adam J.

2009-01-01

Before implantation, the porcine endometrium and trophoblast synthesize elevated amounts of luteoprotective prostaglandin E2 (PGE2). We hypothesized that embryo signal, estradiol-17β (E2) and PGE2 modulate expression of key enzymes in PG synthesis: prostaglandin-endoperoxide synthase-2 (PTGS2), PGE synthase (mPGES-1), PGF synthase (PGFS), and prostaglandin 9-ketoreductase (CBR1); as well as PGE2 receptor (PTGER2 and 4) expression and signaling within the endometrium. We determinated the site of action of PGE2 in endometrium during the estrous cycle and pregnancy. Endometrial tissue explants obtained from gilts (n=6) on days 11-12 of the estrous cycle were treated with vehicle (control), PGE2 (100 nM), E2 (1-100 nM) or phorbol 12-myristate 13-acetate (100 nM, positive control). E2 increased PGE2 secretion through elevating expression of mPGES-1 mRNA and PTGS2 and mPGES-1 protein in endometrial explants. By contrast, E2 decreased PGFS and CBR1 protein expression. E2 also stimulated PTGER2 but not PTGER4 protein content. PGE2 enhanced mPGES-1 and PTGER2 mRNA as well as PTGS2, mPGES-1 and PTGER2 protein expression. PGE2 had no effect on PGFS, CBR1 and PTGER4 expression and PGF2α release. Treatment of endometrial tissue with PGE2 increased cAMP production. Co-treatment with PTGER2 antagonist (AH6809) but not PTGER4 antagonist (GW 627368X) inhibited significantly PGE2-mediated cAMP production. PTGER2 protein was localized in luminal and glandular epithelium and blood vessels of endometrium, and was significantly up-regulated on days 11-12 of pregnancy. Our results suggest that E2, prevents luteolysis through enzymatic modification of PG synthesis and that E2, PGE2 and endometrial PTGER2 are involved in PGE2 positive feedback loop in porcine endometrium. PMID:19359378

Prostaglandin F2α 7 d prior to initiation of the 7-d CO-synch + CIDR protocol failed to enhance estrus response and pregnancy rates in beef heifers.

PubMed

Oosthuizen, Nicola; Canal, Luara B; Fontes, Pedro L P; Sanford, Carla D; DiLorenzo, Nicolas; Dahlen, Carl R; Seidel, George E; Lamb, G Cliff

2018-04-14

To determine the effects of administration of 25 mg of PGF2α 7 d prior to the initiation of the 7-d CO-Synch + controlled internal drug release (CIDR) fixed-time AI (TAI) protocol, 985 Bos taurus beef heifers were enrolled in a completely randomized design at 9 locations from April to July of 2016. Within location, all heifers were randomly assigned to 1 of 2 treatments: 1) CONTROL (n = 496); 100 µg injection of GnRH and a CIDR insert for 7 d [day 7], administration of 25 mg of PGF2α at CIDR removal [day 0], followed by a second injection of GnRH and TAI 54 ± 2 h later; or 2) PRESYNCH (n = 489); same as CONTROL but heifers received an additional injection of 25 mg of PGF2α 7 d prior [day 14] to CIDR insertion. Estrous detection patches were applied to all heifers on day 14 and were evaluated for estrual activity on day 7. Similarly, estrus alert patches were placed on all heifers on day 0 and evaluated for estrual activity at the time of TAI. Pregnancy was diagnosed via transrectal ultrasonography between 35 and 55 d after TAI. The percentage of heifers exhibiting estrus between days 14 and 7 was greater (P < 0.001) for the PRESYNCH (70.1 ± 2.4%) than the CONTROL (41.1 ± 2.3%) treatment, whereas the percentage of heifers exhibiting estrus between day 0 and TAI was greater (P < 0.001) for the CONTROL (55.6 ± 2.4%) than the PRESYNCH (39.7 ± 2.5%) treatment. Estrus response rates differed (P < 0.001) among locations. Pregnancy rates to TAI differed (P = 0.023) among locations; however, they did not differ (P = 0.739) between CONTROL and PRESYNCH treatments (45.4 ± 2.5 vs. 43.2 ± 2.5%, respectively). Final breeding season pregnancy rates did not differ (P = 0.811) between treatments. Therefore, an injection of PGF2α 7 d prior to initiation of the 7-d CO-Synch + CIDR protocol failed to improve pregnancy rates to TAI in replacement beef heifers.

Follicular dynamics, interval to ovulation and fertility after AI in short-term progesterone and PGF2α oestrous synchronization protocol in sheep.

PubMed

Cox, J F; Allende, R; Lara, E; Leiva, A; Díaz, T; Dorado, J; Saravia, F

2012-12-01

The study was aimed to assess the influence that short-term progesterone treatments have on follicular dynamics, oestrus and ovulation in sheep. The treatment was tested thereafter in a field trial to assess its fertility after AI with fresh semen. In a first experiment, 12 ewes without CL were grouped to receive a new (n = 6) or used CIDR (n = 6) for 7 days and blood samples were obtained to follow plasma progesterone profiles. In a second experiment, 39 cycling ewes were synchronized by a 7-day P4+PGF2α protocol using a new (n = 20) or a 7-day used CIDR (n = 19). Half of both groups received 400 IU eCG and half remained untreated as controls. Ultrasound ovarian examination and oestrous detection were used to compare follicular dynamics, oestrus and ovulation in both groups. In a third experiment, 288 ewes in 3 farms were synchronized by the short-term P4+PGF2α+eCG protocol and ewes were AI with fresh semen 24 h after oestrous detection. Lambing performance was used to test the fertility of the treatment. In Experiment 1, ewes with new inserts presented higher P4 concentration than ewes with used inserts throughout the sampling period (p < 0.05) and exhibited a P4 peak at days 1-2 of the treatment that was not observed in ewes with used inserts. In Experiment 2, ewes treated with new and used inserts show similar ovarian and behavioral traits (p > 0.10). However, ewes treated with eCG show shorter interval to oestrus (p = 0.004) and tend to have larger mature CL (p = 0.06). In Experiment 3, oestrous presentation and lambing performance after AI with fresh semen was considered normal compared to published results. Results suggest that the oestrous synchronization protocol based on P4+PGF2α allows little control of follicular dynamics without compromising fertility after AI with fresh semen provided that eCG is added at the end of the treatment. © 2012 Blackwell Verlag GmbH.

Greater γ-tocopherol status during acute smoking abstinence with nicotine replacement therapy improved vascular endothelial function by decreasing 8-iso-15(S)-prostaglandin F2α

PubMed Central

Mah, Eunice; Pei, Ruisong; Guo, Yi; Masterjohn, Christopher; Ballard, Kevin D; Taylor, Beth A; Taylor, Alan W; Traber, Maret G; Volek, Jeff S

2015-01-01

Nicotine replacement therapy (NRT) improves the long-term success rate of smoking cessation, but induces oxidative stress and inflammatory responses that may delay the restoration of vascular endothelial function (VEF). No studies have examined co-therapy of NRT-assisted smoking abstinence with γ-tocopherol (γ-T), a vitamin E form with antioxidant and anti-inflammatory activities, on improvements in VEF. In a randomized, double-blind, placebo-controlled study, healthy smokers (25 ± 1 y old; mean ± SEM) received NRT and abstained from smoking for 24 h with placebo (n = 12) or oral administration of γ-T-rich mixture of tocopherols (γ-TmT; n = 11) that provided 500 mg γ-T. Brachial artery flow-mediated dilation (FMD), and biomarkers of nitric oxide metabolism, antioxidant status, inflammation, and lipid peroxidation [8-iso-prostaglandin F2α stereoisomers (8-iso-15(R)-PGF2α and 8-iso-15(S)-PGF2α)] were measured prior to and after 24 h of smoking abstinence. Smoking abstinence with NRT regardless of γ-TmT similarly decreased urinary naphthol (P < 0.05) without affecting plasma cotinine. γ-TmT increased plasma γ-T by 4-times and the urinary metabolite of γ-T, γ-carboxyethyl-chromanol, by three times. Smoking abstinence with γ-TmT, but not smoking abstinence alone, increased FMD without affecting plasma nitrate/nitrite or the ratio of asymmetric dimethylarginine/arginine. Urinary 8-iso-15(S)-PGF2α decreased only in those receiving γ-TmT and was inversely correlated to FMD (R = −0.43, P < 0.05). Circulating markers of inflammation were unaffected by smoking abstinence or γ-TmT. Short-term NRT-assisted smoking abstinence with γ-TmT, but not NRT-assisted smoking abstinence alone, improved VEF by decreasing 8-iso-15(S)-PGF2α, a vasoconstrictor that was otherwise unaffected by NRT-assisted smoking abstinence. PMID:25361769

GMP-grade platelet lysate enhances proliferation and migration of tenon fibroblasts.

PubMed

Carducci, Augusto; Scafetta, Gaia; Siciliano, Camilla; Carnevale, Roberto; Rosa, Paolo; Coccia, Andrea; Mangino, Giorgio; Bordin, Antonella; Vingolo, Enzo Maria; Pierelli, Luca; Lendaro, Eugenio; Ragona, Giuseppe; Frati, Giacomo; De Falco, Elena

2016-01-01

Tenon's fibroblasts (TFs), widely employed as in vitro model for many ophthalmological studies, are routinely cultured with FBS. Platelet Lysate (PL), a hemoderivate enriched with growth factors and cytokines has been largely tested in several clinical applications and as substitute of FBS in culture. Here, we investigate whether PL can exert biological effects on TF populations similarly to other cell types. Results show that PL significantly enhances cell proliferation and migration vs. FBS, without influencing cell size/granularity. Upregulation of EGF, VEGF, KDR, MMP2-9, FAK mRNA levels also occurs and phosphorylation of AKT but not of ERK1/2 is significantly enhanced. The inhibition of the PI3kinase/AKT pathway with the specific inhibitor wortmannin, decreases PL-induced cell migration but not proliferation. Condition supernatants containing PL show increased bioavailability of Nitric Oxide and reduced levels of 8-Iso-PGF2-alpha, correlating with cell proliferation and migration. Pro-angiogenic/inflammatory soluble factors (GRO, Angiogenin, EGF, I-309, PARC) are exclusively or greater expressed in media containing PL than FBS. GMP-grade PL preparations positively influence in vitro biological effects of TFs representing a suitable and safer alternative to FBS.

The efficacy and safety of adding either vildagliptin or glimepiride to ongoing metformin therapy in patients with type 2 diabetes mellitus.

PubMed

Kim, Gyuri; Oh, Sewon; Jin, Sang-Man; Hur, Kyu Yeon; Kim, Jae Hyeon; Lee, Moon-Kyu

2017-08-01

To compare the effects of either vildagliptin or glimepiride on glycemic variability, oxidative stress, and endothelial parameters in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone. In this randomized, open-label, parallel study, 34 patients with T2DM being treated with metformin having an HbA1c of 7.0-10.0% were allocated into either the vildagliptin or glimepiride group. A mixed-meal tolerance test and 72-hour continuous glucose monitoring were conducted, and urinary 8-iso-prostaglandinF 2α (PGF 2α ) and endothelial-dependent flow-mediated dilatation (FMD) were evaluated at baseline and after 12 weeks of treatment. Similar significant improvements in HbA1c level were shown in both vildagliptin (-0.8%) and glimepiride (-0.9%) groups after treatment (Ps<0.001). The mean amplitude of glycemic excursions (MAGE) and the mean of daily differences (MODD) were significantly decreased by vildagliptin (P = 0.044 and P = 0.031, respectively) but not by glimepiride. Glimepiride was significantly associated with a higher incidence of hypoglycemia than vildagliptin (P = 0.005). There were no significant differences in urinary 8-iso-PGF 2α or FMD between the two groups. Vildagliptin effectively improved glucose level with a significantly greater reduction in glycemic variability and hypoglycemia than glimepiride in patients with T2DM ongoing metformin therapy. The two drugs showed no significant differences in urinary 8-iso-PGF 2α and FMD. NCT01404676.

Association between adverse pregnancy outcome and imbalance in angiogenic regulators and oxidative stress biomarkers in gestational hypertension and preeclampsia.

PubMed

Turpin, Cornelius A; Sakyi, Samuel A; Owiredu, William K B A; Ephraim, Richard K D; Anto, Enoch O

2015-08-25

Gestational hypertension (GH) and Preeclampsia, (PE) are the most complicated amongst hypertensive disorders of pregnancy. The mechanism that links hypertension in pregnancy to adverse maternal outcomes is not fully understood though some relate this to endothelial dysfunction originating from an imbalanced angiogenic regulators and oxidative stress biomarkers. This study assessed the correlation between angiogenic regulators and oxidative stress biomarker levels with adverse pregnancy outcomes among GH and PE participants. A cohort of pregnant women who received antenatal care at the Obstetrics and Gynaecology department of the Komfo Anokye Teaching Hospital (KATH) were followed. During their antenatal visits, 100 developed PE and 70 developed GE, of these, 50 PE and 50 GH gave informed consent. Their blood samples were taken at time of diagnosis and 48 h post-partum. 50 other aged-matched women who did not develop neither GH nor PE were selected as controls. Placental growth factor (PLGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and 8-epi-prostaglandin F2alpha (8-epi-PGF2α) levels were estimated by ELISA and total antioxidant capacity (T-AOC) was measured spectrophotometrically. Graphpad Prism was used for data analysis. Median levels of sFlt-1, 8-epi-PGF2α and sFlt-1/PLGF were elevated among participants with PE co-existing with intrauterine fetal death (IUFD), placental abruptio, placental previa, HELLP syndrome and intrauterine growth restriction (IUGR) compared to PE without adverse outcomes (p = 0.041, p = 0.005, p = 0.0002). Levels of PLGF, T-AOC and PLGF/sFlt-1 were significantly reduced among participants with PE co-existing with IUFD, placental abruptio, placental previa, HELLP syndrome and IUGR compared to PE without adverse outcomes (p = 0.0013, p = 0.006, p < 0.0001). A significant negative correlation of IUGR (p = 0.0030; p < 0.0001), placental abruptio (p < 0.0001; p < 0.0001), IUFD (p < 0.0001; p < 0.0001), stillbirth (p = 0.0183 and p < 0.000), and postpartum haemorrhage (PPH) (p = 0.0420; p = 0.0044) were associated with both PLGF and T-AOC whilst a significant positive correlation of IUGR, placental abruptio (p < 0.0001; p < 0.0001), IUFD (p < 0.0001; p < 0.0001), stillbirth (p < 0.0001; p < 0.0001), and PPH (p = 0.0043; p = 0.0039) were observed with both sFlt-1 and 8-epi-PGF2α in PE. Imbalance in the levels of angiogenic regulators and oxidative stress biomarkers correlates with adverse pregnancy outcomes among PE participants. Early identification of these imbalance would alert health care givers in anticipation of adverse pregnancy outcome and thus increased surveillance during pregnancy and parturition and measures to ameliorate the adverse outcome.

Early effects of equine FSH (eFSH) treatment on hormonal and reproductive parameters in mares intended to carry their own pregnancy.

PubMed

Raz, Tal; Gray, Allister; Hunter, Barbara; Card, Claire

2009-10-01

Superovulatory treatment may potentially increase the embryo recovery rate and the per-cycle pregnancy rate in normal or subfertile mares that are managed properly. However, some studies suggest a possible negative effect of superovulatory treatment on ovarian follicular maturation and embryo viability. Objectives of the present study were to investigate the early effects of eFSH treatment in reproductively normal mares in terms of: folliculogenesis, pregnancy rate, early embryonic development, reproductive tract parameters (tone and edema), and serum estradiol-17beta and progesterone concentrations. Reproductively sound mares (n=26) were evaluated daily by transrectal palpation and ultrasonography. Five days after spontaneous ovulation, mares were randomly assigned to one of two treatment groups. In the eFSH group, mares (n=16 estrous cycles) were administered eFSH twice daily; beginning when a follicle > or =20mm was detected, and continuing until at least one follicle reached a diameter of > or =35 mm. PGF2alpha was administered 2 days following initiation of eFSH therapy, and hCG was administered approximately 36h after cessation of eFSH therapy. In the control group, mares (n=26 estrous cycles) were administered PGF2alpha 7 days after spontaneous ovulation, and hCG when a follicle > or =35 mm was detected. All mares were bred with fresh semen, monitored for ovulation (Day 0), and evaluated for pregnancy on Days 11-16. Serum estradiol-17beta and progesterone concentrations were analyzed using radioimmunoassay on the Day of hCG administration, and Days 8, 11 and 16. Mares treated with eFSH had more follicles > or =30 mm at the time of hCG administration (2.6+/-0.4 compared with 1.1+/-0.1; P<0.01), and more ovulations (2.3+/-0.5 compared with 1.1+/-0.3; P<0.01). However, pregnancy rates were not significantly different between groups (50%; 8/16 compared with 62%; 16/26). Mean overall daily growth rate of embryonic vesicles from Day 11 to 16 was not statistically different between the two groups (3.3+/-0.3 compared with 3.7+/-0.1 mm/day) (P=0.2); however, was more variable (P<0.01) in the eFSH group (95%CI: 2.6-3.8mm/day) than in the control group (95%CI: 3.5-3.9 mm/day). Administration of eFSH modified the reproductive tract variables and serum concentrations of progesterone and estradiol-17beta on the days that oocyte maturation, fertilization, and early embryonic development are expected to occur. These alterations may be related to the greater incidence of non-ovulatory follicles (25% compared with 0%), fewer embryos per ovulation rate (0.3+/-0.1 compared with 0.6+/-0.1), and the lesser than expected pregnancy rates in the eFSH-treated mares.

Prostaglandins, steroids and reception (an attempt to model the structure of the active centers of adrenoreception).

PubMed

Podymov, V K; Piruzyan, L A; Gladkikh, S P; Kats, M M; Nizhnii, S V

1980-01-01

On the basis of numerous results of investigations on adrenergic systems, an orientational model of the adrenoreceptor (AR) is postulated. Its active center includes low-molecular-weight components--prostaglandins (PGE, PGF), steroids (cortisone, hydrocortisone), S+-adenosylmethionine, Ca, Mg, and Mn ions. Appraisal of the stereospecific characteristics of such a functional unit of AR explains the difference in the nature and magnitude of the effects of interaction of the catecholamines, their agonists and antagonists will the so-called alpha- and beta-AR. Depending on the organ or tissue in which the AR is located, its protein subunits comprise adenylcyclase (beta-AR) or Na,K-ATPase (alpha-AR). An obligatory component of the AR is catechol-O-methyltransferase. The model elaborated describes satisfactorily the molecular mechanisms of action of many pharmacological agents, explains why attempts to isolate and reconstruct the AR have proved fruitless, and gives grounds for rejecting the hypothesis that there exist steroid, prostaglandin, and purinergic receptors, linking the exceptionally high and diverse activity of these biologically active substances with their participation in adrenoreception among other reasons. A conception of the active centers of the AR as low-molecular-weight entities permits the explanation of such phenomena as the desensitization of the AR, the "interconversion" of beta-AR into alpha-AR with a change in the parameters of the medium, and certain components of the pathogenesis of bronchial asthma, etc.

Melatonin prevents experimental preterm labor and increases offspring survival.

PubMed

Domínguez Rubio, Ana P; Sordelli, Micaela S; Salazar, Ana I; Aisemberg, Julieta; Bariani, María V; Cella, Maximiliano; Rosenstein, Ruth E; Franchi, Ana M

2014-03-01

Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that intra-amniotic infections may be a significant and potentially preventable cause of preterm birth. This work assessed the effect of melatonin in a murine model of inflammation-associated preterm delivery which mimics central features of preterm infection in humans. For this purpose, preterm labor was induced in BALB/c mice by intraperitoneal injections of bacterial lipopolysaccharide (LPS) at 10.00 hr (10 μg LPS) and 13.00 hr (20 μg LPS) on day 15 of pregnancy. On day 14 of pregnancy, a pellet of melatonin (25 mg) had been subcutaneously implanted into a group of animals. In the absence of melatonin, a 100% incidence of preterm birth was observed in LPS-treated animals, and the fetuses showed widespread damage. By comparison, treatment with melatonin prevented preterm birth in 50% of the cases, and all pups from melatonin-treated females were born alive and their body weight did not differ from control animals. Melatonin significantly prevented the LPS-induced rises in uterine prostaglandin (PG) E2 , PGF2α, and cyclooxygenase-2 protein levels. In addition, melatonin prevented the LPS-induced increase in uterine nitric oxide (NO) production, inducible NO synthase protein, and tumor necrosis factor-alpha (TNFα) levels. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent preterm labor and to increase offspring survival. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Aspirin provocation increases 8-iso-PGE2 in exhaled breath condensate of aspirin-hypersensitive asthmatics.

PubMed

Mastalerz, Lucyna; Januszek, Rafał; Kaszuba, Marek; Wójcik, Krzysztof; Celejewska-Wójcik, Natalia; Gielicz, Anna; Plutecka, Hanna; Oleś, Krzysztof; Stręk, Paweł; Sanak, Marek

2015-09-01

Isoprostanes are bioactive compounds formed by non-enzymatic oxidation of polyunsaturated fatty acids, mostly arachidonic, and markers of free radical generation during inflammation. In aspirin exacerbated respiratory disease (AERD), asthmatic symptoms are precipitated by ingestion of non-steroid anti-inflammatory drugs capable for pharmacologic inhibition of cyclooxygenase-1 isoenzyme. We investigated whether aspirin-provoked bronchoconstriction is accompanied by changes of isoprostanes in exhaled breath condensate (EBC). EBC was collected from 28 AERD subjects and 25 aspirin-tolerant asthmatics before and after inhalatory aspirin challenge. Concentrations of 8-iso-PGF2α, 8-iso-PGE2, and prostaglandin E2 were measured using gas chromatography/mass spectrometry. Leukotriene E4 was measured by immunoassay in urine samples collected before and after the challenge. Before the challenge, exhaled 8-iso-PGF2α, 8-iso-PGE2, and PGE2 levels did not differ between the study groups. 8-iso-PGE2 level increased in AERD group only (p=0.014) as a result of the aspirin challenge. Urinary LTE4 was elevated in AERD, both in baseline and post-challenge samples. Post-challenge airways 8-iso-PGE2 correlated positively with urinary LTE4 level (p=0.046), whereas it correlated negatively with the provocative dose of aspirin (p=0.027). A significant increase of exhaled 8-iso-PGE2 after inhalatory challenge with aspirin was selective and not present for the other isoprostane measured. This is a novel finding in AERD, suggesting that inhibition of cyclooxygenase may elicit 8-iso-PGE2 production in a specific mechanism, contributing to bronchoconstriction and systemic overproduction of cysteinyl leukotrienes. Copyright © 2015 Elsevier Inc. All rights reserved.

A role for the endocannabinoid system in premature luteal regression and progesterone withdrawal in lipopolysaccharide-induced early pregnancy loss model.

PubMed

Schander, Julieta Aylen; Correa, Fernando; Bariani, María Victoria; Blanco, Julieta; Cymeryng, Cora; Jensen, Federico; Wolfson, Manuel Luis; Franchi, Ana María

2016-11-01

What is the role of the endocannabinoid system (eCS) in the alterations of the endocrine system in a murine model of lipopolysaccharide (LPS)-induced miscarriage? In 7-days pregnant wild type, but not cannabinoid receptor type 1 knockout (CB1-KO) mice, LPS increased COX-2 expression and prostaglandin F 2α (PGF 2α ) production in the uterus leading to lower expression of prolactin receptor in the ovary and a marked regression of corpora lutea (CL), suggesting that the eCS mediates the deleterious effects of LPS on reproductive events. Appropriate systemic progesterone levels are critical for a successful pregnancy outcome. Precocious loss of luteal progesterone (P4) secretion leads to miscarriage in rodents. We have previously shown that LPS administration to pregnant mice induces embryonic resorption accompanied by a dramatic decrease in systemic progesterone levels in a murine model of inflammatory miscarriage, with the eCS mediating these LPS-induced deleterious effects. CD1 wild-type (WT) and CB1-KO mice were randomly allocated to Vehicle (saline; i.p.) or LPS (0.5 μg/g body weight; i.p.) treated groups: (WT-Vehicle; WT-LPS; CB1-KO-Vehicle and CB1-KO-LPS). A single injection was given on day 7 of pregnancy and tissues (blood, ovary, uterus) were collected 6, 12, 24 and 48 h later. P4 and PGF2α plasma levels were determined by radioimmunoassay. Cyclooxygenase-2 (COX-2) mRNA (RT-PCR) and protein (Western blot) content in uterus was assayed. COX-2 and prolactin receptor (PrlR) mRNA levels in the ovary were assayed by RT-PCR. Tissue morphology of the CL was assessed by haematoxylin-eosin staining. Treatment of 7-day pregnant WT mice with LPS induced a P4 withdrawal (p < 0.05), increased in uterine COX-2 mRNA and protein expression (p < 0.05) as well as an increase in uterine PGF 2α production (p < 0.05). These changes were absent in LPS-treated 7-day pregnant CB1-KO mice. In ovarian tissues, LPS treatment to 7-day pregnant WT mice induced a downregulation of PrlR mRNA expression (p < 0.05) together with an increase in COX-2 mRNA expression (p < 0.05) and PGF 2α content (p < 0.05). These effects were absent in the CB1-KO mice. Collectively, our results suggest a role for the eCS mediating LPS-induced deleterious effects on reproductive tissues. An important caveat of this study is the endocrine differences between mice and humans during pregnancy (e.g. P4 is produced by the CL throughout pregnancy in mice, whereas this is not the case in humans), which limits the extrapolation of the results presented here. Our findings provide new insights in the role of the endocannabinoid system in the physiopathology of reproduction as well as the role of this endogenous system as a mediator of LPS deleterious effects on reproductive tissues. None. Dr Ana María Franchi was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2010/0813 and PICT 2013/0097) and by Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2012/0061). The authors have no competing interests. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.For Permissions, please email: journals.permissions@oup.com.

Purulent vaginal discharge in grazing dairy cows: Risk factors, reproductive performance, and prostaglandin F2α treatment.

PubMed

Giuliodori, M J; Magnasco, M; Magnasco, R P; Lacau-Mengido, I M; de la Sota, R L

2017-05-01

The objectives of this study were to assess the association of a 4-point scale of vaginal discharge score (VDS) with time to pregnancy to define criteria for a practical case of purulent vaginal discharge (PVD) in dairy cows, to test the risk factors for PVD, and, finally, the effect of a dose of PGF 2α on cure and reproductive performance. In experiment 1, grazing Holstein cows (n = 2,414) had their vaginal discharge scored at ∼32 d in milk (DIM) on a 4-point scale, the effect of VDS on the hazard of pregnancy by 300 DIM was then assessed to derive a case definition of PVD. Risk factors for PVD and self-cure were also assessed. In experiment 2, grazing Holstein cows (n = 6,326) from 5 herds were checked for PVD at ∼30 DIM. Cows with PVD were assigned to receive one dose of 500 μg of PGF 2α analog (Cloprostenol; Ciclase, Syntex SA, Buenos Aires, Argentina) per cow (odd ear tag number) or to remain untreated (even tag number). Cure was declared if cows presented clear normal vaginal discharge (VDS-0) at visit 2 (∼62 DIM). Data were analyzed with Cox's regression and mixed logistic models. In experiment 1, cows with VDS ≥1 had lower hazard of pregnancy and longer calving to pregnancy interval than cows with VDS-0. This finding was not affected by the time at which the diagnosis was performed. Therefore, a cow ≥21 DIM and having VDS ≥1 was used to define a case of PVD. The odds of PVD were greater in primiparous cows compared with multiparous, in cows with abnormal calving compared with those with normal calving, and in those losing BCS peripartum. In experiment 2, PGF 2α treatment tended to slightly increase the hazard of pregnancy (adjusted hazard ratio = 1.13). Conversely, PGF 2α had no effect on the odds of cure of PVD [adjusted odds ratio (AOR) = 1.19], pregnancy at first service (AOR = 1.03), or pregnancy by 100 DIM (AOR = 0.89) or 200 DIM (AOR = 1.27). In conclusion, cows with VDS ≥1 can be considered to have PVD because of their lower hazard of pregnancy and longer calving to pregnancy interval (up to 48 d). Important risk factors are parity, calving, and body condition score loss peripartum. Optimal time of diagnosis is ≥28 to 35 DIM because cows experience a high self-cure rate. Self-cure is also affected by parity, prepartum BCS, and VDS. Finally, as treatment with one dose of PGF 2α had a small effect on the hazard of pregnancy and no effect on clinical cure, its therapeutic use in grazing dairy cows with PVD is not recommended. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effect of follicle age on conception rate in beef heifers.

PubMed

Abreu, F M; Cruppe, L H; Maquivar, M; Utt, M D; Madsen, C A; Vasconcelos, J L M; Mussard, M L; Day, M L; Geary, T W

2014-03-01

The objective of this study was to determine the effect of age of the ovulatory follicle on fertility in beef heifers. Ovulation was synchronized with the 5 d CO-Synch + controlled intravaginal drug release (CIDR) program in heifers in Montana (MT; n = 162, Hereford and Angus Crossbred) and Ohio (OH; n = 170, Angus Crossbred). All heifers received estradiol benzoate (EB; 1 mg/500 kg BW, [i.m.]) 6 d after the final GnRH of the synchronization program to induce follicular atresia and emergence of a new follicular wave (NFW) followed by prostaglandin F2α (PGF(2α); 25 mg, i.m.) administration either 5 d ("young" follicle [YF]; n = 158) or 9 d ("mature" follicle [MF]; n = 174) after EB. Estrous detection was performed for 5 d after PGF(2α) with AI approximately 12 h after onset of estrus. Ovarian ultrasonography (MT location only) was performed in YF and MF at EB, 5 d after EB, PGF(2α), and AI. Heifers in MT (n = 20) and OH (n = 18) that were not presynchronized or did not initiate a NFW were excluded from further analyses, resulting in 142 and 152 heifers in MT and OH, respectively. Heifers from the MF treatment in MT that initiated a second NFW after EB but before PGF(2α) (MF2; n = 14) were excluded from the primary analysis. In the secondary analysis, the MF2 group was compared to MF and YF treatments in MT. Estrous response was similar (90%; 252/280) between treatments and locations. Proestrus interval (from PGF(2α) to estrus) and age of the ovulatory follicle at AI were similar for MF heifers between locations (54.6 ± 1.7 h and 8.3 ± 0.07 h) but were greater (P < 0.01) for YF heifers in OH (78.5 ± 1.4 h and 5.3 ± 0.06 h) than MT (67.4 ± 1.6 h and 4.8 ± 0.06 h; treatment × location, P < 0.01). However, conception rate did not differ for MF (63.8%; 74/116) and YF (67.0%; 91/136) treatments. In the MT heifers, follicle size and follicle age at AI in the YF treatment (10.4 ± 0.15 mm and 4.8 ± 0.06 d, respectively) was less (P < 0.01) than in the MF treatment (11.0 ± 0.18 mm and 8.3 ± 0.11 d, respectively), but conception rate to AI did not differ between treatments in MT. In the MF2 group proestrus interval was greater (P < 0.01); hence, diameter of the ovulatory follicle and age were similar to that for the YF treatment. Conception rate to AI did not differ between MF2, MF, and YF (61.5, 63.3, and 64.7%, respectively) in MT. In conclusion, manipulation of age of the nonpersistent ovulatory follicle at spontaneous ovulation did not influence conception rate.

Short-term in vivo modifications of platelet NADPH oxidase 2 (NOX2) and prostaglandin F2α in HIV-1 patients on abacavir-based therapies.

PubMed

Pastori, D; Esposito, A; Carnevale, R; Bartimoccia, S; Nocella, C; Fantauzzi, A; Pignatelli, P; Violi, F; Mezzaroma, I

2016-11-01

The aim of the study was to investigate the in vivo effect of abacavir (ABC) on platelet oxidative stress. We performed a randomized pilot study including 39 HIV-1-infected patients, 17 on zidovudine/lamivudine (ZDV/3TC) and 22 on tenofovir/emtricitabine (TDF/FTC). Ten patients on ZDV/3TC and eight patients on TDF/FTC were randomly allocated to switching the nucleoside backbone to ABC/3TC. At baseline and after 6 months, platelet oxidative stress was assessed by platelet NADPH oxidase 2 (NOX2)-derived peptide (sNOX2-dp), a marker of NOX2 activation, and platelet prostaglandin F 2α (8-iso-PGF 2α ). Platelet activation was measured by soluble CD40L (sCD40L). At baseline, no differences between ZDV/3TC or TDF/FTC recipients were found. After 6 months, patients switching from ZDV/3TC showed a decrease of sNOX2-dp (from 20.9±5.7 to 12.5±3.8 pg/ml, p=0.002) and 8-iso-PGF 2α (from 154.3±41.9 to 122.9±28.0 pmol/l, p=0.025). No effects on platelet oxidative stress biomarkers were observed in subjects from TDF/FTC, who showed a significant increase in blood glucose (p=0.043) and total cholesterol (p=0.027). ABC showed no effect on sCD40L levels in both groups. ABC reduced platelet sNOX2-dp and 8-iso-PGF 2α in HIV-1 subjects switching from ZDV/3TC but not in those from TDF/FTC after 6 months. No changes in platelet activation were found in both groups. © 2016 British HIV Association.

