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Sample records for administration increased serum

  1. In vivo administration of IL-1 induces thymic hypoplasia and increased levels of serum corticosterone

    SciTech Connect

    Morrissey, P.J.; Charrier, K.; Alpert, A.; Bressler, L.

    1988-09-01

    Administration of IL-1 alpha or IL-1 beta to normal mice induces a decrease in thymic cellularity, the magnitude of which depends on the number of injections and dose of IL-1. Twice daily injections of 200 ng of IL-1 alpha or -beta for 4 days results in a 90% decrease in thymic cellularity, which regenerated after cessation of treatment. Study of thymocyte subpopulations revealed that the number of CD4+/CD8+ thymocytes was dramatically decreased in IL-1-treated mice. Functional assessment of the CD4-/CD8- population from treated animals showed that these cells had adequate mitogenic responses in vitro and that the proportion of these cells in cycle was not different from control CD4-/CD8- cells. IL-1 treatment also prevented the regeneration of thymic cellularity after irradiation. The use of strains of mice differing genetically at the Ly 1 locus to construct radiation bone marrow chimeras demonstrated that bone marrow-derived thymocyte precursors were able to seed the thymus in the IL-1-treated animals. Again, however, the CD4+/CD8+ thymocyte population was significantly decreased. Thymic repopulation occurred upon cessation of IL-1 therapy. Finally, we determined that a single i.p. injection of IL-1 caused a three-fold increase in serum corticosterone levels, which peaked approximately 3 h after IL-1 administration. Thus, an IL-1-dependent increase in serum corticosterone levels may be responsible for the observed thymic hypoplasia.

  2. Increased serum bile acid concentration following low-dose chronic administration of thioacetamide in rats, as evidenced by metabolomic analysis.

    PubMed

    Jeong, Eun Sook; Kim, Gabin; Shin, Ho Jung; Park, Se-Myo; Oh, Jung-Hwa; Kim, Yong-Bum; Moon, Kyoung-Sik; Choi, Hyung-Kyoon; Jeong, Jayoung; Shin, Jae-Gook; Kim, Dong Hyun

    2015-10-15

    A liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS)-based metabolomics approach was employed to identify endogenous metabolites as potential biomarkers for thioacetamide (TAA)-induced liver injury. TAA (10 and 30mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague-Dawley (SD) rats for 28days. We then conducted untargeted analyses of endogenous serum and liver metabolites. Partial least squares discriminant analysis (PLS-DA) was performed on serum and liver samples to evaluate metabolites associated with TAA-induced perturbation. TAA administration resulted in altered levels of bile acids, acyl carnitines, and phospholipids in serum and in the liver. We subsequently demonstrated and confirmed the occurrence of compromised bile acid homeostasis. TAA treatment significantly increased serum levels of conjugated bile acids in a dose-dependent manner, which correlated well with toxicity. However, hepatic levels of these metabolites were not substantially changed. Gene expression profiling showed that the hepatic mRNA levels of Ntcp, Bsep, and Oatp1b2 were significantly suppressed, whereas those of basolateral Mrp3 and Mrp4 were increased. Decreased levels of Ntcp, Oatp1b2, and Ostα proteins in the liver were confirmed by western blot analysis. These results suggest that serum bile acids might be increased due to the inhibition of bile acid enterohepatic circulation rather than increased endogenous bile acid synthesis. Moreover, serum bile acids are a good indicator of TAA-induced hepatotoxicity. PMID:26222700

  3. Penicillin concentrations in serum, milk, and urine following intramuscular and subcutaneous administration of increasing doses of procaine penicillin G in lactating dairy cows.

    PubMed Central

    Dubreuil, P; Daigneault, J; Couture, Y; Guay, P; Landry, D

    2001-01-01

    Eight healthy, non-pregnant, crossbred Holstein dairy cows (557-682 kg) within their first 3 months of lactation (13-21.5 kg of milk/day) were used. Cows were kept in tie stalls for the whole experiment. The 8 cows were randomly assigned to 2 (IM and SC) 4 x 4 balanced Latin square design experiments. Doses of procaine penicillin G (PPG) (300000 IU/mL) in each square were 7000, 14000, 21000 and 28000 IU/kg and were injected IM or SC once daily for 5 consecutive days. Volumes of PPG per site of injection never exceeded 20 mL. Blood was collected to determine the Cmax, Tmax, and AUC; urine and milk were also taken to measure the persistence of PPG in these fluids. Results show that serum Cmax and Tmax were only slightly affected by increasing the doses or the route of administration, whereas the AUC was linearly increased in relation to the dose injected in both modes of injection. In the urine, Cmax varied from 160 to 388 IU/mL and Tmax from 72-120 h during 5 consecutive days of PPG injection. A dose effect in Cmax was observed only for the IM route of administration and no variation (P > 0.05) was found between the IM and SC routes. Milk Cmax concentrations were only increased by the dose regimen in the IM group. At doses of 21000 and 28000 IU/kg, the IM group had a higher (P > 0.05) Cmax when compared with the SC groups. Milk PPG residues were not detectable over 96 h following the last IM injection, independently of the dose injected. However milk PPG residues were detected for up to 132 h following the last SC injection. These results show that when PPG is injected IM once daily in volumes not exceeding 20 mL/site at doses as high as 28000 IU/kg, the withdrawal period should be at least 96 h. Therefore, in the present model, there was no advantage to inject PPG by SC route to improve PPG kinetic parameters as the AUC, Cmax, or Tmax. PMID:11480523

  4. Serum Survivin Increases in Prolactinoma

    PubMed Central

    Dellal, Fatma Dilek; Niyazoglu, Mutlu; Gorar, Suheyla; Ademoglu, Esranur; Candan, Zehra; Bekdemir, Handan; Hacioglu, Yalcin; Kaya, Fatih Oner

    2015-01-01

    Background Prolactinoma is the most common adult pituitary adenoma. Survivin is a member of the family of inhibitors of apoptosis proteins. Its expression is observed in many tumors. Survivin expression has shown in prolactinoma tissue before but no study exists showing serum survivin level. The aim of the present study was to investigate serum survivin levels in patients with prolactinoma and demonstrate its value in diagnosis of the disease. Methods The group of patients consisted of 25 women, aged from 17 to 51 years. As a control group, 21 healthy women, aged from 22 to 45 years were included. Twenty patients had microprolactinoma, while five patients had macroprolactinoma. All patients had received dopamine agonist treatment. Serum survivin levels were measured in all of the groups. Results Survivin levels were significantly higher in prolactinoma patients compared to controls (19.04 (10 - 38) pg/mL; 15.05 (8 - 22) pg/mL; P = 0.042). There was no difference between microadenoma and macroadenoma patients in survivin levels (19.22 (10 - 38) pg/mL; 18.40 (16 - 22) pg/mL; P = 0.914). In correlation analysis, survivin was not correlated with other parameters. Conclusions We consider that higher survivin levels might be a molecular marker predicting the presence of prolactinoma and may be useful for the diagnosis. But large-scale research is needed to clarify its role in diagnosis of prolactinoma patients. PMID:25699121

  5. Administration of antisomatotropin serum in diabetes mellitus.

    PubMed

    Góth, M; Szabolcs, I

    1981-03-01

    The effect of antisomatotropin serum (ASS), raised in horse against human growth hormone, on the carbohydrate metabolism of diabetics has been investigated. Among the eight diabetic patients treated so far two had GH secreting pituitary adenoma, two insulin-dependent, and four others adult onset diabetes mellitus. The glucose tolerance curve improved in all but one patient. The effect lasted for two--four weeks. Because of this short time of efficiency, the place of ASS in the definite treatment of diabetes mellitus cannot been judged so far, however, its administration in diabetic retinopathy seems to be advantageous. PMID:7227326

  6. Why Block Grants Should Increase Administrative Costs.

    ERIC Educational Resources Information Center

    Baker, Keith

    1983-01-01

    Federal education programs increase costs because they attach fewer strings to funds than state or local grants, and this is likely to lead to administrative empire-building. Bureaucracy tends pathologically as it grows to generate more work for itself independent of true administrative needs. Some policy implications are drawn. (MJL)

  7. Timing of Levothyroxine Administration Affects Serum Thyrotropin Concentration

    PubMed Central

    Bach-Huynh, Thien-Giang; Nayak, Bindu; Loh, Jennifer; Soldin, Steven; Jonklaas, Jacqueline

    2009-01-01

    Context: Patients treated with levothyroxine typically ingest it in a fasting state to prevent food impairing its absorption. The serum thyrotropin concentration is the therapeutic index of levothyroxine action. Objective: The study objective was to determine the effect of the timing of levothyroxine administration in relationship to food on serum thyrotropin levels. Design: Participants were randomized to one of six sequences, each consisting of three 8-wk regimens in a three-period crossover design. These regimens were in a fasting state, at bedtime, and with breakfast. The concentrations of TSH, free T4, and total T3 during each of the three timing regimens were documented. The primary outcome was the difference between serum TSH concentrations under fasting conditions compared with concentrations during the other 8-wk regimens. Setting: The study was conducted in an academic medical center. Participants: Study participants were receiving levothyroxine for treatment of hypothyroidism or thyroid cancer. Results: Sixty-five patients completed the study. The mean thyrotropin concentration was 1.06 ± 1.23 mIU/liter when levothyroxine was administered in the fasting state. When levothyroxine was taken with breakfast, the serum thyrotropin concentration was significantly higher (2.93 ± 3.29 mIU/liter). When levothyroxine was taken at bedtime, the serum TSH concentration was also significantly higher (2.19 ± 2.66 mIU/liter). Conclusion: Nonfasting regimens of levothyroxine administration are associated with higher and more variable serum TSH concentrations. If a specific serum TSH goal is desired, thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion of levothyroxine ensures that TSH concentrations remain within the narrowest target range. PMID:19584184

  8. Central injection of CDP-choline suppresses serum ghrelin levels while increasing serum leptin levels in rats.

    PubMed

    Kiyici, Sinem; Basaran, Nesrin Filiz; Cavun, Sinan; Savci, Vahide

    2015-10-01

    In this study we aimed to test central administration of CDP-choline on serum ghrelin, leptin, glucose and corticosterone levels in rats. Intracerebroventricular (i.c.v.) 0.5, 1.0 and 2.0 µmol CDP-choline and saline were administered to male Wistar-Albino rats. For the measurement of serum leptin and ghrelin levels, blood samples were obtained baseline and at 5, 15, 30, 60 and 120 min following i.c.v. CDP-choline injection. Equimolar doses of i.c.v. choline (1.0 µmol) and cytidine (1.0 µmol) were administered and measurements were repeated throughout the second round of the experiment. Atropine (10 µg) and mecamylamine (50 µg) were injected intracerebroventricularly prior to CDP-choline and measurements repeated in the third round of the experiment. After 1 µmol CDP-choline injection, serum ghrelin levels were suppressed significantly at 60 min (P=0.025), whereas serum leptin levels were increased at 60 and 120 min (P=0.012 and P=0.017 respectively). CDP-choline injections also induced a dose- and time-dependent increase in serum glucose and corticosterone levels. The effect of choline on serum leptin and ghrelin levels was similar with CDP-choline while no effect was seen with cytidine. Suppression of serum ghrelin levels was eliminated through mecamylamine pretreatment while a rise in leptin was prevented by both atropine and mecamylamine pretreatments. In conclusion; centrally injected CDP-choline suppressed serum ghrelin levels while increasing serum leptin levels. The observed effects following receptor antagonist treatment suggest that nicotinic receptors play a role in suppression of serum ghrelin levels,whereas nicotinic and muscarinic receptors both play a part in the increase of serum leptin levels. PMID:26162700

  9. Intrathecal Veratridine Administration Increases MAC in Rats

    PubMed Central

    Zhang, Yi; Sharma, Manohar; Eger, Edmond I; Laster, Michael J.; Hemmings, Hugh C.; Harris, R. Adron

    2008-01-01

    Background Results from several studies point to sodium channels as potential mediators of the immobility produced by inhaled anesthetics. We hypothesized that the intrathecal administration of veratridine, a drug that enhances the activity or effect of sodium channels, should increase MAC. Methods We measured the change in isoflurane MAC caused by intrathecal infusion of various concentrations of veratridine into the lumbothoracic subarachnoid space of rats. We compared these result to those obtained from intracerebroventricular infusion. Results As predicted, intrathecal infusion of veratridine increased MAC. The greatest infused concentration (25 μM) also produced neuronal injury in the hind limbs of two rats and decreased the peak effect on MAC. A concentration of 1.6 μM produced the greatest (21%) increase in MAC. Intraventricular infusion of 1.6 and 6.4 μM veratridine did not alter MAC. Rats given 25 μM died. Conclusion Intrathecal administration of veratradine increases MAC of isoflurane, a finding consistent with a role for sodium channels as potential mediators of the immobility produced by inhaled anesthetics. Implications Intrathecal administration of veratridine can increase MAC, presumably by an effect on sodium channels. PMID:18713899

  10. Determinants that increase the serum resistance of Escherichia coli.

    PubMed Central

    Taylor, P W; Robinson, M K

    1980-01-01

    The rfb locus, determining biosynthesis of O8-specific lipopolysaccharide side chains, was transferred to a rough mutant of Escherichia coli; recombinants producing a complete lipopolysaccharide were more resistant to the complement-mediated bactericidal action of human serum than the rough recipient. Inheritance of the his-linked genes for K27 antigen production did not alter the response to serum. The serum resistance of strains carrying O8 side chains, but not of strains with incomplete lipopolysaccharides, was further increased by inheritance of plasmids R1 and NR1.20 PMID:6995340

  11. An increase of serum lipids after cumulative doses of doxorubicin and epirubicin in experimental animals.

    PubMed

    Stathopoulos, G P; Papadopoulos, N G; Stephanopoulou, A; Dontas, I; Kotsarelis, D; Karayannacos, P E

    1996-01-01

    A wide range of pharmacological actions has been attributed to the anthracyclins. In this study we examined their effect on serum lipids in experimental animals in parallel with histological alterations. Three Wistar rat groups were injected with doxorubicin, epirubicin or normal saline once a week for 12 weeks. Total serum lipids, cholesterol, triglycerides, HDL-cholesterol, transaminases, proteins and alkaline phosphatase were assayed weekly. A proportion of the animals were sacrificed at the same time points and the cardiac muscle, large vessels, liver and abdominal muscle were stained and examined under light microscopy. Serum lipids were found to increase gradually, starting after 8 weeks of drug administration, until the end of the experiment. Tissue damage was noted in the cardiac muscle, abdominal muscle and large vessels, also following an increasing trend. Doxorubicin had a more pronounced effect than epirubicin on both serum lipid increase and tissue destruction. These alterations may contribute to anthracyclin-related cardiac damage. PMID:9042202

  12. Increased serum cortisol binding in chronic active hepatitis

    SciTech Connect

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG.

  13. Effects of oral administration of a calcium-containing gel on serum calcium concentration in postparturient dairy cows.

    PubMed

    Queen, W G; Miller, G Y; Masterson, M A

    1993-02-15

    Various nutritious nutritional-supplement gels are being marketed for use in veterinary medicine. This study was designed to determine whether serum calcium, phosphorous, or magnesium concentrations were different between cows given a gel containing calcium chloride as its active ingredient (treated) and cows given inert carrier gel (control). The study revealed a significant (P < 0.01) increase in serum total calcium concentration within 5 minutes of administration of a calcium gel given to cows within 1 hour of parturition. Serum total calcium concentration had returned to baseline value by 24 hours after calcium gel administration. Serum inorganic phosphorus concentration also increased significantly (P < 0.05) after treatment. Significant changes in serum magnesium concentrations were not detected. PMID:8449800

  14. Serum Sclerostin Increases in Healthy Adult Men during Bed Rest

    PubMed Central

    Fields, E. E.; Yu, E. W.; Pajevic, P. Divieti; Bouxsein, M. L.; Sibonga, J. D.; Zwart, S. R.; Smith, S. M.

    2012-01-01

    Context: Animal models and human studies suggest that osteocytes regulate the skeleton's response to mechanical unloading in part by an increase in sclerostin. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Objective: We determined changes in serum sclerostin and bone turnover markers in healthy adult men undergoing controlled bed rest. Design, Setting, and Participants: Seven healthy adult men (31 ± 3 yr old) underwent 90 d of 6° head down tilt bed rest at the University of Texas Medical Branch Institute for Translational Sciences-Clinical Research Center. Outcomes: Serum sclerostin, PTH, vitamin D, bone resorption and formation markers, urinary calcium and phosphorus excretion, and 24-h pooled urinary markers of bone resorption were evaluated before bed rest [baseline (BL)] and at bed rest d 28 (BR-28), d 60 (BR-60), and d 90 (BR-90). Bone mineral density was measured at BL, BR-60, and 5 d after the end of the study (BR+5). Data are reported as mean ± sd. Results: Consistent with prior reports, bone mineral density declined significantly (1–2% per month) at weight-bearing skeletal sites. Serum sclerostin was elevated above BL at BR-28 (+29 ± 20%; P = 0.003) and BR-60 (+42 ± 31%; P < 0.001), with a lesser increase at BR-90 (+22 ± 21%; P = 0.07). Serum PTH levels were reduced at BR-28 (−17 ± 16%; P = 0.02) and BR-60 (−24 ± 14%; P = 0.03) and remained lower than BL at BR-90 (−21 ± 21%; P = 0.14), but did not reach statistical significance. Serum bone turnover markers were unchanged; however, urinary bone resorption markers and calcium were significantly elevated at all time points after bed rest (P < 0.01). Conclusions: In healthy men subjected to controlled bed rest for 90 d, serum sclerostin increased, with a peak at 60, whereas serum PTH declined, and urinary calcium and bone resorption markers increased. PMID:22767636

  15. Serum Calcium Increase Correlates With Worsening of Lipid Profile

    PubMed Central

    Gallo, Luigia; Faniello, Maria C.; Canino, Giovanni; Tripolino, Cesare; Gnasso, Agostino; Cuda, Giovanni; Costanzo, Francesco S.; Irace, Concetta

    2016-01-01

    Abstract Despite the well-documented role of calcium in cell metabolism, its role in the development of cardiovascular disease is still under heavy debate. Several studies suggest that calcium supplementation might be associated with an increased risk of coronary heart disease, whereas others underline a significant effect on lowering high blood pressure and hyperlipidemia. The purpose of this study was to investigate, in a large nonselected cohort from South Italy, if serum calcium levels correlate with lipid values and can therefore be linked to higher individual cardiovascular risk. Eight-thousand-six-hundred-ten outpatients addressed to the Laboratory of Clinical Biochemistry, University of Magna Græcia, Catanzaro, Italy from January 2012 to December 2013 for routine blood tests, were enrolled in the study. Total HDL-, LDL- and non-HDL colesterol, triglycerides, and calcium were determined with standard methods. We observed a significant association between total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, triglycerides, and serum calcium in men and postmenopause women. Interestingly, in premenopause women, we only found a direct correlation between serum calcium, total cholesterol, and HDL-cholesterol. Calcium significantly increased while increasing total cholesterol and triglycerides in men and postmenopause women. Our results confirm that progressive increase of serum calcium level correlates with worsening of lipid profile in our study population. Therefore, we suggest that a greater caution should be used in calcium supplement prescription particularly in men and women undergoing menopause, in which an increase of serum lipids is already known to be associated with a higher cardiovascular risk. PMID:26937904

  16. Serum neopterin is not increased in obese juveniles.

    PubMed

    Mangge, Harald; Freytag, Florian; Almer, Gunter; Weghuber, Daniel; Bauer-Denk, Carmen; Fuchs, Dietmar

    2011-01-01

    Objective. Cardiovascular disease is associated with inflammation and immune activation, concentrations of immune activation markers like neopterin predict outcome in adults. Methods. Serum neopterin concentrations and early metabolic and pre-atherosclerotic symptoms were analyzed in 295 obese juveniles and 101 normal weight controls of similar age. Additionally, the influence of a 12 months weight reduction program on neopterin levels was investigated in 31 obese juveniles. Results. Intima-media thickness of common carotid arteries (IMT) and the concentrations of C-reactive protein (CRP) were increased in the obese juveniles (P < .001). Also triglycerides, oxidized LDL, fasted insulin levels, HOMA-index, leptin, liver transaminases and uric acid were increased compared to the controls. However, serum neopterin was decreased in the obese versus non-obese juveniles (P < .03). The intervention consisting of regular sports, nutritional devices, and a psychologic attendance led after 12 months to an increase of neopterin concentration (P < .05; paired test). Conclusions. Neopterin concentrations in juvenile obesity behaved considerably different from what was demonstrated in adults, levels did not correlate with metabolic and pre-atherosclerotic symptoms found in early phases although early vascular burden and chronic low grade inflammation was indicated by increased IMT and CRP. Neopterin concentrations increased after a 12 months intervention program. PMID:21274279

  17. L-tyrosine administration increases acetylcholinesterase activity in rats.

    PubMed

    Ferreira, Gabriela K; Carvalho-Silva, Milena; Gonçalves, Cinara L; Vieira, Júlia S; Scaini, Giselli; Ghedim, Fernando V; Deroza, Pedro F; Zugno, Alexandra I; Pereira, Talita C B; Oliveira, Giovanna M T; Kist, Luiza W; Bogo, Maurício R; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

    2012-12-01

    Tyrosinemia is a rare genetic disease caused by mutations on genes that codify enzymes responsible for tyrosine metabolism. Considering that tyrosinemics patients usually present symptoms associated with central nervous system alterations that ranges from slight decreases in intelligence to severe mental retardation, we decided to investigate whether acute and chronic administration of L-tyrosine in rats would affect acetylcholinesterase mRNA expression and enzymatic activity during their development. In our acute protocol, Wistar rats (10 and 30 days old) were killed one hour after a single intraperitoneal L-tyrosine injection (500 mg/kg) or saline. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old) and rats were killed 12 h after last injection. Acetylcholinesterase activity was measured by Ellman's method and acetylcholinesterase expression was carried out by a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay. We observed that acute (10 and 30 days old rats) and chronic L-tyrosine administration increased acetylcholinesterase activity in serum and all tested brain areas (hippocampus, striatum and cerebral cortex) when compared to control group. Moreover, there was a significant decrease in mRNA levels of acetylcholinesterase in hippocampus was observed after acute protocol (10 and 30 days old rats) and in striatum after chronic protocol. In case these alterations also occur in the brain of the patients, our results may explain, at least in part, the neurological sequelae associated with high plasma concentrations of tyrosine seen in patients affected by tyrosinemia type II. PMID:23046746

  18. Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant.

    PubMed

    Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

    2015-01-01

    The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant. PMID:25750999

  19. Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant

    PubMed Central

    Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

    2015-01-01

    The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant. PMID:25750999

  20. Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 level.

    PubMed

    Kashihara, T; Ohki, A; Kobayashi, T; Sato, T; Nishizawa, H; Ogawa, K; Tako, H; Kawakami, F; Tsuji, M; Tamaoka, K

    1998-06-01

    CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or = 10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC. PMID:9658330

  1. Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents

    PubMed Central

    Mawad, Habib; Laurin, Louis-Philippe; Naud, Jean-François; Leblond, François A.; Henley, Nathalie; Vallée, Michel; Pichette, Vincent; Leblanc, Martine

    2016-01-01

    OBJECTIVE The aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function. METHODS We measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration. RESULTS Baseline serum creatinine was 57.8 ± 34.5 µmol/L and remained stable. Urinary IL-18 levels increased significantly at three hours (10.7 vs. 7.3 ng/mg creatinine; P < 0.05). Similarly, urinary NAG levels increased significantly at three hours (3.9 vs. 2.2 IU/mg creatinine; P < 0.001). For both these markers, the difference was no longer significant at 24 hours. No statistically significant differences were observed for urinary and serum neutrophil gelatinase-associated lipocalin levels and for serum cystatin C levels. CONCLUSIONS Urinary IL-18 and NAG levels increased transiently after administration of gadolinium-based contrast agents in patients with normal renal function. PMID:27398022

  2. Influence of experimental alcohol administration on serum immunoglobulin levels: contrasting effects on IgE and other immunoglobulin classes.

    PubMed

    Alonso, M; Gomez-Rial, J; Gude, F; Vidal, C; Gonzalez-Quintela, A

    2012-01-01

    In humans, alcoholic liver disease is associated with hypergammaglobulinemia, particularly with high serum concentrations of IgA. Furthermore, alcohol consumption is associated with high concentrations of IgE and low concentrations of IgG. However, there is little experimental evidence to corroborate these observational findings. The objective of the present study was to investigate the potential short-term effects of alcohol administration on serum immunoglobulin concentrations in mice, and the potential influence of sex and strain on these effects. Eight mouse groups were defined by strain (Swiss vs C57BL/6), sex (male vs female), and experimental procedure (alcohol administration vs control diet). Alcohol was administered in a semi-liquid diet (6.5%v/v); control animals received an isocaloric semi-liquid diet. Immunoglobulin concentrations (IgE, IgA, IgM, IgG1, IgG2a, IgG2b, and IgG3) were measured at baseline and weekly thereafter for 4 weeks. Serum Th1 (interferon-gamma) and Th2 (IL-4 and IL-13) cytokines were measured at week 4. We found significant variations in baseline immunoglobulin concentrations depending upon mouse sex and strain. Alcohol administration was quickly followed by an increase in serum IgE concentrations in all experimental groups. IgE increase was correlated with serum IL-13 increase. In contrast, alcohol administration was not associated with significant changes in serum IgA and IgM concentration, and appeared to decrease IgG subclass concentrations. Alcohol effects on immunoglobulin concentrations were independent of mouse strain and sex. In conclusion, alcohol administration in mice had contrasting effects on IgE and other immunoglobulin classes. This experimental evidence confirms observational results in humans. PMID:23058015

  3. Increases in Serum Estrone Sulfate Level Are Associated with Increased Mammographic Density during Menopausal Hormone Therapy

    PubMed Central

    Crandall, Carolyn J.; Guan, Min; Laughlin, Gail A.; Ursin, Giske A.; Stanczyk, Frank Z.; Ingles, Sue A.; Barrett-Connor, Elizabeth; Greendale, Gail A.

    2009-01-01

    Background Menopausal hormone therapy increases mammographic density. We determined whether increases in serum estrone sulfate (E1S) levels during menopausal hormone therapy predict increased mammographic density. Methods We measured percent mammographic density and serum E1S levels in 428 participants of the Postmenopausal Estrogen/Progestin Interventions study who were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg alone, CEE + daily medroxyprogesterone acetate (MPA) 2.5 mg, CEE + cyclical MPA (10 mg days 1-12 per 28-day cycle), or CEE + cyclical micronized progesterone (10 mg days 1-12). Serum E1S levels were determined by RIA. Information about covariates was determined by annual questionnaire. Using linear regression, we determined the association between change in E1S level from baseline to 12 months and change in percent mammographic density (by semiquantitative interactive threshold method). Results After controlling for baseline mammographic density, age, body mass index, alcohol intake, parity, smoking, ethnicity, physical activity, and age at first pregnancy, mammographic density increased by 1.3% for every 1 ng/mL increase in E1S level (P < 0.0001). The association between change in E1S level and change in mammographic density differed by treatment group (greater effect in CEE + cyclical MPA group versus CEE group; P = 0.05). After controlling for treatment group, change in the ratio of E1S to E1 was also positively associated with change in mammographic density. Conclusions Increases in serum E1S levels during menopausal hormone therapy are associated with increases in mammographic density. The relative contribution of E1S and E1 to stimulation of breast tissue awaits further elucidation. PMID:18628419

  4. Low serum testosterone increases mortality risk among male dialysis patients.

    PubMed

    Carrero, Juan Jesús; Qureshi, Abdul Rashid; Parini, Paolo; Arver, Stefan; Lindholm, Bengt; Bárány, Peter; Heimbürger, Olof; Stenvinkel, Peter

    2009-03-01

    Men treated with hemodialysis (HD) have a very poor prognosis and an elevated risk of premature cardiovascular disease (CVD). In the general population, associations between low testosterone concentrations and cardiovascular risk have been suggested. We performed a prospective observational study involving a well characterized cohort of 126 men treated with HD to examine the relationship between testosterone concentration and subsequent mortality during a mean follow-up period of 41 mo. Independent of age, serum creatinine, and sexual hormone binding globulin (SHBG), testosterone levels inversely and strongly associated with the inflammatory markers IL-6 and CRP. Patients with a clinical history of CVD had significantly lower testosterone levels. During follow up, 65 deaths occurred, 58% of which were a result of CVD. Men with testosterone values in the lowest tertile had increased all-cause and CVD mortality (crude hazard ratios [HRs] 2.03 [95% CI 1.24 to 3.31] and 3.19 [1.49 to 6.83], respectively), which persisted after adjustment for age, SHBG, previous CVD, diabetes, ACEi/ARB treatment, albumin, and inflammatory markers, but was lost after adjustment for creatinine. In summary, among men treated with HD, testosterone concentrations inversely correlate with all-cause and CVD-related mortality, as well as with markers of inflammation. Hypogonadism may be an additional treatable risk factor for patients with chronic kidney disease. PMID:19144759

  5. Increasing Equity in Administrative Leadership: A Regents' Model.

    ERIC Educational Resources Information Center

    Powell, Jack V.

    1992-01-01

    Describes Georgia State Board of Regents's model for increasing the presence of African American in administrative positions in the Georgia state university system. A postdoctoral internship program selected faculty members with an interest in administration in higher education. The author's own participation is described. (SLD)

  6. Ibuprofen administration attenuates serum TNF-{alpha} levels, hepatic glutathione depletion, hepatic apoptosis and mouse mortality after Fas stimulation

    SciTech Connect

    Cazanave, Sophie; Vadrot, Nathalie; Tinel, Marina; Berson, Alain; Letteron, Philippe; Larosche, Isabelle; Descatoire, Veronique; Feldmann, Gerard; Robin, Marie-Anne |; Pessayre, Dominique |

    2008-09-15

    Fas stimulation recruits neutrophils and activates macrophages that secrete tumor necrosis factor-{alpha} (TNF-{alpha}), which aggravates Fas-mediated liver injury. To determine whether nonsteroidal anti-inflammatory drugs modify these processes, we challenged 24-hour-fasted mice with the agonistic Jo2 anti-Fas antibody (4 {mu}g/mouse), and treated the animals 1 h later with saline or ibuprofen (250 mg/kg), a dual cyclooxygenase (COX)-1 and COX-2 inhibitor. Ibuprofen attenuated the Jo2-mediated recruitment/activation of myeloperoxidase-secreting neutrophils/macrophages in the liver, and attenuated the surge in serum TNF-{alpha}. Ibuprofen also minimized hepatic glutathione depletion, Bid truncation, caspase activation, outer mitochondrial membrane rupture, hepatocyte apoptosis and the increase in serum alanine aminotransferase (ALT) activity 5 h after Jo2 administration, to finally decrease mouse mortality at later times. The concomitant administration of pentoxifylline (decreasing TNF-{alpha} secretion) and infliximab (trapping TNF-{alpha}) likewise attenuated the Jo2-mediated increase in TNF-{alpha}, the decrease in hepatic glutathione, and the increase in serum ALT activity 5 h after Jo2 administration. The concomitant administration of the COX-1 inhibitor, SC-560 (10 mg/kg) and the COX-2 inhibitor, celecoxib (40 mg/kg) 1 h after Jo2 administration, also decreased liver injury 5 h after Jo2 administration. In contrast, SC-560 (10 mg/kg) or celecoxib (40 or 160 mg/kg) given alone had no significant protective effects. In conclusion, secondary TNF-{alpha} secretion plays an important role in Jo2-mediated glutathione depletion and liver injury. The combined inhibition of COX-1 and COX-2 by ibuprofen attenuates TNF-{alpha} secretion, glutathione depletion, mitochondrial alterations, hepatic apoptosis and mortality in Jo2-treated fasted mice.

  7. Serum Concentration and Drug Effect After Intravenous and Rectal Administration of Diazepam

    PubMed Central

    Lundgren, Stefan

    1987-01-01

    In a randomized crossover study on sedation in outpatient oral surgery, the relation between the serum profile and the drug effect profile for intravenously (i.v.) and rectally administered diazepam was studied. Both sedation methods were found to be equally efficient at a mean dose of 0.25 mg/kg (range, 0.14—0.45) for i.v. administration, and 0.53 mg/kg (range, 0.50—0.58) for rectal administration. Both the serum concentration and the effect reached their mean peaks at the same time; however, this was 15 min later after rectal sedation than after i.v. sedation. Intravenous administration yielded a significantly higher serum concentration of diazepam at the clinical endpoint than did rectal administration, but the mean effect levels at the clinical endpoint were equal for both sedation methods. No linear correlation between log-serum concentration and the patient's estimation of effect was found. PMID:3481512

  8. Changes in Serum TSH and T4 Levels after Switching the Levothyroxine Administration Time from before Breakfast to before Dinner

    PubMed Central

    Ala, S.; Akha, O.; Kashi, Z.; Bahar, A.; Askari Rad, H.; Sasanpour, N.; Shiva, A.

    2015-01-01

    Background. Levothyroxine is commonly used in the treatment of patients with hypothyroidism. Levothyroxine is most often administered in the morning, on an empty stomach, in order to increase its oral absorption. However, many patients have difficulties taking levothyroxine in the morning. Aim. The aim of this study was evaluating the effect of changing levothyroxine administration time from before breakfast to before dinner on the serum levels of TSH and T4. Subjects and Methods. Fifty patients between 18 and 75 years old with hypothyroidism were included in the study and were randomly divided into two groups. Each group received two tablets per day (one levothyroxine tablet and one placebo tablet) 30 minutes before breakfast and 1 hour before dinner. After two months, the administration time for the tablets was changed for each group, and the new schedule was continued for a further two-month period. The serum TSH and T4 levels were measured before and after treatment in each group. Results. Changing the levothyroxine administration time resulted in 1.47 ± 0.51 µIU/mL increase in TSH level (p = 0.001) and 0.35 ± 1.05 µg/dL decrease in T4 level (p = 0.3). Conclusions. Changing the levothyroxine administration time from before breakfast to before dinner reduced the therapeutic efficacy of levothyroxine. PMID:26136778

  9. Pyoderma gangrenosum with increased levels of serum cytokines.

    PubMed

    Kozono, Kana; Nakahara, Takeshi; Kikuchi, Satoko; Itoh, Eriko; Kido-Nakahara, Makiko; Furue, Masutaka

    2015-12-01

    A 66-year-old woman presented after an episode of accidental trauma with a painful ulcer on her scalp which rapidly enlarged in size, accompanied by central necrosis and undermining ulceration. The patient's past history was negative for underlying systemic disease, although she had had a similar post-traumatic intractable leg ulcer 3 years prior, which was unresponsive to surgical management but successfully treated with systemic steroids. A biopsied specimen from the scalp showed marked neutrophilic infiltrates in the dermis, compatible with a diagnosis of pyoderma gangrenosum (PG). The large ulcerative lesion responded very well to oral steroid therapy, showing rapid epithelialization. Serum levels of granulocyte colony-stimulating factor and interleukin-6 were significantly elevated prior to treatment, with decrease to normal levels after treatment. Serum tumor necrosis factor (TNF)-α and granulocyte macrophage colony-stimulating factor levels were within normal limits. The significance and pathogenic role of cytokine burst in PG is reviewed and discussed. PMID:26047254

  10. Serum Pharmacochemistry Analysis Using UPLC-Q-TOF/MS after Oral Administration to Rats of Shenfu Decoction

    PubMed Central

    He, Jia-le; Zhao, Jia-wei; Ma, Zeng-chun; Wang, Yu-guang; Liang, Qian-de; Tan, Hong-ling; Xiao, Cheng-rong; Tang, Xiang-lin; Gao, Yue

    2015-01-01

    The purpose of this study was to study the serum pharmacochemistry of SFD as well as the material basis through analyzing the constituents absorbed in blood. The SFD was orally administrated to Wistar rats at 20 g·kg−1, and Ultra Performance Liquid Chromatography (UPLC) fingerprints of SFD were created. Serum samples were collected for analysis, and further data processing used MarkerLynx XS software. 19 ginsenosides and 16 alkaloids were detected in SFD. The absorption of alkaloids (mainly monoester diterpenoid alkaloids) increased when Aconitum carmichaeli Debx. was combined with Panax ginseng, while the ginsenosides remained stable. Diester diterpenoid alkaloids were not present in the serum samples. A suitable serum pharmacochemistry method was successfully established to study pharmacological effects and potential improvements in formulation. This may also be useful for toxicity reduction. We suspect that the increased absorption of the monoester diterpenoid alkaloids from the mixture of Panax and Radix, compared to the Panax only extract, may be the reason for the combination of the two herbs in popular medicine formulas in China. PMID:26273317

  11. Intragastric administration of glutamate increases REM sleep in rats.

    PubMed

    Datta, Karuna; Kumar, Deependra; Mallick, Hruda Nanda

    2013-10-01

    Monosodium glutamate, a umami taste substance is commonly used flavor enhancer. The effect of intragastric administration of 1.5 ml of 0.12M monosodium glutamate on sleep-wake was studied in 10 adult male Wistar rats. Sleep-wake parameters were recorded through chronically implanted electroencephalogram, electrooculogram and electromyogram electrodes using a digital recording system (BIOPAC system Inc. BSL PRO 36, USA). The sleep-wake was recorded for 6h after the intragastric administration of either glutamate or saline. Sleep-wake stages were analyzed as wake, slow wave sleep and REM sleep. Compared to saline, intragastric administration of glutamate significantly increased REM sleep duration and episode frequency. REM sleep duration was increased in all the three 2h bins, 10:00-12:00 h (p=0.037), 12:00-14:00 h (p=0.037) and 14:00-16:00 h (p=0.007). The slow wave sleep and total sleep time were not affected. It is concluded that intragastric glutamate administration increases REM sleep. PMID:24055576

  12. Increased Soluble CD155 in the Serum of Cancer Patients.

    PubMed

    Iguchi-Manaka, Akiko; Okumura, Genki; Kojima, Hiroshi; Cho, Yukiko; Hirochika, Rei; Bando, Hiroko; Sato, Toyomi; Yoshikawa, Hiroyuki; Hara, Hisato; Shibuya, Akira; Shibuya, Kazuko

    2016-01-01

    Emerging evidence suggests that DNAM-1 (CD226) play an important role in the recognition of tumor cells and their lysis by cytotoxic T lymphocytes (CTL) and NK cells. Although the DNAM-1 ligand CD155 is ubiquitously expressed in various tissues, many human tumors significantly upregulate the expression of CD155; DNAM-1 on CTL and NK cells may be involved in tumor immunity. However, unlike those in mice, human tissues also express soluble isoforms of CD155 (sCD155) that lack the transmembrane region. Here, we show that sCD155 levels were significantly higher in the sera of 262 patients with lung, gastrointestinal, breast, and gynecologic cancers than in sera from healthy donors. In addition, the sCD155 levels were significantly higher in patients with early stage (stages 1 and 2) gastric cancer than in healthy donors, and were significantly higher in patients with advanced stage (stages 3 and 4) disease than in patients in those with early stage disease and healthy donors. Moreover, the sCD155 levels were significantly decreased after surgical resection of cancers. Thus, sCD155 level in serum may be potentially useful as a biomarker for cancer development and progression. PMID:27049654

  13. [Diagnosis of an increased serum level of ferritin].

    PubMed

    Lorcerie, B; Audia, S; Samson, M; Millière, A; Falvo, N; Leguy-Seguin, V; Berthier, S; Bonnotte, B

    2015-08-01

    The discovery of a hyperferritinemia is most of the time fortuitous. The diagnostic approach aims at looking for the responsible etiology and at verifying if an iron hepatic overload is present or not. Three diagnostic steps are proposed. The clinical elements and a few straightforward biological tests are sufficient at first to identify one of the four main causes: alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome. None of these causes is associated with a significant iron hepatic overload. If the transferring saturation coefficient is raised (>50%) a hereditary hemochromatosis should be discussed. Secondly, less common disorders will be discussed. Among these, only the chronic hematological disorders either acquired or congenital are at risk of iron hepatic overload. Thirdly, if a doubt persists in the etiologic research, and the serum ferritin level is very high or continues to rise, it is essential to verify that there is no iron hepatic overload. For that purpose, the MRI with study of the iron overload is the main test, which will guide the therapeutic attitude. Identification of more than a single etiology occurs in more than 40% of the cases. PMID:25640247

  14. Increased Soluble CD155 in the Serum of Cancer Patients

    PubMed Central

    Iguchi-Manaka, Akiko; Okumura, Genki; Kojima, Hiroshi; Cho, Yukiko; Hirochika, Rei; Bando, Hiroko; Sato, Toyomi; Yoshikawa, Hiroyuki; Hara, Hisato; Shibuya, Akira; Shibuya, Kazuko

    2016-01-01

    Emerging evidence suggests that DNAM-1 (CD226) play an important role in the recognition of tumor cells and their lysis by cytotoxic T lymphocytes (CTL) and NK cells. Although the DNAM-1 ligand CD155 is ubiquitously expressed in various tissues, many human tumors significantly upregulate the expression of CD155; DNAM-1 on CTL and NK cells may be involved in tumor immunity. However, unlike those in mice, human tissues also express soluble isoforms of CD155 (sCD155) that lack the transmembrane region. Here, we show that sCD155 levels were significantly higher in the sera of 262 patients with lung, gastrointestinal, breast, and gynecologic cancers than in sera from healthy donors. In addition, the sCD155 levels were significantly higher in patients with early stage (stages 1 and 2) gastric cancer than in healthy donors, and were significantly higher in patients with advanced stage (stages 3 and 4) disease than in patients in those with early stage disease and healthy donors. Moreover, the sCD155 levels were significantly decreased after surgical resection of cancers. Thus, sCD155 level in serum may be potentially useful as a biomarker for cancer development and progression. PMID:27049654

  15. Elevated serum progesterone/ MII oocyte ratio on the day of human chorionic gonadotropin administration can predict impaired endometrial receptivity

    PubMed Central

    Aflatoonian, Abbas; Davar, Robab; Hojjat, Farzaneh

    2014-01-01

    Background: Increased serum progesterone on the day of human chorionic gonadotropin administration may affect in vitro fertilization (IVF) outcome. Objective: The aim of this study was to evaluate whether progesterone elevation on the day of human chorionic gonadotropin administration is associated with poor IVF outcome. Materials and Methods: To determine the relationship between serum progesterone on the day of HCG and the outcome of IVF-embryo transfer treatment, 378 infertile patients undergoing IVF-embryo transfer at Yazd Research and Clinical Center for Infertility from October 2009 to March 2011 were prospectively studied. Results: In this study, absolute p-value and P/E2 ratio were not a good predictor outcome of in-vitro fertilization but progesterone per metaphase II were predictive of implantation rate and pregnancy rate with statistically significant results but had no effect on the fertilization rate. Conclusion: We suggest avoided the increased progesterone that the cause of advanced endometrial maturation and impaired endometrial receptivity. If the progesterone is greater than 0.32 per oocyte metaphase II, the embryo transfer can be canceled and freezing all embryos for future transfer must be considered, to increase acceptance of the endometrium and thus increase the success rate. PMID:25071852

  16. Ceftiofur derivates in serum and endometrial tissue after intramuscular administration in healthy mares.

    PubMed

    Witte, T S; Bergwerff, A A; Scherpenisse, P; Drillich, M; Heuwieser, W

    2010-08-01

    Endometritis is one of the major problems in the horse breeding industry. The use of antibiotics for treatment of endometritis in the mare is recommended as best practice. The intrauterine application of antibiotics, however, has been under discussion over the last years because of concerns about its efficacy. The systemic use of antibiotics has been considered more effective because of its better distribution within the uterus. The objective of the present study was to determine the concentration of ceftiofur derivates in serum and endometrial tissue after intramuscular administration. Specifically, the authors tested the hypothesis that ceftiofur concentrations in serum and endometrial tissue remain above the minimum inhibitory concentration (MIC) for common uterine pathogens for 24 h. Nine mares in estrus received a single dose of 2.2 mg/kg ceftiofur hydrochloride intramuscular per kg of body weight. Blood samples and endometrial tissue were obtained immediately before treatment (-1 h) and 2 h and 24 h after treatment. Endometrial tissue was collected with a Kevorkian biopsy punch. Additional blood samples were collected 4 h and 10 h after treatment from the jugular veins. For determination of ceftiofur derivates in serum and endometrial tissue a high performance liquid chromatography (HPLC) assay was used. Results in serum and uterine tissue revealed greatest concentration of ceftiofur at 2 h and lowest concentrations at 24 h after treatment. Concentrations of ceftiofur at 2 and 24 h after treatment were significantly greater in serum than in endometrial tissue, but remained above the reported MIC for Streptococcus equi zooepidemicus and Escherichia coli in both serum and endometrial tissue until 24 h after treatment. PMID:20494421

  17. Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients.

    PubMed

    Enooku, Kenichiro; Nakagawa, Hayato; Soroida, Yoko; Ohkawa, Ryunosuke; Kageyama, Yuko; Uranbileg, Baasanjav; Watanabe, Naoko; Tateishi, Ryosuke; Yoshida, Haruhiko; Koike, Kazuhiko; Yatomi, Yutaka; Ikeda, Hitoshi

    2014-08-15

    Serum mitochondrial creatine kinase (MtCK) activity was reportedly increased in cirrhotic patients although less prominent than that in hepatocellular carcinoma (HCC) patients. To elucidate the clinical significance of serum MtCK activity in chronic liver disease, 171 chronic hepatitis C patients were enrolled. Serum MtCK activity in study subjects was correlated with serum albumin, platelet counts, liver stiffness values and serum aspartate and alanine aminotransferase. In mouse fibrotic liver induced by bile duct ligation, ubiquitous MtCK mRNA and protein expressions were significantly enhanced and its immunoreactivity was increased, predominantly in hepatocytes. During the mean follow-up period of 2.7 years, HCC developed in 21 patients, in whom serum MtCK activity was significantly higher than that in patients without HCC development. Multivariate Cox regression analysis revealed that higher serum MtCK activity was a risk for HCC development. A cutoff value of MtCK for the prediction of HCC development was determined as 9.0 U/L on receiver operating characteristics analysis, where area under receiver operating characteristics curve was 0.754, with a sensitivity of 61.9%, a specificity of 92.8% and a high negative predictive value of 94.2%. Cumulative incidence of HCC was significantly higher in patients with serum MtCK activity of >9.0 U/L compared to those with serum MtCK activity of ≤ 9.0 U/L even in patients with elevated liver stiffness value, >15 kPa. In conclusion, serum MtCK activity may be increased correlatively with the stage of liver fibrosis and hepatocellular damage. Increased serum MtCK activity is an independent risk for hepatocarcinogenesis in chronic hepatitis C patients. PMID:24420733

  18. Increase of serum vascular endothelial growth factors in wet beriberi: two case reports.

    PubMed

    Imai, Noboru; Kubota, Mai; Saitou, Mayu; Yagi, Nobuyasu; Serizawa, Masahiro; Kobari, Masahiro

    2012-01-01

    Beriberi is a disease caused by thiamine deficiency resulting in peripheral neuropathy and myocardial dysfunction. Increases in vascular endothelial growth factor (VEGF) are seen in polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes, called POEMS syndrome. We present herein two cases of wet beriberi accompanied by a moderate increase in VEGF level. Serum VEGF decreased after treatment in both cases. Our experience with these cases suggests that beriberi should be considered in the differential diagnosis of polyneuropathy with a moderate increase in serum VEGF, and that the serum VEGF level may be a therapeutic marker for beriberi. PMID:22504253

  19. Intranasal administration of oxytocin increases human aggressive behavior.

    PubMed

    Ne'eman, R; Perach-Barzilay, N; Fischer-Shofty, M; Atias, A; Shamay-Tsoory, S G

    2016-04-01

    Considering its role in prosocial behaviors, oxytocin (OT) has been suggested to diminish levels of aggression. Nevertheless, recent findings indicate that oxytocin may have a broader influence on increasing the salience of social stimuli and may therefore, under certain circumstances, increase antisocial behaviors such as aggression. This controversy led to the following speculations: If indeed oxytocin promotes primarily prosocial behavior, administration of OT is expected to diminish levels of aggression. However, if oxytocin mainly acts to increase the salience of social stimuli, it is expected to elevate levels of aggression following provocation. In order to test this assumption we used the Social Orientation Paradigm (SOP), a monetary game played against a fictitious partner that allows measuring three types of responses in the context of provocation: an aggressive response - reducing a point from the fictitious partner, an individualistic response - adding a point to oneself, and a collaborative response - adding half a point to the partner and half a point to oneself. In the current double-blind, placebo-controlled, within-subject study design, 45 participants completed the SOP task following the administration of oxytocin or placebo. The results indicated that among subjects naïve to the procedure oxytocin increased aggressive responses in comparison with placebo. These results support the saliency hypothesis of oxytocin and suggest that oxytocin plays a complex role in the modulation of human behavior. PMID:26862988

  20. Effects of stress on serum triglycerides, nonsterified fatty acids, and total cholesterol levels in male rats after ethanol administration

    SciTech Connect

    Hershock, D.; Vogel, W.H. )

    1989-02-09

    Serum triglycerides, nonesterified fatty acids (NEFA), and total cholesterol were determined during one hour immobilization stress in adult male Sprague-Dawley rats after ethanol administration (2g/kg, i.p.). Stress and ethanol effects were evaluated in two experiments: (1) rats maintained on Purina Rodent Chow for six weeks and fasted for 24 hours; and (2) rats maintained on the same diet supplemented with 1% cholesterol and 10% peanut oil for six weeks and nonfasted prior to experimentation. Blood was obtained from indwelling jugular catheters. In each experiment, differences were seen in triglyceride and NEFA levels but not in total cholesterol. In the regular diet-fed rats (1), serum triglyceride levels were not affected by either stress or ethanol. However, NEFA levels did show differences in the response to ethanol and stress. A 63% decrease from baseline after 5{prime} of stress was partially abolished by ethanol; instead, a 24% increase was observed. Also, a stress-induced increase in NEFA which occurred after 15{prime} was not observed in the ethanol treated rats; rather, a decrease in NEFA was noted. Total cholesterol did not change in response to stress or ethanol. In the high cholesterol diet-fed rats (2), ethanol did not suppress a stress-induced increase in triglyceride levels. NEFA levels in ethanol-treated rats were higher during the first 15{prime} of stress as compared to stress alone. A decrease in NEFA was however seen in the ethanol-treated rats after 30{prime} of stress and these levels remained lower than the stress alone group. A diet-induced increase in total cholesterol levels was observed; however, no changes were seen due to either or ethanol. Thus, ethanol administration prior to acute immobilization stress did affect serum triglyceride and NEFA levels but did not change total cholesterol.

  1. Dietary Mannoheptulose Increases Fasting Serum Glucagon Like Peptide-1 and Post-Prandial Serum Ghrelin Concentrations in Adult Beagle Dogs

    PubMed Central

    McKnight, Leslie L.; Eyre, Ryan; Gooding, Margaret A.; Davenport, Gary M.; Shoveller, Anna Kate

    2015-01-01

    Simple Summary There is increased interest in the use of nutraceuticals for weight management in companion animals. A nutraceutical can broadly be considered a food (or a part of) that provides a health benefit. Mannoheptulose (MH), a sugar found in avocados, is being investigated as a nutraceutical for dogs. In this study, dogs fed a diet containing MH had increased concentrations of blood biomarkers related to energy intake. In addition, dogs fed MH were less physically active than dogs fed a control diet. These findings suggest that dietary MH has the ability to alter energy intake and lower daily energy expenditure. Abstract There is a growing interest in the use of nutraceuticals for weight management in companion animals. The purpose of this study was to determine the effects of mannoheptulose (MH), a sugar in avocados that inhibits glycolysis, on energy metabolism in adult Beagle dogs. The study was a double-blind, randomized controlled trial where dogs were allocated to a control (CON, n = 10, 10.1 ± 0.4 kg) or MH containing diet (168 mg/kg, n = 10, 10.3 ± 0.4 kg). Blood was collected after an overnight fast and 1 h post-feeding (week 12) to determine serum satiety related hormones and biochemistry. Resting and post-prandial energy expenditure and respiratory quotient were determined by indirect calorimetry (weeks 4 and 8). Physical activity was measured using an accelerometer (weeks 3, 7, 11). Body composition was assessed using dual X-ray absorptiometry (week 12). MH significantly (p < 0.05) increased fasting serum glucagon-like peptide-1 and post-prandial serum ghrelin. MH tended (p < 0.1) to increase fasting serum gastric inhibitory peptide and decrease physical activity. Together, these findings suggest that dietary MH has the ability to promote satiation and lowers daily energy expenditure. PMID:26479244

  2. Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

    PubMed

    Delamaide Gasper, Joy A; Barnes Heller, Heidi L; Robertson, Michelle; Trepanier, Lauren A

    2015-04-01

    Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally. PMID:25098448

  3. Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the DESIR Cohort

    PubMed Central

    Nocturne, Gaetane; Pavy, Stephan; Boudaoud, Saida; Seror, Raphaèle; Goupille, Philippe; Chanson, Philippe; van der Heijde, Désirée; van Gaalen, Floris; Berenbaum, Francis; Mariette, Xavier; Briot, Karine; Feydy, Antoine; Claudepierre, Pascal; Dieudé, Philippe; Nithitham, Joanne; Taylor, Kimberly E.; Criswell, Lindsey A.; Dougados, Maxime; Roux, Christian; Miceli-Richard, Corinne

    2015-01-01

    Objectives To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors. Methods The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and <3 years) suggestive of AxSpA. DKK-1 and SOST serum levels were assessed at baseline and were compared between the subgroup of patients fulfilling ASAS criteria for SpA (n = 486; 68.6%) and 80 healthy controls. Results Mean SOST serum levels were lower in ASAS+ patients than healthy controls (49.21 ± 25.9 vs. 87.8 ± 26 pmol/L; p<0.0001). In multivariate analysis, age (p = 5.4 10−9), CRP level (p<0.0001) and serum DKK-1 level (p = 0.001) were associated with SOST level. Mean DKK-1 serum levels were higher in axial SpA patients than controls (30.03 ± 15.5 vs. 11.6 ± 4.2 pmol/L; p<0.0001). In multivariate analysis, DKK-1 serum levels were associated with male gender (p = 0.03), CRP level (p = 0.006), SOST serum level (p = 0.002) and presence of sacroiliitis on radiography (p = 0.05). Genetic association testing of 10 SNPs encompassing the DKK-1 locus failed to demonstrate a significant contribution of genetics to control of DKK-1 serum levels. Conclusions DKK-1 serum levels were increased and SOST levels were decreased among a large cohort of patients with early axial SpA compared to healthy controls. DKK-1 serum levels were mostly associated with biological inflammation and SOST serum levels. PMID:26313358

  4. Increased serum levels of soluble vascular endothelial-cadherin in patients with systemic vasculitis.

    PubMed

    Chen, Tao; Guo, Zai-Pei; Cao, Na; Qin, Sha; Li, Meng-Meng; Jia, Rui-Zhen

    2014-08-01

    Henoch-Schönlein purpura (HSP) is a commonest systemic vasculitis (SV) in childhood characterized by an inflammatory reaction directed at vessels. Endothelial damage and perivascular leukocyte infiltrates are vital in the development of HSP. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule, which plays critical roles in angiogenesis and endothelial integrity. Herein, we investigated the serum levels of soluble VE-cadherin (sVE-cadherin) in patients with HSP and other forms of SV. The serum levels of sVE-cadherin in 30 patients with HSP, together with patients with urticarial vasculitis, allergic vasculitis, Behcet disease, psoriasis vulgaris (PV) and atopic dermatitis (AD) and 26 health controls were measured by enzyme-linked immunosorbent assay. Serum levels of sVE-cadherin were significantly increased in patients with HSP in acute stage and patients with other forms of SV but not in patients with PV or AD. Moreover, Serum sVE-cadherin levels in HSP patients were correlated with the severity of this disease and serum concentrations of IgA anticardiolipin antibodies and vascular endothelial growth factor. Taken together, we show firstly that serum sVE-cadherin is abnormally increased in HSP patients. Increased serum levels of sVE-cadherin might be a novel biomarker for evaluating the severity of HSP and useful for identifying the presence of SV in inflammatory skin conditions. PMID:24469639

  5. Tissue and serum concentrations of amikacin after intramuscular and intrauterine administration to mares in estrus.

    PubMed Central

    Orsini, J A; Park, M I; Spencer, P A

    1996-01-01

    Concentrations of amikacin in endometrial tissue and plasma were studied in mares in estrus after intrauterine infusion of 1.0 or 2.0 g once a day for 3 consecutive d, and after 9.7 or 14.5 mg/kg body weight (BW) had been injected intramuscularly once a day for 3 consecutive d to determine concentrations of amikacin sulfate in plasma and endometrial tissues, and whether parenteral administration provides any advantages over intramuscular infusion. No amikacin was detected in serum at the 1.0 g dose. At the infusion dose of 2.0 g once a day, very low levels of serum amikacin were detected at 1 and 4 h postinfusion on the 1st treatment day. Amikacin was found to penetrate the endometrium after intramuscular injection; however, the levels attained were not as high as those achieved following intrauterine infusion. Based on the tissue and serum concentrations of amikacin, an intrauterine infusion at a dose of 4.4 mg/kg BW/d would appear to be an appropriate therapeutic regimen for the treatment of gram-negative endometritis. PMID:8681283

  6. Acute lithium administration selectively lowers tyrosine levels in serum and brain

    PubMed Central

    McFarlane, Hewlet G.; Steele, John; Vinion, Keenan; Bongiovanni, Rodolfo; Double, Manda; Jaskiw, George E.

    2016-01-01

    Lithium exerts anti-dopaminergic behavioral effects. We examined whether some of these might be mediated by changes in brain levels of tyrosine (TYR), the precursor to dopamine. Lithium chloride (LiCl2) 3.0 mEq/kg IP acutely lowered serum TYR and the ratio of serum TYR to other large neutral amino acids (LNAAs); it also selectively lowered striatum TYR levels as measured in tissue or in vivo. While LiCl2 3.0 mEq/kg IP also augmented haloperidol (0.19 mg/kg SC)-induced catalepsy, this lithium effect was not attenuated by administration of TYR 100 mg/kg IP. We conclude that lithium acutely and selectively lowers brain TYR by lowering serum levels of tyrosine relative to the LNAAs that compete with it for transport across the blood–brain barrier. However, the lowering of TYR does not appear to significantly contribute to the ability of lithium to potentiate haloperidol-mediated catalepsy. PMID:21962398

  7. Inflammation induced by increased frequency of intermittent hypoxia is attenuated by tempol administration.

    PubMed

    Zhang, J; Zheng, L; Cao, J; Chen, B; Jin, D

    2015-12-01

    The levels of serum inflammatory cytokines and the activation of nuclear factor kappa B (NF-κB) and hypoxia inducible factor-1α (HIF-1α) in heart tissues in response to different frequencies of intermittent hypoxia (IH) and the antioxidant tempol were evaluated. Wistar rats (64 males, 200-220 g) were randomly divided into 6 experimental groups and 2 control groups. Four groups were exposed to IH 10, 20, 30, or 40 times/h. The other 2 experimental groups were challenged with IH (30 times/h) plus tempol, either beginning on day 0 (IH30T0) or on day 29 (IH30T29). After 6 weeks of challenge, serum levels of tumor necrosis factor (TNF)-α, intracellular adhesion molecule (ICAM)-1, and interleukin-10 were measured, and western blot analysis was used to detect NF-κB p65 and HIF-1α in myocardial tissues. Serum levels of TNF-α and ICAM-1 and myocardial expression of NF-κB p65 and HIF-1α were all significantly higher in IH rats than in controls (P<0.001). Increased IH frequency resulted in more significant changes. Administration of tempol in IH rats significantly reduced levels of TNF-α, ICAM-1, NF-κB and HIF-1α compared with the non-tempol-treated group (F=16.936, P<0.001). IH induced an inflammatory response in a frequency-dependent manner. Additionally, HIF-1α and NF-κB were increased following IH administration. Importantly, tempol treatment attenuated this effect. PMID:26397969

  8. Inflammation induced by increased frequency of intermittent hypoxia is attenuated by tempol administration

    PubMed Central

    Zhang, J.; Zheng, L.; Cao, J.; Chen, B.; Jin, D.

    2015-01-01

    The levels of serum inflammatory cytokines and the activation of nuclear factor kappa B (NF-κB) and hypoxia inducible factor-1α (HIF-1α) in heart tissues in response to different frequencies of intermittent hypoxia (IH) and the antioxidant tempol were evaluated. Wistar rats (64 males, 200-220 g) were randomly divided into 6 experimental groups and 2 control groups. Four groups were exposed to IH 10, 20, 30, or 40 times/h. The other 2 experimental groups were challenged with IH (30 times/h) plus tempol, either beginning on day 0 (IH30T0) or on day 29 (IH30T29). After 6 weeks of challenge, serum levels of tumor necrosis factor (TNF)-α, intracellular adhesion molecule (ICAM)-1, and interleukin-10 were measured, and western blot analysis was used to detect NF-κB p65 and HIF-1α in myocardial tissues. Serum levels of TNF-α and ICAM-1 and myocardial expression of NF-κB p65 and HIF-1α were all significantly higher in IH rats than in controls (P<0.001). Increased IH frequency resulted in more significant changes. Administration of tempol in IH rats significantly reduced levels of TNF-α, ICAM-1, NF-κB and HIF-1α compared with the non-tempol-treated group (F=16.936, P<0.001). IH induced an inflammatory response in a frequency-dependent manner. Additionally, HIF-1α and NF-κB were increased following IH administration. Importantly, tempol treatment attenuated this effect. PMID:26397969

  9. Reduced serum concentration is permissive for increased in vitro endocrine differentiation from murine embryonic stem cells.

    PubMed

    Vincent, Robert K; Odorico, Jon S

    2009-07-01

    Embryonic stem cells (ESCs) have been shown to be capable of differentiating into pancreatic progenitors and insulin-producing cells in vitro. However, before ESC derivatives can be used in clinical settings, efficient selective differentiation needs to be achieved. Essential to improving ESC differentiation to islet endocrine cells is an understanding of the influences of extrinsic signals and transcription factors on cell specification. Herein, we investigate the influence of serum-supplemented growth conditions on the differentiation of murine ESCs to endocrine lineages in the context of over-expression of two pancreatic transcription factors, Pdx1 and Ngn3. To study the effect of different serum formulations and concentrations on the ability of murine ESCs to differentiate into endocrine cells in vitro, cells were grown into embryoid bodies and then differentiated in various serum replacement (SR), fetal calf serum (FCS) and serum-free conditions. Using immunohistochemistry and quantitative real-time RT-PCR (QPCR), we found that, of the conditions tested, 1% SR differentiation medium resulted in the highest levels of insulin-1 mRNA and significantly increased the total number of insulin-expressing cells. Applying this knowledge to cell lines in which Pdx1 or Ngn3 transgene expression could be induced by exposure to doxycycline we differentiated TetPDX1 and TetNgn3 ESCs under conditions of either 10% FCS or 1% SR medium. In the presence of 10% serum, induced expression of either Pdx1 or Ngn3 in differentiating ESCs resulted in modest increases in hormone transcripts and cell counts. However, changing the serum formulation from 10% FCS to 1% SR significantly enhanced the number of insulin+/C-peptide+ cells in parallel with increased insulin-1 transcript levels in both inducible cell lines. In summary, these data demonstrate that induced expression of key pancreatic transcription factors in combination with low serum/SR concentrations increases endocrine cell

  10. Serum Amyloid-Beta Levels are Increased in Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Bu, Xian-Le; Cao, Guo-Qiang; Shen, Lin-Lin; Xiang, Yang; Jiao, Shu-Sheng; Liu, Yu-Hui; Zhu, Chi; Zeng, Fan; Wang, Qing-Hua; Wang, Ye-Ran; He, Yong; Zhou, Hua-Dong; Wang, Yan-Jiang

    2015-11-01

    Chronic obstructive pulmonary disease (COPD) is associated with cognitive decline, but the molecular link between COPD and dementia or Alzheimer's disease (AD) remains unclear. This study was aimed to investigate whether serum Aβ levels are correlated with COPD. 77 cognitively normal COPD patients and 45 age- and gender-matched normal controls were admitted to the study. Serum Aβ40 and Aβ42 levels were measured using ELISA kits. Serum C-reactive protein (CRP), interleukin 6 (IL-6), and procalcitonin (PCT) measurements were done using standard laboratory methods. Pulmonary function tests were performed to assess the pulmonary function and determine the degree of lung damage. Significantly increased levels of serum Aβ40, Aβ42, and total Aβ levels were found in patients with COPD in comparison with normal controls. In COPD patients, serum Aβ levels were higher in subjects with serum CRP, IL-6, and PCT upper the limit of normal. Moreover, serum Aβ levels were dramatically higher in COPD patients with worse pulmonary function. Our study suggests that cognitively normal COPD patients may undergo AD-related pathological changes, and COPD might facilitate AD-type pathogenesis. PMID:26243505

  11. Uncommon serum creatine phosphokinase and lactic dehydrogenase increase during diosmin therapy: two case reports

    PubMed Central

    2014-01-01

    Introduction Short-term administration of diosmin is usually considered safe, with only minor side effects (stomach and abdominal pain, diarrhea, dermatological disorders, and headache) occasionally observed. Within a 4-year period, a general practitioner noticed 17 cases of mild, diosmin-induced side effects, two of which showed particular interest. Cases presentation Case 1: A 55-year-old Caucasian woman presented with chronic leg venous insufficiency. She was prescribed diosmin 450mg twice a day. After 5 days of therapy, she developed pain in the legs (myalgia), and diosmin therapy was suspended. She made a spontaneous attempt of drug rechallenge and her leg pain reappeared. Thus, she underwent blood analysis, which showed elevation of creatine phosphokinase levels. Creatine phosphokinase values normalized only after prolonged discontinuation of the therapy. Case 2: A 79-year-old Caucasian man, who was diagnosed with acute hemorrhoidal syndrome. After 21 days of continuous diosmin treatment, increased levels of serum lactic dehydrogenase were detected. In both cases a comprehensive analysis of all possible causes for enzyme elevation was made. Conclusions A feasible hypothesis to explain these rare effects could be that exaggerated adrenergic activity occurred on microcirculation, leading to an excessive peripheral vasoconstriction and subsequent ischemic damage. An individual predisposition is strongly suggested. A concurrence of events was probably responsible for the elevation of nonspecific tissue necrosis markers. Physicians and patients must be aware of these rare, but possible, adverse drug reactions. PMID:24934505

  12. Serum elevation of B lymphocyte stimulator does not increase regulatory B cells in glioblastoma patients undergoing immunotherapy.

    PubMed

    Saraswathula, Anirudh; Reap, Elizabeth A; Choi, Bryan D; Schmittling, Robert J; Norberg, Pamela K; Sayour, Elias J; Herndon, James E; Healy, Patrick; Congdon, Kendra L; Archer, Gerald E; Sanchez-Perez, Luis; Sampson, John H

    2016-02-01

    Regulatory B cells that secrete IL-10 (IL-10(+) Bregs) represent a suppressive subset of the B cell compartment with prominent anti-inflammatory capacity, capable of suppressing cellular and humoral responses to cancer and vaccines. B lymphocyte stimulator (BLyS) is a key regulatory molecule in IL-10(+) Breg biology with tightly controlled serum levels. However, BLyS levels can be drastically altered upon chemotherapeutic intervention. We have previously shown that serum BLyS levels are elevated, and directly associated, with increased antigen-specific antibody titers in patients with glioblastoma (GBM) undergoing lymphodepletive temozolomide chemotherapy and vaccination. In this study, we examined corresponding IL-10(+) Breg responses within this patient population and demonstrate that the IL-10(+) Breg compartment remains constant before and after administration of the vaccine, despite elevated BLyS levels in circulation. IL-10(+) Breg frequencies were not associated with serum BLyS levels, and ex vivo stimulation with a physiologically relevant concentration of BLyS did not increase IL-10(+) Breg frequency. However, BLyS stimulation did increase the frequency of the overall B cell compartment and promoted B cell proliferation upon B cell receptor engagement. Therefore, using BLyS as an adjuvant with therapeutic peptide vaccination could promote humoral immunity with no increase in immunosuppressive IL-10(+) Bregs. These results have implications for modulating humoral responses in human peptide vaccine trials in patients with GBM. PMID:26759007

  13. Increased antibacterial activity against Escherichia coli in bovine serum after the induction of endotoxin tolerance.

    PubMed

    Hill, A W; Shears, A L; Hibbitt, K G

    1976-07-01

    Small amounts of endotoxin injected intramuscularly into cows induced endotoxin pyrogenic tolerance and an increase in the rate at which the serum killed a strain of Escherichia coli. Most of the difference between normal serum and serum from the endotoxin-tolerant animal was shown to be due to a bentonite-adsorbable factor other than lysozyme or beta-lysin. The antibacterial activity was not completely removed from either type of serum after bentonite adsorption. Electron microscope studies and measurement of the rate of release of radioactively labeled cytoplasmic contents showed that the bentonite-adsorbable factor was important in the final breakdown of the cell membrane and release of cellular contents. The antibacterial system was totally dependent on complement, and the importance of antibodies could not be entirely ruled out because adsorption at O C with homologous cells eliminated the killing activity. PMID:780275

  14. Mechanisms of an increased level of serum iron in gamma-irradiated mice.

    PubMed

    Xie, Li-hua; Zhang, Xiao-hong; Hu, Xiao-dan; Min, Xuan-yu; Zhou, Qi-fu; Zhang, Hai-qian

    2016-03-01

    The potential mechanisms underlying the increase in serum iron concentration in gamma-irradiated mice were studied. The gamma irradiation dose used was 4 Gy, and cobalt-60 ((60)Co) source was used for the irradiation. The dose rate was 0.25 Gy/min. In the serum of irradiated mice, the concentration of ferrous ions decreased, whereas the serum iron concentration increased. The concentration of ferrous ions in irradiated mice returned to normal at 21 day post-exposure. The concentration of reactive oxygen species in irradiated mice increased immediately following irradiation but returned to normal at 7 day post-exposure. Serum iron concentration in gamma-irradiated mice that were pretreated with reduced glutathione was significant lower (p < 0.01) than that in mice exposed to gamma radiation only. However, the serum iron concentration was still higher than that in normal mice (p < 0.01). This change was biphasic, characterized by a maximal decrease phase occurring immediately after gamma irradiation (relative to the irradiated mice) and a recovery plateau observed during the 7th and 21st day post-irradiation, but serum iron recovery was still less than that in the gamma-irradiated mice (4 Gy). In gamma-irradiated mice, ceruloplasmin activity increased and serum copper concentration decreased immediately after irradiation, and both of them were constant during the 7th and 21st day post-irradiation. It was concluded that ferrous ions in irradiated mice were oxidized to ferric ions by ionizing radiation. Free radicals induced by gamma radiation and ceruloplasmin mutually participated in this oxidation process. The ferroxidase effect of ceruloplasmin was achieved by transfer of electrons from ferrous ions to cupric ions. PMID:26511140

  15. Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor

    PubMed Central

    Furuhashi, Masato; Matsumoto, Megumi; Hiramitsu, Shinya; Omori, Akina; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Hideaki; Ishii, Junnichi; Miura, Tetsuji

    2016-01-01

    Background Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Methods Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. Results At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Conclusions Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2. Trial Registration UMIN-CTR Clinical Trial UMIN000018151 PMID:27124282

  16. Effect of quantity and route of administration of manganese monoxide on feed intake and serum manganese in ruminants

    SciTech Connect

    Black, J.R.; Ammerman, C.B.; Henry, P.R.

    1985-02-01

    The experiment investigated effects of high quantities of manganese and route of administration (diet versus capsule-dosed) on feed intake and blood characteristics in sheep. Twenty-four Florida native or Florida native by St. Croix crossbred wethers, 47 kg initially, were assigned randomly to eight treatments including basal diet supplemented with 0, 3000, 6000, or 9000 ppm manganese as a reagent grade manganese monoxide or basal diet plus gelatin capsules containing the equivalent of 0, 3000, 6000, or 9000 ppm manganese based on intake of the previous day. Three sheep per treatment were provided feed and tap water for ad libitum intake. Sheep were fed basal diet for 7 days followed by a 21-day experimental period, then placed back on the basal diet for 7 days. Average daily feed intake was reduced by increasing supplemental manganese, regardless of route. Animals dosed by capsule consumed less feed than those administered manganese in the diet. Serum manganese increased as manganese supplementation increased, but route of administration had no effect.

  17. Increased serum osteopontin levels in autistic children: relation to the disease severity.

    PubMed

    Al-ayadhi, Laila Y; Mostafa, Gehan A

    2011-10-01

    Autoimmunity to brain may play an etiopathogenic role in autism. Osteopontin is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. Osteopontin induces IL-17 production by T-helper 17 lymphocytes, the key players in the pathogenesis of autoimmune disorders. Anti-osteopontin treatment reduces the clinical severity of some autoimmune neuroinflammatory diseases by reducing IL-17 production. We are the first to measure serum osteopontin levels, by ELISA, in 42 autistic children in comparison to 42 healthy-matched children. The relationship between serum osteopontin levels and the severity of autism, which was assessed by using the Childhood Autism Rating Scale (CARS), was also studied. Autistic children had significantly higher serum osteopontin levels than healthy controls (P<0.001). Increased serum osteopontin levels were found in 80.95% (34/42) of autistic children. Children with severe autism had significantly higher serum osteopontin levels than patients with mild to moderate autism (P=0.02). Moreover, serum osteopontin levels of autistic patients had significant positive correlations with CARS (P=0.007). In conclusions, serum osteopontin levels were increased in many autistic children and they were significantly correlated to the severity of autism. Further wide-scale studies are warranted to shed light on the etiopathogenic role of osteopontin in autism and to investigate its relation to IL-17 and brain-specific auto-antibodies, which are indicators of autoimmunity, in these patients. The therapeutic role of anti-osteopontin antibodies in amelioration of autistic manifestations should also be studied. PMID:21521652

  18. Increased (/sup 125/I)trypsin-binding in serum from cystic fibrosis patients

    SciTech Connect

    Cox, K.L.; Frates, R.C. Jr.; Sheikholislam, B.M.; Iwahashi-Hosoda, C.K.

    1982-01-01

    The capacities of normal and cystic fibrosis (CF) sera to bind to exogenous human (/sup 125/I)trypsin were compared. Sera from eight older CF patients bound significantly more exogenous human (/sup 125/I)trypsin than did sera from eight normal subjects (p less than 0.001). Disregarding the increased trypsin-binding (TB) of CF sera, serum immunoreactive trypsinogen (SIRT) levels were not detectable in these eight older CF patients. However, when SIRT levels were corrected for TB, four CF patients had normal SIRT concentrations and four had low but detectable SIRT levels. As compared to five normal newborns' sera, serum from a newborn with CF had normal TB and the SIRT levels were very high. In conclusion, increased TB in CF serum lowers results of SIRT assays. Therefore, unless SIRT levels are corrected for TB, results obtained from currently available SIRT kits may be invalid.

  19. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

  20. Increased serum inhibin B levels in postmenopausal women with altered thyroid function.

    PubMed

    Viceconti, N; Luisi, S; Nardo, S; Gargano, L; Franchi, A; Sibilla, R; Canettieri, G; Petraglia, F; Centanni, M

    2003-08-01

    Hyper- and hypothyroidism have significant effects on the female reproductive system. However, little in the way of data is available on the relationship between ovarian paracrine control and thyroid function. This study was aimed at characterising the serum levels of inhibin B in relation to altered thyroid function. Serum inhibin B and FSH levels were measured in 91 women (51 regularly cycling and 40 postmenopausal). The mean serum concentration of inhibin B in euthyroid cycling women (0.025 +/- 0.018 microg/l) was similar to that observed in hyper- and hypothyroid patients (0.022 +/- 0.015 and 0.018 +/- 0.014 microg/l, respectively, p=ns). Inhibin B levels were obviously reduced (-72%) in euthyroid postmenopausal women. In contrast, in hyper- and hypothyroid postmenopausal women, inhibin B levels remained substantially at the premenopausal level. So far, serum inhibin B appeared to be significantly increased in both hyperthyroid patients (0.025 +/- 0.014 microg/l; p<0.0001) and in hypothyroid patients (0.016 +/- 0.006 microg/l; p=0.0006). Altered thyroid function did not affect FSH levels at fertile age. However, a significant decrease of FSH levels was observed in hyper- and hypothyroid (-52% and -43%, respectively) postmenopausal women. Nevertheless, these FSH levels remained in the postmenopausal range. These results indicate that an altered thyroid function affects serum inhibin B levels in postmenopausal women. PMID:12953168

  1. Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males.

    PubMed

    Griffin, Éadaoin W; Mullally, Sinéad; Foley, Carole; Warmington, Stuart A; O'Mara, Shane M; Kelly, Aine M

    2011-10-24

    Physical activity has been reported to improve cognitive function in humans and rodents, possibly via a brain-derived neurotrophic factor (BDNF)-regulated mechanism. In this study of human subjects, we have assessed the effects of acute and chronic exercise on performance of a face-name matching task, which recruits the hippocampus and associated structures of the medial temporal lobe, and the Stroop word-colour task, which does not, and have assessed circulating concentrations of BDNF and IGF-1 in parallel. The results show that a short period of high-intensity cycling results in enhancements in performance of the face-name matching, but not the Stroop, task. These changes in cognitive function were paralleled by increased concentration of BDNF, but not IGF-1, in the serum of exercising subjects. 3 weeks of cycling training had no effect on cardiovascular fitness, as assessed by VO2 scores, cognitive function, or serum BDNF concentration. Increases in fitness, cognitive function and serum BDNF response to acute exercise were observed following 5 weeks of aerobic training. These data indicate that both acute and chronic exercise improve medial temporal lobe function concomitant with increased concentrations of BDNF in the serum, suggesting a possible functional role for this neurotrophic factor in exercise-induced cognitive enhancement in humans. PMID:21722657

  2. Increases in Serum CYFRA21-1 Concentration during Successful Treatment with Crizotinib

    PubMed Central

    Kanaji, Nobuhiro; Tadokoro, Akira; Watanabe, Naoki; Inoue, Takuya; Ishii, Tomoya; Dobashi, Hiroaki; Bandoh, Shuji

    2014-01-01

    Case series Patient: — Final Diagnosis: — Symptoms: — Medication: — Clinical Procedure: — Specialty: — Objective: Unexpected drug reaction Background: Increases in tumor marker concentrations usually suggest disease progression. Cases Report: We here describe on 3 patients with non-small cell lung cancer whose serum concentrations of CYFRA21-1 increased in spite of successful treatment with crizotinib. Discontinuation of crizotinib resulted in a rapid decrease in serum CYFRA21-1 concentrations in all cases. In 1 patient with progressive disease, in spite of increasing the dose of crizotinib, CYFRA21-1 concentrations decreased. Conclusions: Crizotinib can induce increases in CYFRA21-1 concentration without disease progression. Pulmonologists and oncologists should be aware of this novel phenomenon, and focus on interpretation of CYFRA21-1 concentrations in monitoring tumor response to crizotinib treatment. PMID:25380070

  3. Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection

    PubMed Central

    2012-01-01

    Background Hepatitis C Virus (HCV), a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA) regulate inflammation (miR-155, -146a and -125b) as well as hepatocyte function (miR-122). Methods Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined miRNAs in the circulation and in peripheral monocytes of patients with chronic HCV infection to evaluate if specific miRNA expression correlated with HCV infection. Results We found that monocytes from chronic HCV infected treatment-naïve (cHCV) but not treatment responder patients showed increased expression of miR-155, a positive regulator of TNFα, and had increased TNFα production compared to monocytes of normal controls. After LPS stimulation, miR-155 levels were higher in monocytes from cHCV patients compared to controls. MiR-125b, which has negative regulatory effects on inflammation, was decreased in cHCV monocytes compared to controls. Stimulation of normal monocytes with TLR4 and TLR8 ligands or HCV core, NS3 and NS5 recombinant proteins induced a robust increase in both miR-155 expression and TNFα production identifying potential mechanisms for in vivo induction of miR-155. Furthermore, we found increased serum miR-155 levels in HCV patients compared to controls. Serum miR-125b and miR-146a levels were also increased in HCV patients. Serum levels of miR-122 were elevated in cHCV patients and correlated with increased ALT and AST levels and serum miR-155 levels. Conclusion In conclusion, our novel data demonstrate that miR-155, a positive regulator of inflammation, is upregulated both in monocytes and in the serum of patients with chronic HCV infection. Our study suggests that HCV core, NS3, and NS5 proteins or TLR4 and TLR8 ligands can mediate increased miR-155 and TNF

  4. Serum concentrations of penicillin after intramuscular administration of procaine, benzyl, and benethamine penicillin in children with pneumonia.

    PubMed

    Shann, F; Linnemann, V; Gratten, M

    1987-02-01

    Serum concentrations of penicillin were measured in 37 children with pneumonia. The mean serum concentration of penicillin was greater than 1.0 microgram/mL for 11 hours after intramuscular administration of 48,000 U/kg benethamine penicillin compound (nine children), for 26 hours after 48,000 U/kg aqueous procaine penicillin (10 children), and for 40 hours after 79,000 U/kg aqueous procaine penicillin (seven children). After intramuscular administration of 35,000 U/kg benzyl penicillin in 11 children, the serum concentration was 13.3 +/- 7.4 micrograms/mL (mean +/- SD) 30 minutes after the injection, and 4.9 +/- 3.2 micrograms/mL after 3 hours. Our findings lend support to the World Health Organization recommendation that children with mild pneumonia in developing countries be given daily intramuscular injections of 50,000 U/kg aqueous procaine penicillin. PMID:3806306

  5. Radiotherapy for Rectal Cancer Is Associated With Reduced Serum Testosterone and Increased FSH and LH

    SciTech Connect

    Bruheim, Kjersti Svartberg, Johan; Carlsen, Erik; Dueland, Svein; Haug, Egil; Skovlund, Eva; Tveit, Kjell Magne; Guren, Marianne G.

    2008-03-01

    Purpose: It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. Methods and Materials: All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone binding globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. Results: Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. Conclusions: Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.

  6. Human chorionic gonadotropin increases serum progesterone, number of corpora lutea and angiogenic factors in pregnant sheep.

    PubMed

    Coleson, Megan P T; Sanchez, Nicole S; Ashley, Amanda K; Ross, Timothy T; Ashley, Ryan L

    2015-07-01

    Early gestation is a critical period when implantation and placental vascularization are established, processes influenced by progesterone (P4). Although human chorionic gonadotropin (hCG) is not endogenously synthesized by livestock, it binds the LH receptor, stimulating P4 synthesis. We hypothesized treating pregnant ewes with hCG would increase serum P4, number of corpora lutea (CLs) and concepti, augment steroidogenic enzymes, and increase membrane P4 receptors (PAQRs) and angiogenic factors in reproductive tissues. The objective was to determine molecular alterations induced by hCG in pregnant sheep that may promote pregnancy. Ewes received either 600 IU of hCG or saline i.m. on day 4 post mating. Blood samples were collected daily from day 0 until tissue collection for serum P4 analysis. Reproductive tissues were collected on either day 13 or 25 of gestation and analyzed for PAQRs, CXCR4, proangiogenic factors and steroidogenic enzymes. Ewes receiving hCG had more CL and greater serum P4, which remained elevated. On day 25, StAR protein production decreased in CL from hCG-treated ewes while HSD3B1 was unchanged; further, expression of CXCR4 significantly increased and KDR tended to increase. PAQR7 and CXCR4 protein was increased in caruncle tissue from hCG-treated ewes. Maternal hCG exposure influenced fetal extraembryonic tissues, as VEGFA, VEGFB, FLT1, and ANGPT1 expression increased. Our results indicate hCG increases serum P4 due to augmented CL number per ewe. hCG treatment resulted in greater PAQR7 and CXCR4 in maternal endometrium and promoted expression of proangiogenic factors in fetal extraembryonic membranes. Supplementing livestock with hCG may boost P4 levels and improve reproductive efficiency. PMID:25861798

  7. Agomelatine Increases BDNF Serum Levels in Depressed Patients in Correlation with the Improvement of Depressive Symptoms

    PubMed Central

    Pettorruso, Mauro; De Berardis, Domenico; Varasano, Paola Annunziata; Lucidi Pressanti, Gabriella; De Remigis, Valeria; Valchera, Alessandro; Ricci, Valerio; Di Nicola, Marco; Janiri, Luigi; Biggio, Giovanni; Di Giannantonio, Massimo

    2016-01-01

    Background: Agomelatine modulates brain-derived neurotrophic factor expression via its interaction with melatonergic and serotonergic receptors and has shown promising results in terms of brain-derived neurotrophic factor increase in animal models. Methods: Twenty-seven patients were started on agomelatine (25mg/d). Venous blood was collected and brain-derived neurotrophic factor serum levels were measured at baseline and after 2 and 8 weeks along with a clinical assessment, including Hamilton Depression Rating Scale and Snaith-Hamilton Pleasure Scale. Results: Brain-derived neurotrophic factor serum concentration increased after agomelatine treatment. Responders showed a significant increase in brain-derived neurotrophic factor levels after 2 weeks of agomelatine treatment; no difference was observed in nonresponders. Linear regression analysis showed that more prominent brain-derived neurotrophic factor level variation was associated with lower baseline BDNF levels and greater anhedonic features at baseline. Conclusions: Patients affected by depressive disorders showed an increase of brain-derived neurotrophic factor serum concentration after a 2-week treatment with agomelatine. The increase of brain-derived neurotrophic factor levels was found to be greater in patients with lower brain-derived neurotrophic factor levels and marked anhedonia at baseline. PMID:26775293

  8. Effects of amycenone on serum levels of tumor necrosis factor-α, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration.

    PubMed

    Yao, Wei; Zhang, Ji-chun; Dong, Chao; Zhuang, Cun; Hirota, Susumu; Inanaga, Kazutoyo; Hashimoto, Kenji

    2015-09-01

    Accumulating evidence suggests that inflammation plays a role in the pathophysiology of depression and that anti-inflammatory substances have antidepressant effects. Amycenone is obtained from extracts of the Yamabushitake (Hericium erinaceum). The purpose of this study is to examine whether amycenone shows anti-inflammatory and antidepressant effects in an inflammation-induced mouse model of depression. First, we examined the effects of amycenone on the serum levels of the pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), and the anti-inflammatory cytokine, interleukin-10 (IL-10), after intraperitoneal administration of the bacterial endotoxin lipopolysaccharide (LPS). Oral administration of amycenone (50, 100, or 200mg/kg) markedly blocked an increase in the serum TNF-α levels after a single administration of LPS (0.5mg/kg). Furthermore, amycenone (200mg/kg) markedly increased the serum IL-10 levels by a single administration of LPS (0.5mg/kg). Next, we examined the effects of amycenone on depression-like behaviors in the tail-suspension test (TST) and forced swimming test (FST). Pretreatment with amycenone (200mg/kg) significantly attenuated LPS (0.5mg/kg)-induced increase of the immobility time by the TST and FST, indicating antidepressant effects of amycenone. In addition, oral administration of paroxetine (30mg/kg) showed anti-inflammatory and antidepressant effects in the same model. These findings suggest that amycenone has antidepressant effects in LPS-induced inflammation model of depression. Therefore, amycenone could represent a potential supplement to prevent inflammation-related depression. PMID:26150007

  9. Increased serum gamma-glutamyltransferase levels are associated with ventricular instability in type 2 diabetes.

    PubMed

    Wang, Kun; Li, Ling; Wu, Yang; Yang, Yu; Chen, Jie; Zhang, Danyu; Liu, Zhoujun; Xu, Juan; Cao, Meng; Mao, Xiaodong; Liu, Chao

    2016-04-01

    The purpose of our study is to examine the association between serum GGT levels and ventricular instability in Chinese patients with T2DM. We conducted a cross-sectional, community-based study in Nanjing, China from June to November 2011. Among 10,050 patients aged 40-79 years, we enrolled 2444 with pre-diabetes, 2496 with T2DM, and 4521 without diabetes (non-diabetes). Electrocardiograms were performed to measure the QT interval corrected for heart rate (QTc) and QT interval dispersion (QTd). Serum GGT levels, metabolic parameters, body mass index, and blood pressure were also measured. We found that there were no significant associations of increased QTc/QTd with serum GGT levels in participants with pre-existing T2DM and non-diabetes, after adjusting for age, duration of diabetes, and metabolic parameters. Even after adjustment, higher risks of QTc ≥ 440 ms/√s and QTd ≥ 58 ms were found in participants with serum GGT levels ≥49 U/L compared with those with <15 U/L in the pre-diabetes (QTc: OR 1.96, 95 % CI 1.23-2.47; QTd: OR 1.34, 95 % CI 1.07-1.94) and newly diagnosed T2DM (QTc: OR 2.01, 95 % CI 1.39-2.51; QTd: OR 1.53, 95 % CI 1.03-1.99) groups. We conclude that Increased serum GGT levels are associated with some markers of ventricular repolarization abnormalities in the early stage of T2DM. PMID:26433737

  10. Caloric restriction increases serum testosterone concentrations in obese male subjects by two distinct mechanisms.

    PubMed

    Schulte, D M; Hahn, M; Oberhäuser, F; Malchau, G; Schubert, M; Heppner, C; Müller, N; Güdelhöfer, H; Faust, M; Krone, W; Laudes, M

    2014-04-01

    The concentration of serum testosterone is mainly regulated by the testicular function, which is under control of the central hypothalamic-pituitary-gonadal axis. A certain amount of testosterone is converted into β-estradiol by adipose tissue. Obesity in men is often associated with decreased androgen levels. The aim of the present study was to examine the effect of caloric restriction on serum testosterone levels in obese men. Dietary intervention study was performed with a very low calorie diet (800 kcal/d) for 12 weeks. Thirteen obese human male subjects (median body mass index: 42.7 kg/m2) were included. Body composition was assessed by impedance analysis. Insulin sensitivity was estimated by leptin-to-adiponectin ratio (LAR). Testosterone (T), β-estradiol, albumin, sex hormone-binding globulin (SHBG), LH, and FSH serum concentrations were measured by enzyme immunoassays. Statistical analysis was performed on baseline and values after 3 months. Caloric restriction significantly increased total testosterone (6.97 nmol/l to 13.21 nmol/l; p=0.001) and SHBG (22.11 nmol/l to 42.12 nmol/l; p=0.001) concentrations in serum. This is caused by a significant improvement of the testicular function (LH/T: 0.36-0.20; p=0.005) and a significant reduction of the T/β-estradiol conversion rate (73.59-104.29; p=0.003). There was a significant negative correlation of improvement of testicular function and LAR (rs=-0.683 (p=0.042)). In obese men caloric restriction significantly increases the serum testosterone concentration. This is achieved by 2 distinct mechanisms, that is, improvement of testicular function and reduced conversion of testosterone to β-estradiol by aromatase activity of the adipose tissue. PMID:24198220

  11. Low T3 syndrome in canine babesiosis associated with increased serum IL-6 concentration and azotaemia.

    PubMed

    Zygner, Wojciech; Gójska-Zygner, Olga; Bąska, Piotr; Długosz, Ewa

    2015-06-30

    Low triiodothyronine (T3) syndrome, also named euthyroid sick syndrome or non-thyroidal illness syndrome, has been recognized in canine babesiosis caused by Babesia rossi, where it manifested by lowering of the serum thyrotropin (TSH), total thyroxin (TT4) and free thyroxin (FT4) concentrations. This syndrome has also been observed in critical diseases in humans and animals, and the severity of the disease is considered an important factor in lowering of thyroid hormone concentrations. Interleukin-6 (IL-6) plays a role in the development of low T3 syndrome by causing a decrease in deiodinases 1 and 2 activity and increased activity of deiodinase 3, enzymes involved in the conversion of thyroxin (T4) to T3. The purpose of this study was to compare the concentrations of serum thyroid hormones and TSH between healthy dogs and dogs with babesiosis, and to determine correlations between serum IL-6 concentration and serum total T3 (TT3), TT4, FT4, and TSH concentrations, and the level of azotaemia in dogs with babesiosis. The concentrations of IL-6, TT3, TT4, FT4, TSH, urea and creatinine were determined in 13 dogs with canine babesiosis caused by Babesia canis and in 10 healthy dogs. The results of this study showed decreases in TT3, TT4, FT4, and TSH and increases in IL-6, urea and creatinine concentrations in affected dogs in comparison to healthy dogs. The concentration of IL-6 was negatively correlated with TT3 and TSH concentrations and the TT3 concentration was negatively correlated with serum urea and creatinine concentrations. This study showed low T3 syndrome in canine babesiosis, which was confirmed by the determination of the T3 concentration, and demonstrates that in canine babesiosis the T3 concentration is associated with IL-6 concentration. PMID:25976636

  12. Increased serum concentrations of tumour necrosis factor in beta thalassaemia: effect of bone marrow transplantation.

    PubMed Central

    Meliconi, R; Uguccioni, M; Lalli, E; Nesci, S; Delfini, C; Paradisi, O; Lucarelli, G; Gasbarrini, G; Facchini, A

    1992-01-01

    AIMS: Serum concentrations of tumour necrosis factor-alpha (TNF) were determined in beta thalassemic patients before and after bone marrow transplantation (BMT) to evaluate whether changes in TNF concentrations after BMT were related to immune mediated complications. METHODS: Serum TNF concentrations were determined by enzyme linked immunoassay (EIA) in paired samples from 71 patients with beta thalassemia before and after BMT. Serial samples from 13 patients were also studied for up to six months after BMT. Forty one normal healthy children matched for sex and age were studied as controls. RESULTS: beta thalassemic patients had high serum TNF concentrations before transplantation compared with controls. These were not related to sex, age, duration of disease, number of blood transfusions, transferrin concentrations or splenectomy. DQw1 positive patients showed significantly lower TNF concentrations than non-DQw1 cases. Patients with severe liver fibrosis had significantly higher TNF concentrations. No correlation was found between TNF values and BMT outcome before transplantation but TNF alpha values fell significantly after BMT. The decrease persisted only in patients with successful engraftment. In serial samples studied for up to six months after BMT, TNF values decreased but in four out of five patients with graft rejection and in all five with acute graft versus host disease (GVHD) sharp increases occurred at the time of clinical symptoms. No correlation was found between the degree of GVHD and serum TNF-alpha concentrations nor between TNF-alpha concentrations after BMT and the presence of bacterial, viral, and fungal infections. CONCLUSIONS: About 50% of beta thalassemic patients have increased serum TNF, and the changes after BMT are related to the occurrence of immune mediate complications. The persistence of low TNF concentrations after successful engraftment may be due to the preparative regimen and the lack of adverse immune reactions. PMID:1740519

  13. Transient increase of serum IgD levels after allogeneic bone-marrow transplantation.

    PubMed Central

    Korver, K; Radl, J; Schellekens, P T; Vossen, J M

    1988-01-01

    Serum IgD levels were followed longitudinally twice a week for up to 100 days in 60 children undergoing allogeneic bone-marrow transplantation (n = 52) or immunosuppression (n = 8) for the treatment of leukaemia, severe aplastic anaemia or severe combined immunodeficiency. In 40 out of the 49 post-transplantation periods analysed (82%), a transient sharp increase of serum IgD was detected, irrespective of initial disease. A similar peak was found in one out of five children after immunosuppressive treatment. A second IgD peak was only recorded in grafted patients (14/49 post-transfusion periods). Peak levels of IgD ranged from 1.3 to 185.7 IU/ml (median 12.2 IU/ml), which represents a 2.6 to 22.4-fold increase over 'baseline' levels. In the transplanted leukaemia and aplastic anaemia patients, the rise of serum IgD occurred at the same time (geometric mean 16 days after transplantation) and was shown to represent heterogeneous polyclonal IgD in six of them. The onset of the serum IgD peak was significantly delayed in children suffering from severe combined immunodeficiency (P less than 0.05) and was demonstrated in one patient to consist of homogeneous IgD. No relation was found between either the occurrence of clinical acute graft-versus-host disease or infections after treatment, and the time of onset of IgD elevations. To detect transient serum IgD peaks as described here, frequent sampling of sera is necessary. The origin of the early IgD peaks seems to reside within the recipient's cells by an unknown mechanism. The late IgD peaks are most probably an expression of gradual reconstitution of the immune system following bone-marrow transplantation. PMID:3044651

  14. IL-33 circulating serum levels are increased in patients with non-segmental generalized vitiligo.

    PubMed

    Vaccaro, Mario; Cicero, Francesca; Mannucci, Carmen; Calapai, Gioacchino; Spatari, Giovanna; Barbuzza, Olga; Cannavò, Serafinella P; Gangemi, Sebastiano

    2016-09-01

    IL-33 is a recently identified cytokine, encoded by the IL-33 gene, which is a member of the IL-1 family that drives the production of T-helper-2 (Th-2)-associated cytokines. Serum levels of IL-33 have been reported to be up-regulated in various T-helper (Th)-1/Th-17-mediated diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel. To investigate whether cytokine imbalance plays a role in the pathogenesis of vitiligo, we performed a case-control association study by enzyme-linked immunosorbent assay of IL-33 in our patients. IL-33 serum levels were measured by a quantitative enzyme immunoassay technique in patients with non-segmental generalized vitiligo and compared with those of healthy controls. IL-33 serum levels in patients with vitiligo were significantly increased than those in healthy controls. There was a positive correlation of IL-33 serum levels with extension of vitiligo and disease activity. This study suggests a possible systemic role of IL-33 in the pathogenesis of vitiligo. Inhibiting IL-33 activity might be a novel therapeutic strategy in the treatment of autoimmune inflammatory disease, like vitiligo. PMID:27388717

  15. Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy.

    PubMed

    Klein, Anders B; Jennum, Poul; Knudsen, Stine; Gammeltoft, Steen; Mikkelsen, Jens D

    2013-06-01

    Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction in hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesized that serum levels of these factors are altered in patients with narcolepsy compared to healthy controls without sleep disturbances. Polysomnography data was obtained and serum BDNF and NGF levels measured using ELISA, while hypocretin was measured using RIA. Serum BDNF levels were significantly higher in narcolepsy patients than in healthy controls (64.2±3.9 ng/ml vs. 47.3±2.6 ng/ml, P<0.01), while there were no significant differences in NGF levels. As expected, narcolepsy patients had higher BMI compared to controls, but BMI did not correlate with the serum BDNF levels. The change in BDNF levels was not related to disease duration and sleep parameters did not correlate with BDNF in narcolepsy patients. The mechanisms behind the marked increase in BDNF levels in narcolepsy patients remain unknown. PMID:23570723

  16. Increased serum levels of apoptosis in deficit syndrome schizophrenia patients: a preliminary study

    PubMed Central

    Beyazyüz, Murat; Küfeciler, Tarkan; Bulut, Leyla; Ünsal, Cüneyt; Albayrak, Yakup; Akyol, Esra Soydaş; Baykal, Saliha; Kuloglu, Murat; Hashimoto, Kenji

    2016-01-01

    Background Schizophrenia is a chronic and debilitating disorder, the etiology of which remains unclear. Apoptosis is a programmed cell death mechanism that might be implicated in neuropsychiatric disorders, including schizophrenia. In this study, we aimed to compare the serum levels of apoptosis among deficit schizophrenia (DS) syndrome patients, nondeficit schizophrenia (NDS) patients, and healthy controls (HCs). Patients and methods After the inclusion and exclusion criteria were applied, 23 DS patients, 46 NDS patients, and 33 HCs were included in the study. The serum apoptosis levels were measured using a quantitative sandwich enzyme immunoassay with human monoclonal antibodies directed against DNA and histones. Results There was a significant difference among the three groups in terms of the levels of apoptosis (F2,96=16.58; P<0.001). The serum apoptosis levels in the DS and NDS groups were significantly higher than those in the HC group. Furthermore, the serum apoptosis levels in the DS group were significantly higher than the levels in the NDS group. Conclusion This study suggests that increased levels of apoptosis may be implicated in the pathophysiology of DS syndrome. However, further studies are needed to support the role of apoptosis in DS. PMID:27307738

  17. Reversible increase of serum activin A levels in women with Graves' disease.

    PubMed

    Centanni, M; Viceconti, N; Luisi, S; Reis, F M; Gargano, L; Maiani, F; Franchi, A; Canettieri, G; Petraglia, F

    2002-12-01

    The aim of this study was to analyze the serum levels of activin A in hyperthyroid patients with Graves' disease. Serum activin A and FSH levels were measured in a total of 93 females (64 regularly cycling and 29 post-menopausal). Of these, 20 were hyperthyroid patients with Graves disease, 33 were euthyroid goitrous patients (20 had autoimmune thyroiditis AT and 13 only had goiter) representing the internal control group and 40 were healthy subjects representing the external control group. Serum levels of activin A were higher in goitrous patients with AT than in control subjects (p=0.0388). Activin A levels were almost doubled in the cycling and in post-menopausal hyperthyroid women (0.91+/-0.21 vs 0.43+/-0.07 microg/l; p<0.0001 and 0.92+/-0.22 vs 0.48+/-0.24 microg/l; p=0.0001, respectively). In 10 cycling hyperthyroid patients, studied even after methimazole treatment, that increase was substantially reversed, once euthyroidism was attained (p=0.002). These findings indicate that thyroid function and autoimmune processes significantly affect serum levels of activin A in patients with Graves' disease. PMID:12553556

  18. Pharmacokinetic study on pradofloxacin in the dog – Comparison of serum analysis, ultrafiltration and tissue sampling after oral administration

    PubMed Central

    2013-01-01

    Background Pradofloxacin, a newly developed 8-cyano-fluoroquinolone, show enhanced activity against Gram-positive organisms and anaerobes to treat canine and feline bacterial infections. The purpose of this cross-over study was to measure the unbound drug concentration of pradofloxacin in the interstitial fluid (ISF) using ultrafiltration and to compare the kinetics of pradofloxacin in serum, ISF and tissue using enrofloxacin as reference. Results After oral administration of enrofloxacin (5 mg/kg) and pradofloxacin (3 mg/kg and 6 mg/kg, respectively), serum collection and ultrafiltration in regular intervals over a period of 24 h were performed, followed by tissue sampling at the end of the third dosing protocol (pradofloxacin 6 mg/kg). Peak concentrations of pradofloxacin (3 mg/kg) were 1.55±0.31 μg/ml in the ISF and 1.85±0.23 μg/ml in serum and for pradofloxacin (6 mg/kg) 2.71±0.81 μg/kg in the ISF and 2.77±0.64 μg/kg in serum; both without a statistical difference between ISF and serum. Comparison between all sampling approaches showed no consistent pattern of statistical differences. Conclusions Despite some technical shortcomings the ultrafiltration approach appears to be the most sensitive sampling technique to estimate pharmacokinetic values of pradofloxacin at the infection site. Pharmacokinetics – Pradofloxacin – Ultrafiltration – Dog – Oral Administration. PMID:23410255

  19. Does rosuvastatin increase serum levels of 25-hydroxy-vitamin D?

    PubMed Central

    Glossmann, Hartmut H.; Blumthaler, Mario

    2012-01-01

    An observational study and a “clinical trial” seem to prove that rosuvastatin (but not fluvastatin) dramatically increases serum levels of 25-(OH)-D3 (three-fold above starting values). A critical analysis of the two publications, presented below, raises serious concerns. Conclusions from these two studies have already been drawn in the scientific literature.It is argued that claiming or believing in a “novel pleiotropic effect of rosuvastatin” may be misleading and premature. PMID:22870344

  20. Treatment with lithium prevents serum thyroid hormone increase after thionamide withdrawal and radioiodine therapy in patients with Graves' disease.

    PubMed

    Bogazzi, Fausto; Bartalena, Luigi; Campomori, Alberto; Brogioni, Sandra; Traino, Claudio; De Martino, Fabio; Rossi, Giuseppe; Lippi, Francesco; Pinchera, Aldo; Martino, Enio

    2002-10-01

    Serum thyroid hormone concentrations increase after radioiodine (RAI) therapy for Graves' disease. This phenomenon has been ascribed to either antithyroid drug withdrawal before RAI therapy or release of preformed thyroid hormones into the bloodstream from the RAI-damaged thyroid. Lithium blocks the release of iodine and thyroid hormones from the thyroid, thus enhancing the effectiveness of RAI therapy. Changes in serum-free thyroxine (FT4) and triiodothyronine (FT3) levels after methimazole (MMI) discontinuation and RAI therapy were evaluated in a prospective, randomized, control study of 36 patients with Graves' disease. After a 3- to 4-month course of MMI, patients were assigned to one of three groups: G1 (RAI alone); G2 (RAI plus lithium for 6 d starting on the day of RAI therapy); or G3 (RAI plus lithium for 19 d starting on the day of MMI withdrawal). G1-G2 patients had an increase in serum FT4 and FT3 levels from 13.5 +/- 6.5 to 19.8 +/- 9.2 pmol/liter and 5.0 +/- 2.0 to 8.0 +/- 4.8 pmol/liter, respectively (P < 0.0001), 2-5 d after MMI withdrawal, but G3 patients showed no changes. In the 30 d after RAI therapy, mean serum FT4 values increased in G1 patients (P = 0.02), peaking at 3-7 d (P < 0.05) but not in G2 and G3 patients. Serum FT3 levels decreased in G1, G2, and G3 (P = 0.03, P = 0.001, P = 0.02, respectively). Hyperthyroidism was cured in 8 of 12 G1 patients, 11 of 12 G2 patients, and 11 of 12 G3 patients (P = 0.31). Control of hyperthyroidism was prompter in G2 (P = 0.08) and G3 (P < 0.05) than in G1 patients. Patients in the three groups received a similar dose of RAI, but the committed radiation to the thyroid was higher in G3 (563 +/- 174 Gray) and G2 (588 +/- 347 Gray) than in G1 (429 +/- 204 Gray) (P < 0.03). In conclusion, the results of the present study demonstrate that: 1) MMI withdrawal is associated with a slight rise in serum thyroid hormone levels; 2) a further increase occurs after RAI therapy; 3) changes in serum thyroid hormone

  1. Serum levels of sex steroids and metabolites following 12 weeks of intravaginal 0.50% DHEA administration.

    PubMed

    Ke, Yuyong; Labrie, Fernand; Gonthier, Renaud; Simard, Jean-Nicolas; Bergeron, Danielle; Martel, Céline; Vaillancourt, Mario; Montesino, Marlene; Lavoie, Lyne; Archer, David F; Balser, John; Moyneur, Erick

    2015-11-01

    The objective of the present phase III, placebo-controlled, double-blind, prospective and randomized study was to confirm the efficacy of daily intravaginal administration of 0.50% dehydroepiandrosterone (DHEA; prasterone) ovules for 12 weeks on moderate to severe dyspareunia (or pain at sexual activity) as most bothersome symptom of vulvovaginal atrophy (VVA) while having serum steroid concentrations within normal postmenopausal values. To this end, serum levels of DHEA, DHEA-sulfate (DHEA-S), Androst-5-ene-diol-3β, 17β-diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4-dione), estrone (E1), estradiol (E2), estrone sulfate (E1-S), androsterone glucuronide (ADT-G), and androstane-3α, 17β-diol 17-glucuronide (3α-diol-17G) were measured by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). In agreement with the mechanisms of intracrinology, all serum sex steroids and metabolites concentrations after 12 weeks of daily intravaginal administration of 0.50% DHEA remain well within the limits of normal postmenopausal women. More specifically, the 12-week serum E2 concentration was measured at 22% below the average normal postmenopausal value (3.26 versus 4.17 pg/ml), thus eliminating any fear of E2 exposure outside the vagina. In addition, serum E1-S, a particularly reliable indicator of global estrogenic activity, shows serum levels practically superimposable to the value observed in normal postmenopausal women (219 versus 220 pg/ml). Similarly, serum ADT-G, the major metabolite of androgens, remains within normal postmenopausal values. The present data confirm the intracellular transformation of DHEA in the vagina resulting in local efficacy without any systemic exposure to sex steroids, observations which are in agreement with the physiological mechanisms of menopause. PMID:26291918

  2. Serum Prosaposin Levels Are Increased in Patients with Advanced Prostate Cancer

    PubMed Central

    Koochekpour, Shahriar; Hu, Siyi; Vellasco-Gonzalez, Cruz; Bernardo, Ruiz; Azabdaftari, Gissue; Dalin, Guo-xiang; Zhau, Haiyen E.; Chung, Leland W.; Vessella, Robert L.

    2012-01-01

    BACKGROUND We previously cloned prosaposin (PSAP) from metastatic castrate-resistant prostate cancer (mCRPCa) cells and demonstrated its genomic amplification and/or overexpression in metastatic PCa cell lines, xenografts, and lymph node metastases. The clinicohistopathological significance of serum-PSAP levels and its tissue expression and association with predictive or prognostic variable in primary or advanced PCa are not known. METHODS We examined PSAP expression by immunohistochemical staining during early embryogenic development of the prostate and within a large tissue microarray which included 266 benign and malignant prostate tissues. In addition, serum PSAP levels in the age-adjusted normal male population and in 154 normal individuals and patients with primary or mCRPCa were measured by an ELISA assay. RESULTS Univariate and multivariate analyses revealed a significant and inverse association between PSAP expression and clinical stage II and III tumors, dominant Gleason patterns 3 and 4, and seminal vesicle invasion. In the normal male population, the lowest serum-PSAP level was detected before puberty, peaked at the most reproductive age group (20–39 years old), and then, decreased to a range between the two groups for men above 40 years old. Regardless of age and when compared with normal individuals, serum-PSAP levels significantly decreased in primary organ-confined PCa, but increased in those with mCRPCa. CONCLUSION Our results show that PSAP has the potential to differentiate between primary and advanced PCa. Additional large-scale studies are needed to define the usefulness of tissue expression or serum-PSAP levels as a diagnostic or prognostic marker or as a therapeutic target in PCa. PMID:21630292

  3. Increased Concentrations of Interleukin-33 in the Serum and Cerebrospinal Fluid of Patients with Multiple Sclerosis

    PubMed Central

    Jafarzadeh, Abdollah; Mahdavi, Roya; Jamali, Mitra; Hajghani, Hossain; Nemati, Maryam; Ebrahimi, Hossain-Ali

    2016-01-01

    Objectives Interleukin (IL)-33 is a cytokine with both pro- and anti-inflammatory effects involved in the pathogenesis of some inflammatory diseases. The purpose of this investigation was to evaluate the serum and cerebrospinal fluid (CSF) IL-33 concentrations in patients with multiple sclerosis (MS). Methods Blood specimens were obtained from 140 patients with MS (46 males and 94 females) with various disease patterns and treatment plans and 140 healthy subjects (47 males and 93 females), who acted as a control group. CSF samples were collected from 20 MS group and 20 sex- and age-matched patients with other neurological diseases of nonautoimmune etiology. The serum and CSF concentrations of IL-33 were measured by the enzyme-linked immunosorbent assay. Results The serum and CSF IL-33 levels were significantly higher in the MS group compared to the control group (p<0.001 and p<0.050, respectively). The serum IL-33 concentrations were also significantly higher in newly diagnosed (untreated) patients and patients treated with methylprednisolone or with interferon-β and methylprednisolone compared to the healthy patient group (p<0.007, p<0.002, and p<0.010, respectively). Moreover, the serum IL-33 concentrations in patients with relapsing-remitting (RRMS), primary progressive (PPMS), and secondary progressive (SPMS) forms of the disease were significantly higher than in the healthy control group (p<0.006, p<0.001, and p<0.020, respectively). Conclusions Our results showed increased concentrations of IL-33 in patients with MS including both untreated and treated MS patients and patients with the RRMS, SPMS, and PPMS forms. This suggests that IL-33 may be involved in the pathogenesis of all MS forms and treatment with methylprednisolone or both interferon-β plus methylprednisolone has no influence on IL-33 concentrations. PMID:26813806

  4. Intranasal administration of oxytocin increases compassion toward women

    PubMed Central

    Palgi, Sharon; Klein, Ehud

    2015-01-01

    It has been suggested that the degree of compassion—the feeling of warmth, understanding and kindness that motivates the desire to help others, is modulated by observers’ views regarding the target’s vulnerability and suffering. This study tested the hypothesis that as compassion developed to protect vulnerable kinships, hormones such as oxytocin, which have been suggested as playing a key role in ‘tend-and-befriend’ behaviors among women, will enhance compassion toward women but not toward men. Thirty subjects participated in a double-blind, placebo-controlled, within-subject study. Following administration of oxytocin/placebo, participants listened to recordings of different female/male protagonists describing distressful emotional conflicts and were then asked to provide compassionate advice to the protagonist. The participants’ responses were coded according to various components of compassion by two clinical psychologists who were blind to the treatment. The results showed that in women and men participants oxytocin enhanced compassion toward women, but did not affect compassion toward men. These findings indicate that the oxytocinergic system differentially mediates compassion toward women and toward men, emphasizing an evolutionary perspective that views compassion as a caregiving behavior designed to help vulnerable individuals. PMID:24711542

  5. Intranasal administration of oxytocin increases compassion toward women.

    PubMed

    Palgi, Sharon; Klein, Ehud; Shamay-Tsoory, Simone G

    2015-03-01

    It has been suggested that the degree of compassion-the feeling of warmth, understanding and kindness that motivates the desire to help others, is modulated by observers' views regarding the target's vulnerability and suffering. This study tested the hypothesis that as compassion developed to protect vulnerable kinships, hormones such as oxytocin, which have been suggested as playing a key role in 'tend-and-befriend' behaviors among women, will enhance compassion toward women but not toward men. Thirty subjects participated in a double-blind, placebo-controlled, within-subject study. Following administration of oxytocin/placebo, participants listened to recordings of different female/male protagonists describing distressful emotional conflicts and were then asked to provide compassionate advice to the protagonist. The participants' responses were coded according to various components of compassion by two clinical psychologists who were blind to the treatment. The results showed that in women and men participants oxytocin enhanced compassion toward women, but did not affect compassion toward men. These findings indicate that the oxytocinergic system differentially mediates compassion toward women and toward men, emphasizing an evolutionary perspective that views compassion as a caregiving behavior designed to help vulnerable individuals. PMID:24711542

  6. Substantial Increases Occur in Serum Activins and Follistatin during Lung Transplantation

    PubMed Central

    de Kretser, David M.; Bensley, Jonathan G.; Phillips, David J.; Levvey, Bronwyn J.; Snell, Greg I.; Lin, Enjarn; Hedger, Mark P.; O’Hehir, Robyn E.

    2016-01-01

    Background Lung transplantation exposes the donated lung to a period of anoxia. Re-establishing the circulation after ischemia stimulates inflammation causing organ damage. Since our published data established that activin A is a key pro-inflammatory cytokine, we assessed the roles of activin A and B, and their binding protein, follistatin, in patients undergoing lung transplantation. Methods Sera from 46 patients participating in a published study of remote ischemia conditioning in lung transplantation were used. Serum activin A and B, follistatin and 11 other cytokines were measured in samples taken immediately after anaesthesia induction, after remote ischemia conditioning or sham treatment undertaken just prior to allograft reperfusion and during the subsequent 24 hours. Results Substantial increases in serum activin A, B and follistatin occurred after the baseline sample, taken before anaesthesia induction and peaked immediately after the remote ischemia conditioning/sham treatment. The levels remained elevated 15 minutes after lung transplantation declining thereafter reaching baseline 2 hours post-transplant. Activin B and follistatin concentrations were lower in patients receiving remote ischemia conditioning compared to sham treated patients but the magnitude of the decrease did not correlate with early transplant outcomes. Conclusions We propose that the increases in the serum activin A, B and follistatin result from a combination of factors; the acute phase response, the reperfusion response and the use of heparin-based anti-coagulants. PMID:26820896

  7. Serum clara cell protein: a sensitive biomarker of increased lung epithelium permeability caused by ambient ozone.

    PubMed

    Broeckaert, F; Arsalane, K; Hermans, C; Bergamaschi, E; Brustolin, A; Mutti, A; Bernard, A

    2000-06-01

    Ozone in ambient air may cause various effects on human health, including decreased lung function, asthma exacerbation, and even premature mortality. These effects have been evidenced using various clinical indicators that, although sensitive, do not specifically evaluate the O(3)-increased lung epithelium permeability. In the present study, we assessed the acute effects of ambient O(3) on the pulmonary epithelium by a new approach relying on the assay in serum of the lung-specific Clara cell protein (CC16 or CC10). We applied this test to cyclists who exercised for 2 hr during episodes of photochemical smog and found that O(3) induces an early leakage of lung Clara cell protein. The protein levels increased significantly into the serum from exposure levels as low as 0.060-0.084 ppm. Our findings, confirmed in mice exposed to the current U.S. National Ambient Air Quality Standards for O(3) (0.08 ppm for 8 hr) indicate that above the present natural background levels, there is almost no safety margin for the effects of ambient O(3) on airway permeability. The assay of CC16 in the serum represents a new sensitive noninvasive test allowing the detection of early effects of ambient O(3) on the lung epithelial barrier. PMID:10856027

  8. Association between increased serum thyrotropin concentration and the oldest old: what do we know?

    PubMed Central

    Duarte, Glaucia Cruzes; Cendoroglo, Maysa Seabra; Araújo, Lara Miguel Quirino; Almada, Clineu de Mello

    2015-01-01

    To assess studies that evaluate the relation between serum thyrotropin concentration, very old subjects, and their events. We searched the PubMed, SciELO, and LILACS databases for articles published between 2004 and 2012. Our search was restricted to studies involving humans aged 65 years or older, and written in English, Spanish, or Portuguese. Studies that evaluated the association between elevated serum thyrotropin concentration among elderly subjects with subclinical hypothyroidism were chosen since at least in part they included a subpopulation of individuals aged 80 years and above. Thirteen studies were selected. No significant increase in risk of cardiovascular events, coronary heart disease, or total mortality was observed. Elevated thyrotropin concentration was associated with longevity. More randomized controlled trials are required to better define the potential benefits of elevated thyrotropin concentration in this oldest old population, hormone replacement, and longevity. PMID:25807244

  9. Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

    PubMed Central

    Ortiz, Genaro Gabriel; Macías-Islas, Miguel Ángel; Pacheco-Moisés, Fermín P.; Cruz-Ramos, José A.; Sustersik, Silvia; Barba, Elías Alejandro; Aguayo, Adriana

    2009-01-01

    Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old) and 7 men (5 aged from 20 to 30 and 2 were > 40 years old) fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites), lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals), and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress. PMID:19242067

  10. Increased serum clearance of oligomannose species present on a human IgG1 molecule

    PubMed Central

    Alessandri, Leslie; Ouellette, David; Acquah, Aima; Rieser, Mathew; LeBlond, David; Saltarelli, Mary; Radziejewski, Czeslaw; Fujimori, Taro; Correia, Ivan

    2012-01-01

    The role of Fc glycans on clearance of IgG molecule has been examined by various groups in experiments where specific glycans have been enriched or the entire spectrum of glycans was studied after administration in pre-clinical or clinical pharmacokinetic (PK) studies. The overall conclusions from these studies are inconsistent, which may result from differences in antibody structure or experimental design. In the present study a well-characterized recombinant monoclonal IgG1 molecule (mAb-1) was analyzed from serum samples obtained from a human PK study. mAb-1 was recovered from serum using its ligand cross-linked to Sepharose beads. The overall purity and recovery of all isoforms were carefully evaluated using a variety of methods. Glycans were then enzymatically cleaved, labeled using 2-aminobenzamide and analyzed by normal phase high performance liquid chromatography. The assays for recovering mAb-1 from serum and subsequent glycan analysis were rigorously qualified at a lower limit of quantitation of 15 μg/mL, thus permitting analysis to day 14 of the clinical PK study. Eight glycans were monitored and classified into two groups: (1) the oligomannose type structures (M5, M6 and M7) and (2) fucosylated biantennary oligosaccharides (FBO) structures (NGA2F, NA1F, NA2F, NA1F-GlcNAc and NGA2F-GlcNAc). We observed that the oligomannose species were cleared at a much faster rate (40%) than FBOs and conclude that high mannose species should be carefully monitored and controlled as they may affect PK of the therapeutic; they should thus be considered an important quality attribute. These observations were only possible through the application of rigorous analytical methods that we believe will need to be employed when comparing innovator and biosimilar molecules. PMID:22669558

  11. Serum thyroxine concentration before and after administration of thyrotropin-stimulating hormone decreases with chronological age in the dog

    SciTech Connect

    Weller, R.E.; Park, J.F.; Kinnas, T.C.; Stevens, D.L.

    1983-06-01

    Thyroid function in the dog was evaluated as a function of increasing chronological age. Ninety-one dogs between the ages of 14.6 and 160.8 months were evaluated. Basal serum triiodothyronine (T/sub 3/) concentration, basal serum thyroxine (T/sub 4/) and serum T/sub 4/ concentration following stimulation by thyrotropin were found to decrease with age. The results suggested that age may be an important factor in interpreting thyroid profiles in the dog. 17 refs., 4 figs., 1 tab.

  12. Effect of repeated administration of antidepressant drugs on the serum and brain concentration of testosterone and its metabolites.

    PubMed

    Przegaliński, E; Warchoł-Kania, A; Budziszewska, B; Jaworska, L

    1987-01-01

    A repeated oral treatment (twice daily, for 21 consecutive days) with 10 mg/kg of antidepressants imipramine, amitriptyline, citalopram, mianserin affects the level of testosterone and its metabolites (5 alpha-dihydrotestosterone and estradiol-17 beta) in the serum and brain structures (cerebral cortex, hypothalamus). Citalopram and mianserin increased significantly the serum testosterone concentration, while imipramine and amitriptyline reduced the concentration of 5 alpha-dihydrotestosterone. In the cerebral cortex a reduction in 5 alpha-dihydrotestosterone after imipramine, and in the hypothalamus a decrease in testosterone level after amitriptyline were observed. None of the investigated drugs influenced estradiol-17 beta concentration in the serum or in the brain. PMID:3503989

  13. Serum concentrations of tamoxifen and its metabolites increase with age during steady-state treatment.

    PubMed

    Lien, Ernst A; Søiland, Håvard; Lundgren, Steinar; Aas, Turid; Steen, Vidar M; Mellgren, Gunnar; Gjerde, Jennifer

    2013-09-01

    It has been suggested that the concentrations of tamoxifen and its demethylated metabolites increase with age. We measured the serum concentrations of the active tamoxifen metabolites, 4OHtamoxifen (4OHtam), 4-hydroxy-N-desmethyltamoxifen (4OHNDtam, Endoxifen), tamoxifen and its demethylated metabolites. Their relations to age were examined. One hundred fifty-one estrogen receptor and/or progesterone receptor positive breast cancer patients were included. Their median (range) age was 57 (32-85) years. Due to the long half-life of tamoxifen, only patients treated with tamoxifen for at least 80 days were included in the study in order to insure that the patients had reached steady-state drug levels. Tamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Their serum concentrations were related to the age of the patients. To circumvent effects of cytochrome (CYP) 2D6 polymorphisms we also examined these correlations exclusively in homozygous extensive metabolizers. The concentrations of 4OHNDtam, tamoxifen, NDtam (N-desmethyltamoxifen), and NDDtam (N-desdimethyltamoxifen) were positively correlated to age (n = 151, p = 0.017, 0.045, 0.011, and 0.001 respectively). When exclusively studying the CYP2D6 homozygous extensive metabolizers (n = 86) the correlation between 4OHNDtam and age increased (p = 0.008). Up to tenfold inter-patient variation in the serum concentrations was observed. The median (inter-patient range) concentration of 4OHNDtam in the age groups 30-49, 50-69, and >69 years were 65 (24-89), 116 (25-141), and 159 (26-185) ng/ml, respectively. We conclude that the serum concentrations of 4OHNDtam (endoxifen), tamoxifen, and its demethylated metabolites increase with age during steady-state tamoxifen treatment. This may represent an additional explanation why studies on the effects of CYP2D6 polymorphisms on outcome in tamoxifen-treated breast cancer patients have been inconsistent. The observed high inter-patient range

  14. No exercise-induced increase in serum BDNF after cycling near a major traffic road.

    PubMed

    Bos, I; Jacobs, L; Nawrot, T S; de Geus, B; Torfs, R; Int Panis, L; Degraeuwe, B; Meeusen, R

    2011-08-15

    Commuting by bike has a clear health enhancing effect. Moreover, regular exercise is known to improve brain plasticity, which results in enhanced cognition and memory performance. Animal research has clearly shown that exercise upregulates brain-derived neurotrophic factor (BDNF - a neurotrophine) enhancing brain plasticity. Studies in humans found an increase in serum BDNF concentration in response to an acute exercise bout. Recently, more evidence is emerging suggesting that exposure to air pollution (such as particulate matter (PM)) is higher in commuter cyclists compared to car drivers. Furthermore, exposure to PM is linked to negative neurological effects, such as neuroinflammation and cognitive decline. We carried-out a cross-over experiment to examine the acute effect of exercise on serum BDNF, and the potential effect-modification by exposure to traffic-related air pollution. Thirty eight physically fit, non-asthmatic volunteers (mean age: 43, 26% women) performed two cycling trials, one near a major traffic road (Antwerp Ring, R1, up to 260,000 vehicles per day) and one in an air-filtered room. The air-filtered room was created by reducing fine particles as well as ultrafine particles (UFP). PM10, PM2.5 and UFP were measured. The duration (∼20min) and intensity of cycling were kept the same for each volunteer for both cycling trials. Serum BDNF concentrations were measured before and 30min after each cycling trial. Average concentrations of PM10 and PM2.5 were 64.9μg/m(3) and 24.6μg/m(3) in cycling near a major ring way, in contrast to 7.7μg/m(3) and 2.0μg/m(3) in the air-filtered room. Average concentrations of UFP were 28,180 particles/cm(3) along the road in contrast to 496 particles/cm(3) in the air-filtered room. As expected, exercise significantly increased serum BDNF concentration after cycling in the air-filtered room (+14.4%; p=0.02). In contrast, serum BDNF concentrations did not increase after cycling near the major traffic route (+0.5%; p

  15. In postmenopausal osteoporosis the bone increasing effect of monofluorophosphate is not dependent on serum fluoride.

    PubMed

    Rigalli, A; Pera, L; Morosano, M; Masoni, A; Bocanera, R; Tozzini, R; Puche, R C

    1999-01-01

    According to previous pharmacokinetic studies the bioavailability of fluorine (F) from sodium monofluorophosphate (MFP) doubles that of sodium fluoride (NaF). This paper reports a study designed to verify whether the vertebral bone mass increasing effect of NaF (30 mg F/day) was comparable to that of MFP (15 mg F/day), given for 18 months to osteoporotic postmenopausal women. The BMD of lumbar vertebrae of both groups showed significant increases (MFP: 60 +/- 15 mg/cm2, NaF: and 71 +/- 12 mg/cm2) over basal levels (P < 0.001). The difference between treatments was not significant (P = 0.532). The serum levels of ionic F (the mitogenic species on osteoblasts) were not related to the above mentioned effects. In NaF-treated patients, the fasting levels of total serum F increased significantly (6.7 +/- 0.9 microM vs. Basal: 2.0 +/- 0.8 microM; P < 0.001). This phenomenon was accounted for by ionic fluoride that increased over 20-fold (6.5 +/- 1.9 microM vs. Basal: 0.3 +/- 0.04 microM). In MFP-treated patients the fasting serum levels of total (7.0 +/- 0.7 microM vs. Basal: 2.2 +/- 0.9 M) and diffusible F (0.5 +/- 0.02 microM vs. Basal 0.2 +/- 0.02 microM) increased significantly (P < 0.001). The increase in the non diffusible F fraction is accounted for by protein-bound F, probably by the complexes formed between MFP and alpha 2-macroglobulin and C3. Serum diffusible F was formed by two fractions: ionic F and F bound to low molecular weight macromolecule/s (2,200 +/- 600 Da), in approximately equal amounts. The general information afforded by the present observations support the hypothesis that ionic F is released progressively during the metabolism of MFP bound to alpha 2-macroglobulin and C3. These phenomena explain why comparable effects to those obtained with 30 mg F/d of NaF could by obtained with one half the dose of MFP. PMID:10413893

  16. Participation of decreased serum cholesteryl ester transfer activity, independent of increased serum lipoprotein(a), in angina pectoris in normolipemic elderly subjects.

    PubMed

    Miyashita, Y; Morimoto, S; Fukuo, K; Imanaka, S; Koh, E; Tamatani, M; Ogihara, T

    1992-01-01

    The cholesteryl ester transfer activity (CETA) is a measurement of the transfer of cholesteryl ester from HDL to VLDL, LDL or peripheral cells. Its role in the development of early coronary heart disease is not clear. In the present study, serum levels of CETA, lipoprotein(a) [Lp(a)] and other lipid-related factors were compared in 10 normal young subjects, 28 healthy elderly subjects and 14 normolipemic elderly patients with angina pectoris. Compared to the young normals and healthy elderly subjects, the elderly patients with angina pectoris showed significantly decreased mean serum CETA levels, and significantly increased mean serum levels of Lp(a) and apoprotein B. These results may indicate that decreased serum values of CETA participate in the development of angina pectoris in normolipemic elderly patients. PMID:1427124

  17. Influence of nandrolone decanoate administration on serum lipids and liver enzymes in rats

    PubMed Central

    Samieinasab, Mohammad Reza; Shahraki, Mohammad Reza; Samieinasab, Fatemah; Najafi, Somayeh

    2015-01-01

    BACKGROUND Anabolic-androgenic steroids have been associated with several side effects range. This experimental study was conducted to evaluate the effects of nandrolone decanoate (ND, an anabolic steroid) on lipid profile and liver enzymes in rats in Iran. METHODS Forty adult male and female of Wistar strain rats were randomly assigned to four groups of 10 animals each: male control, female control, ND-male treated (15 mg/kg b.w./day), and ND-female treated (15 mg/kg b.w./day). Serum concentrations of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in all studied groups. RESULTS Treating rats with ND (case group) resulted in a significant elevation of TC (69.4 ± 8.7), TG (101.6 ± 32.9) and ALT (72.2 ± 13.8) and significant reduction of LDL (6.4 ± 2.6) and AST (138.7 ± 19.4) as compared to control group in female rats. ND supplementation (case group) significantly increased TC (64.4 ± 6.2), AST (255.0 ± 32.0), and ALT (84.3 ± 3.8) in comparison with the control group in male rats. CONCLUSION Overall, our result indicated that the ND use can cause a negative effect on lipid profile and liver enzyme in rats. PMID:26478734

  18. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increases endoxifen serum concentrations without increasing side effects.

    PubMed

    Dezentjé, V O; Opdam, F L; Gelderblom, H; Hartigh den, J; Van der Straaten, T; Vree, R; Maartense, E; Smorenburg, C H; Putter, H; Dieudonné, A S; Neven, P; Van de Velde, C J H; Nortier, J W R; Guchelaar, H-J

    2015-10-01

    Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment. CYP2D6 poor and intermediate metabolizers may need a personalized increased tamoxifen dose to achieve effective endoxifen serum concentrations, without increasing toxicity. From a prospective study population of early breast cancer patients using tamoxifen (CYPTAM: NTR1509), 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during 2 months. The escalated dose was calculated by multiplying the individual's endoxifen level at baseline relative to the average endoxifen concentration observed in CYP2D6 extensive metabolizers by 20 mg (120 mg maximum). Endoxifen levels and tamoxifen toxicity were determined at baseline and after 2 months, just before patients returned to the standard dose of 20 mg. Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (p < 0.001; p = 0.002, respectively) without increasing side effects. In intermediate metabolizers, dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers. In poor metabolizers, the mean endoxifen level increased from 24 to 81 % of the mean concentration in extensive metabolizers. In all patients, the endoxifen threshold of 5.97 ng/ml (=16.0 nM) reported by Madlensky et al. was reached following dose escalation. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increased endoxifen concentrations without increasing short-term side effects. Whether such tamoxifen dose escalation is effective and safe in view of long-term toxic effects is uncertain and needs to be explored. PMID:26369533

  19. Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies

    SciTech Connect

    Wang, Yuehai; Huang, Ziyang; Lu, Huixia; Lin, Huili; Wang, Zhenhua; Chen, Xiaoqing; Ouyang, Qiufang; Tang, Mengxiong; Hao, Panpan; Ni, Jingqin; Xu, Dongming; Zhang, Mingxiang; Zhang, Qunye; Lin, Ling; and others

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer Titers of ANA and anti-dsDNA antibodies were higher in ApoE{sup -/-} than C57B6/L mice. Black-Right-Pointing-Pointer Spleen was greater and splenocyte apoptosis lower in ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer Level of TLR4 was lower in spleen tissue of ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer The TLR4 pathway may participate in maintaining the balance of splenocyte apoptosis. Black-Right-Pointing-Pointer The TLR4 pathway may participate in antibody production in spleen tissue. -- Abstract: Apolipoprotein E-knockout (ApoE{sup -/-}) mice, atherosclerosis-prone mice, show an autoimmune response, but the pathogenesis is not fully understood. We investigated the pathogenesis in female and male ApoE{sup -/-} mice. The spleens of all ApoE{sup -/-} and C57BL/6 (B6) mice were weighed. The serum IgG level and titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody were assayed by ELISA. Apoptosis of spleen tissue was evaluated by TUNEL. TLR4 level in spleen tissue was tested by immunohistochemistry and Western blot analysis. Levels of MyD88, p38, phosphorylated p38 (pp38), interferon regulatory factor 3 (IRF3) and Bcl-2-associated X protein (Bax) in spleen tissue were detected by Western blot analysis. We also survey the changes of serum autoantibodies, spleen weight, splenocyte apoptosis and the expressions of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue in male ApoE{sup -/-} mice after 4 weeks of lipopolysaccharide (LPS), Toll-like receptor 4 ligand, administration. ApoE{sup -/-} mice showed splenomegaly and significantly increased serum level of IgG and titers of ANA and anti-dsDNA antibody as compared with B6 mice. Splenocyte apoptosis and the expression of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue were significantly lower in ApoE{sup -/-} than B6 mice. The expression of TLR4, MyD88, IRF3, pp38, and Bax differed by sex in ApoE{sup -/-} spleen tissue. The

  20. Effect of Increasing Maximal Aerobic Exercise on Serum Muscles Enzymes in Professional Field Hockey Players

    PubMed Central

    Hazar, Muhsin; Otağ, Aynur; Otağ, İlhan; Sezen, Mehmet; Sever, Ozan

    2015-01-01

    Background and Objectives: Exercise results in oxidative enzyme increase and micro-injuries in skeletal muscles. The aim of this study was to investigate the effect of maximal aerobic exercise on serum muscle enzymes in professional field hockey players. This study aims to determine the effect of increasing maximal aerobic exercise on creatine kinase (CK), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. Material and Methods: 31 young professional field hockey players (13 female and 18 male players) volunteered for this study. All participants underwent the shuttle run test. Blood samples were taken from each participant before the shuttle run test. Post test blood samples were taken immediately after exercise and one hour after respectively. Pre and post test CK, CK-MB, AST and ALT values were measured by means of auto analyzer using original kits. Results: The acute post test measure of the CK level increased in male (p=0.002) and female (p=0.00) sportsmen. CK-MB values obtained one hour after the exercise was lower than those before the exercise in males (p=0.02). In females (p=0.017) and males (p=0.05) AST activity significantly increased immediately after exercise and decreased to resting activity 1 h recovery. ALT significantly increased immediately after exercise in female (p=0.03) and male (p=0.00) athletes and after 1 h recovery ALT activities decreased below resting values. Conclusion: The timing and severity of exercise used in our study increased CK values, decreased CK-MB values and AST, ALT values increased in female and male field hockey players. PMID:25948428

  1. The vitamin E-binding protein afamin increases in maternal serum during pregnancy

    PubMed Central

    Hubalek, Michael; Buchner, Hannes; Mörtl, Manfred G.; Schlembach, Dietmar; Huppertz, Berthold; Firulovic, Branka; Köhler, Wolfgang; Hafner, Erich; Dieplinger, Benjamin; Wildt, Ludwig; Dieplinger, Hans

    2014-01-01

    Background Afamin is a liver-derived plasma glycoprotein with vitamin E-binding properties and a putative function in fertility. This study evaluated serum afamin concentrations during and postpartum to uncomplicated pregnancies and investigated a potential association between afamin concentrations and pregnancy outcome. Methods Afamin serum concentrations were measured in women with uncomplicated pregnancies in a retrospective cohort (n = 466) at different gestational ages and a prospective observational study (n = 76) in the first, second and third trimester. Furthermore, afamin was determined in the first trimester in a cross-sectional pilot study including women with preeclampsia (PE), pregnancy-induced hypertension (PIH) and women without pregnancy complications (n = 13 each). Finally, expression of afamin was investigated in human placental tissue by RT-PCR and immunohistochemistry. Results Afamin concentrations increased linearly almost two-fold during pregnancy in both retrospective and prospective studies in women without pregnancy complications with median afamin serum concentrations of 61.9 mg/l, 79.6 mg/l, and 98.6 mg/l in the first, second, and third trimester, respectively. After delivery, median afamin concentrations decreased to baseline values of 54.6 mg/l. In the pilot study with pregnancy complications, women with PE displayed significantly higher median afamin concentrations than did women with uncomplicated pregnancy (70.0 mg/l vs. 55.4 mg/l, P = 0.007). Expression analyses revealed no placental afamin expression at either mRNA or protein level in uncomplicated pregnancy. Conclusion A linear increase in the maternally expressed glycoprotein afamin during pregnancy may serve as basic reference for subsequent investigations of afamin in pregnancy-related disorders. PMID:24768783

  2. Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations

    SciTech Connect

    Mason-Garcia, M.; Vigh, S.; Comaru-Schally, A.M.; Redding, T.W.; Somogyvari-Vigh, A.; Horvath, J.; Schally, A.V.

    1985-03-01

    A sensitive and specific radioimmunoassay for (6-D-tryptophan)luteinizing hormone-releasing hormone ((D-Trp/sup 6/)LH-RH) was developed and used for following the rate of liberation of (D-Trp/sup 6/)LH-RH from a long-acting delivery systems based on a microcapsule formulation. Rabbit antibodies were generated against (D-Trp/sup 6/)LH-RH conjugated to bovine serum albumin with glutaraldehyde. Crossreactivity with LH-RH was less than 1%; there was no significant cross-reactivity with other peptides. The minimal detectable dose of (D-Trp/sup 6/)LH-RH was 2 pg per tube. In tra- and interassay coefficients of variation were 8% and 10%, respectively. The radioimmunoassay was suitable for direct determination of (D-Trp/sup 6/)LH-RH in serum, permitting the study of blood levels of the analog after single injections into normal men and after one-a-month administration of microcapsules to rats. In men, 90 min after subcutaneous injection of 250 ..mu..g of the peptide, serum (D-Trp/sup 6/)LH-RH rose to 6-12 ng/ml. Luteinizing hormone was increased 90 min and 24 hr after the administration of the analog. Several batches of microcapsules were tested in rats and the rate of release of (D-Trp/sup 6/)LH-RH was followed. The improved batch of microcapsules of (D-Trp/sup 6/)LH-RH increased serum concentrations of the analog for 30 days or longer after intramuscular injection.

  3. Interleukin-17 SNPs and serum levels increase ulcerative colitis risk: A meta-analysis

    PubMed Central

    Li, Juan; Tian, Hao; Jiang, Hui-Jun; Han, Bin

    2014-01-01

    AIM: To investigate the associations of interleukin-17 (IL-17) genetic polymorphisms and serum levels with ulcerative colitis (UC) risk. METHODS: Relevant articles were identified through a search of the following electronic databases, excluding language restriction: (1) the Cochrane Library Database (Issue 12, 2013); (2) Web of Science (1945-2013); (3) PubMed (1966-2013); (4) CINAHL (1982-2013); (5) EMBASE (1980-2013); and (6) the Chinese Biomedical Database (1982-2013). Meta-analysis was conducted using STATA 12.0 software. Crude odds ratios and standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were calculated. All of the included studies met all of the following five criteria: (1) the study design must be a clinical cohort or a case-control study; (2) the study must relate to the relationship between IL-17A/F genetic polymorphisms or serum IL-17 levels and the risk of UC; (3) all patients must meet the diagnostic criteria for UC; (4) the study must provide sufficient information about single nucleotide polymorphism frequencies or serum IL-17 levels; and (5) the genotype distribution of healthy controls must conform to the Hardy-Weinberg equilibrium (HWE). The Newcastle-Ottawa Scale (NOS) criteria were used to assess the methodological quality of the studies. The NOS criteria included three aspects: (1) subject selection: 0-4; (2) comparability of subjects: 0-2; and (3) clinical outcome: 0-3. NOS scores ranged from 0 to 9, with a score ≥ 7 indicating good quality. RESULTS: Of the initial 177 articles, only 16 case-control studies met all of the inclusion criteria. A total of 1614 UC patients and 2863 healthy controls were included in this study. Fourteen studies were performed on Asian populations, and two studies on Caucasian populations. Results of the meta-analysis revealed that IL-17A and IL-17F genetic polymorphisms potentially increased UC risk under both allele and dominant models (P < 0.001 for all). The results also

  4. Effect of Glutathione Administration on Serum Levels of Reactive Oxygen Metabolites in Patients with Paraquat Intoxication: A Pilot Study

    PubMed Central

    Kim, Jung-Hoon; Gil, Hyo-Wook; Yang, Jong-Oh; Lee, Eun-Young

    2010-01-01

    Background/Aims Based on preliminary in vitro data from a previous study, we proposed that 50 mg/kg glutathione (GSH) would be adequate for suppressing reactive oxygen species in patients with acute paraquat (PQ) intoxication. Methods Serum levels of reactive oxygen metabolites (ROM) were measured before and after the administration of 50 mg/kg GSH to each of five patients with acute PQ intoxication. Results In one patient, extremely high pretreatment ROM levels began to decrease prior to GSH administration. However, in the remaining four cases, ROM levels did not change significantly prior to GSH administration. ROM levels decreased significantly after GSH administration in all cases. In two cases, ROM levels decreased below that observed in the general population; one of these patients died after a cardiac arrest at 3 hours after PQ ingestion, while the other represented the sole survivor of PQ intoxication observed in this study. In the survivor, ROM levels decreased during the first 8 hours of GSH treatment, and finally dropped below the mean ROM level observed in the general population. Conclusions Treatment with 50 mg/kg GSH significantly suppressed serum ROM levels in PQ-intoxicated patients. However, this dose was not sufficient to suppress ROM levels when the PQ concentration was extremely high. PMID:20830225

  5. Increase of urinary and serum hydroxyproline in subjects exposed to cadmium

    SciTech Connect

    Nishino, H.; Tanaka, T.; Shiroishi, K.; Sato, S. ); Naruse, Y.; Kagamimori, S. )

    1991-10-01

    Itai-itai disease (I disease) is characterized mainly by renal tubular damage and osteomalacia accompanied by osteoporosis in subjects with long-term ingestion of excessive cadmium (Cd). Most of the studies on the osteopathies of this disease have focused on mineral metabolism. For a better understanding of the osteopathies of I disease, the authors have been interested in collagen metabolism in relation to that of minerals. It is possible that the increased urinary concentration of Hyp may be associated with the osteopathies of patients with I disease. To provide more information about the increased urinary concentration resulting from Cd exposure the measurement of serum concentration of Hyp was also carried out in the present study.

  6. Effectiveness of different corticosterone administration methods to elevate corticosterone serum levels, induce depressive-like behavior, and affect neurogenesis levels in female rats.