Hormonal regulation of the alpha-ketoglutarate dehydrogenase complex in the isolated perfused rat liver.

PubMed

Rashed, H M; Waller, F M; Patel, T B

1988-04-25

The metabolic flux through the alpha-ketoglutarate dehydrogenase reaction in perfused livers was monitored by measuring the rate of 14CO2 production from [1-14C]alpha-ketoglutarate. The rates of 14CO2 production and glucose production from [1-14C]alpha-ketoglutarate were increased with increasing perfusate alpha-ketoglutarate concentrations. Vasopressin, angiotensin II, and the alpha 1-adrenergic agonist phenylephrine stimulated transiently by 2.5-fold the metabolic flux through the alpha-ketoglutarate dehydrogenase reaction in the presence and absence of Ca2+ in the perfusion medium. High concentrations of glucagon (1 x 10(-8) M) and 8-p-chlorophenylthio-cAMP (100 microM) (data not shown) also stimulated transiently the metabolic flux through the alpha-ketoglutarate dehydrogenase reaction. However, lower glucagon concentrations (1 x 10(-9) M) stimulated the rate of 14CO2 production from [1-14C]alpha-ketoglutarate only under conditions optimized to fix the cellular oxidation-reduction state at an intermediate level, when glucagon (1 x 10(-9) M)-mediated elevation of cAMP content was greater than that observed under highly oxidizing and reducing conditions. These data indicate that agonists which increase cytosolic free Ca2+ levels stimulate the metabolic flux through the alpha-ketoglutarate dehydrogenase complex. Furthermore, the data presented here demonstrate for the first time that physiological glucagon concentrations stimulate the metabolic flux through the alpha-ketoglutarate dehydrogenase reaction only under conditions known to be optimal for glucagon-mediated Ca2+ mobilization in the isolated perfused rat liver.

Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, S.B.; Halenda, S.P.; Bylund, D.B.

1991-02-01

The effect of alpha 2-adrenergic receptor activation on adenylate cyclase activity in Chinese hamster ovary cells stably transfected with the alpha 2A-adrenergic receptor gene is biphasic. At lower concentrations of epinephrine forskolin-stimulated cyclic AMP production is inhibited, but at higher concentrations the inhibition is reversed. Both of these effects are blocked by the alpha 2 antagonist yohimbine but not by the alpha 1 antagonist prazosin. Pretreatment with pertussis toxin attenuates inhibition at lower concentrations of epinephrine and greatly potentiates forskolin-stimulated cyclic AMP production at higher concentrations of epinephrine. alpha 2-Adrenergic receptor stimulation also causes arachidonic acid mobilization, presumably via phospholipasemore » A2. This effect is blocked by yohimbine, quinacrine, removal of extracellular Ca2+, and pretreatment with pertussis toxin. Quinacrine and removal of extracellular Ca2+, in contrast, have no effect on the enhanced forskolin-stimulated cyclic AMP production. Thus, it appears that the alpha 2-adrenergic receptor in these cells can simultaneously activate distinct signal transduction systems; inhibition of adenylate cyclase and stimulation of phospholipase A2, both via G1, and potentiation of cyclic AMP production by a different (pertussis toxin-insensitive) mechanism.« less

Analysis of hydrogen H-alpha observations of the coma of Comet P/Halley

NASA Technical Reports Server (NTRS)

Smyth, William H.; Marconi, M. L.; Scherb, Frank; Roesler, Fred L.

1993-01-01

The Monte Carlo Particle Trajectory Model of Combi and Smyth (1988) is used here to analyze observations of the H-alpha coma of Comet Halley. The solar excitation mechanism for the H-alpha emissions line is described. The H2O production rates derived for the H-alpha brightness measurements are shown to be very consistent with the H2O production rates determined from other Comet Halley observations of the H, O, and OH comae. Revised H2O production rates determined from 6300 A brightness measurements are presented.

Effectiveness of a short-term treatment with progesterone injections on synchrony of lambing and fertility in tropical hair sheep.

PubMed

Knights, Marlon; Ramgattie, Reeza; Siew, Narendra; Singh-Knights, Doolarie; Bourne, Gregory

2011-06-01

The efficacy of using a low cost system for delivering progesterone as part of an estrous synchronization protocol in sheep was evaluated. In experiment 1, Barbados Black Belly ewes (n=34) and ewe lambs (n=35; 37.5±0.9 kg) were assigned to be untreated, control animals (C), or to receive PGF(2α) on d0 (PG), or receive two injections of progesterone (200mg, i.m. each) on D -5 and on D -2.5, prior to PGF(2α), on D 0 (2PPG). Treatment with 2PPG increased the proportion of animals lambing to the first service (P<0.05), an effect that was greater in ewe lambs than ewes (treatment × parity; P<0.05). The interval from ram introduction to lambing and the mean lambing day was less (P=0.04) in the 2PPG-treated animals compared to control animals. In Experiment 2, lactating ewes from experiment 1 (n=61) 60-85 days postpartum were assigned within parity and number of lambs reared to remain nursing (S; n=29) or weaned (W; n=32) 3 weeks prior to treatment with the 2PPG protocol. There was no effect of treatment on the proportion of animals lambing to the first service or overall, interval from ram introduction to lambing and lambing interval. An 8-month lambing interval was observed in ewes in which estrus was synchronized regardless of physiological state. In conclusion, the two-progesterone injection synchronization protocol may be used as a practical low cost and efficient method of synchronizing estrus to reduce the lambing interval and maximize productivity in tropical breeds of sheep. Copyright © 2011 Elsevier B.V. All rights reserved.

Hormone regulates endometrial function via cooperation of endoplasmic reticulum stress and mTOR-autophagy.

PubMed

Yang, Diqi; Jiang, Tingting; Liu, Jianguo; Hong, Jin; Lin, Pengfei; Chen, Huatao; Zhou, Dong; Tang, Keqiong; Wang, Aihua; Jin, Yaping

2017-12-05

In ruminant, the receptive endometrium and the elongation of the hatched blastocyst are required to complete the process of implantation. However, the mechanisms regulating goat endometrial function during the peri-implantation period of pregnancy are still unclear. In this study, EECs were treated with progesterone, estradiol, and interferon-tau (IFNT). We have found that endoplasmic reticulum (ER) stress was activated under hormones treatment. To identify the cellular mechanism of regulation of endometrial function, we investigated the effect of ER stress activator thapsigargin (TG) and inhibitor 4 phenyl butyric acid (4-PBA) on EECs. We found that TG, which activated the three branches of UPR, increased the expression of genes associated with promoting conceptus elongation and cellular attachment, significantly up-regulated the spheroid attachment rate and PGE 2 /PGF 2α ratio. 4-PBA pre-treatment inhibited UPR and inhibited promoting conceptus elongation and cellular attachment related genes, but the spheroid attachment rate and PGE 2 /PGF 2α ratio were not changed significantly. Moreover, knockdown of ATF6 via shATF6 promoted the conceptus elongation related genes, but increased the dissolution of the corpus luteum. Besides, blocking ATF6 attenuated autophagy by activating mammalian target of rapamycin (mTOR) pathway. Moreover, rapamycin (mTOR inhibitor) pre-treatment inhibited the expression of promoting conceptus elongation and increased PGE 2 /PGF 2α ratio. Taken together, our study indicated that physiological level of ER stress may contribute to early pregnancy success, and ATF6 signaling pathway cooperated with autophagy to regulate endometrial function by modulating mTOR pathway. © 2017 Wiley Periodicals, Inc.

Reversibility of antigestagenic action of antiprogestin onapristone by exogenous progestagens during early pregnancy in guinea pig.

PubMed

Singh, M M; Fähnrich, M; Hasan, S H; Elger, W

1995-09-01

Ability of progesterone, gestodene, promegestone and cyproterone acetate (CPA) to reverse antigestagenic action of onapristone in adult female guinea pigs was investigated. Onapristone (10 mg/kg, s.c.) administered on post-conception days 8-11 caused resorption of implantations and vaginal bleeding in all animals. Simultaneous administration of progesterone, gestodene or promegestone on days 7-13 successfully reversed antigestagenic action of this antiprogestin, since most animals supplemented with these progestagens had viable implantations at autopsy on day 14. CPA was, however, ineffective and animals supplemented with it had only resorbed implantations and blood in uterus and vagina like that in onapristone per se treated animals. High plasma progesterone and low PGFM concentration were generally observed in all pregnant animals bearing viable implantations. PGFM (13, 14-dihydro-15-keto PGF2 alpha) was significantly elevated by day 14 in onapristone-treated (Group II) and CPA-supplemented (Group X) animals. No discernible effect on pregnancy or post-implantation embryonic development was observed in animals treated per se with these progestagens.

[Factors influencing conception rate after synchronization of ovulation and timed artificial insemination--a review].

PubMed

Tenhagen, B A

2005-04-01

This review describes factors that affect conception rate after synchronization of ovulation and timed artificial insemination. Intervals of 7 days between GnRH and PGF2alpha, 48 hours to the second GnRH treatment and a further 16 to 20 hours to the timed insemination have been proven to be most effective. Conception rates (CR) increase as lactation progresses up to 100 days in milk. Primiparous cows have higher CR than older cows. Anovular cows at the start of the synchronization protocols have poor CR. These are highest for cows started in early dioestrus. While poor body condition and some post partum and post insemination health disorders have negative effects on the CR, a significant effect of postpartum chronic endometritis could not be demonstrated. High milk yield was also not shown to have a negative effect on CR in almost all studies, while the negative effect of heat stress on fertility is also found in Ovsynch cows. However, the negative effects of high milk yields and heat stress on AI submission rates are overcome by the timed insemination protocol.

Effect of phosphate-based glass fibre surface properties on thermally produced poly(lactic acid) matrix composites.

PubMed

Mohammadi, Maziar Shah; Ahmed, Ifty; Muja, Naser; Rudd, Christopher D; Bureau, Martin N; Nazhat, Showan N

2011-12-01

Incorporation of soluble bioactive glass fibres into biodegradable polymers is an interesting approach for bone repair and regeneration. However, the glass composition and its surface properties significantly affect the nature of the fibre-matrix interface and composite properties. Herein, the effect of Si and Fe on the surface properties of calcium containing phosphate based glasses (PGs) in the system (50P(2)O(5)-40CaO-(10-x)SiO(2)-xFe(2)O(3), where x = 0, 5 and 10 mol.%) were investigated. Contact angle measurements revealed a higher surface energy, and surface polarity as well as increased hydrophilicity for Si doped PG which may account for the presence of surface hydroxyl groups. Two PG formulations, 50P(2)O(5)-40CaO-10Fe(2)O(3) (Fe10) and 50P(2)O(5)-40CaO-5Fe(2)O(3)-5SiO(2) (Fe5Si5), were melt drawn into fibres and randomly incorporated into poly(lactic acid) (PLA) produced by melt processing. The ageing in deionised water (DW), mechanical property changes in phosphate buffered saline (PBS) and cytocompatibility properties of these composites were investigated. In contrast to Fe10 and as a consequence of the higher surface energy and polarity of Fe5Si5, its incorporation into PLA led to increased inorganic/organic interaction indicated by a reduction in the carbonyl group of the matrix. PLA chain scission was confirmed by a greater reduction in its molecular weight in PLA-Fe5Si5 composites. In DW, the dissolution rate of PLA-Fe5Si5 was significantly higher than that of PLA-Fe10. Dissolution of the glass fibres resulted in the formation of channels within the matrix. Initial flexural strength was significantly increased through PGF incorporation. After PBS ageing, the reduction in mechanical properties was greater for PLA-Fe5Si5 compared to PLA-Fe10. MC3T3-E1 preosteoblasts seeded onto PG discs, PLA and PLA-PGF composites were evaluated for up to 7 days indicating that the materials were generally cytocompatible. In addition, cell alignment along the PGF orientation was observed showing cell preference towards PGF.

Effects of electroacupuncture on luteal regression and steroidogenesis in ovarian hyperstimulation syndrome model rat.

PubMed

Huang, Xuan; Chen, Li; Xia, You-Bing; Xie, Min; Sun, Qin; Yao, Bing

2018-03-15

Electroacupuncture (EA) is an effective and safe therapeutic method widely used for treating clinical diseases. Previously, we found that EA could decrease serum hormones and reduce ovarian size in ovarian hyperstimulation syndrome (OHSS) rat model. Nevertheless, the mechanisms that contribute to these improvements remain unclear. HE staining was used to count the number of corpora lutea (CL) and follicles. Immunohistochemical and ELISA were applied to examine luteal functional and structural regression. Immunoprecipitation was used for analyzing the interaction between NPY (neuropeptide Y) and COX-2; western blotting and qRT-PCR were used to evaluate the expressions of steroidogenic enzymes and PKA/CREB pathway. EA treatment significantly reduced the ovarian weight and the number of CL, also decreased ovarian and serum levels of PGE2 and COX-2 expression; increased ovarian PGF2α levels and PGF2α/PGE2 ratio; decreased PCNA expression and distribution; and increased cyclin regulatory inhibitor p27 expression to have further effect on the luteal formation, and promote luteal functional and structural regression. Moreover, expression of COX-2 in ovaries was possessed interactivity increased expression of NPY. Furthermore, EA treatment lowered the serum hormone levels, inhibited PKA/CREB pathway and decreased the expressions of steroidogenic enzymes. Hence, interaction with COX-2, NPY may affect the levels of PGF2α and PGE2 as well as impact the proliferation of granulosa cells in ovaries, thus further reducing the luteal formation, and promoting luteal structural and functional regression, as well as the ovarian steroidogenesis following EA treatment. EA treatment could be an option for preventing OHSS in ART. Copyright © 2018 Elsevier Inc. All rights reserved.

Age-related differences in pulmonary inflammatory responses to JP-8 jet fuel aerosol inhalation.

PubMed

Wang, S; Young, R S; Witten, M L

2001-02-01

Our previous studies have demonstrated that JP-8 jet fuel aerosol inhalation induced lung injury and dysfunction. To further examine JP-8 jet fuel-induced inflammatory mechanisms, a total of 40 male C57BL/6 mice (young, 3.5 months; adult, 12 months; half in each age group) were randomly assigned to the exposure or control groups. Mice were nose-only exposed to room air or atmospheres of 1000 mg/m3 JP-8 jet fuel for 1 h/day for 7 days. Lung injury was assessed by pulmonary mechanics, respiratory permeability, lavaged cell profile, and chemical mediators in bronchoalveolar lavage fluid (BALF). The young and adult mice exposed to JP-8 jet fuel had similar values with regards to increased lung dynamic compliance, lung permeability, BALF cell count, and decreased PGE2. However, there were several different responses between the young-versus-adult mice with respect to BALF cell differential, TNF-alpha, and 8-iso-PGF2,, levels after exposure to JP-8 jet fuel. These data suggest that JP-8 jet fuel may have different inflammatory mechanisms leading to lung injury and dysfunction in the younger-versus-adult mice.

Reproductive performance of donor mares subsequent to eFSH treatment in early vernal transition: Comparison between the first, second, and mid-season estrous cycles of the breeding season.

PubMed

Raz, Tal; Hunter, Barbara; Carley, Sylvia; Card, Claire

2009-11-01

The objective was to compare the reproductive performances associated with the first (Cycle-1), second (Cycle-2), and mid-season (MS-Cycle) ovulations of the breeding season in donor mares that were treated with equine-FSH (eFSH) in the early vernal transition. Mares (n=15) kept under ambient light were examined ultrasonographically per-rectum starting January 30. When an ovarian follicle > or =25mm in diameter was detected, twice daily eFSH treatments were initiated. The eFSH treatments ceased when a follicle > or =35mm was detected, and 36h later hCG was administered. Thereafter, mares were artificially inseminated every 48h until ovulation (Day 0). Trans-cervical embryo recovery attempts were performed on Day 8, and subsequently PGF2alpha was administered. Equine FSH was not administered in the subsequent estrous cycles. In Cycle-2 and in the MS-Cycle, hCG was administered when a follicle > or =35mm was detected; breeding, embryo recovery, and PGF2alpha administration, were similar to Cycle-1. Mares had an untreated estrous cycle (no treatment or breeding) between Cycle-2 and the MS-Cycle. All mares developed follicle(s) > or =35mm after 4.9+/-0.6 days of eFSH treatment, and subsequently ovulations occurred; mean (95% CI) interval from treatment initiation to ovulation was 7.9 (6.5-9.3) days. The number of preovulatory follicles (> or =30mm) at the time of hCG administration (Cycle-1: 2.2+/-0.3 compared with Cycle-2: 1.0+/-0 compared with MS-Cycle: 1.1+/-0.1 follicles), and the number of ovulations (2.5+/-0.4 compared with 1.0+/-0 compared with 1.1+/-0.1 ovulations) were greater (p<0.05) in Cycle-1. Nevertheless, mean embryo numbers did not differ among cycles (0.8+/-0.2 compared with 0.5+/-0.1 compared with 0.5+/-0.1 embryo/mare). On average, embryo morphology grade was less (p<0.05) in Cycle-1 as compared to non-eFSH cycles (combined Cycle-2 and MS-Cycle). This impaired embryo quality could be due to a seasonal effect, or negative effect of the eFSH treatment, which was possibly related to alterations in the hormonal environment (estradiol-17beta and progesterone). A prolonged IOI (>21 days) was recorded in 7 of 15 mares following the Cycle-1 ovulation, but not subsequently. In conclusion, eFSH treatment of vernal transitional donor mares stimulated ovulation within only few days of treatment, and the following embryo recovery rate was at least as good as in the subsequent estrous cycles; however, on average, embryos were morphologically impaired. In subsequent estrous cycles in the breeding season, ovulations, embryo recovery rates, and embryo variables did not appear to be negatively affected; however, the first inter-ovulatory interval of the breeding season was prolonged in approximately half of the mares.

The effect of DDT and its metabolite (DDE) on prostaglandin secretion from epithelial cells and on contractions of the smooth muscle of the bovine oviduct in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wrobel, Michal H.; Mlynarczuk, Jaroslaw; Kotwica, Jan, E-mail: janko@pan.olsztyn.pl

2012-03-01

The insecticide DDT and its metabolite (DDE), due to their lipolytic nature and resistance to biodegradation, are accumulated in the living tissues. In cows, DDT and DDE were found to affect prostaglandin (PG) secretion from the endometrium and contractions of the myometrium. In this study, the impact of both xenobiotics (0.1, 1, 10 or 100 ng/ml) on the function of epithelial cells and muscle strips of bovine oviducts from 1 to 5 day of the oestrous cycle was examined. Therefore the concentration of PGE2 and PGFM (a metabolite of PGF2α) in culture media, mRNA expression of genes involved in PGsmore » synthesis in epithelial cells and the force and amplitude of strips contractions were measured after 2 and 24 or 48 h of incubation. Neither DDT nor DDE affected the viability of cells after 48 h (P > 0.05). Both DDT and DDE increased the concentrations of PGFM in culture medium and secretion of PGE2 after only 2 h of cell culture (P < 0.05). Similar effects were seen for the influence of DDE on amount of PGFM after 48 h, while DDT decreased secretion of PGE2 (P < 0.05). DDT after 2 h increased (P < 0.05) mRNA expression of PGF2α synthase (PGFS), while both xenobiotics decreased (P < 0.05) mRNA expression of cyclooxygenase-2 (COX-2) after 24 h. DTT also increased the force of isthmus contractions after 2 h, as did both xenobiotics after 48 h (P < 0.05). Moreover, after 2 and 48 h, DDE stimulated the amplitude of contractions of the isthmus as well as the ampulla, (P < 0.05). The effect of both compounds on oviduct contractions was diminished by indomethacin, which blocks PG synthesis. We conclude that oviductal secretion of prostaglandins is affected, by DDT and DDE. The influence of these xenobiotics on PGF2α and PGE2 secretion and ratio may be part of the mechanism by which both DDT and its metabolite disturb the contractions of oviductal muscle. -- Highlights: ► DDT and its metabolite – DDE are accumulated in the living tissues. ► The insecticides affected PGF2α and PGE2 release from epithelial cells of oviduct. ► They also stimulated markedly the contractions of oviductal strips. ► Prostaglandins were involved in the effect of insecticides on oviduct function.« less

Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor. alpha. : Relevance to genetic predisposition to systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacob, C.O.; Fronek, Z.; Koo, M.

1990-02-01

The authors report on the production of tumor necrosis factor (TNF)-{alpha} and TNF-{beta} by mitogen-activated peripheral blood lymphocytes or enriched monocyte subpopulations from human leukocyte antigen (HLA)-typed healthy subjects. The results indicate that HLA-DR2- and DQw1-positive donors frequently exhibit low production of TNF-{alpha}, whereas DR3- and DR4-positive subjects show high levels of TNF-{alpha} production. No correlation between TNF-{alpha} levels and HLA-A, -B, and -C genotype was found. The relevance of this quantitative polymorphism to the genetic predisposition to lupus nephritis in systemic lupus erythematosus (SLE) patients was investigated. DR2, DQw1-positive SLE patients show low levels of TNF-{alpha} inducibility; this genotypemore » is also associated with an increased incidence of lupus nephritis. DR3-positive SLE patients, on the other hand, are not predisposed to nephritis, and these patients have high TNF-{alpha} production. DR4 haplotype is associated with high TNF-{alpha} inducibility and is negatively correlated with lupus nephritis. These data may help explain the strong association between HLA-DR2, DQw1 in SLE patients and their susceptibility to nephritis.« less

The administration of exogenous prostaglandin may improve ovulation in pacu (Piaractus mesopotamicus).

PubMed

Criscuolo-Urbinati, E; Kuradomi, R Y; Urbinati, E C; Batlouni, S R

2012-12-01

Based on the reports of unsuccessful ovulation in pacu (Piaractus mesopotamicus) by fish farmers and researchers undertaking artificial reproduction programs, we evaluated the use of prostaglandin F (PGF) to improve pacu ovulation. This study was conducted during two spawning seasons (2009/2010 and 2010/2011) with two samplings in the first season and one sampling in the second season. A total of 45 females was sampled in this study. The control group was injected with carp pituitary extract (crude extract, 6 mg/kg), and the treatment group received PGF (2 mL per fish in the 2009/2010 season and 5 mL per fish in the 2010/2011 season) in addition to the crude extract. In both seasons, 100% (N = 4, 2009/2010 first sampling; N = 5, 2009/2010 second sampling; and N = 3, 2010/2011) of the PGF-treated fish spawned. In contrast, 53.0% (N = 9) and 83.3% (N = 10) of the control fish spawned in the first and second samplings of the 2009/2010 season, respectively, and only 25.0% (N = 1) spawned in the 2010/2011 season. Fecundity, fertility, and hatching rates did not differ (P > 0.05) between the treated and control fish. Based on oocyte volume frequency analysis, ovaries of the control fish had more (P < 0.05) vitellogenic oocytes with germinal vesicle breakdown that remained unovulated after spawning, whereas more (P < 0.05) of previtellogenic oocytes were present in the ovaries of the PGF-treated fish. In conclusion, administration of exogenous prostaglandin may improve the outcome of hormonally induced spawning in tropical migratory fish. Copyright © 2012 Elsevier Inc. All rights reserved.

Refractoriness of the gravid rat uterus to tocolytic and biochemical effects of atrial natriuretic peptide.

PubMed Central

Potvin, W.; Varma, D. R.

1990-01-01

1. Effects of atrial natriuretic peptide (ANP) on tension development, particulate guanylate cyclase activity and guanosine 3':5'-cyclic monophosphate (cyclic GMP) concentrations of uteri from oestrogen-treated, progesterone-treated, ovariectomized and pregnant rats were determined in vitro. 2. ANP inhibited the tension development by myometrial tissues from oestrogen-treated virgin rats and the sterile horn of 10 to 14 day pregnant rats but not of the uterus from pregnant and progesterone-treated rats. 3. Inhibition of cyclo-oxygenase and lipoxygenase activities did not restore the tocolytic activity of ANP on gravid uterus. ANP exerted a tocolytic effect on nongravid uterus submaximally stimulated by prostaglandin F2 alpha (PGF2 alpha), oxytocin, vasopressin, angiotensin II or 5-hydroxytryptamine (5-HT). 4. Ovariectomy decreased the tocolytic effects of ANP, which could be restored by oestrogen treatment. 5. The refractoriness to the tocolytic effect of ANP in pregnant rats was not accompanied by a decrease in its relaxant effects on isolated aortic strips. 6. Tocolytic effects of isoprenaline, isobutylmethyl xanthine and hydroxylamine were not influenced by pregnancy or progesterone treatment. Up to a concentration of 3 mM, sodium nitroprusside did not affect myometrial tension development. 7. Pregnancy and progesterone treatment markedly inhibited ANP-induced increases in myometrial particulate guanylate cyclase activity and cyclic GMP concentrations but did not influence the effects of ANP on aortic cyclic GMP concentrations. 8. It is concluded that exposure of the myometrium to circulating and placentally-produced progesterone is responsible for the pregnancy-induced decrease in the effects of ANP on myometrial particulate guanylate cyclase activity and cyclic GMP concentrations and in turn on myometrial tension development. PMID:1974161

Partial agonist clonidine mediates alpha(2)-AR subtypes specific regulation of cAMP accumulation in adenylyl cyclase II transfected DDT1-MF2 cells.

PubMed

Limon-Boulez, I; Bouet-Alard, R; Gettys, T W; Lanier, S M; Maltier, J P; Legrand, C

2001-02-01

alpha2-Adrenergic receptor (alpha(2)-AR) activation in the pregnant rat myometrium at midterm potentiates beta(2)-AR stimulation of adenylyl cyclase (AC) via Gbetagamma regulation of the type II isoform of adenylyl cyclase. However, at term, alpha(2)-AR activation inhibits beta(2)-AR stimulation of AC. This phenomenon is associated with changes in alpha(2)-AR subtype expression (midterm alpha(2A/D)-AR > alpha(2B)-AR; term alpha(2B) >or =alpha(2A/D)-AR), without any change in ACII mRNA, suggesting that alpha(2A/D)- and alpha(2B)-AR differentially regulate beta(2)-cAMP production. To address this issue, we have stably expressed the same density of alpha(2A/D)- or alpha(2B)-AR with AC II in DDT1-MF2 cells. Clonidine (partial agonist) increased beta(2)-AR-stimulated cAMP production in alpha(2A/D)-AR-ACII transfectants but inhibited it in alpha(2B)-AR-ACII transfectants. In contrast, epinephrine (full agonist) enhanced beta(2)-stimulated ACII in both alpha(2A)- and alpha(2B)-ACII clonal cell lines. 4-Azidoanilido-[alpha-(32)P]GTP-labeling of activated G proteins indicated that, in alpha(2B)-AR transfectants, clonidine activated only Gi(2), whereas epinephrine, the full agonist, effectively coupled to Gi(2) and Gi(3). Thus, partial and full agonists selectively activate G proteins that lead to drug specific effects on effectors. Moreover, these data indicate that Gi(3) activation is required for potentiation of beta(2)-AR stimulation of AC by alpha(2A/D) and alpha(2B)-AR in DDT1-MF2 cells. This may reflect an issue of the amount of Gbetagamma released upon receptor activation and/or betagamma composition of Gi(3) versus Gi(2).

Heat stress, the follicle, and its enclosed oocyte: mechanisms and potential strategies to improve fertility in dairy cows.

PubMed

Roth, Z

2008-07-01

Reduced reproductive performance of lactating cows during the summer is associated with decreased thermoregulatory competence due to intensive genetic selection for high milk production. This review examines the immediate and delayed effects of heat stress on follicular function and describes some potential strategies for their alleviation. It focuses on how heat stress affects the follicle and its enclosed oocyte, suggesting that perturbations in the follicular microenvironment, to which the oocytes are exposed for long periods of development, reduce their developmental competence. Among the potential alterations are reduction in gonadotropin secretion, alteration in follicular growth, attenuation of dominance, and disruption of steroidogenesis. Evaporative cooling methods are the most common strategy used to alleviate the effect of heat stress; however, there is a compelling need to find additional ways to improve fertility during the summer and autumn. Hormonal treatment to enhance removal of the impaired follicles by synchronization of follicular waves with GnRH and PGF2 alpha is suggested. An alternative method is stimulation of follicular growth by a brief treatment with bST or FSH. Other strategies, such as timed AI and embryo transfer, have been recently used, making the optimization of embryo cryopreservation procedures highly relevant. Protection of the ovarian pool of oocytes from thermal stress via nutritional manipulations or administration of antioxidants or other survival factors should also be considered. A better understanding of the underlying mechanisms by which heat stress impairs fertility may lead to the development of additional approaches to alleviate these effects.

Localization of TGF-β and TGF-β receptor in bovine term placentome and expression differences between spontaneous and induced parturition.

PubMed

Hirayama, Hiroki; Koyama, Keisuke; Sawai, Ken; Fujii, Takashi; Naito, Akira; Fukuda, Shigeo; Kageyama, Soichi

2015-11-01

Mechanisms of detachment of fetal membrane after parturition in cattle are poorly understood. Glucocorticoids trigger the initiation of parturition and may facilitate the placental maturation. We compared the disappearance of trophoblast binucleate cells (BNCs) and expression of transforming growth factor-β (TGFB) in term placentomes between spontaneous and induced parturition to investigate the influences of glucocorticoids on the placental maturity. Cows were delivered spontaneously (SP group) or after the administration of prostaglandin (PG) F(2)α (PG group); dexamethasone, PGF(2)α, and estriol (DEX group); and triamcinolone acetonide, PGF(2)α, and betamethasone (BET group) and placentomes were collected immediately after parturition. The number of BNCs in hematoxylin and eosin stained section was examined. Protein localization and mRNA levels of TGFB and its receptor (TGFBR) were analyzed using immunohistochemistry and qRT-PCR, respectively. TGFB1 is characteristically localized in the maternal septum in caruncle in contrast to TGFB2 and TGFB3, which are mainly found in cotyledonary villi and maternal epithelial cells. TGFBR1 and TGFBR2 colocalized in BNCs. The number of BNCs was lower in the SP group than in PG and DEX groups. mRNA levels of TGFB1, TGFBR1 and TGFBR2 in the SP group differed from PG and DEX groups. There was no difference between SP and BET groups in all analyses. These results indicate that parturition inductions using PGF(2)α or dexamethasone were not able to induce disappearance of BNCs and change of TGFB signaling. Results in the BET group suggest that investigation into types, dose, and dosage schedule of glucocorticoids may facilitate placental maturation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of the Plant Growth Facility for Use in the Shuttle Middeck and Test Units for Ground-Based Experiments

NASA Technical Reports Server (NTRS)

Chapman, David K.; Wells, H. William

1996-01-01

The plant growth facility (PGF), currently under development as a Space Shuttle middeck facility for the support of research on higher plants in microgravity, is presented. The PGF provides controlled fluorescent lighting and the active control of temperature, relative humidity and CO2 concentration. These parameters are designed to be centrally controlled by a dedicated microprocessor. The status of the experiment can be displayed for onboard analysis, and will be automatically archived for post-flight analysis. The facility is designed to operate for 15 days and will provide air filtration to remove ethylene and trace organics with replaceable potassium permanganate filters. Similar ground units will be available for pre-flight experimentation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, Thomas J.; Markillie, Lye MENG.

The thromboxane A{sub 2} (TXA{sub 2}) receptor (TP) is represented by two alternatively spliced forms, termed the platelet/placental (TP-P) and endothelial (TP-E) type receptors. Experimental evidence suggests that TP isoforms may be regulated by novel ligands termed the isoprostanes, which paradoxically act as TP agonists in smooth muscle and TP antagonists in platelet preparations. Here we have investigated whether prototypical isoprostanes (8-iso-PG{sub 2{sub {alpha}}} and 8-iso-PGE{sub 2}) regulate the activity of TP isoforms expressed in Chinese Hamster Ovary (CHO) cells using activator protein-1 (AP-1)-luciferase activity as a reporter. AP-1-luciferase activity was increased by a TP agonist (U46619) in CHO cellsmore » transfected with the human TP-P and TP-E receptors and this response was fully inhibited by TP antagonists (ISAP, SQ29,548). AP-1-luciferase activity was potently (nM) increased by 8-iso-PGE2 in CHO TP-P and TP-E cells, and this response was partially inhibited by cotreatment of cells with TP antagonists, while 8-iso-PGF{sub 2{sub {alpha}}} was without effect. Cyclooxygenase inhibitors did not abolish 8-iso-PGE{sub 2} mediated AP-1-luciferase activity, indicating that this response is not dependent on de novo TXA2 biosynthesis. Interestingly, 8-iso-PGE{sub 2}-mediated AP-1-luciferase activity was near maximal in naive cells between 1-10 nM concentrations, and this response was not inhibited by TP antagonist or reproduced by agonists for TP or EP1/EP3 receptors. These observations (1) support a role for novel ligands in the regulation of TP-dependent signaling, (2) indicate that TP-P and TP-E couple to AP-1, (3) provide further evidence that isoprostanes function as TP agonists in a cell-type specific fashion, and (4) indicate that additional targets regulated by 8-iso-PGE{sub 2} couple to AP-1.« less

Application of a statistical design to the optimization of parameters and culture medium for alpha-amylase production by Aspergillus oryzae CBS 819.72 grown on gruel (wheat grinding by-product).

PubMed

Kammoun, Radhouane; Naili, Belgacem; Bejar, Samir

2008-09-01

The production optimization of alpha-amylase (E.C.3.2.1.1) from Aspergillus oryzae CBS 819.72 fungus, using a by-product of wheat grinding (gruel) as sole carbon source, was performed with statistical methodology based on three experimental designs. The optimisation of temperature, agitation and inoculum size was attempted using a Box-Behnken design under the response surface methodology. The screening of nineteen nutrients for their influence on alpha-amylase production was achieved using a Plackett-Burman design. KH(2)PO(4), urea, glycerol, (NH(4))(2)SO(4), CoCl(2), casein hydrolysate, soybean meal hydrolysate, MgSO(4) were selected based on their positive influence on enzyme formation. The optimized nutrients concentration was obtained using a Taguchi experimental design and the analysis of the data predicts a theoretical increase in the alpha-amylase expression of 73.2% (from 40.1 to 151.1 U/ml). These conditions were validated experimentally and revealed an enhanced alpha-amylase yield of 72.7%.

Dose-response relationships of polycyclic aromatic hydrocarbons exposure and oxidative damage to DNA and lipid in coke oven workers.

PubMed

Kuang, Dan; Zhang, Wangzhen; Deng, Qifei; Zhang, Xiao; Huang, Kun; Guan, Lei; Hu, Die; Wu, Tangchun; Guo, Huan

2013-07-02

Polycyclic aromatic hydrocarbons (PAHs) are known to induce reactive oxygen species and oxidative stress, but the dose-response relationships between exposure to PAHs and oxidative stress levels have not been established. In this study, we recruited 1333 male coke oven workers, monitored the levels of environmental PAHs, and measured internal PAH exposure biomarkers including 12 urinary PAH metabolites and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, as well as the two oxidative biomarkers urinary 8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α). We found that the total concentration of urinary PAH metabolites and plasma BPDE-Alb adducts were both significantly associated with increased 8-OHdG and 8-iso-PGF2α in both smokers and nonsmokers (all p < 0.05). This exposure-response effect was also observed for most PAH metabolites (all p(trend) < 0.01), except for 4-hydroxyphenanthrene and 8-OHdG (p(trend) = 0.108). Furthermore, it was shown that only urinary 1-hydroxypyrene has a significant positive association with both 8-OHdG and 8-iso-PGF2α after a Bonferroni correction (p < 0.005). Our results indicated that urinary ΣOH-PAHs and plasma BPDE-Alb adducts can result in significant dose-related increases in oxidative damage to DNA and lipids. Furthermore, when a multianalyte method is unavailable, our findings demonstrate that urinary 1-hydroxypyrene is a useful biomarker for evaluating total PAHs exposure and assessing oxidative damage in coke oven workers.

Laboratory markers of mast cell and basophil activation in monitoring rush immunotherapy in bee venom-allergic children.

PubMed

Cichocka-Jarosz, Ewa; Dorynska, Agnieszka; Pietrzyk, Jacek J; Spiewak, Radoslaw

2011-08-01

To evaluate markers of mast cell and basophil activation in children undergoing the initial phase of honeybee venom immunotherapy (VIT). Five children (four boys and one girl) aged 9.5-18 years with severe systemic bee sting reactions and confirmed IgE-mediated allergy were enrolled. Plasma and urine concentrations of 9α,11β-PGF2 and serum tryptase levels were measured at four time points and peripheral blood basophil count and CD63 expression were measured at three time points in the course of VIT, including 5-day rush initial immunotherapy (cumulative dose of 223 µg of bee venom allergen) and two subsequent maintenance doses of 100 µg. In the first 40 days of VIT, there was a decrease in mean plasma levels of 9α,11β-PGF2 (from 41.5 to 27.9 pg/ml; p < 0.05), accompanied by an increase in baseline basophil activation (from 2 to 15%; p < 0.05). The median serum tryptase levels increased from 3.45 to 4.40 ng/ml during rush phase and subsequently returned to initial values (statistically not significant). In four patients, the basophil activation test in response to bee venom allergens remained positive throughout the study. The fifth patient was basophil activation test-negative at all three measurements, and a post hoc analysis revealed clinical peculiarities that are discussed in the paper. Our preliminary results indicate that plasma levels of 9α,11β-PGF2 decrease while numbers of activated basophils increase during the initial phase of bee venom rush immunotherapy in children.

Injectable caltrop fruit saponin protects against ischemia-reperfusion injury in rat brain.

PubMed

Yan, Ling-Geng; Lu, Yin; Zheng, Shi-Zhong; Wang, Ai-Yun; Li, Meng-Qiu; Ruan, Jun-Shan; Zhang, Lei

2011-01-01

The present study aimed to investigate the protective effects of injectable caltrop fruit saponin preparation (ICFSP) on ischemia-reperfusion injury in rat brain. Rats were injected with ICFSP and then subjected to cerebral ischemia-reperfusion injury induced by middle cerebral artery occlusion. Then the neurological deficit score was evaluated by Bederson's method. The infarct size was assessed by TTC staining. The content of malondialdehyde (MDA) and nitric oxide (NO), and the activity of superoxide dismutase (SOD) in rat cerebrum were measured with kits, and the content of 6 K prostaglandin F1α (6-K-PGF 1α), thromboxane B2 (TXB2) and endothelin (ET) in blood plasma was measured by radioimmunoassay. The results demonstrated that ICFSP led to a decrease in infarct size (p < 0.01), neurological deficit score (p < 0.05) and plasma content of TXB2 and ET (p < 0.05), and an increase of the plasma level of 6-K-PGF 1α (p < 0.05) and SOD activity in cerebrum, where the MDA and NO content were decreased. The treatment improved forelimb function. ICFSP showed a similar potency compared to that of Ligustrazine hydrochloride parenteral solution (LHPS) and nimodipine (Nim). We concluded that ICFSP protects the brain damage caused by ischemia-reperfusion injury in rats, and this may be closely related to the regulation of reactive oxygen species (MDA and SOD activity) and NO levels in the rat cerebrum, as well as vasoactive factors in the plasma (6-K-PGF 1α, TXB2 and ET).

Effects of Mountain Ultra-Marathon Running on ROS Production and Oxidative Damage by Micro-Invasive Analytic Techniques.

PubMed

Mrakic-Sposta, Simona; Gussoni, Maristella; Moretti, Sarah; Pratali, Lorenza; Giardini, Guido; Tacchini, Philippe; Dellanoce, Cinzia; Tonacci, Alessandro; Mastorci, Francesca; Borghini, Andrea; Montorsi, Michela; Vezzoli, Alessandra

2015-01-01

Aiming to gain a detailed insight into the physiological mechanisms involved under extreme conditions, a group of experienced ultra-marathon runners, performing the mountain Tor des Géants® ultra-marathon: 330 km trail-run in Valle d'Aosta, 24000 m of positive and negative elevation changes, was monitored. ROS production rate, antioxidant capacity, oxidative damage and inflammation markers were assessed, adopting micro-invasive analytic techniques. Forty-six male athletes (45.04±8.75 yr, 72.6±8.4 kg, 1.76±0.05 m) were tested. Capillary blood and urine were collected before (Pre-), in the middle (Middle-) and immediately after (Post-) Race. Samples were analyzed for: Reactive Oxygen Species (ROS) production by Electron Paramagnetic Resonance; Antioxidant Capacity by Electrochemistry; oxidative damage (8-hydroxy-2-deoxy Guanosine: 8-OH-dG; 8-isoprostane: 8-isoPGF2α) and nitric oxide metabolites by enzymatic assays; inflammatory biomarkers (plasma and urine interleukin-6: IL-6-P and IL-6-U) by enzyme-linked immunosorbent assays (ELISA); Creatinine and Neopterin by HPLC, hematologic (lactate, glucose and hematocrit) and urine parameters by standard analyses. Twenty-five athletes finished the race, while twenty-one dropped out of it. A significant increase (Post-Race vs Pre) of the ROS production rate (2.20±0.27 vs 1.65±0.22 μmol.min-1), oxidative damage biomarkers (8-OH-dG: 6.32±2.38 vs 4.16±1.25 ng.mg-1 Creatinine and 8-isoPGF2α: 1404.0±518.30 vs 822.51±448.91 pg.mg-1Creatinine), inflammatory state (IL-6-P: 66.42±36.92 vs 1.29±0.54 pg.mL-1 and IL-6-U: 1.33±0.56 vs 0.71±0.17 pg.mL1) and lactate production (+190%), associated with a decrease of both antioxidant capacity (-7%) and renal function (i.e. Creatinine level +76%) was found. The used micro-invasive analytic methods allowed us to perform most of them before, during and immediately after the race directly in the field, by passing the need of storing and transporting samples for further analysis. Considered altogether the investigated variables showed up that exhaustive and prolonged exercise not only promotes the generation of ROS but also induces oxidative stress, transient renal impairment and inflammation.

Abnormal TNF-alpha production in diabetes-prone BB rats: enhanced TNF-alpha expression and defective PGE2 feedback inhibition.

PubMed Central

Rothe, H; Ongören, C; Martin, S; Rösen, P; Kolb, H

1994-01-01

Upon stimulation with lipopolysaccharide (LPS), peritoneal macrophages from diabetes-prone Bio-Breeding (BB) rats secrete more tumour necrosis factor-alpha (TNF-alpha) than macrophages from diabetes-resistant BB or normal Wistar rats. Enhanced transcription was demonstrated by Northern blot analysis and at the single cell level by mRNA: RNA hybridization. Cytofluorometry analysis showed 2-4 times more plasma membrane and total cell-associated TNF-alpha in macrophages of diabetes-prone BB rats. The analysis of fluorescence intensity showed a single peak, and TNF-alpha mRNA was found in > 90% of macrophages. These findings exclude TNF hypersecretion as being due to an abnormal subfraction of cells. TNF-alpha gene hyperexpression in diabetes-prone BB rats was not due to mutations in the regulatory regions of the promoter, which could be shown by cloning and sequencing of the TNF-alpha promoter in the three rat strains. When searching for other regulatory defects we found the production of prostaglandin E2 (PGE2) in response to LPS to be up to 10 times lower in macrophages from diabetes-prone BB rats than from Wistar rats. Furthermore, BB rats macrophages required significantly higher concentrations of PGE2 for suppression of TNF-alpha secretion. We conclude that abnormal TNF-alpha production in macrophages from diabetes-prone BB rats is due to enhanced gene transcription and translation and that this is associated with defective PGE2 feedback inhibition. Images Figure 1 Figure 2 PMID:8206514

Traditional Chinese medicine Guizhi Fuling capsule used for therapy of dysmenorrhea via attenuating uterus contraction.

PubMed

Sun, Lan; Liu, Lina; Zong, Shaobo; Wang, Zhengzhong; Zhou, Jun; Xu, Zhiliang; Ding, Gang; Xiao, Wei; Kou, Junping

2016-09-15

Guizhi Fuling formula, a well-known Chinese herbal formula recorded in the Eastern Han Dynasty, is composed of Cinnamomum cassia (L.) J.Presl (Cassia bark), Poria cocos (Schw.) Wolf (Poria), Paeonia suffruticosa andrews (Moutan Cortex), Paeonia lactiflora Pall (Herbaceous peony), and Amygdalus persica L.(Persicae Semen). It has clinical efficacy of activating blood circulation to dissipate blood stasis and is commonly used for the treatment of primary dysmenorrhea. However, its therapeutic mechanism has not been clearly elucidated. The aim of this study is to reveal molecular mechanisms of action using in vivo and in vitro experimental models. The ICR mouse uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment. Mice were given GZFLC (0.54, 1.08g/kg) by gavage. The levels of NO, PGF2α and Ca(2+) in uterine tissue were determined according to instructions. Cyclooxygenase-2 (COX-2) and oxytocin receptor (OTR) proteins in uterine tissue were assessed by Western Blot. Mouse isolated uterus strips were mounted in tissue organ baths containing Locke's solution. The contractile responses were recorded with Power Lab recording system. The effect of GZFLC on spontaneous uterine contraction, and uterine contraction induced by oxytocin, PGF2α was observed. Myometrial cells were exposed to oxytocin (5U/L) to induce calcium release, and the effect of GZFLC and its components (PL, PGG, CA) on intracellular Ca(2+) was analyzed with fluorometry imaging. In vivo study demonstrated that GZFLC significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 55%. It also decreased the levels of NO, PGF2α and Ca(2+) in oxytocin-induced mice uterine tissue. Moreover, Western blot analysis showed that COX-2 and OTR expressions in uterine tissue of dysmenorrhea mice were significantly reduced. GZFLC inhibited spontaneous uterus contractions in a dose-dependent manner, and the IC50 value was 0.99mg/ml. The IC50 values of GZFLC on PGF2α, oxytocin-induced contractions were 1.45mg/ml, 3.53mg/ml, respectively. Further in vitro studies indicated that GZFLC and its components (PL, PGG, CA) could restrain intracellular calcium levels in favour of uteri relaxation. Both in vivo and in vitro results indicated that GZFLC possessed a significant spasmolytic effect on uterine tetanic contraction. The present study provides in vivo and in vitro experimental evidence to support the use of GZFLC for the clinical treatment of primary dysmenorrheal (PD). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Role of carbonic anhydrase in basal and stimulated bicarbonate secretion by the guinea pig duodenum.

PubMed

Muallem, R; Reimer, R; Odes, H S; Schwenk, M; Beil, W; Sewing, K F

1994-05-01

The role of carbonic anhydrase in the process of proximal duodenal mucosal bicarbonate secretion was investigated in the guinea pig. In a series of experiments in vivo, the duodenum was perfused with 24 mmol/liter NaHCO3 solution (+ NaCl for isotonicity) to ensure that active duodenal HCO3- secretion against a concentration gradient was measured. Acetazolamide (80 mg/kg) was infused intravenously to examine the role of carbonic anhydrase on basal and agonist-stimulated HCO3- secretion. Acetazolamide abolished basal HCO3- secretion and significantly decreased HCO3- secretion after stimulation with dibutyryl 5'-cyclic adenosine monophosphate (dBcAMP, 10(-5) mol/kg), dibutyryl 5'-cyclic guanosine monophosphate (dBcGMP, 10(-5) mol/kg), prostaglandin E2 (PGE2, 10(-6) mol/kg), PGF2 alpha (10(-6) mol/kg), tetradecanoyl-phorbol-acetate (TPA, 10(-7) mol/kg), glucagon (10(-7) mol/kg), vasoactive intestinal polypeptide (VIP, 10(-8) mol/kg), and carbachol (10(-8) mol/kg). Utilizing a fluorescence technique, we could detect the enzyme carbonic anhydrase in equal amounts in villous and crypt cells of the proximal duodenal epithelium; no activity was demonstrated in tissues pretreated with acetazolamide. In conclusion, carbonic anhydrase is required for both basal and stimulated duodenal HCO3- secretion.

Losartan reverses COX-2-dependent vascular dysfunction in offspring of hyperglycaemic rats.

PubMed

de Queiroz, Diego Barbosa; Ramos-Alves, Fernanda Elizabethe; Santos-Rocha, Juliana; Duarte, Gloria Pinto; Xavier, Fabiano Elias

2017-09-01

This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT 1 R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day -1 ) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements. COX-2 expression was analyzed by Western blot; TxA 2 , PGE 2 and PGF 2α release was measured using commercial kits. O-DR showed increased blood pressure, impaired acetylcholine-induced vasodilation and increased noradrenaline-induced vasoconstriction than O-CR. All these parameters were normalized by losartan in O-DR. Pre-incubation of MRA with indomethacin (COX-1/2 inhibitor), NS-398 (COX-2 inhibitor) or tempol (superoxide dismutase mimetic) increased relaxation to acetylcholine and reduced contraction to noradrenaline only in O-DR. COX-2 expression, TxA 2 , PGE 2 and PGF 2α release were increased in O-DR. In losartan-treated O-DR, NS-398, indomethacin or tempol failed to produce any effect on acetylcholine or noradrenaline responses. Losartan treatment reduced COX-2 expression, TxA 2 , PGE 2 and PGF 2α release in O-DR. The present results reveal that chronic losartan administration in O-DR normalizes endothelial function in MRA by correcting the existing COX-2 overexpression and the imbalance between endothelium-derived relaxing and contracting factors. These findings not only support the beneficial effects of AT 1 receptor antagonist in O-DR, but also suggest the implication of angiotensin II as a putative mediator of hyperglycemia-programmed vascular dysfunction in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Fertility after implementation of long- and short-term progesterone-based ovulation synchronization protocols for fixed-time artificial insemination in beef heifers.

PubMed

Kasimanickam, R; Schroeder, S; Hall, J B; Whittier, W D

2015-04-15

Two experiments were conducted to evaluate the effect of long-term (LT; a 14-day controlled internal drug release insert [CIDR]-PGF2α [PGF]-GnRH) and short-term (ST; 5-day CO-Synch + CIDR) progesterone-based protocols on pregnancy rate to fixed-time artificial insemination (FTAI) in beef heifers. In experiment 1, Angus cross beef heifers (N = 1887) at nine locations received a body condition score and a reproductive tract score (RTS). Within the herd, heifers were randomly assigned to LT-72 and ST-56 protocol groups. Heifers in the LT-72 group received a CIDR from Days 0 to 14, followed by 25 mg of PGF 16 days later (Day 30). Heifers in the ST-56 group received a CIDR and 100 μg of gonadorelin hydrochloride (GnRH) on Day 25 followed by 25 mg of PGF at CIDR removal on Day 30 and a second dose of PGF 6 hours later (Day 30). Artificial insemination was performed at 56 hours (Day 32) after CIDR removal for the ST-56 group and at 72 hours (Day 33) after CIDR removal for the LT-72 group, and all heifers were given GnRH (100 μg, intramuscular) at the time of AI. In experiment 2, Angus cross beef heifers (N = 718) at four locations received a body condition score and an RTS. Within the herd, heifers were randomly assigned to LT-72 and ST-72 protocol groups. The protocol was similar to experiment 1 except that AI was performed at 72 hours after CIDR removal for both LT-72 and ST-72 groups. In experiment 1, no difference in AI pregnancy rates between the LT-72 and ST-56 groups was observed (54.5% [489 of 897] and 55.5% [549 of 990], respectively; P = 0.92) after accounting for the RTS. The AI pregnancy rates for heifers with RTS 3 or less, 4, and 5 were 52.6%, 53.6%, and 59.9%, respectively (P < 0.05). In experiment 2, controlling for the RTS, no difference in AI pregnancy rates was observed between the LT-72 and ST-72 groups, 56.9% (198 of 347) and 57.8% (214 of 371), respectively (P = 0.87). The AI pregnancy rates for heifers with RTS 3 or less, 4, and 5 were 49.3%, 58.4%, and 62.1%, respectively (P < 0.05). In conclusion, heifers synchronized for fixed-time AI with LT and ST protocols resulted in a similar AI pregnancy rate. Approximately, 55% of the herd was pregnant to one insemination in 33 days with the LT protocol compared with just 8 days with the ST protocol. Copyright © 2015 Elsevier Inc. All rights reserved.

The Elsevier trophoblast research award lecture: Impacts of placental growth factor and preeclampsia on brain development, behaviour, and cognition.

PubMed

Rätsep, Matthew T; Hickman, Andrew F; Croy, B Anne

2016-12-01

Preeclampsia (PE) is a significant gestational disorder affecting 3-5% of all human pregnancies. In many PE pregnancies, maternal plasma is deficient in placental growth factor (PGF), a placentally-produced angiokine. Beyond immediate fetal risks associated with acute termination of the pregnancy, offspring of PE pregnancies (PE-F1) have higher long-term risks for hypertension, stroke, and cognitive impairment compared to F1s from uncomplicated pregnancies. At present, mechanisms that explain PE-F1 gains in postpartum risks are poorly understood. Our laboratory found that mice genetically-deleted for Pgf have altered fetal and adult brain vascular development. This is accompanied by sexually dimorphic alterations in anatomic structure in the adult Pgf -/- brain and impaired cognitive functions. We hypothesize that cerebrovascular and neurological aberrations occur in fetuses exposed to the progressive development of PE and that these brain changes impair cognitive functioning, enhance risk for stroke, elevate severity of stroke, and lead to worse stroke outcomes. These brain and placental outcomes may be linked to down-regulated PGF gene expression in early pre-implantation embryos, prior to gastrulation. This review explores our hypothesis that there are mechanistic links between low PGF detection in maternal plasma prodromal to PE, PE, and altered brain vascular, structural, and functional development amongst PE-F1s. We also include a summary of preliminary outcomes from a pilot study of 7-10 year old children that is the first to report magnetic resonance imaging, magnetic resonance angiography, and functional brain region assessment by eye movement control studies in PE-F1s. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation and characterization of PVDF-glass fiber composite membrane reinforced by interfacial UV-grafting copolymerization.

PubMed

Luo, Nan; Xu, Rongle; Yang, Min; Yuan, Xing; Zhong, Hui; Fan, Yaobo

2015-12-01

A novel inorganic-organic composite membrane, namely poly(vinylidene fluoride) PVDF-glass fiber (PGF) composite membrane, was prepared and reinforced by interfacial ultraviolet (UV)-grafting copolymerization to improve the interfacial bonding strength between the membrane layer and the glass fiber. The interfacial polymerization between inorganic-organic interfaces is a chemical cross-linking reaction that depends on the functionalized glass fiber with silane coupling (KH570) as the initiator and the polymer solution with acrylamide monomer (AM) as the grafting block. The Fourier transform infrared spectrometer-attenuated total reflectance (FTIR-ATR) spectra and the energy dispersive X-ray (EDX) pictures of the interface between the glass fiber and polymer matrix confirmed that the AM was grafted to the surface of the glass fiber fabric and that the grafting polymer was successfully embedded in the membrane matrix. The formation mechanisms, permeation, and anti-fouling performance of the PGF composite membrane were measured with different amounts of AM in the doping solutions. The results showed that the grafting composite membrane improved the interfacial bonding strength and permeability, and the peeling strength was improved by 32.6% for PGF composite membranes with an AM concentration at 2wt.%. Copyright © 2015. Published by Elsevier B.V.

The Structure of a Quasi-Keplerian Accretion Disk around Magnetized Stars

NASA Astrophysics Data System (ADS)

Habumugisha, Isaac; Jurua, Edward; Tessema, Solomon B.; Simon, Anguma K.

2018-06-01

In this paper, we present the complete structure of a quasi-Keplerian thin accretion disk with an internal dynamo around a magnetized neutron star. We assume a full quasi-Keplerian disk with the azimuthal velocity deviating from the Keplerian fashion by a factor of ξ (0 < ξ < 2). In our approach, we vertically integrate the radial component of the momentum equation to obtain the radial pressure gradient equation for a thin quasi-Keplerian accretion disk. Our results show that, at large radial distance, the accretion disk behaves in a Keplerian fashion. However, close to the neutron star, pressure gradient force (PGF) largely modifies the disk structure, resulting into sudden dynamical changes in the accretion disk. The corotation radius is shifted inward (outward) for ξ > 1 (for ξ < 1), and the position of the inner edge with respect to the new corotation radius is also relocated accordingly, as compared to the Keplerian model. The resulting PGF torque couples with viscous torque (when ξ < 1) to provide a spin-down torque and a spin-up torque (when ξ > 1) while in the advective state. Therefore, neglecting the PGF, as has been the case in previous models, is a glaring omission. Our result has the potential to explain the observable dynamic consequences of accretion disks around magnetized neutron stars.

Effects of a single bout of strenuous exercise on platelet activation in female ApoE/LDLR-/- mice.

PubMed

Przyborowski, K; Kassassir, H; Wojewoda, M; Kmiecik, K; Sitek, B; Siewiera, K; Zakrzewska, A; Rudolf, A M; Kostogrys, R; Watala, C; Zoladz, J A; Chlopicki, S

2017-11-01

Strenuous physical exercise leads to platelet activation that is normally counterbalanced by the production of endothelium-derived anti-platelet mediators, including prostacyclin (PGI 2 ) and nitric oxide (NO). However, in the case of endothelial dysfunction, e.g. in atherosclerosis, there exists an increased risk for intravascular thrombosis during exercise that might be due to an impairment in endothelial anti-platelet mechanisms. In the present work, we evaluated platelet activation at rest and following a single bout of strenuous treadmill exercise in female ApoE/LDLR - /- mice with early (3-month-old) and advanced (7-month-old) atherosclerosis compared to female age-matched WT mice. In sedentary and post-exercise groups of animals, we analyzed TXB 2 generation and the expression of platelet activation markers in the whole blood ex vivo assay. We also measured pre- and post-exercise plasma concentration of 6-keto-PGF 1α , nitrite/nitrate, lipid profile, and blood cell count. Sedentary 3- and 7-month-old ApoE/LDLR - /- mice displayed significantly higher activation of platelets compared to age-matched wild-type (WT) mice, as evidenced by increased TXB 2 production, expression of P-selectin, and activation of GPIIb/IIIa receptors, as well as increased fibrinogen and von Willebrand factor (vWf) binding. Interestingly, in ApoE/LDLR - /- but not in WT mice, strenuous exercise partially inhibited TXB 2 production, the expression of activated GPIIb/IIIa receptors, and fibrinogen binding, with no effect on the P-selectin expression and vWf binding. Post-exercise down-regulation of the activated GPIIb/IIIa receptor expression and fibrinogen binding was not significantly different between 3- and 7-month-old ApoE/LDLR - /- mice; however, only 7-month-old ApoE/LDLR - /- mice showed lower TXB 2 production after exercise. In female 4-6-month-old ApoE/LDLR - /- but not in WT mice, an elevated pre- and post-exercise plasma concentration of 6-keto-PGF 1α was observed. In turn, the pre- and post-exercise plasma concentrations of nitrite (NO 2 - ) and nitrate (NO 3 - ) were decreased in ApoE/LDLR - /- as compared to that in age-matched WT mice. In conclusion, we demonstrated overactivation of platelets in ApoE/LDLR - /- as compared to WT mice. However, platelet activation in ApoE/LDLR - /- mice was not further increased by strenuous exercise, but was instead attenuated, a phenomenon not observed in WT mice. This phenomenon could be linked to compensatory up-regulation of PGI 2 -dependent anti-platelet mechanisms in ApoE/LDLR - /- mice.

Systemic production of IFN-alpha by garlic (Allium sativum) in humans.

PubMed

Bhattacharyya, Mau; Girish, G V; Karmohapatra, Soumendra K; Samad, S A; Sinha, Asru K

2007-05-01

The effect of foods on the production of interferon-alpha (IFN-alpha) is currently unknown. Garlic (Allium sativum) used as a folk medicine is reported to stimulate nitric oxide (NO) production. We investigated the systemic increase of NO due to the ingestion of garlic on the plasma IFN-alpha level in normal volunteers. Normal volunteers (10 groups, 10 in each group) ate 2 g fresh garlic, and plasma NO and IFN-alpha levels were determined after 2 and 4 h. The participants were also asked to eat garlic for various periods of time, and plasma NO and IFN-alpha were similarly assayed. Ingestion of 2 g fresh, but not boiled, garlic was found to increase the basal plasma level of NO from 2.7 +/- 0.1 microM to 8.76 +/- 0.21 microM at 2 and 4 h, respectively. The basal plasma IFN-alpha level increased from 9.51 +/- 0.26 nM to 46.3 +/- 1.2 nM in normal volunteers (n = 10) at the same time. The chronic eating of garlic was found to maintain IFN-alpha at high levels for at least 7 days. The exposure of neutrophils to garlic in vivo or in vitro, which also stimulated synthesis of NO in these cells, was found to stimulate IFN-alpha synthesis as measured by the stimulation of IFN-alpha mRNA synthesis. Thus, consumption of garlic resulted in stimulated synthesis of NO and, in turn, IFN-alpha in humans, which could be beneficial in viral or proliferative diseases.

Des-aspartate-angiotensin I causes specific release of PGE2 and PGI2 in HUVEC via the angiotensin AT1 receptor and biased agonism.

PubMed

Wen, Qiang; Lee, Kok-Onn; Sim, Sai-Zhen; Xu, Xiao-Guang; Sim, Meng-Kwoon

2015-12-05

DAA-I (des-aspartate-angiotensin I), an endogenous angiotensin, had been shown earlier to ameliorate animal models of cardiovascular diseases via the angiotensin AT1 receptor and prostaglandins. The present study investigated further the action of DAA-I on the release of PGE2, PGI2, PGF2α and TXA2 in HUVEC. 10(-11)-10(-8)M DAA-I and 15min incubation specifically released PGE2 and PGI2. The release was inhibited by losartan and indomethacin but not by PD123319 and NS398 indicating that the angiotensin AT1 receptor and COX-1 mediate the release. At concentrations higher than 10(-7)M, DAA-I mimics the action of angiotensin II by releasing TXA2 but had no effect on the production of PGF2α. At similar concentrations and 4h incubation, DAA-I increased the release of the 4 prostaglandins via the angiotensin AT1 receptor and COX-2, again mimicking the action of angiotensin II. HUVEC that were preincubated with DAA-I or angiotensin II, released similar profiles of prostaglandins when incubated with arachidonic acid after the angiotensin had been washed off. We postulate that the internalized DAA-I/receptor complex remains active and mediates the conversion of arachidonic acid to the respective prostaglandins. The release of PGE2 and PGI2 via the angiotensin AT1 receptor and COX-1 is a novel specific action of DAA-I and is likely responsible for its beneficial effects seen in earlier studies. This specific action is definable as a biased agonism of the angiotensin AT1 receptor, which identifies DAA-I as a novel biased agonist and potential therapeutic that is able to produce specific prostaglandins at nanomolar concentrations. Copyright © 2015 Elsevier B.V. All rights reserved.

Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice

PubMed Central

1991-01-01

Antigens and infectious agents that stimulate interferon alpha(IFN- alpha) production in mice induce antibody responses that are predominantly of the immunoglobulin (Ig)G2a isotype and contain little or no IgE. This suggested the possibility that IFN-alpha might have a role in directing Ig isotype selection. Consistent with this possibility, we have found that injection of mice with recombinant mouse IFN-alpha suppresses IgE secretion, enhances IgG2a secretion, and has no independent effect on IgG1 secretion in mice stimulated with a foreign anti-IgD antibody. Injection of mice with polyinosinic acid.polycytidylic acid (poly I.C), an inducer of macrophage IFN-alpha production, also suppresses the anti-IgD antibody-induced IgE response and stimulates the IgG2a response; these effects are blocked by a sheep antibody that neutralizes mouse IFN-alpha/beta. Both recombinant IFN- alpha and poly I.C have maximum IgE suppressive and IgG2a stimulatory effects when injected early in the anti-IgD antibody-induced immune response. Addition of IFN-alpha to mouse B cells cultured with lipopolysaccharide (LPS) + interleukin 4 (IL-4) suppresses both IgG1 and IgE production, but much less potently than IFN-gamma. IFN-alpha suppresses anti-IgD antibody-induced increases in the level of splenic IL-4 mRNA, but enhances the anti-IgD antibody-induced increase in the splenic level of IFN-gamma mRNA. These results are consistent with the effect of IFN-alpha on Ig isotype expression in mice, as IL-4 stimulates IgE and suppresses IgG2a secretion while IFN-gamma exerts opposite effects. These observations suggest that antigen presenting cells, by secreting IFN-alpha early in the course of an immune response, can influence the nature of that response both through direct effects on B cells and by influencing the differentiation of T cells. PMID:1940796

N-acetylcysteine attenuates TNF-alpha-induced human vascular endothelial cell apoptosis and restores eNOS expression.