    PubMed

    Kott, J M; Mooney-Leber, S M; Shoubah, F A; Brummelte, S

    2016-01-15

    High levels of chronic stress or stress hormones are associated with depressive-like behavior in animal models. However, slight elevations in corticosterone (CORT) - the major stress hormone in rodents - have also been associated with improved performances, albeit in a sex-dependent manner. Some of the discrepancies in the literature regarding the effects of high CORT levels may be due to different administrations methods. The current study aims to compare the effects of ∼40mg/kg given either via subcutaneous injection, through an implanted pellet, or in the drinking water, for ∼21days on CORT serum levels, depressive-like behavior in the forced swim test (FST), and neurogenesis levels in the dentate gyrus (DG) in adult female rats. We found that animals exposed to the daily injections showed elevated CORT levels throughout the administration period, while the pellet animals showed only a transient increase, and drinking water animals revealed no elevation in CORT in serum. In addition, only the injection group exhibited higher levels of immobility in the FST. Interestingly, animals receiving CORT via injection or drinking water had lower numbers of doublecortin-positive cells in the ventral DG one week after the last CORT administration compared to animals implanted with a CORT pellet. These results will contribute to the growing literature on the effects of chronic CORT exposure and may help to clarify some of the discrepancies among previous studies, particularly in females. PMID:26556064

  7. Serum D-Dimer Concentrations are Increased after Pediatric Traumatic Brain Injury

    PubMed Central

    Berger, Rachel P.; Fromkin, Janet; Rubin, Pam; Snyder, John; Richichi, Rudolph; Kochanek, Patrick

    2015-01-01

    Objective To determine whether d-dimer would be increased in children with traumatic brain injury (TBI), specifically mild abusive head trauma (AHT). Study design D-dimer was measured using multiplex bead technology in 195 children <4 years old (n=93 controls without TBI, n=102 cases with TBI) using previously collected serum. D-dimer was then measured prospectively in a clinical setting in 44 children (n=24 controls, n=20 cases). Receiver operator curves (ROC) were generated for prospective data. Results In both the retrospective and prospective cohorts, median (25th–75th percentile) d-dimer was significantly higher in cases vs. controls. An ROC demonstrated an area under the curve (AUC) of 0.91 (95% CI: 0.83 – 0.99) in the prospective cohort. At a cut-off of 0.59μg/L, the sensitivity and specificity for identification of a case was 90% and 75%, respectively. Conclusions Our data suggest that serum d-dimer may be able to be used to identify which young children at risk for AHT might benefit from a head computer tomography or other additional evaluation. Additional data are needed in order to better identify the clinical scenarios which may result in false positive or false negative d-dimer concentrations. PMID:25454315

  8. Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis.

    PubMed

    Kraut, Jeffrey A; Xing, Shelly Xiaolei

    2011-09-01

    An increase in serum osmolality and serum osmolal gap with or without high-anion-gap metabolic acidosis is an important clue to exposure to one of the toxic alcohols, which include methanol, ethylene glycol, diethylene glycol, propylene glycol, or isopropanol. However, the increase in serum osmolal gap and metabolic acidosis can occur either together or alone depending on several factors, including baseline serum osmolal gap, molecular weight of the alcohol, and stage of metabolism of the alcohol. In addition, other disorders, including diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis, can cause high-anion-gap metabolic acidosis associated with an increased serum osmolal gap and therefore should be explored in the differential diagnosis. It is essential for clinicians to understand the value and limitations of osmolal gap to assist in reaching the correct diagnosis and initiating appropriate treatment. In this teaching case, we present a systematic approach to diagnosing high serum osmolality and increased serum osmolal gap with or without high-anion-gap metabolic acidosis. PMID:21794966

  9. Midlevel Administrators' Pay Increases Slightly but Doesn't Match Inflation

    ERIC Educational Resources Information Center

    Fuller, Andrea

    2012-01-01

    Salaries for midlevel administrators rose by a median of 2 percent this year over last year, matching the median pay increase for senior administrators and coming in slightly higher than the 1.9-percent median increase for faculty members, says an annual report released by the College and University Professional Association for Human Resources.…

  10. Increased serum urea to creatinine ratio and its negative correlation with arterial pressure in canine babesiosis.

    PubMed

    Zygner, Wojciech; Gójska-Zygner, Olga

    2014-09-01

    The increase of the serum urea to creatinine ratio (UCR) was observed in dogs infected with Babesia canis. Previous studies have suggested that decrease of blood pressure can be one of the reasons for this phenomenon. In this work statistically significant increase of the UCR was observed in dogs with babesiosis. Comparison of the UCR between 23 azotaemic dogs and 25 non-azotaemic dogs infected with Babesia canis showed statistically significantly higher mean of the UCR in azotaemic dogs. Correlations between UCR and systolic, diastolic and mean arterial pressure (SAP, DAP and MAP) in 48 dogs infected with B. canis were negative (UCR and SAP: r = -0.3909; UCR and DAP: r = -0.3182; UCR and MAP: r = -0.3682) and statistically significant (p < 0.05). This result may indicate contribution of hypotension in the increase of the UCR in canine babesiosis. However, the correlations were not high, and there was no statistically significant correlation between UCR and arterial pressures in azotaemic dogs. Thus, it seems that decrease of blood pressure in dogs with babesiosis explains only partially the cause of increased UCR in infected dogs. The other authors suggested hyperureagenesis and myocardial injury as a potential reason for the increased UCR in canine babesiosis. Thus, further studies are needed to determine causes of increased UCR in dogs with babesiosis, especially on the connection between UCR changes and the concentrations of plasma cardiac troponins and ammonia, and the occurrence of occult blood on fecal examination. PMID:25119372

  11. Exercise increases serum endostatin levels in female and male patients with diabetes and controls

    PubMed Central

    2014-01-01

    Background Type 2 diabetes mellitus (T2DM) is often associated with atherosclerotic changes in coronary vessels, most notably plaques. The angiostatic parameter endostatin is able to inhibit angiogenesis in tissue as well as in plaques and therefore plays an important role in physiological and pathological neovascularisation. The aim of the present study was to investigate sex-specific differences and the influence of exercise on circulating endostatin levels in patients suffering from diabetes, and control subjects. Methods In total, 42 T2DM-patients and 45 control subjects were investigated. They underwent a graded physical stress test (ergometry). Serum endostatin levels were measured in venous blood at rest and directly after reaching maximum workload. Results Females showed significantly higher endostatin levels at baseline measurements compared to men, independently of their underlying disease. In both female and male T2DM-patients endostatin levels were significantly lower compared to controls. Both groups and sexes showed a significant increase of endostatin after physical stress, whereas the extent of endostatin-increase was between 10.59-15.05%. Conclusion Middle-aged healthy female individuals as well as female T2DM-patients showed higher circulating serum endostatin levels compared to males, suggesting a hormonal influence on baseline circulating endostatin amounts. Exercise-induced increase in endostatin is also observable in patients suffering from T2DM. Concerning vascularisation, lower endostatin levels in T2DM might be advantageous. Concerning plaque stability, lower levels might be prejudicial. Trial registration Clinical Trial Registration-URL: http://clinicaltrials.gov/ct2/results?term=NCT01165515 PMID:24393402

  12. Advanced Gestational Age Increases Serum Carbohydrate-Deficient Transferrin Levels in Abstinent Pregnant Women

    PubMed Central

    Bakhireva, Ludmila N.; Cano, Sandra; Rayburn, William F.; Savich, Renate D.; Leeman, Lawrence; Anton, Raymond F.; Savage, Daniel D.

    2012-01-01

    Aims: Carbohydrate-deficient transferrin (%CDT) is a well-established and highly specific biomarker for sustained heavy consumption of alcohol. However, in pregnant women, the specificity of this biomarker might be affected by advanced gestational age, even after accounting for increased transferrin concentrations in pregnancy. The goal of this prospective study was to assess the variability in %CDT during pregnancy among alcohol-abstaining patients. Methods: Patients were recruited during one of the first prenatal care visits and followed-up to term. Abstinence was confirmed by maternal self-report and by alcohol biomarkers. Biomarkers assessed in the mother included serum gamma-glutamyltranspeptidase, urine ethyl glucuronide and ethyl sulfate, and whole blood phosphatidylethanol (PEth). In addition, PEth was measured in a dry blood spot card obtained from a newborn. For %CDT analysis, serum samples were collected at baseline and at term and analyzed by an internationally validated high-performance liquid chromatography and spectrophotometric detection method. Results: At recruitment (mean gestational age 22.6 ± 7.3 weeks), the mean %CDT concentration was 1.49 ± 0.30%, while at term, it increased to 1.67 ± 0.28% (P = 0.001). Using a conventional cutoff concentration %CDT >1.7%, 22.9 and 45.7% of the sample would be classified as ‘positive’ for this biomarker at recruitment and at term, respectively (P = 0.011 ). Conclusion: These results suggest that a conventional cutoff of 1.7% might be too low for pregnant women and would generate false-positive results. We propose that %CDT >2.0% be used as a cutoff concentration indicative of alcohol exposure in pregnant women. The sensitivity of %CDT at this cutoff for heavy drinking during pregnancy needs to be assessed further. PMID:22878591

  13. Parenteral nutrition in short bowel syndrome patients, regardless of its duration, increases serum proinflammatory cytokines.

    PubMed

    Bizari, Letícia; da Silva Santos, Andressa Feijó; Foss, Norma Tiraboschi; Marchini, Júlio Sérgio; Suen, Vivian Marques Miguel

    2016-07-01

    Short bowel syndrome is a severe malabsorption disorder, and prolonged parenteral nutrition is essential for survival in some cases. Among the undesirable effects of long-term parenteral nutrition is an increase in proinflammatory cytokines. The aim of the present study was to measure the serum levels of interleukin-6, interleukin-10, tumor necrosis factor alpha, and transforming growth factor beta, in patients with short bowel syndrome on cyclic parenteral nutrition and patients who had previously received but no longer require parenteral nutrition. The study was cross-sectional and observational. Three groups were studied as follows: Parenteral nutrition group, 9 patients with short bowel syndrome that receive cyclic parenteral nutrition; Oral nutrition group, 10 patients with the same syndrome who had been weaned off parenteral nutrition for at least 1 year prior to the study; Control group, 13 healthy adults, matched for age and sex to parenteral and oral groups. The following data were collected: age, tobacco use, drug therapies, dietary intake, body weight, height, blood collection. All interleukins were significantly higher in the parenteral group compared with the control group as follows: interleukin-6: 22 ± 19 vs 1.5 ± 1.4 pg/mL, P= .0002; transforming growth factor β: 854 ± 204 vs 607 ± 280 pg/mL, P= .04; interleukin-10: 8 ± 37 vs 0.6 ± 4, P= .03; tumor necrosis factor α: 20 ± 8 vs 8 ± 4 pg/mL, P< .0001. We concluded that parenteral nutrition in short bowel syndrome patients, regardless of its duration, increases serum proinflammatory cytokines. PMID:27267135

  14. Increasing and decreasing phases of ferritin and hemosiderin iron determined by serum ferritin kinetics.

    PubMed

    Saito, Hiroshi; Hayashi, Hisao; Tomita, Akihiro; Ohashi, Haruhiko; Maeda, Hideaki; Naoe, Tomoki

    2013-08-01

    We attempted to clarify the mechanism of the storage iron metabolism. A new program of serum ferritin kinetics was applied for studying the increasing and decreasing phases of ferritin and hemosiderin iron in iron addition and removal in patients with a normal level of iron stores or iron overload. The change of ferritin iron in response to iron addition and removal was rapid in the initial stage, but it was slow later. In contrast, the change of hemosiderin iron was slow in the initial stage, but it became rapid later. These changes of ferritin and hemosiderin iron suggest that the turnover of ferritin iron is preferential to that of hemosiderin iron, and that the initially existed ferritin iron is gradually replaced by the ferritin iron recovered by taking iron from hemosiderin in iron mobilization. The crossing of the increasing curves of ferritin and hemosiderin iron in iron addition indicates a switching of the principal storage iron from ferritin to hemosiderin. The crossing point shifted toward a higher storage iron level in the increase of iron deposition. Iron storing capacity can be increased not only by the transformation of ferritin into hemosiderin, but also by the expansion of cell space as seen by hepatomegaly in hereditary hemochromatosis. The amounts of hemosiderin iron exceeded ferritin iron in all 10 patients with chronic hepatitis C even though they had normal storage iron levels. This suggests it is difficult to store iron in the form of ferritin in chronic hepatitis C. PMID:24640177

  15. Antibody Responses in Serum, Secretions, and Urine of Man After Parenteral Administration of Vaccines

    PubMed Central

    Sirisinha, Stitaya; Charupatana, Chinda

    1970-01-01

    The nature of antibody activities associated with purified immunoglobulin fractions of serum, secretions (whole saliva, parotid secretion, and intestinal secretion), and urine of a volunteer after subcutaneous booster injections with rabies virus, poliovirus, diphtheria and tetanus toxoids, and typhoid-paratyphoid-cholera vaccines was investigated. The results showed that the pattern of antibody responses in these fluids differed from one antigen to another. Serum-antibody responses to killed-bacterial vaccine were associated mainly with the immunoglobulin M (IgM) component, slight activities were detected in the IgG, and only traces of activities, if any, were found in the IgA. These antibodies were primarily of the secretory IgA type in whole saliva and parotid secretion. Slight activities were also observed in the urinary IgG fraction. Responses to inactivated viral vaccine and toxoids were almost exclusively associated with the serum IgG component. Some antitoxic activities to diphtheria and tetanus toxins were noted in a low-molecular-weight urinary immunoglobulin component. PMID:16557795

  16. Increased Serum Level of Cyclopropaneoctanoic Acid 2-Hexyl in Patients with Hypertriglyceridemia-Related Disorders.

    PubMed

    Mika, Adriana; Stepnowski, Piotr; Chmielewski, Michal; Malgorzewicz, Sylwia; Kaska, Lukasz; Proczko, Monika; Ratnicki-Sklucki, Krzysztof; Sledzinski, Maciej; Sledzinski, Tomasz

    2016-07-01

    We recently reported the presence of various cyclopropane fatty acids-among them, cyclopropaneoctanoic acid 2-hexyl-in the adipose tissue of obese women. The aim of this study was to verify whether the presence of cyclopropaneoctanoic acid 2-hexyl in human serum was associated with obesity or chronic kidney disease (both being related to dyslipidemia), and to find potential associations between the serum level of this compound and specific markers of the these conditions. The serum concentration of cyclopropaneoctanoic acid 2-hexyl was determined by gas chromatography-mass spectrometry (GC-MS) in non-obese controls, obese patients, obese patients after a 3-month low-calorie diet, and individuals with chronic kidney disease. Obese patients and those with chronic kidney disease presented with higher serum levels of cyclopropaneoctanoic acid 2-hexyl than controls. Switching obese individuals to a low-calorie (low-lipid) diet resulted in a reduction in this fatty acid concentration to the level observed in controls. Cyclopropaneoctanoic acid 2-hexyl was also found in foods derived from animal fat. Serum concentrations of triacylglycerols in the analyzed groups followed a pattern similar to that for serum cyclopropaneoctanoic acid 2-hexyl, and these variables were positively correlated with each other among the studied groups. Patients with hypertriglyceridemia-related conditions presented with elevated serum levels of cyclopropaneoctanoic acid 2-hexyl. Our findings suggest that its high serum level is related to high serum triacylglycerol concentrations rather than to body mass or BMI. PMID:27003900

  17. Increased serum HMGB1 levels in patients with Henoch-Schönlein purpura.

    PubMed

    Chen, Tao; Guo, Zai-Pei; Wang, Wen-Ju; Qin, Sha; Cao, Na; Li, Meng-Meng

    2014-06-01

    High-mobility group box-1 (HMGB1) has been implicated as a pro-inflammatory cytokine in the pathogenesis of various inflammatory and autoimmune diseases. However, information about HMGB1 in Henoch-Schönlein purpura (HSP) is still unclear. Herein, we investigated the role of HMGB1 in patients with HSP and the pro-inflammatory effects of HMGB1 on human dermal microvascular endothelial cell line (HMEC-1). Serum HMGB1 levels in patients with HSP together with patients with allergic vasculitis (AV) and urticarial vasculitis (UV) were detected by enzyme-linked immunosorbent assay (ELISA). HMEC-1 cells were treated with HMGB1 at concentrations ranging from 4 ng/ml to 100 ng/ml. Serum HMGB1 levels were significantly increased in patients with HSP, AV and UV, when compared with those in control group. Moreover, abundant cytoplasmic expression of HMGB1 was observed in endothelial cells in lesional skin of HSP patients. Using membrane cytokine antibody array, we indicate that HMGB1 markedly induced TNF-α and IL-6 release in cultured supernatant. Furthermore, by real-time quantitative PCR and ELISA, the effects of HMGB1 on these cytokines production in HMEC-1 cells were established. Finally, Western blot data revealed that HMGB1 can induce phosphorylation of inhibitor of κB-α (IκBα) and the nuclear translocation of nuclear factor-κB (NF-κB) p65 in HMEC-1 cells. In conclusion, this study provides first observations on the association of HMGB1 with HSP. We suggest that HMGB1 may be an important mediator of endothelial inflammation through the induction of TNF-α and IL-6 production and may play a crucial role in the pathogenesis of HSP. PMID:24758390

  18. Increase of serum potassium in the upright posture in selective hypoaldosteronism.

    PubMed

    Radó, J P; Simatupang, T; Boer, P; Mees, E J

    1979-01-01

    The effect of a 4 hr upright posture on serum potassium (SK) levels was investigated in a certain group of hospitalized renal patients with selective hypoaldosteronism and in healthy subjects. Significant (p less than 0.001) postural increase in SK (0.4 MMol/L) was found only in the 3 young patients with chronic glomerulonephritis and hypoaldosteronism who presented with hyperkalemia (5.84 +/- 0.13 mMol/L) as outpatients, but showed a marked improvement toward normokalemia (4.95 +/- 0.13 mMol/L; p less than 0.001) within the hospital without any specific treatment. In healthy persons in the fastqng condition the influence of the upright position of short duration (45 min) was also studied on SK and a very small but significant increase (0.15 mMol/L) was found. It was concluded: 1. the postural SK INCREASE MAY OFFER AN--AT LEAST PARTIAL--EXPLANTATION FOR THE "OUTPATIENT HYPERKALEMIA", 2. The normal activity of renin-angiotensinaldosterone system may play a role in the counteraction of the trend for SK rise in the upright posture. PMID:428908

  19. 20 CFR 641.870 - Under what circumstances may the administrative cost limitation be increased?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Under what circumstances may the administrative cost limitation be increased? 641.870 Section 641.870 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT...

  20. Extension Master Gardener Intranet: Automating Administration, Motivating Volunteers, Increasing Efficiency, and Facilitating Impact Reporting

    ERIC Educational Resources Information Center

    Bradley, Lucy K.; Cook, Jonneen; Cook, Chris

    2011-01-01

    North Carolina State University has incorporated many aspects of volunteer program administration and reporting into an on-line solution that integrates impact reporting into daily program management. The Extension Master Gardener Intranet automates many of the administrative tasks associated with volunteer management, increasing efficiency, and…

  1. Vascular endothelial growth factor (VEGF) is increased in serum, but not in cerebrospinal fluid in HIV associated CNS diseases.

    PubMed

    Sporer, B; Koedel, U; Paul, R; Eberle, J; Arendt, G; Pfister, H-W

    2004-02-01

    Vascular endothelial growth factor (VEGF) is a potent angiogenic and mitogenic peptide, which also induces several mediators that may play a role in HIV induced CNS damage. VEGF levels were determined in cerebrospinal fluid (CSF) and serum samples from patients with (n = 8) and without (n = 19) directly HIV associated CNS disorders and HIV negative control patients (n = 18). VEGF serum but not CSF levels were significantly increased in HIV infected patients with (381.1 (78.9) pg/ml) HIV associated CNS diseases compared with those without (120.8 (13.1) pg/ml) and HIV negative control patients (133.1(14.8) pg/ml). Serum samples from patients with untreated HIV associated encephalopathy (HIVE, n = 3) contained the highest VEGF levels (583.9 (71.5) pg/ml). In two patients VEGF serum levels were reduced during antiretroviral therapy. However, regardless of effective viral suppression, patients with HIVE still had higher levels compared with HIV infected patients without HIVE. A relevant increase of serum VEGF was not observed in patients without HIVE though high HI viral load. We conclude that HIVE is associated with increased serum VEGF levels. Further studies are warranted to elucidate the role of VEGF in HIVE. PMID:14742610

  2. Coenzyme Q10 Administration Increases Brain Mitochondrial Concentrations and Exerts Neuroprotective Effects

    NASA Astrophysics Data System (ADS)

    Matthews, Russell T.; Yang, Lichuan; Browne, Susan; Baik, Myong; Flint Beal, M.

    1998-07-01

    Coenzyme Q10 is an essential cofactor of the electron transport chain as well as a potent free radical scavenger in lipid and mitochondrial membranes. Feeding with coenzyme Q10 increased cerebral cortex concentrations in 12- and 24-month-old rats. In 12-month-old rats administration of coenzyme Q10 resulted in significant increases in cerebral cortex mitochondrial concentrations of coenzyme Q10. Oral administration of coenzyme Q10 markedly attenuated striatal lesions produced by systemic administration of 3-nitropropionic acid and significantly increased life span in a transgenic mouse model of familial amyotrophic lateral sclerosis. These results show that oral administration of coenzyme Q10 increases both brain and brain mitochondrial concentrations. They provide further evidence that coenzyme Q10 can exert neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.

  3. Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage.

    PubMed Central

    Bruunsgaard, H; Galbo, H; Halkjaer-Kristensen, J; Johansen, T L; MacLean, D A; Pedersen, B K

    1997-01-01

    1. This study was performed to test the hypothesis that the exercise-induced increase in circulating cytokine levels is associated with muscle damage. Nine healthy young male subjects performed two high-intensity bicycle exercise trials separated by two weeks. The first trial consisted of 30 min of normal bicycle exercise (concentric exercise), whereas the second consisted of 30 min of braking with reversed revolution (eccentric exercise). The work loads were chosen to give the same increases in heart rate and catecholamine levels in the blood during each trial. 2. Significant increases (P < 0.05) in plasma concentration of creatine kinase (CK), aspartate aminotransferase and alanine aminotransferase were observed only after the eccentric exercise. Furthermore, the level of interleukin-6 (IL-6) in serum increased significantly after the eccentric exercise and was significantly correlated to CK concentration in the following days, whereas no significant changes were found after the concentric exercise. 3. The total concentration of lymphocytes increased significantly (P < 0.05) as a result of eccentric compared with concentric exercise. This was mainly due to a significantly more pronounced recruitment of natural killer (NK) cells and CD8 positive cells (CD8+ cells) during the eccentric trial. However, no significant differences between the two types of work were found in regard to the circulating concentration of monocytes. The concentration of neutrophils was only significantly increased 2 h after the concentric exercise. 4. The finding that high-intensity eccentric exercise caused a more pronounced increase in the plasma level of IL-6, compared with concentric exercise, supports the hypothesis that the post-exercise cytokine production is related to skeletal muscle damage. The fact that no differences between eccentric and concentric exercise were found in the recruitment of most blood mononuclear cell subsets to the blood supports the hypothesis that the

  4. NZ-GMP Approved Serum Improve hDPSC Osteogenic Commitment and Increase Angiogenic Factor Expression.

    PubMed

    Spina, Anna; Montella, Roberta; Liccardo, Davide; De Rosa, Alfredo; Laino, Luigi; Mitsiadis, Thimios A; La Noce, Marcella

    2016-01-01

    Human dental pulp stem cells (hDPSCs), selected from the stromal-vascular fraction of dental pulp, are ecto-mesenchymal stem cells deriving from neural crests, successfully used in human bone tissue engineering. For their use in human therapy GMP procedures are required. For instance, the use of fetal bovine serum (FBS) is strongly discouraged in clinical practice due to its high risk of prions and other infections for human health. Alternatively, clinical grade sera have been suggested, including the New Zealand FBS (NZ-FBS). Therefore, the aim of this study was to evaluate the behavior of hDPSCs expanded in culture medium containing NZ-FBS. Since it was widely demonstrated hDPSCs display relevant capabilities to differentiate into osteogenic and angiogenic lineages, we performed a comparative study to assess if these features are also retained by cultivating the cells with a safer serum never tested on this cell line. hDPSCs were grown using NZ-FBS and conventional (C-FBS) for 7, 14, and 21 days, in both 2D and 3D cultures. Growth curves, expression of bone-related markers, calcification and angiogenesis were evaluated. NZ-FBS induced significant cell growth with respect to C-FBS and promoted an earlier increase expression of osteogenic markers, in particular of those involved in the formation of mineralized matrix (BSP and OPN) within 14 days. In addition, hDPSCs cultured in presence of NZ-FBS were found to produce higher mRNA levels of the angiogenic factors, such as VEGF and PDGFA. Taken together, our results highlight that hDPSCs proliferate, enhance their osteogenic commitment and increase angiogenic factors in NZ-FBS containing medium. These features have also been found when hDPSC were seeded on the clinical-grade collagen I scaffold (Bio-Gide®), leading to the conclusion that for human therapy some procedures and above all the use of GMP-approved materials have no negative impact. PMID:27594842

  5. NZ-GMP Approved Serum Improve hDPSC Osteogenic Commitment and Increase Angiogenic Factor Expression

    PubMed Central

    Spina, Anna; Montella, Roberta; Liccardo, Davide; De Rosa, Alfredo; Laino, Luigi; Mitsiadis, Thimios A.; La Noce, Marcella

    2016-01-01

    Human dental pulp stem cells (hDPSCs), selected from the stromal-vascular fraction of dental pulp, are ecto-mesenchymal stem cells deriving from neural crests, successfully used in human bone tissue engineering. For their use in human therapy GMP procedures are required. For instance, the use of fetal bovine serum (FBS) is strongly discouraged in clinical practice due to its high risk of prions and other infections for human health. Alternatively, clinical grade sera have been suggested, including the New Zealand FBS (NZ-FBS). Therefore, the aim of this study was to evaluate the behavior of hDPSCs expanded in culture medium containing NZ-FBS. Since it was widely demonstrated hDPSCs display relevant capabilities to differentiate into osteogenic and angiogenic lineages, we performed a comparative study to assess if these features are also retained by cultivating the cells with a safer serum never tested on this cell line. hDPSCs were grown using NZ-FBS and conventional (C-FBS) for 7, 14, and 21 days, in both 2D and 3D cultures. Growth curves, expression of bone-related markers, calcification and angiogenesis were evaluated. NZ-FBS induced significant cell growth with respect to C-FBS and promoted an earlier increase expression of osteogenic markers, in particular of those involved in the formation of mineralized matrix (BSP and OPN) within 14 days. In addition, hDPSCs cultured in presence of NZ-FBS were found to produce higher mRNA levels of the angiogenic factors, such as VEGF and PDGFA. Taken together, our results highlight that hDPSCs proliferate, enhance their osteogenic commitment and increase angiogenic factors in NZ-FBS containing medium. These features have also been found when hDPSC were seeded on the clinical-grade collagen I scaffold (Bio-Gide®), leading to the conclusion that for human therapy some procedures and above all the use of GMP-approved materials have no negative impact. PMID:27594842

  6. Long-term testosterone administration increases visceral fat in female to male transsexuals.

    PubMed

    Elbers, J M; Asscheman, H; Seidell, J C; Megens, J A; Gooren, L J

    1997-07-01

    The amount of intraabdominal (visceral) fat is an important determinant of disturbances in lipid and glucose metabolism. Cross-sectional studies in women have found associations between high androgen levels and visceral fat accumulation. The causal relation between these phenomena is unknown. We, therefore, studied prospectively the effect of testosterone administration on body fat distribution in 10 young, nonobese, female to male transsexuals undergoing sex reassignment. Before, after 1 yr, and after 3 yr of testosterone administration, magnetic resonance images were obtained at the level of the abdomen, hip, and thigh to quantify both sc and visceral fat depots. After 1 yr of testosterone administration, sc fat depots at all levels showed significant reductions compared to baseline measurements. The mean visceral fat area did not change significantly, but subjects who gained weight in the first year after testosterone administration showed an increase in visceral fat. After 3 yr of testosterone administration, sc fat depots were no longer significantly lower compared to pretreatment measurements, but the mean visceral fat depot had increased significantly by 13 cm2 (95% confidence interval, 4-22 cm2), a relative increase of 47% (95% confidence interval, 8-91%) from baseline. The increase in visceral fat was most pronounced in those subjects who had gained weight. We conclude that long term testosterone administration in young, nonobese, female subjects increases the amount of visceral fat. In addition, an increase in weight in this hyperandrogenic state leads to a preferential storage of fat in the visceral depot. PMID:9215270

  7. Comparison Between Preoperative Administration of Methylprednisolone With its Administration Before and During Congenital Heart Surgery on Serum Levels of IL-6 And IL-10

    PubMed Central

    Abbasi Tashnizi, Mohammad; Soltani, Ghasem; Moeinipour, Ali Asghar; Ayatollahi, Hossein; Tanha, Amir Saber; Jarahi, Lida; Sepehri Shamloo, Alireza; Zirak, Nahid

    2013-01-01

    Background Steroid administration during cardiopulmonary bypass is considered to improve cardiopulmonary function by modulating inflammations caused by bypass. Objectives This study was performed to compare effectiveness of preoperative and intraoperative methylprednisolone (MP) to preoperative methylprednisolone alone in post bypass inflammatory (IL-6) and anti-inflammatory (IL-10) factors. Patients and Methods Fifty pediatric patients undergoing cardiopulmonary bypass surgery from August 2011 to 2012 in the cardiac surgery department of Imam Reza Hospital, the major center for CPB, in Mashhad, Iran were randomly assigned to receive preoperative and intraoperative MP (30 mg/kg, 4 hours before bypass and in bypass prime, number 25) or preoperative MP only (30 mg/kg, number 25). Before and after bypass, four and 24 hours after bypass, serum IL-6 and IL-10 were measured by ELISA. Results In both groups, no significant difference with variation of expression for IL-6 (inflammatory factor) and IL-10 (anti-inflammatory factor) in different times after bypass was observed. Conclusions No significant difference in reducing post bypass inflammation between preoperative steroid treatment and combined preoperative and intraoperative steroid administration reported and they had the same effects. PMID:23682327

  8. Fever and increased serum IL-1 activity as a systemic manifestation of acute phototoxicity in New Zealand White rabbits.

    PubMed

    Ansel, J C; Luger, T A; Green, I

    1987-07-01

    Ultraviolet (UV) radiation is a significant environmental hazard for humans and animals. Although the clinical effect of an acute UV exposure such as cutaneous inflammation, malaise, somnolence, chills, and fever have been appreciated for many years, the underlying mechanisms mediating these effects are poorly understood. Since chills and fever are the most dramatic systemic sequelae after a prolonged exposure to UV, we specifically examined the effect of whole-body UV irradiation on core body temperature and serum endogenous pyrogen activity of New Zealand White rabbits, correlating this with serum interleukin 1 (IL-1) activity and alterations of serum divalent cation levels. We found that an acute dose of UV irradiation (Westinghouse FS-40 lamps, 0.2 mJ/cm2/s X 8 h) resulted in a significant increase in the core body temperature 2 h post UV (0.8 degree C), peaking 5 h post UV (1.8 degree C), and returning to normal 24 h post UV. Likewise, the sera from the UV-irradiated rabbits had significant endogenous pyrogen activity when transferred into naive recipient animals, causing an increase in core body temperature within 45 min (0.65 +/- 0.12 degree C), decreasing over the next 2 h, and returning to normal 6 h post injection. No endotoxin contamination was detected in any serum samples. This post-UV febrile response was accompanied by a prolonged increase in serum IL-1 activity (5-10 X) and a significant alteration in serum divalent cation levels, with the rabbits becoming euthermic even as the serum IL-1 levels remained elevated. These findings provide new information concerning the pathogenesis and kinetics of these systemic effects after an acute dose of UV irradiation. PMID:3496401

  9. Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

    PubMed Central

    Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

    2016-01-01

    AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. RESULTS: The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers. PMID:26937145

  10. Serum SNTF Increases in Concussed Professional Ice Hockey Players and Relates to the Severity of Postconcussion Symptoms.

    PubMed

    Siman, Robert; Shahim, Pashtun; Tegner, Yelverton; Blennow, Kaj; Zetterberg, Henrik; Smith, Douglas H

    2015-09-01

    Biomarkers for diffuse axonal injury could have utilities for the acute diagnosis and clinical care of concussion, including those related to sports. The calpain-derived αII-spectrin N-terminal fragment (SNTF) accumulates in axons after traumatic injury and increases in human blood after mild traumatic brain injury (mTBI) in relation to white matter abnormalities and persistent cognitive dysfunction. However, SNTF has never been evaluated as a biomarker for sports-related concussion. Here, we conducted longitudinal analysis of serum SNTF in professional ice hockey players, 28 of whom had a concussion, along with 45 players evaluated during the preseason, 17 of whom were also tested after a concussion-free training game. Compared with preseason levels, serum SNTF increased at 1 h after concussion and remained significantly elevated from 12 h to 6 days, before declining to preseason baseline. In contrast, serum SNTF levels were unchanged after training. In 8 players, postconcussion symptoms resolved within a few days, and in these cases serum SNTF levels were at baseline. On the other hand, for the 20 players withheld from play for 6 days or longer, serum SNTF levels rose from 1 h to 6 days postconcussion, and at 12-36 h differed significantly from the less-severe concussions (p=0.004). Serum SNTF exhibited diagnostic accuracy for concussion, especially so with delayed return to play (area under the curve=0.87). Multi-variate analyses of serum SNTF and tau improved the diagnostic accuracy, the relationship with the delay in return to play, and the temporal window beyond tau alone. These results provide evidence that blood SNTF, a biomarker for axonal injury after mTBI, may be useful for diagnosis and prognosis of sports-related concussion, as well as for guiding neurobiologically informed decisions on return to play. PMID:25419578

  11. The 5XFAD Mouse Model of Alzheimer's Disease Exhibits an Age-Dependent Increase in Anti-Ceramide IgG and Exogenous Administration of Ceramide Further Increases Anti-Ceramide Titers and Amyloid Plaque Burden

    PubMed Central

    Dinkins, Michael B.; Dasgupta, Somsankar; Wang, Guanghu; Zhu, Gu; He, Qian; Kong, Ji Na; Bieberich, Erhard

    2015-01-01

    We present evidence that 5XFAD Alzheimer's disease model mice develop an age-dependent increase in antibodies against ceramide, suggesting involvement of autoimmunity against ceramide in Alzheimer's disease pathology. To test this, we increased serum anti-ceramide IgG (2-fold) by ceramide administration and analyzed amyloid plaque formation in 5XFAD mice. There were no differences in soluble or total amyloid-β levels. However, females receiving ceramide had increased plaque burden (number, area, and size) compared to controls. Ceramide-treated mice showed an increase of serum exosomes (up to 3-fold using Alix as marker), suggesting that systemic anti-ceramide IgG and exosome levels are correlated with enhanced plaque formation. PMID:25720409

  12. Verification Survey: NASFAA Survey Shows Administrative Burden Increasing for Financial Aid Offices. Quick Scan Survey Results

    ERIC Educational Resources Information Center

    National Association of Student Financial Aid Administrators (NJ1), 2009

    2009-01-01

    More than three in four college financial aid offices reported an increase in the number of cases where they must verify information on the Free Application for Federal Student Aid (FAFSA), according to the National Association of Student Financial Aid Administrators' (NASFAA's) latest Quick-Scan Survey. The increase in the number of verification…

  13. Increased IL-35 serum levels in systemic sclerosis and association with pulmonary interstitial involvement.

    PubMed

    Dantas, Andréa Tavares; Gonçalves, Sayonara Maria Calado; Pereira, Michelly Cristiny; Gonçalves, Rafaela Silva Guimarães; Marques, Cláudia Diniz Lopes; Rego, Moacyr Jesus Barreto de Melo; Pitta, Ivan da Rocha; Duarte, Angela Luzia Branco Pinto; Pitta, Maira Galdino da Rocha

    2015-09-01

    The objective of this study is to assess the serum IL-35 level and its association with clinical manifestations in patients with systemic sclerosis (SSc). IL-35 serum levels were measured by ELISA from 56 patients with SSc and 53 healthy controls. Association of IL-35 serum levels were sought with clinical parameters. Serum IL-35 levels were significantly higher in SSc patients (5.08 ± 0.76 pg/ml) than in healthy individuals (1.89 ± 0.69 pg/ml; p < 0.0001). Patients with lung fibrosis had higher IL-35 levels than those without fibrosis (7.75 ± 1.36 and 3.08 ± 0.70 pg/ml, respectively, p = 0.0022). IL-35 is elevated in the serum of patients with SSc and is associated with lung fibrosis. Our findings suggest that this cytokine can have a role in fibrotic diseases, but further studies are needed to address the role of IL-35 in the pathogenesis of SSc. PMID:26160266

  14. Increased Interleukin-17 and decreased BAFF serum levels in drug-free acute schizophrenia.

    PubMed

    El Kissi, Yousri; Samoud, Samar; Mtiraoui, Ahlem; Letaief, Leila; Hannachi, Neila; Ayachi, Mouna; Ali, Bechir Ben Hadj; Boukadida, Jalel

    2015-01-30

    Hypotheses regarding an immune-cytokine basis of schizophrenia have been postulated with controversial findings and a lack of data related to many cytokines. The aim of this study was to assess serum levels of Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Transforming Growth Factor-β (TGF-β), Interleukin-17 (IL-17) and B-cell Activating Factor (BAFF) in schizophrenic patients and to determine correlations between cytokine levels and clinical parameters. Serum cytokine levels were measured with ELISA techniques in 60 neuroleptic-free patients on acute phase of the disease (BPRS≥40) and 28 healthy controls matched for age and sex. Current symptoms were assessed with Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). No significant difference was found between patients and controls regarding IFN-γ serum levels. IL-4 was not detected in both groups. Patients exhibited significantly higher IL-17 and lower BAFF serum levels. IL-17 and BAFF levels were negatively correlated in schizophrenic patients. SANS global score was negatively correlated with IL-17 and positively correlated with IFN-γ serum levels. These results argue against the involvement of Th1 or Th2 population cells in schizophrenia. IL-17 and BAFF could be valuable markers for schizophrenia. PMID:25453636

  15. Meloxicam, an inhibitor of cyclooxygenase-2, increases the level of serum G-CSF and might be usable as an auxiliary means in G-CSF therapy.

    PubMed

    Hofer, M; Pospísil, M; Znojil, V; Holá, J; Vacek, A; Streitová, D

    2008-01-01

    Hematopoiesis-modulating action of meloxicam, a cyclooxyge-nase-2 inhibitor, has been evaluated in mice. Increased serum level of granulocyte colony-stimulating factor (G-CSF) after meloxicam administration has been found in sublethally gamma-irradiated animals. In further experiments hematopoiesis-stimulating effects of meloxicam and G-CSF given alone or in combination have been investigated. Granulocyte/macrophage progenitor cells counts were used to monitor these effects. Meloxicam and exogenous G-CSF did not act synergistically when given in combination, but could be mutually substituted during their repeated administration. The results suggest a promising possibility of using meloxicam as an auxiliary drug reducing the high costs of G-CSF therapy of myelosuppression. PMID:17552878

  16. Serum lipid and fatty acid profiles in adriamycin-treated rats after administration of L-carnitine.

    PubMed

    Hong, Young Mi; Kim, Hae Soon; Yoon, Hye-Ran

    2002-02-01

    Cardiomyopathy induced by Adriamycin (ADR) is a cause of congestive heart failure. Recently, it has been suggested that ADR inhibits the carnitine palmitoyltransferase system (CPT I) and consequently the transport of long-chain fatty acids across mitochondrial membranes. This study was devised to ascertain how ADR affects serum lipid and fatty acid metabolism in rats given ADR with and without L-carnitine supplementation. Male Sprague-Dawley rats were divided into four groups. The first group was the control. The second group was given intraperitoneal injections of ADR (5 mg/kg) twice a week over a period of 2 wk. The third group received the same dose of ADR plus L-carnitine (200 mg/kg). The fourth group was injected with L-carnitine only. Serum lipids (total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol) and fatty acid levels were determined on the first, eighth, and 15th d after injection of ADR. ADR caused an increase of serum total cholesterol, triglyceride, and LDL cholesterol compared with the control group. HDL cholesterol was similar between two groups. Similarly, total fatty acids, especially C16-C18 fatty acids, were significantly elevated after injection of ADR. Striking reduction in these substances was observed when L-carnitine was added (p < 0.05). This study is the first report regarding the reversal effect of L-carnitine in connection with FFA profiles (C6-C18) in the serum of ADR-induced cardiomyopathic rats. This study also supports the view that ADR causes cardiomyopathy because it interferes with fatty acid metabolism, and we hypothesize that there is a possible protective effect of L-carnitine. PMID:11809922

  17. Serum but not follicular fluid cytokine levels are increased in stimulated versus natural cycle IVF: a multiplexed assay study.

    PubMed

    Bersinger, N A; Kollmann, Z; Von Wolff, M

    2014-12-01

    Throughout follicular growth the number of immune cells increases, enhanced under stimulation with exogenous gonadotropins. This treatment, however, may adversely influence folliculogenesis and negatively affect oocyte quality through modifications in the follicular concentrations of cytokines released by these immune cells. We studied this hypothesis by systematically analysing the concentrations of cytokines present in the serum and follicular fluid at the time of follicular aspiration in conventional gonadotropin-stimulated (c-IVF) cycles in comparison with natural cycle IVF (NC-IVF) in which the follicles were naturally matured. Our study involved 37 NC-IVF and 39 c-IVF cycles including 13 women who underwent both therapies. Mean age was 35.3 ± 4.6 (SD) and 34.2 ± 3.7 years in the NC-IVF and c-IVF groups (ns). Thirteen cytokines were determined in matched serum and FF samples. Interleukin (IL)-4, TNF-α, RANTES, eotaxin and interferon-gamma-induced protein-10 concentrations were lower in FF than in serum. IL-6, -8, -10, -18, monocyte chemotactic protein-1 (MCP-1), VEGF and leukaemia inhibitory factor (LIF) showed higher median levels in FF than in serum, indicating possible ovarian production. Most of these markers were also increased in concentration in the stimulated (c-IVF) than in the NC groups in the serum, but not in the follicular fluid. This finding can be attributed to the increased number of active follicles present after controlled ovarian stimulation. IL-8 was reduced in c-IVF cycles. Our study did not reveal differences in follicular fluid but in serum cytokine concentrations, suggesting that the follicular immune system might not be significantly affected by gonadotropin stimulation. PMID:25103590

  18. Differential analysis of transient increases of serum cTnI in response to handling in rats

    PubMed Central

    Mikaelian, Igor; Dunn, Michael E; Mould, Diane R; Hirkaler, Gerard; Geng, Wanping; Coluccio, Denise; Nicklaus, Rosemary; Singer, Thomas; Reddy, Micaela

    2013-01-01

    Serum cardiac troponins are the key biomarkers of myocardial necrosis in humans and in preclinical species. The use of ultrasensitive assays for serum cardiac troponin I (cTnI) as a biomarker in safety studies is hampered by interindividual differences. In this study, we investigated the effect of handling procedures on serum cTnI and explored modeling and simulation approaches to mitigate the impact of these interindividual differences. Femoral-catheterized male Crl:WI(Han) rats (n = 16/group) were left undisturbed in their cages with no handling; subjected to 5 min of isoflurane/O2 anesthesia (A); or placed into a rodent restrainer followed by simulated tail vein injection (RR). Serum cTnI concentrations were assessed over a 24-h period using an ultrasensitive assay, and the study was repeated for confirmation. The mean serum cTnI concentration pre-procedure was 4.2 pg/mL, and remained stable throughout the duration of the study in the rats submitted to the A procedure. Serum cTnI concentrations increased transiently after the RR procedure with a median time to maximum concentration (Tmax), of 1 and 2 h and a mean maximum value concentration (Cmax), of 53.0 and 7.2 pg/mL in the initial and repeat studies, respectively. A population pharmacodynamic model identified interindividual, procedure- and study-specific effects on serum cTnI concentrations in rats. It is concluded that a modeling and simulation approach more appropriately describes and statistically analyzes the data obtained with this ultrasensitive assays. PMID:25505566

  19. Higher serum 25-hydroxyvitamin D levels in school-age children are inconsistently associated with increased calcium absorption

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing serum 25-hydroxyvitamin D (25-OHD) in adults may enhance calcium absorption (Ca-abs). There are few similar pediatric data leading to uncertainty about the optimal target for 25-OHD to maximize Ca-abs.Our objective was to evaluate the relationship between 25-OHD and Ca-abs in a large coho...

  20. Switching from posaconazole suspension to tablets increases serum drug levels in leukemia patients without clinically relevant hepatotoxicity.

    PubMed

    Jung, Dong Sik; Tverdek, Frank P; Kontoyiannis, Dimitrios P

    2014-11-01

    We evaluated posaconazole serum concentrations and hepatotoxicity in 12 leukemia patients who transitioned from posaconazole suspension to tablets. Patients who switched to tablets had significantly increased posaconazole concentrations (median: suspension, 748 ng/ml; tablet, 1,910 ng/ml; P < 0.01) without clinically relevant hepatotoxicity. PMID:25199774

  1. Increased Trypanosoma brucei cathepsin-L activity inhibits human serum-mediated trypanolysis

    PubMed Central

    Alsford, Sam

    2016-01-01

    Most African trypanosomes, including the veterinary species Trypanosoma brucei brucei and T. congolense are susceptible to lysis by human serum. A recent study by Alsford et al. [PLoS Pathogens (2014) 10, e1004130] has identified a T. b. brucei lysosomal cathepsin with an inhibitory effect on human serum’s trypanolytic action.

  2. Fasciola hepatica in vitro: increased susceptibility to fasciolicides in a defined serum-free medium.

    PubMed

    Jenkins, D C; Topley, P; Rapson, E B

    1987-08-01

    The cidal properties of some phenolic, halogenated diphenyl, salicylanilide, benzimidazole and diaminophenoxyalkane anthelmintics, against 6-week-old worms of Fasciola hepatica were assessed in vitro. In a conventional fluke culture medium containing RPMI 1640, supplemented with serum with or without rabbit erythrocytes or pink-ghosts, only the halogenated diphenyl and salicylanilide compounds showed activity at concentrations equal to or less than 100 microM. However, when basal, serum and cell-free RPMI 1640 was used, all compounds other than diamphenethide were highly active, their minimum lethal concentrations being some 25-125 times lower under these conditions. The inclusion of rabbit liver microsomes in the basal culture medium resulted in diamphenethide exhibiting cidal activity equivalent to that seen when its free-amine active metabolite was assayed. The possibility that the activity of many of these compounds was masked in vitro because of their serum binding properties is discussed. Recommendations are made that in vitro screens for new fasciolicides should be carried out in serum-free medium and that additional replicates containing mammalian liver microsomes and liver cytosolic extracts be included as means for the metabolic activation of certain otherwise undetectable prodrugs. PMID:3670897

  3. Maternal serum soluble CD30 is increased in pregnancies complicated with acute Pyelonephritis

    PubMed Central

    Kusanovic, Juan Pedro; Romero, Roberto; Espinoza, Jimmy; Gotsch, Francesca; Edwin, Samuel; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Soto, Eleazar; Erez, Offer; Mazaki-Tovi, Shali; Than, Nandor Gabor; Friel, Lara; Yoon, Bo Hyun; Mazor, Moshe; Hassan, Sonia

    2007-01-01

    Objectives Normal pregnancy is characterized by activation of the innate immunity and suppression of the adaptive limb of the immune response. However, pregnant women are more susceptible to the effects of infection and microbial products than non-pregnant women. CD30 is a member of the tumor necrosis factor receptor superfamily and is preferentially expressed by activated T cells producing Th2-type cytokines. Its soluble form (sCD30) is proposed to be an index of Th2 immune response. High serum concentrations of sCD30 have been found in the acute phase of viral infections, such as HIV-1 and hepatitis B. There is, however, conflicting evidence about serum sCD30 concentration in patients with bacterial infections. The objective of this study was to determine whether there are changes in the serum concentration of sCD30 in pregnant women with pyelonephritis. Methods This cross-sectional study included normal pregnant women (N=89) and pregnant women with pyelonephritis (N=41). Maternal serum concentration of sCD30 was measured by a specific and sensitive enzyme-linked immunoassay. Non-parametric tests were used for comparisons. A p value <0.05 was considered statistically significant. Results (1) Pregnant women with pyelonephritis had a significantly higher median serum concentration of sCD30 than those with a normal pregnancy (median: 44.3 U/ml, range: 16–352.5 vs. median: 29.7 U/ml, range: 12.2–313.2, respectively; p<0.001); and (2) No significant differences were found in the median maternal serum concentration of sCD30 between pregnant women with pyelonephritis who had a positive blood culture compared to those with a negative blood culture (median:47.7 U/mL, range: 17.1–118.8 vs. median: 42.6 U/mL, range: 16–352.5, respectively; p=0.86). Conclusions Acute pyelonephritis during pregnancy is associated with a higher maternal serum concentration of sCD30 than normal pregnancy. This finding is novel, and suggests that pregnant women with pyelonephritis may

  4. Increased serum triglyceride clearance and elevated high-density lipoprotein 2 and 3 cholesterol during treatment of primary hypertriglyceridemia with bezafibrate☆

    PubMed Central

    Sakuma, Nagahiko; Ikeuchi, Reiko; Hibino, Takeshi; Yoshida, Takayuki; Mukai, Seiji; Akita, Sachie; Yajima, Kazuhiro; Miyabe, Hiromichi; Goto, Toshihiko; Takada, Norio; Ohte, Nobuyuki; Kunimatu, Mitoshi; Kimura, Genjiro

    2003-01-01

    Background Hypertriglyceridemia accompanied by low levels of high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. High-density lipoprotein 2 (HDL2) and 3 (HDL3) are believed to suppress the progress of atherosclerosis through reverse cholesterol transport. As a result, peripheral tissues can be protected against excessive accumulation of cholesterol. Although bezafibrate is known to accelerate the increase of HDL-C, results are not standardized regarding increases of HDL3 and HDL2 subfractions. Objective This study assessed the effects of bezafibrate on serum triglyceride (TG) fractional clearance rate (K2) and HDL2 and HDL3 cholesterol (HDL2-C and HDL3-C, respectively) levels in patients with primary hypertriglyceridemia (serum TG ≥150 mg/dL). Methods Outpatients with primary hypertriglyceridemia were enrolled in this 8-week study conducted at the Third Department of Internal Medicine, Nagoya City University Hospital (Nagoya, Japan). Oral bezafibrate was administered at a dose of 400 mg/d (200-mg tablet BID, morning and evening) for 8 weeks. After 8 weeks, serum levels of total cholesterol (TC), TG, HDL-C, HDL2-C, and HDL3-C were measured. A fat emulsion tolerance test to assess K2 and measurements of plasma lipoprotein lipase (LPL) mass, LPL activity, and hepatic triglyceride lipase (HTGL) activity in postheparin plasma were performed before bezafibrate administration and after the course of treatment. Results Sixteen patients (10 men, 6 women; mean [SD] age, 54 [12] years [range, 30–69 years]; mean [SD] body mass index, 23 [2] kg/m2) entered the study. The following findings were observed in male and female patients after 8 weeks of treatment. A statistically significant reduction was observed in mean serum TG level (P<0.01). Significant increases were seen in HDL-C, HDL2-C, and HDL3-C (all P<0.01), K2 (P<0.01), and in plasma LPL mass (P<0.01) and LPL activity (P<0.05). TC level and HTGL activity did not change

  5. Serum Calcium Increase Correlates With Worsening of Lipid Profile: An Observational Study on a Large Cohort From South Italy.

    PubMed

    Gallo, Luigia; Faniello, Maria C; Canino, Giovanni; Tripolino, Cesare; Gnasso, Agostino; Cuda, Giovanni; Costanzo, Francesco S; Irace, Concetta

    2016-02-01

    Despite the well-documented role of calcium in cell metabolism, its role in the development of cardiovascular disease is still under heavy debate. Several studies suggest that calcium supplementation might be associated with an increased risk of coronary heart disease, whereas others underline a significant effect on lowering high blood pressure and hyperlipidemia. The purpose of this study was to investigate, in a large nonselected cohort from South Italy, if serum calcium levels correlate with lipid values and can therefore be linked to higher individual cardiovascular risk.Eight-thousand-six-hundred-ten outpatients addressed to the Laboratory of Clinical Biochemistry, University of Magna Græcia, Catanzaro, Italy from January 2012 to December 2013 for routine blood tests, were enrolled in the study. Total HDL-, LDL- and non-HDL colesterol, triglycerides, and calcium were determined with standard methods.We observed a significant association between total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, triglycerides, and serum calcium in men and postmenopause women. Interestingly, in premenopause women, we only found a direct correlation between serum calcium, total cholesterol, and HDL-cholesterol. Calcium significantly increased while increasing total cholesterol and triglycerides in men and postmenopause women.Our results confirm that progressive increase of serum calcium level correlates with worsening of lipid profile in our study population. Therefore, we suggest that a greater caution should be used in calcium supplement prescription particularly in men and women undergoing menopause, in which an increase of serum lipids is already known to be associated with a higher cardiovascular risk. PMID:26937904

  6. Increased Circulating Th17 Cells, Serum IL-17A, and IL-23 in Takayasu Arteritis

    PubMed Central

    Misra, Durga Prasanna; Chaurasia, Smriti

    2016-01-01

    Introduction. Th17, γδT, NK, and NKT cells in peripheral blood and serum IL-17 and IL-23 in Takayasu arteritis (TA) were measured and correlated with disease activity. Methods. Th17 (anti-CD3APC, CD4PECy7, and IL-17PE), NKT, NK (anti-CD3APC, CD56FITC), and γδT (anti-CD3FITC and γδTCRAPC) cells were enumerated by flow cytometry in peripheral blood of 30 patients with TA (ACR1990 criteria) and 20 healthy controls, serum IL-17 and IL-23 measured by ELISA. Relation with disease activity (NIH criteria, ITAS2010) was analyzed (using nonparametric tests, median with interquartile range). Results. Mean age of patients was 33.47 ± 11.78 years (25 females); mean symptom duration was 7.1 ± 5.3 years. 13 were not on immunosuppressants; 12 were active (ITAS2010 ≥ 4). The percentage of Th17 cells was significantly expanded in TA (patients 2.1 (1.5–3.2) versus controls 0.75 (0.32–1.2); p < 0.0001) with no differences in other cell populations. Serum IL-17 and IL-23 (pg/mL) in patients (6.2 (4.6–8.5) and 15 (14.9–26.5), resp.) were significantly higher (p < 0.001) than controls (3.9 (3.9–7.3) and undetectable median value, resp.). Subgroup analysis revealed no correlation of Th17 cells, serum IL-17, and IL-23 with disease activity or medications, nor any significant difference before and after medication. Conclusions. There is significant expansion of Th17 cells and elevated serum IL-17 and IL-23 levels in TA patients compared to healthy controls. PMID:27034824

  7. Increased Circulating Th17 Cells, Serum IL-17A, and IL-23 in Takayasu Arteritis.

    PubMed

    Misra, Durga Prasanna; Chaurasia, Smriti; Misra, Ramnath

    2016-01-01

    Introduction. Th17, γδT, NK, and NKT cells in peripheral blood and serum IL-17 and IL-23 in Takayasu arteritis (TA) were measured and correlated with disease activity. Methods. Th17 (anti-CD3APC, CD4PECy7, and IL-17PE), NKT, NK (anti-CD3APC, CD56FITC), and γδT (anti-CD3FITC and γδTCRAPC) cells were enumerated by flow cytometry in peripheral blood of 30 patients with TA (ACR1990 criteria) and 20 healthy controls, serum IL-17 and IL-23 measured by ELISA. Relation with disease activity (NIH criteria, ITAS2010) was analyzed (using nonparametric tests, median with interquartile range). Results. Mean age of patients was 33.47 ± 11.78 years (25 females); mean symptom duration was 7.1 ± 5.3 years. 13 were not on immunosuppressants; 12 were active (ITAS2010 ≥ 4). The percentage of Th17 cells was significantly expanded in TA (patients 2.1 (1.5-3.2) versus controls 0.75 (0.32-1.2); p < 0.0001) with no differences in other cell populations. Serum IL-17 and IL-23 (pg/mL) in patients (6.2 (4.6-8.5) and 15 (14.9-26.5), resp.) were significantly higher (p < 0.001) than controls (3.9 (3.9-7.3) and undetectable median value, resp.). Subgroup analysis revealed no correlation of Th17 cells, serum IL-17, and IL-23 with disease activity or medications, nor any significant difference before and after medication. Conclusions. There is significant expansion of Th17 cells and elevated serum IL-17 and IL-23 levels in TA patients compared to healthy controls. PMID:27034824

  8. Lafutidine, a novel histamine H2-receptor antagonist, increases serum calcitonin gene-related peptide in rats after water immersion-restraint stress.

    PubMed

    Sato, Hiroshi; Kawashima, Kousaku; Yuki, Mika; Kazumori, Hideaki; Rumi, Mohammad Azharul Karim; Ortega-Cava, Cesar Francisco; Ishihara, Shunji; Kinoshita, Yoshikazu

    2003-02-01

    Lafutidine is a novel histamine H(2)-receptor antagonist with a potent and long-lasting anti-acid secretory effect that has also been found to have a potent gastroprotective effect. We investigated the effect of lafutidine on gastric mucosal injury induced in rats with the use of water-immersion restraint stress (WRS) by examining serum calcitonin gene-related peptide (CGRP) concentrations, which we measured with the use of an enzyme immunometric assay. WRS-induced mucosal erosive injury in the stomach was reduced significantly by both lafutidine and famotidine pretreatment (from 7.79 +/- 2.02 mm(2) to 3.09 +/- 0.74 mm(2) and 4.05 +/- 1.18 mm(2), respectively). A single administration of lafutidine or famotidine did not change the serum CGRP concentration from the control value when these drugs were administered without WRS. Lafutidine pretreatment before WRS caused a significant increase in serum CGRP concentration compared with famotidine (lafutidine, 86.64 +/- 9.52 pg/mL; famotidine, 47.55 +/- 4.35 pg/mL; control, 58.43 +/- 6.07 pg/mL). Our results suggest that lafutidine augments CGRP release from the rat stomach when administered before the induction of WRS. PMID:12577045

  9. Feeding a Modified Fish Diet to Bottlenose Dolphins Leads to an Increase in Serum Adiponectin and Sphingolipids.

    PubMed

    Sobolesky, Philip M; Harrell, Tyler S; Parry, Celeste; Venn-Watson, Stephanie; Janech, Michael G

    2016-01-01

    Feeding a modified fish diet has been suggested to improve insulin sensitivity in bottlenose dolphins; however, insulin sensitivity was not directly measured. Since demonstrating an improvement in insulin sensitivity is technically difficult in dolphins, we postulated that directional changes in the hormone axis: fibroblast growth factor 21 (FGF21)/Adiponectin/Ceramide (Cer), could provide further support to this hypothesis. We measured 2-h post-prandial serum FGF21, total adiponectin, percent unmodified adiponectin, ceramide, and sphingosine levels from dolphins fed a diet rich in heptadecanoic acid (C17:0) over 24 weeks. Serum FGF21 was quantified by ELISA with an observed range of 129-1599 pg/ml, but did not significantly change over the 24-week study period. Total adiponectin levels (mean ± SD) significantly increased from 776 ± 400 pmol/ml at week 0 to 1196 ± 467 pmol/ml at week 24. The percent unmodified adiponectin levels (mean ± SD) decreased from 23.8 ± 6.0% at week 0 to 15.2 ± 5.2% at week 24. Interestingly, although FGF21 levels did not change, there was a good correlation between FGF21 and total adiponectin (ρ = 0.788, P < 0.001). We quantified the abundances of serum ceramides and sphingosines (SPH) because adiponectin has a defined role in sphingolipid metabolism through adiponectin receptor-mediated activation of ceramidases. The most abundant ceramide in dolphin sera was Cer 24:1 comprising 49% of the ceramides measured. Significant reductions were observed in the unsaturated Cer 18:1, Cer 20:1, and Cer 24:1, whereas significant increases were observed in saturated Cer 22:0, Cer 24:0, and Cer 26:0. However, total serum ceramides did not change. Significant elevations were detected for total sphingosine, dihydrosphingosine, sphingosine-1-phosphate, and dihydrosphingosine-1-phosphate. Proteomic analysis of the serum proteins revealed few changes in serum proteins over the study period. In conclusion

  10. Feeding a Modified Fish Diet to Bottlenose Dolphins Leads to an Increase in Serum Adiponectin and Sphingolipids

    PubMed Central

    Sobolesky, Philip M.; Harrell, Tyler S.; Parry, Celeste; Venn-Watson, Stephanie; Janech, Michael G.

    2016-01-01

    Feeding a modified fish diet has been suggested to improve insulin sensitivity in bottlenose dolphins; however, insulin sensitivity was not directly measured. Since demonstrating an improvement in insulin sensitivity is technically difficult in dolphins, we postulated that directional changes in the hormone axis: fibroblast growth factor 21 (FGF21)/Adiponectin/Ceramide (Cer), could provide further support to this hypothesis. We measured 2-h post-prandial serum FGF21, total adiponectin, percent unmodified adiponectin, ceramide, and sphingosine levels from dolphins fed a diet rich in heptadecanoic acid (C17:0) over 24 weeks. Serum FGF21 was quantified by ELISA with an observed range of 129–1599 pg/ml, but did not significantly change over the 24-week study period. Total adiponectin levels (mean ± SD) significantly increased from 776 ± 400 pmol/ml at week 0 to 1196 ± 467 pmol/ml at week 24. The percent unmodified adiponectin levels (mean ± SD) decreased from 23.8 ± 6.0% at week 0 to 15.2 ± 5.2% at week 24. Interestingly, although FGF21 levels did not change, there was a good correlation between FGF21 and total adiponectin (ρ = 0.788, P < 0.001). We quantified the abundances of serum ceramides and sphingosines (SPH) because adiponectin has a defined role in sphingolipid metabolism through adiponectin receptor-mediated activation of ceramidases. The most abundant ceramide in dolphin sera was Cer 24:1 comprising 49% of the ceramides measured. Significant reductions were observed in the unsaturated Cer 18:1, Cer 20:1, and Cer 24:1, whereas significant increases were observed in saturated Cer 22:0, Cer 24:0, and Cer 26:0. However, total serum ceramides did not change. Significant elevations were detected for total sphingosine, dihydrosphingosine, sphingosine-1-phosphate, and dihydrosphingosine-1-phosphate. Proteomic analysis of the serum proteins revealed few changes in serum proteins over the study period. In conclusion

  11. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis

    PubMed Central

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  12. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis.

    PubMed

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  13. Studies on the increase in serum concentrations of urea cycle amino acids among subjects exposed to cadmium

    SciTech Connect

    Nishino, H.; Shiroishi, K. ); Kagamimori, S.; Naruse, Y. ); Watanabe, M. )

    1988-05-01

    Itai-itai disease (I disease) is a combination of renal tubular damage and osteomalacia accompanied by osteoporosis among subjects exposed to cadmium (Cd). When the renal tubular damage progresses, the excretion of amino acids, especially, threonine, hydroxyproline, proline, citrulline, ornithine, arginine, etc. increase in urine. It was reported that the increase in urinary excretion of citrulline, arginine and ornithine may be associated with an inhibition of urea synthesis in the urea cycle. The authors have found that serum citrulline, arginine and ornithine also increased in I disease patients. In order to investigate the mechanism of the increase in these serum amino acids, comparative studies were performed using both healthy subjects and patients with renal disease as control groups.

  14. Studies on the increase in serum concentrations of urea cycle amino acids among subjects exposed to cadmium

    SciTech Connect

    Nishino, H.; Shiroishi, K.; Kagamimori, S.; Naruse, Y.; Watanabe, M.

    1988-04-01

    Itai-itai disease (I disease) is a combination of renal tubular damage and osteomalacia accompanied by osteoporosis among subjects exposed to cadmium (Cd). When the renal tubular damage progresses, the excretion of amino acids, especially, threonine, hydroxyproline, proline, citrulline, ornithine, arginine increased in urine. It has been reported that the increase in urinary excretion of citrulline, arginine and ornithine may be associated with an inhibition of urea synthesis in the urea cycle. The authors have found that serum citrulline, arginine and ornithine also increased in I disease patients. In order to investigate the mechanism of the increase in these serum amino acids, comparative studies were performed using both healthy subjects and patients with renal disease as control groups.

  15. Association Between HLA Haplotypes and Increased Serum Levels of IgG4 in Patients with Primary Sclerosing Cholangitis

    PubMed Central

    Berntsen, Natalie L.; Klingenberg, Olav; Juran, Brian D.; de Valle, Maria Benito; Lindkvist, Björn; Lazaridis, Konstantinos N.; Boberg, Kirsten Muri; Karlsen, Tom H.; Hov, Johannes Roksund

    2015-01-01

    Increased serum levels of immunoglobulin (Ig)G4 have been reported in 9%–15% of patients with primary sclerosing cholangitis (PSC); it is not clear whether this increase contributes to pathogenesis. We performed genetic analyses of the HLA complex in patients with PSC from Norway, Sweden, and the United States. We found an association between levels of IgG4 above the upper reference limit and specific HLA haplotypes. These patients had a significantly lower frequency of the strongest PSC risk factor, HLA-B* 08, than patients without increased IgG4, and significantly higher frequencies of HLA-B* 07 and DRB1*15. HLA genotype might therefore affect the serum concentration IgG4, and increased IgG4 might be a marker of a distinct phenotype of PSC. PMID:25655558

  16. Association Between HLA Haplotypes and Increased Serum Levels of IgG4 in Patients With Primary Sclerosing Cholangitis.

    PubMed

    Berntsen, Natalie L; Klingenberg, Olav; Juran, Brian D; Benito de Valle, Maria; Lindkvist, Björn; Lazaridis, Konstantinos N; Boberg, Kirsten Muri; Karlsen, Tom H; Hov, Johannes Roksund

    2015-05-01

    Increased serum levels of IgG4 have been reported in 9%-15% of patients with primary sclerosing cholangitis (PSC); it is not clear whether this increase contributes to pathogenesis. We performed genetic analyses of the HLA complex in patients with PSC from Norway, Sweden, and from the United States. We found an association between levels of IgG4 above the upper reference limit and specific HLA haplotypes. These patients had a significantly lower frequency of the strongest PSC risk factor, HLA-B*08, than patients without increased IgG4, and significantly higher frequencies of HLA-B*07 and HLA-DRB1*15. HLA genotype therefore might affect the serum concentration of IgG4, and increased IgG4 might be a marker of a distinct phenotype of PSC. PMID:25655558

  17. Serum Bilirubin Is Inversely Associated with Increased Arterial Stiffness in Men with Pre-Hypertension but Not Normotension

    PubMed Central

    Huang, Yao-Hsien; Yang, Yi-Ching; Lu, Feng-Hwa; Sun, Zih-Jie; Wu, Jin-Shang; Chang, Chih-Jen

    2016-01-01

    Objective Serum bilirubin level has shown to be inversely associated with coronary atherosclerosis, and may serve as a protective biomarker of coronary artery disease. Serum bilirubin has also been shown to be negatively associated with brachial-ankle pulse wave velocity (baPWV) in men without a history of hypertension, and in men with hypertension. It is unknown whether such associations can be observed in the pre-hypertensive or normotensive population. This study thus aimed to investigate the relationship between serum bilirubin level and increased arterial stiffness in subjects with pre-hypertension and normotension for both genders. Methods A cross-sectional sample of 3,399 apparently healthy subjects undergoing a medical check-up at National Cheng Kung University Hospital was enrolled between October 2006 and August 2009, after excluding subjects with serum total bilirubin level greater than 20.52 μmol/L. Increased arterial stiffness was defined as baPWV of 1,400 cm/s or higher as the dichotomous variable and bilirubin as the continuous variable. Results Based on multiple linear regression analysis, serum bilirubin level was inversely associated with baPWV in non-hypertensive men (β = -0.066, p < 0.001) but not in non-hypertensive women. In addition, the inverse relationship between bilirubin level and baPWV was found statistically significant only in pre-hypertensive men (β = -0.110, p < 0.001). Multiple logistic regression analysis showed that serum bilirubin was inversely associated with increased arterial stiffness in men with pre-hypertension (odds ratio = 0.955, 95% confidence interval = 0.916–0.996, p < 0.05) but not normotension after adjustment for other confounding factors. However, the relationship between total bilirubin level and increased arterial stiffness did not reach statistical significance for female subjects with pre-hypertension and normotension. Conclusion Serum bilirubin is inversely associated with increased arterial stiffness in

  18. C. albicans increases cell wall mannoprotein, but not mannan, in response to blood, serum and cultivation at physiological temperature

    PubMed Central

    Kruppa, Michael; Greene, Rachel R; Noss, Ilka; Lowman, Douglas W; Williams, David L

    2011-01-01

    The cell wall of Candida albicans is central to the yeasts ability to withstand osmotic challenge, to adhere to host cells, to interact with the innate immune system and ultimately to the virulence of the organism. Little is known about the effect of culture conditions on the cell wall structure and composition of C. albicans. We examined the effect of different media and culture temperatures on the molecular weight (Mw), polymer distribution and composition of cell wall mannan and mannoprotein complex. Strain SC5314 was inoculated from frozen stock onto yeast peptone dextrose (YPD), blood or 5% serum agar media at 30 or 37°C prior to mannan/mannoprotein extraction. Cultivation of the yeast in blood or serum at physiologic temperature resulted in an additive effect on Mw, however, cultivation media had the greatest impact on Mw. Mannan from a yeast grown on blood or serum at 30°C showed a 38.9 and 28.6% increase in Mw, when compared with mannan from YPD-grown yeast at 30°C. Mannan from the yeast pregrown on blood or serum at 37°C showed increased Mw (8.8 and 26.3%) when compared with YPD mannan at 37°C. The changes in Mw over the entire polymer distribution were due to an increase in the amount of mannoprotein (23.8–100%) and a decrease in cell wall mannan (5.7–17.3%). We conclude that C. albicans alters the composition of its cell wall, and thus its phenotype, in response to cultivation in blood, serum and/or physiologic temperature by increasing the amount of the mannoprotein and decreasing the amount of the mannan in the cell wall. PMID:21515585

  19. S-Adenosyl-L-methionine increases serum BUN and creatinine in cisplatin-treated mice.

    PubMed

    Ochoa, Bernardo; Bobadilla, Norma; Arrellín, Gerardo; Herrera, Luis A

    2009-01-01

    Cisplatin is an effective antineoplastic agent in the treatment of various solid tumors, although its full clinical utility is limited because of its renal toxicity. Several measures to protect the kidneys from cisplatin toxicity have been investigated and implemented in clinical trials; however, none of these were completely effective or without secondary effects. The aim of this study was to investigate S-adenosyl-L-methionine (SAM) as an agent that protects against cisplatin nephrotoxicity without affecting the antineoplastic activity of cisplatin. The cytotoxic effect was evaluated in cultured HeLa cells treated with cisplatin, SAM, and the combination cisplatin + SAM. No modification of the cytotoxic effect of cisplatin was induced by SAM. Similarly, SAM did not influence the antitumoral activity of cisplatin observed in HeLa cells implanted in nude mice. However, a significant increase in renal dysfunction was induced by SAM in animals treated with cisplatin. To our knowledge, this is the first report of a potential severe adverse effect of SAM administration, which should be considered for further evaluation due to the wide use of SAM as a nutritional supplement in humans. PMID:19064128

  20. The Leadership Roles of Distance Learning Administrators (DLAs) in Increasing Educational Value and Quality Perceptions

    ERIC Educational Resources Information Center

    McFarlane, Donovan A.

    2011-01-01

    This paper examines the leadership roles of distance learning administrators (DLAs) in light of the demand and need for value and quality in educational distance learning programs and schools. The author explores the development of distance learning using available and emerging technologies in relation to increased demand for education, training,…

  1. The Michigan Model Pilot: Increasing the Number of Female Administrators in Michigan Public Schools.

    ERIC Educational Resources Information Center

    Michigan State Dept. of Education, Lansing.

    The Michigan Model provides a 3-year plan for school districts to increase the number of women in administration. Nineteen objectives address six key role groups--three external to the school district (professional educational organizations, local community groups, and parent/community members) and three internal to the district…

  2. Alcohol administration increases cocaine craving but not cocaine cue attentional bias

    PubMed Central

    Marks, Katherine R.; Pike, Erika; Stoops, William W.; Rush, Craig R.