PubMed

Xia, Zhengyuan; Liu, Min; Wu, Yong; Sharma, Vijay; Luo, Tao; Ouyang, Jingping; McNeill, John H

2006-11-21

The circulatory inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is increased in pathological conditions, such as diabetes, which initiate or exacerbate vascular endothelial injury. Both nitric oxide (NO) and reactive oxygen species may play a dual role (i.e., inhibiting or promoting) in TNF-alpha-induced endothelial cell apoptosis. We investigated the effects of the antioxidant N-acetylcysteine on TNF-alpha-induced apoptosis in human vascular endothelial cell (cell line ECV304) apoptosis, NO production and lipid peroxidation. Cultured vascular endothelial cell (ECV304) were either not treated (control), or treated with TNF-alpha (40 ng/ml) alone or TNF-alpha in the presence of N-acetylcysteine at 30 mmol/l or 1 mmol/l, respectively, for 24 h. Cell viability was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Cell apoptosis was assessed by flow cytometry. TNF-alpha-induced endothelial cell apoptosis was associated with increased inducible NO synthase but reduced endothelial NO synthase (eNOS) protein expression. NO production and the levels of the lipid peroxidation product malondialdehyde were concomitantly increased. Treatment with NAC at 30 mmol/l restored eNOS expression and further increased NO production as compared to TNF-alpha alone, resulting in improved cell viability and reduced apoptosis. This was accompanied by increased superoxide dismutase activity, increased glutathione peroxidase production and reduced malondialdehyde levels. N-acetylcysteine at 1 mmol/l, however, did not have significant effects on TNF-alpha-induced endothelial cell apoptosis and cell viability despite it slightly enhanced glutathione peroxidase production. N-acetylcysteine attenuation of TNF-alpha-induced human vascular endothelial cell apoptosis is associated with the restoration of eNOS expression.

Pregnancy rates for embryos transferred from early postpartum beef cows into recipients with normal estrous cycles.

PubMed

Schrick, F N; Inskeep, E K; Butcher, R L

1993-09-01

Survival rate of embryos from first ovulations of postpartum cows with SHORT (6.9 +/- 0.3 days; n = 35) or NORMAL (17.1 +/- 0.3 days; n = 42) luteal phases and quality of the embryos on Day 6 were compared. At 19 to 23 days postpartum, cows were allotted to receive a norgestomet implant for 9 days (normal luteal phase) or to serve as untreated controls (short luteal phase). Calves were weaned 7 days after initiation of treatment to induce behavioral estrus in cows for mating. In 25 cows, growth of the ovulatory follicle was monitored by ultrasonography. On Day 6 after estrus, embryos were recovered nonsurgically, and live embryos were transferred into recipient cows exhibiting normal estrous cycles. The medium used to flush the embryos from the uterus of each donor cow was assayed for prostaglandin F2 alpha (PGF2 alpha). Days from calf removal to estrus and size of ovulatory follicles at ovulation (4.1 +/- 0.3 days and 16.7 +/- 0.7 mm, respectively) did not differ between NORMAL and SHORT cows. Interval from detection of the ovulatory follicle to ovulation was longer in NORMAL (10 +/- 0.7 days) than in SHORT cows (8 +/- 0.6 days; p < 0.05). Rates of recovery of an embryo or ovum (64%), rates of fertilization (65%), and quality or stage of development of Day 6 embryos did not differ between SHORT and NORMAL cows. Overall pregnancy rate from recovered oocytes was 13% for SHORT and 32% for NORMAL cows (p = 0.06); survival of fertilized oocytes was 23% for SHORT and 47% for NORMAL cows (p = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of H(2)O(2) generation by calcium in brain mitochondria respiring on alpha-glycerophosphate.

PubMed

Tretter, Laszlo; Takacs, Katalin; Kövér, Kinga; Adam-Vizi, Vera

2007-11-15

It has been reported recently (Tretter et al., 2007b) that in isolated guinea pig brain mitochondria supported by alpha-glycerophosphate (alpha-GP) reactive oxygen species (ROS) are produced through the reverse electron transport (RET) in the respiratory chain and by alpha-glycerophosphate dehydrogenase (alpha-GPDH). We studied the effect of calcium on the generation of H(2)O(2) as measured by the Amplex Red fluorescent assay in this model. H(2)O(2) production in alpha-GP-supported mitochondria was increased significantly in the presence of 100, 250, and 500 nM Ca(2+), respectively. In addition, Ca(2+) enhanced the membrane potential, the rate of oxygen consumption, and the NAD(P)H autofluorescence in these mitochondria. Direct measurement of alpha-GPDH activity showed that Ca(2+) stimulated the enzyme by decreasing the Km for alpha-GP. In those mitochondria where RET was eliminated by the Complex I inhibitor rotenone (2 microM) or due to depolarization by ADP (1 mM), the rate of H(2)O(2) formation was smaller and the stimulation of H(2)O(2) generation by Ca(2+) was prevented partly, but the stimulatory effect of Ca(2+) was still significant. These data indicate that in alpha-GP-supported mitochondria activation of alpha-GPDH by Ca(2+) leads to an accelerated RET-mediated ROS generation as well as to a stimulated ROS production by alpha-GPDH.

Dark chocolate inhibits platelet isoprostanes via NOX2 down-regulation in smokers.

PubMed

Carnevale, R; Loffredo, L; Pignatelli, P; Nocella, C; Bartimoccia, S; Di Santo, S; Martino, F; Catasca, E; Perri, L; Violi, Francesco

2012-01-01

Dark chocolate is reported to decrease platelet activation but the underlying mechanism is still undefined. Dark chocolate is rich in polyphenols that could exert an antiplatelet action via inhibition of oxidative stress. The aim of the present study was to assess if dark chocolate inhibits platelet reactive oxidant species (ROS) formation and platelet activation. Twenty healthy subjects (HS) and 20 smokers were randomly allocated to receive 40 g of dark (cocoa > 85%) or milk chocolate (cocoa < 35%) in a cross-over, single-blind study. There was an interval of 7 days between the two phases of the study. At baseline and 2 h after chocolate ingestion, platelet recruitment (PR), platelet ROS, platelet isoprostane 8-ISO-prostaglandin F2α (8-iso-PGF2α), Thromboxane (TxA2) and platelet activation of NOX2, the catalytic sub-unit of NADPH oxidase, and serum epicatechin were measured. Compared with HS, smokers showed enhanced PR, platelet formation of ROS and eicosanoids and NOX2 activation. After dark chocolate, platelet ROS (-48%, P < 0.001), 8-iso-PGF2α (-10%, P < 0.001) and NOX2 activation (-22%, P < 0.001) significantly decreased; dark chocolate did not affect platelet variables in HS. No effect of milk chocolate was detected in both groups. Serum epicatechin increased after dark chocolate in HS (from 0.454 ± 0.3 nm to 118.3 ± 53.7 nm) and smokers (from 0.5 ± 0.28 nm to 120.9 ± 54.2 nm). Platelet incubation with 0.1-10 μm catechin significantly reduced PR, platelet 8-iso-PGF2α and ROS formation and NOX2 activation only in platelets from smokers. Dark chocolate inhibits platelet function by lowering oxidative stress only in smokers; this effect seems to be dependent on its polyphenolic content. © 2011 International Society on Thrombosis and Haemostasis.

The role of adrenergic activation on murine luteal cell viability and progesterone production.

PubMed

Wang, Jing; Tang, Min; Jiang, Huaide; Wu, Bing; Cai, Wei; Hu, Chuan; Bao, Riqiang; Dong, Qiming; Xiao, Li; Li, Gang; Zhang, Chunping

2016-09-15

Sympathetic innervations exist in mammalian CL. The action of catecholaminergic system on luteal cells has been the focus of a variety of studies. Norepinephrine (NE) increased progesterone secretion of cattle luteal cells by activating β-adrenoceptors. In this study, murine luteal cells were treated with NE and isoprenaline (ISO). We found that NE increased the viability of murine luteal cells and ISO decreased the viability of luteal cells. Both NE and ISO promoted the progesterone production. Nonselective β-adrenergic antagonist, propranolol reversed the effect of ISO on cell viability but did not reverse the effect of NE on cell viability. Propranolol blocked the influence of NE and ISO on progesterone production. These results reveal that the increase of luteal cell viability induced by NE is not dependent on β-adrenergic activation. α-Adrenergic activation possibly contributes to it. Both NE and ISO increased progesterone production through activating β-adrenergic receptor. Further study showed that CyclinD2 is involved in the increase of luteal cell induced by NE. 3β-Hydroxysteroid dehydrogenase, LHR, steroidogenic acute regulatory protein (StAR), and PGF2α contribute to the progesterone production induced by NE and ISO. Copyright © 2016 Elsevier Inc. All rights reserved.

The relationship between work ability and oxidative stress in Japanese workers.

PubMed

Ohta, Masanori; Kumashiro, Masaharu; Eguchi, Yasumasa; Morita, Yusaku; Konno, Yoshimasa; Yamato, Hiroshi

2014-01-01

Work ability is based on the balance between personal resources and work demand. This study focused on the personal resources component of work ability. The aims of this study were to elucidate the association between work ability and cardiovascular (CV) risk factors, particularly oxidative stress, and to estimate the effect of a community-implemented lifestyle modification programme on work ability and CV risk factors. Urinary 8-iso-prostaglandin F2α (PGF2α), a biomarker of oxidative stress, was negatively correlated with psychological resources, as measured by the Work Ability Index (WAI). Overall WAI score was unchanged following the programme, while CV risk factors and antioxidative activity improved. A reduction in PGF2α levels was correlated with an improvement in subjective work ability relative to job demands, as assessed by a WAI item. Taken together, the results suggest that lifestyle modification programmes enhance the personal resources component of work ability and are associated with a reduction in oxidative stress.

Regulation of tumour necrosis factor production by adrenal hormones in vivo: insights into the antiinflammatory activity of rolipram.

PubMed Central

Pettipher, E. R.; Labasi, J. M.; Salter, E. D.; Stam, E. J.; Cheng, J. B.; Griffiths, R. J.

1996-01-01

1. The role of adrenal hormones in the regulation of the systemic and local production of tumour necrosis factor (TNF alpha) was examined in male Balb/c mice. 2. Intraperitoneal injection of 0.3 mg E. coli lipopolysaccharide (LPS, 0111:B4) led to high levels of circulating TNF alpha without stimulating TNF alpha production in the peritoneal cavity. Systemic production of TNF alpha in response to LPS was increased in adrenalectomized animals and in normal animals treated with the beta-adrenoceptor antagonist, propranolol. The glucocorticoid antagonist, RU 486, did not modify systemic TNF alpha production. These results indicate that systemic TNF alpha production is regulated by adrenaline but not by corticosterone. 3. When mice were primed with thioglycollate, TNF alpha was produced in the peritoneal cavity in response to low dose LPS (1 micrograms). The levels of TNF alpha in the peritoneal cavity were not enhanced by adrenalectomy or by treatment with either propranolol or RU 486, indicating local production of TNF alpha in the peritoneal cavity is not regulated by adrenaline or corticosterone. 4. The phosphodiesterase type IV (PDE-IV) inhibitor, rolipram, inhibited both the systemic production of TNF alpha in response to high dose endotoxin (ED50 = 1.3 mg kg-1) and the local production of TNF alpha in the peritoneal cavity in response to low dose endotoxin (ED50 = 9.1 mg kg-1). In adrenalectomized mice there was a slight reduction in the ability of rolipram to inhibit the systemic production of TNF alpha (ED50 = 3.3 mg kg-1) while the ability of rolipram to inhibit the local production of TNF alpha in the peritoneal cavity was virtually abolished (24% inhibition at 30 mg kg-1). The glucocorticoid antagonist, RU 486, also reduced the ability of rolipram to inhibit local TNF alpha production while propranolol was without effect. 5. Systemic treatment with rolipram increased the plasma concentrations of corticosterone in normal mice but not in adrenalectomized mice indicating that rolipram can cause adrenal stimulation in vivo. 6. In summary, these data indicate that systemic production of TNF alpha in response to high dose endotoxin is controlled differently from the local production of TNF alpha in response to low dose endotoxin. The systemic production of TNF alpha is regulated by catecholamines, but not by corticosterone, while the local production of TNF alpha in the peritoneal cavity is not regulated by basal levels of either catecholamines or corticosterone. 7. These data also show that the ability of rolipram to inhibit the local production of TNF alpha is dependent on the release of corticosterone from the adrenal glands. PMID:8730750

Regulation of tumour necrosis factor production by adrenal hormones in vivo: insights into the antiinflammatory activity of rolipram.

PubMed

Pettipher, E R; Labasi, J M; Salter, E D; Stam, E J; Cheng, J B; Griffiths, R J

1996-04-01

1. The role of adrenal hormones in the regulation of the systemic and local production of tumour necrosis factor (TNF alpha) was examined in male Balb/c mice. 2. Intraperitoneal injection of 0.3 mg E. coli lipopolysaccharide (LPS, 0111:B4) led to high levels of circulating TNF alpha without stimulating TNF alpha production in the peritoneal cavity. Systemic production of TNF alpha in response to LPS was increased in adrenalectomized animals and in normal animals treated with the beta-adrenoceptor antagonist, propranolol. The glucocorticoid antagonist, RU 486, did not modify systemic TNF alpha production. These results indicate that systemic TNF alpha production is regulated by adrenaline but not by corticosterone. 3. When mice were primed with thioglycollate, TNF alpha was produced in the peritoneal cavity in response to low dose LPS (1 micrograms). The levels of TNF alpha in the peritoneal cavity were not enhanced by adrenalectomy or by treatment with either propranolol or RU 486, indicating local production of TNF alpha in the peritoneal cavity is not regulated by adrenaline or corticosterone. 4. The phosphodiesterase type IV (PDE-IV) inhibitor, rolipram, inhibited both the systemic production of TNF alpha in response to high dose endotoxin (ED50 = 1.3 mg kg-1) and the local production of TNF alpha in the peritoneal cavity in response to low dose endotoxin (ED50 = 9.1 mg kg-1). In adrenalectomized mice there was a slight reduction in the ability of rolipram to inhibit the systemic production of TNF alpha (ED50 = 3.3 mg kg-1) while the ability of rolipram to inhibit the local production of TNF alpha in the peritoneal cavity was virtually abolished (24% inhibition at 30 mg kg-1). The glucocorticoid antagonist, RU 486, also reduced the ability of rolipram to inhibit local TNF alpha production while propranolol was without effect. 5. Systemic treatment with rolipram increased the plasma concentrations of corticosterone in normal mice but not in adrenalectomized mice indicating that rolipram can cause adrenal stimulation in vivo. 6. In summary, these data indicate that systemic production of TNF alpha in response to high dose endotoxin is controlled differently from the local production of TNF alpha in response to low dose endotoxin. The systemic production of TNF alpha is regulated by catecholamines, but not by corticosterone, while the local production of TNF alpha in the peritoneal cavity is not regulated by basal levels of either catecholamines or corticosterone. 7. These data also show that the ability of rolipram to inhibit the local production of TNF alpha is dependent on the release of corticosterone from the adrenal glands.

Fast-adapting mechanoreceptors are important for force control in precision grip but not for sensorimotor memory.

PubMed

Park, Susanna B; Davare, Marco; Falla, Marika; Kennedy, William R; Selim, Mona M; Wendelschafer-Crabb, Gwen; Koltzenburg, Martin

2016-06-01

Sensory feedback from cutaneous mechanoreceptors in the fingertips is important in effective object manipulation, allowing appropriate scaling of grip and load forces during precision grip. However, the role of mechanoreceptor subtypes in these tasks remains incompletely understood. To address this issue, psychophysical tasks that may specifically assess function of type I fast-adapting (FAI) and slowly adapting (SAI) mechanoreceptors were used with object manipulation experiments to examine the regulation of grip force control in an experimental model of graded reduction in tactile sensitivity (healthy volunteers wearing 2 layers of latex gloves). With gloves, tactile sensitivity decreased significantly from 1.9 ± 0.4 to 12.3 ± 2.2 μm in the Bumps task assessing function of FAI afferents but not in a grating orientation task assessing SAI afferents (1.6 ± 0.1 to 1.8 ± 0.2 mm). Six axis force/torque sensors measured peak grip (PGF) and load (PLF) forces generated by the fingertips during a grip-lift task. With gloves there was a significant increase of PGF (14 ± 6%), PLF (17 ± 5%), and grip and load force rates (26 ± 8%, 20 ± 8%). A variable-weight series task was used to examine sensorimotor memory. There was a 20% increase in PGF when the lift of a light object was preceded by a heavy relative to a light object. This relationship was not significantly altered when lifting with gloves, suggesting that the addition of gloves did not change sensorimotor memory effects. We conclude that FAI fibers may be important for the online force scaling but not for the buildup of a sensorimotor memory. Copyright © 2016 the American Physiological Society.

Numerical performance and throughput benchmark for electronic structure calculations in PC-Linux systems with new architectures, updated compilers, and libraries.

PubMed

Yu, Jen-Shiang K; Hwang, Jenn-Kang; Tang, Chuan Yi; Yu, Chin-Hui

2004-01-01

A number of recently released numerical libraries including Automatically Tuned Linear Algebra Subroutines (ATLAS) library, Intel Math Kernel Library (MKL), GOTO numerical library, and AMD Core Math Library (ACML) for AMD Opteron processors, are linked against the executables of the Gaussian 98 electronic structure calculation package, which is compiled by updated versions of Fortran compilers such as Intel Fortran compiler (ifc/efc) 7.1 and PGI Fortran compiler (pgf77/pgf90) 5.0. The ifc 7.1 delivers about 3% of improvement on 32-bit machines compared to the former version 6.0. Performance improved from pgf77 3.3 to 5.0 is also around 3% when utilizing the original unmodified optimization options of the compiler enclosed in the software. Nevertheless, if extensive compiler tuning options are used, the speed can be further accelerated to about 25%. The performances of these fully optimized numerical libraries are similar. The double-precision floating-point (FP) instruction sets (SSE2) are also functional on AMD Opteron processors operated in 32-bit compilation, and Intel Fortran compiler has performed better optimization. Hardware-level tuning is able to improve memory bandwidth by adjusting the DRAM timing, and the efficiency in the CL2 mode is further accelerated by 2.6% compared to that of the CL2.5 mode. The FP throughput is measured by simultaneous execution of two identical copies of each of the test jobs. Resultant performance impact suggests that IA64 and AMD64 architectures are able to fulfill significantly higher throughput than the IA32, which is consistent with the SpecFPrate2000 benchmarks.

Requirement for IFN-gamma in IL-12 production induced by collaboration between v(alpha)14(+) NKT cells and antigen-presenting cells.

PubMed

Yang, Y F; Tomura, M; Ono, S; Hamaoka, T; Fujiwara, H

2000-12-01

Two cytokines IL-4 and IL-12 are known to determine the balance between T(h)1 and T(h)2 development. In addition to IL-4 production of V(alpha)14(+) NKT cells, they have recently been demonstrated to have the capacity to stimulate IL-12 production by antigen-presenting cells (APC). This study demonstrates that IFN-gamma is absolutely required for the NKT cell-stimulated IL-12 production. Culture of B cell-depleted spleen cells from C57BL/6 mice with alpha-galactosylceramide (alpha-GalCer) capable of selectively stimulating V(alpha)14/J(alpha)281(+) NKT cells resulted in the production of IL-12 together with IL-4. Whereas IL-4 production occurred in culture of IFN-gamma(-/-) C57BL/6 splenocytes, the same culture failed to generate IL-12 production. While IL-12 production induced during culture of V(alpha)14(+) NKT cells and APC depended on the interaction between CD40 ligand on NKT cells and CD40 on APC, the expression levels of these key molecules were comparable in cells from wild-type and IFN-gamma(-/-) mice. Addition of rIFN-gamma to alpha-GalCer stimulated IFN-gamma(-/-) splenocyte culture, and administration of rIFN-gamma to alpha-GalCer-injected IFN-gamma(-/-) mice resulted in the restoration of IL-12 production in vitro and in vivo. These results illustrate a mandatory role for IFN-gamma in V(alpha)14(+) NKT cell-stimulated IL-12 production by APC.

Trimethyltin-activated cyclooxygenase stimulates tumor necrosis factor-alpha release from glial cells through reactive oxygen species.

PubMed

Viviani, B; Corsini, E; Pesenti, M; Galli, C L; Marinovich, M

2001-04-15

Exposure of a primary culture of glial cells to the classical neurotoxicant trimethyltin (TMT) results in the release of prostaglandin (PG)E(2) and tumor necrosis factor (TNF)-alpha. Prior treatment of glial cells with either the nonspecific inhibitor of cyclooxygenase and lypoxygenase eicosatetraynoic acid (ETYA) or the cyclooxygenase inhibitor indomethacin completely prevented TMT-induced PGE(2) production and TNF-alpha release, suggesting a role for cyclooxygenase metabolites in TMT-induced TNF-alpha release. Exposure of glial cells to increasing concentrations of PGE(2) or other prostanoids did not increase TNF-alpha synthesis, while the presence of exogenous PGE(2) during treatment of glial cells with TMT actually suppressed TNF-alpha release. The activation of arachidonic acid metabolism produces reactive oxygen species (ROS). Scavenging of ROS by means of the antioxidant trolox prevented the TMT-induced release of TNF-alpha from glial cells, while indomethacin was found to suppress ROS formation induced by 1 microM TMT in glial cells. These results suggest that activation of arachidonic acid metabolism causes TNF-alpha release through the production of ROS rather than PGE(2). Indeed, PGE(2) may exert negative feedback on the release of TNF-alpha. Copyright 2001 Academic Press.

The inhibition of nicotine-evoked relaxation of the guinea-pig isolated basilar artery by some analgesic drugs and progesterone

PubMed Central

Rhodes, Keith F; Buckingham, Julia C; Kennard, Christopher

1999-01-01

The purpose of this study was to investigate the mechanism of nicotine-evoked relaxation of the guinea-pig isolated basilar artery and to study the effects of drugs associated with the aetiology or treatment of migraine on the nicotine response. The guinea-pig isolated basilar artery, pre-contracted with prostaglandin F2α (PGF2α), in the presence of atropine (3 μM) and guanethidine (3 μM), relaxed on addition of nicotine (0.1 mM) in approximately 50% of preparations. The responses to nicotine were of short duration and blocked in preparations pre-treated for 10 min with capsaicin (1 μM) and are therefore probably a consequence of the stimulation of trigeminal C fibre terminals. Responses to nicotine were reduced in the presence of 5-carboxamidotryptamine, 5-hydroxytryptamine and sumatriptan in that order of potency. This is consistent with a 5-HT1 receptor mechanism. These agonists evoked small additional contractions in vessels pre-contracted with PGF2α. Indomethacin (0.3–10 μM), aspirin (10–30 μM), and nitro-L-arginine methyl ester (L-NAME, 0.1 mM) reduced nicotine-evoked relaxation of the basilar artery, suggesting the involvement of both nitric oxide and cyclo-oxygenase products in this response. Progesterone (1 μM) markedly reduced the response to nicotine, a possible reflection of the ion channel blocking activity of high concentrations of this compound. The guinea-pig basilar artery is a preparation in which the effects of drugs on responses to stimulation of trigeminal nerve terminals can be studied in vitro and may thus be of interest in assessing the actions of drugs used in treatment of headache. PMID:10193781

Linkage of the Na,K-ATPase alpha 2 and beta 1 genes with resting and exercise heart rate and blood pressure: cross-sectional and longitudinal observations from the Quebec Family Study.

PubMed

Rankinen, T; Pérusse, L; Dériaz, O; Thériault, G; Chagnon, M; Nadeau, A; Bouchard, C

1999-03-01

To investigate whether genetic variations in the genes encoding the alpha and beta subunits of the Na,K-ATPase are linked with hemodynamic phenotypes. Cross-sectional data based on 533 subjects (no antihypertensive medication) were obtained from 150 families of phase 2 of the Quebec Family Study, together with longitudinal data from 338 subjects (105 families) who had been measured 12 years earlier in phase 1 of the Quebec Family Study. Restriction fragment length polymorphisms were examined at the alpha 2 (exon 1 and exon 21-22 with BglII) and beta 1 (Msp I and Pvu II) loci of Na,K-ATPase. Hemodynamic phenotypes measured included systolic and diastolic blood pressure, heart rate and rate-pressure product at rest and during low-intensity exercise. Sib-pair analysis revealed relatively strong linkages (P = 0.0003-0.002) between the resting heart rate and rate-pressure product and the alpha 2 exon 21-22 marker and alpha 2 haplotype. Moreover, the alpha 2 exon 21-22 marker showed suggestive linkages (P = 0.01 to 0.043) with resting systolic blood pressure and exercise diastolic blood pressure, heart rate and rate-pressure product, and the alpha 2 haplotype with exercise diastolic blood pressure and rate-pressure product and the 12-year change in resting systolic blood pressure (P = 0.03 to 0.05). Both the beta 1 Msp I marker and the beta 1 haplotype were linked with the resting rate-pressure product (P = 0.007 and 0.003, respectively), and all beta 1 markers showed linkage with the change in resting systolic blood pressure (P = 0.00005 to 0.024). In men, there was a significant (P = 0.01) interaction between the alpha 2 exon 21-22 genotype and the postglucose plasma insulin level with regard to resting systolic blood pressure. These data suggest that the alpha 2 and beta 1 genes of Na,K-ATPase contribute to the regulation of hemodynamic phenotypes in healthy subjects.

The New Era of Precision Cosmology: Testing Gravity at Large Scales

NASA Technical Reports Server (NTRS)

Prescod-Weinstein, Chanda

2011-01-01

Cosmic acceleration may be the biggest phenomenological mystery in cosmology today. Various explanations for its cause have been proposed, including the cosmological constant, dark energy and modified gravities. Structure formation provides a strong test of any cosmic acceleration model because a successful dark energy model must not inhibit the development of observed large-scale structures. Traditional approaches to studies of structure formation in the presence of dark energy ore modified gravity implement the Press & Schechter formalism (PGF). However, does the PGF apply in all cosmologies? The search is on for a better understanding of universality in the PGF In this talk, I explore the potential for universality and talk about what dark matter haloes may be able to tell us about cosmology. I will also discuss the implications of this and new cosmological experiments for better understanding our theory of gravity.

Determination of the top-quark pole mass and strong coupling constant from the t t-bar production cross section in pp collisions at $$\\sqrt{s}$$ = 7 TeV

DOE PAGES

Chatrchyan, Serguei

2014-08-21

The inclusive cross section for top-quark pair production measured by the CMS experiment in proton-proton collisions at a center-of-mass energy of 7 TeV is compared to the QCD prediction at next-to-next-to-leading order with various parton distribution functions to determine the top-quark pole mass,more » $$m_t^{pole}$$, or the strong coupling constant, $$\\alpha_S$$. With the parton distribution function set NNPDF2.3, a pole mass of 176.7$$^{+3.0}_{-2.8}$$ GeV is obtained when constraining $$\\alpha_S$$ at the scale of the Z boson mass, $$m_Z$$, to the current world average. Alternatively, by constraining $$m_t^{pole}$$ to the latest average from direct mass measurements, a value of $$\\alpha_S(m_Z)$$ = 0.1151$$^{+0.0028}_{-0.0027}$$ is extracted. This is the first determination of $$\\alpha_S$$ using events from top-quark production.« less

N-acetylcysteine attenuates TNF-alpha-induced p38 MAP kinase activation and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells.

PubMed

Hashimoto, S; Gon, Y; Matsumoto, K; Takeshita, I; Horie, T

2001-01-01

1. We have previously shown that tumour necrosis factor-alpha (TNF-alpha) activates p38 mitogen-activated protein (MAP) kinase to produce interleukin-8 (IL-8) by human pulmonary vascular endothelial cells. Reactive oxygen species (ROS) including H(2)O(2) generated by TNF-alpha can act as signalling intermediates for cytokine induction; therefore, scavenging ROS by anti-oxidants is important for the regulation of cytokine production. However, the effect of N-acetylcysteine (NAC), which acts as a precursor of glutathione (GSH) synthesis, on TNF-alpha-induced activation of p38 MAP kinase pathway and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells has not been determined. To clarify these issues, we examined the effect of NAC on TNF-alpha-induced activation of p38 MAP kinase, MAP kinase kinase (MKK) 3 and MKK6 which are upstream regulators of p38 MAP kinase, and p38 MAP kinase-mediated IL-8 production. 2. Human pulmonary vascular endothelial cells that had been preincubated with NAC were stimulated with TNF-alpha and then the activation of p38 MAP kinase and MKK3/MKK6 in the cells and IL-8 concentrations in the culture supernatants were determined. 3. Intracellular GSH levels increased in NAC-treated cells. 4. NAC attenuated TNF-alpha-induced activation of p38 MAP kinase and MKK3/MKK6. 5. NAC attenuated p38 MAP kinase-mediated IL-8 production by TNF-alpha-stimulated cells. 6. These results indicate that the cellular reduction and oxidation (redox) regulated by intracellular GSH is critical for TNF-alpha-induced activation of p38 MAP kinase pathway and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells, and we emphasize that anti-oxidant therapy is an important strategy for the treatment of acute lung injury.

The effect of numbers of frozen-thawed boar sperm and addition of prostaglandin F2α at insemination on fertility in pigs.

PubMed

Knox, Robert V; Yantis, Brandon M

2014-12-30

Frozen-thawed boar sperm (FTS) has reduced fertility compared to liquid semen. Exogenous prostaglandin administered at insemination has been reported to improve cases of low fertility. This experiment tested the effect of number of FTS and addition of prostaglandin (PGF2α) on fertility. The experiment was performed in replicates using weaned sows (n=24) and synchronized gilts (n=94). All females were induced into estrus using PG600® at weaning or following estrus synchronization. At estrus, females received 0.5, 1.0, or 2 billion motile FTS (n=9 boars) with 0 or 5mg of PGF2α added into each AI dose at insemination. Inseminations occurred at 24 and 36h after onset of estrus and ovulation was monitored by ultrasound. Pregnancy and litter size were determined for sows at farrowing and d 50 of gestation for gilts at slaughter. There was no effect of PGF2α and no interaction with dose of FTS or parity on fertility (P>0.10). Pregnancy rate was affected by FTS dose (P<0.001) with 2.0×10(9) (76.3%) greater than 0.5×10(9) (46.2%) and 1.0×10(9) sperm (48.8±8.0%). Pregnancy rate was not affected by parity (P>0.10) but was influenced by boar (P<0.05). Number of fetuses was also affected by FTS dose (P<0.001) with 2.0×10(9) (10.1) and 1.0×10(9) (9.4) producing more pigs than 0.5×10(9) sperm (6.9±0.9). Litter size was also affected by parity (P=0.001) and boar (P<0.01). These results indicate that AI using 2.0×10(9) FTS can result in acceptable pregnancy rates and litter sizes but with no measurable benefit for addition of prostaglandin. Copyright © 2014 Elsevier B.V. All rights reserved.

Screening of a thiamine-auxotrophic yeast for alpha-ketoglutaric acid overproduction.

PubMed

Zhou, Jingwen; Zhou, Haiyan; Du, Guocheng; Liu, Liming; Chen, Jian

2010-09-01

To obtain a thiamine-auxotrophic yeast strain that overproduces alpha-ketoglutaric acid (alpha-KG) from glycerol and to investigate nutrient effects on alpha-KG production. Yeast strain WSH-Z06, a thiamine auxotroph that gave high yields of alpha-KG from glycerol, was obtained by screening for ampicillin/kanamycin resistance and thiamine auxotrophy. The strain was identified as Yarrowia lipolytica based on physiological, chemical, and phylogenetic analysis. The ability of the strain to convert glycerol to alpha-KG was analysed by investigating the effects of nutritional factors, including thiamine, riboflavin, nitrogen sources, and calcium ion. Thiamine and calcium ion concentration had the greatest effect on alpha-KG accumulation. Under optimal conditions, a yield of 39.2 g l(-1)alpha-KG was obtained from 100 g l(-1) glycerol, with 16.84 g l(-1) pyruvate as a by-product. The current work provides a method for screening for an alpha-KG overproducer. Nutrients have a significant impact on alpha-KG production in the yeast strain presented here. The alpha-KG-overproducing yeast strain Y. lipolytica WSH-Z06 is a promising parent strain for further metabolic engineering to lower by-product accumulation and accelerate glycerol utilization.

Nitric oxide production and monoamine oxidase activity in cancer patients during interferon-alpha therapy.

PubMed

Fekkes, Durk; Van Gool, Arthur R; Bannink, Marjolein; Sleijfer, Stefan; Kruit, Wim H J; van der Holt, Bronno; Eggermont, Alexander M M; Hengeveld, Michiel W; Stoter, Gerrit

2009-10-01

Both increased and decreased nitric oxide (NO) synthesis have been reported in patients treated with interferon-alpha (IFN-alpha). Animal studies showed that IFN-alpha administration results in increased levels of biogenic amines, subsequent activation of monoamine oxidases (MAOs), and finally in a change in NO production due to the H(2)O(2) generated by MAOs. We examined the potential relationship between NO production in plasma and MAO-B activity in platelets of 43 cancer patients during 8 weeks of treatment with IFN-alpha. NO synthesis was quantitated by measuring both the ratio of citrulline and arginine (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels. Compared to baseline, MAO activity and NOx increased, while the CIT/ARG-ratio decreased. No associations were found between NOx, MAO and CIT/ARG-ratio. Only few associations were observed between changes in the biochemical parameters and changes in psychopathology induced by IFN-alpha, of which the association between changes in CIT and lassitude was the most consistent. The results suggest that peripheral NO production and MAO activity are unrelated to each other, and that peripheral changes in these biochemical parameters induced by IFN-alpha are unlikely to contribute to definite psychiatric disturbance.

Effect of parathyroid hormone and calcium ions on substrate oxidation by isolated glomeruli of the rat.

PubMed

Wang, M S; Kurokawa, K

1981-11-05

Effect of Ca2+ and parathyroid hormone (PTH) on 14 CO2 production from certain metabolic substrates by isolated glomeruli of rat kidney were examined. Increasing calcium concentration in the incubation medium inhibited 14CO2 production from 14C-labeled alpha-ketoglutarate and succinate, stimulated 14CO2 production from [1-14C]glucose and [1-14C]glutamate, but was without effect on that from [6-14C]glucose. PTH in the presence but not in the absence of Ca2+ inhibited 14CO2 production from labeled alpha-ketoglutarate and glutamate but not from labeled glucose. Additions of cyclic AMP as well as hormonal agents known to act directly on the glomureli, such as histamine, epinephrine, prostaglandin E2, vasopressin, angiotensin II and insulin, did not alter 14 CO2 production from labeled alpha-ketoglutarate. These data show the presence of calcium-dependent inhibitory actions on PTH on oxidation of alpha-ketoglutarate and glutamate which may be independent of cyclic AMP. These metabolic effects of PTH may underlie the alteration in the glomerular ultrafiltration coefficient and glomerular filtration induced by the hormone.

Effect of calcium soaps of fatty acids and administration of somatotropin on milk production, preovulatory follicular development, and plasma and follicular fluid lipid composition in high yielding dairy cows.

PubMed

Moallem, U; Folman, Y; Bor, A; Arav, A; Sklan, D

1999-11-01

The effect of fat and bovine somatotropin (bST) on preovulatory follicular hormones and lipids was evaluated by feeding cows for 150 d from parturition a control diet, a control diet plus 0.55 kg/d of calcium soaps of fatty acids, or a control diet with 500 mg of bST injected every 14 d. Fourteen days after a synchronized or natural estrus, cows were injected with a PGF2 alpha analogue; 48 h later, follicular fluid from all ovarian follicles > 8 mm was aspirated. Cows fed fat or injected with bST produced more milk and milk solids than did control cows, and cows on the bST treatment lost more body condition after calving than did cows on the other treatments. Both treatments changed the proportion of estradiol-active follicles (> 400 ng of estradiol/ml of follicular fluid) and the correlation between follicular fluid estradiol concentration and the total number large follicles per cow. In follicles aspirated between 60 and 90 DIM the percentage of estradiol-active follicles was 67, 40, and 0 for cows on the control, calcium soaps of fatty acids, and bST treatments, respectively. After 90 DIM, no differences existed between treatments in the percentage of estradiol-active follicles. Estradiol concentration in follicular fluid was correlated with DIM at follicle aspiration (r = 0.51). The proportion of oleic acid in free fatty acids in plasma at 50 DIM was lower in control cows and was lower in follicular fluid of estradiol-active follicles. Both calcium soaps of fatty acids and bST had a considerable effect on follicular development and activity and the composition of fatty acids in follicles.

A new experimental approach in endothelium-dependent pharmacological investigations on isolated porcine coronary arteries mounted for impedance planimetry

PubMed Central

Tankó, László B; Mikkelsen, Erich O; Simonsen, Ulf

1999-01-01

The aim of this study was to investigate whether the balloon-based impedance planimetry technique could be a useful tool in endothelium-dependent investigations. Porcine large coronary arteries contracted with prostaglandin F2α (PGF2α, 10 μM) did not relax to bradykinin (0.1 nM–0.1 μM), but did relax to sodium nitroprusside (SNP, 10 μM). However, after eversion of the segments, bradykinin induced relaxations with pD2 values and maximal responses of 8.78±0.09 and 75±2% (n=6), respectively. Incubation with captopril (1 μM) did not reveal a relaxation to bradykinin in the normal vessel configuration and had no influence on the concentration-relaxation relationship in everted segments. Lowering the luminal pressure in contracted segments from 131±5 mmHg (isometric, n=5) to 60 mmHg (isobaric, n=5) did not facilitate the action of bradykinin. Eversion of segments did not influence the concentration-response relationship for K+ (4.7–125 mM), PGF2α (0.3–30 μM), and SNP (30 nM–30 μM), although the time-courses of responses were faster when the agents were added from the intimal compared to the adventitial side of the preparation. In the same everted segment contracted with PGF2α, the concentration-response relationship for bradykinin was not different under isometric and isobaric conditions. These results indicate that, (1) reduced endothelium-dependent relaxations to adventitially administered substances can be ascribed to a diffusion barrier in the vessel wall, while enzymatic degradation, luminal pressure and precontractile responses seem not to play a role, (2) impedance planimetry applied to everted cylindrical segments could be a useful experimental approach in pharmacological studies of endothelium-dependent responses under isobaric and isometric conditions. PMID:10498848

Protective effects of flavanol-rich dark chocolate on endothelial function and wave reflection during acute hyperglycemia.

PubMed

Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; Ruggieri, Fabrizio; Blumberg, Jeffrey B; Stornello, Michele; Ferri, Claudio

2012-09-01

Nitric oxide plays a pivotal role in regulating vascular tone. Different studies show endothelial function is impaired during hyperglycemia. Dark chocolate increases flow-mediated dilation in healthy and hypertensive subjects with and without glucose intolerance; however, the effect of pretreatment with dark chocolate on endothelial function and other vascular responses to hyperglycemia has not been examined. Therefore, we aimed to investigate the effects of flavanol-rich dark chocolate administration on (1) flow-mediated dilation and wave reflections; (2) blood pressure, endothelin-1 and oxidative stress, before and after oral glucose tolerance test (OGTT). Twelve healthy volunteers (5 males, 28.2±2.7 years) randomly received either 100 g/d dark chocolate or flavanol-free white chocolate for 3 days. After 7 days washout period, volunteers were switched to the other treatment. Flow-mediated dilation, stiffness index, reflection index, peak-to-peak time, blood pressure, endothelin-1 and 8-iso-PGF(2α) were evaluated after each treatment phase and OGTT. Compared with white chocolate, dark chocolate ingestion improved flow-mediated dilation (P=0.03), wave reflections, endothelin-1 and 8-iso-PGF(2α) (P<0.05). After white chocolate ingestion, flow-mediated dilation was reduced after OGTT from 7.88±0.68 to 6.07±0.76 (P=0.027), 6.74±0.51 (P=0.046) at 1 and 2 h after the glucose load, respectively. Similarly, after white chocolate but not after dark chocolate, wave reflections, blood pressure, and endothelin-1 and 8-iso-PGF(2α) increased after OGTT. OGTT causes acute, transient impairment of endothelial function and oxidative stress, which is attenuated by flavanol-rich dark chocolate. These results suggest cocoa flavanols may contribute to vascular health by reducing the postprandial impairment of arterial function associated with the pathogenesis of atherosclerosis.

cap alpha. /sub 2/-Adrenergic receptor-mediated sensitization of forskolin-stimulated cyclic AMP production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, S.B.; Toews, M.L.; Turner, J.T.

1987-03-01

Preincubation of HT29 human colonic adenocarcinoma cells with ..cap alpha../sub 2/-adrenergic agonists resulted in a 10- to 20-fold increase in forskolin-stimulated cyclic AMP production as compared to cells preincubated without agonist. Similar results were obtained using either a (/sup 3/H)adenine prelabeling assay or a cyclic AMP radioimmunoassay to measure cyclic AMP levels. This phenomenon, which is termed sensitization, is ..cap alpha../sub 2/-adrenergic receptor-mediated and rapid in onset and reversal. Yohimbine, an ..cap alpha../sub 2/-adrenergic receptor-selective antagonist, blocked norepinephrine-induced sensitization, whereas prazosin (..cap alpha../sub 1/-adrenergic) and sotalol (..beta..-adrenergic) did not. The time for half-maximal sensitization was 5 min and the half-timemore » for reversal was 10 min. Only a 2-fold sensitization of cyclic AMP production stimulated by vasoactive intestinal peptide was observed, indicating that sensitization is relatively selective for forskolin. Sensitization reflects an increased production of cyclic AMP and not a decreased degradation of cyclic AMP, since incubation with a phosphodiesterase inhibitor and forskolin did not mimic sensitization. Increasing the levels of cyclic AMP during the preincubation had no effect on sensitization, indicating that sensitization is not caused by decreased cyclic AMP levels during the preincubation. This rapid and dramatic sensitization of forskolin-stimulated cyclic AMP production is a previously unreported effect that can be added to the growing list of ..cap alpha../sub 2/-adrenergic responses that are not mediated by a decrease in cyclic AMP.« less

Thalidomide reduces tumour necrosis factor alpha and interleukin 12 production in patients with chronic active Crohn's disease.

PubMed

Bauditz, J; Wedel, S; Lochs, H

2002-02-01

Thalidomide improves clinical symptoms in patients with therapy refractory Crohn's disease, as shown in two recent studies. The mechanism of this effect however is still unknown. Suppression of tumour necrosis factor alpha (TNF-alpha) by thalidomide has been suggested as a possible mechanism. However, effects on other cytokines have not been adequately investigated. The aim of our study was to investigate the effects of thalidomide on cytokine production in patients with inflammatory bowel disease (IBD). Ten patients with therapy refractory IBD (nine Crohn's disease, one ulcerative colitis) received thalidomide 300 mg daily in a 12 week open label study. Production of TNF-alpha, interleukin (IL)-1 beta, IL-6, and IL-12 was investigated in short term cultures of stimulated colonic lamina propria mononuclear cells (LPMC) and peripheral blood monocytes (PBMC) before and after 12 weeks of treatment. LPMC were also cultured with graded doses of thalidomide. Three patients discontinued treatment because of sedative side effects. In the other patients, disease activity decreased significantly, with four patients achieving remission. Production of TNF-alpha and IL-12 decreased during treatment with thalidomide: LPMC (TNF-alpha: 42.3 (8.3) pg/ml v 16.4 (6.3); IL-12: 9.7 (3.3) v 5.0 (2.5); p<0.04) and PBMC (TNF-alpha: 62.8 (14.6) v 22.5 (9.2); p<0.02). Production of IL-1 beta and IL-6 did not change significantly. Culturing of LPMC with thalidomide showed a dose dependent decrease in TNF-alpha and IL-12 production. The clinical effects of thalidomide in Crohn's disease may be mediated by reduction of both TNF-alpha and IL-12.

Characteristics of alpha-glycerophosphate-evoked H2O2 generation in brain mitochondria.

PubMed

Tretter, Laszlo; Takacs, Katalin; Hegedus, Vera; Adam-Vizi, Vera

2007-02-01

Characteristics of reactive oxygen species (ROS) production in isolated guinea-pig brain mitochondria respiring on alpha-glycerophosphate (alpha-GP) were investigated and compared with those supported by succinate. Mitochondria established a membrane potential (DeltaPsi(m)) and released H(2)O(2) in parallel with an increase in NAD(P)H fluorescence in the presence of alpha-GP (5-40 mm). H(2)O(2) formation and the increase in NAD(P)H level were inhibited by rotenone, ADP or FCCP, respectively, being consistent with a reverse electron transfer (RET). The residual H(2)O(2) formation in the presence of FCCP was stimulated by myxothiazol in mitochondria supported by alpha-GP, but not by succinate. ROS under these conditions are most likely to be derived from alpha-GP-dehydrogenase. In addition, huge ROS formation could be provoked by antimycin in alpha-GP-supported mitochondria, which was prevented by myxothiazol, pointing to the generation of ROS at the quinol-oxidizing center (Q(o)) site of complex III. FCCP further stimulated the production of ROS to the highest rate that we observed in this study. We suggest that the metabolism of alpha-GP leads to ROS generation primarily by complex I in RET, and in addition a significant ROS formation could be ascribed to alpha-GP-dehydrogenase in mammalian brain mitochondria. ROS generation by alpha-GP at complex III is evident only when this complex is inhibited by antimycin.

Methanol extract of Xanthium strumarium L. possesses anti-inflammatory and anti-nociceptive activities.

PubMed

Kim, In-Tae; Park, Young-Mi; Won, Jong-Heon; Jung, Hyun-Ju; Park, Hee-Juhn; Choi, Jong-Won; Lee, Kyung-Tae

2005-01-01

As an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the effects of the methanol extract of the semen of Xanthium strumarium L. (MEXS) on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) production in RAW 264.7 cells. Our data indicate that MEXS is a potent inhibitor of NO, PGE2 and TNF-alpha production. Consistent with these findings, the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2 and TNF-alpha mRNA were down-regulated in a concentration-dependent manner. Furthermore, MEXS inhibited nuclear factor kappa B (NF-kappaB) DNA binding activity and the translocation of NF-kappaB to the nucleus by blocking the degradation of inhibitor of kappa B-alpha (IkappaB-alpha). We further evaluated the anti-inflammatory and anti-nociceptive activities of MEXS in vivo. MEXS (100, 200 mg/kg/d, p.o.) reduced acute paw edema induced by carrageenin in rats, and showed analgesic activities in an acetic acid-induced abdominal constriction test and a hot plate test in mice. Thus, our study suggests that the inhibitions of iNOS, COX-2 expression, and TNF-alpha release by the methanol extract of the semen of Xanthium strumarium L. are achieved by blocking NF-kappaB activation, and that this is also responsible for its anti-inflammatory effects.

Protective effect of thalidomide on endotoxin-induced liver injury.

PubMed

Enomoto, Nobuyuki; Takei, Yoshiyuki; Hirose, Miyoko; Kitamura, Tsuneo; Ikejima, Kenichi; Sato, Nobuhiro

2003-08-01

Activation of Kupffer cells by lipopolysaccharide (LPS) plays a pivotal role in the onset of pathophysiological events that occur during endotoxemia, and intracellular calcium concentration ([Ca2+]i) is involved in LPS-stimulated cytokine production. Tumor necrosis factor (TNF)-alpha is produced exclusively by the monocyte-macrophage lineage, which is mostly made up of Kupffer cells, and thalidomide has been shown to reduce TNF-alpha production from macrophages. However, there is increasing evidence that TNF-alpha may play a role in the initiation or progression of multiple organ failure syndrome. Therefore, the purpose of this work was to determine whether thalidomide could prevent LPS-induced liver injury. Rats were given a single oral dose of thalidomide (5 mg/kg). To assess the sensitization of Kupffer cells, LPS (5 or 10 mg/kg) was administered intravenously, and mortality, liver histology, and transaminases were evaluated 24 hr later. Kupffer cells were isolated 2 hr after thalidomide treatment. After the addition of LPS, [Ca2+]i was measured by using a microspectrofluorometer with the fluorescent indicator fura-2, and TNF-alpha was measured by enzyme-linked immunosorbent assay. LPS caused focal necrosis with neutrophil infiltration in the liver. Moreover, LPS dramatically increased transaminases. These pathologic parameters and increases of serum transaminases were diminished markedly by thalidomide. In isolated Kupffer cells, LPS-induced increases in [Ca2+]i and TNF-alpha production were suppressed by treatment with thalidomide. To further explore the mechanism by which thalidomide directly abrogated Kupffer cell sensitivity to LPS, we determined the effect of thalidomide (5 microM) in vitro on LPS-induced [Ca2+]i response and TNF-alpha production. With the addition of thalidomide (5 microM) in vitro to the culture media for 2 hr before LPS, these parameters were suppressed. Thalidomide prevents LPS-induced liver injury via mechanisms dependent on the suppression of TNF-alpha production from Kupffer cells.

Design and control of rotating soil-like substrate plant-growing facility based on plant water requirement and computational fluid dynamics simulation

NASA Astrophysics Data System (ADS)

Hu, Dawei; Li, Leyuan; Liu, Hui; Zhang, Houkai; Fu, Yuming; Sun, Yi; Li, Liang

It is necessary to process inedible plant biomass into soil-like substrate (SLS) by bio-compost to realize biological resource sustainable utilization. Although similar to natural soil in structure and function, SLS often has uneven water distribution adversely affecting the plant growth due to unsatisfactory porosity, permeability and gravity distribution. In this article, SLS plant-growing facility (SLS-PGF) were therefore rotated properly for cultivating lettuce, and the Brinkman equations coupled with laminar flow equations were taken as governing equations, and boundary conditions were specified by actual operating characteristics of rotating SLS-PGF. Optimal open-control law of the angular and inflow velocity was determined by lettuce water requirement and CFD simulations. The experimental result clearly showed that water content was more uniformly distributed in SLS under the action of centrifugal and Coriolis force, rotating SLS-PGF with the optimal open-control law could meet lettuce water requirement at every growth stage and achieve precise irrigation.

Identification of a novel compound that inhibits iNOS and COX-2 expression in LPS-stimulated macrophages from Schisandra chinensis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, You Jin; Park, Sun Young; Kim, Sun Gun

2010-01-22

A novel {alpha}-iso-cubebenol, which has anti-inflammatory effects in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, was isolated from the fruits of Schisandra chinensis. {alpha}-iso-cubebenol inhibited LPS-induced nitric oxide (NO) and prostaglandin E{sub 2} (PGE{sub 2}) production. Consistent with these findings, {alpha}-iso-cubebenol also reduced the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at the protein and mRNA levels in a concentration-dependent manner. {alpha}-iso-cubebenol also inhibited LPS-induced nuclear translocation of the NF-{kappa}B p65 subunit. Furthermore, {alpha}-iso-cubebenol suppressed the phosphorylation of ERK, JNK, and p38 kinase induced by LPS. Since the novel {alpha}-iso-cubebenol blocked the production of several pro-inflammatory mediators induced by LPSmore » in macrophages, the molecule can be useful material for the development of anti-inflammatory agents against bacterial infections or endotoxin.« less

Acidity-controlled selective oxidation of alpha-pinene, isolated from Indonesian pine's turpentine oils (pinus merkusii)

NASA Astrophysics Data System (ADS)

Masruri; Farid Rahman, Mohamad; Nurkam Ramadhan, Bagus

2016-02-01

Alpha-pinene was isolated in high purity from turpentine oil harvested from Pinus merkusii plantation. The recent investigation on selective oxidation of alpha-pinene using potassium permanganate was undertaken under acidic conditions. The result taught the selective oxidation of alpha-pinene in acidic using potassium permanganate lead to the formation of 2-(3-acetyl-2,2-dimethylcyclobutyl)acetaldehyde or pinon aldehyde. The study method applied reaction in various different buffer conditions i.e. pH 3, 4, 5, and 6, respectively, and each reaction product was monitored using TLC every hour. Product determination was undertaken on spectrometry basis such as infrared, ultra violet-visible, gas chromatography- and liquid chromatography-mass spectrometry.

Effects of tumor necrosis factor-alpha and interferon-gamma on expressions of matrix metalloproteinase-2 and -9 in human bladder cancer cells.

PubMed

Shin, K Y; Moon, H S; Park, H Y; Lee, T Y; Woo, Y N; Kim, H J; Lee, S J; Kong, G

2000-10-31

We have investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon (INF-gamma), the potent Bacillus Calmette-Guerin (BCG)-induced cytokines on the production of MMP-2, MMP-9, TIMP-1, TIMP-2 and MT1-MMP in high grade human bladder cancer cell lines, T-24, J-82 and HT-1376 cell lines. MMP-2 expression and activity were decreased in T-24 cells treated with both cytokines in a dose dependent manner. However, J-82 cells treated with TNF-alpha and INF-gamma revealed dose dependent increases of MMP-9 expression and activity with similar baseline expression and activity of MMP-2. HT-1376 cells after exposure to TNF-alpha only enhanced the expression and activity of MMP-9. These results indicate that TNF-alpha and INF-gamma could regulate the production of MMP-2 or MMP-9 on bladder cancer cells and their patterns of regulation are cell specific. Furthermore, this diverse response of bladder cancer cells to TNF-alpha and INF-gamma suggests that BCG immunotherapy may enhance the invasiveness of bladder cancer in certain conditions with induction of MMPs.

Crystal structure and magnetic properties of '{alpha} Prime Prime -Fe{sub 16}N{sub 2}' containing residual {alpha}-Fe prepared by low-temperature ammonia nitridation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamashita, S.; Masubuchi, Y.; Nakazawa, Y.

2012-10-15

Slight enhancement of saturation magnetization to 219 A m{sup 2} kg{sup -1} was observed from 199 A m{sup 2} kg{sup -1} for the original {alpha}-Fe on the intermediate nitrided mixture of '{alpha} Prime Prime -Fe{sub 16}N{sub 2}' with residual {alpha}-Fe among the low temperature ammonia nitridation products under 5 T magnetic field at room temperature. The value changed not linearly against the yield as had been expected. Crystal structure refinement indicated that the phase similar to {alpha} Prime Prime -Fe{sub 16}N{sub 2} had deviations on its lattice constants and positional parameters, compared to previously reported values for {alpha} Prime Primemore » -Fe{sub 16}N{sub 2}. Spin-polarized total energy calculations were performed using the projector-augmented wave method as implemented in the Vienna ab-initio simulation package (VASP) to calculate magnetic moment on the refined crystal structure of the intermediate '{alpha} Prime Prime -Fe{sub 16}N{sub 2}'. The calculations supported the observed magnetization enhancement in the intermediate nitridation product. - Graphical abstract: Crystal structural parameters slightly change in the intermediate nitrided '{alpha} Prime Prime -Fe{sub 16}N{sub 2}' from those in {alpha} Prime Prime -Fe{sub 16}N{sub 2} to show the magnetization maxima in the mixture of '{alpha} Prime Prime -Fe{sub 16}N{sub 2}' and the residual {alpha}-F. Highlights: Black-Right-Pointing-Pointer Larger magnetization was observed than the value of Fe{sub 16}N{sub 2} on its intermediate nitrided mixture with residual {alpha}-Fe. Black-Right-Pointing-Pointer The enhancement was related to the crystal structural deviation from Fe{sub 16}N{sub 2} on the intermediate nitride. Black-Right-Pointing-Pointer It was supported by spin-polarized total energy calculation using the deviated structure.« less

Role of arachidonic acid and protein kinase C during maturation-inducing hormone-dependent meiotic resumption and ovulation in ovarian follicles of Atlantic croaker

USGS Publications Warehouse

Patino, R.; Yoshizaki, G.; Bolamba, D.; Thomas, P.

2003-01-01

The roles of arachidonic acid (AA) and protein kinase C (PKC) during in vitro maturation-inducing hormone (MIH)-dependent meiotic resumption (maturation) and ovulation were studied in ovarian follicles of Atlantic croaker (Micropogonias undulatus). The requirement for cyclooxygenase (COX) metabolites of AA was examined using a nonspecific COX inhibitor, indomethacin (IM), as well as two COX products, prostaglandin (PG) F2?? and PGE2, whereas the role of lipoxygenase (LOX) was investigated using a specific LOX inhibitor, nordihydroguaiaretic acid (NDGA). The involvement of PKC was examined using phorbol 12-myristate 13-acetate (PMA), a PKC activator, as well as GF109203X (GF), a specific inhibitor of PKC and 1-(5-isoquin- olinesulfonyl)-2-methylpiperazine (H7), nonspecific inhibitor of protein kinases. Genomic mechanisms were examined with the transcription-inhibitor actinomycin D (ActD) and the functionality of heterologous (oocyte-granulosa) gap junctions (GJ) with a dye transfer assay. The AA (100 ??M) and PGF2?? (5 ??M) did not induce maturation, and NDGA (10 ??M) did not affect MIH-dependent maturation. However, IM (100 ??M) partially inhibited MIH-dependent maturation. Conversely, AA and both PGs induced, and IM and NDGA inhibited, MIH-dependent ovulation in matured follicles. The PMA (1 ??g/ml) did not induce maturation but caused ovulation in matured follicles, whereas PKC inhibitors (GF, 5 ??M; H7, 50??M) did not affect MIH-dependent maturation but inhibited MIH- and PMA-dependent ovulation. The PMA-dependent ovulation was inhibited by IM but not by NDGA. In addition, ActD (5 ??M) blocked MIH-dependent, but not PMA-dependent, ovulation, and PGF2?? restored MIH-dependent ovulation in ActD-blocked follicles. The AA and PGs did not induce, and GF did not inhibit, MIH-dependent heterologous GJ uncoupling. In conclusion, AA and PKC mediate MIH-dependent ovulation but not meiotic resumption or heterologous GJ uncoupling in croaker follicles, but a permissive role of COX products of AA during maturation is possible. A novel model of MIH-dependent ovulation is proposed in which 1) LOX and COX metabolites of AA are both required for ovulation, but at upstream and downstream sites of the pathway, respectively, relative to PKC, and 2) PKC is downstream of genomic activation.

Membrane-derived second messenger regulates x-ray-mediated tumor necrosis factor alpha gene induction.

PubMed Central

Hallahan, D E; Virudachalam, S; Kuchibhotla, J; Kufe, D W; Weichselbaum, R R

1994-01-01

Cells adapt to adverse environmental conditions through a wide range of responses that are conserved throughout evolution. Physical agents such as ionizing radiation are known to initiate a stress response that is triggered by the recognition of DNA damage. We have identified a signaling pathway involving the activation of phospholipase A2 and protein kinase C in human cells that confers x-ray induction of the tumor necrosis factor alpha gene. Treatment of human cells with ionizing radiation or H2O2 was associated with the production of arachidonic acid. Inhibition of phospholipase A2 abolished radiation-mediated arachidonate production as well as the subsequent activation of protein kinase C and tumor necrosis factor alpha gene expression. These findings demonstrate that ionizing radiation-mediated gene expression in human cells is regulated in part by extranuclear signal transduction. One practical application of phospholipase A2 inhibitors is to ameliorate the adverse effects of radiotherapy associated with tumor necrosis factor alpha production. Images PMID:8197153

CD90-positive cells, an additional cell population, produce laminin {alpha}2 upon transplantation to dy{sup 3k}/dy{sup 3k} mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukada, So-ichiro; Yamamoto, Yukiko; Segawa, Masashi

2008-01-01

Laminin {alpha}2 is a component of skeletal and cardiac muscle basal lamina. A defect of the laminin {alpha}2 chain leads to severe congenital muscular dystrophy (MDC1A) in humans and dy/dy mice. Myogenic cells including myoblasts, myotubes, and myofibers in skeletal muscle are a possible source of the laminin {alpha}2 chain, and myogenic cells are thus proposed as a cell source for congenital muscular dystrophy therapy. However, we observed production of laminin {alpha}2 in non-myogenic cells of normal mice, and we could enrich these laminin {alpha}2-producing cells in CD90{sup +} cell fractions. Intriguingly, the number of CD90{sup +} cells increased dramaticallymore » during skeletal muscle regeneration in mice. This fraction did not include myogenic cells but exhibited a fibroblast-like phenotype. Moreover, these cells were resident in skeletal muscle, not derived from bone marrow. Finally, the production of laminin {alpha}2 in CD90{sup +} cells was not dependent on fusion with myogenic cells. Thus, CD90{sup +} cells are a newly identified additional cell fraction that increased during skeletal muscle regeneration in vivo and could be another cell source for therapy for lama2-deficient muscular dystrophy.« less

Prostaglandins as mediators of acidification in the urinary bladder of Bufo marinus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frazier, L.W.; Yorio, T.

1990-05-01

Experiments were performed to determine whether prostaglandins (PG) play a role in H+ and NH4+ excretion in the urinary bladder of Bufo marinus. Ten paired hemibladders from normal toads were mounted in chambers. One was control and the other hemibladder received PGE2 in the serosal medium (10(-5) M). H+ excretion was measured by change in pH in the mucosal fluid and reported in units of nmol (100 mg tissue)-1 (min)-1. NH4+ excretion was measured colorimetrically and reported in the same units. The control group H+ excretion was 8.4 +/- 1.67, while the experimental group was 16.3 +/- 2.64 (P lessmore » than 0.01). The NH4+ excretion in the experimental and control group was not significantly different. Bladders from toads in a 48-hr NH4+Cl acidosis (metabolic) did not demonstrate this response to PGE2 (P greater than 0.30). Toads were put in metabolic acidosis by gavaging with 10 ml of 120 mM NH4+Cl 3 x day for 2 days. In another experiment, we measured levels of PG in bladders from control (N) and animals placed in metabolic acidosis (MA). Bladders were removed from the respective toad, homogenized, extracted, and PG separated using high-pressure liquid chromatography and quantified against PG standards. The results are reported in ng (mg tissue)-1. PGE2 fraction in N was 1.09 +/- 0.14 and in MA was 3.21 +/- 0.63 (P less than 0.01). PGF1 alpha, F2 alpha and I2 were not significantly different in N and MA toads. Bladders were also removed from N and MA toads, and incubated in Ringer's solution containing (3H)arachidonic acid (0.2 microCi/ml) at 25 degrees C for 2 hr. Bladders were then extracted for PG and the extracts separated by thin layer chromatography. PG were identified using standards and autoradiography, scraped from plates, and counted in a scintillation detector. The results are reported in cpm/mg tissue x hr +/- SEM.« less

Cytochrome P4502E1 primes macrophages to increase TNF-alpha production in response to lipopolysaccharide.

PubMed

Cao, Qi; Mak, Ki M; Lieber, Charles S

2005-07-01

Kupffer cells become activated in response to elevated levels of LPS during ethanol feeding, but the role of ethanol in the molecular processes of activation remains unclear. Because cytochrome P4502E1 (CYP2E1) is upregulated in Kupffer cells after ethanol, we hypothesized that this effect primes Kupffer cells, sensitizing them to increase TNF-alpha production in response to LPS. However, cultured Kupffer cells rapidly lose their CYP2E1. This difficulty was overcome by transfecting CYP2E1 to RAW 264.7 macrophages. Macrophages with stable increased CYP2E1 expression (E2) displayed increased levels of CD14/Toll-like receptor 4, NADPH oxidase and H2O2, accompanied by activation of ERK1/2, p38, and NF-kappaB. These increases primed E2 cells, sensitizing them to LPS stimuli, with amplification of LPS signaling, resulting in increased TNF-alpha production. Diphenyleneiodonium, a NADPH oxidase inhibitor, and diallyl sulfide, a CYP2E1 inhibitor, decreased approximately equally H2O2 levels in E2 cells, suggesting that NADPH oxidase and CYP2E1 contribute equally to H2O2 generation. Because CYP2E1 expression also enhanced the levels of the membrane localized NADPH oxidase subunits p47phox and p67phox, thereby contributing to the oxidase activation, it may augment H2O2 generation via this mechanism. H2O2, derived in part from NADPH and CYP2E1, activated ERK1/2 and p38. ERK1/2 stimulated TNF-alpha production via activation of NF-kappaB, whereas p38 promoted TNF-alpha production by stabilizing TNF-alpha mRNA. Oxidant generation after CYP2E1 overexpression appears to be central to macrophage priming and their sensitization to LPS. Accordingly, CYP2E1 priming could explain the sensitization of Kupffer cells to LPS activation by ethanol, a critical early step in alcoholic liver disease.

Surface Water and Energy Budgets for Sub-Saharan Africa in GFDL Coupled Climate Model

NASA Astrophysics Data System (ADS)

Tian, D.; Wood, E. F.; Vecchi, G. A.; Jia, L.; Pan, M.

2015-12-01

This study compare surface water and energy budget variables from the Geophysical Fluid Dynamics Laboratory (GFDL) FLOR models with the National Centers for Environmental Prediction (NCEP) Climate Forecast System Reanalysis (CFSR), Princeton University Global Meteorological Forcing Dataset (PGF), and PGF-driven Variable Infiltration Capacity (VIC) model outputs, as well as available observations over the sub-Saharan Africa. The comparison was made for four configurations of the FLOR models that included FLOR phase 1 (FLOR-p1) and phase 2 (FLOR-p2) and two phases of flux adjusted versions (FLOR-FA-p1 and FLOR-FA-p2). Compared to p1, simulated atmospheric states in p2 were nudged to the Modern-Era Retrospective Analysis for Research and Applications (MERRA) reanalysis. The seasonal cycle and annual mean of major surface water (precipitation, evapotranspiration, runoff, and change of storage) and energy variables (sensible heat, ground heat, latent heat, net solar radiation, net longwave radiation, and skin temperature) over a 34-yr period during 1981-2014 were compared in different regions in sub-Saharan Africa (West Africa, East Africa, and Southern Africa). In addition to evaluating the means in three sub-regions, empirical orthogonal functions (EOFs) analyses were conducted to compare both spatial and temporal characteristics of water and energy budget variables from four versions of GFDL FLOR, NCEP CFSR, PGF, and VIC outputs. This presentation will show how well each coupled climate model represented land surface physics and reproduced spatiotemporal characteristics of surface water and energy budget variables. We discuss what caused differences in surface water and energy budgets in land surface components of coupled climate model, climate reanalysis, and reanalysis driven land surface model. The comparisons will reveal whether flux adjustment and nudging would improve depiction of the surface water and energy budgets in coupled climate models.

Surface chemistry reactions of alpha-terpineol [(R)-2-(4-methyl-3-cyclohexenyl)isopropanol] with ozone and air on a glass and a vinyl tile.