    2015-01-01

    Background Alcohol consumption is a known antecedent to cocaine relapse. Through associative conditioning, it is hypothesized that alcohol increases incentive motivation for cocaine and thus the salience of cocaine-related cues, which are important in maintaining drug-taking behavior. Cocaine-using individuals display a robust cocaine cue attentional bias as measured by fixation time during the visual probe task. The purpose of the present study was to evaluate the influence of alcohol administration on cocaine cue attentional bias using eye-tracking technology to directly measure attentional allocation. Methods Twenty current cocaine users completed a double-blind, placebo-controlled, within-subjects study that tested the effect of three doses of alcohol (0.00, 0.325, 0.65 g/kg alcohol) on cocaine cue attentional bias using the visual probe task with eye-tracking technology. The participant-rated and physiological effects of alcohol were also assessed. Results Participants displayed a robust cocaine cue attentional bias following both placebo and alcohol administration as measured by fixation time, but not response time. Alcohol administration did not influence cocaine cue attentional bias, but increased craving for cocaine in a dose dependent manner. Alcohol produced prototypic psychomotor and participant-rated effects. Conclusions Alcohol administration increases cocaine craving but not cocaine cue attentional bias. Alcohol-induced cocaine craving suggests that alcohol increases incentive motivation for cocaine but not the salience of cocaine-related cues. PMID:26331880

  3. Acute dichloroacetate administration increases skeletal muscle free glutamine concentrations after burn injury.

    PubMed Central

    Ferrando, A A; Chinkes, D L; Wolf, S E; Matin, S; Herndon, D N; Wolfe, R R

    1998-01-01

    OBJECTIVE: To investigate the hypothesis that the stimulation of pyruvate oxidation by dichloroacetate (DCA) administration would increase the level of intramuscular glutamine in severely burned patients. SUMMARY BACKGROUND DATA: The level of intramuscular glutamine decreases in response to severe injury, and the rate of intramuscular glycolysis and pyruvate oxidation is elevated. Intramuscular glutamine concentrations have been correlated to muscle protein synthesis. METHODS: Six studies were conducted on five patients with burns >40% total body surface area. Patients were studied in the fed state during an 8-hour stable isotope infusion. After 5 hours, DCA (30 mg/kg) was administered for 30 minutes. RESULTS: Analysis of muscle biopsy samples taken at 5 and 8 hours of the study revealed a 32% increase in intracellular glutamine levels after DCA administration. Increased intracellular glutamine concentrations did not affect skeletal muscle protein synthesis as determined by a three-pool arteriovenous model or by the direct incorporation of isotope into skeletal muscle protein. DCA administration resulted in a decrease in plasma lactate but no change in alanine de novo synthesis or intracellular concentration. CONCLUSIONS: These results suggest that acute DCA administration can increase intramuscular glutamine concentration, but that this acute elevation does not affect muscle protein metabolism. Images Figure 4. PMID:9712571

  4. Increased delivery of gallium-67 to tumors using serum-stable liposomes

    SciTech Connect

    Ogihara-Umeda, I.; Kojima, S.

    1988-04-01

    Gallium-67 chelated to nitrilotriacetic acid was encapsulated in liposomes composed of various phospholipids, and /sup 67/Ga delivery potential to the tumor after intravenous injection of these liposomes was examined. Tumor uptake of the liposomes themselves and their stability in the serum were also studied. It was found that liposomes composed of distearoylphosphatidylcholine, diarachidoylphosphatidylcholine, or sphingomyelin with cholesterol (molar ratio of phospholipid:cholesterol, 2:1) could be taken by the tumor effectively and could deliver large amounts of /sup 67/Ga to the tumor. They could also give high /sup 67/Ga accumulation ratios (tumor to the other tissues). The study of liposomal stability in the serum suggested that the marked /sup 67/Ga accumulation in the tumor resulted from the serum stability of the liposomal bilayer, i.e., the stable liposomes in the blood circulation could reach the tumor in large quantities after i.v. injection. These observations indicate that liposomes with an appropriate lipid composition may be an excellent tool to accumulate /sup 67/Ga in tumors.

  5. Circulating T helper 9 cells and increased serum interleukin-9 levels in patients with knee osteoarthritis.

    PubMed

    Qi, Changlin; Shan, Yuxing; Wang, Jing; Ding, Fupeng; Zhao, Ding; Yang, Teng; Jiang, Yanfang

    2016-05-01

    The purpose of this study was to examine the roles of T helper 9 (Th9) cells and the serum interleukin (IL)-9 level in the pathogenesis of osteoarthritis (OA). The numbers of IL-9(+)  CD4(+)  CD8(-) T cells, interferon (IFN)-γ+ CD4(+)  CD8(-) T cells, IL-4(+) CD4(+)  CD8(-) T cells, and IL-17A(+ ) CD4(+ ) CD8(-) T cells in 25 OA patients and 13 healthy controls (HC) were examined by flow cytometry. The serum concentrations of IL-9, IL-4, IL-17A, and IFN-γ were also determined. The numbers of CD4(+) CD45RO(+) T cells, Th9 cells, Th1 cells, and Th17 cells in OA patients were significantly higher than those in HCs. Furthermore, serum IL-9, IL-17A, and IFN-γ levels in OA patients were higher than those in HCs. The number of Th9 cells was positively correlated with the number of Th17 cells in OA patients. Furthermore, greater numbers of Th9 cells were positively associated with elevated C-reactive protein, and both Th9 cells and IL-9 levels were positively correlated with the Western Ontario and McMaster Universities Osteoarthritis index in OA patients. Th9 cell numbers and IL-9 levels are correlated with OA patient symptoms and joint functionality and may be a marker of disease activity. PMID:26926842

  6. Inosine to increase serum and CSF urate in Parkinson disease: A randomized, placebo-controlled trial

    PubMed Central

    2014-01-01

    Importance Convergent biological, epidemiological and clinical data identified urate elevation as a candidate strategy for slowing disability progression in Parkinson disease (PD). Objective To determine the safety, tolerability and urate-elevating capability of the urate precursor inosine in early PD; and to assess its suitability and potential design features for a disease-modification trial. Design The Safety of URate Elevation in PD (SURE-PD) study, a randomized, double-blind, placebo-controlled, dose-ranging trial of inosine, enrolled participants from 2009–2011 and followed them for up to 25 months. Setting Outpatient visits to 17 credentialed clinical study sites of the Parkinson Study Group across the United States. Participants Seventy-five consenting adults (mean age 62; 55% women) with early PD not yet requiring symptomatic treatment and a serum urate concentration below 6 mg/dL (the approximate population median) were enrolled. Intervention Participants were randomized to one of three treatment arms: placebo or inosine titrated to produce mild (6.1–7.0 mg/dL) or moderate (7.1–8.0 mg/dL) serum urate elevation using 500 mg capsules taken orally up to two thrice daily. They were followed for up to 24 months (median 18) on study drug plus 1 washout month. Main Outcome Measures The pre-specified primary outcomes were absence of unacceptable serious adverse events (safety), continued treatment without adverse event requiring dose reduction (tolerability), and elevation of urate assessed serially in serum and once (at 3 months) in cerebrospinal fluid (CSF). Results Serious adverse events (17), including infrequent cardiovascular events, occurred at the same or lower rates in inosine groups relative to placebo. No participant developed gout and three receiving inosine developed symptomatic urolithiasis. Treatment was tolerated by 95% of participants at 6 months, and no participant withdrew due to an adverse event. Serum urate rose by 2.3 and 3.0 mg/dL in

  7. Analysis of the Constituents in Rat Serum after Oral Administration of Fufang Zhenzhu Tiaozhi Capsule by UPLC-Q-TOF-MS/MS.

    PubMed

    Zhong, Xunlong; Guo, Jiao; Wang, Laiyou; Luo, Duosheng; Bei, Weijian; Chen, Yuanyuan; Yan, Kangqi; Peng, Junhui

    2012-02-01

    A rapid and sensitive UPLC/Q-TOF-MS method has been established for analysis of the constituents in rat serum after oral administration of Fufang Zhenzhu Tiaozhi (FTZ) capsule, an effective compound prescription for treating hyperlipidemia in the clinic. The UPLC/MS information of samples was obtained first in FTZ preparation and FTZ-treated rat serum. Mass spectra were acquired in both negative and positive ion modes. Thirty-six constituents in rat serum after oral administration of FTZ were detected, including the alkaloids, ginsenosides, pentacyclic triterpenes, and their metabolites. These chemicals were identified based on the retention time and mass spectrometry data with those of authentic standards or comparison of the literatures reports. Twenty-seven prototype components originated from FTZ and nine were the metabolites of the FTZ constituents. These results shed light on the potential active constituents of the complex traditional Chinese medicinal formulas. PMID:22307991

  8. Increased serum hepcidin-25 level and increased tumor expression of hepcidin mRNA are associated with metastasis of renal cell carcinoma

    PubMed Central

    2009-01-01

    Background Hepcidin has an important role in iron metabolism. We investigated whether hepcidin was involved in renal cell carcinoma (RCC). Methods We measured serum hepcidin-25 levels in 32 patients by liquid chromatograpy (LC)-mass spectrometry (MS)/MS, and assessed hepcidin mRNA expression in paired tumor and non-tumor tissue samples from the surgical specimens of 53 consecutive patients with RCC by real-time reverse transcription polymerase chain reaction. Results The serum hepcidin-25 level was higher in patients with metastatic RCC than nonmetastatic RCC (P < 0.0001), and was positively correlated with the serum interleukin-6 and C-reactive protein levels (P < 0.001). Expression of hepcidin mRNA was lower in tumor tissues than in non-tumor tissues (P < 0.0001). The serum hepcidin-25 level was not correlated with the expression of hepcidin mRNA in the corresponding tumor tissue specimens from 32 patients. Hepcidin mRNA expression in tumor tissue was correlated with metastatic potential, but not with histological differentiation or tumor stage. Kaplan-Meier analysis showed that over expression of hepcidin mRNA was related to shorter overall survival in RCC patients. Univariate analysis (Cox proportional hazards model) showed that the hepcidin mRNA level was an independent prognostic factor for overall survival. Conclusion Our findings suggest that a high serum hepcidin-25 level may indicate the progression of RCC, and that upregulation of hepcidin mRNA expression in tumor tissue may be related to increased metastatic potential. PMID:19656379

  9. Effects of escitalopram, R-citalopram, and reboxetine on serum levels of tumor necrosis factor-α, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration.

    PubMed

    Dong, Chao; Zhang, Ji-chun; Yao, Wei; Ren, Qian; Yang, Chun; Ma, Min; Han, Mei; Saito, Ryo; Hashimoto, Kenji

    2016-05-01

    Inflammation plays a role in the pathophysiology of depression. The purpose of this study is to examine whether the selective serotonin reuptake inhibitor (SSRI) escitalopram, its inactive enantiomer R-citalopram, and selective noradrenaline reuptake inhibitor (NRI) reboxetine, show anti-inflammatory and antidepressant effects in an inflammation-induced model of depression. Pretreatment with escitalopram (1, 3, or 10mg/kg, i.p.) markedly blocked an increase in the serum levels of pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), after a single administration of lipopolysaccharide (LPS; 0.5mg/kg). Furthermore, escitalopram (3 or 10mg/kg) significantly increased the serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) by a single administration of LPS. In contrast, pretreatment with R-citalopram (10mg/kg, i.p.) or reboxetine (10mg/kg, i.p.) did not affect the alterations in serum levels of TNF-α and IL-10 after LPS administration. Co-administration of reboxetine with escitalopram did not show anti-inflammatory effects. Pretreatment with escitalopram (10mg/kg) significantly attenuated LPS-induced increase of the immobility time in the tail-suspension test (TST) and forced swimming test (FST). In contrast, pretreatment with R-citalopram (10mg/kg), or reboxetine (10mg/kg) did not alter LPS-induced increase of immobility time of TST and FST. Interestingly, co-administration of reboxetine with escitalopram did not show antidepressant effect in this model. These findings suggest that escitalopram, but not R-citalopram and reboxetine, has anti-inflammatory and antidepressant effects in LPS-treated model of depression, and that reboxetine can antagonize the effects of escitalopram in the inflammation model. Therefore, it is likely that serotonergic system plays a key role in the pathophysiology of inflammation-induced depression. PMID:26892759

  10. Chronic administration of nalmefene leads to increased food intake and body weight gain in mice.

    PubMed

    Chen, Richard Z; Huang, Ruey-Ruey C; Shen, Chun-Pyn; MacNeil, Douglas J; Fong, Tung M

    2004-07-01

    Nalmefene is an orally available opioid receptor antagonist that has been shown to suppress appetite in humans, but its effects on chronic food intake and body weight remain unclear. Here, we report that chronic (21-day) oral administration of nalmefene at 2 or 10 mg/kg/day in diet-induced obese (DIO) mice led to significant increases (9-11%) in cumulative food intake. Mice in the nalmefene-treated groups also gained body weight at a rate faster than the control. Body composition analysis showed that the extra body weight gains in the treated animals were mostly due to increased fat accumulation. Since acute nalmefene treatment showed a trend toward a decrease rather than an increase in food intake, it is possible that the orexigenic effect of chronic oral administration of nalmefene was caused by pharmacologically active metabolites rather than the drug itself. Our results argue against the potential use of nalmefene for treating human obesity. PMID:15219821

  11. Development of Spexin-based Human Galanin Receptor Type II-Specific Agonists with Increased Stability in Serum and Anxiolytic Effect in Mice

    PubMed Central

    Reyes-Alcaraz, Arfaxad; Lee, Yoo-Na; Son, Gi Hoon; Kim, Nam Hoon; Kim, Dong-Kyu; Yun, Seongsik; Kim, Dong-Hoon; Hwang, Jong-Ik; Seong, Jae Young

    2016-01-01

    The novel neuropeptide spexin (SPX) was discovered to activate galanin receptor 2 (GALR2) and 3 (GALR3) but not galanin receptor 1 (GALR1). Although GALR2 is known to display a function, particularly in anxiety, depression, and appetite regulation, the further determination of its function would benefit from a more stable and selective agonist that acts only at GALR2. In the present study, we developed a GALR2-specific agonist with increased stability in serum. As galanin (GAL) showed a low affinity to GALR3, the residues in SPX were replaced with those in GAL, revealing that particular mutations such as Gln5 → Asn, Met7 → Ala, Lys11 → Phe, and Ala13 → Pro significantly decreased potencies toward GALR3 but not toward GALR2. Quadruple (Qu) mutation of these residues still retained potency to GALR2 but totally abolished the potency to both GALR3 and GALR1. The first amino acid modifications or D-Asn1 substitution significantly increased the stability when they are incubated in 100% fetal bovine serum. Intracerebroventricular administration of the mutant peptide with D-Asn1 and quadruple substitution (dN1-Qu) exhibited an anxiolytic effect in mice. Taken together, the GALR2-specific agonist with increased stability can greatly help delineation of GALR2-mediated functions and be very useful for treatments of anxiety disorder. PMID:26907960

  12. A Single Oral Administration of Theaflavins Increases Energy Expenditure and the Expression of Metabolic Genes

    PubMed Central

    Kudo, Naoto; Arai, Yasunori; Suhara, Yoshitomo; Ishii, Takeshi; Nakayama, Tsutomu; Osakabe, Naomi

    2015-01-01

    Theaflavins are polyphenols found in black tea, whose physiological activities are not well understood. This study on mice evaluated the influence of a single oral administration of theaflavins on energy metabolism by monitoring the initial metabolic changess in skeletal muscle and brown adipose tissue (BAT). Oxygen consumption (VO2) and energy expenditure (EE) were increased significantly in mice treated with theaflavin rich fraction (TF) compared with the group administered vehicle alone. There was no difference in locomotor activity. Fasting mice were euthanized under anesthesia before and 2 and 5, 20-hr after treatment with TF or vehicle. The mRNA levels of uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in BAT were increased significantly 2-hr after administration ofTF. The levels of UCP-3 and PGC-1α in the gastrocnemius muscle were increased significantly 2 and 5-hr after administration of TF. The concentration of phosphorylated AMP-activated protein kinase (AMPK) 1α was also increased significantly in the gastrocnemius 2 and 5-hr after treatment with TF. These results indicate that TF significantly enhances systemic energy expenditure, as evidenced by an increase in expression of metabolic genes. PMID:26375960

  13. A Single Oral Administration of Theaflavins Increases Energy Expenditure and the Expression of Metabolic Genes.

    PubMed

    Kudo, Naoto; Arai, Yasunori; Suhara, Yoshitomo; Ishii, Takeshi; Nakayama, Tsutomu; Osakabe, Naomi

    2015-01-01

    Theaflavins are polyphenols found in black tea, whose physiological activities are not well understood. This study on mice evaluated the influence of a single oral administration of theaflavins on energy metabolism by monitoring the initial metabolic changess in skeletal muscle and brown adipose tissue (BAT). Oxygen consumption (VO2) and energy expenditure (EE) were increased significantly in mice treated with theaflavin rich fraction (TF) compared with the group administered vehicle alone. There was no difference in locomotor activity. Fasting mice were euthanized under anesthesia before and 2 and 5, 20-hr after treatment with TF or vehicle. The mRNA levels of uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in BAT were increased significantly 2-hr after administration ofTF. The levels of UCP-3 and PGC-1α in the gastrocnemius muscle were increased significantly 2 and 5-hr after administration of TF. The concentration of phosphorylated AMP-activated protein kinase (AMPK) 1α was also increased significantly in the gastrocnemius 2 and 5-hr after treatment with TF. These results indicate that TF significantly enhances systemic energy expenditure, as evidenced by an increase in expression of metabolic genes. PMID:26375960

  14. Increased serum sTRAIL levels were correlated with survival in bevacizumab-treated metastatic colon cancer

    PubMed Central

    2012-01-01

    Background Colorectal cancer is the third most common cancer and the third leading cause of cancer-related death. Bevacizumab is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF) for the treatment of metastatic cancer. The parameters of RECIST (Response Evaluation Criteria for Solid Tumors) are not adequate to detect important treatment effects and response. Our goal was to evaluate the possibility of using sTRAIL (serum-soluble TNF-related apoptosis-inducing ligand) and VEGF as markers of treatment efficacy and prognosis in patients with metastatic colon cancer. Methods sTRAIL and VEGF levels were measured by ELISA in the sera of 16 bevacizumab-treated metastatic colon cancer patients and 10 presumably healthy age-matched controls. The measurements were taken before and after treatment for comparison purposes. Results Elevated levels of sTRAIL were found in seven out of 16 patients after bevacizumab treatment. Although these patients had a median survival time of 20.6 months, the remaining bevacizumab-treated patients who did not show an increase in sTRAIL had a median survival time of 9.4 months. As expected, serum VEGF levels were decreased in all patients who received bevacizumab therapy and showed no correlation between serum VEGF levels and patient survival (data not shown). Conclusions Serum sTRAIL levels might be a useful predictor of prognosis in metastatic colon cancer, in the early evaluation stages following bevacizumab treatment. PMID:22313795

  15. Treatment of muscle injuries by local administration of autologous conditioned serum: a pilot study on sportsmen with muscle strains.

    PubMed

    Wright-Carpenter, T; Klein, P; Schäferhoff, P; Appell, H J; Mir, L M; Wehling, P

    2004-11-01

    Muscle injuries represent a major part of sports injuries and are a challenging problem in traumatology. Strain injuries are the most common muscle injuries after contusions. These injuries can lead to significant pain and disability causing time to be lost to training and competition. Despite the frequency of strain injuries the treatment available is limited and is generally not sufficient to enhance muscle regeneration efficiently when fast resumption of sport activity is a primary target. A number of growth factors play a specific role in regeneration and it has been proven that a previously described method of physically and chemically stimulating whole blood (to produce autologous conditioned serum) induces concentration increases in FGF-2, HGF, and TGF-beta1. A preliminary study was conducted on muscle strain injuries in professional sportsmen receiving either: 1. autologous conditioned serum (ACS) or 2. Actovegin/Traumeel treatment as control. Assessment of recovery from injury was done by: 1. sport professional's ability to participate to 100 % under competition conditions in their respective sport and 2. MRI analysis. A significant difference in the recovery time from injury was demonstrated: 16.6 +/- 0.9 in the ACS treated instead of 22.3 +/- 1.2 (mean +/- SEM) days in the Actovegin/Traumeel control group (p = 0.001). MRI analysis supported the observed acceleration of the lesion recovery time. We conclude that ACS injection is a promising approach to reduce the time to recovery from muscle injury. PMID:15532001

  16. [A case of pulmonary asbestosis with slightly increased serum IgE concentration and histopathological changes resembling DIP].

    PubMed

    Ikeno, Y; Asai, S; Mashimoto, H; Shimokawa, I; Iwasaki, K; Matsuo, T; Ikeda, T; Minami, H

    1993-02-01

    A 68-year-old male presented with cough and sputum. He had suffered from these symptoms for ten years prior to admission. Chest roentgenogram revealed reticulonodular shadows in the lower fields of both lungs. CT scan of the chest revealed an interstitial pattern in the lower field of both lungs. Honeycombing and bullous pattern were also present in the subpleural area. The patient had a history of dust and asbestos inhalation while working as an electrician. Eosinophilia of the peripheral blood and BALF, and a slightly increased serum IgE concentration were noted. Open lung biopsy revealed interstitial fibrosis with intra-alveolar macrophage accumulation and asbestos bodies. The histopathological features resembled UIP and DIP, although DIP is uncommon in pulmonary asbestosis. The slightly increased serum IgE concentration was considered to be an additional effect of asbestos. This is a case of pulmonary asbestosis with intriguing immunological and histopathological features. PMID:8515602

  17. Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic disease.

    PubMed

    Nakamura, Tatsufumi; Satoh, Katsuya; Fukuda, Taku; Kinoshita, Ikuo; Nishiura, Yoshihiro; Nagasato, Kunihiko; Yamauchi, Atsushi; Kataoka, Yasufumi; Nakamura, Tadahiro; Sasaki, Hitoshi; Kumagai, Kenji; Niwa, Masami; Noguchi, Mitsuru; Nakamura, Hideki; Nishida, Noriyuki; Kawakami, Atsushi

    2014-06-01

    The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction is immunomodulatory treatment, with drugs such as corticosteroid hormone and interferon-α, at present. However, there are many issues in long-term treatment with these drugs, such as insufficient effects and various side effects. We now urgently need to develop other therapeutic strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely used in Europe for the past 50 years as a thrombosis prophylaxis and for the treatment of phlebitis. We conducted a clinical trial to test the effect of subcutaneous administration of PPS in 12 patients with HAM/TSP in an open-labeled design. There was a marked improvement in lower extremity motor function, based on reduced spasticity, such as a reduced time required for walking 10 m and descending a flight of stairs. There were no significant changes in HTLV-I proviral copy numbers in peripheral blood contrary to the inhibitory effect of PPS in vitro for intercellular spread of HTLV-I. However, serum soluble vascular cell adhesion molecule (sVCAM)-1 was significantly increased without significant changes of serum level of chemokines (CXCL10 and CCL2). There was a positive correlation between increased sVCAM-1and reduced time required for walking 10 m. PPS might induce neurological improvement by inhibition of chronic inflammation in the spinal cord, through blocking the adhesion cascade by increasing serum sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has the potential to be a new therapeutic tool for HAM/TSP. PMID:24671717

  18. Brain-derived neurotrophic factor serum concentrations in acute depressive patients increase during lithium augmentation of antidepressants.

    PubMed

    Ricken, Roland; Adli, Mazda; Lange, Claudia; Krusche, Esther; Stamm, Thomas J; Gaus, Sebastian; Koehler, Stephan; Nase, Sarah; Bschor, Tom; Richter, Christoph; Steinacher, Bruno; Heinz, Andreas; Rapp, Michael A; Borgwardt, Stefan; Hellweg, Rainer; Lang, Undine E

    2013-12-01

    In recent years, lithium has proved an effective augmentation strategy of antidepressants in both acute and treatment-resistant depression. Neuroprotective and procognitive effects of lithium have been evidenced. Brain-derived neurotrophic factor (BDNF) has been shown to play a key role in the pathophysiology of several neurological and psychiatric disorders. The BDNF hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and its restoration may underlie the therapeutic efficacy of antidepressant treatments. Brain-derived neurotrophic factor serum concentrations were measured in a total of 83 acutely depressed patients before and after 4 weeks of lithium augmentation. A significant BDNF increase has been found during treatment (F2,81 = 5.04, P < 0.05). Brain-derived neurotrophic factor concentrations at baseline correlated negatively with relative Hamilton Depression Scale change after treatment with lithium (n = 83; r = -0.23; P < 0.05). This is the first study showing that lithium augmentation of an antidepressant strategy can increase BDNF serum concentrations. Our study replicates previous findings showing that serum BDNF levels in patients with depressive episodes increase during effective antidepressant treatment. Further studies are needed to separate specific effects of different antidepressants on BDNF concentration and address potential BDNF downstream mechanisms. PMID:24018547

  19. AP2-NR4A3 transgenic mice display reduced serum epinephrine because of increased catecholamine catabolism in adipose tissue.

    PubMed

    Walton, R Grace; Zhu, Xiaolin; Tian, Ling; Heywood, Elizabeth B; Liu, Jian; Hill, Helliner S; Liu, Jiarong; Bruemmer, Dennis; Yang, Qinglin; Fu, Yuchang; Garvey, W Timothy

    2016-07-01

    The NR4A orphan nuclear receptors function as early response genes to numerous stimuli. Our laboratory has previously demonstrated that overexpression of NR4A3 (NOR-1, MINOR) in 3T3-L1 adipocytes enhances insulin-stimulated glucose uptake. To assess the in vivo effect of NR4A3 on adipocytes, we generated transgenic mice with NR4A3 overexpression driven by the adipocyte fatty acid-binding protein (AP2) promoter (AP2-NR4A3 mice). We hypothesized that AP2-NR4A3 mice would display enhanced glucose tolerance and insulin sensitivity. However, AP2-NR4A3 mice exhibit metabolic impairment, including increased fasting glucose and insulin, impaired glucose tolerance, insulin resistance, decreased serum free fatty acids, and increased low-density lipoprotein-cholesterol. AP2-NR4A3 mice also display a significant reduction in serum epinephrine due to increased expression of catecholamine-catabolizing enzymes in adipose tissue, including monoamine oxidase-A. Furthermore, enhanced expression of monoamine oxidase-A is due to direct transcriptional activation by NR4A3. Finally, AP2-NR4A3 mice display cardiac and behavioral alterations consistent with chronically low circulating epinephrine levels. In conclusion, overexpression of NR4A3 in adipocytes produces a complex phenotype characterized by impaired glucose metabolism and low serum catecholamines due to enhanced degradation by adipose tissue. PMID:27166283

  20. 17β-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

    PubMed

    Mason, Julie K; Kharotia, Shikhil; Wiggins, Ashleigh K A; Kitson, Alex P; Chen, Jianmin; Bazinet, Richard P; Thompson, Lilian U

    2014-08-01

    Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status. PMID:24913495

  1. Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone.

    PubMed

    Besheer, Joyce; Fisher, Kristen R; Lindsay, Tessa G; Cannady, Reginald

    2013-09-01

    Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5-0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals. PMID:23643750

  2. Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

    PubMed

    Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

    2015-01-01

    Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread. PMID:25433717

  3. Prophylactic Chronic Zinc Administration Increases Neuroinflammation in a Hypoxia-Ischemia Model

    PubMed Central

    Tomas-Sanchez, Constantino; Blanco-Alvarez, Victor Manuel; Gonzalez-Barrios, Juan Antonio; Martinez-Fong, Daniel; Garcia-Robles, Guadalupe; Soto-Rodriguez, Guadalupe; Torres-Soto, Maricela; Gonzalez-Vazquez, Alejandro; Aguilar-Peralta, Ana Karina; Garate-Morales, José-Luis; Aguilar-Carrasco, Luis-Angel; Limón, Daniel I.; Cebada, Jorge

    2016-01-01

    Acute and subacute administration of zinc exert neuroprotective effects in hypoxia-ischemia animal models; yet the effect of chronic administration of zinc still remains unknown. We addressed this issue by injecting zinc at a tolerable dose (0.5 mg/kg weight, i.p.) for 14 days before common carotid artery occlusion (CCAO) in a rat. After CCAO, the level of zinc was measured by atomic absorption spectrophotometry, nitrites were determined by Griess method, lipoperoxidation was measured by Gerard-Monnier assay, and mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors was measured by qRT-PCR, whereas nitrotyrosine, chemokines, and their receptors were assessed by ELISA and histopathological changes in the temporoparietal cortex-hippocampus at different time points. Long-term memory was evaluated using Morris water maze. Following CCAO, a significant increase in nitrosative stress, inflammatory chemokines/receptors, and cell death was observed after 8 h, and a 2.5-fold increase in zinc levels was detected after 7 days. Although CXCL12 and FGF2 protein levels were significantly increased, the long-term memory was impaired 12 days after reperfusion in the Zn+CCAO group. Our data suggest that the chronic administration of zinc at tolerable doses causes nitrosative stress, toxic zinc accumulation, and neuroinflammation, which might account for the neuronal death and cerebral dysfunction after CCAO.

  4. Oral Administration of Recombinant Lactococcus lactis Expressing the Cellulase Gene Increases Digestibility of Fiber in Geese.

    PubMed

    Zhou, Haizhu; Gao, Yunhang; Gao, Guang; Lou, Yujie

    2015-12-01

    Enhancing cellulose digestibility in animals is important for improving the utilization of forage, which can decrease the amount of food used in animal production. The aim of the present study was to achieve recombinant expression of the cellulase gene in Lactococcus lactis and evaluate the effects of oral administration of the recombinant L. lactis on fiber digestibility in geese. Cellulase (Cell) and green fluorescent protein (GFP) genes were cloned into a L. lactis expression vector (pNZ8149) to construct the recombinant expression plasmid (pNZ8149-GFP-Cell). Then, the recombinant expression plasmid was transformed into L. lactis (NZ3900) competent cells by electroporation to obtain recombinant L. lactis (pNZ8149-GFP-Cell/NZ3900) in which protein expression was induced by Nisin. Expression of GFP and Cell by the recombinant L. lactis was confirmed using SDS-PAGE, fluorescence detection, and Congo red assays. A feeding experiment showed that oral administration of pNZ8149-GFP-Cell/NZ3900 significantly increased the digestibility of dietary fiber in geese fed either a maize stalk diet or a rice chaff diet. Therefore, oral administration of recombinant L. lactis cells expressing the cellulase gene increases fiber digestibility in geese, offering a way to increase the utilization of dietary fiber in geese. PMID:26341925

  5. Insufficient insulin administration to diabetic rats increases substrate utilization and maintains lactate production in the kidney.

    PubMed

    Laustsen, Christoffer; Lipsø, Kasper; Ostergaard, Jakob Appel; Nørregaard, Rikke; Flyvbjerg, Allan; Pedersen, Michael; Palm, Fredrik; Ardenkjær-Larsen, Jan Henrik

    2014-12-01

    Good glycemic control is crucial to prevent the onset and progression of late diabetic complications, but insulin treatment often fails to achieve normalization of glycemic control to the level seen in healthy controls. In fact, recent experimental studies indicate that insufficient treatment with insulin, resulting in poor glycemic control, has an additional effect on progression of late diabetic complications, than poor glycemic control on its own. We therefore compared renal metabolic alterations during conditions of poor glycemic control with and without suboptimal insulin administration, which did not restore glycemic control, to streptozotocin (STZ)-diabetic rats using noninvasive hyperpolarized (13)C-pyruvate magnetic resonance imaging (MRI) and blood oxygenation level-dependent (BOLD) (1)H-MRI to determine renal metabolic flux and oxygen availability, respectively. Suboptimal insulin administration increased pyruvate utilization and metabolic flux via both anaerobic and aerobic pathways in diabetic rats even though insulin did not affect kidney oxygen availability, HbA1c, or oxidative stress. These results imply direct effects of insulin in the regulation of cellular substrate utilization and metabolic fluxes during conditions of poor glycemic control. The study demonstrates that poor glycemic control in combination with suboptimal insulin administration accelerates metabolic alterations by increasing both anaerobic and aerobic metabolism resulting in increased utilization of energy substrates. The results demonstrate the importance of tight glycemic control in insulinopenic diabetes, and that insulin, when administered insufficiently, adds an additional burden on top of poor glycemic control. PMID:25501426

  6. Cocaine self-administration produces a persistent increase in dopamine D2 High receptors.

    PubMed

    Briand, Lisa A; Flagel, Shelly B; Seeman, Philip; Robinson, Terry E

    2008-08-01

    Cocaine addicts are reported to have decreased numbers of striatal dopamine D2 receptors. However, in rodents, repeated cocaine administration consistently produces hypersensitivity to the psychomotor activating effects of both indirect dopamine agonists, such as cocaine itself, and importantly, to direct-acting D2 receptor agonists. The current study reports a possible resolution to this long-standing paradox. The dopamine D2 receptor exists in both a low and a high-affinity state, and dopamine exerts its effects via the more functionally relevant high-affinity D2 receptor (D2 High). We report here that cocaine self-administration experience produces a large (approximately 150%) increase in the proportion of D2 High receptors in the striatum with no change in the total number of D2 receptors, and this effect is evident both 3 and 30 days after the discontinuation of cocaine self-administration. Changes in D2 High receptors would not be evident with the probes used in human (and non-human primate) imaging studies. We suggest, therefore, that cocaine addicts and animals previously treated with cocaine may be hyper-responsive to dopaminergic drugs in part because an increase in D2 High receptors results in dopamine supersensitivity. This may also help explain why stimuli that increase dopamine neurotransmission, including drugs themselves, are so effective in producing relapse in individuals with a history of exposure to cocaine. PMID:18284941

  7. Blackcurrant seed press residue increases tocopherol concentrations in serum and stool whilst biomarkers in stool and urine indicate increased oxidative stress in human subjects.

    PubMed

    Helbig, Dorit; Wagner, Andreas; Glei, Michael; Basu, Samar; Schubert, Rainer; Jahreis, Gerhard

    2009-08-01

    Berry seeds are a tocopherol-rich by-product of fruit processing without specific commercial value. In a human intervention study, the physiological impact of blackcurrant seed press residue (PR) was tested. Thirty-six women (aged 24 +/- 3 years; twenty non-smokers, sixteen smokers) consumed 250 g bread/d containing 8% PR for a period of 4 weeks (period 3). Comparatively, a control bread without PR (250 g/d) was tested (period 2) and baseline data were obtained (period 1). Blood, stool and 24 h urine were collected during a 5 d standardised diet within each period. Tocopherol and Fe intakes were calculated from food intake. In serum, tocopherol concentration and Fe parameters were determined. In urine, oxidative stress markers 8-oxo-2'-deoxyguanosine, 8-iso-PGF2alpha and inflammatory response marker 15-keto-dihydro-PGF2alpha were analysed. Stool tocopherol concentration, genotoxicity of faecal water (comet assay) and antioxidant capacity of stool (aromatic hydroxylation of salicylic acid) were determined. Fe and total tocopherol intake, total tocopherol concentrations in serum and stool, and genotoxicity of faecal water increased with PR bread consumption (P < 0.05). The antioxidant capacity of stool decreased between baseline and intervention, expressed by increased formation of 2,3- and 2,5-dihydroxybenzoic acid in vitro (P < 0.05). In smokers, 8-oxo-2'-deoxyguanosine increased with PR consumption (P < 0.05). Prostane concentrations were unaffected by PR bread consumption. In summary, the intake of bread containing blackcurrant PR for 4 weeks increased serum and stool total tocopherol concentrations. However, various biomarkers indicated increased oxidative stress, suggesting that consumption of ground berry seed may not be of advantage. PMID:19302719

  8. Increased serum levels of lipocalin-1 and -2 in patients with stable chronic obstructive pulmonary disease

    PubMed Central

    Wang, Xiao-ru; Li, Yong-pu; Gao, Shui; Xia, Wei; Gao, Kun; Kong, Qing-hua; Qi, Hui; Wu, Ling; Zhang, Jing; Qu, Jie-ming; Bai, Chun-xue

    2014-01-01

    Despite a number of studies on biomarkers in chronic obstructive pulmonary disease (COPD), only a few disease-related markers have been identified, yet we still have no satisfactory markers specific to innate immune system and neutrophil activation, which is essential in airway inflammation in COPD. Recent biological studies indicated that lipocalins (LCNs) might be involved in airway inflammation and innate immunity; however, results from available studies on the association of LCNs with COPD are not consistent. We carried out a multicenter prospective observational cohort study to investigate the differences in serum levels of LCN1 and LCN2 between subjects with COPD (n=58) and healthy controls (n=29). Several validated inflammatory markers, including C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-8, were measured. The correlation of LCN1 and LCN2 with clinical features such as smoking habits, lung function, symptoms, and disease category was also analyzed. When comparing with healthy controls, serum levels of LCN1 (66.35±20.26 ng/mL versus 41.16±24.19 ng/mL, P<0.001) and LCN2 (11.29±3.92 ng/mL versus 6.09±5.13 ng/mL, P<0.001) were both elevated in subjects with COPD after adjusting for age, sex, smoking habits, and inflammatory biomarkers. Smoking history and tobacco exposure, as quantified by pack-year, had no impact on systemic expressions of LCN1 and LCN2 in our study. Blood levels of LCN1 and LCN2, respectively, were negatively correlated to COPD Assessment Test and Modified Medical British Research Council score (P<0.001). Disease category by Global Initiative for Chronic Obstructive Lung Disease grade 1–4 or group A–D was not associated with levels of LCNs. Patient-reported exacerbations and body mass index were also tested, but no relationship with LCNs was found. In summary, serum concentrations of LCN1 and LCN2 were both elevated in patients with COPD, with their levels correlating to COPD Assessment Test and

  9. Administration of Escherichia coli endotoxin to rat increases liver mass and hepatocyte volume in vivo.

    PubMed Central

    Qian, D; Brosnan, J T

    1996-01-01

    We have established, in vivo, an increase in liver mass and hepatocyte volume after a single intraperitoneal administration, to fasted rats, of Escherichia coli lipopolysaccharide (0127:B8) at 3 mg/kg. The phenomenon was time- and dose-dependent and could be prevented by treatment with polyclonal antiserum against tumour necrosis factor-alpha (TNF-alpha) before the endotoxin injection. Endotoxin caused an increase of 26% in the hepatic mass compared with fasted controls at 24 h. An increase of 27% in the hepatic water content underlay the altered hepatic mass which could not be accounted for by a change in the volume of hepatic blood and/or interstitial fluid (measured in vivo), suggesting an expansion in the hepatocellular volume. This is supported by an increase of 25% in the K+ content of the endotoxic livers. Morphometric study confirmed a 15% increase in hepatocyte volume after endotoxin administration. The data are discussed in the light of possible metabolic effects of increased hepatocyte volume. PMID:8573081

  10. Serum DHEA-S increases in dogs naturally infected with Ehrlichia canis.

    PubMed

    Rondelli, M C H; Munhoz, T D; Catandi, P B; Freschi, C R; Palacios Junior, R J G; Machado, R Z; Tinucci-Costa, M

    2015-06-01

    Adrenocortical disturbances are expected in canine ehrlichiosis due to the immunological challenges caused by infection and consequent inflammation. Thus, this study aimed to evaluate the occurrence of adrenocortical hormonal alterations in dogs naturally infected with Ehrlichia canis (n = 21) as positively confirmed by the presence of anti-E. canis antibodies (Dot-ELISA) and nested PCR (nPCR). Serum dehydroepiandrosterone sulfate (DHEA-S) concentrations were assessed via ELISA before and one hour after ACTH stimulation. Another 10 healthy dogs were subjected to the same stimulation protocol and used as controls. The results revealed that baseline and post-ACTH DHEA-S concentrations were significantly greater in sick dogs, regardless of gender, and this finding illustrates the stress induced by naturally acquired ehrlichiosis in dogs. PMID:25956636

  11. Prolactin, Androstenedione and IGF1 Serum Concentrations During Induced Follicular Growth by eCG Administration in the Bitch.

    PubMed

    Stornelli, M C; García Mitacek, M C; Praderio, R G; Nuñez Favre, R; de la Sota, R L; Stornelli, M A

    2016-02-01

    The oestrus cycle in the domestic bitch, a monoestrous species, differs considerably from that of other veterinary domestic animals species. In the bitch the combined use of eCG and hCG is effective to induce oestrus predictably and safely (Stornelli et al., Theriogenology, 78, 2012 and 1056). Although several studies were done to describe the hormonal changes during the canine oestrus cycle, to our knowledge none was done to describe the hormonal changes during induced follicular growth after the administration of eCG. The aim of this work was to study prolactin (PRL), insulin-like growth factor (IGF1) and androstenedione (ANDR) serum concentrations during follicular growth induced by a single dose of eCG administered to late anoestrous bitches. PRL and ANDR concentrations were lower before than after eCG TRT (before eCG vs pro-oestrus, oestrus and dioestrus; 4.3 ± 1.8 ng/ml vs 6.5 ± 1.6 ng/ml, p < 0.05; 0.08 ± 0.2 ng/ml vs 0.42 ± 0.16 ng/ml, p < 0.05). Conversely, IGF1 concentrations were similar before and after eCG TRT (286.0 ng/ml ±32.2, p > 0.53). Additionally, PRL concentrations were similar before oestrus compared to during oestrus and dioestrus (6.9 ± 1.7 ng/ml, p > 0.19). Furthermore, IGF1 concentrations were higher before and during oestrus compared to first day of dioestrus (286.1 ± 29.8vs 200.4 ± 29.2 ng/ml, p < 0.01). On the contrary, ANDR concentrations were lower before and during oestrus compared to first day of diestrum (0.35 ± 0.17 ng/ml and 0.38 ± 0.15 vs 0.68 ± 0.17 ng/ml, p < 0.05). These results show that treatment with a single injection of 50 IU/kg of eCG in late anoestrous bitches successfully induced changes in follicular growth which were paralleled with changes in PRL, IGF1 and ANDR serum concentration similar to those occurring during a normally occurring oestrous cycle. In addition, our results suggest that IGF1 in the bitch could play an important role in ovarian folliculogenesis. PMID:26695709

  12. The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats

    NASA Technical Reports Server (NTRS)

    Dobnig, H.; Turner, R. T.

    1997-01-01

    PTH treatment can result in dramatic increases in cancellous bone volume in normal and osteopenic rats. However, this potentially beneficial response is only observed after pulsatile treatment; continuous infusion of PTH leads to hypercalcemia and bone abnormalities. The purpose of these studies was to determine the optimal duration of the PTH pulses. A preliminary study revealed that human PTH-(1-34) (hPTH) is cleared from circulation within 6 h after sc administration of an anabolic dose of the hormone (80 microg/kg). To establish the effects of gradually extending the duration of exposure to hPTH without increasing the daily dose, we programmed implanted Alzet osmotic pumps to deliver the 80 microg/kg x day dose of the hormone during pulses of 1, 2, and 6 h/day, or 40 microg/kg x day continuously. Discontinuous infusion was accomplished by alternate spacing of external tubing with hPTH solution and sesame oil. After 6 days of treatment, we evaluated serum chemistry and bone histomorphometry. As negative and positive controls, groups of rats received pumps that delivered vehicle only and 80 microg/kg x day hPTH by daily sc injection, respectively. Dynamic and static bone histomorphometry revealed that the daily sc injection and 1 h/day infusion dramatically increased osteoblast number and bone formation in the proximal tibial metaphysis, whereas longer infusion resulted in systemic side-effects, including up to a 10% loss in body weight, hypercalcemia, and histological changes in the proximal tibia resembling abnormalities observed in patients with chronic primary hyperparathyroidism, including peritrabecular marrow fibrosis and focal bone resorption. Infusion for as little as 2 h/day resulted in minor weight loss and changes in bone histology that were intermediate between sc and continuous administration. The results demonstrate that the therapeutic interval for hPTH exposure is brief, but that programmed administration of implanted hormone is a feasible

  13. Evaluation of IgG concentration and IgG subisotypes in foals with complete or partial failure of passive transfer after administration of intravenous serum or plasma.

    PubMed

    McClure, J T; DeLuca, J L; Lunn, D P; Miller, J

    2001-11-01

    The purpose of this study was to evaluate the ability of an equine plasma product i.v. and a concentrated serum product i.v. to deliver antibodies to 46 foals with failure of passive transfer (FPT). Treatment of FPT was as per manufacturers recommendations, using plasma (950 ml/unit) or a concentrated serum product (250 ml/unit). Significant variables affecting the 3 day post-transfusion serum immunoglobulin G (IgG) concentration of foals included body weight, pretransfusion IgG concentration, number of product units transfused, foaling season and product administered. Plasma treatment had a greater increase in post-transfusion serum IgG concentrations compared to the serum product treatment mainly because plasma contained approximately twice the amount of IgG per unit as the serum product. The change in equine influenza virus and tetanus toxoid-specific IgGa, IgGb, and IgG(T) titres was measured in foals from pretransfusion to 3 days post-transfusion. For each gram of IgG transfused, the change in antigen-specific IgG subisotypes were similar for both treatment groups. The results of this study suggest that similar foal serum IgG concentrations can be achieved 3 days post-transfusion by administering 1 unit of plasma or 2-3 units of serum product. PMID:11770990

  14. Increased MMP-7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia.

    PubMed

    Kerola, Anna; Lampela, Hanna; Lohi, Jouko; Heikkilä, Päivi; Mutanen, Annika; Hagström, Jaana; Tervahartiala, Taina; Sorsa, Timo; Haglund, Caj; Jalanko, Hannu; Pakarinen, Mikko P

    2016-07-01

    The molecular mechanisms underlying progressive liver fibrosis following surgical treatment of biliary atresia (BA) remain unclear. Our aim was to address hepatic gene and protein expression and serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after successful portoenterostomy (PE), and relate them to histological signs of liver injury, clinical follow-up data and biochemical markers of hepatic function. LIver biopsies and serum samples were obtained from 25 children after successful PE at median age of 3.3 years. Serum MMP concentrations were determined by enzyme-linked immune sorbent assay. Hepatic gene expression of MMPs and TIMPs was analyzed using real-time reverse-transcription PCR. Liver expression of MMP-7 and cytokeratin-7 was studied using immunohistochemistry. Despite effective clearance of biochemical and histological cholestasis following PE, BA patients showed increased hepatic gene expression of MMP-7 (29-fold, p < 0.001), MMP-2 (3.1-fold, p < 0.001), MMP-14 (1.7-fold, p = 0.007), and TIMP-1 (1.8-fold, p < 0.001), when compared to controls. Similar to a biliary epithelial marker cytokeratin-7, expression of MMP-7 localized in biliary epithelium of bile ducts and ductal proliferations and periportal hepatocytes and was increased (p < 0.001) in relation to controls. BA patients had 6-fold higher serum levels of MMP-7 (p < 0.001), which correlated positively with hepatic MMP-7 gene (r = 0.548, p = 0.007) and protein (r = 0.532, p = 0.007) expression. Patients showed a positive correlation between biliary MMP-7 expression and Metavir fibrosis stage (r = 0.605, p = 0.001) and portal fibrosis grade (r = 0.606, p = 0.001). Neither similarly increased MMP-7 expression nor correlation with liver fibrosis was observed in patients with intestinal failure-associated liver disease and comparable Metavir stage. In conclusion, our findings support an unique role of altered

  15. Chronic Cladribine Administration Increases Amyloid Beta Peptide Generation and Plaque Burden in Mice

    PubMed Central

    Hayes, Crystal D.; Dey, Debleena; Palavicini, Juan Pablo; Wang, Hongjie; Araki, Wataru; Lakshmana, Madepalli K.

    2012-01-01

    Background The clinical uses of 2-chloro-2′-deoxyadenosine (2-CDA) or cladribine which was initially prescribed to patients with hematological and lymphoid cancers is now extended to treat patients with multiple sclerosis (MS). Previous data has shown that 2-CDA has high affinity to the brain and readily passes through the blood brain barrier reaching CSF concentrations 25% of that found in plasma. However, whether long-term administration of 2-CDA can lead to any adverse effects in patients or animal models is not yet clearly known. Methodology Here we show that exposure of 2-CDA to CHO cells stably expressing wild-type APP751 increased generation and secretion of amyloid β peptide (Aβ) in to the conditioned medium. Interestingly, increased Aβ levels were noticed even at non-toxic concentrations of 2-CDA. Remarkably, chronic treatment of APdE9 mice, a model of Alzheimer's disease with 2-CDA for 60 days increased amyloid plaque burden by more than 1-fold. Increased Aβ generation appears to result from increased turnover of APP as revealed by cycloheximide-chase experiments. Additionally, surface labeling of APP with biotin and immunoprecipitation of surface labeled proteins with anti-biotin antibody also indicated increased APP at the cell surface in 2-CDA treated cells compared to controls. Increased turnover of APP by 2-CDA in turn might be a consequence of decreased protein levels of PIN 1, which is known to regulate cis-trans isomerization and phosphorylation of APP. Most importantly, like many other oncology drugs, 2-CDA administration led to significant delay in acquiring a reward-based learning task in a T maze paradigm. Conclusions Taken together, these data provide compelling evidence for the first time that chronic 2-CDA administration can increase amyloidogenic processing of APP leading to robustly increased plaque burden which may be responsible for the observed deficits in learning skills. Thus chronic treatment of mice with 2-CDA can have

  16. Increase in Sialylation and Branching in the Mouse Serum N-glycome Correlates with Inflammation and Ovarian Tumour Progression

    PubMed Central

    Saldova, Radka; Piccard, Helene; Pérez-Garay, Marta; Harvey, David J.; Struwe, Weston B.; Galligan, Marie C.; Berghmans, Nele; Madden, Stephen F.; Peracaula, Rosa; Opdenakker, Ghislain; Rudd, Pauline M.

    2013-01-01

    Ovarian cancer is the most lethal gynaecological cancer and is often diagnosed in late stage, often as the result of the unavailability of sufficiently sensitive biomarkers for early detection, tumour progression and tumour-associated inflammation. Glycosylation is the most common posttranslational modification of proteins; it is altered in cancer and therefore is a potential source of biomarkers. We investigated the quantitative and qualitative effects of anti-inflammatory (acetylsalicylic acid) and pro-inflammatory (thioglycolate and chlorite-oxidized oxyamylose) drugs on glycosylation in mouse cancer serum. A significant increase in sialylation and branching of glycans in mice treated with an inflammation-inducing compound was observed. Moreover, the increases in sialylation correlated with increased tumour sizes. Increases in sialylation and branching were consistent with increased expression of sialyltransferases and the branching enzyme MGAT5. Because the sialyltransferases are highly conserved among species, the described changes in the ovarian cancer mouse model are relevant to humans and serum N-glycome analysis for monitoring disease treatment and progression might be a useful biomarker. PMID:24023608

  17. Enterostatin deficiency increases serum cholesterol but does not influence growth and food intake in mice.

    PubMed

    Miller, Rita; D'Agostino, Dymphna; Erlanson-Albertsson, Charlotte; Lowe, Mark E

    2009-10-01

    A pentapeptide released from procolipase, enterostatin, selectively attenuates dietary fat intake when administered peripherally or centrally. Enterostatin may act through the afferent vagus nerve and in the hypothalamus and amygdala, primarily in the central nucleus of the amygdala. To investigate the physiological role of endogenous enterostatin, we created an enterostatin-deficient, colipase-sufficient (Ent(-/-)) mouse. Ent(-/-) mice are viable, normally active, and fertile. They exhibit normal growth on low-fat and high-fat diets. Furthermore, Ent(-/-) mice develop diet-induced obesity, as do Ent(+/+) mice, and have normal responses to a two-macronutrient choice diet and to a switch from a high-fat to a low-fat diet. Levels of total serum (P = 0.004) and non-HDL (P

  18. Increased serum nIgM in voluntarily physically active rats: a potential role for B-1 cells.

    PubMed

    Elphick, Gwendolyn F; Greenwood, Benjamin N; Campisi, Jay; Fleshner, Monika

    2003-02-01

    Moderate, habitual physical activity improves health, possibly because of beneficial changes in immune function. For example, physical activity can increase natural killer cell cytotoxicity, T cell proliferation, and macrophage function but has minimal impact on antigen-driven B-2-mediated immunoglobulin (Ig) responses. The following studies tested whether physical activity selectively impacts nonantigen-driven B-1-natural IgM (nIgM) but not antigen-driven B-2 Ig. Adult male, pathogen-free Sprague-Dawley rats in a barrier facility voluntarily ran in wheels from 7 to 56 days or were housed in an enriched environment for 56 days. Rats received either no antigen or keyhole limpet hemocyanin (KLH) to assess the B-2 response. Blood samples assessed serum nIgM, total IgG, total serum protein, anti-KLH IgM, and anti-KLH IgG. Physically active rats had higher serum nIgM after 7 days of running, and nIgM remained elevated over 56 days of running. In contrast, free-wheel running produced no changes in total IgG, total serum protein, anti-KLH IgM, and anti-KLH IgG. Environmental enrichment did not alter immune measures from controls. These results suggest that B-1, not B-2, cell responses are selectively impacted by physical activity. Because nIgM is important in multiple aspects of the immune response, an elevation in this innate humoral component could contribute to improved immunity in physically active organisms. PMID:12391051

  19. [Lysozyme activity (LZM) and unsaturated vitamin B-12-binding capacity (NZW vit B-12) in the serum following prednisone administration in patients with bone marrow aplasia with pancotypenia].

    PubMed

    Wysocki, H; Wierusz-Wysocka, B; Fenrych, W; Prazmowska-Owczarek, B

    1978-01-01

    In 18 patients with bone marrow aplasia with pancytopenia lysozyme activity and unsaturated vitamin B12-binding capacity in the serum were determined. These investigations, together with determinations of peripheral blood polymorphonuclear count, were done again after prednisone administration. In all cases a significant fall was found in the NZW vit B12 and LZM activity in the serum. A slight rise in the polymorphonuclear count in the 24th hour of the study was associated with a rise in the NZW wit. B12 in the serum, and decreased LZM activity. This confirmed the previously demonstrated complex character of corticosteroid action on the system of polymorphonuclears. These results point also to the usefulness of determination of unsaturated vitamin B12-binding capacity for evaluating the value of the total granulocyte pool in granulocytopenia. PMID:735710

  20. Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity.

    PubMed

    Thomsen, J J; Rentsch, R L; Robach, P; Calbet, J A L; Boushel, R; Rasmussen, P; Juel, C; Lundby, C

    2007-11-01

    The effects of recombinant human erythropoietin (rHuEpo) treatment on aerobic power (VO2max) are well documented, but little is known about the effects of rHuEpo on submaximal exercise performance. The present study investigated the effect on performance (ergometer cycling, 20-30 min at 80% of maximal attainable workload), and for this purpose eight subjects received either 5,000 IU rHuEpo or placebo every second day for 14 days, and subsequently a single dose of 5,000 IU/placebo weekly/10 weeks. Exercise performance was evaluated before treatment and after 4 and 11 weeks of treatment. With rHuEpo treatment VO2max increased (P<0.05) by 12.6 and 11.6% in week 4 and 11, respectively, and time-to-exhaustion (80% VO2max) was increased by 54.0 and 54.3% (P<0.05) after 4 and 11 weeks of treatment, respectively. However, when normalizing the workload to the same relative intensity (only done at time point week 11), TTE was decreased by 26.8% as compared to pre rHuEpo administration. In conclusion, in healthy non-athlete subjects rHuEpo administration prolongs submaximal exercise performance by about 54% independently of the approximately 12% increase in VO2max. PMID:17668232

  1. Increased serum IgA concentration and plasmablast frequency in patients with age-related macular degeneration.

    PubMed

    Yu, Honghua; Yuan, Ling; Yang, Yahan; Ma, Suihong; Peng, Lianghong; Wang, Yong; Zhang, Chu; Li, Tao

    2016-05-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among senior citizens of developed countries, with currently unknown etiology. Despite the close associations between AMD development and inhibitory complement factor H mutations, the first step of complement activation, which is the antibody response in AMD patients, has not been studied. Here, we obtained blood and tear samples from AMD patients and Non-AMD controls. We found that compared to Non-AMD controls, AMD subjects had increased IgA titers in serum and tear, and had elevated levels of circulating antibody-secreting plasmablasts. The increase in antibody titer was limited to the IgA isotype, since no significant differences were observed in IgM and IgG isotypes between AMD patients and Non-AMD controls. Interestingly, this increased antibody response in AMD patients was correlated with disease severity, as late AMD patients had increased IgA titers in serum and tear, as well as elevated plasmablast frequency after staphylococcal enterotoxin B stimulation, compared to early AMD patients. Together, our results implicated a role of overreactive IgA responses in AMD pathogenesis. PMID:26827241

  2. Increase of the seizure threshold in C57BL/6 mice after citicoline administration.

    PubMed

    Karpova, M N; Zin'kovskii, K A; Kuznetsova, L V; Klishina, N V

    2015-01-01

    We studied the dose-dependent effect of preventive intraperitoneal injection of citicoline (cytidine 5'-diphosphocholine) on acute generalized epileptiform activity in C57Bl/6 mice. The duration of citicoline action was also evaluated. Administration of citicoline in doses of 500 and 1000 mg/kg 1 h before treatment with the convulsant agent pentylenetetrazole produced an anticonvulsant effect. This effect was manifested in an increase of the threshold of clonic seizures and tonic phase of seizures with lethal outcome. Moreover, the latency of seizure development was elevated under these conditions. The anticonvulsant effect of citicoline persisted for 6 h after its injection. PMID:25573358

  3. Serum-derived exosomes from mice with highly metastatic breast cancer transfer increased metastatic capacity to a poorly metastatic tumor.

    PubMed

    Gorczynski, Reginald M; Erin, Nuray; Zhu, Fang

    2016-02-01

    Altered interaction between CD200 and CD200R represents an example of "checkpoint blockade" disrupting an effective, tumor-directed, host response in murine breast cancer cells. In CD200R1KO mice, long-term cure of EMT6 breast cancer, including metastatic spread to lung and liver, was achieved in BALB/c mice. The reverse was observed with 4THM tumors, an aggressive, inflammatory breast cancer, with increased tumor metastasis in CD200R1KO. We explored possible explanations for this difference. We measured the frequency of circulating tumor cells (CTCs) in peripheral blood of tumor bearers, as well as lung/liver and draining lymph nodes. In some cases mice received infusions of exosomes from nontumor controls, or tumor bearers, with/without additional infusions of anticytokine antibodies. The measured frequency of circulating tumor cells (CTCs) in peripheral blood was equivalent in the two models in WT and CD200R1KO mice. Increased metastasis in EMT6 tumor bearers was seen in vivo following adoptive transfer of serum, or serum-derived exosomes, from 4THM tumor bearers, an effect which was attenuated by anti-IL-6, and anti-IL-17, but not anti-TNFα, antibody. Anti-IL-6 also attenuated enhanced migration of EMT6 cells in vitro induced by 4THM serum or exosomes, or recombinant IL-6. Exosome cytokine proteomic profiles responses in 4THM and EMT6 tumor-bearing mice were regulated by CD200:CD200R interactions, with attenuation of both IL-6 and IL-17 in 4THM CD200(tg) mice, and enhanced levels in 4THM CD200R1KO mice. We suggest these cytokines act on the microenvironment at sites within the host, and/or directly on tumor cells themselves, to increase metastatic potential. PMID:26725371

  4. Sulfation of Lower Chlorinated Polychlorinated Biphenyls Increases Their Affinity for the Major Drug-Binding Sites of Human Serum Albumin.

    PubMed

    Rodriguez, Eric A; Li, Xueshu; Lehmler, Hans-Joachim; Robertson, Larry W; Duffel, Michael W

    2016-05-17

    The disposition of toxicants is often affected by their binding to serum proteins, of which the most abundant in humans is serum albumin (HSA). There is increasing interest in the toxicities of environmentally persistent polychlorinated biphenyls (PCBs) with lower numbers of chlorine atoms (LC-PCBs) due to their presence in both indoor and outdoor air. PCB sulfates derived from metabolic hydroxylation and sulfation of LC-PCBs have been implicated in endocrine disruption due to high affinity-binding to the thyroxine-carrying protein, transthyretin. Interactions of these sulfated metabolites of LC-PCBs with HSA, however, have not been previously explored. We have now determined the relative HSA-binding affinities for a group of LC-PCBs and their hydroxylated and sulfated derivatives by selective displacement of the fluorescent probes 5-dimethylamino-1-naphthalenesulfonamide and dansyl-l-proline from the two major drug-binding sites on HSA (previously designated as Site I and Site II). Values for half-maximal displacement of the probes indicated that the relative binding affinities were generally PCB sulfate ≥ OH-PCB > PCB, although this affinity was site- and congener-selective. Moreover, specificity for Site II increased as the numbers of chlorine atoms increased. Thus, hydroxylation and sulfation of LC-PCBs result in selective interactions with HSA which may affect their overall retention and toxicity. PMID:27116425

  5. Role of the increased noradrenergic neurotransmission in drug self-administration.

    PubMed

    Wee, Sunmee; Wang, Zhixia; He, Rong; Zhou, Jia; Kozikowski, Alan P; Woolverton, William L

    2006-04-28

    Psychostimulants increase extracellular monoamine concentrations in the CNS. While the contributions of dopamine (DA) and serotonin (5-HT) to the reinforcing effect of psychostimulants have been examined, less is known about the involvement of norepinephrine (NE). In the present study, cocaine, desipramine (DMI) and JZ-III-84 were made available to rhesus monkeys (n=4) responding under a progressive-ratio (PR) schedule. These compounds vary in their in vitro selectivities for blocking NE uptake relative to DA from high (DMI) to modest (JZ-III-84) to non-selective (cocaine). Additionally, cocaine mixed with DMI in mg/kg dose-ratios of 1:1 to 1:3 was made available for self-administration. NE uptake inhibition by the mixture of cocaine and DMI at a ratio of 1:3 was evaluated in an ex vivo uptake assay. Cocaine (0.01-0.1 mg/(kg injection)) and JZ-III-84 (0.001-0.1 mg/(kg injection)) functioned as positive reinforcers with sigmoidal or biphasic dose-response functions, whereas DMI failed to do so. The addition of DMI to cocaine did not systemically alter self-administration of cocaine. In the ex vivo uptake assay, the addition of DMI to cocaine significantly increased the NE uptake inhibition compared to cocaine. These results support the conclusion that CNS NE is not involved in the reinforcing mechanism of psychostimulants. PMID:16213110

  6. Increased serum pancreatitis associated protein (PAP) concentration after longterm alcohol consumption: further evidence for regular subclinical pancreatic damage after heavy drinking?

    PubMed Central

    Nordback, I; Jaakkola, M; Iovanna, J L; Dagorn, J C

    1995-01-01

    It has been shown recently that longterm but not short term heavy drinking of alcohol frequently results in increased serum activities of pancreatic enzymes suggesting subclinical pancreatic injury. Serum pancreatitis associated protein (PAP) is a novel protein, whose synthesis in the acinar cells and release into serum is specifically induced by acute pancreatic damage. This study was performed to further characterise the alcohol induced subclinical pancreatic injury by using serum PAP measurements. Three groups were studied: (1) control group (n = 25), (2) short term drinking group (n = 20), who consumed 2.0 g of ethanol per kg body weight during four hours, and (3) longterm drinking group (n = 32), who were admitted to withdrawal clinic after a median 30 months heavy drinking period. Serum PAP concentration was low in the control group (8 (5 to 12) micrograms/l, geometric mean (95% confidence intervals)). In the short term drinking group serum PAP was in the range of the control group values during 56 hours after drinking. Longterm drinking induced at least a 10-fold increase in serum PAP, the highest concentrations being seen on day 2 after drinking had ended (106 (61 to 184) micrograms/l). The patients did not develop abdominal symptoms, increased blood white cell count, or increased serum C reactive protein concentration. These results further support the suggestion that heavy longterm drinking often induces subclinical pancreatic damage, but not clinical pancreatitis. PMID:7890213

  7. Administration of MPTP acutely increases glucose utilization in the substantia nigra of primates.

    PubMed

    Palombo, E; Porrino, L J; Bankiewicz, K S; Crane, A M; Kopin, I J; Sokoloff, L

    1988-06-21

    The quantitative 2-[14C]deoxyglucose autoradiographic method was used to map the regional distribution of the acute effects of administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), on local cerebral glucose utilization in rhesus monkeys. Metabolic activity was increased (+80%) in the substantia nigra pars compacta, which has been shown to be the main target site of MPTP toxicity. Metabolic activity was also increased in the nucleus paranigralis, nucleus parabrachialis pigmentosus, and ventral lamella of the inferior olive. In contrast, substantial decreases in glucose utilization were found diffusely distributed throughout many of the other structures examined, most prominently in portions of the cerebral cortex, thalamus, and cerebellum. PMID:3261197

  8. Increased Serum Uric Acid Levels Blunt the Antihypertensive Efficacy of Lifestyle Modifications in Children at Cardiovascular Risk.

    PubMed

    Viazzi, Francesca; Rebora, Paola; Giussani, Marco; Orlando, Antonina; Stella, Andrea; Antolini, Laura; Valsecchi, Maria Grazia; Pontremoli, Roberto; Genovesi, Simonetta

    2016-05-01

    Primary hypertension is a growing concern in children because of the obesity epidemic largely attributable to western lifestyles. Serum uric acid is known to be influenced by dietary habits, correlates with obesity, and could represent a risk factor for hypertension. Preliminary studies in children highlighted uric acid as a potentially modifiable risk factor for the prevention and treatment of hypertension. The effect of lifestyle changes (increase of physical activity and dietary modifications) on blood pressure values, weight status, and serum uric acid levels in a cohort of 248 children referred for cardiovascular risk assessment were evaluated over a mean 1.5-year follow-up. At baseline, 48% of children were obese and 50% showed blood pressure values >90th percentile. At follow-up, a significant improvement in weight class (24% obese;P<0.0001) and blood pressure category (22% >90th percentile;P<0.0001) was found. Systolic blood pressure z-score (P<0.0001), uric acid value (P=0.0056), and puberty at baseline (P=0.0048) were independently associated with higher systolic blood pressure z-score at follow-up, whereas a negative association was observed with body mass index z-score decrease during follow-up (P=0.0033). The risk of hypertension at follow-up was associated with body mass index (P=0.0025) and systolic blood pressure (P<0.0001) z-score at baseline and inversely related to delta body mass index (P=0.0002), whereas the risk of showing hypertension ≥99th percentile was more than doubled for each baseline 1 mg/dL increase of serum uric acid (P=0.0130). Uric acid is a powerful determinant of blood pressure over time, independent of lifestyle modifications. PMID:27021006

  9. Enhanced AMPA receptor activity increases operant alcohol self-administration and cue-induced reinstatement.

    PubMed

    Cannady, Reginald; Fisher, Kristen R; Durant, Brandon; Besheer, Joyce; Hodge, Clyde W

    2013-01-01

    Long-term alcohol exposure produces neuroadaptations that contribute to the progression of alcohol abuse disorders. Chronic alcohol consumption results in strengthened excitatory neurotransmission and increased α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA) receptor signaling in animal models. However, the mechanistic role of enhanced AMPA receptor activity in alcohol-reinforcement and alcohol-seeking behavior remains unclear. This study examined the role of enhanced AMPA receptor function using the selective positive allosteric modulator, aniracetam, in modulating operant alcohol self-administration and cue-induced reinstatement. Male alcohol-preferring (P-) rats, trained to self-administer alcohol (15%, v/v) versus water were pre-treated with aniracetam to assess effects on maintenance of alcohol self-administration. To determine reinforcer specificity, P-rats were trained to self-administer sucrose (0.8%, w/v) versus water, and effects of aniracetam were tested. The role of aniracetam in modulating relapse of alcohol-seeking was assessed using a response contingent cue-induced reinstatement procedure in P-rats trained to self-administer 15% alcohol. Aniracetam pre-treatment significantly increased alcohol-reinforced responses relative to vehicle treatment. This increase was not attributed to aniracetam-induced hyperactivity as aniracetam pre-treatment did not alter locomotor activity. AMPA receptor involvement was confirmed because 6,7-dinitroquinoxaline-2,3-dione (AMPA receptor antagonist) blocked the aniracetam-induced increase in alcohol self-administration. Aniracetam did not alter sucrose-reinforced responses in sucrose-trained P-rats, suggesting that enhanced AMPA receptor activity is selective in modulating the reinforcing function of alcohol. Finally, aniracetam pre-treatment potentiated cue-induced reinstatement of alcohol-seeking behavior versus vehicle-treated P-rats. These data suggest that enhanced glutamate activity at AMPA

  10. Glycogen overload by postexercise insulin administration abolished the exercise-induced increase in GLUT4 protein.

    PubMed

    Chou, Chia-Hau; Tsai, Yin-Lan; Hou, Chien-Wen; Lee, Hsing-Hao; Chang, Wei-Hsiang; Lin, Tzi-Wen; Hsu, Tung-Hsiung; Huang, Yi-Jen; Kuo, Chia-Hua

    2005-12-01

    To elucidate the role of muscle glycogen storage on regulation of GLUT4 protein expression and whole-body glucose tolerance, muscle glycogen level was manipulated by exercise and insulin administration. Sixty Sprague-Dawley rats were evenly separated into three groups: control (CON), immediately after exercise (EX0), and 16 h after exercise (EX16). Rats from each group were further divided into two groups: saline- and insulin-injected. The 2-day exercise protocol consisted of 2 bouts of 3-h swimming with 45-min rest for each day, which effectively depleted glycogen in both red gastrocnemius (RG) and plantaris muscles. EX0 rats were sacrificed immediately after the last bout of exercise on second day. CON and EX16 rats were intubated with 1 g/kg glucose solution following exercise and recovery for 16 h before muscle tissue collection. Insulin (0.5 microU/kg) or saline was injected daily at the time when glucose was intubated. Insulin injection elevated muscle glycogen levels substantially in both muscles above saline-injected group at CON and EX16. With previous day insulin injection, EX0 preserved greater amount of postexercise glycogen above their saline-injected control. In the saline-injected rats, EX16 significantly increased GLUT4 protein level above CON, concurrent with muscle glycogen supercompensation. Insulin injection for EX16 rats significantly enhanced muscle glycogen level above their saline-injected control, but the increases in muscle GLUT4 protein and whole-body glucose tolerance were attenuated. In conclusion, the new finding of the study was that glycogen overload by postexercise insulin administration significantly abolished the exercise-induced increases in GLUT4 protein and glucose tolerance. PMID:16319996

  11. Increased Serum and Musculotendinous Fibrogenic Proteins following Persistent Low-Grade Inflammation in a Rat Model of Long-Term Upper Extremity Overuse

    PubMed Central

    Gao, Helen G. L.; Fisher, Paul W.; Lambi, Alex G.; Wade, Christine K.; Barr-Gillespie, Ann E.; Popoff, Steven N.; Barbe, Mary F.

    2013-01-01

    We examined the relationship between grip strength declines and muscle-tendon responses induced by long-term performance of a high-repetition, low-force (HRLF) reaching task in rats. We hypothesized that grip strength declines would correlate with inflammation, fibrosis and degradation in flexor digitorum muscles and tendons. Grip strength declined after training, and further in weeks 18 and 24, in reach limbs of HRLF rats. Flexor digitorum tissues of reach limbs showed low-grade increases in inflammatory cytokines: IL-1β after training and in week 18, IL-1α in week 18, TNF-α and IL-6 after training and in week 24, and IL-10 in week 24, with greater increases in tendons than muscles. Similar cytokine increases were detected in serum with HRLF: IL-1α and IL-10 in week 18, and TNF-α and IL-6 in week 24. Grip strength correlated inversely with IL-6 in muscles, tendons and serum, and TNF-α in muscles and serum. Four fibrogenic proteins, TGFB1, CTGF, PDGFab and PDGFbb, and hydroxyproline, a marker of collagen synthesis, increased in serum in HRLF weeks 18 or 24, concomitant with epitendon thickening, increased muscle and tendon TGFB1 and CTGF. A collagenolytic gelatinase, MMP2, increased by week 18 in serum, tendons and muscles of HRLF rats. Grip strength correlated inversely with TGFB1 in muscles, tendons and serum; with CTGF-immunoreactive fibroblasts in tendons; and with MMP2 in tendons and serum. Thus, motor declines correlated with low-grade systemic and musculotendinous inflammation throughout task performance, and increased fibrogenic and degradative proteins with prolonged task performance. Serum TNF-α, IL-6, TGFB1, CTGF and MMP2 may serve as serum biomarkers of work-related musculoskeletal disorders, although further studies in humans are needed. PMID:24015193

  12. Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

    PubMed

    Liu, Chao; Zhen, Yuzhi; Zhao, Qingzhen; Zhai, Jian-Long; Liu, Kunshen; Zhang, Jian-Xin

    2016-07-01

    Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF. PMID:27144905

  13. Increasing Access to Health Administrative Data with ICES Data & Analytic Services.

    PubMed

    Ishiguro, Lisa; Saskin, Refik; Vermeulen, Marian J; Yates, Erika; Gunraj, Nadia; Victor, J Charles

    2016-01-01

    The Institute for Clinical Evaluative Sciences (ICES) is one of only a few organizations in Ontario permitted to access, link and analyze health administrative data for the purpose of generating evidence to inform decisions in policy and practice. Although ICES is a leading research institute, its access to the data has historically been restricted to scientists with an ICES affiliation. This requirement, designed to meet ICES' data privacy and security obligations, created barriers with respect to the widespread use of Ontario's data assets. In 2014, as part of the government's commitment to the Strategy for Patient-Oriented Research, ICES launched the Data & Analytic Services platform, which is aimed at increasing access to data and analytic services to investigators external to ICES. In making the data widely available to the broader research community, this initiative engages investigators involved in front-line care, stimulates new avenues of research and fosters collaboration that was previously challenging or unfeasible. PMID:27133600

  14. Prolonged withdrawal following cocaine self-administration increases resistance to punishment in a cocaine binge.

    PubMed

    Gancarz-Kausch, Amy M; Adank, Danielle N; Dietz, David M

    2014-01-01

    Drug addiction is characterized by compulsive drug-taking behaviors and a high propensity to relapse following drug cessation. Drug craving and seeking can increase during a period of abstinence, but this phenomenon is not observed in drug-induced reinstatement models. To investigate the effect of withdrawal on cocaine relapse, rats were exposed to extended-access cocaine self-administration and subjected to either 1 or 30 d of withdrawal. When tested during 12 h unlimited access to cocaine (binge), the duration of the withdrawal did not influence cocaine intake. However, using a histamine punishment procedure that greatly suppresses drug-taking behavior, we demonstrate that longer periods of abstinence from cocaine induce a greater persistence in responding for drug in the face of negative consequences. PMID:25363133

  15. NOAA Would Receive an 11% Increase Under Obama Administration's Proposed Budget

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2013-05-01

    The White House's proposed fiscal year (FY) 2014 budget for the National Oceanic and Atmospheric Administration (NOAA) would provide the agency with 5.45 billion, 11% above the FY 2012 spend plan of 4.91 billion (see Table ). The proposal, which was sent to Congress on 10 April, would increase funding for operations, research, and facilities to 3.41 billion (up 7.97% over FY 2012) and for procurement, acquisition, and construction to 2.12 billion (up 17.51%). The budget proposal uses the FY 2012 spend plan as a comparison because Congress approved the FY 2013 appropriations only a few weeks before the FY 2014 proposal was released.

  16. Substantially increased sildenafil bioavailability after sublingual administration in children with congenital heart disease: two case reports

    PubMed Central

    2014-01-01

    Introduction Pulmonary hypertension is a progressive disease of diverse origin with devastating consequences in adults as well as in children. The phosphodiesterase 5 inhibitor sildenafil successfully lowers pulmonary vascular resistance. However, because of its poor enteral absorption, resulting in ineffective plasma concentrations, responses in infants and children are often erratic. Case presentations We report the cases of two Caucasian boys, one born at term (case 1) and one aged 2.5 years (case 2), who had structural cardiac and pulmonary defects accompanied by symptomatic pulmonary hypertension. They received sildenafil enterally and sublingually and also intravenously in one of them. Plasma samples were taken at various time points to determine the plasma concentrations of sildenafil and its partially active metabolite. Sildenafil and N-desmethyl sildenafil were quantified using a validated liquid chromatography/mass spectrometry method. Oxygen partial pressure was determined from routine arterial blood gas samples. Conclusion In agreement with previous observations in adults, we found that sublingual sildenafil was more extensively absorbed in our two pediatric patients. After sublingual administration, sildenafil plasma concentrations increased by 314% to 361% compared to enteral dosing. Concurrently, the metabolic ratio increased, suggesting not only that the overall absorption was enhanced but also that first-pass metabolism was partially bypassed. In case 2, the free fraction of sildenafil was 0.9%, which is considerably less than in adults (4%), suggesting that, in case 2, higher plasma concentration would have been needed to achieve effects similar to those in adults. Sublingual sildenafil appears to be a promising alternative route of administration in children with poor enteral absorption. PMID:24885923

  17. Interleukin-2 administration after modified radical mastectomy in breast cancer therapy increases peripheral regulatory T cells

    PubMed Central

    Li, Yunli; Zhou, Lei; Sun, Bei; Li, Xiaoxiao; Duan, Kaiming; Wu, Yuhui; Ouyang, Wen

    2015-01-01

    Background: Breast cancer (BC) deaths are a major concern worldwide, and modified radical mastectomy (MRM) still represents a primary therapeutic strategy. Post-surgery administration of interleukin (IL)-2 for BC therapy has been implemented in China recently. Although its impact on regulatory T cells (Tregs) has been documented in some cancer types, such as melanoma, the IL-2-mediated changes in the Treg composition after MRM in BC treatment remain unknown. Methods: As registered with the Chinese Clinical Trial Registry, 34 newly diagnosed BC patients, aged 20-65 years, were enrolled in this trial. Patients were randomized to the IL-2-treated group (n=15) and the untreated control group (n=19). Peripheral blood mononuclear cells were isolated at time points of pre-operation (PreOP) and post-operation Day 1 (POD1), POD3, and POD7. Cells were subjected to flow cytometric assays to identify CD4+ CD25+ Foxp3+ Tregs, as well as real-time quantitative polymerase chain reaction analysis of FOXP3 expression. Results: We found that the surgery caused a significant decrease in the percentage of Tregs on POD1, followed by a significant increase characterized by a peak value on POD7 with a more than 18% increase relative to the Pre-OP levels. We observed that the Treg percentages in the IL-2-treated group were significantly greater than those in the control group on POD3 and POD7, whereas no such statistical difference was observed on POD1. The FOXP3 expression analysis revealed consistent trends as observed by flow cytometry. Conclusions: Post-operative administration of IL-2 amplifies the surgery-induced augmentation of both Tregs and FOXP3 expression in BC therapy. PMID:26221334

  18. Chronic administration of antipsychotics attenuates ongoing and ketamine-induced increases in cortical γ oscillations.

    PubMed

    Anderson, Paul M; Pinault, Didier; O'Brien, Terence J; Jones, Nigel C

    2014-11-01

    Noncompetitive N-methyl-d-aspartate receptor (NMDAr) antagonists can elicit many of the symptoms observed in schizophrenia in healthy humans, and induce a behavioural phenotype in animals relevant to psychosis. These compounds also elevate the power and synchrony of gamma (γ) frequency (30-80 Hz) neural oscillations. Acute doses of antipsychotic medications have been shown to reduce ongoing γ power and to inhibit NMDAr antagonist-mediated psychosis-like behaviour in rodents. This study aimed to investigate how a chronic antipsychotic dosing regimen affects ongoing cortical γ oscillations, and the electrophysiological and behavioural responses induced by the NMDAr antagonist ketamine. Male Wistar rats were chronically treated with haloperidol (0.25 mg/kg/d), clozapine (5 mg/kg/d), LY379268 (0.3 mg/kg/d) or vehicle for 28 d, delivered by subcutaneous (s.c.) osmotic pumps. Weekly electrocorticogram (ECoG) recordings were acquired. On day 26, ketamine (5 mg/kg, s.c.) was administered, and ECoG and locomotor activity were simultaneously measured. These results were compared with data generated previously following acute treatment with these antipsychotics. Sustained and significant decreases in ongoing γ power were observed during chronic administration of haloperidol (64%) or clozapine (43%), but not of LY379268 (2% increase), compared with vehicle. Acute ketamine injection concurrently increased γ power and locomotor activity in vehicle-treated rats, and these effects were attenuated in rats chronically treated with all three antipsychotics. The ability of haloperidol or clozapine to inhibit ketamine-induced elevation in γ power was not observed following acute administration of these drugs. These results indicate that modulation of γ power may be a useful biomarker of chronic antipsychotic efficacy. PMID:24964190

  19. In vitro increase of mean corpuscular volume difference (dMCV) as a marker for serum hypertonicity in dogs.

    PubMed

    Reinhart, Jennifer M; Yancey, Misty R; Pohlman, Lisa M; Schermerhorn, Thomas

    2014-06-01

    Spurious increase in erythrocyte mean corpuscular volume (MCV) on automated cell analyzers is a well-characterized lab error in hypertonic patients. A difference between automated and manual MCV (dMCV) greater than 2 fl has been shown to predict hypertonicity in humans. The purpose of this study was to investigate dMCV as a marker for serum hypertonicity in dogs and to examine the relationship between dMCV and three methods of estimating serum tonicity: measured (OsMM), calculated (OsMC), and calculated effective (OsMCE) osmolalities. OsMC, OsMCE, and dMCV were calculated from routine blood values and OsMM was directly measured in 121 dogs. The dMCV of hypertonic dogs was significantly larger than that of normotonic dogs for all three osmolality methods. dMCV predicted hypertonicity as estimated by OsMM better than it predicted hypertonicity as estimated by OsMC and OsMCE. A cutoff of 2.96 fl yielded the best sensitivity (76%) and specificity (71%) for hypertonicity estimated by OsMM. PMID:24656345

  20. Increased serum concentrations of soluble CD95/Fas and caspase 1/ICE in patients with acute angina

    PubMed Central

    Ankersmit, H J; Weber, T; Auer, J; Roth, G; Brunner, M; Kvas, E; Moser, B; Spreitzer, S; Lassnig, E; Maurer, E; Hartl, P; Wolner, E; Boltz-Nitulescu, G; Eber, B

    2004-01-01

    Objectives: To investigate the expression of death inducing receptors in the sera of patients with stable and unstable angina. Design: 80 consecutive patients with stable (n  =  40) or unstable (n  =  40) angina pectoris were studied. Serum concentrations of soluble CD95 (sCD95), soluble CD95 ligand (sCD95L; CD178), tumour necrosis factor (TNF) α, soluble TNFα receptor type 1 (sTNFR1), and interleukin 1β converting enzyme (ICE; caspase 1) were measured by enzyme linked immunosorbent assay (ELISA). Results: Significant increases in the concentrations of sCD95 and ICE (p < 0.001 and p < 0.023, respectively) were found in the serum from patients with unstable angina relative to those with stable angina. There were no significant differences in the concentrations of sCD95L, TNF α, and sTNFR1 between the groups. Conclusions: These data provide the first evidence that sCD95 and ICE are important serological markers that may help to discriminate between stable and unstable angina. This observation may warrant further clinical study to elucidate the clinical impact of sCD95 and ICE in acute coronary syndromes. PMID:14729783

  1. Increased Serum Interleukin-9 Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Pathogenic Role or Just an Epiphenomenon?

    PubMed

    Dantas, Andréa Tavares; Marques, Claudia Diniz Lopes; da Rocha Junior, Laurindo Ferreira; Cavalcanti, Mariana Brayner; Gonçalves, Sayonara Maria Calado; Cardoso, Pablo Ramon Gualberto; Mariz, Henrique de Ataide; Rego, Moacyr Jesus Barreto de Melo; Duarte, Angela Luzia Branco Pinto; Pitta, Ivan da Rocha; Pitta, Maira Galdino da Rocha

    2015-01-01

    The purpose of this paper was to evaluate the levels of IL-9 in patients with SLE and RA compared with controls and the association of IL-9 levels with clinical and laboratory parameters. IL-9 levels were assessed in 117 SLE patients, 67 RA patients, and 24 healthy controls by ELISA. Clinical and laboratory parameters were recorded. The IL-9 serum levels were significantly higher in RA patients (4,77 ± 3,618 pg/mL) and in SLE patients (12,26 ± 25,235 pg/mL) than in healthy individuals (1,22 ± 0,706 pg/mL) (p < 0,001). In SLE patients, there were no statistically significant associations or correlations between the levels of IL-9 and SLEDAI or other clinical and laboratorial parameters, with the exception of disease time, which showed a statistically significant negative correlation with IL-9 levels (r = -0,1948; p = 0,0378). In RA patients, no association or statistically significant correlation was observed with disease duration, DAS28, HAQ, rheumatoid factor positivity, or erosions on radiography. These data demonstrated increased serum levels of IL-9 in SLE and RA patients, but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target. PMID:26078482

  2. Increased Serum Interleukin-9 Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Pathogenic Role or Just an Epiphenomenon?

    PubMed Central

    Dantas, Andréa Tavares; Marques, Claudia Diniz Lopes; da Rocha Junior, Laurindo Ferreira; Cavalcanti, Mariana Brayner; Gonçalves, Sayonara Maria Calado; Cardoso, Pablo Ramon Gualberto; Mariz, Henrique de Ataide; Rego, Moacyr Jesus Barreto de Melo; Duarte, Angela Luzia Branco Pinto; Pitta, Ivan da Rocha; Pitta, Maira Galdino da Rocha

    2015-01-01

    The purpose of this paper was to evaluate the levels of IL-9 in patients with SLE and RA compared with controls and the association of IL-9 levels with clinical and laboratory parameters. IL-9 levels were assessed in 117 SLE patients, 67 RA patients, and 24 healthy controls by ELISA. Clinical and laboratory parameters were recorded. The IL-9 serum levels were significantly higher in RA patients (4,77 ± 3,618 pg/mL) and in SLE patients (12,26 ± 25,235 pg/mL) than in healthy individuals (1,22 ± 0,706 pg/mL) (p < 0,001). In SLE patients, there were no statistically significant associations or correlations between the levels of IL-9 and SLEDAI or other clinical and laboratorial parameters, with the exception of disease time, which showed a statistically significant negative correlation with IL-9 levels (r = −0,1948;  p = 0,0378). In RA patients, no association or statistically significant correlation was observed with disease duration, DAS28, HAQ, rheumatoid factor positivity, or erosions on radiography. These data demonstrated increased serum levels of IL-9 in SLE and RA patients, but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target. PMID:26078482

  3. Association of Increased Serum Leptin with Ameliorated Anemia and Malnutrition in Stage 5 Chronic Kidney Disease Patients after Parathyroidectomy

    PubMed Central

    Jiang, Yao; Zhang, Jingjing; Yuan, Yanggang; Zha, Xiaoming; Xing, Changying; Shen, Chong; Shen, Zhixiang; Qin, Chao; Zeng, Ming; Yang, Guang; Mao, Huijuan; Zhang, Bo; Yu, Xiangbao; Sun, Bin; Ouyang, Chun; Xu, Xueqiang; Ge, Yifei; Wang, Jing; Zhang, Lina; Cheng, Chen; Yin, Caixia; Zhang, Jing; Chen, Huimin; Ma, Haoyang; Wang, Ningning

    2016-01-01

    Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) <23 kg/m2. Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD. PMID:27307101

  4. Association of Increased Serum Leptin with Ameliorated Anemia and Malnutrition in Stage 5 Chronic Kidney Disease Patients after Parathyroidectomy.

    PubMed

    Jiang, Yao; Zhang, Jingjing; Yuan, Yanggang; Zha, Xiaoming; Xing, Changying; Shen, Chong; Shen, Zhixiang; Qin, Chao; Zeng, Ming; Yang, Guang; Mao, Huijuan; Zhang, Bo; Yu, Xiangbao; Sun, Bin; Ouyang, Chun; Xu, Xueqiang; Ge, Yifei; Wang, Jing; Zhang, Lina; Cheng, Chen; Yin, Caixia; Zhang, Jing; Chen, Huimin; Ma, Haoyang; Wang, Ningning

    2016-01-01

    Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) <23 kg/m(2). Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD. PMID:27307101

  5. [Pulmonary Sequestration Associated with Increased Serum Tumor Markers;Report of a Case].

    PubMed

    Asanuma, Kozo; Ueda, Mamoru; Kusano, Kenji; Sato, Shintaro; Harasawa, Keiji; Ishizu, Hideki

    2016-08-01

    A 51-year-old woman visited our hospital with chief complaints of cough and fever. A chest X-ray detected an abnormal shadow in the right lung field. A chest computed tomography scan showed solid consolidation at S10 of the right lung. A blood test revealed elevated levels of the tumor markers, CEA(12.1 ng/ml), SLX (134 U/ml) and CA19-9 (76.2 U/ml). Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed abnormally increased 18F-FDG uptake with an SUV max of 11.29. Lung cancer was strongly suspected, and the surgery was performed. Abnormal blood vessels were found within the pulmonary ligament. Intraoperative rapid pathology indicated no malignancy, and the final diagnosis was pulmonary sequestration. PMID:27476573

  6. 13C natural abundance in serum retinol acts as a biomarker for increases in dietary provitamin A.

    PubMed

    Howe, Julie A; Valentine, Ashley R; Hull, Angela K; Tanumihardjo, Sherry A

    2009-02-01

    The natural isotopic composition of 13C and 12C in tissues is largely determined by the diet. Sources of provitamin A carotenoids (e.g., vegetables) typically have a lower 13C to 12C ratio (13C:12C) than preformed vitamin A sources (i.e., dairy and meat) from corn-fed animals, which are prevalent in the US. The 13C:12C of serum retinol (13C:12C-retinol) was evaluated as a biomarker for vegetable intake in a 3-mo dietary intervention designed to promote weight-loss by increased vegetable consumption or reduced calorie and fat intake. Subjects were 21-50 y of age with a BMI between 30-40 kg/m2 and were enrolled from one geographic area in the US. The high vegetable group (n=20) was encouraged to increase daily vegetable and fruit consumption to 0.95 liter vegetables and 0.24-0.35 liter fruits. The caloric reduction group (n=17) was encouraged to lower caloric intake by 500 kcal and consumeSerum retinol and provitamin A carotenoid concentrations; intake of preformed vitamin A, provitamin A, and fat; and body weight, fat mass, and lean mass were analyzed for correlations to 13C:12C-retinol. 13C:12C-Retinol decreased in the vegetable group after intervention (P=0.050) and the correlation with provitamin A intake was approaching significance (P=0.079). 13C:12C-Retinol did not change in the caloric reduction group (P=0.43). 13C:12C-Retinol changes with the vitamin A source in the diet and can be used as a biomarker for increases in dietary provitamin A vegetable intake. PMID:19116317

  7. Increased Serum Levels of LIGHT/TNFSF14 in Nonalcoholic Fatty Liver Disease: Possible Role in Hepatic Inflammation

    PubMed Central

    Otterdal, Kari; Haukeland, John Willy; Yndestad, Arne; Dahl, Tuva B; Holm, Sverre; Segers, Filip M; Gladhaug, Ivar P; Konopski, Zbigniew; Damås, Jan Kristian; Halvorsen, Bente; Aukrust, Pål

    2015-01-01

    Objectives: The tumor necrosis factor superfamily member 14, LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes), has been involved in various autoimmune disorders and has been shown to influence hepatic lipid metabolism. We hypothesized that LIGHT could also have a pathogenic role in nonalcoholic fatty liver disease (NAFLD). Methods: Serum levels of LIGHT in NAFLD patients and control subjects, as well as LIGHT and interleukin (IL)-8 released from Huh7 (human hepatoma cell line) hepatocytes, were determined by enzyme-linked immunosorbent assay. The mRNA expression of LIGHT in the liver tissue and mRNA levels of LIGHT and IL-8 in Huh7 hepatocytes were assessed by real-time quantitative reverse transcription-PCR. Results: (i) Serum levels of LIGHT were significantly elevated in NAFLD patients (n=66) as compared with healthy controls (n=16), with no differences between simple steatosis (n=34) and nonalcoholic steatohepatitis (NASH) (n=32). (ii) Within the liver, NAFLD patients (n=14) had significantly increased mRNA levels of the two LIGHT receptors, herpes virus entry mediator and lymphotoxin β receptor (LTβR), as compared with controls (n=7), with no difference between simple steatosis (n=8) and NASH (n=6). (iii) LIGHT markedly increased the release of IL-8 in Huh7 hepatocytes in a time- and dose-dependent manner. (iv) The reactive oxygen species (ROS) H2O2 (hydrogen peroxide) enhanced the LIGHT-mediated release of IL-8 in Huh7 hepatocytes. Conclusion: We show increased levels of LIGHT and its two membrane-bound receptors in NAFLD, potentially promoting hepatic inflammation through ROS interaction. Our findings should encourage further studies on the role of LIGHT in NAFLD development and progression. PMID:26133108

  8. Effect of oral administration of kefir on serum proinflammatory cytokines on 5-FU induced oral mucositis in patients with colorectal cancer.

    PubMed

    Topuz, E; Derin, D; Can, G; Kürklü, E; Cinar, S; Aykan, F; Cevikbaş, A; Dişçi, R; Durna, Z; Sakar, B; Saglam, S; Tanyeri, H; Deniz, G; Gürer, U; Taş, F; Guney, N; Aydiner, A

    2008-12-01

    In order to investigate the effect of kefir consumption on mucositis induced by 5-FU based chemotherapy (CT), we monitored the systemic immune response by measurement of the serum proinflammatory cytokine levels and we evaluated the anti-microbial effect of kefir with an agar diffusion method. Forty patients with colorectal cancer were included in this randomized prospective study. On the first 5 days of each CT cycle, the study group received oral lavage with kefir and then swallowed 250 ml of kefir while control group received oral lavage with 0.09% NaCl twice a day. Before and after every cycle of CT, the oral mucosa was assessed. Serum proinflammatory cytokine levels were evaluated before the initiation and after the third and the sixth cycle. Kefir was administered in 99 out of 205 courses. Mucositis developed in 27.3% of the courses given with kefir administration and in 21.7% of the courses given with 0.9% NaCl oral rinses. The difference between the two groups was not statistically significant (p > 0.05). When we compared the serum proinflammatory cytokine levels of the two groups at the baseline and following the third and the sixth cycles, we again found no statistically significant difference (p > 0.05). Kefir consumption at the mentioned doses made no statistically significant effect on serum proinflammatory cytokine levels and on the incidence of mucositis development in cancer patients. Under in vitro conditions, kefir inhibits only Staphylococcus epidermidis. PMID:18762864

  9. Tragopogon porrifolius improves serum lipid profile and increases short-term satiety in rats.

    PubMed

    Zeeni, Nadine; Daher, Costantine F; Saab, Lea; Mroueh, Mohamad

    2014-01-01

    Tragopogon porrifolius (white salsify) is an edible plant commonly used in folk medicine in Lebanon and neighbouring countries. This study investigates the effect of the aqueous extract of the aerial part of T. porrifolius on lipemia and appetite regulation using a rat model. Food intake, abdominal fat percentage, blood lipid profile, liver weight and liver enzymes were assessed following 4 weeks of extract intake via drinking water (50, 100, or 250 mg/kg body weight) in standard high-carbohydrate and high-fat dietary conditions. In a separate study, the short term effect of a preload of T. porrifolius extract on food intake was evaluated. Results showed that consumption of the plant extract for a period of four weeks resulted in a marked improvement of the lipid profile (triglycerides, total cholesterol, LDL and HDL cholesterol). Body weight, food intake and intra-abdominal fat were also lower in animals given the plant extract (100 and 250 mg/kg). In addition, T. porrifolius extract preload produced a dose dependent decrease in food intake observed over 24h. The intake of T. porrifolius aqueous extract therefore improved lipemia and increased satiety in rats with no visible adverse effects. PMID:24099703

  10. Serum Eotaxin-1 is Increased in Extremely Low Birth Infants with Bronchopulmonary Dysplasia or Death

    PubMed Central

    Kandasamy, Jegen; Roane, Claire; Szalai, Alexander; Ambalavanan, Namasivayam

    2015-01-01

    Background Early systemic inflammation in extremely low birth weight (ELBW) infants is associated with an increased risk of bronchopulmonary dysplasia (BPD). Our objective was to identify circulating biomarkers and develop prediction models for BPD/death soon after birth. Methods Blood samples from postnatal day 1 were analyzed for CRP by ELISA and for 39 cytokines/chemokines by a multiplex assay in 152 ELBW infants. The primary outcome was physiologic BPD or death by 36w. CRP, cytokines, and clinical variables available at ≤24 h were used for forward stepwise regression and Classification and Regression Tree (CART) analysis to identify predictors of BPD/death. Results Overall, 24% developed BPD and 35% died or developed BPD. Regression analysis identified birth weight and eotaxin (CCL11) as the two most significant variables. CART identified FiO2 at 24h (11% BPD/death if FiO2 ≤28%, 49% if >28%) and eotaxin in infants with FiO2>28% (29% BPD/death if eotaxin was ≤84 pg/ml; 65% if >84) as variables most associated with outcome. Conclusion Eotaxin measured on the day of birth is useful for identifying ELBW infants at risk of BPD/death. Further investigation is required to determine if eotaxin is involved in lung injury and pathogenesis of BPD. PMID:26270578

  11. Serum from patients with ankylosing spondylitis can increase PPARD, fra-1, MMP7, OPG and RANKL expression in MG63 cells

    PubMed Central

    Hu, Zaiying; Lin, Dongfang; Qi, Jun; Qiu, Minli; Lv, Qing; Li, Qiuxia; Lin, Zhiming; Liao, Zetao; Pan, Yunfeng; Jin, Ou; Wu, Yuqiong; Gu, Jieruo

    2015-01-01

    OBJECTIVES: To explore the effects of serum from patients with ankylosing spondylitis on the canonical Wnt/β-catenin pathway and to assess whether the serum has an osteogenic effect in MG63 cells. METHODS: MG63 cells were cultured with serum from 45 ankylosing spondylitis patients, 30 healthy controls, or 45 rheumatoid arthritis patients. The relative PPARD, fra-1, MMP7, OPG and RANKL mRNA levels were measured using quantitative real-time polymerase chain reaction. Associations between gene expression and patient demographics and clinical assessments were then analyzed. RESULTS: MG63 cells treated with serum from ankylosing spondylitis patients had higher PPARD, fra-1, MMP7 and OPG gene expression than did cells treated with serum from controls or rheumatoid arthritis patients (all p<0.05). RANKL expression was higher in MG63 cells treated with serum from patients with ankylosing spondylitis or rheumatoid arthritis than in those treated with serum from controls (both p<0.05). The OPG/RANKL ratio was also higher in MG63 cells treated with serum from ankylosing spondylitis patients than in those treated with serum from controls (p<0.05). No associations were found between the expression of the five genes and the patient demographics and clinical assessments (all p>0.05). CONCLUSIONS : Serum from ankylosing spondylitis patients increases PPARD, fra-1, MMP7, OPG and RANKL expression and the OPG/RANKL ratio in MG63 cells; these effects may be due to the stimulatory effect of the serum on the Wnt pathway. PMID:26602520

  12. Increased concentrations of inflammatory mediators in unstable angina: correlation with serum troponin T

    PubMed Central

    Mazzone, A; De Servi, S; Mazzucchelli, I; Bossi, I; Ottini, E; Vezzoli, M; Meloni, F; Lotzinker, M; Mariani, G

    2001-01-01

    OBJECTIVE—To measure plasma interferon γ, monocyte chemotactic protein-1 (MCP-1), and interleukin 6 and to assess their correlation with cardiac troponin T in unstable angina.
DESIGN—Blood sampling in patients undergoing coronary arteriography for known or suspected ischaemic heart disease.
PATIENTS—76 patients divided in three groups: 29 with unstable angina (group 1), 28 with stable angina (group 2), and 19 without ischaemic heart disease and with angiographically normal coronary arteries (group 3).
MAIN OUTCOME MEASURES—Plasma interleukin 6, interferon γ, MCP-1, and troponin T in the three groups of patients.
RESULTS—Interleukin 6 was increased in group 1 (median 2.19 (range 0.53-50.84) pg/ml) compared with the control group (1.62 (0.79-3.98) pg/ml) (p < 0.005), whereas interferon γ was higher in group 1 (range 0-5.51 pg/ml) than in the other two groups (range 0-0.74 pg/ml and 0-0.37 pg/ml; p < 0.005 and p < 0.001, respectively). Patients with unstable angina (group 1) and positive troponin T had higher concentrations of interferon γ than those with negative troponin T (0-5.51 pg/ml v 0-0.60 pg/ml, p < 0.001). Plasma MCP-1 was also higher in group 1 (median 267 (range 6-8670) pg/ml) than in the other two groups (134 (19-890) pg/ml and 84.5 (5-325) pg/ml; p < 0.005 and p < 0.001, respectively), and among group 1 patients with a positive troponin T assay than in those with normal troponin T (531 (14.5-8670) pg/ml v 69 (6-3333) pg/ml; p < 0.01). There was no difference in plasma interleukin 6 in group 1 patients between those with and without raised troponin T.
CONCLUSIONS—The inflammatory cytokines interferon γ and MCP-1 are increased in patients with unstable angina, particularly in those with raised concentrations of troponin T, suggesting that they are probably related to myocardial cell damage or to plaque rupture and thrombus formation.


Keywords: inflammatory cytokines; troponin

  13. Conventional hemofiltration during cardiopulmonary bypass increases the serum lactate level in adult cardiac surgery

    PubMed Central

    Soliman, Rabie; Fouad, Eman; Belghith, Makhlouf; Abdelmageed, Tarek

    2016-01-01

    Objective: To evaluate the effect of hemofiltration during cardiopulmonary bypass on lactate level in adult patients who underwent cardiac surgery. Design: An observational study. Setting: Prince Sultan cardiac center, Riyadh, Saudi Arabia. Participants: The study included 283 patients classified into two groups: Hemofiltration group (n=138), hemofiltration was done during CPB. Control group (n = 145), patients without hemofiltration. Interventions: Hemofiltration during cardiopulmonary bypass. Measurements and Main Results: Monitors included hematocrit, lactate levels, mixed venous oxygen saturation, amount of fluid removal during hemofiltration and urine output. The lactate elevated in group H than group C (P < 0.05), and the PH showed metabolic acidosis in group H (P < 0.05). The mixed venous oxygen saturation decreased in group H than group C (P < 0.05). The number of transfused packed red blood cells was lower in group H than group C (P < 0.05). The hematocrit was higher in group H than group C (P < 0.05). The urine output was lower in group H than group C (P < 0.05). Conclusions: Hemofiltration during cardiopulmonary bypass leads to hemoconcentration, elevated lactate level and increased inotropic support. There are some recommendations for hemofiltration: First; Hemofiltration should be limited for patients with impaired renal function, positive fluid balance, reduced response to diuretics or prolonged bypass time more than 2 hours. Second; Minimal amount of fluids should be administered to maintain adequate cardiac output and reduction of priming volumes is preferable to maintain controlled hemodilution. Third; it should be done before weaning of or after cardiopulmonary bypass and not during the whole time of cardiopulmonary bypass. PMID:26750673

  14. Association of Serum Apolipoprotein B with the Increased Risk of Diabetes in Korean Men.

    PubMed

    Lim, Hyo Hee; Kim, Oh Yoen

    2016-07-01

    This study aimed to investigate the association of Apolipoprotein B (ApoB) with the risk of diabetes in Koreans. Korean men (n = 790, 40-79 years) who had been never diagnosed for diabetes before participating were enrolled. Subjects were categorized into normal fasting glucose (NFG, n = 519), impaired fasting glucose (IFG, n = 188) and newly-onset diabetes (n = 83) according to fasting glucose levels. Age was not significantly different among the subgroups. Mean values of BMI, waist circumference, Blood pressure(BP), triglyceride, non-HDL cholesterol were significantly higher in IFG or newly-onset diabetic subjects compared to NFG subjects. The levels of glucose, insulin, free fatty acid, insulin resistance and ApoB were highest in diabetic patients and lowest in NFG subjects. According to ApoB level, subjects were divided into two groups (high-ApoB group: ≥ 87.0 mg/dL vs. low-ApoB group: < 87.0 mg/dL). The risk of diabetes was higher in the high-ApoB group than the low-ApoB group [OR0: 2.392, (95% CI: 1.470-3.893), P0 < 0.001]. This association was maintained after adjusted for age and BMI [OR1: 2.228, (95% CI: 1.362-3.646), P1 = 0.001] and further adjustment for blood pressure, triglyceride, HDL-cholesterol, LDL-cholesterol, non-HDL-cholesterol, ApoA1 and adiponectin [OR2: 1.984, (95% CI: 1.001-4.064), P2 = 0.049]. The association was much greater in subjects with metabolic syndrome (MetS) [OR1: 2.805 (95% CI: 1.137-5.737), P1 = 0.005] than in those without [OR1: 1.917 (95% CI: 0.989-3.718), P1 = 0.054]. After 3-month, further investigation was randomly performed in subjects with NFG or IFG who agreed to reinvestigation. Multiple stepwise regression analysis revealed that net change of ApoB levels was a main contributor to the net change of glucose levels (standardized b-coefficient: 0.315, p = 0.002). In conclusion, ApoB levels are closely associated with the increased risk of diabetes in Korean men. PMID:27482524

  15. Association of Serum Apolipoprotein B with the Increased Risk of Diabetes in Korean Men

    PubMed Central

    Lim, Hyo Hee

    2016-01-01

    This study aimed to investigate the association of Apolipoprotein B (ApoB) with the risk of diabetes in Koreans. Korean men (n = 790, 40-79 years) who had been never diagnosed for diabetes before participating were enrolled. Subjects were categorized into normal fasting glucose (NFG, n = 519), impaired fasting glucose (IFG, n = 188) and newly-onset diabetes (n = 83) according to fasting glucose levels. Age was not significantly different among the subgroups. Mean values of BMI, waist circumference, Blood pressure(BP), triglyceride, non-HDL cholesterol were significantly higher in IFG or newly-onset diabetic subjects compared to NFG subjects. The levels of glucose, insulin, free fatty acid, insulin resistance and ApoB were highest in diabetic patients and lowest in NFG subjects. According to ApoB level, subjects were divided into two groups (high-ApoB group: ≥ 87.0 mg/dL vs. low-ApoB group: < 87.0 mg/dL). The risk of diabetes was higher in the high-ApoB group than the low-ApoB group [OR0: 2.392, (95% CI: 1.470-3.893), P0 < 0.001]. This association was maintained after adjusted for age and BMI [OR1: 2.228, (95% CI: 1.362-3.646), P1 = 0.001] and further adjustment for blood pressure, triglyceride, HDL-cholesterol, LDL-cholesterol, non-HDL-cholesterol, ApoA1 and adiponectin [OR2: 1.984, (95% CI: 1.001-4.064), P2 = 0.049]. The association was much greater in subjects with metabolic syndrome (MetS) [OR1: 2.805 (95% CI: 1.137-5.737), P1 = 0.005] than in those without [OR1: 1.917 (95% CI: 0.989-3.718), P1 = 0.054]. After 3-month, further investigation was randomly performed in subjects with NFG or IFG who agreed to reinvestigation. Multiple stepwise regression analysis revealed that net change of ApoB levels was a main contributor to the net change of glucose levels (standardized b-coefficient: 0.315, p = 0.002). In conclusion, ApoB levels are closely associated with the increased risk of diabetes in Korean men. PMID:27482524

  16. Acute ingestion of catechin-rich green tea improves postprandial glucose status and increases serum thioredoxin concentrations in postmenopausal women.

    PubMed

    Takahashi, Masaki; Miyashita, Masashi; Suzuki, Katsuhiko; Bae, Seong-Ryu; Kim, Hyeon-Ki; Wakisaka, Takuya; Matsui, Yuji; Takeshita, Masao; Yasunaga, Koichi

    2014-11-14

    Elevated postprandial hyperglycaemia and oxidative stress increase the risks of type 2 diabetes and CVD. Green tea catechin possesses antidiabetic properties and antioxidant capacity. In the present study, we examined the acute and continuous effects of ingestion of catechin-rich green tea on postprandial hyperglycaemia and oxidative stress in healthy postmenopausal women. Participants were randomly assigned into the placebo (P, n 11) or green tea (GT, n 11) group. The GT group consumed a catechin-rich green tea (catechins 615 mg/350 ml) beverage per d for 4 weeks. The P group consumed a placebo (catechins 92 mg/350 ml) beverage per d for 4 weeks. At baseline and after 4 weeks, participants of each group consumed their designated beverages with breakfast and consumed lunch 3 h after breakfast. Venous blood samples were collected in the fasted state (0 h) and at 2, 4 and 6 h after breakfast. Postprandial glucose concentrations were 3 % lower in the GT group than in the P group (three-factor ANOVA, group × time interaction, P< 0·05). Serum concentrations of the derivatives of reactive oxygen metabolites increased after meals (P< 0·05), but no effect of catechin-rich green tea intake was observed. Conversely, serum postprandial thioredoxin concentrations were 5 % higher in the GT group than in the P group (three-factor ANOVA, group × time interaction, P< 0·05). These findings indicate that an acute ingestion of catechin-rich green tea has beneficial effects on postprandial glucose and redox homeostasis in postmenopausal women. PMID:25230741

  17. Continuous but not intermittent administration of growth hormone to hypophysectomized rats increases apolipoprotein-E secretion from cultured hepatocytes.

    PubMed

    Sjöberg, A; Oscarsson, J; Edén, S; Olofsson, S O

    1994-02-01

    Hypophysectomy of female rats has been shown to decrease the serum levels of apolipoprotein E (apoE). Continuous but not intermittent administration of GH to hypophysectomized (HX) rats increases these levels to those of normal rats, indicating that the sexually dimorphic secretion of GH is important in the regulation of apoE metabolism. In this study, these effects of GH were further investigated by studying the biosynthesis and secretion of apoE from isolated hepatocytes. Hepatocytes were isolated from HX rats as well as from HX rats that had received hormonal treatment with T4 and cortisol (C) or T4 and C together with GH given either as two daily sc injections (GH x 2) or as a continuous infusion (GHc). Hypophysectomy decreased by 47% the amount of apoE present in the culture medium after a 4-h incubation. Treatment of HX rats with T4 and C alone or in combination with GH x 2 did not influence the amount apoE present in the medium, whereas treatment with T4, C, and GHc increased the amount of apoE to that of normal controls. The different levels of apoE in the medium was not due to differences in the disappearance of apoE, indicating that it was caused by changes in the rate of apoE secretion. Consistent with this, hypophysectomy decreased the rate of intracellular accumulation of apoE measured by incubation of the cells with [35S]methionine for 0, 8, and 20 min. Treatment with T4, C, and GHc increased the rate of accumulation, but T4, C, and GH x 2 had no effect. The differences in the initial rate of intracellular accumulation of apoE were not due to variations in apoE messenger RNA pools or to differences in the degradation of apoE at a step early in the secretory pathway. These results indicate that the differences in the initial rate of accumulation of apoE results from differences in the translational rate. The major amount of apoE that was secreted to the medium appeared in the high-density lipoprotein fraction, whereas small amounts were present in the

  18. The Western dietary pattern is associated with increased serum concentrations of free estradiol in postmenopausal women: implications for breast cancer prevention.

    PubMed

    Sánchez-Zamorano, Luisa María; Flores-Luna, Lourdes; Angeles-Llerenas, Angélica; Ortega-Olvera, Carolina; Lazcano-Ponce, Eduardo; Romieu, Isabelle; Mainero-Ratchelous, Fernando; Torres-Mejía, Gabriela

    2016-08-01

    Little is known about the possible influence of food consumption on the serum concentrations of endogenous sex hormones in postmenopausal women. We evaluated the relationships of the Western dietary pattern with serum concentrations of free estradiol and testosterone of postmenopausal women to test the hypothesis that a highly Western dietary pattern is associated with high serum concentrations of these hormones. We used data from a representative subsample of 305 women from the control group of a population-based case-control study conducted in Mexico from 2004 to 2007. A Western dietary pattern index value was compared with log natural serum concentrations of testosterone and estradiol using multiple linear regression models. The median values of serum concentrations of free estradiol and testosterone were 0.26 pg/mL (interquartile range, 0.14-0.43) and 0.40 pg/mL (interquartile range, 0.30-0.70), respectively. A multiple linear regression model showed that for each unit increase in the Western dietary pattern index, there was a 16.2% increase in the serum concentrations of free estradiol (β=0.15; 95% confidence interval [CI], 0.01-0.29); for each additional serving per week of chicken eggs, the increase was 31.0% (β=0.27; 95% CI, 0.106-0.441); for each additional serving per week of red meat, the increase was 64.9% (β=0.50; 95% CI, 0.01-1.01). There was no relationship found between dietary patterns and serum concentrations of free testosterone. The present findings suggest that intake of a Western diet, particularly of chicken eggs and meat, increases serum concentrations of free estradiol; these results have implications for breast cancer prevention. PMID:27440539

  19. 77 FR 5027 - Food and Drug Administration Transparency Initiative: Exploratory Program To Increase Access to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ..., (76 FR 3825, January 21, 2011), FDA recounted the actions it had already implemented, as well as those... of availability of this report on October 4, 2011 (76 FR 61366), FDA sought public comment on these... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Transparency...

  20. Serum HER2 levels are increased in cats with mammary carcinomas and predict tissue HER2 status

    PubMed Central

    Soares, Maria; Ribeiro, Rita; Najmudin, Shabir; Gameiro, Andreia; Rodrigues, Rita; Cardoso, Fátima; Ferreira, Fernando

    2016-01-01

    HER2 is overexpressed in about 30% of feline mammary carcinomas (FMC) and in 15-30% of breast cancers. Women with HER2-positive breast tumors are associated with shorter survival. This study aimed to optimize the detection and quantification of serum HER2 (sHER2) in cats and to evaluate its potential in diagnosing cats with mammary carcinomas (MC) overexpressing HER2. A prospective study was conducted in 60 queens showing MC and 20 healthy animals. Pre-operative serum samples were collected for sHER2 quantification using two immunoassays: ELISA and Dot blot assay. sHER2 levels were compared with tissue HER2 status assessed by immunohistochemistry. Queens with FMC showed significantly higher mean levels of sHER2 by both ELISA and Dot blot assay. A significant difference in the sHER2 levels was also found between cats with HER2-positive MC and those with low-expressing HER2 MC. A significant correlation between sHER2 levels and tumor HER2 status was also found, particularly when ELISA was used (r = 0.58, p < 0.0001). The value of 10 ng/ml was proposed as the optimal cutoff for both immunoassays by ROC analysis. Like in humans, sHER2 levels are increased in cats with MC HER2-positive, strongly suggesting that evaluation of sHER2 levels can be very useful in feline oncology. The results show that ELISA and Dot blot assay can replace the immunohistochemistry technique, due to their efficacy and lower costs for diagnostic purposes and for monitoring the response to anti-HER2 therapies in cats. PMID:26909614

  1. Serum HER2 levels are increased in cats with mammary carcinomas and predict tissue HER2 status.

    PubMed

    Soares, Maria; Ribeiro, Rita; Najmudin, Shabir; Gameiro, Andreia; Rodrigues, Rita; Cardoso, Fátima; Ferreira, Fernando

    2016-04-01

    HER2 is overexpressed in about 30% of feline mammary carcinomas (FMC) and in 15-30% of breast cancers. Women with HER2-positive breast tumors are associated with shorter survival. This study aimed to optimize the detection and quantification of serum HER2 (sHER2) in cats and to evaluate its potential in diagnosing cats with mammary carcinomas (MC) overexpressing HER2. A prospective study was conducted in 60 queens showing MC and 20 healthy animals. Pre-operative serum samples were collected for sHER2 quantification using two immunoassays: ELISA and Dot blot assay. sHER2 levels were compared with tissue HER2 status assessed by immunohistochemistry. Queens with FMC showed significantly higher mean levels of sHER2 by both ELISA and Dot blot assay. A significant difference in the sHER2 levels was also found between cats with HER2-positive MC and those with low-expressing HER2 MC. A significant correlation between sHER2 levels and tumor HER2 status was also found, particularly when ELISA was used (r = 0.58, p < 0.0001). The value of 10 ng/ml was proposed as the optimal cutoff for both immunoassays by ROC analysis. Like in humans, sHER2 levels are increased in cats with MC HER2-positive, strongly suggesting that evaluation of sHER2 levels can be very useful in feline oncology. The results show that ELISA and Dot blot assay can replace the immunohistochemistry technique, due to their efficacy and lower costs for diagnostic purposes and for monitoring the response to anti-HER2 therapies in cats. PMID:26909614

  2. Planning and Delivering Instruction with Increasing Class Sizes in Educational Administration Program Coursework: Modeling Leadership Skills for New Professors Transitioning from K-12 Administration

    ERIC Educational Resources Information Center

    Stebbins, Gary

    2009-01-01

    Increased class sizes and advising responsibilities are the new realities in California's graduate programs of Educational Administration. In order to effectively meet new challenges, professors must make adjustments in venue, plan meticulously, utilize technology, distribute leadership, and implement alternative grading systems. This is a…

  3. Comparative kinetics of serum and vitreous humor digoxin concentrations in a guinea pig model. Part I: Intravenous administration of digoxin

    SciTech Connect

    Donnelly, B.; Balkon, J.; Bidanset, J.H.; Belmonte, A.; Barletta, M.; Manning, T. )

    1991-03-01

    The pharmacokinetics of a single intravenous dose of digoxin in the guinea pig was investigated with emphasis on the penetration of digoxin into the vitreous humor. A controlled study was undertaken and data was collected which indicated that digoxin follows an open, two-compartment pharmacokinetic model with a terminal half-life of 318 minutes. The data indicated that the ratio of vitreous concentrations to serum concentrations were determined to be equal following an initial tissue distribution phase.

  4. The new E.U. Animal Transport Regulation: improved welfare and health or increased administration?

    PubMed

    Hartung, J

    2006-03-01

    There is public discussion of the new E.U. Animal Transport Regulation No 1/2005 of Dec. 2004 and its advantages and draw-backs. This Regulation is no longer a Directive, so that it is directly applicable in the Members States. Although the Regulation is recognised to have great potential to improve welfare and health of transported animals, it will also increase administrative work. Most improvements will come through better education and the increased responsibilities of animal attendants, drivers, keepers and transport organisers, and through the stricter control mechanisms (log book, training, instructions etc.) and the introduction of the GPS control systems to further enhance the transparency of animal movements. The formats of the transport certificates used in all Member States will be harmonised. Technical records will be kept on air temperature and water consumption. Contact offices in all member states for transport affairs will improve the exchange of data between the responsible authorities and harmonise control and surveillance practice. Specific regulations are now in place for horses (broken, unbroken, registered) and for the transport age of young animals (piglets, lambs, calves, foals). In spite of some substantial improvements there are still significant gaps in our knowledge of both normal and long transports, for example optimal journey times, food and water supply on long transports, environmental factors such as vibration, motion, light and ventilation requirements in different European geographical regions. The same is true for the epidemiological aspects of the prevention of disease transmission; for example, very little is known about the bacterial and particulate emissions of the animal transport vehicles which travel across Europe. A serious drawback of the regulation is the fact that it does not abolish the unloading of animals on long transports to rest for 24 h at staging points, so that the concomitant risks to health and welfare

  5. Analysis of the effects of increasing doses of ionizing radiation to the exteriorized rat ovary on follicular development, atresia, and serum gonadotropin levels

    SciTech Connect

    Jarrell, J.; YoungLai, E.V.; Barr, R.; O'Connell, G.; Belbeck, L.; McMahon, A.

    1986-02-01

    There is increasing interest in the effects of environmental and therapeutic agents on the reproductive system, in particular, the ovary. To study the effects of controlled doses of ionizing radiation to the ovary, Sprague-Dawley rats had their ovaries exteriorized and subjected to increasing doses of radiation. There was a significant increase in ovarian follicular atresia, a significant increase in serum follicle-stimulating hormone levels, but no change in serum luteinizing hormone levels. This experimental protocol may facilitate the testing putative radioprotectants.

  6. 13C Natural Abundance in Serum Retinol Acts as a Biomarker for Increases in Dietary Provitamin A

    PubMed Central

    Howe, Julie A; Valentine, Ashley R; Hull, Angela K; Tanumihardjo, Sherry A

    2009-01-01

    The natural isotopic composition of 13C and 12C in tissues is largely determined by the diet. Sources of provitamin A carotenoids (e.g., vegetables) typically have a lower 13C to 12C ratio (13C:12C) than preformed vitamin A sources (i.e., dairy and meat) from corn-fed animals, which are prevalent in the US. The 13C:12C of serum retinol (13C:12C-retinol) was evaluated as a biomarker for vegetable intake in a 3-mo dietary intervention designed to promote weight-loss by increased vegetable consumption or reduced calorie and fat intake. Subjects were 21–50 y of age with a BMI between 30–40 kg/m2 and were enrolled from one geographic area in the US. The high vegetable group (n = 20) was encouraged to increase daily vegetable and fruit consumption to 0.95 liter vegetables and 0.24–0.35 liter fruits. The caloric reduction group (n = 17) was encouraged to lower caloric intake by 500 kcal and consume ≤25% kcal from fat daily. Provided meals supplied 75–100% vegetable and fruit goals and 50–67% kcal and fat g per day. Carotenoid supplementation was discontinued by subjects during the study. Serum retinol and provitamin A carotenoid concentrations; intake of preformed vitamin A, provitamin A, and fat; and body weight, fat mass, and lean mass were analyzed for correlations to 13C:12C-retinol. 13C:12C-Retinol decreased in the vegetable group after intervention (P = 0.050) and the correlation with provitamin A intake was approaching significance (P = 0.079). 13C:12C-Retinol did not change in the caloric reduction group (P = 0.43). 13C:12C-Retinol changes with the vitamin A source in the diet and can be used as a biomarker for increases in dietary provitamin A vegetable intake. PMID:19116317

  7. Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels

    PubMed Central

    Chang, Ming-Kang; Kramer, Ina; Huber, Thomas; Kinzel, Bernd; Guth-Gundel, Sabine; Leupin, Olivier; Kneissel, Michaela

    2014-01-01

    We identified previously in vitro LRP4 (low-density lipoprotein receptor-related protein 4) as a facilitator of the WNT (Wingless-type) antagonist sclerostin and found mutations disrupting this function to be associated with high bone mass in humans similar to patients lacking sclerostin. To further delineate the role of LRP4 in bone in vivo, we generated mice lacking Lrp4 in osteoblasts/osteocytes or osteocytes only. Lrp4 deficiency promoted progressive cancellous and cortical bone gain in both mutants, although more pronouncedly in mice deficient in osteoblast/osteocyte Lrp4, consistent with our observation in human bone that LRP4 is most strongly expressed by osteoblasts and early osteocytes. Bone gain was related primarily to increased bone formation. Interestingly, Lrp4 deficiency in bone dramatically elevated serum sclerostin levels whereas bone expression of Sost encoding for sclerostin was unaltered, indicating that osteoblastic Lrp4 retains sclerostin within bone. Moreover, we generated anti-LRP4 antibodies selectively blocking sclerostin facilitator function while leaving unperturbed LRP4–agrin interaction, which is essential for neuromuscular junction function. These antibodies increased bone formation and thus cancellous and cortical bone mass in skeletally mature rodents. Together, we demonstrate a pivotal role of LRP4 in bone homeostasis by retaining and facilitating sclerostin action locally and provide a novel avenue to bone anabolic therapy by antagonizing LRP4 sclerostin facilitator function. PMID:25404300

  8. Cytotoxic factor induced in murine serum after intravenous administration of a dehydrogenation polymer of p-coumaric acid (a synthetic lignin).

    PubMed

    Kohara, A; Shimizu, N; Kawazoe, Y

    1998-10-01

    A cytotoxic factor (CF) toward cultured murine leukemia L1210 cells was induced in mouse serum by intravenous injection of a dehydrogenation polymer of p-coumaric acid (DHP-pCA). When the serum from the treated mice was diluted with ethanol, CF was preserved in its supernatant (EtOH-sup). An EtOH-sup prepared from untreated control mice also showed cytotoxicity, although at much higher concentrations. The CF activity of EtOH-sups from both treated and untreated mice was completely eliminated by acid treatment at pH 2 at 90 degrees C for 30 min but kept intact by alkali treatment. In addition, the CF activity of both EtOH-sups was not affected by digestion with chymotrypsin. CF was recovered in a neutral MeOH-eluate from a DEAE-cellulofine column but not in HCI-MeOH eluate, in which lignified materials including DHP-pCA should have been recovered. These findings strongly suggest that CF is not a metabolite of DHP-pCA but an endogenous component of the normal serum which is augmented by DHP-pCA administration. PMID:9821818

  9. From Genotype to Phenotype: Nonsense Variants in SLC13A1 Are Associated with Decreased Serum Sulfate and Increased Serum Aminotransferases

    PubMed Central

    Tise, Christina G.; Perry, James A.; Anforth, Leslie E.; Pavlovich, Mary A.; Backman, Joshua D.; Ryan, Kathleen A.; Lewis, Joshua P.; O’Connell, Jeffrey R.; Yerges-Armstrong, Laura M.; Shuldiner, Alan R.

    2016-01-01

    Using genomic applications to glean insights into human biology, we systematically searched for nonsense single nucleotide variants (SNVs) that are rare in the general population but enriched in the Old Order Amish (Amish) due to founder effect. We identified two nonlinked, nonsense SNVs (R12X and W48X) in SLC13A1 (allele frequencies 0.29% and 0.74% in the Amish; enriched 1.2-fold and 3.7-fold, compared to the outbred Caucasian population, respectively). SLC13A1 encodes the apical sodium-sulfate cotransporter (NaS1) responsible for sulfate (re)absorption in the kidneys and intestine. SLC13A1 R12X and W48X were independently associated with a 27.6% (P = 2.7 × 10−8) and 27.3% (P = 6.9 × 10−14) decrease in serum sulfate, respectively (P = 8.8 × 10-20 for carriers of either SLC13A1 nonsense SNV). We further performed the first exome- and genome-wide association study (ExWAS/GWAS) of serum sulfate and identified a missense variant (L348P) in SLC26A1, which encodes the basolateral sulfate-anion transporter (Sat1), that was associated with decreased serum sulfate (P = 4.4 × 10−12). Consistent with sulfate’s role in xenobiotic detoxification and protection against acetaminophen-induced hepatotoxicity, SLC13A1 nonsense SNV carriers had higher aminotransferase levels compared to noncarriers. Furthermore, SLC26A1 L348P was associated with lower whole-body bone mineral density (BMD) and higher serum calcium, consistent with the osteochondrodysplasia exhibited by dogs and sheep with naturally occurring, homozygous, loss-of-function mutations in Slc13a1. This study demonstrates the power and translational potential of systematic identification and characterization of rare, loss-of-function variants and warrants additional studies to better understand the importance of sulfate in human physiology, disease, and drug toxicity. PMID:27412988

  10. Supraphysiologic glucocorticoid administration increased biomechanical bone strength of rats' vertebral body

    PubMed Central

    Najar, Azam; Fridoni, Mohammadjavad; Rezaei, Fatemesadat; Bayat, Saba

    2015-01-01

    The aim of this study is to assess the effects of different glucocorticoid administration protocols on biomechanical properties of the first lumbar vertebral body in rats. We divided 40 male rats into the following groups: control, dexamethasone (7 mg/week), dexamethasone (0.7 mg/week), methylprednisolone (7 mg/kg/week), methylprednisolone (5 mg/kg twice weekly), dexamethasone (7 mg/kg three times per week), dexamethasone (0.7 mg/kg three times per week, and low-level laser treated rats. Lumbar vertebrae in rats were exposed to the pulsed laser. We conducted a biomechanical test to examine the mechanical properties of vertebral body in rats' lumbar bone. Supraphysiologic glucocorticoid administration protocols did not impair the biomechanical properties of rats' vertebral bodies compared to control and laser-treated rats. Supraphysiologic glucocorticoid administration caused an anabolic effect on the vertebral bodies. PMID:26755921

  11. A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase

    PubMed Central

    Fu, Zhiyao; Abou-Samra, Abdul B.; Zhang, Ren

    2015-01-01

    Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses. PMID:26687026

  12. Low Serum Potassium Levels Increase the Infectious-Caused Mortality in Peritoneal Dialysis Patients: A Propensity-Matched Score Study

    PubMed Central

    Ribeiro, Silvia Carreira; Figueiredo, Ana Elizabeth; Barretti, Pasqual; Pecoits-Filho, Roberto; de Moraes, Thyago Proenca

    2015-01-01

    Background and Objectives Hypokalemia has been consistently associated with high mortality rate in peritoneal dialysis. However, studies investigating if hypokalemia is acting as a surrogate marker of comorbidities or has a direct effect in the risk for mortality have not been studied. Thus, the aim of this study was to analyze the effect of hypokalemia on overall and cause-specific mortality. Design, Setting, Participants and Measurements This is an analysis of BRAZPD II, a nationwide prospective cohort study. All patients on PD for longer than 90 days with measured serum potassium levels were used to verify the association of hypokalemia with overall and cause-specific mortality using a propensity match score to reduce selection bias. In addition, competing risks were also taken into account for the analysis of cause-specific mortality. Results There was a U-shaped relationship between time-averaged serum potassium and all-cause mortality of PD patients. Cardiovascular disease was the main cause of death in the normokalemic group with 133 events (41.8%) followed by PD-non related infections, n=105 (33.0%). Hypokalemia was associated with a 49% increased risk for CV mortality after adjustments for covariates and the presence of competing risks (SHR 1.49; CI95% 1.01-2.21). In contrast, in the group of patients with K <3.5mEq/L, PD-non related infections were the main cause of death with 43 events (44.3%) followed by cardiovascular disease (n=36; 37.1%). For PD-non related infections the SHR was 2.19 (CI95% 1.52-3.14) while for peritonitis was SHR 1.09 (CI95% 0.47-2.49). Conclusions Hypokalemia had a significant impact on overall, cardiovascular and infectious mortality even after adjustments for competing risks. The causative nature of this association suggested by our study raises the need for intervention studies looking at the effect of potassium supplementation on clinical outcomes of PD patients. PMID:26091005

  13. Trichomonas vaginalis NTPDase and ecto-5'-nucleotidase hydrolyze guanine nucleotides and increase extracellular guanosine levels under serum restriction.

    PubMed

    Menezes, Camila Braz; Durgante, Juliano; de Oliveira, Rafael Rodrigues; Dos Santos, Victor Hugo Jacks Mendes; Rodrigues, Luiz Frederico; Garcia, Solange Cristina; Dos Santos, Odelta; Tasca, Tiana

    2016-05-01

    Trichomonas vaginalis is the aethiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease in the world. The purinergic signaling pathway is mediated by extracellular nucleotides and nucleosides that are involved in many biological effects as neurotransmission, immunomodulation and inflammation. Extracellular nucleotides can be hydrolyzed by a family of enzymes known as ectonucleotidases including the ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) family which hydrolyses nucleosides triphosphate and diphosphate as preferential substrates and ecto-5'-nucleotidase which catalyzes the conversion of monophosphates into nucleosides. In T. vaginalis the E-NTPDase and ecto-5'-nucleotidase activities upon adenine nucleotides have already been characterized in intact trophozoites but little is known concerning guanine nucleotides and nucleoside. These enzymes may exert a crucial role on nucleoside generation, providing the purine sources for the synthesis de novo of these essential nutrients, sustaining parasite growth and survival. In this study, we investigated the hydrolysis profile of guanine-related nucleotides and nucleoside in intact trophozoites from long-term-grown and fresh clinical isolates of T. vaginalis. Knowing that guanine nucleotides are also substrates for T. vaginalis ectoenzymes, we evaluated the profile of nucleotides consumption and guanosine uptake in trophozoites submitted to a serum limitation condition. Results show that guanine nucleotides (GTP, GDP, GMP) were substrates for T. vaginalis ectonucleotidases, with expected kinetic parameters for this enzyme family. Different T. vaginalis isolates (two from the ATCC and nine fresh clinical isolates) presented a heterogeneous hydrolysis profile. The serum culture condition increased E-NTPDase and ecto-5'-nucleotidase activities with high consumption of extracellular GTP generating enhanced GDP, GMP and guanosine levels as demonstrated by HPLC, with final

  14. Dietary freshwater clam (Corbicula fluminea) extract suppresses accumulation of hepatic lipids and increases in serum cholesterol and aminotransferase activities induced by dietary chloretone in rats.

    PubMed

    Chijimatsu, Takeshi; Umeki, Miki; Kobayashi, Satoru; Kataoka, Yutaro; Yamada, Koji; Oda, Hiroaki; Mochizuki, Satoshi

    2015-01-01

    We investigated the ameliorative effect of freshwater clam extract (FCE) on fatty liver, hypercholesterolemia, and liver injury in rats exposed to chloretone. Furthermore, we examined the effects of major FCE components (fat and protein fractions) to determine the active components in FCE. Chloretone increased serum aminotransferase activities and led to hepatic lipid accumulation. Serum aminotransferase activities and hepatic lipid content were lower in rats fed total FCE or fat/protein fractions of FCE. Expression of fatty acid synthase and fatty acid desaturase genes was upregulated by chloretone. Total FCE and fat/protein fractions of FCE suppressed the increase in gene expression involved in fatty acid synthesis. Serum cholesterol levels increased twofold upon chloretone exposure. Total FCE or fat/protein fractions of FCE showed hypocholesterolemic effects in rats with hypercholesterolemia induced by chloretone. These suggest that FCE contains at least two active components against fatty liver, hypercholesterolemia, and liver injury in rats exposed to chloretone. PMID:25704646

  15. U.S. Public Administration Programs: Increasing Academic Achievement by Identifying and Utilizing Student Learning Styles

    ERIC Educational Resources Information Center

    Naylor, Lorenda A; Wooldridge, Blue; Lyles, Alan

    2014-01-01

    Global economic shifts are forcing universities to become more competitive and operationally efficient. As a result, universities emphasize access, affordability, and achievement. More specifically, U.S. universities have responded by emphasizing course assessment, retention rates, and graduation rates. Both university administrators and faculty…

  16. Serum IL-12 Is Increased in Mexican Obese Subjects and Associated with Low-Grade Inflammation and Obesity-Related Parameters

    PubMed Central

    Suárez-Álvarez, K.; Solís-Lozano, L.; Leon-Cabrera, S.; González-Chávez, A.; Gómez-Hernández, G.; Quiñones-Álvarez, M. S.; Serralde-Zúñiga, A. E.; Hernández-Ruiz, J.; Ramírez-Velásquez, J.; Galindo-González, F. J.; Zavala-Castillo, J. C.; De León-Nava, M. A.; Robles-Díaz, G.; Escobedo, G.

    2013-01-01

    Interleukin-(IL-) 12 has been recently suggested to participate during development of insulin resistance in obese mice. Nevertheless, serum IL-12 levels have not been accurately determined in overweight and obese humans. We thus studied serum concentrations of IL-12 in Mexican adult individuals, examining their relationship with low-grade inflammation and obesity-related parameters. A total of 147 healthy individuals, 43 normal weight, 61 overweight, and 43 obese subjects participated in the study. Circulating levels of IL-12, tumor necrosis factor-alpha (TNF-α), leptin, insulin, glucose, total cholesterol, and triglyceride were measured after overnight fasting in all of the study subjects. Waist circumference and body fat percentage were recorded for all the participants. Serum IL-12 was significantly higher in overweight and obese individuals than in normal weight controls. Besides being strongly related with body mass index (r = 0.5154), serum IL-12 exhibited a significant relationship with abdominal obesity (r = 0.4481), body fat percentage (r = 0.5625), serum glucose (r = 0.3158), triglyceride (r = 0.3714), and TNF-α (r = 0.4717). Thus, serum levels of IL-12 are increased in overweight and obese individuals and show a strong relationship with markers of low-grade inflammation and obesity in the Mexican adult population. Further research is needed to understand the role of IL-12 in developing obesity-associated alterations in humans. PMID:23533314

  17. Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol.

    PubMed

    Gillard, Baiba K; Rosales, Corina; Pillai, Biju K; Lin, Hu Yu; Courtney, Harry S; Pownall, Henry J

    2010-11-16

    Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high-density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM) that contains the cholesterol esters (CE) of up to ∼400000 HDL particles and apo E as its major protein. Similar SOF reaction products are obtained with HDL, total plasma lipoproteins, and whole plasma. We hypothesized that hepatic uptake of CERM-CE via multiple apo E-dependent receptors would be faster than that of HDL-CE. We tested our hypothesis using human hepatoma cells and lipoprotein receptor-specific Chinese hamster ovary (CHO) cells. The uptake of [(3)H]CE by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was 2.4 and 4.5 times faster, respectively, than from control HDL. CERM-[(3)H]CE uptake was inhibited by LDL and HDL, suggestive of uptake by both the LDL receptor (LDL-R) and scavenger receptor class B type I (SR-BI). Studies in CHO cells specifically expressing LDL-R and SR-BI confirmed CERM-[(3)H]CE uptake by both receptors. RAP and heparin inhibit CERM-[(3)H]CE but not HDL-[(3)H]CE uptake, thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases the rate of CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase the level of hepatic disposal of plasma cholesterol in a way that is therapeutically useful. PMID:20879789

  18. Increasing serum Pre-adipocyte factor-1 (Pref-1) correlates with decreased body fat, increased free fatty acids, and level of recent alcohol consumption in excessive alcohol drinkers

    PubMed Central

    Liangpunsakul, Suthat; Bennett, Rachel; Westerhold, Chi; Ross, Ruth A.; Crabb, David W.; Lai, Xianyin; Witzmann, Frank A.

    2014-01-01

    Background Patients with alcoholic liver disease have been reported to have a significantly lower percentage of body fat (%BF) than controls. The mechanism for the reduction in %BF in heavy alcohol users has not been elucidated. In adipose tissue, Pref-1 is specifically expressed in pre-adipocytes but not in adipocytes. Pref-1 inhibits adipogenesis and elevated levels are associated with reduced adipose tissue mass. We investigated the association between serum Pref-1 and %BF, alcohol consumption, and serum free fatty acids (FFA) in a well-characterized cohort of heavy alcohol users compared to controls. Methods One hundred forty-eight subjects were prospectively recruited. The Time Line Follow-Back (TLFB) questionnaire was used to quantify the amount of alcohol consumed over the 30-day period before their enrollment. Anthropometric measurements were performed to calculate %BF. Serum Pref-1 and FFA were measured. Results Fifty-one subjects (mean age 32 ± 9 years, 88% men) were non-excessive drinkers whereas 97 were excessive drinkers (mean age 41 ± 18 years, 69% men). Compared to non-excessive drinkers, individuals with excessive drinking had significantly higher levels of Pref-1 (p < 0.01), FFA (p < 0.001), and lower %BF (p = 0.03). Serum levels of Pref-1 were associated with the amount of alcohol consumed during the previous 30 days. Serum Pref-1 was negatively correlated with %BF, but positively associated with serum FFA. Conclusions Our data suggest that elevated Pref-1 levels in excessive drinkers might inhibit the expansion of adipose tissue, decreasing %BF in alcoholics. Further work is needed to validate these findings and to better understand the role of Pref-1 and its clinical significance in subjects with heavy alcohol use. PMID:25449367

  19. Increasing serum pre-adipocyte factor-1 (Pref-1) correlates with decreased body fat, increased free fatty acids, and level of recent alcohol consumption in excessive alcohol drinkers.

    PubMed

    Liangpunsakul, Suthat; Bennett, Rachel; Westerhold, Chi; Ross, Ruth A; Crabb, David W; Lai, Xianyin; Witzmann, Frank A

    2014-12-01

    Patients with alcoholic liver disease have been reported to have a significantly lower percentage of body fat (%BF) than controls. The mechanism for the reduction in %BF in heavy alcohol users has not been elucidated. In adipose tissue, Pref-1 is specifically expressed in pre-adipocytes but not in adipocytes. Pref-1 inhibits adipogenesis and elevated levels are associated with reduced adipose tissue mass. We investigated the association between serum Pref-1 and %BF, alcohol consumption, and serum free fatty acids (FFA) in a well-characterized cohort of heavy alcohol users compared to controls. One hundred forty-eight subjects were prospectively recruited. The Time Line Follow-Back (TLFB) questionnaire was used to quantify the amount of alcohol consumed over the 30-day period before their enrollment. Anthropometric measurements were performed to calculate %BF. Serum Pref-1 and FFA were measured. Fifty-one subjects (mean age 32 ± 9 years, 88% men) were non-excessive drinkers whereas 97 were excessive drinkers (mean age 41 ± 18 years, 69% men). Compared to non-excessive drinkers, individuals with excessive drinking had significantly higher levels of Pref-1 (p<0.01), FFA (p < 0.001), and lower %BF (p = 0.03). Serum levels of Pref-1 were associated with the amount of alcohol consumed during the previous 30 days. Serum Pref-1 was negatively correlated with %BF, but positively associated with serum FFA. Our data suggest that elevated Pref-1 levels in excessive drinkers might inhibit the expansion of adipose tissue, decreasing %BF in alcoholics. Further work is needed to validate these findings and to better understand the role of Pref-1 and its clinical significance in subjects with heavy alcohol use. PMID:25449367

  20. Long-term garlic or micronutrient supplementation, but not anti-Helicobacter pylori therapy, increases serum folate or glutathione without affecting serum vitamin B-12 or homocysteine in a rural Chinese population.

    PubMed

    Wang, Yujue; Zhang, Lian; Moslehi, Roxana; Ma, Junling; Pan, Kaifeng; Zhou, Tong; Liu, Weidong; Brown, Linda Morris; Hu, Yuangreng; Pee, David; Gail, Mitchell H; You, Weicheng

    2009-01-01

    The effects of a 7.3-y supplementation with garlic and micronutrients and of anti-Helicobacter pylori treatment with amoxicillin (1 g twice daily) and omeprazole (20 mg twice daily) on serum folate, vitamin B-12, homocysteine, and glutathione concentrations were assessed in a rural Chinese population. A randomized, double-blind, placebo-controlled, factorial trial was conducted to compare the ability of 3 treatments to retard the development of precancerous gastric lesions in 3411 subjects. The treatments were: 1) anti-H. pylori treatment with amoxicillin and omeprazole; 2) 7.3-y supplementation with aged garlic and steam-distilled garlic oil; and 3) 7.3-y supplementation with vitamin C, vitamin E, and selenium. All 3 treatments were given in a 2(3) factorial design to subjects seropositive for H. pylori infection; only the garlic supplement and vitamin and selenium supplement were given in a 2(2) factorial design to the other subjects. Thirty-four subjects were randomly selected from each of the 12 treatment strata. Sera were analyzed after 7.3 y to measure effects on folate, vitamin B-12, homocysteine, and glutathione concentrations. Regression analyses adjusted for age, gender, and smoking indicated an increase of 10.2% (95%CI: 2.9-18.1%) in serum folate after garlic supplementation and an increase of 13.4% (95%CI: 5.3-22.2%) in serum glutathione after vitamin and selenium supplementation. The vitamin and selenium supplement did not affect other analytes and the amoxicillin and omeprazole therapy did not affect any of the variables tested. In this rural Chinese population, 7.3 y of garlic supplementation increased the serum folate concentration and the vitamin and selenium supplement increased that of glutathione, but neither affected serum concentrations of vitamin B-12 or homocysteine. PMID:19056661

  1. Interferon-Free Treatment of Hepatitis C Virus in HIV/Hepatitis C Virus-Coinfected Subjects Results in Increased Serum Low-Density Lipoprotein Concentration.