PubMed

Ham, J E; Wells, J R

2008-10-01

The surface-phase reaction products of alpha-terpineol [(R)-2-(4-methyl-3-cyclohexenyl)isopropanol] with ozone (O(3)), air or nitrogen (N(2)) on both a glass and vinyl flooring tile were investigated using the recently published FLEC Automation and Control System (FACS). The FACS was used to deliver O(3) (100 ppb), air or N(2) to the surface at a specified flow rate (300 ml/min) and relative humidity (50%) after application of a 1.6%alpha-terpineol solution in methanol. Oxidation products were detected using the derivatization agents: O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine and N,O-bis(trimethysilyl)trifluoroacetamide. The positively identified reaction products were glyoxal, methylglyoxal and 4-oxopentanal. The proposed oxidation products based on previously published VOC/O(3) reaction mechanisms were: 4-methylcyclohex-3-en-1-one, 6-hydroxyhept-en-2-one, 3-(1-hydroxy-1-methylethyl)-6-methylcyclohex-2-en-1-one) and one surface-enhanced reaction product: 5-(1-hydroxy-1-methylethyl)-2-methylcyclohex-2-en-1-one. Though similar products were observed in gas-phase alpha-terpineol/O(3) reactions, the ratio of the reaction products were different suggesting stabilization of larger molecular weight species by the surface. Emission profiles of these oxidation products over 72 h are also reported. Volatile organic compounds (VOCs) can interact with indoor initiators [such as hydroxyl radicals (OH*), ozone and nitrate radicals (NO(3)*)] to form a number of oxygenated by-products in the gas-phase. However, when VOCs are applied to or are present on the surface, heterogeneous chemistry with indoor initiators can also occur. The surface can influence the reaction mechanism to produce new surface reaction products. The work, described here, shows the interaction of alpha-terpineol (major component of pine oil) with ozone and air on both glass and vinyl flooring. These results demonstrated emissions of oxygenated organic compounds as a result of reaction and that further investigations of this chemistry are required to accurately estimate indoor occupant exposures.

Alpha-ketoisocaproate is not a true substrate for ATP production by pancreatic beta-cell mitochondria.

PubMed

Lembert, N; Idahl, L A

1998-03-01

The ability of alpha-ketoisocaproate (KIC) to induce ATP production in isolated mitochondria from pancreatic beta-cells was examined with a bioluminometric method. There was no ATP production from KIC when tested alone or in combination with malate (1 mmol/l), nor did DL-beta-hydroxybutyrate induce mitochondrial ATP production, whereas palmitoyl-carnitine and pyruvate were efficient stimulators of mitochondrial ATP production in the presence of an equimolar concentration of malate. However, KIC stimulated the mitochondrial ATP production when tested in combination with glutamate (10 mmol/l). The concentration necessary to obtain half-maximal stimulation was approximately 50 micromol/l KIC, and maximal activity, comparable to that obtained with fatty acids, was reached at 1 mmol/l KIC. Higher KIC concentrations inhibited the mitochondrial ATP production, whereas a plateau was attained at 1 mmol/l KIC in the presence of glutamine. Ca2+ stimulated the maximal mitochondrial ATP production induced by KIC. Maximal stimulation was obtained with 300 nmol/l Ca2+ in the presence of 0.3 mmol/l KIC. Ca2+ reduced the concentration of KIC necessary for half-maximal stimulation to <30 micromol/l. Leucine stimulated the mitochondrial ATP production in the presence of glutamate to the same extent as KIC. Half-maximal stimulation was observed with 2 mmol/l leucine. There were no additive effects on mitochondrial ATP production when KIC and leucine were tested in combination. The results demonstrate that KIC by itself is not a mitochondrial substrate for ATP production. KIC must transaminate with glutamate or glutamine to yield alpha-ketoglutarate and leucine. Since leucine allosterically activates glutamate dehydrogenase, which also produces alpha-ketoglutarate, the insulinogenic effect of KIC may in part be due to the intramitochondrial generation of alpha-ketoglutarate. Since KIC-induced ATP production reaches a plateau already at micromolar concentrations (i.e., far below the concentrations at which KIC induces insulin release), it is proposed here that the catabolism of KIC may induce additional signals related to insulin release.

Comparison of cell wall proteins of Saccharomyces cerevisiae as anchors for cell surface expression of heterologous proteins.

PubMed Central

Van der Vaart, J M; te Biesebeke, R; Chapman, J W; Toschka, H Y; Klis, F M; Verrips, C T

1997-01-01

The carboxyl-terminal regions of five cell wall proteins (Cwp1p, Cwp2p, Ag alpha 1p, Tip1p, and Flo1p) and three potential cell wall proteins (Sed1p, YCR89w, and Tir1p) all proved capable of immobilizing alpha-galactosidase in the cell wall of Saccharomyces cerevisiae. The fraction of the total amount of fusion protein that was localized to the cell wall varied depending on the anchor domain used. The highest proportion of cell wall incorporation was achieved with Cwp2p, Ag alpha 1p, or Sed1p as an anchor. Although 80% of these fusion proteins were incorporated in the cell wall, the total production of alpha-galactosidase-Ag alpha 1p was sixfold lower than that of alpha-galactosidase-Cwp2p and eightfold lower than that of alpha-galactosidase-Sed1p. Differences in mRNA levels were not responsible for this discrepancy, nor was an intracellular accumulation of alpha-galactosidase-Ag alpha 1p detectable. A lower translation efficiency of the alpha-galactosidase-AG alpha 1 fusion construct is most likely to be responsible for the low level of protein production. alpha-Galactosidase immobilized by the carboxyl-terminal 67 amino acids of Cwp2p was most effective in the hydrolysis of the high-molecular-weight substrate guar gum from Cyamopsis tetragonoloba. This indicates that the use of a large anchoring domain does not necessarily result in a better exposure of the immobilized enzyme to the exterior of the yeast cell. PMID:9023939

Immunoreactive transforming growth factor alpha is commonly present in colorectal neoplasia.

PubMed Central

Tanaka, S.; Imanishi, K.; Yoshihara, M.; Haruma, K.; Sumii, K.; Kajiyama, G.; Akamatsu, S.

1991-01-01

Surgical specimens from 19 patients with invasive colorectal cancers and 12 specimens of normal mucosa from the same patients were examined immunohistochemically for the production of the immunoreactive (IR-) transforming growth factor (TGF)-alpha and IR-epidermal growth factor (EGF) with an anti-TGF-alpha monoclonal antibody (MAb) OAL-MTG01 and anti-EGF MAb KEM-10. Immunoreactive TGF-alpha was detected in 16 (84.2%) of 19 colorectal cancers. In contrast, there was no IR-TGF-alpha in the gland cells of normal mucosa. Immunoreactive EGF was detected in 7 (36.8%) of 19 colorectal cancers and 1 (8.3%) of 12 cases of normal mucosa. The production of both IR-TGF-alpha and IR-EGF in colorectal cancer did not differ by histologic type and Dukes' stage. Immunoreactive TGF-alpha was detected at significantly higher incidence than IR-EGF in colorectal cancer. These results indicate that IR-TGF-alpha should prove valuable as a possible tumor marker in colorectal cancers, and it may be very useful in understanding the biology of colorectal cancer. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:1853928

Genome Improvement at JGI-HAGSC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grimwood, Jane; Schmutz, Jeremy J.; Myers, Richard M.

Since the completion of the sequencing of the human genome, the Joint Genome Institute (JGI) has rapidly expanded its scientific goals in several DOE mission-relevant areas. At the JGI-HAGSC, we have kept pace with this rapid expansion of projects with our focus on assessing, assembling, improving and finishing eukaryotic whole genome shotgun (WGS) projects for which the shotgun sequence is generated at the Production Genomic Facility (JGI-PGF). We follow this by combining the draft WGS with genomic resources generated at JGI-HAGSC or in collaborator laboratories (including BAC end sequences, genetic maps and FLcDNA sequences) to produce an improved draft sequence.more » For eukaryotic genomes important to the DOE mission, we then add further information from directed experiments to produce reference genomic sequences that are publicly available for any scientific researcher. Also, we have continued our program for producing BAC-based finished sequence, both for adding information to JGI genome projects and for small BAC-based sequencing projects proposed through any of the JGI sequencing programs. We have now built our computational expertise in WGS assembly and analysis and have moved eukaryotic genome assembly from the JGI-PGF to JGI-HAGSC. We have concentrated our assembly development work on large plant genomes and complex fungal and algal genomes.« less

Determining Proportion of Exfoliative Vaginal Cell during Various Stages of Estrus Cycle Using Vaginal Cytology Techniques in Aceh Cattle

PubMed Central

Siregar, Tongku N.; Melia, Juli; Rohaya; Thasmi, Cut Nila; Masyitha, Dian; Wahyuni, Sri; Rosa, Juliana; Nurhafni; Panjaitan, Budianto; Herrialfian

2016-01-01

The aim of this study was to investigate the period of estrus cycle in aceh cattle, Indonesia, based on vaginal cytology techniques. Four healthy females of aceh cattle with average weight of 250–300 kg, age of 5–7 years, and body condition score of 3-4 were used. All cattle were subjected to ultrasonography analysis for the occurrence of corpus luteum before being synchronized using intramuscular injections of PGF2 alpha 25 mg. A vaginal swab was collected from aceh cattle, stained with Giemsa 10%, and observed microscopically. Period of estrus cycle was predicted from day 1 to day 24 after estrus synchronization was confirmed using ultrasonography analysis at the same day. The result showed that parabasal, intermediary, and superficial epithelium were found in the vaginal swabs collected from proestrus, metestrus, and diestrus aceh cattle. Proportions of these cells in the particular period of estrus cycle were 36.22, 32.62, and 31.16 (proestrus); 21.33, 32.58, and 46.09 (estrus); 40.75, 37.58, and 21.67 (metestrus); and 41.07, 37.38, and 21.67 (diestrus), respectively. In conclusion, dominant proportion of superficial cell that occurred in estrus period might be used as the base for determining optimal time for insemination. PMID:26977335

Non-Invasive Pregnancy Diagnosis in Big Cats using the PGFM (13,14-dihydro-15-keto-PGF2α) Assay

PubMed Central

Chandrasekhar, Mithileshwari; Jewgenow, Katarina; Umapathy, Govindhaswamy

2015-01-01

Non-invasive monitoring of hormones using feces has become a vital tool for reproductive management and reliable pregnancy diagnosis in big cats. Previous studies described the PGF2α metabolite (PGFM) as an indicator of pregnancy in various feline species. The present study aimed to standardize pregnancy detection in big cats like the tiger (Panthera tigris), jaguar (Panthera onca) and lion (Panthera leo) using fecal samples. High-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LCMS) were performed to identify PGFM in feces. An EIA developed against 9α,11α-dihydroxy-15-oxo-prost-5-en-1-oic acid-BSA was used to assay PGFM in fecal samples of the Bengal tiger, Asiatic lion and jaguar. The PGFM levels increased after 9 weeks of pregnancy and remained elevated until parturition. All animals showed elevated levels of PGFM in the last trimester of pregnancy, thus making PGFM a reliable tool for pregnancy diagnosis during this period that can be useful in captive breeding programs in these species. PMID:26633886

A defective retroviral vector encoding human interferon-alpha2 can transduce human leukemic cell lines.

PubMed

Austruy, E; Bagnis, C; Carbuccia, N; Maroc, C; Birg, F; Dubreuil, P; Mannoni, P; Chabannon, C

1998-01-01

Using the LXSN backbone, a defective retroviral vector (LISN) was constructed that encodes the human interferon (IFN)-alpha2 (hIFN-alpha2) gene and the neomycin resistance gene; the hIFN-alpha2 gene was cloned from human placental genomic DNA. High titers of the LISN retrovirus were produced by the amphotropic packaging cell line GP+envAM12. LISN is able to infect three human hematopoietic and leukemic cell lines: K562, LAMA-84, and TF-1. G418-resistant cells were detected in a similar proportion after infection with either the LISN retroviral vector or the LnLSN retroviral vector (encoding the nlsLacZ gene instead of hIFN-alpha2), suggesting that hIFN-alpha2 does not inhibit (or only partially inhibits) the production of retroviral particles by the packaging cell line and the infection of human cells. LISN-infected cells express and secrete hIFN-alpha2 as demonstrated by Northern blot analysis of poly(A)+ RNA, detection of the intracellular protein by fluorescence-activated cell sorter analysis, and detection of secreted hIFN-alpha in cell supernatants using an enzyme-linked immunosorbent assay. Retrovirally produced hIFN-alpha2 is biologically active, as demonstrated by the partial inhibition of the growth of K562 and TF-1, the modulation of the expression of cell surface antigens, the induction of the (2'-5') oligoadenylate synthetase, and, for LAMA-84, the down-modulation of the BCR-ABL protein. We conclude that the infection of human leukemic cell lines with a retroviral vector encoding hIFN-alpha2 is feasible and induces the expected biological effects. This experimental model will be useful in investigating the possibility of transducing normal and leukemic cells and hematopoietic progenitors and in determining the consequences of the autocrine production of hIFN-alpha2 on the behavior of these cells.

Preliminary results from fault-slip analysis of the Pärvie neotectonic postglacial fault zone, northern Sweden

NASA Astrophysics Data System (ADS)

Backstrom, Ann; Viola, Giulio; Rantakokko, Nina; Jonsson, Erik; Ask, Maria

2013-04-01

Our study aims at constraining the paleostress field evolution of neotectonic postglacial faulting in northern Sweden. Postglacial faulting is a special type of intraplate faulting triggered by the retreat of continental glaciers and by the induced changes of the local stress field. We investigated the longest known post-glacial fault (PGF) in Scandinavia, the Pärvie PGF. It is 155 km long and consists of a series of 3-10 m high fault scarps developed in several rock types such as mafic and felsic meta-volcanic rocks, and in the north, Archean granites and gneisses. Most of the scarps trend north-northeast and dip steeply to the west. A smaller sibling fault to the east (the Lansjärv PGF) displaces postglacial sediments. It is interpreted as resulting from a great earthquake (M≤8.2) at the end or just after the last glaciation (~10 ky B.P.). Microseismic activity is still present along the Pärvie fault zone. Unfortunately, the stress history of the Pärvie PGF before the last glaciation is poorly known. To reconstruct its stress history, we have performed fault-slip analysis. Fault slip data have been collected from two profiles across the Pärvie PGF in the Corruvagge valley and in Kamasjaure in the north, and Stora Sjöfallet in the southern part of the fault zone. Cross-cutting relationships, fracture mineralization and structural features of the brittle overprint of the rocks have been used to suggest a conceptual model of the brittle history of the fault. Ca. 40 kinematically constrained fault planes were used in the inversion study in addition to ca. 1060 fractures. Preliminary results indicate that the oldest generation of fractures are coated by pink plagioclase and clinoamphibole. The key mineral epidote is prominent along cataclastic structures. Rarly multiple kinematic indicators are identified along the same fracture, indicating polyphase reactivation. Epidote coating is found along fractures from all the computed stress-fields, indicating that epidote coating is diagnostic of the early faulting phases as well as of the youngest. Four distinct stress fields were identified, whereof the youngest is assigned to the Pärvie PG faulting event. This study confirms that postglacial faulting have reactivated an old fault system, which had accommodated at least three earlier episodes of brittle deformation. Comparison with paleostress studies of regional significance elsewhere in Fennoscandia makes it possible to tentatively assign these older events to a deformation phase shortly after the Svecokarelian orogeny, around 1,7 Ga, and one stress-field that can be either the stress field during the Sveconorwegian or Caledonian orogeny. An extensional phase has also been identified but not further constrained, yet.

A soluble form of IL-13 receptor alpha 1 promotes IgG2a and IgG2b production by murine germinal center B cells.

PubMed

Poudrier, J; Graber, P; Herren, S; Gretener, D; Elson, G; Berney, C; Gauchat, J F; Kosco-Vilbois, M H

1999-08-01

A functional IL-13R involves at least two cell surface proteins, the IL-13R alpha 1 and IL-4R alpha. Using a soluble form of the murine IL-13R alpha 1 (sIL-13R), we reveal several novel features of this system. The sIL-13R promotes proliferation and augmentation of Ag-specific IgM, IgG2a, and IgG2b production by murine germinal center (GC) B cells in vitro. These effects were enhanced by CD40 signaling and were not inhibited by an anti-IL4R alpha mAb, a result suggesting other ligands. In GC cell cultures, sIL-13R also promoted IL-6 production, and interestingly, sIL-13R-induced IgG2a and IgG2b augmentation was absent in GC cells isolated from IL-6-deficient mice. Furthermore, the effects of the sIL-13R molecule were inhibited in the presence of an anti-IL-13 mAb, and preincubation of GC cells with IL-13 enhanced the sIL-13R-mediated effects. When sIL-13R was injected into mice, it served as an adjuvant-promoting production to varying degrees of IgM and IgG isotypes. We thus propose that IL-13R alpha 1 is a molecule involved in B cell differentiation, using a mechanism that may involve regulation of IL-6-responsive elements. Taken together, our data reveal previously unknown activities as well as suggest that the ligand for the sIL-13R might be a component of the IL-13R complex or a counterstructure yet to be defined.

Lack of effect of the alpha2C-adrenoceptor Del322-325 polymorphism on inhibition of cyclic AMP production in HEK293 cells.

PubMed

Montgomery, M D; Bylund, D B

2010-02-01

The alpha(2C)-adrenoceptor has multiple functions, including inhibiting release of noradrenaline from presynaptic nerve terminals. A human alpha(2C) polymorphism, Del322-325, a potential risk factor for heart failure, has been reported to exhibit reduced signalling in CHO cells. To further understand the role of the Del322-325 polymorphism on receptor signalling, we attempted to replicate and further study the reduced signalling in HEK293 cells. Human alpha(2C) wild-type (WT) and Del322-325 adrenoceptors were stably transfected into HEK293 cells. Radioligand binding was performed to determine affinities for both receptors. In intact cells, inhibition of forskolin-stimulated cyclic AMP production by WT and Del322-325 clones with a range of receptor densities (200-2320 fmol.mg(-1) protein) was measured following agonist treatment. Noradrenaline, brimonidine and clonidine exhibited similar binding affinities for WT and Del322-325. Brimonidine and clonidine also had similar efficacies and potencies for both receptors for the inhibition of cyclic AMP production at all receptor densities tested. A linear regression analysis comparing efficacy and potency with receptor expression levels showed no differences in slopes between WT and Del322-325. The alpha(2C) WT and Del322-325 adrenoceptors exhibited similar binding properties. Additionally, inhibition of cyclic AMP production by Del322-325 was similar to that of WT over a range of receptor densities. Therefore, in intact HEK293 cells, the alpha(2C)-Del322-325 polymorphism does not exhibit reduced signalling to adenylyl cyclase and may not represent a clinically important phenotype.

Growth-related gene product {alpha}: A chemotactic cytokine for neutrophils in rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koch, A.E.; Pope, R.M.; Shah, M.R.

Leukocyte recruitment is critical in the inflammation seen in rheumatoid arthritis (RA). To determine whether the chemokine growth-related gene product {alpha} (gro{alpha}) plays a role in this process, we examined synovial tissue (ST), synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF contained more antigenic gro{alpha} (mean 5.3 {+-} 1.9 ng/ml) than did SFs from either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p < 0.05). RA plasma contained more gro{alpha} (mean 4.3 {+-} 1.8 ng/ml) than normal plasma (mean 0.1 ng/ml) (p < 0.05). RA ST fibroblasts (1.2 x 10{sup 5}/cells/ml RPMImore » 1640/24 h) produced antigenic gro{alpha} (mean 0.2 {+-} 0.1 ng/ml), and this production was increased significantly upon incubation with TNF-{alpha} (mean 1.3 {+-} 0.3 ng/ml) or IL-1{beta} (mean 2.3 {+-} 0.6 ng/ml) (p < 0.05). Cells from RA SF also produced gro{alpha}: neutrophils (PMNs) (10{sup 7} cells/ml/24 h) produced 3.7 {+-} 0.7 ng/ml. RA SF mononuclear cells produced gro{alpha}, particularly upon incubation with LPS or PHA. Immunoreactive ST gro{alpha} was found in greater numbers of RA compared with either OA or normal lining cells, as well as in RA compared with OA subsynovial macrophages (p < 0.05). IL-8 accounted for a mean of 36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil-activating peptide-78 accounted for 34%, and gro{alpha} for 28%, of this activity. Combined neutralization of all three chemokines in RA SFs resulted in a mean decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These results indicate that gro{alpha} plays an important role in the ingress of PMNs into the RA joint. 54 refs., 6 figs., 1 tab.« less

alpha-Galactosidase from Bacillus megaterium VHM1 and its application in removal of flatulence-causing factors from soymilk.

PubMed

Patil, Aravind Goud G; K, Praveen Kumar S; Mulimani, Veerappa H; Veeranagouda, Yaligara; Lee, Kyoung

2010-11-01

A bacterial strain capable of producing extracellular alpha-galactosidase was isolated from sugar cane industrial waste soil sample. Microbiological, physiological, and biochemical studies revealed that isolate belonged to Bacillus sp,. Furthermore, 16S rDNA sequence analysis of new isolates was identified as Bacillus megaterium VHM1. The production of alpha-galactosidase was optimized by various physical culture conditions. Guar gum and yeast extract acted as the best carbon and nitrogen source, respectively for the production of alpha-galactosidase. The enzyme showed an optimum pH at 7.5 and was stable over a pH between 5 and 9. The enzyme was optimally active in 55degreesC and the enzyme was thermostable with half life of 120 minutes at 55 degrees C and lost their 90%, residual activity in 120 minutes at 60 degrees C. alpha-Galactosidase was strongly inhibited by Ag2, Cu2, and Hg2+ at 1mM concentration. The metal ions Fe2, Mn2+, and Mg2+ had no effect on alpha-galactosidase activity, Zn2+,Ni2+, and Ca2+ reduced the enzyme activity slightly. The B megaterium VHM1 enzyme treatment completely hydrolyzed flatulence-causing sugars of soymilk within one and half hour.

Radiation-induced changes in the profile of spinal cord serotonin, prostaglandin synthesis, and vascular permeability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siegal, T.; Pfeffer, M.R.

To investigate the profile of biochemical and physiological changes induced in the rat spinal cord by radiation, over a period of 8 months. The thoraco-lumbar spinal cords of Fisher rats were irradiated to a dose of 15 Gy. The rats were then followed and killed at various times afterward. Serotonin (5-HT) and its major metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed as well as prostaglandin synthesis. Microvessel permeability was assessed by quantitative evaluation of Evans blue dye extravasation. None of the rats developed neurologic dysfunction, and histologic examination revealed only occasional gliosis in the ventral white matter at 240 days aftermore » irradiation. Serotonin levels were unchanged at 2, 14, and 56 days after radiation but increased at 120 and 240 days in the irradiated cord segments when compared to both the nonirradiated thoracic and cervical segments (p < 0.01) and age-matched controls (p < 0.03). The calculated utilization ratio of serotonin (5-HIAA/5-HT) remained unchanged. Immediately after radiation (at 3 and 24 h) an abrupt but brief increase in the synthesis of prostaglandin-E{sub 2} (PGE{sub 2}), thromboxane (TXB{sub 2}), and prostacyclin [6 keto-PGF1{alpha} (6KPGF)] was noted, which returned to normal at 3 days. This was followed after 7 and 14 days by a significant fall off in synthesis of all three prostaglandins. Thereafter, at 28, 56, 120, and 240 days, escalated production of thromboxane followed, white prostacyclin synthesis remained markedly reduced (-88% of control level at 240 days). Up to 7 days after radiation the calculated TXB{sub 2}/6KPGF ratio remained balanced, regardless of the observed abrupt early fluctuations in their rate of synthesis. Later, between 7 and 240 days after radiation, a significant imbalance was present which became more pronounced over time. In the first 24 h after radiation, a 104% increase in microvessel permeability was observed which returned to normal by 3 days. 57 refs., 3 figs.« less

Influence of cultivating conditions on the alpha-galactosidase biosynthesis from a novel strain of Penicillium sp. in solid-state fermentation.

PubMed

Wang, C L; Li, D F; Lu, W Q; Wang, Y H; Lai, C H

2004-01-01

The work is intended to achieve optimum culture conditions of alpha-galactosidase production by a mutant strain Penicillium sp. in solid-state fermentation (SSF). Certain fermentation parameters involving incubation temperature, moisture content, initial pH value, inoculum and load size of medium, and incubation time were investigated separately. The optimal temperature and moisture level for alpha-galactosidase biosynthesis was found to be 30 degrees C and 50%, respectively. The range of pH 5.5-6.5 was favourable. About 40-50 g of medium in 250-ml flask and inoculum over 1.0 x 10(6) spores were suitable for enzyme production. Seventy-five hours of incubation was enough for maximum alpha-galactosidase production. Substrate as wheat bran supplemented with soyabean meal and beet pulp markedly improved the enzyme yield in trays. Under optimum culture conditions, the alpha-galactosidase activity from Penicillium sp. MAFIC-6 indicated 185.2 U g(-1) in tray of SSF. The process on alpha-galactosidase production in laboratory scale may have a potentiality of scaling-up.

Hot topic: Comparison of sex-sorted and conventional semen within a fixed-time artificial insemination protocol designed for dairy heifers.

PubMed

Mallory, D A; Lock, S L; Woods, D C; Poock, S E; Patterson, D J

2013-02-01

The objective was to compare pregnancy per AI (P/AI) with conventional (CON) or sex-sorted (SS) semen from a single sire within a fixed-time AI (FTAI) program designed for dairy heifers. Holstein heifers (n=240) were assigned to treatment (CON or SS) according to body weight and reproductive tract score. All heifers underwent FTAI by using the "Show-Me-Synch" protocol [controlled internal drug release (CIDR) insert from d 0 to 14 followed by PGF(2α) (25mg i.m.) 16d after insert removal (d 30) with GnRH (100 µg i.m.) and FTAI at 66 h after PGF(2α)]. A single professional technician performed the FTAI. Heifers were fitted with heat detection patches at PGF(2α) to characterize estrous response. Estrous response did not differ between CON (63/120; 53%) and SS (70/120; 58%) treatments. The CON heifers, however, achieved greater FTAI P/AI (82/120; 68%) compared with SS (45/120; 38%) heifers. The P/AI did not differ for CON heifers that exhibited or failed to exhibit estrus before FTAI [44/63 (70%) vs. 38/57(67%), respectively]. For SS heifers, however, those that exhibited estrus had greater P/AI compared with those that failed to exhibit estrus [32/70 (46%) vs. 13/50 (26%)]. Pregnancy per AI resulting from FTAI was greater for heifers that were inseminated with CON semen compared with those that received SS semen. The expression of estrus before FTAI did not affect P/AI when CON semen was used, whereas the P/AI with SS semen was greater for heifers detected in estrus. Further studies are required to develop strategies for using sex-sorted semen when inseminating heifers at predetermined fixed times on the basis of expression of estrus before FTAI. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Reduced maximal oxygen consumption and overproduction of proinflammatory cytokines in athletes.

PubMed

Vaisberg, Mauro; de Mello, Marco Tulio; Seelaender, Marília Cerqueira Leite; dos Santos, Ronaldo Vagner Thomatieli; Costa Rosa, Luis Fernando Bicudo Pereira

2007-01-01

It was the aim of this study to evaluate whether chronic pain in athletes is related to performance, measured by the maximum oxygen consumption and production of hormones and cytokines. Fifty-five athletes with a mean age of 31.9 +/- 4.2 years engaged in regular competition and showing no symptoms of acute inflammation, particularly fever, were studied. They were divided into 2 subgroups according to the occurrence of pain. Plasma concentrations of adrenaline, noradrenaline, cortisol, prolactin, growth hormone and dopamine were measured by radioimmunoassay, and the production of the cytokines interleukin (IL)-1, IL-2, IL-4, IL-6, tumor necrosis factor-alpha, interferon-alpha and prostaglandin E(2) by whole-blood culture. Maximal oxygen consumption was determined during an incremental treadmill test. There was no change in the concentration of stress hormones, but the athletes with chronic pain showed a reduction in maximum oxygen consumption (22%) and total consumption at the anaerobic threshold (25%), as well as increased cytokine production. Increases of 2.7-, 8.1-, 1.7- and 3.7-fold were observed for IL-1, IL-2, tumor necrosis factor-alpha and interferon-alpha, respectively. Our data show that athletes with chronic pain have enhanced production of proinflammatory cytokines and lipid mediators and reduced performance in the ergospirometric test. (c) 2008 S. Karger AG, Basel.

Temporal dynamics of sensorimotor integration in speech perception and production: independent component analysis of EEG data

PubMed Central

Jenson, David; Bowers, Andrew L.; Harkrider, Ashley W.; Thornton, David; Cuellar, Megan; Saltuklaroglu, Tim

2014-01-01

Activity in anterior sensorimotor regions is found in speech production and some perception tasks. Yet, how sensorimotor integration supports these functions is unclear due to a lack of data examining the timing of activity from these regions. Beta (~20 Hz) and alpha (~10 Hz) spectral power within the EEG μ rhythm are considered indices of motor and somatosensory activity, respectively. In the current study, perception conditions required discrimination (same/different) of syllables pairs (/ba/ and /da/) in quiet and noisy conditions. Production conditions required covert and overt syllable productions and overt word production. Independent component analysis was performed on EEG data obtained during these conditions to (1) identify clusters of μ components common to all conditions and (2) examine real-time event-related spectral perturbations (ERSP) within alpha and beta bands. 17 and 15 out of 20 participants produced left and right μ-components, respectively, localized to precentral gyri. Discrimination conditions were characterized by significant (pFDR < 0.05) early alpha event-related synchronization (ERS) prior to and during stimulus presentation and later alpha event-related desynchronization (ERD) following stimulus offset. Beta ERD began early and gained strength across time. Differences were found between quiet and noisy discrimination conditions. Both overt syllable and word productions yielded similar alpha/beta ERD that began prior to production and was strongest during muscle activity. Findings during covert production were weaker than during overt production. One explanation for these findings is that μ-beta ERD indexes early predictive coding (e.g., internal modeling) and/or overt and covert attentional/motor processes. μ-alpha ERS may index inhibitory input to the premotor cortex from sensory regions prior to and during discrimination, while μ-alpha ERD may index sensory feedback during speech rehearsal and production. PMID:25071633

DNA catabolites in triathletes: effects of supplementation with an aronia-citrus juice (polyphenols-rich juice).

PubMed

García-Flores, Libia Alejandra; Medina, Sonia; Cejuela-Anta, Roberto; Martínez-Sanz, José Miguel; Abellán, Ángel; Genieser, Hans-Gottfried; Ferreres, Federico; Gil-Izquierdo, Ángel

2016-04-01

In this study we analyzed whether our aronia-citrus juice (ACJ, the composition is based on a mixture of 95% citrus juice with 5% of Aronia melanocarpa juice), rich in polyphenols, and physical exercise had an effect on seven catabolites of DNA identified in plasma and on a urine isoprostane (8-iso-PGF2α). Sixteen elite triathletes on a controlled diet for triathlon training (45 days) were used in this clinical trial. Our results show a decrease in the 8-hydroxy-2'-deoxyguanosine concentration due to chronic physical exercise. The ACJ intake and physical exercise maintained the guanosine-3',5'-cyclic monophosphate plasmatic concentrations and decreased the concentration of 8-hydroxyguanine as well as urinary values of 8-iso-PGF2α. Finally, we observed a significant increase in the 8-nitroguanosine levels in triathletes after ACJ intake, compared to the placebo stage. It is concluded that the combination of the intake of ACJ, rich in polyphenolic compounds, with adequate training was able to influence the plasmatic and urinary values of oxidative stress biomarkers. This suggests a positive effect on the oxidative damage and potential associations with DNA repair mechanisms.

Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin.

PubMed

Liu, Yan-Li; Lin, Hai-Ming; Zou, Rong; Wu, Jun-Chao; Han, Rong; Raymond, Laurence N; Reid, Paul F; Qin, Zheng-Hong

2009-02-01

Cobratoxin (CTX), the long-chain alpha-neurotoxin from Thailand cobra venom, has been demonstrated to have analgesic action in rodent pain models. The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adjuvant arthritis (AA) in rats. Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats. Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA. Histopathological changes in synoviocytes were examined under a microscope. Involvement of the cholinergic system in the effects of CTX was examined by pretreatment of animals with the alpha(7) nicotinic receptor (alpha(7)-nAChR) antagonist methyllycaconitine (MLA). CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal. The levels of TNF-alpha, IL-1 and IL-2 in the serum of AA rats were increased, whereas the level of IL-10 was decreased. Histopathological examination of synoviocytes showed pronounced inflammation and accumulation of collagen. The administration of CTX (17.0 microg/kg, ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia. CTX also reduced the production of TNF-alpha, IL-1, and IL-2 but increased the production of IL-10 and altered pathohistological changes. The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg, sc). These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines. alpha(7)-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX.

Thalidomide inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production via down-regulation of MyD88 expression.