    PubMed

    Townsend, Kerry; Meissner, Eric G; Sidharthan, Sreetha; Sampson, Maureen; Remaley, Alan T; Tang, Lydia; Kohli, Anita; Osinusi, Anu; Masur, Henry; Kottilil, Shyam

    2016-05-01

    Chronic hepatitis C virus (HCV) infection is associated with lower serum concentration of low-density lipoprotein (LDL-C), the primary cholesterol metabolite targeted pharmaceutically to modulate cardiovascular risk. Chronic infection with human immunodeficiency virus (HIV) and treatment with antiretrovirals (ARVs) are associated with dyslipidemia and increased risk of cardiovascular disease. In subjects coinfected with HIV and HCV, lipid abnormalities associated with either infection alone are often attenuated. Treatment of chronic HCV infection in HIV/HCV-coinfected subjects is now possible with interferon (IFN)-free regimens composed of directly acting antivirals (DAAs). We previously observed a marked increase in serum LDL-C in HCV-monoinfected subjects treated with sofosbuvir and ribavirin (SOF/RBV) that correlated with viral decline in serum, suggesting a direct influence of HCV clearance on serum cholesterol. In the present study, we assessed longitudinal changes in cholesterol in HIV/HCV-coinfected subjects during treatment of HCV genotype-1 (GT1) infection with combination DAA therapy. We report a rapid increase in LDL-C and LDL particle size by week 2 of treatment that was sustained during and after treatment in HIV/HCV-coinfected subjects. No change in serum LDL-C was observed at day 3 of treatment, in spite of a marked reduction in serum HCV viral load, suggesting LDL-C increases do not directly reflect HCV clearance as measured in peripheral blood. After effective DAA therapy for HCV, an increase in LDL should be anticipated in HIV/HCV-coinfected subjects. PMID:26559180

  2. Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study

    PubMed Central

    Vincent, Jean-Louis; Sakr, Yasser; Reinhart, Konrad; Sprung, Charles L; Gerlach, Herwig; Ranieri, V Marco

    2005-01-01

    Introduction Albumin administration in the critically ill has been the subject of some controversy. We investigated the use of albumin solutions in European intensive care units (ICUs) and its relationship to outcome. Methods In a cohort, multicenter, observational study, all patients admitted to one of the participating ICUs between 1 May and 15 May 2002 were followed up until death, hospital discharge, or for 60 days. Patients were classified according to whether or not they received albumin at any time during their ICU stay. Results Of 3,147 admitted patients, 354 (11.2%) received albumin and 2,793 (88.8%) did not. Patients who received albumin were more likely to have cancer or liver cirrhosis, to be surgical admissions, and to have sepsis. They had a longer length of ICU stay and a higher mortality rate, but were also more severely ill, as manifested by higher simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores than the other patients. A Cox proportional hazard model indicated that albumin administration was significantly associated with decreased 30-day survival. Moreover, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in the patients who had received albumin than in those who had not (34.8 versus 20.9% and 41.3 versus 27.7%, respectively, both p < 0.001). Conclusion Albumin administration was associated with decreased survival in this population of acutely ill patients. Further prospective randomized controlled trials are needed to examine the effects of albumin administration in sub-groups of acutely ill patients. PMID:16356223

  3. Increases of CCK mRNA and peptide in different brain areas following acute and chronic administration of morphine.

    PubMed

    Ding, X Z; Bayer, B M

    1993-10-15

    The present study examined whether either acute or chronic administration of morphine resulted in changes in the content of CCK mRNA and CCK immunoactive peptide in selective areas of the rat brain and spinal cord. Two hours after a single injection of morphine (10 mg/kg, s.c.), CCK mRNA significantly increased in the hypothalamus (0.8-fold) and spinal cord (2-fold) relative to the CCK mRNA content in saline-injected controls. No significant differences in CCK mRNA were observed in the frontal cortex, hippocampus, midbrain or brainstem. There were no significant alterations in CCK immunoreactivity in any brain regions and spinal cord after the acute treatment with morphine. Upon repeated morphine administration, the content of CCK mRNA in both the hypothalamus and the spinal cord was further elevated by at least 3-fold. A significant increase of CCK mRNA content in brain stem (2.8-fold) was also observed following chronic morphine administration. In contrast to the acute exposure to morphine, chronic administration resulted in significant increases in CCK immunoactive peptide in hypothalamus (2.6-fold), spinal cord (2.1-fold) and brainstem (1.6-fold), but not in the other brain areas. These results demonstrate that morphine, especially following repeated administrations, stimulates endogenous CCK biosynthesis in selective brain regions. PMID:8242392

  4. Perinatal exposure to low-dose DE-71 increases serum thyroid hormones and gonadal osteopontin gene expression

    PubMed Central

    Blake, Charles A; McCoy, George L; Hui, Yvonne Y; LaVoie, Holly A

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are flame retardants that have been widely used in manufacturing. They are major household and environmental contaminants that bioaccumulate. Humans are exposed primarily through dust inhalation and dietary ingestion of animal products. In animal studies, high doses of penta-brominated diphenyl ethers (penta-BDEs) in the mg/kg body weight (BW) range negatively impact brain development, behavior, memory, circulating thyroid hormone concentrations, the reproductive system and bone development. We investigated the effects of ingestion of a relatively low dose of the penta-BDE mixture DE-71 by pregnant and lactating rats on reproductive and thyroid parameters of the F1 offspring. F0 mothers received 60 μg/kg BW of DE-71 or vehicle daily by gavage from Day 1.5 of pregnancy through lactation (except the day of parturition). F1 pups were sacrificed at 21 d of age or outbred at approximately 80 d of age. Bred F1 females were sacrificed at Day 14.5 of pregnancy or at five months of age. Bred F1 males were sacrificed at five months of age. DE-71 treatment of the mothers affected the F1 females as evidenced by lower body weights at 80 d and five months of age, elevated serum T3 and T4 concentrations at Day 14.5 of pregnancy and increased thyroid gland weight and ovarian osteopontin mRNA at five months of age. Perinatal DE-71 exposure also increased testicular osteopontin mRNA in 21-day-old F1 males. Utilizing a granulosa cell in vitro model, we demonstrated that DE-71 activated the rat osteopontin gene promoter. Our results are the first to demonstrate that PBDEs increase rodent circulating T3 and T4 concentrations and gonadal osteopontin mRNA, and activate the osteopontin gene promoter. These changes may have clinical implications as others have shown associations between human exposure to PBDEs and subclinical hyperthyroidism, and overexpression of ovarian osteopontin has been associated with ovarian cancer. PMID:21367881

  5. Feeding hydroalcoholic extract powder of Lepidium meyenii (maca) increases serum testosterone concentration and enhances steroidogenic ability of Leydig cells in male rats.

    PubMed

    Ohta, Y; Yoshida, K; Kamiya, S; Kawate, N; Takahashi, M; Inaba, T; Hatoya, S; Morii, H; Takahashi, K; Ito, M; Ogawa, H; Tamada, H

    2016-04-01

    Although Lepidium meyenii (maca), a plant growing in Peru's central Andes, has been traditionally used for enhancing fertility and reproductive performance in domestic animals and human beings, effects of maca on reproductive organs are still unclear. This study examined whether feeding the hydroalcoholic extract powder of maca for 6 weeks affects weight of the reproductive organs, serum concentrations of testosterone and luteinising hormone (LH), number and cytoplasmic area of immunohistochemically stained Leydig cells, and steroidogenesis of cultured Leydig cells in 8-week-old male rats. Feeding the extract powder increased weight of seminal vesicles, serum testosterone level and cytoplasmic area of Leydig cells when compared with controls. Weight of prostate gland, serum LH concentration and number of Leydig cells were not affected by the maca treatment. The testosterone production by Leydig cells significantly increased when cultured with 22R-hydroxycholesterol or pregnenolone and tended to increase when cultured with hCG by feeding the extract powder. The results show that feeding the hydroalcoholic extract powder of maca for 6 weeks increases serum testosterone concentration associated with seminal vesicle stimulation in male rats, and this increase in testosterone level may be related to the enhanced ability of testosterone production by Leydig cells especially in the metabolic process following cholesterol. PMID:26174043

  6. High serum levels of proinflammatory markers during epileptogenesis. Can omega-3 fatty acid administration reduce this process?

    PubMed

    Gouveia, Telma Luciana Furtado; Vieira de Sousa, Paula Viviane; de Almeida, Sandro Soares; Nejm, Mariana Bocca; Vieira de Brito, Joíse Marques; Cysneiros, Roberta Monterazzo; de Brito, Marlon Vilela; Salu, Bruno Ramos; Oliva, Maria Luiza Vilela; Scorza, Fúlvio Alexandre; Naffah-Mazzacoratti, Maria da Graça

    2015-10-01

    During the epileptogenic process, several events may occur, such as an important activation of the immune system in the central nervous system. The response to seizure activity results in an inflammation in the brain as well as in the periphery. Moreover, CRP and cytokines may be able to interact with numerous ligands in response to cardiac injury caused by sympathetic stimulation in ictal and postictal states. Based on this, we measured the serum levels of C-reactive protein (CRP) and cytokines during acute, silent, and chronic phases of rats submitted to the pilocarpine model of epilepsy. We have also analyzed the effect of a chronic treatment of these rats with omega-3 fatty acid in CRP and cytokine levels, during an epileptic focus generation. C-reactive protein and cytokines such as IL-1β, IL-6, and TNF-α presented high concentration in the blood of rats, even well after the occurrence of SE. We found reduced levels of CRP and all proinflammatory cytokines in the blood of animals with chronic seizures, treated with omega-3, when compared with those treated with vehicle solution. Taken together, our results strongly suggest that the omega-3 is an effective treatment to prevent SUDEP occurrence due to its capability to act as an anti-inflammatory compound, reducing the systemic inflammatory parameters altered by seizures. PMID:26318793

  7. High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance

    PubMed Central

    Lu, Chia-Wen; Chang, Hao-Hsiang; Yang, Kuen-Cheh; Kuo, Chia-Sheng; Lee, Long-Teng; Huang, Kuo-Chin

    2016-01-01

    Objective Selenium is an essential micronutrient for human health. Although many observational and interventional studies have examined the associations between selenium and diabetes mellitus, the findings were inconclusive. This study aimed to investigate the relationship between serum selenium levels and prevalence of diabetes, and correlated the relationship to insulin resistance and central obesity. Research design and methods This was a hospital-based case–control study of 847 adults aged more than 40 years (diabetes: non-diabetes =1:2) in Northern Taiwan. Serum selenium was measured by an inductively coupled plasma-mass spectrometer. The association between serum selenium and diabetes was examined using multivariate logistic regression analyses. Results After adjusting for age, gender, current smoking, current drinking, and physical activity, the ORs (95% CI, p value) of having diabetes in the second (Q2), third (Q3), and fourth (Q4) selenium quartile groups were 1.24 (95% CI 0.78 to 1.98, p>0.05), 1.90 (95% CI 1.22 to 2.97, p<0.05), and 5.11 (95% CI 3.27 to 8.00, p<0.001), respectively, compared with the first (Q1) quartile group. Further adjustments for waist circumference and homeostatic model assessment-insulin resistance (HOMA-IR) largely removed the association of serum selenium levels with diabetes but not in the highest quartile (compared with Q1, Q3: 1.57, 95% CI 0.91 to 2.70, Q4: 3.79, 95% CI 2.17 to 6.32). Conclusions We found that serum selenium levels were positively associated with prevalence of diabetes. This is the first human study to link insulin resistance and central obesity to the association between selenium and diabetes. Furthermore, the association between selenium and diabetes was independent of insulin resistance and central obesity at high serum selenium levels. The mechanism behind warrants further confirmation. PMID:27547419

  8. Increased serum IgE concentrations during infection and graft versus host disease after bone marrow transplantation.

    PubMed Central

    Walker, S A; Rogers, T R; Perry, D; Hobbs, J R; Riches, P G

    1984-01-01

    Serum IgE concentrations estimated in 25 bone marrow transplant recipients during episodes of infection or graft versus host disease, or both, were raised not only in some patients with acute graft versus host disease but also in many patients with infection. Raised values were not seen in chronic graft versus host disease. The routine estimation of serum IgE in bone marrow transplant recipients had minimal value because of the lack of specificity of the IgE response. PMID:6368605

  9. 9G4 Autoreactivity Is Increased in HIV-Infected Patients and Correlates with HIV Broadly Neutralizing Serum Activity

    PubMed Central

    Kobie, James J.; Alcena, Danielle C.; Zheng, Bo; Bryk, Peter; Mattiacio, Jonelle L.; Brewer, Matthew; LaBranche, Celia; Young, Faith M.; Dewhurst, Stephen; Montefiori, David C.; Rosenberg, Alexander F.; Feng, Changyong; Jin, Xia; Keefer, Michael C.; Sanz, Ignacio

    2012-01-01

    The induction of a broadly neutralizing antibody (BNAb) response against HIV-1 would be a desirable feature of a protective vaccine. Vaccine strategies thus far have failed to elicit broadly neutralizing antibody responses; however a minority of HIV-infected patients do develop circulating BNAbs, from which several potent broadly neutralizing monoclonal antibodies (mAbs) have been isolated. The findings that several BNmAbs exhibit autoreactivity and that autoreactive serum antibodies are observed in some HIV patients have advanced the possibility that enforcement of self-tolerance may contribute to the rarity of BNAbs. To examine the possible breakdown of tolerance in HIV patients, we utilized the 9G4 anti-idiotype antibody system, enabling resolution of both autoreactive VH4-34 gene-expressing B cells and serum antibodies. Compared with healthy controls, HIV patients had significantly elevated 9G4+ serum IgG antibody concentrations and frequencies of 9G4+ B cells, a finding characteristic of systemic lupus erythematosus (SLE) patients, both of which positively correlated with HIV viral load. Compared to the global 9G4−IgD− memory B cell population, the 9G4+IgD− memory fraction in HIV patients was dominated by isotype switched IgG+ B cells, but had a more prominent bias toward “IgM only" memory. HIV envelope reactivity was observed both in the 9G4+ serum antibody and 9G4+ B cell population. 9G4+ IgG serum antibody levels positively correlated (r = 0.403, p = 0.0019) with the serum HIV BNAbs. Interestingly, other serum autoantibodies commonly found in SLE (anti-dsDNA, ANA, anti-CL) did not correlate with serum HIV BNAbs. 9G4-associated autoreactivity is preferentially expanded in chronic HIV infection as compared to other SLE autoreactivities. Therefore, the 9G4 system provides an effective tool to examine autoreactivity in HIV patients. Our results suggest that the development of HIV BNAbs is not merely a consequence of a general breakdown in

  10. Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

    PubMed

    Cho, Jin Hee; Cho, Yun Ha; Kim, Hyo Young; Cha, Seung Ha; Ryu, Hyun; Jang, Wooyoung; Shin, Kyung Ho

    2015-04-01

    Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration. PMID:25820086

  11. Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis.

    PubMed

    Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

    2016-01-01

    In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia's gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus. PMID:26983596

  12. Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis

    PubMed Central

    Liu, Zhi; Liu, Wenshu; Ran, Chao; Hu, Jun; Zhou, Zhigang

    2016-01-01

    In this study, we investigated the risk associated with suspension of probiotics administration in tilapia, an animal model that may mimic immune-compromised conditions in humans. Tilapias were fed for 14 days using a probiotics-supplemented diet, followed by a three-day suspension of probiotics treatment and a subsequent challenge by Aeromonas hydrophila. Unexpectedly, the suspension of a probiotic strain Lactobacillus plantarum JCM1149 significantly triggered susceptibility of the host to A. hydrophila. We further observed that suspension of JCM1149 resulted in host gut microbiota dysbiosis and the subsequent disorder in the intestinal metabolites (bile acids, amino acids, and glucose) and damage in the intestinal epithelium, giving rise to a condition similar to antibiotics-induced gut dysbiosis, which collectively impaired tilapia’s gut health and resistance to pathogenic challenges. Additionally, we determined that JCM1149 adhered relatively poorly to tilapia intestinal mucosa and was rapidly released from the gastrointestinal tract (GIT) after suspension, with the rapid loss of probiotic strain probably being the direct cause of gut dysbiosis. Finally, three other probiotic Lactobacillus strains with low intestinal mucosa binding activity showed similar rapid loss phenotype following administration suspension, and induced higher host susceptibility to infection, indicating that the risk is a generic phenomenon in Lactobacillus. PMID:26983596

  13. Increasing the Use of Group Interventions in a Pediatric Rehabilitation Program: Perceptions of Administrators, Therapists, and Parents

    ERIC Educational Resources Information Center

    Camden, Chantal; Tetreault, Sylvie; Swaine, Bonnie

    2012-01-01

    Objectives: To explore perceptions related to increased utilization of group interventions as a part of the service reorganization within a pediatric rehabilitation program. Methods: Individual interviews with program administrators (n = 13) and focus groups with therapists (n = 19) and parents of children with disabilities (n = 5) were conducted.…

  14. Evaluation of tests for rabies antibody and analysis of serum responses after administration of three different types of rabies vaccines.

    PubMed Central

    Grandien, M

    1977-01-01

    Humoral antibody response to three types of rabies vaccines were assayed by the neutralization (NT), the mixed hemadsorption (MH), and the indirect immunofluorescence (IF) tests. The NT and MH tests were used to detect antibodies combining with antigens at the surface of virions and infected cells, whereas the indirect IF test measured antibodies mainly to the rabies nucleocapsid antigen. After immunization with a human diploid cell vaccine, antibodies were detected by both the NT and the MH test in the 14th- and 30th-day serum samples from each of eight vaccinated persons. There was a good correlation between titers obtained with the two tests in this group of vaccinees. Antibodies elicited by duck embryo and nervous tissue vaccines occurred less frequently and in lower titers. In these groups of vaccinees, 5 of 14 and 5 of 10, respectively, had antibodies detectable by the NT test in the 14th- and 30th-day sera but were negative by the MH test. It is suggested that this was due to the high levels of immunoglobulin M antibodies, which are known to be elicited by daily injections of vaccine. Since antibodies of the immunoglobulin M class are considered to be less important for protection against rabies, the MH test is recommended for immunity determinations. Compared with the NT test, this test also offers the advantage of being technically more convenient because of its capacity for testing numerous sera in a single run. Antibody titers obtained by the indirect IF test in the human diploid cell vaccine group were relatively low. Titers in the duck embryo and nervous tissue vaccine groups were higher but did not correlate with the results of the NT test. PMID:323275

  15. A primary pure yolk sac tumor of the lung exhibiting CDX-2 immunoreactivity and increased serum levels of alkaline phosphatase intestinal isoenzyme.

    PubMed

    Pelosi, Giuseppe; Petrella, Francesco; Sandri, Maria Teresa; Spaggiari, Lorenzo; Galetta, Domenico; Viale, Giuseppe

    2006-07-01

    Malignant extragonadal germ cell tumors primary to the lung are quite uncommon lesions, but pure yolk sac tumor is even more exceptional. This is believed to be the first reported case of yolk sac tumor of the lung in which an intense and diffuse immunoreactivity for CDX2, a marker of intestinal differentiation reportedly expressed also in gonadal yolk sac tumor, was associated with increased serum levels of the alkaline phosphatase intestinal isoform. Nine months after radical surgery and adjuvant chemotherapy, the patient is alive and well without evidence of recurrent or metastatic disease and with serum levels of the alkaline phosphatase intestinal isoform within normal limits. The pathologist should be aware of yolk sac tumor arising in the lung and that alkaline phosphatase intestinal isoform could become an additional serum marker for such a tumor. PMID:16959714

  16. Extremely increased serum carbohydrate antigen 19-9 levels caused by new or resistant infections to previous antibiotics in chronic lung diseases.

    PubMed

    Shin, Ji Young; Yoo, Su Jin; Park, Bo Mi; Jung, Sung Su; Kim, Ju Ock; Lee, Jeong Eun

    2013-09-01

    In this paper, we describe 72-year-old female patient without evidence of malignant disease presented with significantly elevated serum carbohydrate antigen (CA) 19-9 levels by respiratory infections. She was diagnosed with respiratory infections due to Mycobacterium avium complex and Pseudomonas aeruginosa. The serum CA 19-9 levels remarkably increased (1,453-5,300 U/mL; reference range, <37 U/mL) by respiratory infection and abruptly decreased (357-534 U/mL) whenever infection was controlled by specific treatments. This case suggests that serum CA 19-9 levels may be used as a diagnostic marker to indicate new or resistant infections to previous antibiotics in chronic lung diseases without significant changes in chest X-ray findings. PMID:24101938

  17. Smoking is associated with reduced serum paraoxonase, antioxidants and increased oxidative stress in normolipidaemic acute myocardial infarct patients

    PubMed Central

    Kumar, Arun; Biswas, Utpal Kumar

    2011-01-01

    Background Paraoxonase is a high-density lipoprotein (HDL)-associated enzyme that protects lipoproteins from oxidative modifications and from becoming atherogenic in nature. Smoking is a well-known major cardiovascular risk factor that promotes lipid peroxidation (LP). The present study examined the hypothesis that smoking modulates the activity of paraoxonase and depletes antioxidants. Aim The present study evaluated paraoxonase activity, antioxidant status and LP in smoking and non-smoking normolipidaemic acute myocardial infarct (AMI) patients, and results were compared with controls. Settings and design The serum paraoxonase activities, antioxidants and LP were determined in 86 normolipidaemic patients diagnosed of AMI, and 86 age–sex-matched healthy volunteers served as control. Material and methods Serum paraoxonase activities were measured by enzymatic kit. The glutathione peroxidase, superoxide dismutase and catalase activity was determined by standard methods. Malondialdehyde was measured by the thiobarbituric acid reaction, and conjugated diene levels by the Recknagel and Glende method. Serum uric acid, total bilirubin, serum albumin and lipid profiles were analysed by standard methods. Statistics The values were expressed as mean±SD, and data from the patients and control were compared using the Student t test. Results and conclusion The total cholesterol/HDL cholesterol ratio, triglycerides, low-density lipoprotein cholesterol, low-density lipoprotein/HDL cholesterol ratio and triglyceride/HDL cholesterol ratio were significantly higher, and HDL cholesterol significantly lower in smokers compared with non-smoking AMI patients. Superoxide dismutase, glutathione peroxidase and catalase were significantly higher in non-smokers compared with smokers. Serum albumin, uric acid and bilirubin were higher in the control compared with smoking AMI patients. The malondialdehyde and conjugated dienes were significantly higher, and paraoxonase activities were

  18. Increased Serum Levels of Oxytocin in ‘Treatment Resistant Depression in Adolescents (TRDIA)’ Group

    PubMed Central

    Hashimoto, Kenji; Oda, Yasunori; Ishima, Tamaki; Yakita, Madoka; Kurata, Tsutomu; Kunou, Masaru; Takahashi, Jumpei; Kamata, Yu; Kimura, Atsushi; Niitsu, Tomihisa; Komatsu, Hideki; Hasegawa, Tadashi; Shiina, Akihiro; Hashimoto, Tasuku; Kanahara, Nobuhisa; Shimizu, Eiji; Iyo, Masaomi

    2016-01-01

    Objective ‘Treatment-resistant depression’ is depression that does not respond to an adequate regimen of evidence-based treatment. Treatment-resistant depression frequently becomes chronic. Children with treatment-resistant depression might also develop bipolar disorder (BD). The objective of this study was to determine whether serum levels of oxytocin (OXT) in treatment-resistant depression in adolescents (TRDIA) differ from non-treatment-resistant depression in adolescents (non-TRDIA) or controls. We also investigated the relationships between serum OXT levels and the clinical symptoms, severity, and familial histories of adolescent depressive patients. Methods We measured serum OXT levels: TRDIA (n = 10), non-TRDIA (n = 27), and age- and sex- matched, neurotypical controls (n = 25). Patients were evaluated using the Children’s Depression Rating Scale-Revised (CDRS-R) and the Depression Self-Rating Scale for Children-Japanese Version (DSRS-C-J). The patients were also assessed retrospectively using the following variables: familial history of major depressive disorder and BD (1st degree or 2nd degree), history of disruptive mood dysregulation disorder, recurrent depressive disorder (RDD), history of antidepressant activation. Results Serum levels of OXT among the TRDIA and non-TRDIA patients and controls differed significantly. Interestingly, the rates of a family history of BD (1st or 2nd degree), RDD and a history of antidepressant activation in our TRDIA group were significantly higher than those of the non-TRDIA group. Conclusions Serum levels of OXT may play a role in the pathophysiology of TRDIA. PMID:27536785

  19. Administration's Proposed NSF Budget Includes a 5.5% Increase for Geosciences

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2013-04-01

    The fiscal year (FY) 2014 proposed federal budget for the U.S. National Science Foundation (NSF) is $7.63 billion, 7.3% above the FY 2012 actual amount. NSF acting director Cora Marrett said the budget reflects the administration's recognition of NSF and the importance of funding basic research. "We are pleased about where we stand and hope that Congress will be just as pleased with the budget proposal and will help move things forward," she said during a meeting of the NSF Advisory Committee for Geosciences on 11 April. Budget comparisons are to FY 2012 because the 2013 appropriations were enacted at the end of March, less than 2 weeks before President Barack Obama sent the proposed budget to Congress.

  20. The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

    PubMed Central

    Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

    2015-01-01

    The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

  1. Synergistic Increase of Serum BDNF in Alzheimer Patients Treated with Cerebrolysin and Donepezil: Association with Cognitive Improvement in ApoE4 Cases

    PubMed Central

    Alvarez, Irene; Iglesias, Olalla; Crespo, Ignacio; Figueroa, Jesus; Aleixandre, Manuel; Linares, Carlos; Granizo, Elias; Garcia-Fantini, Manuel; Marey, Jose; Masliah, Eliezer; Winter, Stefan; Muresanu, Dafin; Moessler, Herbert

    2016-01-01

    Background: Low circulating brain derived neurotrophic factor may promote cognitive deterioration, but the effects of neurotrophic and combination drug therapies on serum brain derived neurotrophic factor were not previously investigated in Alzheimer’s disease. Methods: We evaluated the effects of Cerebrolysin, donepezil, and the combined therapy on brain derived neurotrophic factor serum levels at week 16 (end of Cerebrolysin treatment) and week 28 (endpoint) in mild-to-moderate Alzheimer’s disease patients. Results: Cerebrolysin, but not donepezil, increased serum brain derived neurotrophic factor at week 16, while the combination therapy enhanced it at both week 16 and study endpoint. Brain derived neurotrophic factor responses were significantly higher in the combination therapy group than in donepezil and Cerebrolysin groups at week 16 and week 28, respectively. Brain derived neurotrophic factor increases were greater in apolipoprotein E epsilon-4 allele carriers, and higher brain derived neurotrophic factor levels were associated with better cognitive improvements in apolipoprotein E epsilon-4 allele patients treated with Cerebrolysin and the combined therapy. Conclusion: Our results indicate a synergistic action of Cerebrolysin and donepezil to increase serum brain derived neurotrophic factor and delaying cognitive decline, particularly in Alzheimer’s disease cases with apolipoprotein E epsilon-4 allele. PMID:27207906

  2. Increased Seizure Latency and Decreased Severity of Pentylenetetrazol-Induced Seizures in Mice after Essential Oil Administration

    PubMed Central

    Koutroumanidou, Eleni; Kimbaris, Athanasios; Kortsaris, Alexandros; Bezirtzoglou, Eugenia; Polissiou, Moschos; Charalabopoulos, Konstantinos

    2013-01-01

    The effect of pretreatment with essential oils (EOs) from eight aromatic plants on the seizure latency and severity of pentylenetetrazol- (PTZ-) induced seizures in mice was evaluated. Weight-dependent doses of Rosmarinus officinalis, Ocimum basilicum, Mentha spicata, Mentha pulegium, Lavandula angustifolia, Mentha piperita, Origanum dictamnus, and Origanum vulgare, isolated from the respective aromatic plants from NE Greece, were administered 60 minutes prior to intraperitoneal (i.p.) injection of a lethal dose of PTZ to eight respective groups of Balb-c mice. Control group received only one i.p. PTZ injection. Motor and behavioral activity of the animals after EOs administration, development of tonic-clonic seizures, seizure latency and severity, and percentage of survival after PTZ administration were determined for each group. All groups of mice treated with the EOs showed reduced activity and stability after the administration of the oil, except for those treated with O. vulgare (100% mortality after the administration of the oil). After PTZ administration, mice from the different groups showed increased latency and reduced severity of seizures (ranging from simple twitches to complete seizures). Mice who had received M. piperita demonstrated no seizures and 100% survival. The different drastic component and its concentration could account for the diversity of anticonvulsant effects. PMID:23819045

  3. Increased seizure latency and decreased severity of pentylenetetrazol-induced seizures in mice after essential oil administration.

    PubMed

    Koutroumanidou, Eleni; Kimbaris, Athanasios; Kortsaris, Alexandros; Bezirtzoglou, Eugenia; Polissiou, Moschos; Charalabopoulos, Konstantinos; Pagonopoulou, Olga

    2013-01-01

    The effect of pretreatment with essential oils (EOs) from eight aromatic plants on the seizure latency and severity of pentylenetetrazol- (PTZ-) induced seizures in mice was evaluated. Weight-dependent doses of Rosmarinus officinalis, Ocimum basilicum, Mentha spicata, Mentha pulegium, Lavandula angustifolia, Mentha piperita, Origanum dictamnus, and Origanum vulgare, isolated from the respective aromatic plants from NE Greece, were administered 60 minutes prior to intraperitoneal (i.p.) injection of a lethal dose of PTZ to eight respective groups of Balb-c mice. Control group received only one i.p. PTZ injection. Motor and behavioral activity of the animals after EOs administration, development of tonic-clonic seizures, seizure latency and severity, and percentage of survival after PTZ administration were determined for each group. All groups of mice treated with the EOs showed reduced activity and stability after the administration of the oil, except for those treated with O. vulgare (100% mortality after the administration of the oil). After PTZ administration, mice from the different groups showed increased latency and reduced severity of seizures (ranging from simple twitches to complete seizures). Mice who had received M. piperita demonstrated no seizures and 100% survival. The different drastic component and its concentration could account for the diversity of anticonvulsant effects. PMID:23819045

  4. [Study of serum concentrations and urinary excretion of secnidazole after oral administration in man. Comparison with tinidazole].

    PubMed

    Populaire, P; Decouvelaere, B; Renard, A; Pasquier, P

    1980-11-01

    Secnidazole, a derivative of 5-nitro imidazole exhibits trichomonacid, amoebicid and antimicrobial properties; it has been studied in view of its biological fate in healthy volunteers (man and woman) comparatively with tinidazole. Both products were administered orally to the same volunteers at the single dose level of 2 g. The seric concentrations and the pharmacokinetic profile were determined up to the 72nd hour after drug administration. The whole urinary excretion (unchanged product + metabolites) during the same period was determined in percent of the administered dose level. Secnidazole is particularly different from tinidazole owing to its slower blood clearance. The apparent average half-life in the ten volunteers (5 men and 5 women) is about 17 hours for secnidazole and 13 hours for tinidazole. However, for both drugs, a difference between men and women was demonstrated: in female volunteers, the decrease in blood concentrations occurs a little quicker than in male volunteers. Regarding urinary excretion, it is also a little greater in female volunteers than in male volunteers. PMID:7003510

  5. Dietary resveratrol administration increases MnSOD expression and activity in mouse brain

    SciTech Connect

    Robb, Ellen L.; Winkelmolen, Lieke; Visanji, Naomi; Brotchie, Jonathan; Stuart, Jeffrey A.

    2008-07-18

    trans-Resveratrol (3,4',5-trihydroxystilbene; RES) is of interest for its reported protective effects in a variety of pathologies, including neurodegeneration. Many of these protective properties have been attributed to the ability of RES to reduce oxidative stress. In vitro studies have shown an increase in antioxidant enzyme activities following exposure to RES, including upregulation of mitochondrial superoxide dismutase, an enzyme that is capable of reducing both oxidative stress and cell death. We sought to determine if a similar increase in endogenous antioxidant enzymes is observed with RES treatment in vivo. Three separate modes of RES delivery were utilized; in a standard diet, a high fat diet and through a subcutaneous osmotic minipump. RES given in a high fat diet proved to be effective in elevating antioxidant capacity in brain resulting in an increase in both MnSOD protein level (140%) and activity (75%). The increase in MnSOD was not due to a substantial proliferation of mitochondria, as RES treatment induced a 10% increase in mitochondrial abundance (Citrate Synthase activity). The potential neuroprotective properties of MnSOD have been well established, and we demonstrate that a dietary delivery of RES is able to increase the expression and activity of this enzyme in vivo.

  6. Increased latencies to initiate cocaine self-administration following laterodorsal tegmental nucleus lesions

    PubMed Central

    Steidl, Stephan; Cardiff, Katherine M.; Wise, Roy A.

    2015-01-01

    Cholinergic input to the ventral tegmental area (VTA), origin of the mesocorticolimbic dopamine system that is critical for cocaine reward, is important for both cocaine seeking and cocaine taking. The laterodorsal tegmental nucleus (LDTg) provides one of the two major sources of excitatory cholinergic input to the VTA, but little is known of the role of the LDTg in cocaine reward. LDTg cholinergic cells express urotensin-II receptors and here we used local microinjections of a conjugate of the endogenous ligand for these receptors with diphtheria toxin (Dtx::UII) to lesion the cholinergic cells of the LDTg in rats previously trained to self-administer cocaine (1 mg/kg/infusion, i.v.). Lesioned rats showed long latencies to initiate cocaine self-administration after treatment with the toxin, which resulted in a reduction in cocaine intake per session. Priming injections reduced latencies to initiate responding for cocaine in lesioned rats, and once they began to respond the rats regulated their moment-to-moment cocaine intake within normal limits. Thus we conclude that while LDTg cholinergic cell loss does not significantly alter the rewarding effects of cocaine, LDTg lesions can reduce the rat’s responsiveness to cocaine-predictive stimuli. PMID:25746513

  7. The Mine Safety and Health Administration's criterion threshold value policy increases miners' risk of pneumoconiosis

    SciTech Connect

    Weeks, J.L.

    2006-06-15

    Background The Mine Safety and Health Administration (MSHA) proposes to issue citations for non-compliance with the exposure limit for respirable coal mine dust when measured exposure exceeds the exposure limit with a 'high degree of confidence.' This criterion threshold value (CTV) is derived from the sampling and analytical error of the measurement method. This policy is based on a combination of statistical and legal reasoning: the one-tailed 95% confidence limit of the sampling method, the apparent principle of due process and a standard of proof analogous to 'beyond a reasonable doubt.' This policy raises the effective exposure limit, it is contrary to the precautionary principle, it is not a fair sharing of the burden of uncertainty, and it employs an inappropriate standard of proof. Its own advisory committee and NIOSH have advised against this policy. For longwall mining sections, it results in a failure to issue citations for approximately 36% of the measured values that exceed the statutory exposure limit. Citations for non-compliance with the respirable dust standard should be issued for any measure exposure that exceeds the exposure limit.

  8. The effect of Plantago major Linnaeus on serum total sialic acid, lipid-bound sialic acid, some trace elements and minerals after administration of 7,12-dimethylbenz(a)anthracene in rats.

    PubMed

    Oto, Gokhan; Ekin, Suat; Ozdemir, Hulya; Levent, Abdulkadir; Berber, Ismet

    2012-05-01

    The present study was designed to evaluate the effect of Plantago major Linnaeus (PM) extract on serum total sialic acid (TSA), lipid-bound sialic acid (LSA), some trace elements (copper (Cu), zinc (Zn) and iron) and mineral levels (magnesium, calcium and sodium) in Wistar albino rat administrated 7,12-dimethylbenz(a)anthracene (DMBA). Rats were divided into three equal groups (n = 6). Group I comprised the control group, group II was treated with DMBA (100 mg/kg, single dose) and group III was treated with DMBA (100 mg/kg single dose) and aqueous extract of PM 100 mg/kg/day for 60 days. After 60 days, statistical analyses showed that TSA and LSA levels in DMBA and DMBA + PM groups were significantly higher compared to the control group (TSA: p < 0.01, p < 0.05; LSA: p < 0.05, p < 0.05, respectively). Serum Zn levels were decreased in subjects treated with DMBA (p < 0.01) and DMBA + PM (p < 0.05) compared to the control group values. Serum Cu levels were increased in DMBA group and PM-treated group compared to the control group values. The results of this investigation showed that the levels of TSA and LSA changed significantly, which are sensitive markers for detecting the toxic effects of DMBA. On the other hand, observed decline in Zn levels in rats from DMBA + PM group might be due to decreased generation of free radicals and oxidative stress. Results from this study suggest that PM may be partially effective in preventing carcinogenesis initiated by environmental carcinogen DMBA. PMID:21996710

  9. Increased serum levels of soluble CD44-isoform v5 in rheumatic diseases are restricted to seropositive rheumatoid arthritis.

    PubMed

    Haberhauer, G; Kittl, E M; Skoumal, M; Hübl, W; Wagner, E; Bayer, P M; Bauer, K; Dunky, A

    1997-01-01

    Serum levels of sCD44v5 were measured in 134 patients with definite inflammatory rheumatic diseases (IRD) using a sandwich type ELISA. 94 patients suffered from erosive IgM-rheumatoid factor positive rheumatoid arthritis (RA+), 20 with undifferentiated seronegative polyarthritis, 12 with osteoarthropathia psoriatica and psoriasis vulgaris, 3 with systemic lupus erythematosus, 3 with scleroderma and 2 with reactive arthritis. Elevated serum levels (> 58 ng/ml to 221 ng/ml; median: 93 ng/ml) were only detected in 54/94 (57%) patients with RA+, but not in other IRD. They correlated with advanced stages of disease (Steinbrocker stages III + IV; p < 0.05), elevated CRP-levels (p < 0.01) and higher measurements of IgM rheumatoid factor. PMID:9150806

  10. Mild to moderate increase of serum calcitonin levels only in presence of large medullary thyroid cancer deposits.

    PubMed

    Pelizzo, M R; Torresan, F; Da Roit, A; Merante Boschin, I; Chondrogiannis, S; Rampin, L; Colletti, P M; Vinjamury, S; Perkins, A J; Rubello, D

    2015-01-01

    Many open questions remain to be elucidated about the diagnosis, treatment and prognosis of medullary thyroid cancer (MTC). The most intriguing concerns the outcome of MTC patients after surgery. Great importance is usually given to serum calcitonin (Ct) and carcinoembryonic (CEA) levels. It is commonly believed that the higher are the levels of these tumor markers and their kinetics (double time and velocity of markers levels) the worst is the prognosis. However, this is not the rule, as there are huge MTC metastatic deposits characterized by low serum Ct and CEA levels, and this condition is not closely related to the outcome of the disease during post-surgical follow-up. A series is reported here of patients who have these characteristics, as well as a description of their prognosis and clinical outcome. PMID:26420439

  11. Placental Protein 13 (galectin-13) has decreased placental expression but increased shedding and maternal serum concentrations in patients presenting with preterm preeclampsia and HELLP syndrome

    PubMed Central

    Than, Nandor Gabor; Rahman, Omar Abdul; Magenheim, Rita; Nagy, Balint; Fule, Tibor; Hargitai, Beata; Sammar, Marei; Hupuczi, Petronella; Tarca, Adi L.; Szabo, Gabor; Kovalszky, Ilona; Meiri, Hamutal; Sziller, Istvan; Rigo, Janos; Romero, Roberto; Papp, Zoltan

    2009-01-01

    Placental Protein 13 (PP13) is a galectin expressed by the syncytiotrophoblast. Women who subsequently develop preterm preeclampsia have low first trimester maternal serum PP13 concentrations. This study revealed that third trimester maternal serum PP13 concentration increased with gestational age in normal pregnancies (p<0.0001), and it was significantly higher in women presenting with preterm preeclampsia (p=0.02) and HELLP syndrome (p=0.01) than in preterm controls. Conversely, placental PP13 mRNA (p=0.03) and protein, as well as cytoplasmic PP13 staining of the syncytiotrophoblast (p<0.05) was decreased in these pathological pregnancies compared to controls. No differences in placental expression and serum concentrations of PP13 were found at term between patients with preeclampsia and control women. In contrast, the immunoreactivity of the syncytiotrophoblast microvillous membrane was stronger in both term and preterm preeclampsia and HELLP syndrome than in controls. Moreover, large syncytial cytoplasm protrusions, membrane blebs and shed microparticles strongly stained for PP13 in preeclampsia and HELLP syndrome. In conclusion, parallel to its decreased placental expression, an augmented membrane shedding of PP13 contributes to the increased third trimester maternal serum PP13 concentrations in women with preterm preeclampsia and HELLP syndrome. PMID:18791734

  12. Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis

    PubMed Central

    Yi, Lang; Hao, Mingju; Lu, Tian; Lin, Guigao; Chen, Lida; Gao, Ming; Fan, Gaowei; Zhang, Dong; Wang, Guojing; Yang, Xin; Li, Yulong; Zhang, Kuo; Zhang, Rui; Han, Yanxi; Wang, Lunan; Li, Jinming

    2016-01-01

    The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA) is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA) patients, and healthy controls (HC) in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28). In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA. PMID:27143816

  13. Increased cathepsin L levels in serum in some patients with ovarian cancer: comparison with CA125 and CA72-4.

    PubMed

    Nishida, Y; Kohno, K; Kawamata, T; Morimitsu, K; Kuwano, M; Miyakawa, I

    1995-03-01

    Our purpose was to determine the correlation between cathepsin L mRNA levels and serum cathepsin L levels of patients with ovarian cancer. Moreover, we compared serum cathepsin L levels with cancer antigen 125 (CA125) and cancer antigen 72-4 (CA72-4) levels. Using an ELISA assay, serum samples of 30 patients with gynecological tumors were analyzed for cathepsin L, CA125, and CA72-4. We also examined whether cathepsin L gene expression was enhanced in ovarian cancer samples, by quantitative Northern blot analysis with a human cathepsin L complementary DNA (cDNA) probe. Significantly increased serum levels of cathepsin L in patients with ovarian cancer (P < 0.05) were observed. We also measured serum levels of CA125 and CA72-4 in the same patients. Compared with CA125 and CA72-4, cathepsin L showed a lower false-positive rate (27.2%) in gynecological diseases, and no correlation was observed between cathepsin L and CA125 or CA72-4 values. Moreover, ovarian cancer samples were found to express higher levels of cathepsin L mRNA than those of uterine cancer, benign ovarian tumor, and normal ovary samples. Our data demonstrated that serum cathepsin L may be useful in the early detection of ovarian cancer. Furthermore, the combination assay consisting of cathepsin L, CA125, and CA72-4 may be a more useful method than those currently in use for the detection of ovarian cancer. PMID:7705668

  14. Chronic metabolic acidosis increases the serum concentration of 1,25-dihydroxyvitamin D in humans by stimulating its production rate. Critical role of acidosis-induced renal hypophosphatemia.

    PubMed Central

    Krapf, R; Vetsch, R; Vetsch, W; Hulter, H N

    1992-01-01

    Chronic metabolic acidosis results in metabolic bone disease, calcium nephrolithiasis, and growth retardation. The pathogenesis of each of these sequelae is poorly understood in humans. We therefore investigated the effects of chronic extrarenal metabolic acidosis on the regulation of 1,25-(OH)2D, parathyroid hormone, calcium, and phosphate metabolism in normal humans. Chronic extrarenal metabolic acidosis was induced by administering two different doses of NH4Cl [2.1 (low dose) and 4.2 (high dose) mmol/kg body wt per d, respectively] to four male volunteers each during metabolic balance conditions. Plasma [HCO3-] decreased by 4.5 +/- 0.4 mmol/liter in the low dose and by 9.1 +/- 0.3 mmol/liter (P < 0.001) in the high dose group. Metabolic acidosis induced renal hypophosphatemia, which strongly correlated with the severity of acidosis (Plasma [PO4] on plasma [HCO3-]; r = 0.721, P < 0.001). Both metabolic clearance and production rates of 1,25-(OH)2D increased in both groups. In the high dose group, the percentage increase in production rate was much greater than the percentage increase in metabolic clearance rate, resulting in a significantly increased serum 1,25-(OH)2D concentration. A strong inverse correlation was observed for serum 1,25-(OH)2D concentration on both plasma [PO4] (r = -0.711, P < 0.001) and plasma [HCO3-] (r = -0.725, P < 0.001). Plasma ionized calcium concentration did not change in either group whereas intact serum parathyroid hormone concentration decreased significantly in the high dose group. In conclusion, metabolic acidosis results in graded increases in serum 1,25-(OH)2D concentration by stimulating its production rate in humans. The increased production rate is explained by acidosis-induced hypophosphatemia/cellular phosphate depletion resulting at least in part from decreased renal tubular phosphate reabsorption. The decreased serum intact parathyroid hormone levels in more severe acidosis may be the consequence of hypophosphatemia and

  15. Down syndrome serum screening also identifies an increased risk for multicystic dysplastic kidney, 2-vessel cord, and hydrocele

    PubMed Central

    Hoffman, Jodi D.; Sullivan, Lisa M.; Mackinnon, Brenda L.; Collins, Jamie; Malone, Fergal D.; Porter, T. Flint; Nyberg, David A.; Comstock, Christine H.; Bukowski, Radek; Berkowitz, Richard L.; Gross, Susan J.; Dugoff, Lorraine; Craigo, Sabrina D.; Timor-Tritsch, Ilan E.; Carr, Stephen R.; Wolfe, Honor M.; D'Alton, Mary E.

    2008-01-01

    Objective The FASTER trial compared 1st and 2nd trimester screening methods for aneuploidy. We examined relationships between maternal serum markers and common congenital anomalies in the pediatric outcome data set of 36,837 subjects. Methods We used nested case control studies, with cases defined by the most common anomalies in our follow-up database, and up to four controls matched by enrollment site, maternal age and race, enrollment gestational age, and infant gender. Serum markers were dichotomized to ≥ 2 or < 0.5 multiples of the median (MoM). Odds ratios and 95% confidence intervals (C.I.) were estimated. Results Statistically significant (p < 0.05) associations were found between inhibin A ≥ 2 MoM and fetal multicystic dysplastic kidney (MCDK) (odds ratio (OR) =27.5, 95% C.I.: 2.8-267.7) and 2-vessel cord (OR=4.22, 95% CI:1.6-10.9), hCG of ≥ 2 MoM with MCDK (OR=19.56, 95% CI: 1.9-196.2) and hydrocele (OR=2.48, 95% CI: 1.3-4.6), and PAPPA ≥ 2.0 MoM with hydrocele (OR=1.88, 95% CI:1.1-3.3). Conclusion In this large prospective study, significant associations were found between several maternal serum markers and congenital anomalies. This suggests potential additional benefits to screening programs that are primarily designed to detect aneuploidy. PMID:19034930

  16. Increased acidic fibroblast growth factor concentrations in the serum and cerebrospinal fluid of patients with Alzheimer's disease.

    PubMed

    Mashayekhi, Farhad; Hadavi, Mahvash; Vaziri, Hamid Reza; Naji, Mohammad

    2010-03-01

    Acidic fibroblast growth factor (aFGF), also called FGF-1, which influences the proliferation and differentiation of various cell types in vitro, was originally isolated from neural tissue. It is released from the ependymal cells of the cerebral third ventricle into the cerebrospinal fluid (CSF). FGF-1 promotes the survival of neurons. Reactive astrocytes express FGF-1 in the brain of patients with Alzheimer's disease (AD). By comparing the CSF proteome of patients with AD and normal controls it might be possible to identify proteins that have a role in AD. Because CSF is in contact with the extracellular space of the brain, modifications in the brain biochemistry could be reflected in the CSF. The aim of this study was to determine concentrations of serum and CSF FGF-1 in patients with AD. This study consisted of 64 CSF samples, from patients with AD (n=32) and those without (normal controls) (n=32). The level of CSF and serum FGF-1 in patients with AD was higher than in patients without AD. We conclude that FGF-1 is a constant component of human serum and CSF and that FGF-1 may be involved in the pathophysiology of AD. PMID:20079650

  17. Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels.

    PubMed

    Berge, Kjetil; Musa-Veloso, Kathy; Harwood, Melody; Hoem, Nils; Burri, Lena

    2014-02-01

    The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings. PMID:24461313

  18. An increase in CD3+CD4+CD25+ regulatory T cells after administration of umbilical cord-derived mesenchymal stem cells during sepsis.

    PubMed

    Chao, Yu-Hua; Wu, Han-Ping; Wu, Kang-Hsi; Tsai, Yi-Giien; Peng, Ching-Tien; Lin, Kuan-Chia; Chao, Wan-Ru; Lee, Maw-Sheng; Fu, Yun-Ching

    2014-01-01

    Sepsis remains an important cause of death worldwide, and vigorous immune responses during sepsis could be beneficial for bacterial clearance but at the price of collateral damage to self tissues. Mesenchymal stem cells (MSCs) have been found to modulate the immune system and attenuate sepsis. In the present study, MSCs derived from bone marrow and umbilical cord were used and compared. With a cecal ligation and puncture (CLP) model, the mechanisms of MSC-mediated immunoregulation during sepsis were studied by determining the changes of circulating inflammation-associated cytokine profiles and peripheral blood mononuclear cells 18 hours after CLP-induced sepsis. In vitro, bone marrow-derived MSCs (BMMSCs) and umbilical cord-derived MSCs (UCMSCs) showed a similar morphology and surface marker expression. UCMSCs had stronger potential for osteogenesis but lower for adipogenesis than BMMSCs. Compared with rats receiving PBS only after CLP, the percentage of circulating CD3+CD4+CD25+ regulatory T (Treg) cells and the ratio of Treg cells/T cells were elevated significantly in rats receiving MSCs. Further experiment regarding Treg cell function demonstrated that the immunosuppressive capacity of Treg cells from rats with CLP-induced sepsis was decreased, but could be restored by administration of MSCs. Compared with rats receiving PBS only after CLP, serum levels of interleukin-6 and tumor necrosis factor-α were significantly lower in rats receiving MSCs after CLP. There were no differences between BMMSCs and UCMSCs. In summary, this work provides the first in vivo evidence that administering BMMSCs or UCMSCs to rats with CLP-induced sepsis could increase circulating CD3+CD4+CD25+ Treg cells and Treg cells/T cells ratio, enhance Treg cell suppressive function, and decrease serum levels of interleukin-6 and tumor necrosis factor-α, suggesting the immunomodulatory association of Treg cells and MSCs during sepsis. PMID:25337817

  19. High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol.

    PubMed

    Welder, Greg; Zineh, Issam; Pacanowski, Michael A; Troutt, Jason S; Cao, Guoqing; Konrad, Robert J

    2010-09-01

    Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of serum LDL-cholesterol (LDL-C) levels. PCSK9 is secreted by the liver into the plasma and binds the hepatic LDL receptor (LDLR), causing its subsequent degradation. We first demonstrated that a moderate dose of atorvastatin (40 mg) increases PCSK9 serum levels, suggesting why increasing statin doses may have diminished efficacy with regard to further LDL-C lowering. Since that initial observation, at least two other groups have reported statin-induced PCSK9 increases. To date, no analysis of the effect of high-dose atorvastatin (80 mg) on PCSK9 over time has been conducted. Therefore, we studied the time course of atorvastatin (80 mg) in human subjects. We measured PCSK9 and lipid levels during a 2-week lead-in baseline period and every 4 weeks thereafter for 16 weeks. We observed that atorvastatin (80 mg) caused a rapid 47% increase in serum PCSK9 at 4 weeks that was sustained throughout 16 weeks of dosing. Importantly, while PCSK9 levels were highly correlated with total cholesterol (TC), LDL-C, and triglyceride (TG) levels at baseline, atorvastatin (80 mg) completely abolished all of these correlations. Together, these results further suggest an explanation for why increasing doses of statins fail to achieve proportional LDL-C lowering. PMID:20525997

  20. Polychlorinated Biphenyl Congeners that Increase the Glucuronidation and Biliary Excretion of Thyroxine Are Distinct from the Congeners that Enhance the Serum Disappearance of Thyroxine

    PubMed Central

    Martin, L. A.; Wilson, D. T.; Reuhl, K. R.; Gallo, M. A.

    2012-01-01

    Polychlorinated biphenyl (PCB) congeners differentially reduce serum thyroxine (T4) in rats, but little is known about their ability to affect biliary excretion of T4. Thus, male Sprague-Dawley rats were orally administered Aroclor-1254, Aroclor-1242 (32 mg/kg per day), PCB-95, PCB-99, PCB-118 (16 mg/kg per day), PCB-126 (40 μg/kg per day), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (3.9 μg/kg per day), or corn oil for 7 days. Twenty-four hours after the last dose, [125I]T4 was administered intravenously, and blood, bile, and urine samples were collected for quantifying [125I]T4 and in bile [125I]T4 metabolites. Serum T4 concentrations were reduced by all treatments, but dramatic reductions occurred in response to Aroclor-1254, PCB-99 [phenobarbital (PB)-type congener], and PCB-118 (mixed-type congener). None of the treatments increased urinary excretion of [125I]T4. Aroclor-1254, PCB-118, TCDD, and PCB-126 (TCDD-type congener) increased biliary excretion of T4-glucuronide by 850, 756, 710, and 573%, respectively, corresponding to marked induction of hepatic UDP-glucuronosyltransferase (UGT) activity toward T4. PCB-95 and PCB-99 did not induce UGT activity; therefore, the increased biliary excretion of T4-glucuronide was related to the affinity of congeners for the aryl hydrocarbon receptor. The disappearance of [125I]T4 from serum was rapid (within 15-min) and was increased by Aroclor-1254, PCB-99 and PCB-118. Thus, reductions in serum T4 in response to PCBs did not always correspond with UGT activity toward T4 or with increased biliary excretion of T4-glucuronide. The rapid disappearance of [125I]T4 from the serum of rats treated with PB-like PCBs suggests that increased tissue uptake of T4 is an additional mechanism by which PCBs may reduce serum T4. PMID:22187485

  1. Oral administration of dehydroepiandrosterone-sulfate (DHEAS) increases in vitro lymphocyte function and improves in vivo response of pigs to immunization against keyhole limpet hemocyanin (KLH) and ovalbumin.

    PubMed

    Burdick, N C; Dominguez, J A; Welsh, T H; Laurenz, J C

    2009-10-01

    The present study tested the hypothesis that the oral administration of DHEAS enhances the in vitro and the in vivo immune response of young pigs. Crossbred, female pigs (80 days of age; 49+/-2 kg) were separated into two treatment groups (n=4/treatment) receiving either 0mg/kg (control) or 1mg/kg DHEAS twice daily (DHEAS) for 5 weeks. On day 7 pigs were immunized against KLH and ovalbumin. Body weight increased weekly throughout the study but did not differ between treatment groups. While white blood cell counts increased in response to immunization but did not differ between treatments, the neutrophil:lymphocyte ratio was enhanced (P<0.05) in DHEAS-supplemented pigs. Concanavalin A (ConA) induced an in vitro dose-dependent increase (P<0.05) in lymphocyte proliferation, but treatment did not affect proliferation prior to immunization. However, lymphocytes isolated from DHEAS-supplemented pigs displayed a greater increase in proliferation following immunization relative to control pigs (P<0.05). Dexamethasone (DEX) attenuated ConA-induced lymphocyte proliferation, with DHEAS-supplemented pigs retaining a greater proliferative response relative to control pigs (P<0.05). Serum IgG concentrations and relative concentrations of antigen-specific IgG increased after immunization with maximum values attained at 21 and 28 days for control and DHEAS-supplemented pigs, respectively. The DHEAS-supplemented pigs had greater (P<0.05) concentrations of IgG and relative concentrations of antigen-specific IgG compared to control pigs. Collectively these data suggest DHEAS supplementation increases the responsiveness of young pigs to antigenic challenge, and may be beneficial for improving their immune function. PMID:19646552

  2. Is There a Role for the Enteral Administration of Serum-Derived Immunoglobulins in Human Gastrointestinal Disease and Pediatric Critical Care Nutrition?

    PubMed

    Van Arsdall, Melissa; Haque, Ikram; Liu, Yuying; Rhoads, J Marc

    2016-05-01

    Twenty years ago, there was profound, international interest in developing oral human, bovine, or chicken egg-derived immunoglobulin (Ig) for the prevention and nutritional treatment of childhood malnutrition and gastrointestinal disease, including acute diarrhea and necrotizing enterocolitis. Although such Ig products were shown to be effective, with both nutritional and antidiarrheal benefits, interest waned because of their cost and because of the perceived risk of bovine serum encephalitis (BSE). BSE is no longer considered a barrier to use of oral Ig, because the WHO has declared the United States to be BSE-free since the early 2000s. Low-cost bovine-derived products with high Ig content have been developed and are regulated as medical foods. These new products, called serum bovine Igs (SBIs), facilitate the management of chronic or severe gastrointestinal disturbances in both children and adults and are regulated by the US Food and Drug Administration. Well-established applications for use of SBIs include human immunodeficiency virus (HIV)-associated enteropathy and diarrhea-predominant irritable bowel syndrome. However, SBIs and other similar products could potentially become important components of the treatment regimen for other conditions, such as inflammatory bowel disease, by aiding in disease control without immunosuppressive side effects. In addition, SBIs may be helpful in conditions associated with the depletion of circulating and luminal Igs and could potentially play an important role in critical care nutrition. The rationale for their use is to facilitate intraluminal microbial antibody coating, an essential process in immune recognition in the gut which is disturbed in these conditions, thereby leading to intestinal inflammation. Thus, oral Ig may emerge as an important "add-on" therapy for a variety of gastrointestinal and nutritional problems during the next decade. PMID:27184280

  3. Acute and chronic caffeine administration increases physical activity in sedentary adults.

    PubMed

    Schrader, Patrick; Panek, Leah M; Temple, Jennifer L

    2013-06-01

    Caffeine is a commonly used stimulant thought to have ergogenic properties. Most studies on the ergogenic effects of caffeine have been conducted in athletes. The purpose of this study was to test the hypothesis that caffeine reduces ratings of perceived exertion and increases liking of physical activity in sedentary adults. Participants completed treadmill walking at 60% to 70% of their maximal heart rate at baseline and for 6 subsequent visits, during which half of the participants were given caffeine (3 mg/kg) and half given placebo in a sports drink vehicle. To investigate the potential synergistic effects of acute and chronic caffeine on self-determined exercise duration, participants were rerandomized to either the same or different condition for the last visit, creating 4 chronic/acute treatment groups (placebo/placebo, placebo/caffeine, caffeine/placebo, caffeine/caffeine). Participants rated how much they liked the activity and perceived exertion at each visit. There was a main effect of time on liking of physical activity, with liking increasing over time and an interaction of sex and caffeine treatment on liking, with liking of activity increasing in female participants treated with caffeine, but not with placebo. There was no effect of caffeine on ratings of perceived exertion. Individuals who received caffeine on the final test day exercised for significantly longer than those who received placebo. These data suggest that repeated exposure to physical activity significantly increases liking of exercise and reduces ratings of perceived exertion and that caffeine does little to further modify these effects. PMID:23746561

  4. Does Neostigmine Administration Produce a Clinically Important Increase in Postoperative Nausea and Vomiting?

    PubMed Central

    Cheng, Ching-Rong; Sessler, Daniel I.; Apfel, Christian C.

    2005-01-01

    Neostigmine is used to antagonize neoromuscluar blocker-induced residual neuromuscular paralysis. Despite a previous meta-analysis, the effect of neostigmine on postoperative nausea and vomiting (PONV) remains unresolved. We reevaluated the effect of neostigmine on PONV while considering the different anticholinergics as potentially confounding factors. We performed a systematic literature search using Medline, Embase, Cochrane library, reference listings, and hand searching with no language restriction through December 2004 and identified 10 clinical, randomized, controlled trials evaluating neostigmine's effect on PONV. Data on nausea or vomiting from 933 patients were extracted for the early (0-6 h), delayed (6-24 h), and overall postoperative periods (0-24 h) and analyzed with RevMan 4.2 (Cochrane Collaboration, Oxford, UK) and multiple logistic regression analysis. The combination of neostigmine with either atropine or glycopyrrolate did not significantly increase the incidence of overall (0-24 h) vomiting (relative risk (RR) 0.91 [0.70-1.18], P=0.48) or nausea (RR 1.24 [95% CI: 0.98-1.59], P=0.08). Multiple logistic regression analysis indicated that that there was not a significant increase in the risk of vomiting with large compared with small doses of neostigmine. In contrast to a previous analysis, we conclude that there is insufficient evidence to conclude that neostigmine increases the risk of PONV. PMID:16243993

  5. Oral administration of lithium increases tissue magnesium contents but not plasma magnesium level in rats.

    PubMed

    Kiełczykowska, Małgorzata; Musik, Irena; Hordyjewska, Anna; Boguszewska, Anna; Lewandowska, Anna; Pasternak, Kazimierz

    2007-01-01

    The aim of this work was to determine the influence of different doses of lithium on magnesium concentration in plasma and tissues of rats. For a period of eight weeks rats had been provided with aqueous solutions of Li(2)CO(3) whose concentrations were established as follows: 0.7; 1.4; 2.6; 3.6; 7.1; 10.7 mmol Li(+)/l. Magnesium concentration was determined in plasma and tissue supernatants. Lithium caused no changes in magnesium concentration in plasma, whereas Mg concentration in tissues was found to be enhanced, although the degree of the increment depended on the studied tissue. In the liver, brain and heart muscle, the increase was statistically insignificant vs. control. In the kidney, the higher Li doses were required to result in the significant Mg enhancement, whereas in femoral muscle all the used doses caused well-marked Mg increase vs. control. Positive correlations between average daily Li intake and tissue Mg concentration in the kidney (r = 0.650) and femoral muscle (r = 0.696) were found. In conclusion, the present study indicates that the different Li doses disturbed tissue homeostasis of magnesium. The increase in Mg tissue concentration, observed in groups receiving higher Li doses can influence nervous-muscular excitability. PMID:17652829

  6. A SINGLE HIGH DOSE OF METHAMPHETAMINE INCREASES COCAINE SELF-ADMINISTRATION BY DEPLETION OF STRIATAL DOPAMINE IN RATS

    PubMed Central

    XI, Z.-X.; KLEITZ, H. K.; DENG, X.; LADENHEIM, B.; PENG, X.-Q.; LI, X.; GARDNER, E. L.; STEIN, E. A.; CADET, J. L.

    2013-01-01

    Psychostimulant addicts often take high doses of drugs, and high doses of psychostimulants such as methamphetamine (METH) are neurotoxic to striatal dopamine (DA) terminals. Yet, the effects of high doses of METH on drug-seeking and drug-taking behavior have not been examined. In the present study, we found that single high doses of METH in rats (10–20 mg/kg) dose-dependently increased cocaine self-administration under fixed-ratio 2 (FR2) reinforcement conditions, while higher doses (40 mg/kg×1 or 10 mg/kg/2 h×4) caused high mortality among rats maintained on daily cocaine self-administration. The increased cocaine self-administration appeared to be a compensatory response to reduced cocaine reward after METH, because the same doses of METH caused a dose-dependent reduction both in “breakpoint” levels for cocaine self-administration under progressive-ratio reinforcement and in nucleus accumbens DA response to acute cocaine. Further, METH (10–20 mg/kg) produced large DA release (4000%–6000% over baseline), followed by a significant reduction in striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) contents, but without significant changes in striatal DA transporter levels. These findings suggest that the present high doses of METH caused striatal DA depletion or hypofunction without severe damage in DA terminals, which may contribute to the increased cocaine-taking behavior observed in the present study. Provided that the present doses of METH may mimic METH overdose incidents in humans, the present findings suggest that METH-induced DA depletion or neurotoxicity may lead to an increase in subsequent drug-taking and drug-seeking behavior. PMID:19336247

  7. Chronic administration of caderofloxacin, a new fluoroquinolone, increases hepatic CYP2E1 expression and activity in rats

    PubMed Central

    Liu, Li; Miao, Ming-xing; Zhong, Ze-yu; Xu, Ping; Chen, Yang; Liu, Xiao-dong

    2016-01-01

    Aim: Caderofloxacin is a new fluoroquinolone that is under phase III clinical trials in China. Here we examined the effects of caderofloxacin on rat hepatic cytochrome P450 (CYP450) isoforms as well as the potential of caderofloxacin interacting with co-administered drugs. Methods: Male rats were treated with caderofloxacin (9 mg/kg, ig) once or twice daily for 14 consecutive days. The effects of caderofloxacin on CYP3A, 2D6, 2C19, 1A2, 2E1 and 2C9 were evaluated using a “cocktail” of 6 probes (midazolam, dextromethorphan, omeprazole, theophylline, chlorzoxazone and diclofenac) injected on d 0 (prior to caderofloxacin exposure) and d 15 (after caderofloxacin exposure). Hepatic microsomes from the caderofloxacin-treated rats were used to assess CYP2E1 activity and chlorzoxazone metabolism. The expression of CYP2E1 mRNA and protein in hepatic microsomes was analyzed with RT-PCR and Western blotting, respectively. Results: Fourteen-day administration of caderofloxacin significantly increased the activity of hepatic CYP2E1, leading to enhanced metabolism of chlorzoxazone. In vitro microsomal study confirmed that CYP2E1 was a major metabolic enzyme involved in chlorzoxazone metabolism, and the 14-d administration of caderofloxacin significantly increased the activity of CYP2E1 in hepatic microsomes, resulting in increased formation of 6-hydroxychlorzoxazone. Furthermore, the 14-d administration of caderofloxacin significantly increased the expression of CYP2E1 mRNA and protein in liver microsomes, which was consistent with the pharmacokinetic results. Conclusion: Fourteen-day administration of caderofloxacin can induce the expression and activity of hepatic CYP2E1 in rats. When caderofloxacin is administered, a potential drug-drug interaction mediated by CYP2E1 induction should be considered. PMID:26838075

  8. A single high dose of methamphetamine increases cocaine self-administration by depletion of striatal dopamine in rats.

    PubMed

    Xi, Z-X; Kleitz, H K; Deng, X; Ladenheim, B; Peng, X-Q; Li, X; Gardner, E L; Stein, E A; Cadet, J L

    2009-06-30

    Psychostimulant addicts often take high doses of drugs, and high doses of psychostimulants such as methamphetamine (METH) are neurotoxic to striatal dopamine (DA) terminals. Yet, the effects of high doses of METH on drug-seeking and drug-taking behavior have not been examined. In the present study, we found that single high doses of METH in rats (10-20 mg/kg) dose-dependently increased cocaine self-administration under fixed-ratio 2 (FR2) reinforcement conditions, while higher doses (40 mg/kgx1 or 10 mg/kg/2 hx4) caused high mortality among rats maintained on daily cocaine self-administration. The increased cocaine self-administration appeared to be a compensatory response to reduced cocaine reward after METH, because the same doses of METH caused a dose-dependent reduction both in "break-point" levels for cocaine self-administration under progressive-ratio reinforcement and in nucleus accumbens DA response to acute cocaine. Further, METH (10-20 mg/kg) produced large DA release (4000%-6000% over baseline), followed by a significant reduction in striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) contents, but without significant changes in striatal DA transporter levels. These findings suggest that the present high doses of METH caused striatal DA depletion or hypofunction without severe damage in DA terminals, which may contribute to the increased cocaine-taking behavior observed in the present study. Provided that the present doses of METH may mimic METH overdose incidents in humans, the present findings suggest that METH-induced DA depletion or neurotoxicity may lead to an increase in subsequent drug-taking and drug-seeking behavior. PMID:19336247

  9. Sugar administration to newly emerged Aedes albopictus males increases their survival probability and mating performance.

    PubMed

    Bellini, Romeo; Puggioli, Arianna; Balestrino, Fabrizio; Brunelli, Paolo; Medici, Anna; Urbanelli, Sandra; Carrieri, Marco

    2014-04-01

    Aedes albopictus male survival in laboratory cages is no more than 4-5 days when kept without any access to sugar indicating their need to feed on a sugar source soon after emergence. We therefore developed a device to administer energetic substances to newly emerged males when released as pupae as part of a sterile insect technique (SIT) programme, made with a polyurethane sponge 4 cm thick and perforated with holes 2 cm in diameter. The sponge was imbibed with the required sugar solution and due to its high retention capacity the sugar solution was available for males to feed for at least 48 h. When evaluated in lab cages, comparing adults emerged from the device with sugar solution vs the device with water only (as negative control), about half of the males tested positive for fructose using the Van Handel anthrone test, compared to none of males in the control cage. We then tested the tool in semi-field and in field conditions with different sugar concentrations (10%, 15%, and 20%) and compared results to the controls fed with water only. Males were recaptured by a battery operated manual aspirator at 24 and 48 h after pupae release. Rather high share 10-25% of captured males tested positive for fructose in recollections in the vicinity of the control stations, while in the vicinity of the sugar stations around 40-55% of males were positive, though variability between replicates was large. The sugar positive males in the control test may have been released males that had access to natural sugar sources found close to the release station and/or wild males present in the environment. Only a slight increase in the proportion of positive males was obtained by increasing the sugar concentration in the feeding device from 10% to 20%. Surprisingly, modification of the device to add a black plastic inverted funnel above the container reduced rather than increased the proportion of fructose positive males collected around the station. No evidence of difference in the

  10. Equine Infectious Anemia Virus Envelope Evolution In Vivo during Persistent Infection Progressively Increases Resistance to In Vitro Serum Antibody Neutralization as a Dominant Phenotype

    PubMed Central

    Howe, Laryssa; Leroux, Caroline; Issel, Charles J.; Montelaro, Ronald C.

    2002-01-01

    Equine infectious anemia virus (EIAV) infection of horses is characterized by well-defined waves of viremia associated with the sequential evolution of distinct viral populations displaying extensive envelope gp90 variation; however, a correlation of in vivo envelope evolution with in vitro serum neutralization phenotype remains undefined. Therefore, the goal of the present study was to utilize a previously defined panel of natural variant EIAV envelope isolates from sequential febrile episodes to characterize the effects of envelope variation during persistent infection on viral neutralization phenotypes and to define the determinants of EIAV envelope neutralization specificity. To assess the neutralization phenotypes of the sequential EIAV envelope variants, we determined the sensitivity of five variant envelopes to neutralization by a longitudinal panel of immune serum from the source infected pony. The results indicated that the evolution of the EIAV envelope sequences observed during sequential febrile episodes produced an increasingly neutralization-resistant phenotype. To further define the envelope determinants of EIAV neutralization specificity, we examined the neutralization properties of a panel of chimeric envelope constructs derived from reciprocal envelope domain exchanges between selected neutralization-sensitive and neutralization-resistant envelope variants. These results indicated that the EIAV gp90 V3 and V4 domains individually conferred serum neutralization resistance while other envelope segments in addition to V3 and V4 were evidently required for conferring total serum neutralization sensitivity. These data clearly demonstrate for the first time the influence of sequential gp90 variation during persistent infection in increasing envelope neutralization resistance, identify the gp90 V3 and V4 domains as the principal determinants of antibody neutralization resistance, and indicate distinct complex cooperative envelope domain interactions in

  11. The relationship between metabolic syndrome and increase of metabolic syndrome score and serum vitamin D levels in Korean adults: 2012 Korean National Health and Nutrition Examination Survey.

    PubMed

    Yoon, Hyun; Kim, Gwang Seok; Kim, Sung Gil; Moon, Ae Eun

    2015-07-01

    The present study was conducted to assess the relationship between metabolic syndrome and metabolic syndrome score (MSS) and serum vitamin D levels in adults aged 20 or older (n = 5,483) using 2012 Korean National Health and Nutrition Examination Survey data, which represents national data in Korea. Key study results were as follows: First, serum 25-hydroxyvitamin D [25(OH)D] levels decreased significantly with an increase in MSS (p = 0.004), shown by serum 25(OH)D levels after adjusting the variables (age, gender, BMI, TC, HDL-C, FBS, SBP, and DBP, etc.). These were 17.30 ± 0.16 ng/ml for MSS 0, 17.13 ± 0.15 ng/ml for MSS 1, 17.02 ± 0.16 ng/ml for MSS 2, 16.60 ± 0.20 ng/ml for MSS 3, 16.55 ± 0.28 ng/ml for MSS 4, and 15.52 ± 0.50 ng/ml for MSS 5. Second, after adjusting the related variables, serum 25(OH)D levels were significantly lower (p = 0.004) in the metabolic syndrome group (16.49 ± 0.19 ng/ml) than the non-metabolic syndrome group (17.16 ± 0.09 ng/ml). In conclusion, metabolic syndrome and the increased levels of its components are inversely associated with the serum vitamin D concentration in Korean adults. PMID:26236105

  12. The relationship between metabolic syndrome and increase of metabolic syndrome score and serum vitamin D levels in Korean adults: 2012 Korean National Health and Nutrition Examination Survey

    PubMed Central

    Yoon, Hyun; Kim, Gwang Seok; Kim, Sung Gil; Moon, Ae Eun

    2015-01-01

    The present study was conducted to assess the relationship between metabolic syndrome and metabolic syndrome score (MSS) and serum vitamin D levels in adults aged 20 or older (n = 5,483) using 2012 Korean National Health and Nutrition Examination Survey data, which represents national data in Korea. Key study results were as follows: First, serum 25-hydroxyvitamin D [25(OH)D] levels decreased significantly with an increase in MSS (p = 0.004), shown by serum 25(OH)D levels after adjusting the variables (age, gender, BMI, TC, HDL-C, FBS, SBP, and DBP, etc.). These were 17.30 ± 0.16 ng/ml for MSS 0, 17.13 ± 0.15 ng/ml for MSS 1, 17.02 ± 0.16 ng/ml for MSS 2, 16.60 ± 0.20 ng/ml for MSS 3, 16.55 ± 0.28 ng/ml for MSS 4, and 15.52 ± 0.50 ng/ml for MSS 5. Second, after adjusting the related variables, serum 25(OH)D levels were significantly lower (p = 0.004) in the metabolic syndrome group (16.49 ± 0.19 ng/ml) than the non-metabolic syndrome group (17.16 ± 0.09 ng/ml). In conclusion, metabolic syndrome and the increased levels of its components are inversely associated with the serum vitamin D concentration in Korean adults. PMID:26236105

  13. Evaluation of the circadian profiles of serum dehydroepiandrosterone (DHEA), cortisol, and cortisol/DHEA molar ratio after a single oral administration of DHEA in elderly subjects.

    PubMed

    Ceresini, G; Morganti, S; Rebecchi, I; Freddi, M; Ceda, G P; Banchini, A; Solerte, S B; Ferrari, E; Ablondi, F; Valenti, G

    2000-04-01

    Aging is associated with a selective decline in circulating levels of dehydroepiandrosterone (DHEA) and its sulfate, with no major changes in cortisol secretion. In young subjects, serum levels of both DHEA and cortisol are regulated according to a circadian rhythm, and an age-related attenuation of DHEA, but not cortisol, circadian rhythmicity has been reported. Several trials have evaluated the effects of DHEA supplementation in elderly subjects, although the results are still controversial. However, no data are available on the 24-hour profile of DHEA circulating levels in elderly subjects with DHEA administration. In the present study, we evaluated the circadian rhythms of DHEA, cortisol, and the cortisol/DHEA molar ratio in old subjects treated with either placebo (old-PL) or a single 50-mg dose of DHEA (old-D), both administered orally at 0700 hours. For each variable, the circadian profiles were compared with those obtained in young control subjects. The group of young subjects displayed a circadian rhythm for both DHEA and cortisol serum concentrations but no rhythm for the cortisol/DHEA molar ratio. In the old-PL group, the circadian rhythm of DHEA was completely abolished, whereas significant rhythms for both cortisol and the cortisol/DHEA molar ratio were observed. Particularly, at each time point, the cortisol/DHEA molar ratio was significantly higher in these subjects versus the young group. In the old-D group, the circadian rhythm of DHEA was completely restored and was comparable to that observed in the young group. Analogous to the observations in young subjects, the profile of the cortisol/DHEA molar ratio in old-D subjects did not display any circadian rhythmicity, the values being almost completely comparable to those observed in young controls. Our data demonstrate that the circadian rhythm of DHEA is totally abolished in elderly subjects. A single 50-mg dose of DHEA administered orally at 0700 hours restores the circadian rhythmicity of serum

  14. Behavioral stereotypies induced by "binge' cocaine administration are independent of drug-induced increases in corticosterone levels.

    PubMed

    Spangler, R; Zhou, Y; Schlussman, S D; Ho, A; Kreek, M J

    1997-07-01

    Cocaine administration causes dramatic stereotypic behavior and elevation of circulating corticosterone levels in rodents. The present study tested the possible role of increased corticosterone in mediating stereotypic behavior caused by "binge' pattern cocaine administration. Animals were administered saline or cocaine intraperitoneally for 3 days, with or without pretreatment with a D1 (SCH 23390, 2 mg/kg) or D2 (sulpiride, 50 mg/kg) dopamine receptor antagonist. Three days of cocaine "binges' significantly increased corticosterone levels in vehicle pretreated rats (P < 0.01). Both SCH 23390 and sulpiride pretreatment daily significantly attenuated this increase (P < 0.01). Cocaine administration caused stereotypic behaviors in vehicle pretreatment rats (P < 0.01). These behavioral responses were blocked by the D1 dopamine receptor antagonist SCH 23390, but not by the D2 antagonist sulpiride. These findings reaffirm the dominant role of the D1 receptor in mediating behavioral stereotypy caused by elevations of extracellular dopamine in the synaptic cleft. The fact that the dose of sulpiride used in these studies prevented the elevation of plasma corticosterone caused by cocaine, without blocking the stereotypy caused by cocaine, indicates that this stereotypic behavior does not require drug-induced elevation in circulating levels of corticosterone. PMID:9134155

  15. Decreased bile-acid synthesis in livers of hepatocyte-conditional NADPH-cytochrome P450 reductase-null mice results in increased bile acids in serum.

    PubMed

    Cheng, Xingguo; Zhang, Youcai; Klaassen, Curtis D

    2014-10-01

    NADPH-cytochrome P450 reductase (Cpr) is essential for the function of microsomal cytochrome P450 monooxygenases (P450), including those P450s involved in bile acid (BA) synthesis. Mice with hepatocyte-specific deletion of NADPH-cytochrome P450 reductase (H-Cpr-null) have been engineered to understand the in vivo function of hepatic P450s in the metabolism of xenobiotics and endogenous compounds. However, the impact of hepatic Cpr on BA homeostasis is not clear. The present study revealed that H-Cpr-null mice had a 60% decrease in total BA concentration in liver, whereas the total BA concentration in serum was almost doubled. The decreased level of cholic acid (CA) in both serum and livers of H-Cpr-null mice is likely due to diminished enzyme activity of Cyp8b1 that is essential for CA biosynthesis. Feedback mechanisms responsible for the reduced liver BA concentrations and/or increased serum BA concentrations in H-Cpr-null mice included the following: 1) enhanced alternative BA synthesis pathway, as evidenced by the fact that classic BA synthesis is diminished but chenodeoxycholic acid still increases in both serum and livers of H-Cpr-null mice; 2) inhibition of farnesoid X receptor activation, which increased the mRNA of Cyp7a1 and 8b1; 3) induction of intestinal BA transporters to facilitate BA absorption from the intestine to the circulation; 4) induction of hepatic multidrug resistance-associated protein transporters to increase BA efflux from the liver to blood; and 5) increased generation of secondary BAs. In summary, the present study reveals an important contribution of the alternative BA synthesis pathway and BA transporters in regulating BA concentrations in H-Cpr-null mice. PMID:25034404

  16. Cortisol administration increases hippocampal activation to infant crying in males depending on childhood neglect.

    PubMed

    Bos, Peter A; Montoya, Estrella R; Terburg, David; van Honk, Jack

    2014-10-01

    Animal studies show that exposure to parental neglect alters stress regulation and can lead to neural hyposensitivity or hypersensitivity in response to cortisol, most pronounced in the hippocampus. Cortisol, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, has also been related to parenting more directly, for example, in both sexes, cortisol levels increase when listening to infants crying, possibly to activate and facilitate effective care behavior. Severe trauma is known to negatively affect the HPA-axis in humans; however, it is unknown whether normal variation in parental care in the healthy population can alter sensitivity of the hippocampus to cortisol. Here, we investigate whether variation in experienced neglect changes neural sensitivity to cortisol when humans listen to infant crying, which is an unequivocal signal relevant for care behavior. In a placebo-controlled, within-subject neuroimaging study, we administered 40 mg cortisol to 21 healthy young males without children and used a validated task for measuring neural responses to infant crying. The Dutch version of the Childhood Trauma Questionnaire was used to index participants' early exposure to abuse and neglect. The data show that cortisol markedly increased hippocampal activation toward crying infants, and this effect varied significantly with parental neglect, even in our nonclinical subject sample. Without exposure to severe trauma or neglect, reduced self-experienced quality of parental care in the normal range already substantially increased hippocampal responsivity to cortisol. Altered hippocampal sensitivity to cortisol might be a cross-species marker for the risk of developing later life psychopathology. PMID:24757127

  17. Corticosteroid administration modifies ozone-induced increases in sheep airway blood flow

    SciTech Connect

    Gunther, R.A.; Yousef, M.A.; Schelegle, E.S.; Cross, C.E. )

    1992-09-01

    Recently, we have shown that exposure of intubated conscious sheep to 3 to 4 ppm ozone (O3) for 3 h increases bronchial blood flow (Qbr). The purpose of the present study was to assess the potential role of corticosteroids in modulating this increase. Six nasally intubated sheep were exposed to filtered room air, 3.5 ppm O3 on two separate occasions, and 3.5 ppm O3 plus methyl-prednisone, for 3 h. Qbr was measured using a chronically implanted 20 MHz pulsed Doppler flow probe. Qbr, mean aortic pressure, cardiac output, pulmonary artery pressure, arterial blood gases, and core temperature were monitored. After 3 h of 3.5 ppm O3, Qbr increased from 3.2 +/- 0.5 (mean +/- SEM) to 8.5 +/- 1.6 KHz, whereas bronchial vascular resistance (BVR) decreased from the baseline value of 43.6 +/- 8.0 to 15.0 +/- 3 mm Hg/KHz. With corticosteroids, baseline Qbr was 3.2 +/- 0.6 and BVR was 44.2 +/- 9.7; after 3 h of 3.5 ppm O3, Qbr was 3.3 +/- 0.5 KHz and BVR was 39.0 +/- 8.0 mm Hg/KHz. The two 3.5-ppm O3 exposures without corticosteroids were impressively reproducible. Except for Qbr and BVR, no other measured cardiovascular parameters were affected by O3. The results indicate that corticosteroids are capable of interfering with mediator, neurohumoral, or inflammatory cell mechanisms responsible for vasodilation of the airway microcirculation after O3 exposure, but do not specifically address the specific processes whereby this attenuation occurs.

  18. Functionalized Fullerene Increases NF-κB Activity and Blocks Genotoxic Effect of Oxidative Stress in Serum-Starving Human Embryo Lung Diploid Fibroblasts

    PubMed Central

    Ershova, E. S.; Sergeeva, V. A.; Tabakov, V. J.; Kameneva, L. A.; Voronov, I. I.; Khakina, E. A.; Troshin, P. A.; Kutsev, S. I.; Veiko, N. N.; Kostyuk, S. V.

    2016-01-01

    The influence of a water-soluble [60] fullerene derivative containing five residues of 3-phenylpropionic acid and a chlorine addend appended to the carbon cage (F-828) on serum-starving human embryo lung diploid fibroblasts (HELFs) was studied. Serum deprivation evokes oxidative stress in HELFs. Cultivation of serum-starving HELFs in the presence of 0.1–1 µM F-828 significantly decreases the level of free radicals, inhibits autophagy, and represses expression of NOX4 and NRF2 proteins. The activity of NF-κB substantially grows up in contrast to the suppressed NRF2 activity. In the presence of 0.2–0.25 µM F-828, the DSB rate and apoptosis level dramatically decrease. The maximum increase of proliferative activity of the HELFs and maximum activity of NF-κB are observed at these concentration values. Conclusion. Under the conditions of oxidative stress evoked by serum deprivation the water-soluble fullerene derivative F-828 used in concentrations of 0.1 to 1 µM strongly stimulates the NF-κB activity and represses the NRF2 activity in HELFs.

  19. Early detection of colon cancer by increased serum level of Krebs von den Lungen-6 in a patient with dermatomyositis-associated interstitial pneumonia.

    PubMed

    Fukuhara, Naoko; Tanino, Yoshinori; Sato, Suguru; Fukuhara, Atsuro; Uematsu, Manabu; Nikaido, Takefumi; Misa, Kenichi; Sato, Yasuko; Saito, Junpei; Wang, Xintao; Munakata, Mitsuru

    2015-01-01

    Krebs von den Lungen-6 (KL-6) is a high-molecular-weight glycoprotein which is elevated in serum of patients with interstitial pneumonia (IP). Serum KL-6 level is clinically used for the diagnosis of IP as well as the evaluation of its disease activity. KL-6 is originally identified when exploring novel soluble antigens in patients with lung cancer, and is known to be elevated in patients with several malignant tumors. The risk of malignant tumors is high in IP patients with polymyositis and dermatomyositis (PM/DM), and follow-up of KL-6 levels may allow earlier detection of such tumors. However, to date, there are only a few reports showing the usefulness of following-up serum KL-6 levels for finding malignant tumors in IP patients with PM/DM. Here, we described the first patient in whom increased serum KL-6 led to the diagnosis of colon cancer during follow-up of DM-associated IP. PMID:26422573

  20. Broilers with low serum Mannose-binding Lectin show increased fecal shedding of Salmonella enterica serovar Montevideo.

    PubMed

    Ulrich-Lynge, Sofie L; Juul-Madsen, Helle R; Kjærup, Rikke B; Okimoto, Ron; Abrahamsen, Mitchell S; Maurischat, Sven; Sørensen, Poul; Dalgaard, Tina S

    2016-08-01

    Mannose-binding lectin (MBL) is a key molecule in innate immunity. MBL binds to carbohydrates on the surface of pathogens, initiating the complement system via the lectin-dependent pathway or facilitates opsonophagocytosis. In vivo studies using inbred chicken lines differing in MBL serum concentration indicate that chicken MBL affects Salmonella resistance; further studies are imperative in conventional broiler chickens. In this study 104 conventional day-old chickens (offspring from a cross between Cobb 500 male and female parent breeders) were orally infected with Salmonella enterica subsp. enterica serovar Montevideo. The chickens were divided into two groups based on polymorphisms in their MBL promoter region, designated L/L for low serum concentrations of MBL and L/H for medium serum concentrations of MBL. A semi-quantitative real-time PCR method for detection of Salmonella in cloacal swabs was used, the log10 CFU quantification was based on a standard curve from artificially spiked cloacal swab samples pre-incubated for 8 h with known concentrations of Salmonella ranging from 10(1) to 10(6) CFU/swabs, with an obtained amplification efficiency of 102% and a linear relationship between the log10 CFU and the threshold cycle Ct values of (R(2) = 0.99). The L/L chickens had significantly higher Log10 CFU/swab at week 5 post infection (pi) than the L/H chickens. A repetition of the study with 86 L/L and 18 L/H chickens, also gave significantly higher log10 CFU ± SEM in cloacal swabs, using the semi-quantitative real-time PCR method from L/L chickens than from the L/H chickens at week 5 pi. These results indicate that genetically determined basic levels of MBL may influence S. Montevideo susceptibility. PMID:26994208

  1. Increased serum levels of circulating exosomal microRNA-373 in receptor-negative breast cancer patients.

    PubMed

    Eichelser, Corinna; Stückrath, Isabel; Müller, Volkmar; Milde-Langosch, Karin; Wikman, Harriet; Pantel, Klaus; Schwarzenbach, Heidi

    2014-10-30

    In this study, we compared the blood serum levels of circulating cell-free and exosomal microRNAs, and their involvement in the molecular subtypes of breast cancer patients. Our analyses on cell-free miR-101, miR-372 and miR-373 were performed in preoperative blood serum of 168 patients with invasive breast cancer, 19 patients with benign breast diseases and 28 healthy women. MicroRNAs were additionally quantified in exosomes of 50 cancer patients and 12 healthy women from the same cohort. Relative concentrations were measured by quantitative TaqMan MicroRNA assays and correlated to clinicopathological risk factors. The concentrations of cell-free miR-101 (p=0.013) and miR-373 (p=0.024) were significantly different between patients with breast cancer and benign tumors. A prevalence of miR-101, miR-372 and miR-373 were found in exosomes. The levels of circulating exosomal (but not cell-free) miR-373 were higher in triple negative than luminal carcinomas (p=0.027). Also, estrogen-negative (p=0.021) and progesterone-negative (p=0.01) tumors displayed higher concentrations of exosomal miR-373 than patients with hormone-receptor positive tumors. Overexpression of miR-373 by transfection of MCF-7 cells showed downregulated protein expression of the estrogen receptor, and inhibition of apoptosis induced by camptothecin. Our data indicate that serum levels of exosomal miR-373 are linked to triple negative and more aggressive breast carcinomas. PMID:25333260

  2. [Iron substitution in outpatients in Switzerland: Increase of costs associated with intravenous administration].

    PubMed

    Giger, Max; Achermann, Rita

    2013-01-01

    Iron anaemia and iron-deficient erythropoiesis are treated with oral iron supplements. For chronic haemodialysis or in the case of therapy failure or intolerance to oral iron therapy, intravenous supplements are administered. The costs of iron supplements borne by statutory health care insurance had strongly increased during the observation period from 2006 to 2010. Based on the invoice data of a large health insurance company with a market share of around 18 %, prescription data of iron preparations and laboratory tests were analysed and extrapolated to the Swiss population. During the 5-year observation period, costs of intravenous iron substitution increased by 16.5 m EUR (340.3 %) and the number of individuals treated by 243.5 %. A sharp rise was observed in women of menstruating age, which was mainly due to prescriptions issued by primary care physicians. More than 8 % of intravenous iron substitutions were administered without prior laboratory analysis,and must therefore be regarded as off-label use. A cost-benefit analysis is needed to demonstrate the additional value of intravenous over oral iron supplementation, and intravenous iron supplementation should be administered only to patients with proven iron deficiency. PMID:23916272

  3. Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia.

    PubMed

    Sheikh, Virginia; Porter, Brian O; DerSimonian, Rebecca; Kovacs, Stephen B; Thompson, William L; Perez-Diez, Ainhoa; Freeman, Alexandra F; Roby, Gregg; Mican, JoAnn; Pau, Alice; Rupert, Adam; Adelsberger, Joseph; Higgins, Jeanette; Bourgeois, Jeffrey S; Jensen, Stig M R; Morcock, David R; Burbelo, Peter D; Osnos, Leah; Maric, Irina; Natarajan, Ven; Croughs, Therese; Yao, Michael D; Estes, Jacob D; Sereti, Irini

    2016-02-25

    Idiopathic CD4 lymphopenia (ICL) is a rare syndrome defined by low CD4 T-cell counts (<300/µL) without evidence of HIV infection or other known cause of immunodeficiency. ICL confers an increased risk of opportunistic infections and has no established treatment. Interleukin-7 (IL-7) is fundamental for thymopoiesis, T-cell homeostasis, and survival of mature T cells, which provides a rationale for its potential use as an immunotherapeutic agent for ICL. We performed an open-label phase 1/2A dose-escalation trial of 3 subcutaneous doses of recombinant human IL-7 (rhIL-7) per week in patients with ICL who were at risk of disease progression. The primary objectives of the study were to assess safety and the immunomodulatory effects of rhIL-7 in ICL patients. Injection site reactions were the most frequently reported adverse events. One patient experienced a hypersensitivity reaction and developed non-neutralizing anti-IL-7 antibodies. Patients with autoimmune diseases that required systemic therapy at screening were excluded from the study; however, 1 participant developed systemic lupus erythematosus while on study and was excluded from further rhIL-7 dosing. Quantitatively, rhIL-7 led to an increase in the number of circulating CD4 and CD8 T cells and tissue-resident CD3 T cells in the gut mucosa and bone marrow. Functionally, these T cells were capable of producing cytokines after mitogenic stimulation. rhIL-7 was well tolerated at biologically active doses and may represent a promising therapeutic intervention in ICL. This trial was registered at www.clinicaltrials.gov as #NCT00839436. PMID:26675348

  4. Inflammatory Pain Promotes Increased Opioid Self-Administration: Role of Dysregulated Ventral Tegmental Area μ Opioid Receptors

    PubMed Central

    Hipólito, Lucia; Wilson-Poe, Adrianne; Campos-Jurado, Yolanda; Zhong, Elaine; Gonzalez-Romero, Jose; Virag, Laszlo; Whittington, Robert; Comer, Sandra D.; Carlton, Susan M.; Walker, Brendan M.; Bruchas, Michael R.

    2015-01-01

    Pain management in opioid abusers engenders ethical and practical difficulties for clinicians, often resulting in pain mismanagement. Although chronic opioid administration may alter pain states, the presence of pain itself may alter the propensity to self-administer opioids, and previous history of drug abuse comorbid with chronic pain promotes higher rates of opioid misuse. Here, we tested the hypothesis that inflammatory pain leads to increased heroin self-administration resulting from altered mu opioid receptor (MOR) regulation of mesolimbic dopamine (DA) transmission. To this end, the complete Freund's adjuvant (CFA) model of inflammation was used to assess the neurochemical and functional changes induced by inflammatory pain on MOR-mediated mesolimbic DA transmission and on rat intravenous heroin self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. In the presence of inflammatory pain, heroin intake under an FR schedule was increased for high, but attenuated for low, heroin doses with concomitant alterations in mesolimbic MOR function suggested by DA microdialysis. Consistent with the reduction in low dose FR heroin self-administration, inflammatory pain reduced motivation for a low dose of heroin, as measured by responding under a PR schedule of reinforcement, an effect dissociable from high heroin dose PR responding. Together, these results identify a connection between inflammatory pain and loss of MOR function in the mesolimbic dopaminergic pathway that increases intake of high doses of heroin. These findings suggest that pain-induced loss of MOR function in the mesolimbic pathway may promote opioid dose escalation and contribute to opioid abuse-associated phenotypes. SIGNIFICANCE STATEMENT This study provides critical new insights that show that inflammatory pain alters heroin intake through a desensitization of MORs located within the VTA. These findings expand our knowledge of the interactions between

  5. Intranasal administration of glial-derived neurotrophic factor (GDNF) rapidly and significantly increases whole-brain GDNF level in rats.

    PubMed

    Bender, T S; Migliore, M M; Campbell, R B; John Gatley, S; Waszczak, B L

    2015-09-10

    Previous studies have shown that glial cell line-derived neurotrophic factor (GDNF) exerts significant neuroprotective effects on substantia nigra (SN) neurons in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD). In this study we used enzyme-linked immunosorbent assay (ELISA) to determine GDNF brain levels and distribution to target regions (i.e. striatum and SN) following intranasal administration of GDNF at different time points after administration. Brain levels increased significantly within 1h following a single 50-μg dose of GDNF in a liposomal formulation, returning to baseline by 24h. In a second study, different doses of GDNF (10-150 μg) in phosphate-buffered saline (PBS) were studied at the 1-h time point. Dose-dependent increases in brain GDNF levels were observed with apparent saturation of uptake at doses above 100 μg. Liposomes delivered 10-fold more GDNF to brain than PBS despite yielding similar neuroprotective efficacy in the 6-OHDA model, suggesting incomplete release of GDNF from liposomes in tissue. In a third study, autoradiography was performed on brain sections taken 1h after intranasal (125)I-labeled GDNF. Radioactivity was detected throughout the brain along the rostral-to-caudal axis, indicating that nasally administered GDNF can reach target areas. Collectively, these results demonstrate that intranasal administration of GDNF in liposomes or PBS achieves significant increases in GDNF in target brain areas, supporting use of intranasal administration as a non-invasive means of delivering GDNF to the brain to protect dopamine neurons and arrest disease progression in PD. PMID:26166725

  6. Oral administration of lactulose: a novel therapy for acute carbon monoxide poisoning via increasing intestinal hydrogen production.

    PubMed

    Fan, Dan-Feng; Hu, Hui-Jun; Sun, Xue-Jun; Meng, Xiang-En; Zhang, Yu; Pan, Shu-Yi

    2016-01-01

    It has been known that the pathophysiology of carbon monoxide (CO) poisoning is related to hypoxia, the increased production of reactive oxygen species (ROS) and oxidative stress. Studies have shown that the novel, safe and effective free radical scavenger, hydrogen, has neuroprotective effects in both acute CO poisoning and delayed neuropsychological sequelae in CO poisoning. Orally administered lactulose, which may be used by some intestinal bacteria as a food source to produce endogenous hydrogen, can ameliorate oxidative stress. Based on the available findings, we hypothesize that oral administration of lactulose may be a novel therapy for acute CO poisoning via increasing intestinal hydrogen production. PMID:27000012

  7. Administration of URB597, Oleoylethanolamide or Palmitoylethanolamide Increases Waking and Dopamine in Rats

    PubMed Central

    Murillo-Rodríguez, Eric; Palomero-Rivero, Marcela; Millán-Aldaco, Diana; Arias-Carrión, Oscar; Drucker-Colín, René

    2011-01-01

    Background Oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) are amides of fatty acids and ethanolamine named N-acylethanolamines or acylethanolamides. The hydrolysis of OEA and PEA is catalyzed by the fatty acid amide hydrolase (FAAH). A number of FAAH inhibitors that increase the levels of OEA and PEA in the brain have been developed, including URB597. In the present report, we examined whether URB597, OEA or PEA injected into wake-related brain areas, such as lateral hypothalamus (LH) or dorsal raphe nuclei (DRN) would promote wakefulness (W) in rats. Methodology and Principal Findings Male Wistar rats (250–300 g) were implanted for sleep studies with electrodes to record the electroencephalogram and electromyogram as well as a cannulae aimed either into LH or into DRN. Sleep stages were scored to determine W, slow wave sleep (SWS) and rapid eye movement sleep (REMS). Power spectra bands underly neurophysiological mechanisms of the sleep-wake cycle and provide information about quality rather than quantity of sleep, thus fast Fourier transformation analysis was collected after the pharmacological trials for alpha (for W; α = 8–12 Hz), delta (for SWS; δ = 0.5–4.0 Hz) and theta (for REMS; θ = 6.0–12.0 Hz). Finally, microdialysis samples were collected from a cannula placed into the nucleus accumbens (AcbC) and the levels of dopamine (DA) were determined by HPLC means after the injection of URB597, OEA or PEA. We found that microinjection of compounds (10, 20, 30 µg/1 µL; each) into LH or DRN during the lights-on period increased W and decreased SWS as well as REMS and enhanced DA extracellular levels. Conclusions URB597, OEA or PEA promoted waking and enhanced DA if injected into LH or DRN. The wake-promoting effects of these compounds could be linked with the enhancement in levels of DA and indirectly mediated by anandamide. PMID:21779318

  8. Effectiveness of increasing the frequency of posaconazole syrup administration to achieve optimal plasma concentrations in patients with haematological malignancy.

    PubMed

    Park, Wan Beom; Cho, Joo-Youn; Park, Sang-In; Kim, Eun Jung; Yoon, Seonghae; Yoon, Seo Hyun; Lee, Jeong-Ok; Koh, Youngil; Song, Kyoung-Ho; Choe, Pyoeng Gyun; Yu, Kyung-Sang; Kim, Eu Suk; Bang, Su Mi; Kim, Nam Joong; Kim, Inho; Oh, Myoung-Don; Kim, Hong Bin; Song, Sang Hoon

    2016-07-01

    Few data are available on whether adjusting the dose of posaconazole syrup is effective in patients receiving anti-cancer chemotherapy. The aim of this prospective study was to analyse the impact of increasing the frequency of posaconazole administration on optimal plasma concentrations in adult patients with haematological malignancy. A total of 133 adult patients receiving chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome who received posaconazole syrup 200 mg three times daily for fungal prophylaxis were enrolled in this study. Drug trough levels were measured by liquid chromatography-tandem mass spectrometry. In 20.2% of patients (23/114) the steady-state concentration of posaconazole was suboptimal (<500 ng/mL) on Day 8. In these patients, the frequency of posaconazole administration was increased to 200 mg four times daily. On Day 15, the median posaconazole concentration was significantly increased from 368 ng/mL [interquartile range (IQR), 247-403 ng/mL] to 548 ng/mL (IQR, 424-887 ng/mL) (P = 0.0003). The median increase in posaconazole concentration was 251 ng/mL (IQR, 93-517 ng/mL). Among the patients with initially suboptimal levels, 79% achieved the optimal level unless the steady-state level was <200 ng/mL. This study shows that increasing the administration frequency of posaconazole syrup is effective for achieving optimal levels in patients with haematological malignancy undergoing chemotherapy. PMID:27234674

  9. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

    PubMed

    Macedo, Levy W; Cararo, José H; Maravai, Soliany G; Gonçalves, Cinara L; Oliveira, Giovanna M T; Kist, Luiza W; Guerra Martinez, Camila; Kurtenbach, Eleonora; Bogo, Maurício R; Hipkiss, Alan R; Streck, Emilio L; Schuck, Patrícia F; Ferreira, Gustavo C

    2016-10-01

    Carnosine (β-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders. PMID:26476839

  10. Transforming Growth Factor Beta Receptor 1 Is Increased following Abstinence from Cocaine Self-Administration, but Not Cocaine Sensitization

    PubMed Central

    Gancarz-Kausch, Amy M.; Schroeder, Gabrielle L.; Panganiban, Clarisse; Adank, Danielle; Humby, Monica S.; Kausch, Michael A.; Clark, Stewart D.; Dietz, David M.

    2013-01-01

    The addicted phenotype is characterized as a long-lasting, chronically relapsing disorder that persists following long periods of abstinence, suggesting that the underlying molecular changes are stable and endure for long periods even in the absence of drug. Here, we investigated Transforming Growth Factor-Beta Type I receptor (TGF-β R1) expression in the nucleus accumbens (NAc) following periods of withdrawal from cocaine self-administration (SA) and a sensitizing regimen of non-contingent cocaine. Rats were exposed to either (i) repeated systemic injections (cocaine or saline), or (ii) self-administration (cocaine or saline) and underwent a period of forced abstinence (either 1 or 7 days of drug cessation). Withdrawal from cocaine self-administration resulted in an increase in TGF-β R1 protein expression in the NAc compared to saline controls. This increase was specific for volitional cocaine intake as no change in expression was observed following a sensitizing regimen of experimenter-administered cocaine. These findings implicate TGF-β signaling as a novel potential therapeutic target for treating drug addiction. PMID:24386286

  11. Glutamate supply positively affects serum cholesterol concentrations without increases in total protein and urea around the onset of puberty in goats.

    PubMed

    Meza-Herrera, C A; Calderón-Leyva, G; Soto-Sanchez, M J; Serradilla, J M; García-Martinez, A; Mellado, M; Veliz-Deras, F G

    2014-06-30

    Different neurotransmitter and neuromodulatory systems regulate synthesis and secretion of GnRH. Whereas the endocrine and neural systems are activated in response to the metabolic status and the circulating levels of specific blood metabolites, glutamate receptors have been reported at hepatic level. This study evaluated the possible effect of glutamate supplementation upon changes in serum concentrations across time for total protein (TP), urea (UR) and cholesterol (CL) around the onset of puberty in goats. Prepuberal female goats (n=18) were randomly assigned to: (1) excitatory amino acids group, GLUT, n=10; 16.52±1.04kg live weight (LW), 3.4±0.12 body condition score (BCS) receiving an i.v. infusion of 7mgkg(-1) LW of l-glutamate, and (2) Control group, CONT, n=8; 16.1±1.04kg LW, 3.1±0.12 BCS. General averages for LW (23.2±0.72kg), BCS (3.37±0.10 units), serum TP (65.28±2.46mgdL(-1)), UR (23.42±0.95mgdL(-1)), CL (77.89±1.10mgdL(-1)) as well as the serum levels for TP and UR across time did not differ (P>0.05) between treatments. However, while GLUT positively affected (P<0.05) both the onset (207±9 vs. 225±12 d) and the percentage (70 vs. 25%) of females showing puberty, a treatment×time interaction effect (P<0.05) was observed in the GLUT group, with increases in serum cholesterol, coincident with the onset of puberty. Therefore, in peripuberal glutamate supplemented goats, serum cholesterol profile could act as a metabolic modulator for the establishment of puberty, denoting also a potential role of glutamate as modulator of lipid metabolism. PMID:24811839

  12. [Anti-tetanus immunity among university students and health staff in North Lebanon and administration of anti-tetanus serums in two hospitals].

    PubMed

    Hamze, M; Hlais, S; Dabboussi, F; Mallat, H

    2014-10-01

    Tetanus is a serious illness that kills about one million people a year globally. This study aimed to i) evaluate immunity against tetanus (by antibodies titres in blood) among health staff and students at the Public Health Faculty, Lebanese University, ii) explore the determinants of the anti-tetanus immunity by a questionnaire and iii) estimate anti-tetanic serum use in the emergency departments of two hospitals (1 private, 1 public) in Tripoli. Most of the participants (76.6%) had anti-tetanus antibody titres ≥ 0.1 UI/mL. There was no association between immune status and gender (P = 0.614) but more participants ≤ 25 years were immunized than those > 25 years (P < 0.001) and more students were immunized than employees (P = 0.032). There was an inverse association between anti-tetanus immunity and having visited a physician in the past year (P = 0.009). In 2011, 1037 people received anti-tetanus immunoglobulins at the hospitals, 73% at the private hospital. Vaccination campaigns targetting adults > 25 years may be warranted to assure good anti-tetanus protection and avoid administration of anti-tetanus immunoglobulins in emergency departments. PMID:25356694

  13. Does an increase in the sensitivity of serum thyrotropin assays reduce diagnostic costs for thyroid disease in the community?

    PubMed Central

    Vanderpump, M P; Neary, R H; Manning, K; Clayton, R N

    1997-01-01

    Many authorities now advocate that the first-line assessment of thyroid function should be measurement of thyrotropin (TSH). The latest serum TSH assays (third generation) are more sensitive than the second generation but the reagents are more costly. We have examined whether overall assay reagent costs would be higher or lower with a third-generation assay, in a laboratory that serves a population of almost 500,000. In a prospective study over six weeks, 505 samples with a second-generation serum TSH less than 0.5 mU/L (303 for screening and 202 for monitoring thyroxine therapy) had an additional third-generation TSH analysis. With a second-generation assay for screening, 11% more free thyroxine (FT4) measurements were required to exclude thyrotoxicosis but there was a 42% saving on the reagent budget compared with a third-generation assay. In patients taking thyroxine, 33% more FT4 measurements were required to exclude over-replacement but the calculated saving in reagent costs was 53%. The costs of all other aspects of the two methods were similar. In this community-based sample, the improvement in sensitivity yielded by the third-generation assay at the lower end of the normal range reduced the number of confirmatory FT4 levels required to exclude thyrotoxicosis or over-replacement with thyroxine, but reagent costs were nevertheless higher than for second-generation assays. In financial terms, there is little justification for use of assays with sensitivity greater than the second generation (0.1 mU/L). PMID:9488012

  14. Elevated Serum Leptin Levels are Associated With an Increased Risk of Sentinel Lymph Node Metastasis in Cutaneous Melanoma

    PubMed Central

    Oba, Junna; Wei, Wei; Gershenwald, Jeffrey E.; Johnson, Marcella M.; Wyatt, Cynthia M.; Ellerhorst, Julie A.; Grimm, Elizabeth A.

    2016-01-01

    Abstract The metabolic hormone leptin has been implicated in the pathogenesis of various malignancies and may contribute to the high rate of cancer in obese individuals. We reported that leptin and its receptor are expressed by melanoma tumors and cell lines, and that leptin stimulates proliferation of cultured melanoma cells. Here, we tested the hypothesis that leptin contributes to early melanoma progression by assessing its association with sentinel node positivity in cutaneous melanoma patients. The study enrolled 72 patients who were scheduled to undergo lymphatic mapping and sentinel node biopsy. Fasting blood was obtained before surgery, and serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA) with a “raw” (assay value) and an “adjusted” value (raw value divided by body mass index). Leptin levels and other clinicopathologic parameters were compared between sentinel node positive and negative groups. Logistic regression models were used to predict sentinel node status using leptin and other relevant clinical parameters. The raw and adjusted leptin levels were significantly higher in the 15 patients with positive sentinel nodes. These findings could not be attributed to differences in body mass indices. Univariate models revealed raw leptin, adjusted leptin, Breslow thickness, and mitotic rate as significant predictors of sentinel node status. Leptin levels and Breslow thickness remained significant in multivariate models. Survival and follow-up analysis revealed more aggressive disease in diabetic patients. Elevated serum leptin levels predict sentinel node metastasis in melanoma. Validation of this finding in larger cohorts should enable better stratification of early stage melanoma patients. PMID:26986135

  15. Increased Levels of Antigen-Bound β-Amyloid Autoantibodies in Serum and Cerebrospinal Fluid of Alzheimer’s Disease Patients

    PubMed Central

    Schnack, Cathrin; Tumani, Hayrettin; Otto, Markus; Elbert, Thomas; Kolassa, Iris-Tatjana; Przybylski, Michael; Manea, Marilena; von Arnim, Christine A. F.

    2013-01-01

    Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer’s disease (AD). However, the determination of both free and dissociated Aβ-autoantibodies in serum hitherto has yielded inconsistent results regarding their function and possible biomarker value. Here we report the application of a new sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of antigen-bound Aβ-autoantibodies (intact Aβ-IgG immune complexes) in serum and cerebrospinal fluid (CSF) of a total number of 112 AD patients and age- and gender-matched control subjects. Both serum and CSF levels of Aβ-IgG immune complexes were found to be significantly higher in AD patients compared to control subjects. Moreover, the levels of Aβ-IgG complexes were negatively correlated with the cognitive status across the groups, increasing with declining cognitive test performance of the subjects. Our results suggest a contribution of IgG-type autoantibodies to Aβ clearance in vivo and an increased immune response in AD, which may be associated with deficient Aβ-IgG removal. These findings may contribute to elucidating the role of Aβ-autoantibodies in AD pathophysiology and their potential application in AD diagnosis. PMID:23874844

  16. A diet rich in monounsaturated rapeseed oil reduces the lipoprotein cholesterol concentration and increases the relative content of n-3 fatty acids in serum in hyperlipidemic subjects.

    PubMed

    Gustafsson, I B; Vessby, B; Ohrvall, M; Nydahl, M

    1994-03-01

    The effects of 3 wk on a diet rich in monounsaturated rapeseed oil were compared with those of a diet containing sunflower oil within a lipid-lowering diet. Ninety-five subjects with moderate hyperlipoproteinemia were randomly assigned to one of the two well-controlled diets prepared at the hospital kitchen. Total serum, low-density- and high-density-lipoprotein cholesterol concentrations decreased by 15%, 16%, and 11% (P < 0.001), respectively, on the rapeseed oil diet and by 16%, 14%, and 13% (P < 0.001) on the sunflower oil diet. Serum triglycerides decreased more markedly (by 29%, P < 0.001) on the sunflower oil than on the rapeseed oil diet (14%, P < 0.01). The n-3 fatty acids (20:5 and 22:5) in the serum phospholipids increased significantly on the rapeseed oil diet but decreased on the sunflower oil diet. There was an increase in the alpha-tocopherol concentrations after both diets. The findings indicate that low erucic acid rapeseed oil can replace oils and fats rich in polyunsaturated fatty acids in a lipid-lowering diet. PMID:8116547

  17. Elevated serum IL-35 and increased expression of IL-35-p35 or -EBI3 in CD4+CD25+ T cells in patients with active tuberculosis

    PubMed Central

    Kong, Bin; Liu, Gan-Bin; Zhang, Jun-Ai; Fu, Xiao-Xia; Xiang, Wen-Yu; Gao, Yu-Chi; Lu, Yuan-Bin; Wu, Xian-Jing; Qiu, Feng; Wang, Wan-Dang; Yi, Lai-Long; Zhong, Ji-Xin; Chen, Zheng W; Xu, Jun-Fa

    2016-01-01

    Despite the recent appreciation of interleukin 35 (IL-35) function in inflammatory diseases, little is known for IL-35 response in patients with active tuberculosis (ATB). In the current study, we demonstrated that ATB patients exhibited increases in serum IL-35 and in mRNA expression of both subunits of IL-35 (p35 and EBI3) in white blood cells and peripheral blood mononuclear cells. Consistently, anti-TB drug treatment led to reduction in serum IL-35 level and p35 or EBI3 expression. TB infection was associated with expression of p35 or EBI3 protein in CD4+ but not CD8+ T cells. Most p35+CD4+ T cells and EBI3+CD4+ T cells expressed Treg-associated marker CD25. Our findings may be important in understanding immune pathogenesis of TB. IL-35 in the blood may potentially serve as a biomarker for immune status and prognosis in TB. PMID:27158354

  18. Increased concentration of serum TNF alpha and its correlations with arterial blood pressure and indices of renal damage in dogs infected with Babesia canis.

    PubMed

    Zygner, Wojciech; Gójska-Zygner, Olga; Bąska, Piotr; Długosz, Ewa

    2014-04-01

    Canine babesiosis is a tick-borne disease caused by parasites of the genus Babesia. Tumour necrosis factor alpha (TNF-α) is a cytokine that plays a role in the pathogenesis of canine babesiosis. In this study, the authors determined the concentration of serum TNF-α in 11 dogs infected with Babesia canis and calculated Spearman's rank correlations between the concentration of TNF-α and blood pressure, and between TNF-α and indices of renal damage such as: fractional excretion of sodium (FE(Na(+))), urinary creatinine to serum creatinine ratio (UCr/SCr), renal failure index (RFI), urine specific gravity (USG) and urinary protein to urinary creatinine ratio (UPC). The results demonstrated statistically significant strong negative correlations between TNF-α and systolic arterial pressure (r = -0.7246), diastolic arterial pressure (r = -0.6642) and mean arterial pressure (r = -0.7151). Serum TNF-α concentration was also statistically significantly correlated with FE(Na(+)) (r = 0.7056), UCr/SCr (r = -0.8199), USG (r = -0.8075) and duration of the disease (r = 0.6767). The results of this study show there is an increase of serum TNF-α concentration during canine babesiosis, and the increased TNF-α concentration has an influence on the development of hypotension and renal failure in canine babesiosis. This probably results from the fact that TNF-α is involved in the production of nitric oxide and induction of vasodilation and hypotension, which may cause renal ischaemia and hypoxia, and finally acute tubular necrosis and renal failure. PMID:24553975

  19. Uric acid or 1-methyl uric acid in the urinary bladder increases serum glucose, insulin, true triglyceride, and total cholesterol levels in Wistar rats.

    PubMed

    Balasubramanian, T

    2003-10-01

    In animals deprived of food for a long period, a drop in the fat mass below 5% of the total body mass results in an increase in blood glucocorticoids and uric acid levels, followed by foraging activity. Since the glucocorticoids increase the uric acid excretion, an increase in the level of uric acid in the bladder urine could be the signal for this feeding behaviour and subsequent fat storage. Accumulation of fat is associated with hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and hypercholesterolaemia as seen in the metabolic syndrome or hibernation. It is hypothesized that uric acid or its structurally related compound, 1-methyl uric acid (one of the metabolites of the methyl xanthines namely caffeine, theophylline, and theobromine present in coffee, tea, cocoa, and some drugs), can act on the urinary bladder mucosa and increases the blood glucose, insulin, triglyceride, and cholesterol levels. In rats, perfusion of the urinary bladder with saturated aqueous solution of uric acid or 1-methyl uric acid results in a significant increase in the serum levels of glucose, insulin, true triglyceride, and total cholesterol in comparison with perfusion of the bladder with distilled water at 20, 40, and 80 min. The uric acid or the 1-methyl uric acid acts on the urinary bladder mucosa and increases the serum glucose, insulin, true triglyceride, and total cholesterol levels. PMID:15241498

  20. Laboratory alcohol self-administration experiments do not increase subsequent real-life drinking in young adult social drinkers

    PubMed Central

    Sommer, Christian; Seipt, Christian; Spreer, Maik; Blümke, Toni; Markovic, Alexandra; Jünger, Elisabeth; Plawecki, Martin H.; Zimmermann, Ulrich S.

    2015-01-01

    Background While the utility of experimental free-access alcohol self-administration paradigms is well-established, little data exist addressing the question of whether study participation influences subsequent natural alcohol consumption. We here present drinking reports of young adults before and after participation in intravenous alcohol self-administration studies. Methods Timeline Follow-back (TLFB) drinking reports for the 6 weeks immediately preceding the first, and the 6 weeks after the last experimental alcohol challenge were examined from subjects completing one of two similar alcohol self-administration paradigms. In study 1, eighteen social drinkers (9 females, mean age 24.1 years) participated in 3 alcohol self-infusion sessions up to a maximum blood alcohol concentration (BAC) of 160 mg%. Study 2 involved 60 participants (30 females, mean age 18.3 years) of the Dresden Longitudinal Study on Alcohol Use in Young Adults (D-LAYA), who participated in 2 sessions of alcohol self-infusion up to a maximum BAC of 120 mg%, and a non-exposed age- matched control group of 42 (28 females, mean age 18.4 years) subjects. Results In study 1, participants reported (3.7%) fewer heavy drinking days as well as a decrease of 2.5 drinks per drinking day after study participation compared to pre-study levels (p<.05 respectively).. In study 2, alcohol-exposed participants reported 7.1% and non- alcohol-exposed controls 6.5% fewer drinking days at post-study measurement (p<.001), while percent heavy drinking days and drinks per drinking day did not differ. Conclusion These data suggest that participation in intravenous alcohol self-administration experiments does not increase subsequent real-life drinking of young adults. PMID:25903217

  1. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that

  2. Pancreatic l-Glutamine Administration Protects Pig Islets From Cold Ischemic Injury and Increases Resistance Toward Inflammatory Mediators.

    PubMed

    Brandhorst, Heide; Theisinger, Bastian; Guenther, Bernhard; Johnson, Paul R; Brandhorst, Daniel

    2016-01-01

    The isolation and transplantation of porcine islets represent a future option for the treatment of type 1 diabetic patients. Stringent product release criteria and limited availability of transgenic and specific pathogen-free pigs will essentially require processing of explanted pig pancreata in specialized, possibly remote isolation facilities, whereby pancreata are exposed to cold ischemia due to prolonged tissue transit time. In the present study we investigated whether pancreas oxygenation can be efficiently combined with an antioxidant strategy utilizing intraductal l-glutamine administration. Pig pancreata were intraductally perfused after retrieval and after cold storage in oxygen-precharged perfluorohexyloctane utilizing University of Wisconsin solution supplemented with (n = 16) or without (n = 14) 5 mmol/L l-glutamine. After isolation purified islets were subjected to extensive quality assessment. Islet recovery postpurification was significantly higher in glutamine-treated pancreata (77.0 ± 3.3% vs. 60.3 ± 6.0%, p < 0.05). Glutamine administration increased intraislet content of reduced glutathione (117.8 ± 16.5 vs. 15.9 ± 2.8 ng/ng protein, p < 0.001) associated with increased islet recovery after culture (65.8 ± 12.1% vs. 40.3 ± 11.7%, p < 0.05), enhanced glucose stimulation index (1.82 ± 0.16 vs. 1.38 ± 0.10, p < 0.05), and improved posttransplant function in diabetic nude mice (p < 0.05). Furthermore, intraductally administered glutamine increased pig islet resistance toward reactive oxygen species, nitric oxide, and high-dose proinflammatory cytokines. The present study demonstrates that quality and function of pig islets exposed to warm and cold ischemia can significantly be improved using intraductal l-glutamine administration. As the efficiency of the intraductal route may be inferior compared to intravascular administration further studies should aim on assessment of l

  3. Increased serum levels of soluble l-selectin (CD62L) in patients with active systemic lupus erythematosus (SLE)

    PubMed Central

    Font, J; Pizcueta, P; Ramos-Casals, M; Cervera, R; García-Carrasco, M; Navarro, M; Ingelmo, M; Engel, P

    2000-01-01

    The adhesion molecule l-selectin (CD62L) mediates lymphocyte recirculation and leucocyte rolling on vascular endothelium at sites of inflammation. Serum levels of soluble l-selectin (sl-selectin) were measured in patients with SLE in order to relate these levels to clinical activity and immunological parameters. An ELISA was used to detect the soluble form of human l-selectin (CD62L) in 42 patients with SLE and in 33 healthy individuals. The mean ± s.e.m. values of sl-selectin were 1285 ± 121 ng/ml for patients with SLE and 986 ± 180 ng/ml for healthy blood donors, but there was no significant difference. When patients with active SLE were analysed, higher levels of circulating sl-selectin were found when compared with patients without activity (1497 ± 167 ng/ml versus 941 ± 150 ng/ml; P = 0.028). We found a significant correlation between the levels of sl-selectin and of dsDNA antibodies (r = 0.36, P = 0.044) and between levels of sl-selectin and SLE Disease Activity Index (SLEDAI) score (r = 0.42, P = 0.003). Patients with active SLE studied cross-sectionally showed significant elevations of sl-selectin (CD62L) compared with controls. Thus, the levels of this soluble adhesion molecule correlated with active disease and levels of anti-dsDNA antibodies. PMID:10606979

  4. Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine

    PubMed Central

    Suman, Shubhankar; Kumar, Santosh; Fornace, Albert J.; Datta, Kamal

    2016-01-01

    Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as 56Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of 56Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of 56Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract. PMID:27558773

  5. Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine.

    PubMed

    Suman, Shubhankar; Kumar, Santosh; Fornace, Albert J; Datta, Kamal

    2016-01-01

    Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as (56)Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of (56)Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of (56)Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract. PMID:27558773

  6. Increased serum levels of interleukin-6 and von Willenbrand Factor in early phase of acute coronary syndrome in a young and multiethnic Malaysian population

    PubMed Central

    Tiong, Wen Ni; Fong, Alan Yean Yip; Sim, Edmund Ui Hang; Chan, Hiang Chuan; Ong, Tiong Kiam; Chang, Boon Cheng; Sim, Kui Hian

    2012-01-01

    Objective Interleukin-6 (IL6; proinflammatory marker), von Willebrand Factor (vWF; endothelial dysfunction marker) and P-selectin (platelet activation marker), may play important roles in defining the pathogenesis of vulnerable plaques in acute coronary syndrome (ACS). This study aims to investigate the expression and relationship of these markers in early phases of ACS in a young and multiethnic Malaysian population. Design Peripheral whole blood mRNA, and serum levels of IL6, vWF and P-selectin were measured in 22 patients with ACS, and in 28 controls with angiographically significant coronary artery disease without previous ACS events. Venous blood from ACS patients was obtained within 1 h of hospital admission. Results No significant differences of IL6, vWF and P-selectin mRNA levels between ACS and controls were seen. ACS patients had significantly higher serum levels of IL6 and vWF (p<0.001), compared with controls. P-selectin correlated with IL6 (r=0.697, p=0.003) and vWF (r=0.497, p=0.05) at mRNA levels, indicating a possible association between these three indices of ACS pathogenesis. Conclusions Increased serum levels of IL6 and vWF suggest that inflammation and endothelial dysfunction may play a prominent role in the pathogenesis of the disease during the early phase of ACS.

  7. Repeated cocaine administration increases B-cell leukemia/lymphoma 2 phosphorylation in the rat dorsal striatum.

    PubMed

    Ahn, Sung Min; Jang, Dong Hye; Choe, Eun Sang

    2010-01-01

    Protein phosphorylation caused by drug administration is a critical step in the regulation of behavioral alterations. This study was conducted to determine how repeated exposure to cocaine phosphorylates B-cell leukemia/lymphoma 2 (Bcl2), which may be responsible for the regulation of behavioral alterations in the rat dorsal striatum. The results revealed that repeated systemic injections of cocaine (20 mg/kg) once a day for 7 consecutive days increased the phosphorylation of Bcl2 at serine 70 (Bcl2-S70). However, this increase was reduced by the blockade of dopamine D1 receptors, group I metabotropic glutamate receptors (mGluRs), and N-methyl-D-aspartate (NMDA) receptors. In addition, elevation of behavioral locomotor activity after repeated exposure to cocaine was partially reduced by the inhibition of Bcl2. These data suggest that stimulation of dopamine D1 receptors, group I mGluRs, and NMDA receptors following repeated cocaine administration is necessary for the induction of Bcl2-S70 phosphorylation, which contributes to the expression of behavioral sensitization. PMID:19879923

  8. Decrease in pyridoxal-5'-phosphate concentration and increase in pyridoxal concentration in rat plasma by 4'-O-methylpyridoxine administration.

    PubMed

    Kobayashi, Daisuke; Yoshimura, Teruki; Johno, Atsushi; Ishikawa, Mika; Sasaki, Keiko; Wada, Keiji

    2015-07-01

    Food poisoning from Ginkgo biloba seeds can cause epilepsy because of a decrease in γ-aminobutyric acid (GABA) concentrations in the brain. We previously demonstrated that 4'-O-methylpyridoxine (MPN) is responsible for this observed toxicity of G biloba seeds; however, the mechanism for the decrease in GABA and plasma concentration profile of MPN has not been clarified. Our hypothesis is that MPN induces a decrease in vitamin B6 concentrations, resulting in a decrease in GABA concentration. This study aimed to characterize the plasma concentration profile of MPN and intrinsic vitamin B6 concentrations (pyridoxal [PL], PL-5'-phosphate [PLP], and 4-pyridoxic acid) using a rat model. Plasma concentrations of B6 vitamers after intravenous MPN administration (5 mg/kg) were determined using high-performance liquid chromatography with a fluorescence detector. The half-life of MPN (0.91 ± 0.05 hours) was shorter in rats than the previously reported value in humans. We found a significant decrease in the plasma concentration of PLP, an active form of vitamin B6, after MPN administration. We also observed an increase in plasma PL and 4-pyridoxic acid concentrations; the increase in PL concentration may be caused by either metabolism of MPN to PL or by MPN-mediated inhibition of PL kinase. The present study is the first in vivo study showing relatively rapid elimination of MPN in rats and a decrease in plasma PLP concentration caused by MPN. PMID:26092494

  9. Trans-stilbene oxide administration increased hepatic glucuronidation of morphine but decreased biliary excretion of morphine glucuronide in rats

    SciTech Connect

    Fuhrman-Lane, C.; Fujimoto, J.M.

    1982-09-01

    The effect of the inducing agent trans-stilbene oxide (TSO) on the metabolism and biliary excretion of (/sup 14/C)morphine was studied in the isolated in situ perfused rat liver. After administration of morphine by intraportal injection or by the segmented retrograde intrabiliary injection technique, the TSO-treated group showed a marked decrease in the biliary recovery of morphine as its glucuronide conjugate (morphine-3-glucuronide (MG)). However, recovery of MG in the venous outflow of the single pass perfusate was greatly increased. These findings suggested that TSO treatment enhanced the formation of MG from morphine and changed the primary route of hepatic elimination of MG. TSO treatment also decreased the excretion of morphine (as MG) in the bile of anesthetized renal-ligated rats. This decreased biliary function required several days to develop and appeared closely associated with the inductive effect of TSO. After i.v. administration of (/sup 14/C)MG itself, biliary recovery was also markedly decreased in TSO-treated rats. It is postulated that the effect of the TSO treatment led to either a decrease in canalicular transport of MG into bile or an increase in the efficiency of transfer of MG to the blood at the sinusoidal side of the hepatocyte. Regardless of the mechanism, the results indicate the need to study compartmentalization of drug transport and metabolism functions.

  10. Increased levels of IL-6, sIL-6R, and sgp130 in the aqueous humor and serum of patients with diabetic retinopathy

    PubMed Central

    Chen, Hui; Zhang, Xiongze; Liao, Nanying

    2016-01-01

    Purpose Trans-signaling of interleukin (IL)-6 through its soluble receptor (sIL-6R) is critically involved in the promotion of chronic inflammatory diseases. The aim of the present study was to estimate IL-6, sIL-6R, and soluble gp130 (sgp130, a natural antagonist of IL-6 trans-signaling) concentrations in the serum and aqueous humor (AqH) of patients with diabetic retinopathy (DR). Methods Paired AqH and serum samples were collected from 152 consecutive diabetic patients (105 with DR and 47 without DR, NDR) and 51 healthy controls. The IL-6, sIL-6R, and sgp130 concentrations were measured with multiplex bead immunoassay. Results The sgp130 concentrations in the serum and AqH were statistically significantly elevated in patients with DR compared with the NDR patients and the healthy controls (p<0.001). The sgp130 concentrations in the serum and AqH increased as the DR severity increased (p = 0.008, p<0.001, respectively). Higher serum and AqH concentrations of IL-6 and sIL-6R were also observed in patients with DR when compared with the NDR patients and the healthy controls (p<0.001). The AqH concentration of sgp130 was found to be statistically significantly correlated with sIL-6R and IL-6. Similarly, the IL-6 concentration in the AqH was statistically significantly correlated with sIL-6R (p<0.001). Elevated sgp130, sIL-6R, and IL-6 concentrations in the AqH were associated with longer disease duration and higher body mass index, plasma glucose, and glycosylated hemoglobin (HbA1c). Conclusions The sgp130, IL-6, and sIL-6R concentrations were statistically significantly elevated in patients with DR, suggesting a probable contributing role of the IL-6 trans-signaling pathway to the pathophysiology of DR. PMID:27563232

  11. Increased sexual desire with exogenous testosterone administration in men with obstructive sleep apnea: a randomized placebo-controlled study.

    PubMed

    Melehan, K L; Hoyos, C M; Yee, B J; Wong, K K; Buchanan, P R; Grunstein, R R; Liu, P Y

    2016-01-01

    Testosterone (T) deficiency, sexual dysfunction, obesity and obstructive sleep apnea (OSA) are common and often coexist. T prescriptions have increased worldwide during the last decade, including to those with undiagnosed or untreated OSA. The effect of T administration on sexual function, neurocognitive performance and quality of life in these men is poorly defined. The aim of this study was to examine the impact of T administration on sexual function, quality of life and neurocognitive performance in obese men with OSA. We also secondarily examined whether baseline T might modify the effects of T treatment by dichotomizing on baseline T levels pre-specified at 8, 11 and 13 nmol/L. This was a randomized placebo-controlled study in which 67 obese men with OSA (mean age 49 ± 1.3 years) were randomized to receive intramuscular injections of either 1000 mg T undecanoate or placebo at baseline, week 6 and week 12. All participants were concurrently enrolled in a weight loss program. General and sleep-related quality of life, neurocognitive performance and subjective sexual function were assessed before and 6, 12 and 18 weeks after therapy. T compared to placebo increased sexual desire (p = 0.004) in all men, irrespective of baseline T levels. There were no differences in erectile function, frequency of sexual attempts, orgasmic ability, general or sleep-related quality of life or neurocognitive function (all p = NS). In those with baseline T levels below 8 nmol/L, T increased vitality (p = 0.004), and reduced reports of feeling down (p = 0.002) and nervousness (p = 0.03). Our findings show that 18 weeks of T therapy increased sexual desire in obese men with OSA independently of baseline T levels whereas improvements in quality of life were evident only in those with T levels below 8 nmol/L. These small improvements would need to be balanced against potentially more serious adverse effects of T therapy on breathing. PMID:26610430

  12. Serum ceruloplasmin protein expression and activity increases in iron-deficient rats and is further enhanced by higher dietary copper intake

    PubMed Central

    Ranganathan, Perungavur N.; Lu, Yan; Jiang, Lingli; Kim, Changae

    2011-01-01

    Increases in serum and liver copper content are noted during iron deficiency in mammals, suggesting that copper-dependent processes participate during iron deprivation. One point of intersection between the 2 metals is the liver-derived, multicopper ferroxidase ceruloplasmin (Cp) that is important for iron release from certain tissues. The current study sought to explore Cp expression and activity during physiologic states in which hepatic copper loading occurs (eg, iron deficiency). Weanling rats were fed control or low iron diets containing low, normal, or high copper for ∼ 5 weeks, and parameters of iron homeostasis were measured. Liver copper increased in control and iron-deficient rats fed extra copper. Hepatic Cp mRNA levels did not change; however, serum Cp protein was higher during iron deprivation and with higher copper consumption. In-gel and spectrophotometric ferroxidase and amine oxidase assays demonstrated that Cp activity was enhanced when hepatic copper loading occurred. Interestingly, liver copper levels strongly correlated with Cp protein expression and activity. These observations support the possibility that liver copper loading increases metallation of the Cp protein, leading to increased production of the holo enzyme. Moreover, this phenomenon may play an important role in the compensatory response to maintain iron homeostasis during iron deficiency. PMID:21768302

  13. A single administration of the GnRH antagonist acyline inhibits basal and GnRH-stimulated serum testosterone concentrations in male dogs.

    PubMed

    García Romero, G; Mattioli, G; Rosa, D; Diaz, J D; Abeyá, M; Gobello, C

    2012-06-01

    The objective of this study was to describe testosterone (T) response to GnRH challenge in antagonist-treated dogs over a 30-day period. Eight mongrel dogs were randomly assigned to either the GnRH antagonist acyline 330 μg/kg sc (ACY; n = 4) or a placebo group (PLA; n = 4). The dogs were serially challenged with the GnRH agonist, buserelin 0.2 μg/kg sc on days -1, 1, 3, 7, 10, 14, 21 and 30. On these days, blood samples for T determinations were collected before (-30 min) and 60, 120 and 180 min after the agonist injection. Basal (-30 min) and post-GnRH agonist stimulation T values were compared by anova for repeated measures. Before treatments (day -1), there were no differences in basal T serum concentrations between groups (p > 0.1). After treatments, basal T showed a significant interaction between treatment and day (p < 0.05). Furthermore, when both groups were analysed independently, basal T varied in the ACY (p < 0.01) but not in the PLA group (p > 0.1). On day -1, before treatments, the stimulation tests had only a time effect (p = 0.05) although on days 1 (p < 0.01), 3 (p < 0.01), 7 (p < 0.01), 10 (p < 0.01) and 14 (p < 0.05), the response to the agonist differed between groups, becoming similar on days 21 (p > 0.05) and 30 (p > 0.05). It was concluded that, in dogs, a single administration of the GnRH antagonist prevented canine gonadal axis to physiologically respond to agonistic challenge during 14 days. PMID:22044671

  14. Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines.

    PubMed

    Boström, Elisabeth A; Kindstedt, Elin; Sulniute, Rima; Palmqvist, Py; Majster, Mirjam; Holm, Cecilia Koskinen; Zwicker, Stephanie; Clark, Reuben; Önell, Sebastian; Johansson, Ingegerd; Lerner, Ulf H; Lundberg, Pernilla

    2015-01-01

    Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-κΒ pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in

  15. Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines

    PubMed Central

    Sulniute, Rima; Palmqvist, Py; Majster, Mirjam; Holm, Cecilia Koskinen; Zwicker, Stephanie; Clark, Reuben; Önell, Sebastian; Johansson, Ingegerd; Lerner, Ulf H.; Lundberg, Pernilla

    2015-01-01

    Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-κΒ pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in

  16. Acute Administration of Branched-Chain Amino Acids Increases the Pro-BDNF/Total-BDNF Ratio in the Rat Brain.

    PubMed

    Scaini, Giselli; Morais, Meline O S; Furlanetto, Camila B; Kist, Luiza W; Pereira, Talita C B; Schuck, Patrícia F; Ferreira, Gustavo C; Pasquali, Matheus A B; Gelain, Daniel P; Moreira, José Cláudio F; Bogo, Maurício R; Streck, Emilio L

    2015-05-01

    Maple syrup urine disease (MSUD) is caused by an inborn error in metabolism resulting from a deficiency in the branched-chain α-keto acid dehydrogenase complex activity. This blockage leads to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine, as well as their corresponding α-keto acids and α-hydroxy acids. High levels of BCAAs are associated with neurological dysfunction and the role of pro- and mature brain-derived neurotrophic factor (BDNF) in the neurological dysfunction of MSUD is still unclear. Thus, in the present study we investigated the effect of an acute BCAA pool administration on BDNF levels and on the pro-BDNF cleavage-related proteins S100A10 and tissue plasminogen activator (tPA) in rat brains. Our results demonstrated that acute Hyper-BCAA (H-BCAA) exposure during the early postnatal period increases pro-BDNF and total-BDNF levels in the hippocampus and striatum. Moreover, tPA levels were significantly decreased, without modifications in the tPA transcript levels in the hippocampus and striatum. On the other hand, the S100A10 mRNA and S100A10 protein levels were not changed in the hippocampus and striatum. In the 30-day-old rats, we observed increased pro-BDNF, total-BDNF and tPA levels only in the striatum, whereas the tPA and S100A10 mRNA expression and the immunocontent of S100A10 were not altered. In conclusion, we demonstrated that acute H-BCAA administration increases the pro-BDNF/total-BDNF ratio and decreases the tPA levels in animals, suggesting that the BCAA effect may depend, at least in part, on changes in BDNF post-translational processing. PMID:25681161

  17. Levofloxacin increases the effect of serum deprivation on anoikis of rat nucleus pulposus cells via Bax/Bcl-2/caspase-3 pathway.

    PubMed

    Yang, Si-Dong; Bai, Zhi-Long; Zhang, Feng; Ma, Lei; Yang, Da-Long; Ding, Wen-Yuan

    2014-12-01

    Levofloxacin, a fluoroquinolone, is a widely-used and effective antibiotic. However, various adverse side effects are associated with levofloxacin. The purpose of this study was to further explore the effects of levofloxacin on rat nucleus pulposus cells (NPCs). Inverted phase-contrast microscopy, flow cytometry and caspase-3 activity assays were used and revealed that serum deprivation induced apoptosis, which was markedly increased by levofloxacin in a dose-dependent manner. Simultaneously, levofloxacin decreased cell binding to type II collagen (COL2). Thus, levofloxacin-induced apoptosis exhibits characteristics of anoikis, the process by which cell death is triggered by separation from the extracellular matrix, which contains COL2. Furthermore, real-time quantitative RT-PCR was used to further confirm that levofloxacin downregulates COL2 expression in a dose-dependent manner. At last, western blot was used to find that levofloxacin increased the ratio of Bax/Bcl-2 and active caspase-3 in a dose-dependent manner. Levofloxacin therefore increases the effects of serum deprivation on anoikis by downregulating COL2 in rat NPCs in vitro via Bax/Bcl-2/caspase-3 pathway. This research provides a novel insight into the mechanisms of levofloxacin-induced toxicity and may potentially lead to a better understanding of the clinical effects of levofloxacin, especially in terms of intervertebral disc degeneration. PMID:25224805

  18. Oral adenosine-5’-triphosphate (ATP) administration increases blood flow following exercise in animals and humans

    PubMed Central

    2014-01-01

    Introduction Extracellular adenosine triphosphate (ATP) stimulates vasodilation by binding to endothelial ATP-selective P2Y2 receptors; a phenomenon, which is posited to be accelerated during exercise. Herein, we used a rat model to examine how different dosages of acute oral ATP administration affected the femoral blood flow response prior to, during, and after an exercise bout. In addition, we performed a single dose chronic administration pilot study in resistance trained athletes. Methods Animal study: Male Wistar rats were gavage-fed the body surface area, species adjusted human equivalent dose (HED) of either 100 mg (n=4), 400 mg (n=4), 1,000 mg (n=5) or 1,600 mg (n=5) of oral ATP as a disodium salt (Peak ATP®, TSI, Missoula, MT). Rats that were not gavage-fed were used as controls (CTL, n=5). Blood flow was monitored continuously: a) 60 min prior to, b) during and c) 90 min following an electrically-evoked leg-kicking exercise. Human Study: In a pilot study, 12 college-aged resistance-trained subjects were given 400 mg of ATP (Peak ATP®, TSI, Missoula, MT) daily for 12 weeks, and prior to an acute arm exercise bout at weeks 1, 4, 8, and 12. Ultrasonography-determined volumetric blood flow and vessel dilation in the brachial artery was measured at rest, at rest 30 minutes after supplementation, and then at 0, 3, and 6 minutes after the exercise. Results Animal Study: Rats fed 1,000 mg HED demonstrated significantly greater recovery blood flow (p < 0.01) and total blood flow AUC values (p < 0.05) compared to CTL rats. Specifically, blood flow was elevated in rats fed 1,000 mg HED versus CTL rats at 20 to 90 min post exercise when examining 10-min blood flow intervals (p < 0.05). When examining within-group differences relative to baseline values, rats fed the 1,000 mg and 1,600 mg HED exhibited the most robust increases in blood flow during exercise and into the recovery period. Human study: At weeks 1, 8, and 12, ATP supplementation significantly increased

  19. Increased Phosphorylation of extracellular signal-regulated kinase in trigeminal nociceptive neurons following propofol administration in rats

    PubMed Central

    Shoda, Emi; Kitagawa, Junichi; Suzuki, Ikuko; Nitta-Kubota, Ieko; Miyamoto, Makiko; Tsuboi, Yoshiyuki; Kondo, Masahiro; Masuda, Yuji; Oi, Yoshiyuki; Ren, Ke; Iwata, Koichi

    2009-01-01

    Although propofol (PRO) is widely used in clinic as a hypnotic agent, the underlying mechanisms of its action on pain pathways is still unknown. Sprague-Dawley rats were assigned to receive PRO or pentobarbital (PEN) and were divided into two groups as LIGHT and DEEP hypnotic levels based on the EEG analysis. Rats in each hypnotic level received capsaicin injection into the face and phosphorylated extracellular regulated-kinase (pERK) immunohistochemistry were performed in subnucleus caudalis (Vc) and upper cervical spinal cord. A large number of pERK-like immunoreactive (LI) cells was observed in the trigeminal spinal subnuclei interpolaris and caudalis transition zone (Vi/Vc), middle Vc and transition zone between Vc and upper cervical spinal cord (Vc/C2) in the rats with PEN or PRO administration following capsaicin injection into the whisker pad region. The number of pERK-LI cells in Vi/Vc, middle Vc and Vc/C2 was significantly larger in rats with PRO injection than those with PEN injection. The number of pERK-LI cells was increased following an increase in the dose of PRO but not in PEN. The pERK-LI cells were dominantly distributed in the Vi/Vc, middle Vc and Vc/C2 after the bolus injections of PRO. The expression of pERK-LI cells was depressed after the intravenous lidocaine application before PRO injection. The present findings suggested that PRO induced an enhancement of the activity of trigeminal nociceptive pathways through nociceptors innervating the venous structure, as indicated by a lidocaine-sensitive increase in pERK. This may explain deep pain around the injection regions during intravenous bolus injection of PRO. Perspective: The effect of propofol administration on ERK phosphorylation in the subregions of the spinal trigeminal complex and upper cervical spinal cord neurons were precisely analyzed in rats with PRO injection. A large number of pERK-LI cells was observed following intravenous PRO administration, suggesting an enhancement of

  20. Repeated oral administration of capsaicin increases anxiety-like behaviours with prolonged stress-response in rats.

    PubMed

    Choi, Y-J; Kim, J Y; Yoo, S B; Lee, J-H; Jahng, J W

    2013-09-01

    This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02 percent capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy counts and rostral grooming were significantly increased, and caudal grooming decreased, in capsaicin-treated rats during the ambulatory activity test. In elevated plus maze test, not only the time spent in open arms but also the percent arm entry into open arms was reduced in capsaicin-treated rats compared with control rats. In forced swim test, although swimming duration was decreased, struggling increased in the capsaicin group, immobility duration did not differ between the groups. Repeated oral capsaicin did not affect the basal levels of plasma corticosterone; however, the stress-induced elevation of plasma corticosterone was prolonged in capsaicin treated rats. Oral capsaicin exposure significantly increased c-Fos expression not only in the nucleus tractus of solitarius but also in the paraventricular nucleus. Results suggest that repeated oral exposure to capsaicin increases anxiety-like behaviours in rats, and dysfunction of the hypothalamic-pituitary-adrenal axis may play a role in its pathophysiology. PMID:23938388

  1. The cytoplasmic C-terminus of polycystin-1 increases cell proliferation in kidney epithelial cells through serum-activated and Ca{sup 2+}-dependent pathway(s)

    SciTech Connect

    Manzati, Elisa; Aguiari, Gianluca; Banzi, Manuela; Manzati, Michele; Selvatici, Rita; Falzarano, Sofia; Maestri, Iva; Pinton, Paolo; Rizzuto, Rosario; Senno, Laura del . E-mail: sen@unife.it

    2005-04-01

    Polycystin-1 (PC1) is a large transmembrane protein important in renal differentiation and defective in most cases of autosomal dominant polycystic kidney disease (ADPKD), a common cause of renal failure in adults. Although the genetic basis of ADPKD has been elucidated, molecular and cellular mechanisms responsible for the dysregulation of epithelial cell growth in ADPKD cysts are still not well defined. We approached this issue by investigating the role of the carboxyl cytoplasmic domain of PC1 involved in signal transduction on the control of kidney cell proliferation. Therefore, we generated human HEK293 cells stably expressing the PC1 cytoplasmic tail as a membrane targeted TrkA-PC1 chimeric receptor protein (TrkPC1). We found that TrkPC1 increased cell proliferation through an increase in cytoplasmic Ca{sup 2+} levels and activation of PKC{alpha}, thereby upregulating D1 and D3 cyclin, downregulating p21{sup waf1} and p27{sup kip1} cyclin inhibitors, and thus inducing cell cycle progression from G0/G1 to the S phase. Interestingly, TrkPC1-dependent Ca{sup 2+} increase and PKC{alpha} activation are not constitutive, but require serum factor(s) as parallel component. In agreement with this observation, a significant increase in ERK1/2 phosphorylation was observed. Consistently, inhibitors specifically blocking either PKC{alpha} or ERK1/2 prevented the TrkPC1-dependent proliferation increase. NGF, the TrkA ligand, blocked this increase. We propose that in kidney epithelial cells the overexpression of PC1 C-terminus upregulates serum-evoked intracellular Ca{sup 2+} by counteracting the growth-suppression activity of endogenous PC1 and leading to an increase in cell proliferation.