PubMed

Noman, Abu Shadat M; Koide, Naoki; Hassan, Ferdaus; I-E-Khuda, Imtiaz; Dagvadorj, Jargalsaikhan; Tumurkhuu, Gantsetseg; Islam, Shamima; Naiki, Yoshikazu; Yoshida, Tomoaki; Yokochi, Takashi

2009-02-01

The effect of thalidomide on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production was studied by using RAW 264.7 murine macrophage-like cells. Thalidomide significantly inhibited LPS-induced TNF-alpha production. Thalidomide prevented the activation of nuclear factor (NF)-KB by down-regulating phosphorylation of inhibitory KB factor (IKB), and IKB kinase (IKK)-alpha and IKK-beta Moreover, thalidomide inhibited LPS-induced phosphorylation of AKT, p38 and stress-activated protein kinase (SAPK)/JNK. The expression of myeloid differentiation factor 88 (MyD88) protein and mRNA was markedly reduced in thalidomide-treated RAW 264.7 cells but there was no significant alteration in the expression of interleukin-1 receptor-associated kinase (IRAK) 1 and TNF receptor-associated factor (TRAF) 6 in the cells. Thalidomide did not affect the cell surface expression of Toll-like receptor (TLR) 4 and CD14, suggesting the impairment of intracellular LPS signalling in thalidomide-treated RAW 264.7 cells. Thalidomide significantly inhibited the TNF-alpha production in response to palmitoyl-Cys(RS)-2,3-di(palmitoyloxy) propyl)-Ala-Gly-OH (Pam(3)Cys) as a MyD88-dependent TLR2 ligand. Therefore, it is suggested that thalidomide might impair LPS signalling via down-regulation of MyD88 protein and mRNA and inhibit LPS-induced TNF-alpha production. The putative mechanism of thalidomide-induced MyD88 down-regulation is discussed.

Biotin deficiency up-regulates TNF-alpha production in murine macrophages.

PubMed

Kuroishi, Toshinobu; Endo, Yasuo; Muramoto, Koji; Sugawara, Shunji

2008-04-01

Biotin, a water-soluble vitamin of the B complex, functions as a cofactor of carboxylases that catalyze an indispensable cellular metabolism. Although significant decreases in serum biotin levels have been reported in patients with chronic inflammatory diseases, the biological roles of biotin in inflammatory responses are unclear. In this study, we investigated the effects of biotin deficiency on TNF-alpha production. Mice were fed a basal diet or a biotin-deficient diet for 8 weeks. Serum biotin levels were significantly lower in biotin-deficient mice than biotin-sufficient mice. After i.v. administration of LPS, serum TNF-alpha levels were significantly higher in biotin-deficient mice than biotin-sufficient mice. A murine macrophage-like cell line, J774.1, was cultured in a biotin-sufficient or -deficient medium for 4 weeks. Cell proliferation and biotinylation of intracellular proteins were decreased significantly in biotin-deficient cells compared with biotin-sufficient cells. Significantly higher production and mRNA expression of TNF-alpha were detected in biotin-deficient J774.1 cells than biotin-sufficient cells in response to LPS and even without LPS stimulation. Intracellular TNF-alpha expression was inhibited by actinomycin D, indicating that biotin deficiency up-regulates TNF-alpha production at the transcriptional level. However, the expression levels of TNF receptors, CD14, and TLR4/myeloid differentiation protein 2 complex were similar between biotin-sufficient and -deficient cells. No differences were detected in the activities of the NF-kappaB family or AP-1. The TNF-alpha induction by biotin deficiency was down-regulated by biotin supplementation in vitro and in vivo. These results indicate that biotin deficiency may up-regulate TNF-alpha production or that biotin excess down-regulates TNF-alpha production, suggesting that biotin status may influence inflammatory diseases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimura, Rino; Takahashi, Nobuyuki, E-mail: nobu@kais.kyoto-u.ac.jp; Murota, Kaeko

Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. {yields} PPAR{alpha} activation also increased oxygen consumption rate and CO{sub 2} production and decreased secretion of triglyceride and ApoB from Caco-2 cells. {yields} Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO{sub 2} production in small intestinal epithelial cells. {yields} Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. {yields} It suggested that intestinal lipid metabolism regulated by PPAR{alpha} activation suppresses postprandial lipidemia. -- Abstract: Activation ofmore » peroxisome proliferator-activated receptor (PPAR)-{alpha} which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPAR{alpha} activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPAR{alpha} activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPAR{alpha} agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and production of CO{sub 2} and acid soluble metabolites in enterocytes. Moreover, bezafibrate treatment suppressed postprandial lipidemia after oral administration of olive oil to the mice. These findings indicate that PPAR{alpha} activation suppresses postprandial lipidemia through enhancement of fatty acid oxidation in enterocytes, suggesting that intestinal lipid metabolism regulated by PPAR{alpha} activity is a novel target of PPAR{alpha} agonist for decreasing circulating levels of lipids under postprandial conditions.« less

Tocotrienols suppress proinflammatory markers and cyclooxygenase-2 expression in RAW264.7 macrophages.

PubMed

Yam, Mun-Li; Abdul Hafid, Sitti Rahma; Cheng, Hwee-Ming; Nesaretnam, Kalanithi

2009-09-01

Tocotrienols are powerful chain breaking antioxidant. Moreover, they are now known to exhibit various non-antioxidant properties such as anti-cancer, neuroprotective and hypocholesterolemic functions. This study was undertaken to investigate the anti-inflammatory effects of tocotrienol-rich fraction (TRF) and individual tocotrienol isoforms namely delta-, gamma-, and alpha-tocotrienol on lipopolysaccharide-stimulated RAW264.7 macrophages. The widely studied vitamin E form, alpha-tocopherol, was used as comparison. Stimulation of RAW264.7 with lipopolysaccharide induced the release of various inflammatory markers. 10 mcirog/ml of TRF and all tocotrienol isoforms significantly inhibited the production of interleukin-6 and nitric oxide. However, only alpha-tocotrienol demonstrated a significant effect in lowering tumor necrosis factor-alpha production. Besides, TRF and all tocotrienol isoforms except gamma-tocotrienol reduced prostaglandin E(2) release. It was accompanied by the down-regulation of cyclooxygenase-2 gene expression by all vitamin E forms except alpha-tocopherol. Collectively, the data suggested that tocotrienols are better anti-inflammatory agents than alpha-tocopherol and the most effective form is delta-tocotrienol.

Stereospecific deuteration of alpha-furanosyl azomycin nucleosides: a model reaction for tritium radiolabeling.

PubMed

Kumar, Piyush; Emami, Saeed; McEwan, Alexander J B; Wiebe, Leonard I

2008-06-01

Stereospecific synthesis of 1-alpha-d-(2-deuteroribofuranosyl)-2-nitroimidazole (2'-[(2)H]-alpha-AZR) is reported. This, deuteration was independent of the configuration of C-2' -OH group (arabinose or ribose) in sugar moiety of starting molecules. Slightly better yield (>37%) of the deuterated product, 6, from arabinosyl precursor in comparison to corresponding ribose precursor (29%) was obtained which may reflect better stereochemical availability of C-2' -OH in arabinose during oxidation.

Oxidation of cholesterol moiety of low density lipoprotein in the presence of human endothelial cells or Cu+2 ions: identification of major products and their effects.

PubMed

Bhadra, S; Arshad, M A; Rymaszewski, Z; Norman, E; Wherley, R; Subbiah, M T

1991-04-15

Oxidation of lipoproteins is believed to play a key role in atherogenesis. In this study, low density lipoproteins (LDL) was subjected to oxidation in the presence of either human umbilical vein endothelial cells or with Cu+2 ions and the major oxides formed were identified. While cholesterol-alpha-epoxide (C-alpha EP) was the major product of cholesterol peroxidation in the presence of endothelial cells, cholest-3,5-dien-7-one (CD) predominated in the presence of Cu+2 ion. Both steroids were identified by gas chromatography/mass spectrometry. HDL cholesterol was resistant to oxidation. When tested on human skin fibroblasts in culture C-alpha EP (10 micrograms/ml) caused marked stimulation of 14C-oleate incorporation into cholesterol esters, while CD stimulated cholesterol esterification only mildly. These studies show that a) C-alpha EP is the major peroxidation product of LDL cholesterol moiety in the presence of endothelial cells and b) it causes marked stimulation of cholesterol esterification in cells. C-alpha EP may play a key role in increasing cholesterol esterification noted in atherogenesis.

Effect of ibuprofen on menstrual blood prostaglandin levels in dysmenorrheic women.

PubMed

Pulkkinen, M O; Csapo, A I

1979-07-01

In a randomized crossover study 15 dysmenorrheic women were treated during two consecutive menstrual period, once with the potent prostaglandin-synthesis inhibitor: ibuprofen and once with an identical looking placebo. Each patient was medicated for 12 hours during the first day of her menstrual flow and was subsequently fitted with a cervical cup for the collection of menstrual blood during three hours. In these samples the concentrations of prostaglandin (PG)F and PGE were measured by radioimmunoassay. The patients receiving placebo had high PGF levels 135 +/- 27 ng/ml (Mean +/- S.E.) which were significnatly reduced by Ibuprofen to 24 +/- 5 ng/ml (P less than 0.001). The PGE concentrations decreased from 5 +/- 1 ng/ml to 2 +/- 1 ng/ml (P less than 0.05). Ibuprofen also reduced the menstrual pain significantly (P less than 0.001). These results substantiate the earlier conclusion that a causal relationship exists between effective treatment with PG-synthesis inhibitors and decrease in menstrual blood PG levels, intrauterine pressure and dysmenorrheic pain.

Effects of B group vitamins on reactions of various alpha-hydroxyl-containing organic radicals.

PubMed

Lagutin, P Yu; Shadyro, O I

2005-08-15

Effects of vitamins B1, B2, B6, and pyridoxal phosphate (PPh) on final product formation in radiolysis of aqueous solutions of ethanol, ethylene glycol, alpha-methylglycoside, and maltose were studied. It has been found that vitamin B2 and PPh effectively oxidize R*CHOH species, while suppressing their recombination and fragmentation reactions, thereby increasing the yields of the respective oxidation products. Vitamins B1 and B2 are capable of reducing alcohol radicals to the respective initial molecules, decreasing the yields of the radical transformation products.

An update on cystic ovarian degeneration in cattle.

PubMed

Peter, A T

2004-02-01

Cystic ovarian degeneration (COD) is considered to be one of the most important causes of reproductive failure in cattle. There is a severe economic loss to dairy industry because COD increases days-open in the postpartum period and the culling rates. The disease process is a consequence of a mature follicle that fails to ovulate at the appointed time of ovulation in the oestrous cycle. This anovulatory follicular structure either regresses or persists as a follicular or luteal cyst depending upon its structural/functional characteristics. The cells lining the follicular cyst synthesize oestrogen that, in certain instances, forces the animal to exhibit clinical signs of nymphomania. Besides oestrogen production, as per recent findings, they are also capable of secreting varying amount of progesterone which may dictate their fate. The animals that carry a luteal cyst may tend to be in anoestrus as the higher amount of progesterone secreted by this luteinized structure may change the pattern of gonadotrophins' secretion. Present findings suggest that perturbation of the hypothalamo-hypophyseal-ovarian (HHO) axis, due to many exogenous and endogenous factors, as the cause for anovulation. For example, it has been suggested that lack of hypothalamic or hypophyseal response to the positive feedback effect of oestrogens that are secreted by the dominant follicle as one of the many causes. The non-physiological changes that occur in the receptor expression of the HHO axis for the hormones involved in maturation, deviation, dominance and ovulation of the follicle may be yet another cause. The changes that occur at the cellular and molecular level in the ovary (in response to the factors mentioned above) that contribute to anovulation remain to be documented. This approach would allow us to completely understand the disease process. Hitherto, hormonal preparations that release luteinizing hormone from the anterior pituitary or have luteinizing hormone-like action are used to treat follicular cysts. GnRH belongs to the former group and human chorionic gonadotrophin (hCG) hormone forms the latter group. Treatment with a luteolytic agent, prostaglandin F2alpha (PGF2alpha), is successful if a luteal cyst is diagnosed properly. Many agents may be developed in the future if the cellular and molecular pathways of the disease process are delineated. This article will review recent advances in our understanding of the pathogenesis of COD and suggest direction for future studies to completely understand the disease mechanism. This review will also discuss the existing method of treatments for cysts and methods proposed for treatment of cysts that tend to be refractory in nature.

Presynchronization with Double-Ovsynch improves fertility at first postpartum artificial insemination in lactating dairy cows.

PubMed

Herlihy, M M; Giordano, J O; Souza, A H; Ayres, H; Ferreira, R M; Keskin, A; Nascimento, A B; Guenther, J N; Gaska, J M; Kacuba, S J; Crowe, M A; Butler, S T; Wiltbank, M C

2012-12-01

The objective of this study was to compare circulating progesterone (P4) profiles and pregnancies per AI (P/AI) in lactating dairy cows bred by timed artificial insemination (TAI) following Ovsynch-56 after 2 different presynchronization protocols: Double-Ovsynch (DO) or Presynch-Ovsynch (PS). Our main hypothesis was that DO would increase fertility in primiparous cows, but not in multiparous cows. Within each herd (n=3), lactating dairy cows (n=1,687; 778 primiparous, 909 multiparous) were randomly assigned to DO [n=837; GnRH-7d-PGF(2α)-3d-GnRH-7d-Ovsynch-56 (GnRH-7d-PGF(2α)-56h-GnRH-16hTAI)] or PS (n=850; PGF(2α)-14d-PGF(2α)-12d-Ovsynch-56). In 1 herd, concentrations of P4 were determined at the first GnRH (GnRH1) of Ovsynch-56 and at d 11 after TAI (n=739). In all herds, pregnancy was diagnosed by palpation per rectum at 39 d. In 1 herd, the incidence of late embryo loss was determined at 74d, and data were available on P/AI at the subsequent second service. Presynchronization with DO reduced the percentage of animals with low P4 concentrations (<0.50 ng/mL) at GnRH1 of Ovsynch-56 (5.4 vs. 25.3%, DO vs. PS). A lesser percentage of both primiparous and multiparous cows treated with DO had low P4 concentrations at GnRH1 of Ovsynch-56 (3.3 vs. 19.7%, DO vs. PS primiparous; and 8.8 vs. 31.9%, DO vs. PS multiparous). Presynchronization with DO improved P/AI at the first postpartum service (46.3 vs. 38.2%, DO vs. PS). Statistically, a fertility improvement could be detected for primiparous cows treated with DO (52.5 vs. 42.3%, DO vs. PS, primiparous), but only a tendency could be detected in multiparous cows (40.3 vs. 34.3%, DO vs. PS, multiparous), consistent with our original hypothesis. Presynchronization treatment had no effect on the incidence of late embryo loss after first service (8.5 vs. 5.5%, DO vs. PS). A lower body condition score increased the percentage of cows with low P4 at GnRH1 of Ovsynch-56 and reduced fertility to the TAI. In addition, P4 concentration at d 11 after TAI was reduced by DO. The method of presynchronization at first service had no effect on P/AI at the subsequent second service (34.7 vs. 36.5%, DO vs. PS). Thus, presynchronization with DO induced cyclicity in most anovular cows and improved fertility compared with PS, suggesting that DO could be a useful reproductive management protocol for synchronizing first service in commercial dairy herds. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

GnRH and prostaglandin-based synchronization protocols as alternatives to progestogen-based treatments in sheep.

PubMed

Rekik, M; Haile, A; Abebe, A; Muluneh, D; Goshme, S; Ben Salem, I; Hilali, M El-Dine; Lassoued, N; Chanyalew, Y; Rischkowsky, B

2016-12-01

The study investigated, for cycling sheep, synchronizing protocols simultaneously to the standard "P" protocol using progestogens priming with intravaginal devices and gonadotropin. In November 2014, 90 adult Menz ewes were assigned to either the "P" protocol, "PGF" treatment where oestrus and ovulation were synchronized using two injections of prostaglandin 11 days apart or a "GnRH" treatment where the ewes had their oestrus and ovulation synchronized with GnRH (day 0)-prostaglandin (day 6)-GnRH (day 9) sequence. The ewes were naturally mated at the induced oestrus and the following 36 days. Plasma progesterone revealed that 92% of the ewes were ovulating before synchronization and all, except one, ovulated in response to the applied treatments. All "P" ewes exhibited oestrus during the 96-hr period after the end of the treatments in comparison with only 79.3% and 73.3% for "PGF" and "GnRH" ewes, respectively (p < .05). Onset and duration of oestrus were affected by the hormonal treatment (p < .05); "GnRH" ewes showed oestrus earliest and had the shortest oestrous duration. Lambing rate from mating at the induced oestrus was lower for "P" than for "PGF" ewes (55.6% and 79.3%, respectively; p < .05). The same trait was also lower for "P" than for "PGF" and "GnRH" ewes (70.4%, 89.7% and 86.7%, respectively; p < .05) following the 36-day mating period. Prostaglandin and GnRH analogue-based protocols are promising alternatives for both controlled natural mating and fixed insemination of Menz sheep after the rainy season when most animals are spontaneously cycling. © 2016 Blackwell Verlag GmbH.

[Induced abortion using prostaglandin E2 and F2alpha gel].

PubMed

Lippert, T H; Modly, T

1974-01-01

In this study of 20 patients in the 13th-17th week of pregnancy abortion was induced with intrauterine, extraamniotic application of prostaglandins (PG) E2 or F2 in gel form. The gel composition was as follows: 4% tylose MH 300, 2% glycerine, 1% chlorhexidine digluconate, 83% sterile distilled water and 10% PG stock solution. Both PGE2 and PGF2 gels were used. Final concentration was 2.5 mg E2 or 2.5 mg F2 per g of gel. Gel was applied via transcervical, extraamniotic polyethylene catheter every 2-3 hours. Results: PGE2-gel was used in 14 cases. After 3-4 applications both fetus and placenta were expelled. Average dose used was 4.6 mg E2/patient. First contractions started in 30 minutes; induction to expulsion time was 11 hours 35 minutes. F2-gel given to 6 patients resulted in expulsion of the fetus in all cases but placenta needed removal by curettage in 4 patients. Average dose per patient was 17.7 mg of F2; first contractions in 30 minutes, average expulsion time 17 hours 38 minutes. With both PGs there were painful contractions which were controlled with a combination of pentazocine and Valium. PGE2 caused vomiting in 5 patients. No increased bleeding or postabortion infection occurred. Follow-up curettage was done in all patients to ensure removal of all tissues. Overall evaluation of the PG-gels was considered good. PG stability in gel form is good; during 8 months of preservation in sterile aluminum tubes at -25 degrees Celsius no decline in clinical effectiveness was noted. The gel application is less expensive than the slow-injection pump method.

Dynamics of progesterone, TNF-a and a metabolite of PGF2a in blood plasma of beef cows following embryo transfer

USDA-ARS?s Scientific Manuscript database

Lactating beef cows received an embryo along with no treatment (control; n = 16), controlled internal drug releasing device (CIDR; n = 16), human chorionic gonadotropin (hCG; n = 15), or gonadotropin releasing hormone (GnRH; n = 15) to assess the effectiveness of these treatments in increasing blood...

Surface expression of intraplate postglacial faults in Sweden: from LiDAR data

NASA Astrophysics Data System (ADS)

Abduljabbar, Mawaheb; Ask, Maria; Bauer, Tobias; Lund, Björn; Smith, Colby; Mikko, Henrik; Munier, Raymond

2016-04-01

Large intraplate earthquakes, up to magnitude 8.0±0.3 (Lindblom et al. 2015) are inferred to have occurred in northern Fennoscandia at the end of, or just after the Weichselian deglaciation. More than a dozen large so-called postglacial faults (PGF) have been found in the region. The present-day microseismic activity is rather high in north Sweden, and there is a correlation between microseismicity and mapped PGF scarps: 71% of the observed earthquakes north of 66°N locate within 30 km to the southeast and 10 km to the northwest of PGFs (Lindblom et al., 2015). Surface expressions of PGFs in Sweden have mainly been mapped using aerial photogrammetry and trenching (e.g. Lagerbäck & Sundh 2008). Their detailed surface geometry may be investigated using the new high-resolution elevation model of Sweden (NNH) that has a vertical- and lateral resolution of 2 m and 0.25 m, respectively. With NNH data, known PGFs have been modified, and a number of new potential PGFs have been identified (Smith et al. 2014; Mikko et al. 2015). However, the detailed variation of their surface expression remains to be determined. Our main objective is to constrain the strike and surface offset (i.e., apparent vertical throw because of soil cover overlays the bedrock) across the PGF scarps. We anticipate using the results to constrain direction of fault motion and paleomagnitudes of PGFs, and in numerical analyzes to investigate the nature of PGFs. We have developed a methodology for analyzing PGF-geomorphology from LiDAR data using two main software platforms (Ask et al. 2015): (1) Move2015 by Midland Valley has been used for constructing 3D models of the surface traces of the PGFs to determine apparent vertical throw. The apparent hanging- and footwall cut off lines are digitized, and subsequent computation of coordinates is rather time efficient and provide continuous data of fault and soil geomorphology that can be statistically analyzed; and (2) ArcGIS 10.3 by Esri has mostly been used to derive the slope model for the study area. We successfully tested the methodology within a limited area of the Pärvie fault zone, which is the longest known PGF in the world (Ask et al. 2015). Here, we apply the methodology to PGFs in northern Sweden. Additionally, we are planning to analyse PGFs within a virtual reality environment utilizing the GeoVisionary software platform by Virtalis Ltd. in order to increase accuracy and efficiency and to decrease modelling uncertainties. References Ask et al. 2015. Geomorphology of intraplate postglacial faults in Sweden. AGU, Abstract #83167 Lindblom, et al., 2015. Microearthquakes illuminate the deep structure of the endglacial Pärvie fault, northern Sweden. doi: 10.1093/gji/ggv112 Lagerbäck & Sundh, 2008. Early Holocene faulting and paleoseismicity in northern Sweden. http://resource.sgu.se/produkter/c/c836-rapport.pdf Mikko, et al. 2015. LiDAR-derived inventory of post-glacial fault scarps in Sweden. doi:10.1080/11035897.2015.1036360 Smith, et al., 2014. Surficial geology indicates early Holocene faulting and seismicity, central Sweden. doi: 10.1007/s00531-014-1025-6

Type 5 17β-Hydroxysteroid Dehydrogenase/Prostaglandin F Synthase (AKR1C3): Role In Breast Cancer and Inhibition by Nonsteroidal Antiinflammatory Drug Analogs

PubMed Central

Byrns, Michael C.; Penning, Trevor M.

2011-01-01

Aldo-keto reductase (AKR) 1C3 catalyzes the NADPH dependent reduction of Δ4-androstene-3,17-dione to yield testosterone, reduction of estrone to yield 17β-estradiol and reduction of progesterone to yield 20α-hydroxyprogesterone. In addition, it functions as a prostaglandin (PG) F synthase and reduces PGH2 to PGF2α and PGD2 to 11β-PGF2. Immunohistochemistry showed that AKR1C3 is over expressed in invasive ductal carcinoma of the breast. Retroviral expression of AKR1C3 in MCF-7 breast carcinoma cells shows that each of the assigned reactions occur in a breast cell microenvironment. Steroid and prostaglandin conversions were monitored by radiochromatography. Prostaglandin conversion was validated by a second method using HPLC coupled to APCI-MRM/MS. The combined effect of the AKR1C3 catalyzed 17- and 20-ketosteroid reductions will be to increase the 17β-estradiol : progesterone ratio in the breast. In addition, formation of PGF2 epimers would activate F prostanoid receptors and deprive PPARγ of its putative anti-proliferative PGJ2 ligands. Thus, AKR1C3 is a source of proliferative signals and a potential therapeutic target for hormone dependent and independent breast cancer. Two strategies for AKR1C3 inhibition based on non-steroidal anti-inflammatory drugs were developed. The first strategy uses the Ullmann coupling reaction to generate N-phenylanthranilate derivatives that inhibit AKR1C enzymes without affecting PGH2 synthase (PGHS) 1 or PGHS-2. The second strategy exploits the selective inhibition of AKR1C3 by indomethacin, which did not inhibit highly related AKR1C1 or AKR1C2. Using known structure activity relationships for the inhibition of PGHS-1 and PGHS-2 by indole acetic acids we obtained N-(4-chlorobenzoyl)-melatonin as a specific AKR1C3 inhibitor (KI = 6.0 μM) that does not inhibit PGHS-1, PGHS-2, AKR1C1, or AKR1C2. Both strategies are informed by crystal structures of ternary AKR1C3•NADP+•NSAID complexes. The identification of NSAID analogs as specific inhibitors of AKR1C3 will help validate its role in the proliferation of breast cancer cells. PMID:19010312

Structural damage and changes in eicosanoid metabolites in the gastric mucosa of rats and pigs induced by anti-inflammatory drugs of varying ulcerogenicity.

PubMed

Rainsford, K D

1986-01-01

The object of the studies reviewed here has been to correlate the time-course of ultrastructural changes induced by oral administration of a range of non-steroidal anti-inflammatory (NSAI) drugs with effects on eicosanoid metabolism and drug absorption, so as to discriminate what biochemical/cellular and pharmacological factors account for their varying ulcerogenicity. Oral administration of highly ulcerogenic drugs (e.g. aspirin, diclofenac, indomethacin, piroxicam) to rats causes rapid damage to surface and gastric mucous cells, selective parietal cell damage, and extensive disruption of endothelial cells of submucosal microcapillaries (especially with aspirin) with accompanying extravasation of blood cell components. These changes are coincident with depressed levels of PGE2/6-keto-PGF1 alpha (measured by GC/MS or RIA) and uptake of the drugs (measured by scintillation counting or HPLC). Low ulcerogenic NSAI drugs (e.g. azapropazone, benoxaprofen and fenclofenac) causes very little damage to the surface mucosal cells. Azapropazone has been found to be well absorbed, and benoxaprofen and fenclofenac somewhat more slowly, so for the latter two drugs their low rate of absorption might also be a factor in their reduced ulcerogenicity. Aspirin, azapropazone and benoxaprofen have been shown to reduce 5-HETE levels (RIA), although the latter two drugs were more effective than aspirin. Thus, they result in the inhibition of PG production, by cyclo-oxygenase inhibition (with potential adverse effects from excess oxyradical and/or production of HETE's) with inhibition of the lipoxygenase pathway. The time-sequence of changes induced by single oral doses of indomethacin or other NSAI drugs on the ultrastructure and the prostanoid metabolism of the pig gastric mucosa parallelled those seen in the rat. Attempts to determine whether co-administration of NSAI drugs might reduce the inhibition of PG cyclo-oxygenase by more potent inhibitors (e.g. indomethacin) have been explored as a means for reducing the gastric ulcerogenicity of the latter. The results suggest that pharmacokinetic factors may largely account for the reduced ulcerogenicity of these drug mixtures.

Addition products of alpha-tocopherol with lipid-derived free radicals.

PubMed

Yamauchi, Ryo

2007-01-01

The addition products of alpha-tocopherol with lipid-derived free radicals have been reviewed. Free radical scavenging reactions of alpha-tocopherol take place via the alpha-tocopheroxyl radical as an intermediate. If a suitable free radical is present, an addition product can be formed from the coupling of the free radical with the alpha-tocopheroxyl radical. The addition products of alpha-tocopherol with lipid-peroxyl radicals are 8a-(lipid-dioxy)-alpha-tocopherones, which are hydrolyzed to alpha-tocopherylquinone. On the other hand, the carbon-centered radicals of lipids prefer to react with the phenoxyl radical of alpha-tocopherol to form 6-O-lipid-alpha-tocopherol under anaerobic conditions. The addition products of alpha-tocopherol with peroxyl radicals (epoxylinoleoyl-peroxyl radicals) produced from cholesteryl ester and phosphatidylcholine were detected in the peroxidized human plasma using a high-sensitive HPLC procedure with postcolumn reduction and electrochemical detection. Thus, the formation of these addition products provides us with much information on the antioxidant function of vitamin E in biological systems.

Potential protective effects of Clostridium butyricum on experimental gastric ulcers in mice

PubMed Central

Wang, Fang-Yan; Liu, Jia-Ming; Luo, Hai-Hua; Liu, Ai-Hua; Jiang, Yong

2015-01-01

AIM: To investigate the effects of Clostridium butyricum (C. butyricum) on experimental gastric ulcers (GUs) induced by alcohol, restraint cold stress, or pyloric ligation in mice, respectively. METHODS: One hundred and twenty mice were randomly allocated into three types of gastric ulcer models (n = 40 each), induced by alcohol, restraint cold stress, or pyloric ligation. In each GU model, 40 mice were allocated into four groups (n = 10 each): the sham control group; model group (GU induction without pretreatment); C. butyricum group (GU induction with C. butyricum pretreatment); and Omeprazole group (GU induction with Omeprazole pretreatment). The effects of C. butyricum were evaluated by examining the histological changes in the gastric mucosal erosion area, the activities of superoxide dismutase (SOD) and catalase (CAT), the level of malondialdehyde (MDA), and the contents of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, leukotriene B4 (LTB4) and 6-keto-PGF-1α (degradation product of PGI2) in the gastric tissue. RESULTS: Our data showed that C. butyricum significantly reduced the gastric mucosal injury area and ameliorated the pathological conditions of the gastric mucosa. C. butyricum not only minimized the decreases in activity of SOD and CAT, but also reduced the level of MDA in all three GU models used in this study. The accumulation of IL1-β, TNF-α and LBT4 decreased, while 6-keto-PGF-1α increased with pretreatment by C. butyricum in all three GU models. CONCLUSION: Our data demonstrated the protective effects of pretreatment with C. butyricum on anti-oxidation and anti-inflammation in different types of GU models in mice. Further studies are needed to explore its potential clinical benefits. PMID:26217085

Isoporphyrin intermediate in heme oxygenase catalysis. Oxidation of alpha-meso-phenylheme.

PubMed

Evans, John P; Niemevz, Fernando; Buldain, Graciela; de Montellano, Paul Ortiz

2008-07-11

Human heme oxygenase-1 (hHO-1) catalyzes the O2- and NADPH-dependent oxidation of heme to biliverdin, CO, and free iron. The first step involves regiospecific insertion of an oxygen atom at the alpha-meso carbon by a ferric hydroperoxide and is predicted to proceed via an isoporphyrin pi-cation intermediate. Here we report spectroscopic detection of a transient intermediate during oxidation by hHO-1 of alpha-meso-phenylheme-IX, alpha-meso-(p-methylphenyl)-mesoheme-III, and alpha-meso-(p-trifluoromethylphenyl)-mesoheme-III. In agreement with previous experiments (Wang, J., Niemevz, F., Lad, L., Huang, L., Alvarez, D. E., Buldain, G., Poulos, T. L., and Ortiz de Montellano, P. R. (2004) J. Biol. Chem. 279, 42593-42604), only the alpha-biliverdin isomer is produced with concomitant formation of the corresponding benzoic acid. The transient intermediate observed in the NADPH-P450 reductase-catalyzed reaction accumulated when the reaction was supported by H2O2 and exhibited the absorption maxima at 435 and 930 nm characteristic of an isoporphyrin. Product analysis by reversed phase high performance liquid chromatography and liquid chromatography electrospray ionization mass spectrometry of the product generated with H2O2 identified it as an isoporphyrin that, on quenching, decayed to benzoylbiliverdin. In the presence of H218O2, one labeled oxygen atom was incorporated into these products. The hHO-1-isoporphyrin complexes were found to have half-lives of 1.7 and 2.4 h for the p-trifluoromethyl- and p-methyl-substituted phenylhemes, respectively. The addition of NADPH-P450 reductase to the H2O2-generated hHO-1-isoporphyrin complex produced alpha-biliverdin, confirming its role as a reaction intermediate. Identification of an isoporphyrin intermediate in the catalytic sequence of hHO-1, the first such intermediate observed in hemoprotein catalysis, completes our understanding of the critical first step of heme oxidation.

Silencing alpha-fetoprotein inhibits VEGF and MMP-2/9 production in human hepatocellular carcinoma cell.

PubMed

Meng, Wenbo; Li, Xun; Bai, Zhongtian; Li, Yan; Yuan, Jinqiu; Liu, Tao; Yan, Jun; Zhou, Wence; Zhu, Kexiang; Zhang, Hui; Li, Yumin

2014-01-01

Alpha-fetoprotein not only serves as a diagnostic marker for liver cancer, but also posses a variety of biological functions. However, the role of Alpha-fetoprotein on tumor angiogenesis and cell invasion remains incompletely understood. In this study, we aimed to evaluate if Alpha-fetoprotein can regulate the major angiogenic factors and matrix metalloproteinases in human liver cancer cells. Alpha-fetoprotein silencing was achieved by Stealth RNAi. Expression of Alpha-fetoprotein was examined by a full-automatic electrochemistry luminescence immunity analyzer. Expression of VEGF, VEGFR-2, MMP-9, and MMP-2 was examined by Western blot and immunocytochemistry. Apoptosis was detected by TUNEL assay. Angiogenesis was detected by in vitro angiogenesis assay kit. Silencing of Alpha-fetoprotein led to an increased apoptosis, which was associated with a decreased expression of vascular endothelial growth factor, vascular endothelial growth factor receptor 2, matrix metalloproteinases-2/9. These results suggest that Alpha-fetoprotein may play a regulatory role on angiogenesis and cell invasion during liver cancer development.

Prostaglandin G/H synthase (PGHS)-2 expression in bovine myometrium: influence of steroid hormones and PGHS inhibitors.

PubMed

Doualla-Bell, F; Guay, J M; Bourgoin, S; Fortier, M A

1998-12-01

Prostaglandins (PGs) are important mediators regulating uterine functions during the reproductive process. The objective of this study was to examine, in myocytes from the circular and longitudinal layers of bovine myometrium, the relative levels of mRNA and proteins corresponding to the gene expression of key enzymes (phospholipase A2; prostaglandin G/H synthase-1 [PGHS-1]; prostaglandin G/H synthase-2 [PGHS-2]; prostaglandin I2 synthase) involved in PG biosynthesis. We examined the influence of estradiol-17beta and progesterone on the expression and activity of these enzymes. Treatment of myocytes with progesterone (P4: 10 nM, 24 h) in the absence or presence of estradiol-17beta (E2: 1 nM, 72 h) suppressed PG biosynthesis by approximately 60% in both myometrial layers. No significant effect was observed after E2 treatment. The combined effect of E2 and P4 on PG accumulation was correlated with the modulation of PGHS-2 protein and mRNA levels in the two myometrial layers without affecting other enzymes of the PG cascade. Selective or nonselective inhibition of PGHS activity with CGP 28238 (PGHS-2-specific; a product from Ciba-Geigy: 6-[2, 4-difluorophenoxy]-5-methyl-sulfonylamino-1-indanone) or indomethacin (PGHS-1 and -2) reduced prostacyclin accumulation (measured as 6-keto-PGF1alpha in the culture medium) in a dose-dependent manner in the two myometrial layers. A significant inhibitory effect was obtained at a low concentration of indomethacin (1 nM, p < 0.05) compared to CGP 28238 (10 nM, p < 0. 05). In both myometrial layers, the maximal effect of indomethacin and/or CGP 28238 on PG accumulation was observed at 100 nM and represented 85% and 65% inhibition, respectively. In the presence of phorbol 12-myristate (100 nM), CGP 28238 (10 nM) significantly suppressed PGHS-2 mRNA level by 44.80 +/- 7.67% (p < 0.01) and 27.83 +/- 7.62% (p < 0.05) in the longitudinal and circular layer, respectively. In contrast, indomethacin did not have any significant effect. These data constitute the first quantitative analysis of key enzymes involved in PG biosynthesis in separated myometrial layers. Furthermore, the results provide interesting information on the CGP 28238 drug modulating both enzymatic activity and mRNA expression of PGHS-2.

Ovarian stimulation with follicle-stimulating hormone under increasing or minimal concentration of progesterone in dairy cows.

PubMed

El-Sherry, T M; Matsui, M; Kida, K; Miyamoto, A; Megahed, G A; Shehata, S H; Miyake, Y-I

2010-03-01

The objective of this study was to investigate the effect of the presence or absence of Corpus luteum (CL) on the follicular population during superstimulation in dairy cows (Holstein-Friesian cattle). Animals were divided into two groups as follows: (1) Growing CL group (G1): Cows (n=7) received a total dose of 28 Armour units (AU) follicle-stimulating hormone (FSH) through the first 4 d (twice daily) after spontaneous ovulation (Day 0). (2) CL Absence group (G2): Cows (n=10) received prostaglandin F(2alpha) (PGF(2alpha)) at 9 or 10 d after ovulation. After 36h, all the follicles (larger than 5mm) were aspirated (Day 0). The FSH treatment started 24h after aspiration and continued for 4 d. The number of small (3 to <5mm), medium (5 to <8mm), and large (> or = 8mm) follicles was examined on Days 1, 3, and 5 in all groups. Blood samples were collected daily for 5 d, and progesterone (P(4)), estradiol (E(2)), insulin-like growth factor-1 (IGF-1), and growth hormone (GH) in plasma were measured by enzyme immunoassays. The results showed that in G1, the P(4) level increased gradually from 0.5 ng/mL at Day 1 to 2 ng/mL at Day 5, whereas in G2, the P(4) level was completely below 0.5 ng/mL. All cows of the G2 group showed an increase of E(2) at Day 3 or Day 4 followed by an increase of IGF-1 within 24h, while GH increased concomitantly with the E(2) increase in 8 of 10 trials. On the other hand, cows of the G1 group showed neither E(2) nor IGF-1 increase. Moreover, at the end of the treatment, the number of follicles in the G2 group was significantly increased compared with that of the G1 group (22.8+/-2.0 vs. 11.6+/-2.0). In conclusion, low P(4) level during FSH treatment enhanced multiple follicular growth and E(2) secretion, which was followed by increase of IGF-1 and GH. Therefore, the absence of the CL may play a critical role in the superovulation response by controlling the number of growing follicles. Copyright 2010 Elsevier Inc. All rights reserved.

Identification of 4,5-didemethyl-4-O-alpha-D-glucopyranosylsimmondsin and pinitol alpha-D-galactosides in jojoba seed meal (Simmondsia chinensis).

PubMed

Van Boven, M; Leyssen, T; Busson, R; Holser, R; Cokelaere, M; Flo, G; Decuypere, E

2001-09-01

The isolation and identification of two pinitol alpha-D-galactosides from jojoba meal are described. The products were isolated by a combination of preparative HPLC on silica gel and TLC on amino silica gel and were identified by MS, NMR spectroscopy, and chemical derivatization as 5-O-(alpha-D-galactopyranosyl)-3-O-methyl-D-chiro-inositol or 5-alpha-D-galactopyranosyl-D-pinitol and 2-O-(alpha-D-galactopyranosyl)-3-O-methyl-D-chiro-inositol or 2-alpha-D-galactopyranosyl-D-pinitol. The same preparative HPLC method on silica gel allowed a new simmondsin derivative to be isolated and identified as 4,5-didemethyl-4-O-alpha-D-glucopyranosylsimmondsin mainly by NMR spectroscopy and high-resolution mass spectrometry.

Bioenvironmental Engineer’s Guide to Ionizing Radiation

DTIC Science & Technology

2005-10-01

mercury x-rays 186 (4 % ) - y Ra -226 radon x-rays Luminous Products, Neutron (tl/2: 1600 y) Alpha photons from daughters: Sources (w/ Be ) Rn-222, Po...Radioisotope Thermoelectric (t1,2: 88 y) Generators Pu-239 Alpha uranium x-rays Nuclear Weapons, Neutron (t1 /2: 2.4 x 104 y) Sources (w/ Be ...Calibration Am-241 .60 (36 %) - Static Eliminators, Chemical (h2: 432 y) Alpha n Agent Detectors, Neutron neptunium x-rays Sources (w/ Be ) 11 October 2005

Effect of cultivating conditions on alpha-galactosidase production by a novel Aspergillus foetidus ZU-G1 strain in solid-state fermentation.

PubMed

Liu, Cai-qin; Chen, Qi-he; Cheng, Qian-jun; Wang, Jin-ling; He, Guo-qing

2007-05-01

The work is intended to achieve optimum culture conditions of alpha-galactosidase production by a mutant strain Aspergillus foetidus ZU-G1 in solid-state fermentation (SSF). Certain fermentation parameters involving moisture content, incubation temperature, cultivation period of seed, inoculum volume, initial pH value, layers of pledget, load size of medium and period of cultivation were investigated separately. The optimal cultivating conditions of alpha-galactosidase production in SSF were 60% initial moisture of medium, 28 degrees C incubation temperature, 18 h cultivation period of seed, 10% inoculum volume, 5.0 approximately 6.0 initial pH of medium, 6 layers of pledget and 10 g dry matter loadage. Under the optimized cultivation conditions, the maximum alpha-galactosidase production was 2 037.51 U/g dry matter near the 144th hour of fermentation.

Lyt-2+ cells. Requirements for concanavalin A-induced proliferation and interleukin 2 production.

PubMed

Kern, D E; Lachmann, L B; Greenberg, P D

1987-11-01

The requirements for inducing Lyt-2+ T cell proliferation in response to concanavalin A (Con A) were examined. Purified Lyt-2+ or L3T4+ spleen cells of C57BL/6 origin were stimulated with Con A and syngeneic macrophages (MO) in the presence of monoclonal antibodies to T cell markers or to polymorphic determinants on major histocompatibility complex molecules, and assessed for the ability to proliferate and to produce interleukin (IL) 2. alpha I-Ab failed to inhibit the Con A response of Lyt-2+ cells at dilutions that significantly inhibited the response of L3T4+ cells. In contrast, alphaKb/Db or alpha Lyt-2.2 specifically inhibited the response of Lyt-2+ cells, but not L3T4+ cells. The ability of alpha Kb/Db and of alpha Lyt-2.2 to inhibit the response of Lyt-2+ cells was dependent upon the concentration of Con A. These data demonstrate that optimal triggering of T cell subsets to proliferate and to produce IL-2 in response to Con A requires interactions with the appropriate restricting major histocompatibility complex molecule. The role of accessory cells in Lyt-2+ Con A-induced proliferation and IL-2 production was also investigated. Purified Lyt-2+ cells and purified L3T4+ cells failed to respond to Con A in the absence of MO. IL-1 reconstituted the response when MO were limiting, but failed to restore the response of either Lyt-2+ or L3T4+ cells when T cells were rigorously purified to remove all MO. These results demonstrate that triggering Lyt-2+ T cells, like L3T4+ T cells, requires accessory cells, and that this does not merely reflect a requirement for IL-1 production. Thus, Con A-induced proliferation and IL-2 production by Lyt-2+ T cells requires intimate contact with accessory cells and interactions dependent upon the class I-restricting element.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gharibyan, N.

In order to fully characterize the NIF neutron spectrum, SAND-II-SNL software was requested/received from the Radiation Safety Information Computational Center. The software is designed to determine the neutron energy spectrum through analysis of experimental activation data. However, given that the source code was developed in Sparcstation 10, it is not compatible with current version of FORTRAN. Accounts have been established through the Lawrence Livermore National Laboratory’s High Performance Computing in order to access different compiles for FORTRAN (e.g. pgf77, pgf90). Additionally, several of the subroutines included in the SAND-II-SNL package have required debugging efforts to allow for proper compiling ofmore » the code.« less

A sensitive LC-MS/MS method for the quantification of urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) including pediatric reference interval.

PubMed

Xiao, Yi; Fu, Xiaowei; Pattengale, Paul; Dien Bard, Jennifer; Xu, Yan-Kang; O'Gorman, Maurice R

2016-09-01

Oxidative stress has been implicated in numerous diseases, including arthritis, atherosclerosis, Alzheimer's disease, cancer, diabetes, hypertension, and inflammation. 8-iso-prostaglandin F2α, a member of the F2 isoprostane family, has been well-accepted as a valuable biomarker for the assessment of oxidative stress. We report the development and validation of an ultra-sensitive LC-MS/MS assay for urinary 8-iso-PGF2α measurements in pediatric population. The assay was linear from 0.024 to 20nmol/l (R(2)=0.99). Recoveries were above 85% and matrix effects were below 5%. The variability was determined at nmol/l concentration: the intra-day variability (%CV) ranged from 3.9% to 4.5% (n=20); and the inter-day variability ranged from 4.3% to 5.7% (n=20). The accuracy of our laboratory developed test was evaluated with a clinical reference laboratory (n=39), and a correlation coefficient of 0.9257 was observed. Reference interval were established to be <0.5ng/mg creatinine in a group of pediatric population (2months-18years, n=123). The precision of the assay will allow for accurate assessment of oxidative stress, and is acceptable for patient testing, particularly in pediatric population. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of the specificity of sialyltransferases toward mucin core 2, globo, and related structures. identification of the sialylation sequence and the effects of sulfate, fucose, methyl, and fluoro substituents of the carbohydrate chain in the biosynthesis of selectin and siglec ligands, and novel sialylation by cloned alpha2,3(O)sialyltransferase.

PubMed

Chandrasekaran, E V; Xue, Jun; Xia, Jie; Chawda, Ram; Piskorz, Conrad; Locke, Robert D; Neelamegham, Sriram; Matta, Khushi L

2005-11-29

Sialic acids are key determinants in many carbohydrates involved in biological recognition. We studied the acceptor specificities of three cloned sialyltransferases (STs) [alpha2,3(N)ST, alpha2,3(O)ST, and alpha2,6(N)ST] and another alpha2,3(O)ST present in prostate cancer cell LNCaP toward mucin core 2 tetrasaccharide [Galbeta1,4GlcNAcbeta1,6(Galbeta1,3)GalNAcalpha-O-Bn] and Globo [Galbeta1,3GalNAcbeta1,3Galalpha-O-Me] structures containing sialyl, fucosyl, sulfo, methyl, or fluoro substituents by identifying the products by electrospray ionization tandem mass spectral analysis and other biochemical methods. The Globo precursor was an efficient acceptor for both alpha2,3(N)ST and alpha2,3(O)ST, whereas only alpha2,3(O)ST used its deoxy analogue (d-Fucbeta1,3GalNAcbeta1,3-Gal-alpha-O-Me); 2-O-MeGalbeta1,3GlcNAc and 4-OMeGalbeta1,4GlcNAc were specific acceptors for alpha2,3(N)ST. Other major findings of this study include: (i) alpha2,3 sialylation of beta1,3Gal in mucin core 2 can proceed even after alpha1,3 fucosylation of beta1,6-linked LacNAc. (ii) Sialylation of beta1,3Gal must precede the sialylation of beta1,4Gal for favorable biosynthesis of mucin core 2 compounds. (iii) alpha2,3 sialylation of the 6-O-sulfoLacNAc moiety in mucin core 2 (e.g., GlyCAM-1) is facilitated when beta1,3Gal has already been alpha2,3 sialylated. (iv) alpha2,6(N)ST was absolutely specific for the beta1,4Gal in mucin core 2. Either alpha1,3 fucosylation or 6-O-sulfation of the GlcNAc moiety reduced the activity. Sialylation of beta1,3Gal in addition to 6-O-sulfation of GlcNAc moiety abolished the activity. (v) Prior alpha2,3 sialylation or 3-O-sulfation of beta1,3Gal would not affect alpha2,6 sialylation of Galbeta1,4GlcNAc of mucin core 2. (vi) A 3- or 4-fluoro substituent in beta1,4Gal resulted in poor acceptors for the cloned alpha2,6(N)ST and alpha2,3(N)ST, whereas 4-fluoro- or 4-OMe-Galbeta1,3GalNAcalpha was a good acceptor for cloned alpha2,3(O)ST. (vii) 4-O-Methylation of beta1,4Gal abolished the acceptor ability toward alpha2,6(N)ST but increased the acceptor efficiency considerably toward alpha2,3(N)ST. (viii) Just like LNCaPalpha1,2-FT and Gal-3-O-sulfotransferase T2, the cloned alpha2,3(N)ST which modifies terminal Gal in Galbeta1,4GlcNAc also efficiently utilizes the terminal beta1,3Gal in the Globo backbone. Utilization of C-3 blocked compounds such as 3-O-sulfo-Galbeta1,3GalNAcbeta1,3Galalpha-OMe as acceptors by cloned alpha2,3(O)ST and analyses of the resulting products by lectin chromatography and mass spectrometry indicate that alpha2,3(O)ST is capable of attaching NeuAc to another position in C-3-substituted beta1,3Gal.

Ionizing radiation potentiates the induction of nitric oxide synthase by interferon-gamma (Ifn-gamma) or Ifn-gamma and lipopolysaccharide in bnl cl.2 murine embryonic liver cells: role of hydrogen peroxide.

PubMed

Yoo, J C; Pae, H O; Choi, B M; Kim, W I; Kim, J D; Kim, Y M; Chung, H T

2000-02-01

The effects of ionizing irradiation on the nitric oxide (NO) production in murine embryonic liver cell line, BNL CL.2 cells, were investigated. Various doses (5-40 Gy) of radiation made BNL CL.2 cells responsive to interferon-gamma alone for the production of NO in a dose-dependent manner. Small amounts of lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha) synergized with IFN-gamma in the production of NO from irradiated BNL CL.2 cells, even though LPS or TNF-alpha alone did not induce NO production from the same cells. Immunoblots showed parallel induction of inducible nitric oxide synthase (iNOS). NO production in irradiated BNL CL.2 cells by IFN-gamma or IFN-gamma plus LPS was decreased by the addition of catalase, suggesting that H(2)O(2) produced by ionizing irradiation primed the cells to trigger NO production in response to IFN-gamma or IFN-gamma plus LPS. Furthermore, the treatment of nongamma-irradiated BNL CL.2 cells with H(2)O(2) made the cells responsive to IFN-gamma or IFN-gamma plus LPS for the production of NO. This study shows that ionizing irradiation has the ability to induce iNOS gene expression in responsive to IFN-gamma via the formation of H(2)O(2) in BNL CL.2 murine embryonic liver cells.

IL-2 activation of STAT5 enhances production of IL-10 from human cytotoxic regulatory T cells, HOZOT.

PubMed

Tsuji-Takayama, Kazue; Suzuki, Motoyuki; Yamamoto, Mayuko; Harashima, Akira; Okochi, Ayumi; Otani, Takeshi; Inoue, Toshiya; Sugimoto, Akira; Motoda, Ryuichi; Yamasaki, Fumiyuki; Nakamura, Shuji; Kibata, Masayoshi

2008-02-01

Interleukin (IL)-10 is an immunosuppressive cytokine produced by many cell types, including T cells. We previously reported that a novel type of regulatory T (Treg) cells, termed HOZOT, which possesses a FOXP3+CD4+CD8+CD25+ phenotype and dual suppressor/cytotoxic activities, produced high levels of IL-10. In this study, we examined the mechanisms of high IL-10 production by HOZOT, focusing on Janus activating kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway. We prepared five different types of T cells, including HOZOT from human umbilical cord blood. Cytokine productions of IL-10, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were compared among these T cells after anti-CD3/CD28 antibody stimulation in the presence or absence of IL-2. Specific inhibitors for JAK/STAT, nuclear factor-kappaB (NF-kappaB), and nuclear factor for activated T cell (NFAT) were used to analyze signal transduction mechanisms. IL-10 production by HOZOTs was greatly enhanced by the addition of IL-2. Little or no enhancement of IFN-gamma and TNF-alpha production was observed under the same conditions. The enhancing effect of IL-2 was specific for both HOZOT and IL-10-secreting Treg cells. T helper type 2 cells, whose IL-10 production mechanisms involve GATA-3, failed to show IL-2-mediated enhancement of IL-10. Similar enhancing effects of IL-15 and IFN-alpha suggested a major role of JAK/STAT activation pathway for high IL-10 production. Further inhibitor experiments demonstrated that STAT5 rather than STAT3 was critically involved in this mechanism. Our results demonstrated that IL-2 selectively enhanced production of IL-10 in HOZOT primarily through activation of STAT5, which synergistically acts with NF-kappaB/NFAT activation, implying a novel regulatory mechanism of IL-10 production in Treg cells.

Strong Association between Plasma Dipeptidyl Peptidase-4 Activity and Impaired Cognitive Function in Elderly Population with Normal Glucose Tolerance.

PubMed

Chen, Bo; Zheng, Tianpeng; Qin, Linyuan; Hu, Xueping; Zhang, Xiaoxi; Liu, Yihong; Liu, Hongbo; Qin, Shenghua; Li, Gang; Li, Qinghua

2017-01-01

Objective: Inflammation, oxidative stress, and decreased glucagon-like peptide-1 (GLP-1) are risk factors for cognitive impairment. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing these risk factors. Hence, we investigated the relationship between plasma DPP4 activity and impaired cognitive function in elderly Chinese population with normal glucose tolerance (NGT). Methods: We performed a cross-sectional study using data from 1229 elderly participants (60 years or older) in Guilin. Plasma DPP4 activity, oxidative stress parameters, fasting active GLP-1, and inflammatory markers were measured in all participants. Impaired cognitive function was diagnosed according to the National Institute on Aging-Alzheimer's Association workgroups criteria. Results: Participants in the upper quartile of plasma DPP4 activity had higher C-reactive protein (CRP), interleukin-6 (IL-6), 8-iso-PGF2a, nitrotyrosine, and lower GLP-1 and Montreal Cognitive Assessment (MoCA) scores compared with those in the lowest quartile ( P < 0.001). The odds ratios (ORs) for increased CRP, IL-6, 8-iso-PGF2a, nitrotyrosine, and decreased active GLP-1 were higher with increasing DPP4 quartiles after adjustment for confounders (all P < 0.001). In the highest DPP4 quartile, impaired cognitive function risk was higher (OR, 2.26; 95% confidence interval, 1.36-3.76) than in the lowest quartile after adjustment for potential confounders. The risk for impaired cognitive function increased more with higher levels of DPP4 activity, nitrotyrosine and 8-iso-PGF2a ( P < 0.05), but not with higher IL-6, CRP or lower GLP-1. Conclusion: Plasma DPP4 activity is significantly and independently associated with impaired cognitive function, mainly executive, in elderly Chinese population with NGT. The underlying mechanisms for this association may be partly attributed to the effect of DPP4 on oxidative stress. Plasma DPP4 activity might serve as a risk biomarker or therapeutic target for the prevention and treatment of impaired cognitive function.

Novel oligorhamnosides from the stem bark of Cleistopholis glauca.

PubMed

Seidel, V; Bailleul, F; Waterman, P G

2000-01-01

A reinvestigation of the stem bark of Cleistopholis glauca yielded 14 compounds, of which seven were either novel or had not been previously reported from this species. These were identified as the farnesane sesquiterpene methyl-(2E,6E)-10-oxo-3,7, 11-trimethyl-dodeca-2,6-dienoate (1); the azaanthracene alkaloid cleistopholine (4); two partially acetylated oligorhamnoside derivatives, 1-O-dodecanyl-2,3, 4-tri-O-acetyl-alpha-rhamnopyranosyl-(1-->3)-2, 4-di-O-acetyl-alpha-rhamnopyranosyl-(1-->3)-4-O-acetyl-alpha-rhamnopy ranosyl-(1-->4)-alpha-rhamnopyranoside (6) and 1-O-dodecanyl-2, 4-di-O-acetyl-alpha-rhamnopyranosyl-(1-->3)-2, 4-di-O-acetyl-alpha-rhamnopyranosyl-(1-->3)-4-O-acetyl-alpha-rhamnopy ranosyl-(1-->4)-alpha-rhamnopyranoside (8), for which the trivial names cleistetroside-7 and cleistetroside-6 were assigned, respectively; the dihydrobenzofuran neolignan rel-(2alpha, 3beta)-7-O-methylcedrusin (12); and the flavonoids dihydroquercetin (13) and quercetin (14). Structure assignments of all compounds were established by spectroscopic methods and comparison with published data. The chemosystematic significance of the occurrence of the isolated components is mentioned. Compounds 1, 6, and 8 are novel natural products.

Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha.

PubMed

Corral, L G; Haslett, P A; Muller, G W; Chen, R; Wong, L M; Ocampo, C J; Patterson, R T; Stirling, D I; Kaplan, G

1999-07-01

TNF-alpha mediates both protective and detrimental manifestations of the host immune response. Our previous work has shown thalidomide to be a relatively selective inhibitor of TNF-alpha production in vivo and in vitro. Additionally, we have recently reported that thalidomide exerts a costimulatory effect on T cell responses. To develop thalidomide analogues with increased anti-TNF-alpha activity and reduced or absent toxicities, novel TNF-alpha inhibitors were designed and synthesized. When a selected group of these compounds was examined for their immunomodulatory activities, different patterns of cytokine modulation were revealed. The tested compounds segregated into two distinct classes: one class of compounds, shown to be potent phosphodiesterase 4 inhibitors, inhibited TNF-alpha production, increased IL-10 production by LPS-induced PBMC, and had little effect on T cell activation; the other class of compounds, similar to thalidomide, were not phosphodiesterase 4 inhibitors and markedly stimulated T cell proliferation and IL-2 and IFN-gamma production. These compounds inhibited TNF-alpha, IL-1beta, and IL-6 and greatly increased IL-10 production by LPS-induced PBMC. Similar to thalidomide, the effect of these agents on IL-12 production was dichotomous; IL-12 was inhibited when PBMC were stimulated with LPS but increased when cells were stimulated by cross-linking the TCR. The latter effect was associated with increased T cell CD40 ligand expression. The distinct immunomodulatory activities of these classes of thalidomide analogues may potentially allow them to be used in the clinic for the treatment of different immunopathological disorders.

Glycosides from Bougainvillea glabra.

PubMed

Simon, András; Tóth, Gábor; Duddeck, Helmut; Soliman, Hesham S M; Mahmoud, Ibrahim I; Samir, Hanan

2006-01-01

Three glycosides were isolated from Bougainvillea glabra and their structures were determined by extensive use of 1D and 2D NMR spectroscopy ((1)H and (13)C). First compound was identical to momordin IIc (quinoside D) [beta-D-glucopyranosyl 3-O-[beta-D-xylopyranosyl-(1 --> 3)-O-(beta-D-glucopyranosyluronic acid)] oleanolate], second compound was quercetin 3-O-alpha-L-(rhamnopyranosyl)(1 --> 6)-[alpha-L-rhamnopy-ranosyl(1 --> 2)]-beta-D-galactopyranoside and third compound was its derivative quercetin 3-O-alpha-L-(4-caffeoylrhamnopyranosyl)(1 --> 6)-[alpha-L-rhamnopyranosyl (1 --> 2)]-beta-D-galactopyranoside, a new natural product.

Diastereoselective Diels-Alder reactions of alpha-fluorinated alpha,beta-unsaturated carbonyl compounds: chemical consequences of fluorine substitution. 2.

PubMed

Essers, Michael; Mück-Lichtenfeld, Christian; Haufe, Günter

2002-07-12

Two alpha-fluoro alpha,beta-unsaturated carbonyl compounds, i.e., benzyl 2-fluoroacrylate (3) and 2-fluorooct-1-en-3-one (4), as well as the corresponding nonfluorinated parent compounds, were synthesized and subjected to Diels-Alder reactions with cyclopentadiene. The cycloadditions were conducted thermally, microwave-assisted, and Lewis acid-mediated (TiCl(4)). The fluorinated dienophiles exhibited a lower reactivity and exo diastereoselectivity, while the corresponding nonfluorinated parent compounds reacted endo selectively. DFT calculations suggest that kinetic effects of fluorine determine the stereoselectivity rather than higher thermodynamic stability of the exo products.

Characterization of heterotrimeric collagen molecules in a sea-pen (Cnidaria, Octocorallia).

PubMed

Tillet-Barret, E; Franc, J M; Franc, S; Garrone, R

1992-01-15

The collagen of a primitive invertebrate, the sea-pen Veretillum Cnidaria, Octocorallia), was studied with respect to its molecular-chain composition. The soft extracellular tissues (mesoglea) were solubilized by limited pepsin proteolysis and the collagen was isolated by selective precipitation at 0.7 M NaCl under acidic conditions. The pepsinized molecules were 260 nm in length, as demonstrated by electron microscope studies of rotary-shadowed molecules and of the segment-long-spacing crystallites obtained by dialysis against ATP. SDS/PAGE of the extract produced two main bands susceptible to bacterial collagenase, designated as the alpha 1 and alpha 2 chain, which were differentiated clearly by their CNBr cleavage products and the higher glycosylation rate of the alpha 2 chain. The latter finding corresponds with the high hydroxylysine content of the alpha 2 chain. The alpha 1/alpha 2 chain ratio observed in SDS/PAGE and the fact that only one peak was obtained by concanavalin-A affinity chromatography of a non-denatured 0.7 M NaCl extract demonstrate the alpha 1 [alpha 2]2 molecular structure of this collagen. These results contrast with data on the structure of other coelenterates (i.e. [alpha]3 for sea anemone collagen molecules and alpha 1 alpha 2 alpha 3 for jellyfish collagen molecules). They are discussed in relation to the evolution of collagen.

Production of surfactant and detergent-stable, halophilic, and alkalitolerant alpha-amylase by a moderately halophilic Bacillus sp. Strain TSCVKK.

PubMed

Kiran, Kondepudi Kanthi; Chandra, T S

2008-01-01

A moderately halophilic alkalitolerant Bacillus sp. Strain TSCVKK, with an ability to produce extracellular halophilic, alkalitolerant, surfactant, and detergent-stable alpha-amylase was isolated from soil samples obtained from a salt-manufacturing industry in Chennai. The culture conditions for higher amylase production were optimized with respect to NaCl, substrate, pH, and temperature. Maximum amylase production of 592 mU/ml was achieved in the medium at 48 h with 10% NaCl, 1% dextrin, 0.4% yeast extract, 0.2% tryptone, and 0.2% CaCl(2) at pH 8.0 at 30 degrees C. The enzyme activity in the culture supernatant was highest with 10% NaCl at pH 7.5 and 55 degrees C. The amylase that was partially purified by acetone precipitation was highly stable in various surfactants and detergents. Glucose, maltose, and maltooligosaccharides were the main end products of starch hydrolysis indicating that it is an alpha-amylase.

Production of interferon-alpha in high cell density cultures of recombinant Escherichia coli and its single step purification from refolded inclusion body proteins.

PubMed

Babu, K R; Swaminathan, S; Marten, S; Khanna, N; Rinas, U

2000-06-01

Escherichia coli TG1 transformed with a temperature-regulated interferon-alpha expression vector was grown to high cell density in defined medium containing glucose as the sole carbon and energy source, utilizing a simple fed-batch process. Feeding was carried out to achieve an exponential increase in biomass at growth rates which minimized acetate production. Thermal induction of such high cell density cultures resulted in the production of approximately 4 g interferon-alpha/l culture broth. Interferon-alpha was produced exclusively in the form of insoluble inclusion bodies and was solubilized under denaturing conditions, refolded in the presence of arginine and purified to near homogeneity, utilizing single-step ion-exchange chromatography on Q-Sepharose. The yield of purified interferon-alpha was approximately 300 mg/l with respect to the original high cell density culture broth (overall yield of approximately 7.5% active interferon-alpha). The purified recombinant interferon-alpha was found by different criteria to be predominantly monomeric and possessed a specific bioactivity of approximately 2.5 x 10(8) IU/mg based on viral cytopathic assay.

Effects of pro-inflammatory cytokines, lipopolysaccharide and COX-2 mediators on human colonic neuromuscular function and epithelial permeability.

PubMed

Safdari, B K; Sia, T C; Wattchow, D A; Smid, S D

2016-07-01

Chronic colitis is associated with decreased colonic muscle contraction and loss of mucosal barrier function. Pro-inflammatory cytokines and bacterial lipopolysaccharide (LPS) are important in the generation and maintenance of inflammation. While colitis is associated with upregulated COX-2 -derived prostanoids and nitric oxide (NO), the direct activity of pro-inflammatory cytokines on human colonic neuromuscular function is less clear. This study investigated the effects of IBD-associated pro-inflammatory cytokines IL-17, TNF-α, IL-1β and LPS on human colonic muscle strip contractility, alone and following inhibition of COX-2 or nitric oxide production. In addition, human colonic epithelial Caco-2 cell monolayers were treated with LPS or COX-2 mediators including prostaglandins (PGE2, PGF2α) or their corresponding ethanolamides (PGE2-EA or PGF2α-EA) over 48h and trans-epithelial electrical resistance used to record permeability changes. Longitudinal muscle strips were obtained from healthy colonic resection margins and mounted in organ baths following IL-17, TNF-α, IL-1β and bacterial LPS incubations in an explant setting over 20h. Contraction in response to acetylcholine (ACh) was then measured, before and after either COX-2 inhibition (nimesulide; 10(-5)M) or nitric oxide synthase (NOS) inhibition (l-NNA; 10(-4)M). None of the cytokine or LPS explant incubations affected the potency or maximum cholinergic contraction in vitro, and subsequent COX-2 blockade with nimesulide revealed a significant but similar decrease in potency of ACh-evoked contraction in control, LPS and cytokine-incubated muscle strips. Pre-treatment with l-NNA provided no functional differences in the potency or maximum contractile responses to ACh in cytokine or LPS-incubated colonic longitudinal smooth muscle. Only PGE2 transiently increased Caco-2 monolayer permeability at 24h, while LPS (10μg/ml) increased permeability over 24-48h. These findings indicate that cholinergic contractility in the human colon can be decreased by the blockade of COX-2 generated excitatory prostanoids, but major pro-inflammatory cytokines or LPS do not alter the sensitivity or amplitude of this contraction ex vivo. While PGE2 transiently increase epithelial permeability, LPS generates a significant and sustained increase in permeability indicative of an important role on barrier function at the mucosal interface. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.