  2. Serum gamma glutamyl transferase as a specific indicator of bile duct lesions in the rat liver.

    PubMed Central

    Leonard, T. B.; Neptun, D. A.; Popp, J. A.

    1984-01-01

    Serum gamma-glutamyl transferase (GGT), a marker of hepatic injury used extensively in humans, has been used rarely in rats because its specificity has not been previously defined. Studies were designed for investigation of the specificity of serum GGT activity with the use of cell type specific hepatotoxicants in Fischer 344 rats. Single necrogenic doses of CCl4, allyl alcohol (AA), and alpha-naphthylisothiocyanate (ANIT) were used to produce cell specific injury in centrilobular hepatocytes, periportal hepatocytes, and bile duct cells, respectively. Administration of CCl4 markedly increased serum activities of alanine aminotransferase (ALT), alkaline phosphatase (AP), and serum bile acid concentrations within 24 hours but had no effect on serum GGT activity. ANIT treatment increased serum GGT and AP activities and bile acid concentration 24 hours following administration. Allyl alcohol administration increased serum ALT activity but had no effect on GGT activity. Administration of ANIT in the diet at 0.01%, 0.022%, 0.047%, and 0.1% for 2, 4, and 6 weeks produced dose- and time-dependent increases in serum GGT activity which strongly correlated with quantitative increases in hepatic bile duct volume, which was determined morphometrically. These observations support the use of serum GGT activity in the rat as diagnostic of bile duct cell necrosis when increases are detected shortly after the insult and as an indicator of possible bile duct hyperplasia. Images Figure 1 Figure 3 PMID:6147091

  3. Serum gamma glutamyl transferase as a specific indicator of bile duct lesions in the rat liver.

    PubMed

    Leonard, T B; Neptun, D A; Popp, J A

    1984-08-01

    Serum gamma-glutamyl transferase (GGT), a marker of hepatic injury used extensively in humans, has been used rarely in rats because its specificity has not been previously defined. Studies were designed for investigation of the specificity of serum GGT activity with the use of cell type specific hepatotoxicants in Fischer 344 rats. Single necrogenic doses of CCl4, allyl alcohol (AA), and alpha-naphthylisothiocyanate (ANIT) were used to produce cell specific injury in centrilobular hepatocytes, periportal hepatocytes, and bile duct cells, respectively. Administration of CCl4 markedly increased serum activities of alanine aminotransferase (ALT), alkaline phosphatase (AP), and serum bile acid concentrations within 24 hours but had no effect on serum GGT activity. ANIT treatment increased serum GGT and AP activities and bile acid concentration 24 hours following administration. Allyl alcohol administration increased serum ALT activity but had no effect on GGT activity. Administration of ANIT in the diet at 0.01%, 0.022%, 0.047%, and 0.1% for 2, 4, and 6 weeks produced dose- and time-dependent increases in serum GGT activity which strongly correlated with quantitative increases in hepatic bile duct volume, which was determined morphometrically. These observations support the use of serum GGT activity in the rat as diagnostic of bile duct cell necrosis when increases are detected shortly after the insult and as an indicator of possible bile duct hyperplasia. PMID:6147091

  4. Administration of Myelin Basic Protein Peptides Encapsulated in Mannosylated Liposomes Normalizes Level of Serum TNF-α and IL-2 and Chemoattractants CCL2 and CCL4 in Multiple Sclerosis Patients

    PubMed Central

    Lomakin, Yakov; Belogurov, Alexey; Glagoleva, Irina; Stepanov, Alexey; Zakharov, Konstantin; Okunola, John; Smirnov, Ivan; Genkin, Dmitry; Gabibov, Alexander

    2016-01-01

    We have previously shown that immunodominant MBP peptides encapsulated in mannosylated liposomes (Xemys) effectively suppressed experimental allergic encephalomyelitis (EAE). Within the frames of the successfully completed phase I clinical trial, we investigated changes in the serum cytokine profile after Xemys administration in MS patients. We observed a statistically significant decrease of MCP-1/CCL2, MIP-1β/CCL4, IL-7, and IL-2 at the time of study completion. In contrast, the serum levels of TNF-α were remarkably elevated. Our data suggest that the administration of Xemys leads to a normalization of cytokine status in MS patients to values commonly reported for healthy subjects. These data are an important contribution for the upcoming Xemys clinical trials. PMID:27239100

  5. Neuropeptide Y administration acutely increases hypothalamic corticotropin-releasing factor immunoreactivity: lack of effect in other rat brain regions

    SciTech Connect

    Haas, D.A.; George, S.R.

    1987-12-21

    The effect of acute central administration of Neuropeptide Y (NPY) to adult male rats on the brain content of corticotropin-releasing factor immunoreactivity (CRF-ir) was investigated. The brain regions studied included frontal cortex, hippocampus, medulla-pons, midbrain-thalamus, cerebellum, neurointermediate lobe of pituitary, median eminence and the remaining hypothalamus. CRF-ir was determined in each of these regions using radioimmunoassay specific for rat CRF. CRF-ir was found to be significantly increased in the major site of CRF localization in the brain, the hypothalamus, in NPY-treated rats as compared to vehicle-treated controls either 15 minutes (p<0.025) or 45 minutes (p<0.005) post-injection. This increase was localized to the median eminence (p<0.05 after 15 minutes, p<0.01 after 45 minutes). No statistically significant differences were noted in any of the other brain regions assessed. Plasma adrenocorticotropin levels were also found to increase following NPY treatment, an effect which became significant after 45 minutes (p<0.05). These data show that NPY can alter the content of hypothalamic CRF and may play a role in its regulation. 33 references, 4 figures.

  6. Perceptual distortions and delusional thinking following ketamine administration are related to increased pharmacological MRI signal changes in the parietal lobe.

    PubMed

    Stone, James; Kotoula, Vasileia; Dietrich, Craige; De Simoni, Sara; Krystal, John H; Mehta, Mitul A

    2015-09-01

    Ketamine produces effects in healthy humans that resemble the positive, negative and cognitive symptoms of schizophrenia. We investigated the effect of ketamine administration on brain activity as indexed by blood-oxygen-level-dependent (BOLD) signal change response, and its relationship to ketamine-induced subjective changes, including perceptual distortion. Thirteen healthy participants volunteered for the study. All underwent a 15-min functional MRI acquisition with a ketamine infusion commencing after 5 min (approx 0.26 mg/kg over 20s followed by an infusion of approx. 0.42 mg/kg/h). Following the scan, participants self-rated ketamine-induced effects using the Psychotomimetic States Inventory. Ketamine led to widespread cortical and subcortical increases in BOLD response (FWE-corrected p < 0.01). Self-rated perceptual distortions and delusional thoughts correlated with increased BOLD response in the paracentral lobule (FWE-corrected p < 0.01). The findings suggest that BOLD increases in parietal cortices reflect ketamine effects on circuits that contribute to its capacity to produce perceptual alterations and delusional interpretations. PMID:26152321

  7. Prolonged administration of antidepressant drugs leads to increased binding of [(3)H]MPEP to mGlu5 receptors.

    PubMed

    Nowak, Gabriel; Pomierny-Chamioło, Lucyna; Siwek, Agata; Niedzielska, Ewa; Pomierny, Bartosz; Pałucha-Poniewiera, Agnieszka; Pilc, Andrzej

    2014-09-01

    Metabotropic glutamate 5 (mGlu5) receptors are functionally connected with NMDA receptors. The antidepressant activity of the NMDA receptor antagonist ketamine in both preclinical and clinical studies, along with the antidepressant-like activities of negative allosteric modulators (NAMs) of mGlu5, led us to investigate if prolonged administration of various antidepressant drugs or the mGlu5 NAM, MTEP, causes changes in mGlu5 receptor availability or protein expression or in expression of Homer proteins in the rat brain. Our results clearly show that prolonged treatment with antidepressants with various mechanisms of action (such as escitalopram, reboxetine, milnacipran, moclobemide and imipramine) or with MTEP led to significant increases in [(3)H]MPEP binding in homogenates of the hippocampus and/or cerebral cortex. Increases in mGlu5 expression were also observed, though they did not always parallel the increase in binding. The results indicate that adaptive up-regulation of mGlu5 receptors may be a common change induced by antidepressant drugs. PMID:24796254

  8. Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys

    PubMed Central

    Graham, James L.; Morton, Gregory J.; Bales, Karen L.; Schwartz, Michael W.; Baskin, Denis G.; Havel, Peter J.

    2014-01-01

    Despite compelling evidence that oxytocin (OT) is effective in reducing body weight (BW) in diet-induced obese (DIO) rodents, studies of the effects of OT in humans and rhesus monkeys have primarily focused on noningestive behaviors. The goal of this study was to translate findings in DIO rodents to a preclinical translational model of DIO. We tested the hypothesis that increased OT signaling would reduce BW in DIO rhesus monkeys by inhibiting food intake and increasing energy expenditure (EE). Male DIO rhesus monkeys from the California National Primate Research Center were adapted to a 12-h fast and maintained on chow and a daily 15% fructose-sweetened beverage. Monkeys received 2× daily subcutaneous vehicle injections over 1 wk. We subsequently identified doses of OT (0.2 and 0.4 mg/kg) that reduced food intake and BW in the absence of nausea or diarrhea. Chronic administration of OT for 4 wk (0.2 mg/kg for 2 wk; 0.4 mg/kg for 2 wk) reduced BW relative to vehicle by 3.3 ± 0.4% (≈0.6 kg; P < 0.05). Moreover, the low dose of OT suppressed 12-h chow intake by 26 ± 7% (P < 0.05). The higher dose of OT reduced 12-h chow intake by 27 ± 5% (P < 0.05) and 8-h fructose-sweetened beverage intake by 18 ± 8% (P < 0.05). OT increased EE during the dark cycle by 14 ± 3% (P < 0.05) and was associated with elevations of free fatty acids and glycerol and reductions in triglycerides suggesting increased lipolysis. Together, these data suggest that OT reduces BW in DIO rhesus monkeys through decreased food intake as well as increased EE and lipolysis. PMID:25540103

  9. Exposure to Ionizing Radiation Causes Long-Term Increase in Serum Estradiol and Activation of PI3K-Akt Signaling Pathway in Mouse Mammary Gland

    SciTech Connect

    Suman, Shubhankar; Johnson, Michael D.; Fornace, Albert J.; Datta, Kamal

    2012-10-01

    Purpose: Exposure to ionizing radiation is an established risk factor for breast cancer. Radiation exposure during infancy, childhood, and adolescence confers the highest risk. Although radiation is a proven mammary carcinogen, it remains unclear where it acts in the complex multistage process of breast cancer development. In this study, we investigated the long-term pathophysiologic effects of ionizing radiation at a dose (2 Gy) relevant to fractionated radiotherapy. Methods and Materials: Adolescent (6-8 weeks old; n = 10) female C57BL/6J mice were exposed to 2 Gy total body {gamma}-radiation, the mammary glands were surgically removed, and serum and urine samples were collected 2 and 12 months after exposure. Molecular pathways involving estrogen receptor-{alpha} (ER{alpha}) and phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling were investigated by immunohistochemistry and Western blot. Results: Serum estrogen and urinary levels of the oncogenic estrogen metabolite (16{alpha}OHE1) were significantly increased in irradiated animals. Immunostaining for the cellular proliferative marker Ki-67 and cyclin-D1 showed increased nuclear accumulation in sections of mammary glands from irradiated vs. control mice. Marked increase in p85{alpha}, a regulatory sub-unit of the PI3K was associated with increase in Akt, phospho-Akt, phospho-BAD, phospho-mTOR, and c-Myc in irradiated samples. Persistent increase in nuclear ER{alpha} in mammary tissues 2 and 12 months after radiation exposure was also observed. Conclusions: Taken together, our data not only support epidemiologic observations associating radiation and breast cancer but also, specify molecular events that could be involved in radiation-induced breast cancer.

  10. 1'-Acetoxychavicol acetate ameliorates age-related spatial memory deterioration by increasing serum ketone body production as a complementary energy source for neuronal cells.

    PubMed

    Kojima-Yuasa, Akiko; Yamamoto, Tomiya; Yaku, Keisuke; Hirota, Shiori; Takenaka, Shigeo; Kawabe, Kouichi; Matsui-Yuasa, Isao

    2016-09-25

    1'-Acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Alpinia galangal. Here, we examined the effect of ACA on learning and memory in senescence-accelerated mice prone 8 (SAMP8). In mice that were fed a control diet containing 0.02% ACA for 25 weeks, the learning ability in the Morris water maze test was significantly enhanced in comparison with mice that were fed the control diet alone. In the Y-maze test, SAMP8 mice showed decreased spontaneous alterations in comparison with senescence-accelerated resistant/1 (SAMR1) mice, a homologous control, which was improved by ACA pretreatment. Serum metabolite profiles were obtained by GC-MS analysis, and each metabolic profile was plotted on a 3D score plot. Based upon the diagram, it can be seen that the distribution areas for the three groups were completely separate. Furthermore, the contents of β-hydroxybutyric acid and palmitic acid in the serum of SAMP8-ACA mice were higher than those of SAMP8-control mice and SAMR1-control mice. We also found that SAMR1 mice did not show histological abnormalities, whereas histological damage in the CA1 region of the hippocampus in SAMP8-control mice was observed. However, SAMP8-ACA mice were observed in a similar manner as SAMR1 mice. These findings confirm that ACA increases the serum concentrations of β-hydroxybutyric acid and palmitic acid levels and thus these fuels might contribute to the maintenance of the cognitive performance of SAMP8 mice. PMID:27481192

  11. [Serum immunoglobulin titer of IgA, IgG and IgM during short- and long-term administration of contraceptive hormones].

    PubMed

    Klinger, G; Schubert, H; Stelzner, A; Krause, G; Carol, W

    1978-01-01

    The effect of oral contraceptive use on serum immunoglobulin levels was studied in 82 women who used various combination preparations over a 24 cycle period. IgA, IgM, and IgG concentrations all fell markedly during the first cycle of use, but by the end of the observation period there was no significant deviation from the original levels. The preparation Deposiston caused the greatest decline in serum immunoglobulin levels. PMID:668500

  12. Increased intravenous morphine self-administration following Roux-en-Y gastric bypass in dietary obese rats.

    PubMed

    Biegler, Jessica M; Freet, Christopher S; Horvath, Nelli; Rogers, Ann M; Hajnal, Andras

    2016-05-01

    Roux-en-Y gastric bypass (RYGB) surgery is a commonly performed and very effective method to achieve significant, long-term weight loss. Opioid analgesics are primarily used to manage postoperative pain as fewer alternative medication options are available for bariatric surgery patients than for the general population. Recent clinical studies support a greater risk for substance use following bariatric surgery, including an increased use of opioid medications. The present study is the first to study morphine self-administration in a rat model of RYGB. High fat diet-induced obese (HFD-DIO) rats underwent RYGB (n=14) or sham-surgery with ad libitum HFD (SHAM, n=14) or a restricted amount that resulted in weight matched to the RYGB cohort (SHAM-WM, n=8). An additional normal-diet (ND, n=7), intact (no surgery) group of rats was included. Two months after the surgeries, rats were fitted with jugular catheters and trained on a fixed ratio-2 lick task to obtain morphine intravenously. Both morphine-seeking (number of licks on an empty spout to obtain morphine infusion) and consumption (number of infusion) were significantly greater in RYGB than any control group beginning on day 3 and reached a two-fold increase over a period of two weeks. These findings demonstrate that RYGB increases motivation for taking morphine and that this effect is independent of weight loss. Further research is warranted to reveal the underlying mechanisms and to determine whether increased morphine use represents a risk for opioid addiction following RYGB. Identifying risk factors preoperatively could help with personalized postoperative care to prevent opioid abuse and addiction. PMID:26304761

  13. Lithium Administration to Preadolescent Rats Causes Long-Lasting Increases in Anxiety-Like Behavior and Has Molecular Consequences

    PubMed Central

    Youngs, Rachael M.; Chu, Melissa S.; Meloni, Edward G.; Naydenov, Alipi; Carlezon, William A.; Konradi, Christine

    2014-01-01

    Lithium (Li) is frequently used in the treatment of bipolar disorder (BPD), a debilitating condition that is increasingly diagnosed in children and adolescents. Because the symptoms of BPD in children are different from the typical symptoms in adulthood and have significant overlap with other childhood psychiatric disorders, this disorder is notoriously difficult to diagnose. This raises the possibility that some children not affected by BPD are treated with Li during key periods of brain development. The objective of this investigation was to examine the long-term effects of Li on the developing brain via a series of behavioral and molecular studies in rats. Rat pups were reared on Li chow for 3 weeks. Parallel groups were tested while on Li chow or 2 and 6 weeks after discontinuation of treatment. We found increased measures of anxiety-like behavior at all times tested. Gene microarray studies of the amygdala revealed that Li affected the expression of gene transcripts of the synapse and the cytoskeleton, suggesting that the treatment induced synaptic adjustments. Our study indicates that Li can alter the trajectory of brain development. Although the effects of Li on the normal brain seems unfavorable, effects on the abnormal brain cannot be determined from these studies alone and may well be therapeutic. Our results indicate that Li administration to the normal brain has the potential for lasting adverse effects. PMID:16738246

  14. Increasing Vero viable cell densities for yellow fever virus production in stirred-tank bioreactors using serum-free medium.

    PubMed

    Mattos, Diogo A; Silva, Marlon V; Gaspar, Luciane P; Castilho, Leda R

    2015-08-20

    In this work, changes in Vero cell cultivation methods have been employed in order to improve cell growth conditions to obtain higher viable cell densities and to increase viral titers. The propagation of the 17DD yellow fever virus (YFV) in Vero cells grown on Cytodex I microcarriers was evaluated in 3-L bioreactor vessels. Prior to the current changes, Vero cells were repeatedly displaying insufficient microcarrier colonization. A modified cultivation process with four changes has resulted in higher cell densities and higher virus titers than previously observed for 17DD YFV. PMID:25930117

  15. Increased serum NKG2D-ligands and downregulation of NKG2D in peripheral blood NK cells of patients with major burns.

    PubMed

    Haik, Josef; Nardini, Gil; Goldman, Noga; Galore-Haskel, Gilli; Harats, Moti; Zilinsky, Isaac; Weissman, Oren; Schachter, Jacob; Winkler, Eyal; Markel, Gal

    2016-01-19

    Immune suppression following major thermal injury directly impacts the recovery potential. Limited data from past reports indicate that natural killer cells might be suppressed due to a putative soluble factor that has remained elusive up to date. Here we comparatively study cohorts of patients with Major and Non-Major Burns as well as healthy donors. MICB and ULBP1 are stress ligands of NKG2D that can be induced by heat stress. Remarkably, serum concentration levels of MICB and ULBP1 are increased by 3-fold and 20-fold, respectively, already within 24h post major thermal injury, and are maintained high for 28 days. In contrast, milder thermal injuries do not similarly enhance the serum levels of MICB and ULBP1. This kinetics coincides with a significant downregulation of NKG2D expression among peripheral blood NK cells. Downregulation of NKG2D by high concentration of soluble MICB occurs in cancer patients and during normal pregnancy due to over production by cancer cells or extravillous trophoblasts, respectively, as an active immune-evasion mechanism. In burn patients this seems an incidental outcome of extensive thermal injury, leading to reduced NKG2D expression. Enhanced susceptibility of these patients to opportunistic viral infections, particularly herpes viruses, could be explained by the reduced NKG2D expression. Further studies are warranted for translation into innovative diagnostic or therapeutic technologies. PMID:26745675

  16. Increased serum NKG2D-ligands and downregulation of NKG2D in peripheral blood NK cells of patients with major burns

    PubMed Central

    Haik, Josef; Nardini, Gil; Goldman, Noga; Galore-Haskel, Gilli; Harats, Moti; Zilinsky, Isaac; Weissman, Oren; Schachter, Jacob; Winkler, Eyal; Markel, Gal

    2016-01-01

    Immune suppression following major thermal injury directly impacts the recovery potential. Limited data from past reports indicate that natural killer cells might be suppressed due to a putative soluble factor that has remained elusive up to date. Here we comparatively study cohorts of patients with Major and Non-Major Burns as well as healthy donors. MICB and ULBP1 are stress ligands of NKG2D that can be induced by heat stress. Remarkably, serum concentration levels of MICB and ULBP1 are increased by 3-fold and 20-fold, respectively, already within 24h post major thermal injury, and are maintained high for 28 days. In contrast, milder thermal injuries do not similarly enhance the serum levels of MICB and ULBP1. This kinetics coincides with a significant downregulation of NKG2D expression among peripheral blood NK cells. Downregulation of NKG2D by high concentration of soluble MICB occurs in cancer patients and during normal pregnancy due to over production by cancer cells or extravillous trophoblasts, respectively, as an active immune-evasion mechanism. In burn patients this seems an incidental outcome of extensive thermal injury, leading to reduced NKG2D expression. Enhanced susceptibility of these patients to opportunistic viral infections, particularly herpes viruses, could be explained by the reduced NKG2D expression. Further studies are warranted for translation into innovative diagnostic or therapeutic technologies. PMID:26745675

  17. Administration of a non-NMDA antagonist, GYKI 52466, increases excitotoxic Purkinje cell degeneration caused by ibogaine.

    PubMed

    O'Hearn, E; Molliver, M E

    2004-01-01

    Ibogaine is a tremorigenic hallucinogen that has been proposed for clinical use in treating addiction. We previously reported that ibogaine, administered systemically, produces degeneration of a subset of Purkinje cells in the cerebellum, primarily within the vermis. Ablation of the inferior olive affords protection against ibogaine-induced neurotoxicity leading to the interpretation that ibogaine itself is not directly toxic to Purkinje cells. We postulated that ibogaine produces sustained excitation of inferior olivary neurons that leads to excessive glutamate release at climbing fiber terminals, causing subsequent excitotoxic injury to Purkinje cells. The neuronal degeneration induced by ibogaine provides an animal model for studying excitotoxic injury in order to analyze the contribution of glutamate receptors to this injury and to evaluate neuroprotective strategies. Since non-N-methyl-D-aspartate (NMDA) receptors mediate Purkinje cell excitation by climbing fibers, we hypothesized that 1-4-aminophenyl-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI-52466), which antagonizes non-NMDA receptors, may have a neuroprotective effect by blocking glutamatergic excitation at climbing fiber synapses. To test this hypothesis, rats were administered systemic ibogaine plus GYKI-52466 and the degree of neuronal injury was analyzed in cerebellar sections. The results indicate that the AMPA antagonist GYKI-52466 (10 mg/kg i.p. x 3) does not protect against Purkinje cell injury at the doses used. Rather, co-administration of GYKI-52466 with ibogaine produces increased toxicity evidenced by more extensive Purkinje cell degeneration. Several hypotheses that may underlie this result are discussed. Although the reason for the increased toxicity found in this study is not fully explained, the present results show that a non-NMDA antagonist can produce increased excitotoxic injury under some conditions. Therefore, caution should be exercised before employing glutamate

  18. Subchronic administration of riparin III induces antidepressive-like effects and increases BDNF levels in the mouse hippocampus.

    PubMed

    Vasconcelos, Auriana S; Oliveira, Iris C M; Vidal, Laura T M; Rodrigues, Gabriel C; Gutierrez, Stanley J C; Barbosa-Filho, José M; Vasconcelos, Silvânia M M; de França Fonteles, Marta M; Gaspar, Danielle M; de Sousa, Francisca C F

    2015-08-01

    Riparin III (Rip III) is an alcamide isolated from Aniba riparia that has presented effects of antidepressant and anxiolytic activities in acute stress behavioral models. The trial's goal was to investigate the activity of Rip III in mice exposed to corticosterone-induced chronic depression model. Swiss female mice, 22-25 g, were distributed in following experimental groups: control group (vehicle1: saline containing 0.1% dimethyl sulfoxide and 0.1% Tween-80, SC+ vehicle 2: distilled water emulsified with 2% Tween-80, PO); stressed group (corticosterone, 20 mg/kg, SC, + vehicle 2, orally); Rip III group (50 mg/kg, orally); and fluvoxamine (Flu) group (50 mg/kg, orally). The mice were exposed to the behavioral tests, and posteriorly, Brain-derived neurotrophic factor protein levels were assessed in hippocampal samples. Statistical analysis of the data was performed by one-way anova, followed by Newman-Keuls test. Both administrations of Rip III and Flu significantly reduced the immobility time in tail suspension and forced swimming tests after 21 days without affecting locomotor function. There was also an increase in BDNF protein levels in the mice hippocampus. These findings further support the hypothesis that Rip III could be a new pharmacological target for the treatment of mood disorders. PMID:25846646

  19. Serum- and Glucocorticoid-induced Protein Kinase 1 (SGK1) Increases the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Airway Epithelial Cells by Phosphorylating Shank2E Protein*

    PubMed Central

    Koeppen, Katja; Coutermarsh, Bonita A.; Madden, Dean R.; Stanton, Bruce A.

    2014-01-01

    The glucocorticoid dexamethasone increases cystic fibrosis transmembrane conductance regulator (CFTR) abundance in human airway epithelial cells by a mechanism that requires serum- and glucocorticoid-induced protein kinase 1 (SGK1) activity. The goal of this study was to determine whether SGK1 increases CFTR abundance by phosphorylating Shank2E, a PDZ domain protein that contains two SGK1 phosphorylation consensus sites. We found that SGK1 phosphorylates Shank2E as well as a peptide containing the first SGK1 consensus motif of Shank2E. The dexamethasone-induced increase in CFTR abundance was diminished by overexpression of a dominant-negative Shank2E in which the SGK1 phosphorylation sites had been mutated. siRNA-mediated reduction of Shank2E also reduced the dexamethasone-induced increase in CFTR abundance. Taken together, these data demonstrate that the glucocorticoid-induced increase in CFTR abundance requires phosphorylation of Shank2E at an SGK1 consensus site. PMID:24811177

  20. Increased B7H4 tissue expression correlates with high CA19.9 serum levels and a worse prognosis of pancreatic adenocarcinoma.

    PubMed

    Tsiaousidou, Anastasia; Tsaroucha, A K; Lambropoulou, M; Pitiakoudis, M; Polychronidis, A; Chatzitheoklitos, E; Romanidis, K; Simopoulos, C

    2016-08-01

    Pancreatic cancer (PC) is a leading cause of cancer death worldwide, especially in Western societies. Its aggressive nature and poor prognosis increase the need for identifying new and more accurate diagnostic and prognostic tools. We studied 41 patients who had undergone radical surgical resection for PC, investigated B7H4 protein expression in the PC tissue specimens of these patients by immunohistochemistry and analyzed several clinical and pathological features. The positive expression of the B7H4 antigen was associated with a negative impact of chemotherapy with gemcitabine on patient survival and also correlated with high CA19.9 serum levels and poorly differentiated tumors. Moreover, patients that overexpressed B7H4 antigen had worse prognosis compared to the ones that did not overexpress B7H4. B7H4 antigen is a negative prognostic marker for PC patients and also seems to express resistance of PC patients to chemotherapy with gemcitabine. PMID:25924930

  1. Higher Serum Ferritin Levels Correlate with an Increased Risk of Cutaneous Morbidity in Adult Patients with β-Thalassemia: A Single-Center Retrospective Study.

    PubMed

    Skandalis, Konstantinos; Vlachos, Christoforos; Pliakou, Xanthi; Gaitanis, Georgios; Kapsali, Eleni; Bassukas, Ioannis D

    2016-01-01

    Disturbed iron homeostasis characterizes β-thalassemia and increases its morbidity. Our aim was to retrospectively associate β-thalassemia disease characteristics with treatment-requiring skin conditions. The files of adult β-thalassemia (including sickle β-thalassemia) patients were screened over a 10-year period for treatment-requiring skin disease episodes and their correlation with hematologic diagnoses and epidemiological and serological characteristics. Seventy-eight patients were identified, and 7 (9%) developed at least one relevant episode including cutaneous small-vessel vasculitis (CSVV), urticaria, and leg ulcers. Average ferritin serum level correlated significantly with development of a dermatosis (2,034 ± 799 μg/l in cases vs. 920 ± 907 μg/l in the overall population; p = 0.001, ANOVA). This difference relied exclusively on the high ferritin levels observed in patients with 'generalized' dermatoses (urticaria and CSVV: 3,860 ± 1,220 μg/l) as opposed to values within the normal range in the case of 'localized' ones (leg ulcers: 662 ± 167 μg/l). The employed iron chelation treatment influenced ferritin levels (p = 0.002, Kruskal-Wallis test) since chelation with a single agent seems to increase the risk of a skin disease (p = 0.013, likelihood ratio method). Conclusively, serum ferritin can be evaluated as risk factor for generalized dermatoses, but not for leg ulcers, in patients with the β-thalassemia genotype. This risk can be efficiently controlled with adequate chelation. PMID:26509267

  2. Chronic administration of branched-chain amino acids impairs spatial memory and increases brain-derived neurotrophic factor in a rat model.

    PubMed

    Scaini, Giselli; Comim, Clarissa M; Oliveira, Giovanna M T; Pasquali, Matheus A B; Quevedo, João; Gelain, Daniel P; Moreira, José Cláudio F; Schuck, Patrícia F; Ferreira, Gustavo C; Bogo, Maurício R; Streck, Emilio L

    2013-09-01

    Maple syrup urine disease (MSUD) is a neurometabolic disorder that leads to the accumulation of branched-chain amino acids (BCAAs) and their α-keto branched-chain by-products. Because the neurotoxic mechanisms of MSUD are poorly understood, this study aimed to evaluate the effects of chronic administration of a BCAA pool (leucine, isoleucine and valine). This study examined the effects of BCAA administration on spatial memory and the levels of brain-derived neurotrophic factor (BNDF). We examined both pro-BDNF and bdnf mRNA expression levels after administration of BCAAs. Furthermore, this study examined whether antioxidant treatment prevented the alterations induced by BCAA administration. Our results demonstrated an increase in BDNF in the hippocampus and cerebral cortex, accompanied by memory impairment in spatial memory tasks. Additionally, chronic administration of BCAAs did not induce a detectable change in pro-BDNF levels. Treatment with N-acetylcysteine and deferoxamine prevented both the memory deficit and the increase in the BDNF levels induced by BCAA administration. In conclusion, these results suggest that when the brain is chronically exposed to high concentrations of BCAA (at millimolar concentrations) an increase in BDNF levels occurs. This increase in BDNF may be related to the impairment of spatial memory. In addition, we demonstrated that antioxidant treatment prevented the negative consequences related to BCAA administration, suggesting that oxidative stress might be involved in the pathophysiological mechanism(s) underlying the brain damage observed in MSUD. PMID:23109061

  3. H. hepaticus-induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial-induced immune response

    PubMed Central

    García, Alexis; Zeng, Yu; Muthupalani, Sureshkumar; Ge, Zhongming; Potter, Amanda; Mobley, Melissa W.; Boussahmain, Chakib; Feng, Yan; Wishnok, John S.; Fox, James G.

    2011-01-01

    Chronic microbial infection influence cancer progression but the mechanisms that link them remain unclear. Constitutive androstane receptor (CAR) is a nuclear receptor that regulates enzymes involved in endobiotic and xenobiotic metabolism. CAR activation is a mechanism of xenobiotic tumor promotion, however, the effects of chronic microbial infection on tumor promotion have not been studied in the context of CAR function. Here we report that CAR limits the effects of chronic infection-associated progression of liver cancer. CAR knockout (KO) and wild-type (WT) male mice were treated or not with the tumor initiator diethylnitrosamine (DEN) at 5 weeks of age and then orally inoculated with Helicobacter hepaticus (Hh) or sterile media at 8 weeks of age. At 50 weeks postinoculation mice were euthanized for histopathological, microbiological, molecular, and metabolomic analyses. Hh infection induced comparable hepatitis in WT and KO mice with or without DEN that correlated with significant upregulation of Tnfα and toll receptor Tlr2. Notably, DEN-treated Hh-infected KO mice exhibited increased numbers of liver lobes with dysplasia and neoplasia, as well as increased multiplicity of neoplasia, relative to similarly treated WT mice. Enhanced tumor promotion was associated with decreased hepatic expression of P450 enzymes Cyp2b10 and Cyp3a11, increased expression of Camp, and increased serum concentrations of chenodeoxycholic acid. Together, our findings suggest that liver tumor promotion is enhanced by an impaired metabolic detoxification of endobiotics and a persistent microbial-induced immune response. PMID:21335546

  4. Increasing Coverage in Mass Drug Administration for Lymphatic Filariasis Elimination in an Urban Setting: a Study of Malindi Town, Kenya

    PubMed Central

    Njomo, Doris W.; Mukoko, Dunstan A.; Nyamongo, Nipher K.; Karanja, Joan

    2014-01-01

    Introduction Implementation of Mass Drug Administration (MDA) in urban settings is an obstacle to Lymphatic Filariasis (LF) elimination. No urban-specific guidelines on MDA in urban areas exist. Malindi district urban area had received 4 MDA rounds by the time the current study was implemented. Programme data showed average treatment coverage of 28.4% (2011 MDA), far below recommended minimum of 65–80%. Methods To identify, design and test strategies for increased treatment coverage in urban areas, a quasi-experimental study was conducted in Malindi urban area. Three sub-locations with lowest treatment coverage in 2011 MDA were purposively selected. In the pre-test phase, 947 household heads sampled using systematic random method were interviewed for quantitative data. For qualitative data, 12 Focus Group Discussions (FGDs) with single sex adult and youth male and female groups and 3 with community drug distributors (CDDs) were conducted. Forty in-depth interviews with opinion leaders and self-administered questionnaires with District Public Health officers purposively selected were carried out. The quantitative data were analyzed using SPSS version 16 and statistical significance assessed by χ2 test.The qualitative data were analyzed manually according to study's themes. Results and Discussion The identified strategies were implemented prior to and during 2012 MDA in two sub-locations (experimental) while in the third (control), usual MDA strategies were applied. In the post-test phase, 2012 MDA coverage in experimental and control sub-locations was comparatively assessed for effect of the newly designed strategies on urban MDA. Results indicated improved treatment coverage in experimental sub-locations, 77.1% in Shella and 66.0% in Barani. Central (control) sub-location also attained high coverage, 70.4% indicating average treatment coverage of 71%. Conclusion The identified strategies contributed to increased treatment coverage in experimental sites and

  5. Dietary ɛ-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related Enzymes Activities in Rats

    PubMed Central

    Hosomi, Ryota; Yamamoto, Daiki; Otsuka, Ren; Nishiyama, Toshimasa; Yoshida, Munehiro; Fukunaga, Kenji

    2015-01-01

    ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fatty acid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fatty acid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fatty acid biosynthesis, were enhanced in rats fed EPL diet. The increased fatty acid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fatty acid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis. PMID:25866749

  6. Dietary ɛ-Polylysine Decreased Serum and Liver Lipid Contents by Enhancing Fecal Lipid Excretion Irrespective of Increased Hepatic Fatty Acid Biosynthesis-Related Enzymes Activities in Rats.

    PubMed

    Hosomi, Ryota; Yamamoto, Daiki; Otsuka, Ren; Nishiyama, Toshimasa; Yoshida, Munehiro; Fukunaga, Kenji

    2015-03-01

    ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fatty acid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fatty acid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fatty acid biosynthesis, were enhanced in rats fed EPL diet. The increased fatty acid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fatty acid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis. PMID:25866749

  7. Increased Serum LIGHT Levels Correlate with Disease Progression and Severity of Interstitial Pneumonia in Patients with Dermatomyositis: A Case Control Study

    PubMed Central

    Kotani, Takuya; Takeuchi, Tohru; Ishida, Takaaki; Masutani, Ryota; Isoda, Kentaro; Hata, Kenichiro; Yoshida, Shuzo; Makino, Shigeki; Hanafusa, Toshiaki

    2015-01-01

    Background Activated CD8+ T cells play an important role in the pathogenesis of dermatomyositis (DM) with interstitial pneumonia (IP). Serum CD8+ T-cell activator, LIGHT, and Th1/Th2/Th17 cytokines were measured in DM-IP patients and compared with clinical parameters to investigate their usefulness. Methods The correlations between the clinical findings and serum LIGHT and Th1/Th2/Th17 cytokine levels were investigated in 21 patients with DM-IP (14 with rapidly progressive IP [RPIP] and 7 with chronic IP [CIP], including 4 fatal cases of IP). Results The median serum LIGHT level was 119 (16–335.4) pg/ml, which was higher than that in healthy control subjects and DM patients without IP. The median serum IL–6 level was 14.7 (2.4–154.5) pg/ml (n = 13). The other cytokines were detected in only a few patients. The median serum LIGHT level in DM-RPIP patients (156 [49.6–335.4] pg/ml) was significantly higher than that in DM-CIP patients (94.3 [16–164.2] pg/ml) (P = 0.02). The serum IL–6 level did not correlate with either progression or outcome of DM-IP. ROC curve analysis determined a serum LIGHT level of ≥120 pg/ml to be the cut-off value for the rapid progression of DM-IP. Serum LIGHT levels correlated significantly with %DLco (R = 0.55, P = 0.04) and total ground-glass opacity scores (R = 0.72, P = 0.0002). The serum LIGHT level significantly decreased to 100.5 (12.4–259.3) pg/ml 4 weeks after treatment initiation (P = 0.04). Conclusions The serum LIGHT level may be a promising marker of disease progression and severity in patients with DM-IP. PMID:26448572

  8. Smoking Cessation Is Followed by Increases in Serum Bilirubin, an Endogenous Antioxidant Associated With Lower Risk of Lung Cancer and Cardiovascular Disease

    PubMed Central

    Wu, Ran; Mayne, Susan T.; Jatlow, Peter I.

    2014-01-01

    Introduction: Lower concentrations of serum bilirubin, an endogenous antioxidant, have been associated with risk of many smoking-related diseases, including lung cancer and cardiovascular disease, and current smokers are reported to have lower bilirubin levels than nonsmokers and past smokers. This study evaluates the effects of smoking cessation on bilirubin levels. Methods: In a secondary analysis of a 6-week placebo-controlled trial of naltrexone for smoking cessation, indirect and total bilirubin concentrations were evaluated at baseline and following smoking cessation. Individuals who were continuously abstinent for 6 weeks (n = 155) were compared to those who were not (n = 193). Participants reported smoking ≥20 cigarettes daily at baseline and received smoking cessation counseling, 21mg nicotine patch daily, and either placebo or 1 of 3 doses of naltrexone (25, 50, or 100mg) for 6 weeks. Change in indirect and total bilirubin following the quit date was measured at Weeks 1, 4, and 6 compared to baseline. Results: Individuals who were continuously abstinent from smoking, independent of naltrexone condition, showed a significantly greater mean increase in indirect (~unconjugated) bilirubin (0.06mg/dl, SD = 0.165) compared to those who did not (mean = 0.02, SD = 0.148, p = .015). Similar results were obtained for total bilirubin (p = .037). Conclusions: Smoking cessation is followed by increases in bilirubin concentration that have been associated with lower risk of lung cancer and cardiovascular disease. PMID:24812024

  9. Increased miR-155 expression in peripheral blood mononuclear cells of primary immune thrombocytopenia patients was correlated with serum cytokine profiles.

    PubMed

    Qian, Bao-Hua; Ye, Xin; Zhang, Lei; Sun, Yi; Zhang, Jian-Rong; Gu, Ming-Li; Qin, Qin; Chen, Jie; Deng, An-Mei

    2015-01-01

    We investigated the possible pathogenic role of a microRNA (miR-155) in primary immune thrombocytopenia (ITP). We used quantitative real-time PCR to determine the relative expression of miR-155 and SOCS1 (suppressor of cytokine signaling) mRNA in peripheral blood mononuclear cells (PBMCs) from 28 ITP patients and 28 healthy controls. Cytokine plasma levels were determined by ELISA. Possible associations between miR-155 levels and serum cytokine concentrations were assessed using Spearman or Pearson correlation analysis. Seven naive ITP patients were followed and the effects of medical treatment on miR-155 levels were assessed. Compared to healthy controls, ITP patients had increased miR-155 and decreased SOCS1 mRNA levels. ITP patients also had increased plasma IL-17A and decreased IL-4, IL-10 and TGF-β1 levels. miR-155 levels were negatively correlated with platelet counts, SOCS1 mRNA levels, and the plasma levels of IL-4, IL-10 and TGF-β1, but positively correlated with plasma IL-17A levels. Medical treatment for ITP decreased miR-155 levels. Thus, our results suggest that miR-155 might be involved in the pathogenesis of ITP by regulating cytokine profiles, which may be mediated by miR-155 targeting SOCS1. PMID:25413124

  10. Effect of increasing maximal aerobic exercise on serum gonadal hormones and alpha-fetoprotein in the luteal phase of professional female soccer players

    PubMed Central

    Otağ, Aynur; Hazar, Muhsin; Otağ, İlhan; Beyleroğlu, Malik

    2016-01-01

    [Purpose] The performance of female athletes during their menstrual period has attracted the attention of researchers for many years. It is known that the menstrual period changes with exercise. Alpha-fetoprotein (AFP) is an oncofetal protein. In this study, the effect of maximal aerobic exercise in the luteal phase on some hormones and AFP in female athletes was researched. [Subjects and Methods] Twelve volunteers and healthy female footballers with normal menstrual cycles volunteered for this study as subjects. All the participants performed a shuttle run test. Blood samples were taken before, after, and one hour after exercise. Serum AFP, estrogen, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) values were measured using an auto analyzer and original kits. Heart rate measurements were performed before and after the exercise. [Results] AFP activity had significantly decreased after 1 h of recovery from the exercise in the female soccer players, and estrogen and LH activity had significantly increased immediately after the exercise. Progesterone activity had significantly decreased immediately after the exercise. FSH values had significantly increased immediately after the exercise. [Conclusion] The results of the present study show there were significant decreases in the values of AFP, which is a cancer parameter, 1 hour after the exercise. This result may be valuable in future physiotherapy studies on the relationship between exercise and cancer. PMID:27134362

  11. Steady-State Serum Phenytoin Concentrations After Nasogastric Tube Administration of Immediate-Release Phenytoin Tablets and Extended-Release Phenytoin Capsules: An Open-Label, Crossover, Clinical Trial

    PubMed Central

    Panomvana, Duangchit; Khummuenwai, Napanan; Sra-ium, Supasil; Towanabut, Somchai

    2007-01-01

    Background: When phenytoin is prescribed for administration via nasogastric tube, immediate-release OR) phenytoin tablets are crushed before use and extended-release (ER) phenytoin capsules are opened and only the granules are used. However, it is unknown whether the same dose of these 2 different formulations will result in the same steady-state serum phenytoin concentration. Objective: The aim of this study was to determine whether ER phenytoin capsules can be used interchangeably with IR phenytoin tablets for prophylaxis of posttraumatic seizures. Methods: Inpatients at the neurosurgical ward at Prasat Neurological Institute, Bangkok, Thailand, between October 2004 and October 2005 were enrolled in the study. All patients were initially prescribed IR phenytoin tablets 300 mg/d as a maintenance dose for prophylaxis of posttraumatic seizures. The serum phenytoin concentration was measured after ≥5 days of treatment with IR phenytoin tablets 300 mg/d (two 50-mg tablets every 8 hours) that had been crushed before being administered concomitantly with a blenderized diet through the nasogastric tube. Without a washout period, the dosage form was changed to ER phenytoin capsules (three 100-mg capsules QD). The capsules were opened and the contents were administered concomitantly with the blenderized diet through the nasogastric tube for ≥5 days. The serum phenytoin concentration was again determined. The patients were closely monitored for seizures and adverse events (AEs). Results: Thirty-three patients enrolled in the study and 17 (10 women, 7 men; mean [SD] age, 62.94 [15.94] years [range, 18-89 years]) completed the study. The mean (SD) serum phenytoin concentrations after administration of phenytoin tablets and capsules were 6.03 (5.92) μg/mL and 3.80 (2.71) μg/mL, respectively (P = 0.019). The mean serum phenytoin concentrations, adjusted for low serum albumin concentrations after administration of tablets and capsules, were calculated and reported to be 10

  12. Pharmacokinetics of azithromycin in serum and sinus fluid after administration of extended-release and immediate-release formulations in patients with acute bacterial sinusitis.

    PubMed

    Ehnhage, A; Rautiainen, M; Fang, A F; Sanchez, S P

    2008-06-01

    As high drug levels at the infection site are desirable for optimal activity, this study explored whether one dose of azithromycin extended release (AZ-ER) achieved higher azithromycin exposure in sinus fluid than azithromycin immediate release (AZ-IR) in adults with acute bacterial sinusitis. Subjects received AZ-ER (2g single dose; n=5) or AZ-IR (500mg daily for 3 days; n=4) and blood and sinus aspirates were collected until 120 h after initial dosing. Within 24 h, exposure was four- and three-fold higher with AZ-ER than with AZ-IR in serum and sinus fluid, respectively. Sinus fluid exposure was five- and three-fold higher than serum for AZ-IR and AZ-ER, respectively. Azithromycin concentrations in sinus fluid were maintained up to 120 h. PMID:18456465

  13. [Cardiac effects and glycoside concentrations in serum and urine after oral administration of beta-methy-digoxin to healthy individuals (author's transl)].

    PubMed

    Haasis, R; Larbig, D; Klenk, K O

    1975-06-01

    Six healthy individuals were digitalized orally with beta-methyl-digoxin. The serum glycoside concentration, determined radioimmunologically at the end of the digitalization period was 1.2 +/- 0.22 ng/ml. At this period of time renal excretion attained 55.9% of the daily administered oral dose. The calculated renal clearance of beta-methyl-digoxin was 63 +/- 8.1 ml/min e. g. 57.5 +/- 8.3 ml/min/1.73 m2. After discontinuation of the glycoside the serum half life was 54 h. During the digitalization period the cardiac glycoside effects could be measured by ECG changes, especially a shortening of the QT interval as well as a shortening of the left ventricular ejection time and the pre ejection period, corrected for the heart rate. PMID:1152344

  14. Serum proprotein convertase subtilisin/kexin type 9 concentration is not increased by plant stanol ester consumption in normo- to moderately hypercholesterolaemic non-obese subjects. The BLOOD FLOW intervention study.

    PubMed

    Simonen, Piia; Stenman, Ulf-Håkan; Gylling, Helena

    2015-09-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein (LDL) cholesterol (LDL-C) metabolism by targeting LDL receptors for degradation. Statins increase serum PCSK9 concentration limiting the potential of statins to reduce LDL-C, whereas ezetimibe, inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant stanols also reduce cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Therefore, we performed a controlled, randomized, double-blind study, in which 92 normo- to moderately hypercholesterolaemic subjects (35 males and 57 females) consumed vegetable-oil spread 20 g/day enriched (plant stanol group, n=46) or not (control group, n=46) with plant stanols 3 g/day as ester for 6 months. Fasting blood samples were drawn at baseline and at the end of the study. Serum PCSK9 concentration was analysed with Quantikine Elisa Immunoassay, serum and lipoprotein lipids enzymatically and serum non-cholesterol sterols with GLC. At baseline, PCSK9 concentration varied from 91 to 716 ng/ml with a mean value of 278±11 (S.E.M.) ng/ml with no gender difference. It correlated with serum and LDL-C, serum triglycerides, age, body mass index (BMI) and plasma glucose concentration, but not with variables of cholesterol metabolism when adjusted to serum cholesterol. Plant stanols reduced LDL-C by 10% from controls (P<0.05), but PCSK9 levels were unchanged and did not differ between the groups. In conclusion, the present study demonstrated for the first time that inhibition of cholesterol absorption with plant stanol esters did not affect serum PCSK9 concentration. Thus, plant stanol esters provide an efficient dietary means to lower LDL-C without interfering with the PCSK9 metabolism and in this regard the LDL receptor-mediated cellular cholesterol uptake and removal. PMID:25857271

  15. SYSTEMIC ADMINISTRATION OF KAINIC ACID INCREASES GABA LEVELS IN PERFUSATE FROM THE HIPPOCAMPUS OF RATS IN VIVO

    EPA Science Inventory

    The ventral hippocampi of male, Fischer-344 rats were implanted with microdialysis probes and the effects of systemically administered kainic acid (KA) (8 mg/kg, s.c.) on the in vivo release of amino acids were measured for four hours after administration. n order to measure GABA...

  16. Bovine serum albumin further enhances the effects of organic solvents on increased yield of polymerase chain reaction of GC-rich templates

    PubMed Central

    2012-01-01

    Background While being a standard powerful molecular biology technique, applications of the PCR to the amplification of high GC-rich DNA samples still present challenges which include limited yield and poor specificity of the reaction. Organic solvents, including DMSO and formamide, have been often employed as additives to increase the efficiency of amplification of high GC content (GC > 60%) DNA sequences. Bovine serum albumin (BSA) has been used as an additive in several applications, including restriction enzyme digestions as well as in PCR amplification of templates from environmental samples that contain potential inhibitors such as phenolic compounds. Findings Significant increase in PCR amplification yields of GC-rich DNA targets ranging in sizes from 0.4 kb to 7.1 kb were achieved by using BSA as a co-additive along with DMSO and formamide. Notably, enhancing effects of BSA occurs in the initial PCR cycles with BSA additions having no detrimental impact on PCR yield or specificity. When a PCR was set up such that the cycling parameters paused after every ten cycles to allow for supplementation of BSA, combining BSA and organic solvent produced significantly higher yields relative to conditions using the solvent alone. The co-enhancing effects of BSA in presence of organic solvents were also obtained in other PCR applications, including site-directed mutagenesis and overlap extension PCR. Conclusions BSA significantly enhances PCR amplification yield when used in combination with organic solvents, DMSO or formamide. BSA enhancing effects were obtained in several PCR applications, with DNA templates of high GC content and spanning a broad size range. When added to the reaction buffer, promoting effects of BSA were seen in the first cycles of the PCR, regardless of the size of the DNA to amplify. The strategy outlined here provides a cost-effective alternative for increasing the efficiency of PCR amplification of GC-rich DNA targets over a broad size

  17. Effect of antacid and ascorbic acid on serum salicylate concentration.

    PubMed

    Hansten, P D; Hayton, W L

    1980-01-01

    To determine the effect of antacid or ascorbic acid administration on plateau serum salicylate concentrations, nine healthy subjects were given each of the following treatments by balanced block design: choline salicylate (equivalent to 3.76 or 5.62 Gm/day of aspirin); choline salicylate plus magnesium-aluminum hydroxide (120 ml/day); or choline salicylate plus ascorbic acid (3 Gm/day). In subjects developing a control serum salicylate level above 10 mg/dl, antacid administration produced a decrease in serum salicylate level (mean 19.8 mg/dl vs. 15.8 mg/dl) (P less than 0.01). Ascorbic acid administration was not associated with a significant change in serum salicylate. The reduction in serum salicylate following antacid appears to be due to antacid-induced alkalinization of the urine with resultant increase in renal salicylate clearance. Antacid administration should be considered a potential cause of altered serum salicylate concentration in patients receiving large doses of salicylate. PMID:7400368

  18. A new negroid-specific HindIII polymorphism in the serum amyloid A1 (SAA1) gene increases the usefulness of the SAA locus in linkage studies

    SciTech Connect

    Stevens, G.; Ramsay, M.; Jenkins, T. ); Kluve-Beckerman, B. )

    1993-01-01

    The cDNA probe pSAA82 detects three serum amyloid A (SAA) loci on chromosome 11p. SAA1 and SAA2 have 90% nucleotide identity in exon and intron sequences (1), whereas SAA3 has an average of 70% identity with SAA1 and SAA2 (3). The chromosomal organization of the loci is not yet known. A two-allele polymorphic HindIII site was found within intron 2 of the SAA2 locus (1) with fragments of 3.0 (a2) and 5.0 kb (a1) (previously sized as 2.8 and 4.6 kb, respectively) which occur in Caucasoids, Negroids, and San (formerly [open quote]Bushmen[close quotes]) (2). The discovery of a further, Negroid-specific, polymorphic HindIII restriction site, detected with the same probe, increases its usefulness. This RFLP is associated with the SAA1 locus (6) and is characterized by the presence of two allelic fragments of 3.6 (b1) and 1.4 kb (b2). This HindIII site is also thought to occur within intron 2 because of the strong evolutionary conservation between the SAA1 and SAA2 genes. The polymorphism may therefore either predate the gene duplication event or be present as a result of gene conversion. 6 refs., 1 fig.

  19. The increased binding affinity of curcumin with human serum albumin in the presence of rutin and baicalin: A potential for drug delivery system

    NASA Astrophysics Data System (ADS)

    Liu, Bing-Mi; Zhang, Jun; Hao, Ai-Jun; Xu, Liang; Wang, Dan; Ji, Hui; Sun, Shi-Jie; Chen, Bo-Qi; Liu, Bin

    2016-02-01

    The impacts of rutin and baicalin on the interaction of curcumin (CU) with human serum albumin (HSA) were investigated by fluorescence and circular dichroism (CD) spectroscopies under imitated physiological conditions. The results showed that the fluorescence quenching of HSA by CU was a simultaneous static and dynamic quenching process, irrespective of the presence or absence of flavonoids. The binding constants between CU and HSA in the absence and presence of rutin and baicalin were 2.268 × 105 M- 1, 3.062 × 105 M- 1, and 3.271 × 105 M- 1, indicating that the binding affinity was increased in the case of two flavonoids. Furthermore, the binding distance determined according to Förster's theory was decreased in the presence of flavonoids. Combined with the fact that flavonoids and CU have the same binding site (site I), it can be concluded that they may simultaneously bind in different regions in site I, and formed a ternary complex of flavonoid-HSA-CU. Meanwhile, the results of fluorescence quenching, CD and three-dimensional fluorescence spectra revealed that flavonoids further strengthened the microenvironmental and conformational changes of HSA induced by CU binding. Therefore, it is possible to develop a novel complex involving CU, flavonoid and HSA for CU delivery. The work may provide some valuable information in terms of improving the poor bioavailabiliy of CU.

  20. Serum Dehydroepiandrosterone Sulphate Concentration Is Not a Predictive Factor in IVF Outcomes before the First Cycle of GnRH Agonist Administration in Women with Normal Ovarian Reserve

    PubMed Central

    Kunicki, Michał; Łukaszuk, Krzysztof; Jakiel, Grzegorz; Liss, Joanna

    2015-01-01

    Objective The aim of our study was to determine whether serum dehydroepiandrosterone sulphate (DHEAS) concentration and the models incorporating it could help clinicians to predict IVF outcomes in women with normal ovarian reserve undergoing their first long protocol. Study Design We performed a retrospective analysis of 459 women undergoing cycles of intracytoplasmic sperm injection (ICSI) for the first time in a long GnRH agonist protocol. Results Embryo transfer was performed in 407 women (88.7%). The fertilisation rate was 78.6%. The clinical pregnancy rate was 44.8% per started cycle and 50.6% per embryo transfer. Our univariate model revealed that the best predictors of clinical pregnancy were the number of mature oocytes, the number of embryos transferred and the number of good quality embryos, account for the clinical parameters that reflect ovarian reserve the best being AMH level and AFC. DHEAS did not predict clinical pregnancy (OR 1.001, 95% CI, 0.999–1.004). After adjusting for the number of embryos transferred and class of embryos in a multivariate model, the best predictors were age (OR 0.918, 95% CI, 0.867–0.972) and AFC (OR 1.022, 95% CI, 0.992–1.053). Serum DHEAS levels were positively correlated with AFC (r = 0.098, P<0.039) and testosterone levels (r = 0.371, P<0.001), as well as the number of mature oocytes (r = 0.109, P<0.019); serum DHEAS levels were negatively correlated with age (r = -0.220, P<0.001), follicle-stimulating hormone (FSH), (r = -0.116, P<0.015) and sex hormone-binding globulin (SHBG), (r = -0.193, P<0.001). Conclusions DHEAS concentration (in addition to the known factors of ovarian reserve) does not predict clinical pregnancy in women with normal ovarian reserve who are undergoing ICSI. PMID:25738591

  1. On-line comprehensive two-dimensional HepG2 cell membrane chromatographic analysis system for charactering anti-hepatoma components from rat serum after oral administration of Radix scutellariae: A strategy for rapid screening active compounds in vivo.

    PubMed

    Jia, Dan; Chen, Xiaofei; Cao, Yan; Wu, Xunxun; Ding, Xuan; Zhang, Hai; Zhang, Chuan; Chai, Yifeng; Zhu, Zhenyu

    2016-01-25

    Cell membrane chromatography (CMC) is a bioaffinity chromatography technique for characterizing interactions between drugs and membrane receptors and has been widely used to screen active components from complex samples such as herbal medicines (HMs). However, it has never been applied in vivo due to its relatively high limit of detection (LOD) and the matrix interferences. In this study, a novel on-line comprehensive two-dimensional HepG2/CMC/enrich columns/high performance liquid chromatography/time-of-flight mass spectrometry system was developed to rapidly screen potential anti-hepatoma components from drug-containing serum of rats after oral administration of Radix scutellariae. A matrix interference deduction method with a home-written program in MATLAB was developed, which could successfully eliminate the interference of endogenous substances in serum. Baicalein, wogonin, chrysin, oroxylin A, neobaicalein and rivularin from Radix scutellariae extraction were significantly retained in the HepG2/CMC column. Three potential active components, wogonin, oroxylin A and neobaicalein were firstly screened from the drug-containing serum as well. The cell counting kit-8 assay demonstrated that wogonin, oroxylin A and chrysin showed high inhibitory activities in a dose-dependent manner on HepG2 cells at the concentration of 12.5-200 μM (p<0.05) and the IC50 values were 69.83, 16.66 and 51.6 μM, respectively. Wogonin and oroxylin A, which were screened both from Radix scutellariae extraction and the drug-containing serum, could be selected as lead compounds to obtain good anti-hepatoma effects. The proposed comprehensive 2D CMC system and matrix interference elimination strategy have significant advantages for in vivo screening of active components from complex biological samples and could be applied to other biochromatography models. PMID:26512996

  2. Varenicline, a Partial Agonist at Neuronal Nicotinic Receptors, Reduces Nicotine-Induced Increases in 20% Ethanol Operant Self-Administration in Sprague-Dawley Rats

    PubMed Central

    Bito-Onon, Jade J.; Simms, Jeffrey A.; Chatterjee, Susmita; Holgate, Joan; Bartlett, Selena E.

    2010-01-01

    Alcohol and nicotine use disorders are often treated as separate diseases, despite evidence that approximately 80–90% of alcohol dependent individuals are also heavy smokers. Both nicotine and ethanol have been shown to interact with neuronal nicotinic acetylcholine receptors (nAChRs), suggesting these receptors are a common biological target for the effects of nicotine and ethanol in the brain. There are few studies that have examined the effects of co-administered nicotine and ethanol on the activity of nAChRs in rodents. In the present study, we show that Sprague-Dawley rats, a strain often used for nicotine studies but not as often for voluntary ethanol intake studies, will consume 20% ethanol using both the intermittent-access two-bottle-choice and operant self-administration models without the need for sucrose fading. We show that nicotine (0.2mg/kg and 0.8mg/kg, s.c.) significantly increases operant 20% ethanol self-administration and varenicline (2mg/kg, s.c), a partial agonist at nAChRs, significantly decreases operant ethanol self-administration and nicotine-induced increases in ethanol self-administration. This suggests that nAChRs play an important role in increasing ethanol self-administration and that varenicline may be an efficacious treatment for alcohol and nicotine co-dependencies. PMID:21392178

  3. Subacute Zinc Administration and L-NAME Caused an Increase of NO, Zinc, Lipoperoxidation, and Caspase-3 during a Cerebral Hypoxia-Ischemia Process in the Rat

    PubMed Central

    Blanco-Alvarez, Victor Manuel; Lopez-Moreno, Patricia; Soto-Rodriguez, Guadalupe; Martinez-Fong, Daniel; Rubio, Hector; Gonzalez-Barrios, Juan Antonio; Piña-Leyva, Celia; Torres-Soto, Maricela; Gomez-Villalobos, María de Jesus; Hernandez-Baltazar, Daniel; Eguibar, José Ramon; Ugarte, Araceli; Cebada, Jorge

    2013-01-01

    Zinc or L-NAME administration has been shown to be protector agents, decreasing oxidative stress and cell death. However, the treatment with zinc and L-NAME by intraperitoneal injection has not been studied. The aim of our work was to study the effect of zinc and L-NAME administration on nitrosative stress and cell death. Male Wistar rats were treated with ZnCl2 (2.5 mg/kg each 24 h, for 4 days) and N-ω-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg) on the day 5 (1 hour before a common carotid-artery occlusion (CCAO)). The temporoparietal cortex and hippocampus were dissected, and zinc, nitrites, and lipoperoxidation were assayed at different times. Cell death was assayed by histopathology using hematoxylin-eosin staining and caspase-3 active by immunostaining. The subacute administration of zinc before CCAO decreases the levels of zinc, nitrites, lipoperoxidation, and cell death in the late phase of the ischemia. L-NAME administration in the rats treated with zinc showed an increase of zinc levels in the early phase and increase of zinc, nitrites, and lipoperoxidation levels, cell death by necrosis, and the apoptosis in the late phase. These results suggest that the use of these two therapeutic strategies increased the injury caused by the CCAO, unlike the alone administration of zinc. PMID:23997853

  4. HPLC/Q-TOF-MS-Based Identification of Absorbed Constituents and Their Metabolites in Rat Serum and Urine after Oral Administration of Cistanche deserticola Extract.

    PubMed

    Li, Wen-Lan; Sun, Xiang-Ming; Song, Hui; Ding, Jing-Xin; Bai, Jing; Chen, Qiang

    2015-09-01

    As a famous health food in China, Cistanche deserticola (C. deserticola) suggested an estrogenic activity according to our previous study. However, no one clarifies its active material basis to date. To find more potentially active constituents and elucidate metabolic pathways of metabolites, a method to simultaneously analyze multiple absorbed constituents and metabolites from C. deserticola in rat serum and urine was established using high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF-MS). Based on HPLC/Q-TOF-MS method, a total of 24 components, involving 9 prototype constituents and 15 metabolites in rat serum and urine samples, were tentatively identified based on retention time, ultraviolet spectrum, MS data, compound fragmentation laws, published literatures, and reference substances. Most of the compounds existed in the form of metabolites. The proposed metabolic pathways of main metabolites were discussed, including methylation, demethylation, hydrolysis, hydroxylation, acetoxylation, glucuronidation, dehydrogenation, sulfation, esterification, and so on. Phenylethanoid glycosides were extensively metabolized and mutually transformed in vivo. This investigation provided valuable information for further study of the active ingredients and action mechanism of C. deserticola. PMID:26243042

  5. Serum-free thyroxine concentrations, measured by chemiluminescence assay before and after thyrotropin administration in healthy dogs, hypothyroid dogs, and euthyroid dogs with dermathopathies.

    PubMed Central

    Paradis, M; Pagé, N; Larivière, N; Fontaine, M

    1996-01-01

    The purpose of this study was to determine the usefulness of free thyroxine (FT4) measured by chemiluminescence in evaluating thyroid function in dogs. Total thyroxine (TT4) concentration measured by radioimmunoassay (RIA) and FT4 measured by chemiluminescence were evaluated in 30 healthy dogs, 60 euthyroid dogs with concurrent dermatopathies, and 30 hypothyroid dogs before and after intravenous stimulation with 1 or 2 IU of thyrotropin (TSH). Median basal TT4 and median TT4 concentrations at 4 h post-TSH administration were not significantly different (P < 0.0001) between healthy dogs and euthyroid dogs with dermatopathies, but were significantly higher than those in hypothyroid dogs. In healthy dogs, the median TT4 concentrations at 4 and 6 h post-TSH administration were not significantly different. Median basal FT4 and median FT4 concentrations at 4 h post-TSH administration in healthy dogs were significantly lower (P < 0.0001) than those in euthyroid dogs with dermatopathies, but significantly higher than the same parameters in hypothyroid dogs. There was a significant difference between the median FT4 concentrations at 4 h post-TSH administration and median basal FT4 concentrations for healthy dogs and euthyroid dogs with dermatopathies, but not for hypothyroid dogs. Lastly, in healthy dogs, median FT4 concentrations at 4 and 6 h post-TSH administration were not significantly different. Free thyroxine measured by chemiluminescence was highly correlated (P < 0.0001; Spearman r = 0.91) with FT4 measured by the reference method for free hormone analysis, namely, equilibrium dialysis, when sera from 56 dogs were used. PMID:8705973

  6. Vitamin B(12) Immunoassay on Roche Elecsys 2010: Effects of High Excess Concentration of Serum Vitamin B(12) in CKD Patients on Parenteral Administration.

    PubMed

    Basu, Surupa; Chaudhuri, Subimal

    2011-10-01

    Vitamin B(12) being water soluble is excreted in the urine when administered in excess. The probability of finding an abnormally excess serum concentration would be almost surreal. We report a peculiar clinical situation that may impact the vitamin B(12) immunoassay on the Roche Elecsys 2010 due to excess analyte concentration. In separate episodes (Feb and June 2010), the Biochemistry laboratory of a tertiary-care hospital, Kolkata, India, encountered two critically ill patients with background chronic kidney disease (CKD), low urine output, and on cyanocoabalamin supplementation, who had serum vitamin B(12) concentrations far exceeding expected values; even post dialysis. The B(12) assays (pmol/l) were performed using electrochemiluminiscence immunoassay on Roche Elecsys 2010, the assay validity confirmed by concomitant quality control runs. The immunoassays failed to deliver results, flagged with "signal level below limit". Biotin therapy was ruled out as a possible interferent. In the first episode, re-assay of a repeat draw yielded same outcome; outsourcing on Immulite provided concentration of >738 pmol/l. Serial dilution gave result of >29520 pmol/l on Elecsys 2010. In the second, we gained from past experience. Vitamin B(12) concentration >59040 pmol/l was conveyed to the treating nephrologist the very day. The B(12) immunoassay on the Elecsys 2010 employs sequential incubation steps for competitive binding that is compromised in the event of abnormally excess B(12) concentration in patient sera akin to the prozone effect. This knowledge may be beneficial while assaying sera of CKD patients to avoid financial loss due unnecessary repeats and delay in turnaround time. PMID:23024480

  7. Increased serum concentration of BAFF/APRIL and IgA2 subclass in patients with mixed connective tissue disease complicated by interstitial lung disease.

    PubMed

    Kaneko, Toshiyuki; Amano, Hirofumi; Kawano, Shinya; Minowa, Kentaro; Ando, Seiichiro; Watanabe, Takashi; Nakano, Soichiro; Suzuki, Jun; Morimoto, Shinji; Tokano, Yoshiaki; Takasaki, Yoshinari

    2014-03-01

    B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are known to be crucial for B cell maturation and survival, and increased expression of these factors in various autoimmune diseases has been reported. Human B cells produce two IgA subclasses: IgA1 and IgA2, the latter being abundant in the distal intestine, saliva, colostrum and bronchial fluid. We investigated these parameters in patients with mixed connective tissue disease (MCTD) complicated by interstitial lung disease (ILD+), and compared them with those in MCTD patients without ILD (ILD-). Sixty-three MCTD patients were divided into two groups: 21 ILD+ patients and 42 ILD- patients. In each patient group we analyzed soluble BAFF/APRIL using ELISA, and IgA1 and IgA2 using double immunodiffusion. Furthermore, we analyzed BAFF-APRIL receptors, BCMA, BAFF-R and TACI, using flow cytometry. The ILD+ patients had significantly higher levels of BAFF/APRIL than the ILD- patients. There were significant correlations between BAFF/APRIL, BAFF/KL-6 and APRIL/KL-6. Although there was no significant inter-group difference in the serum IgA1 level, ILD+ patients had a significantly elevated IgA2 level in comparison with ILD- patients. Moreover, although there were no significant inter-group differences in the expression of BCMA, BAFF-R and TACI on B cells, the expression of BAFF-R was significantly decreased in the ILD+ patients. In recent years, relationships between BAFF/APRIL and IgA subclass have been reported. Our results suggest that an elevated level of BAFF/APRIL drives the maturation of B cells, subsequently leading to IgA2 class switching, and possibly to the development of ILD in patients with MCTD. PMID:24252051

  8. Higher serum uric acid level increases risk of prehypertension in subjects with normal glucose tolerance, but not pre-diabetes and diabetes.

    PubMed

    Wu, I-H; Wu, J-S; Sun, Z-J; Lu, F-H; Chang, C-S; Chang, C-J; Yang, Y-C

    2016-08-01

    Although the association between serum uric acid (SUA) levels and prehypertension has been reported in previous studies, it is unknown whether their relationship is similar in subjects with diabetes, pre-diabetes and normal glucose tolerance (NGT). This study thus aimed to investigate the relationship between SUA and prehypertension in subjects with different glycemic status, including NGT, pre-diabetes and diabetes. A total of 12 010 participants were included after excluding subjects with blood pressure ⩾140/90 mm Hg, history of hypertension, leukaemia, lymphoma, hypothyroidism, medication for hypertension and hyperuricemia and missing data. Subjects were divided into four groups based on SUA quartiles (male Q1: ⩽345.0, Q2: 345.0-392.6, Q3: 392.6-440.2, Q4: ⩾440.2 μmol l(-1) and female Q1: ⩽249.8, Q2: 249.8-285.5, Q3: 285.5-333.1, Q4: ⩾333.1 μmol l(-1)). Diabetes, pre-diabetes and NGT were assessed according to the 2010 American Diabetes Association diagnostic criteria. Normotension and prehypertension were defined according to the JNC-7 (The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) criteria. The SUA was significantly higher in prehypertensive subjects as compared with normotensive subjects. SUA, as a continuous variable, was positively associated with prehypertension in subjects with NGT but not pre-diabetes and diabetes. Besides, NGT subjects with the highest quartile of SUA exhibited a higher risk of prehypertension after adjustment for other confounding factors. In pre-diabetes and diabetes groups, none of SUA quartiles was significantly related to prehypertension. SUA was significantly associated with an increased risk of prehypertension in subjects with NGT but insignificantly in subjects with pre-diabetes and diabetes. PMID:26911534

  9. Serum uric acid is associated with increased risk of idiopathic venous thromboembolism in high HDL-C population: A case-control study

    PubMed Central

    YU, MIAO; LING, KEN; TENG, YUNFEI; LI, QIN; MEI, FEI; LI, YIQING; OUYANG, CHENXI

    2016-01-01

    Many studies have indicated that metabolic disorders are positively correlated with idiopathic venous thromboembolism (VTE), whereas the risk factor serum uric acid (SUA) for idiopathic VTE has yet to be investigated. In this retrospective case-control study, 276 idiopathic VTE patients and 536 gender- and age-matched control subjects were included. The subjects in the case and control groups exhibiting common known VTE risk factors and the patients with a first VTE onset in one month were excluded. For the control group, primary and secondary VTE patients were excluded. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and current smoking were significantly associated with idiopathic VTE in the univariate analysis. Hyperuricemia was detected in 56/276 (20.29%) idiopathic patients compared with 71/536 (13.25%) in the control group. HDL-C was considered the most prominent interactive factor for SUA in idiopathic VTE by the interaction analysis. After testing for the interaction terms, SUA was closely associated with idiopathic VTE in the high HDL-C population (P=0.0026 for interaction), while there was no such correlation in the low HDL-C group. The results indicated no obvious correlation between triglyceride and hypertension to idiopathic VTE. In conclusion, SUA is closely associated with an increased risk of idiopathic VTE in the high HDL-C population. The abnormality of SUA may act as an important linkage between atherosclerosis and idiopathic VTE through HDL-C. PMID:27284315

  10. Modernizing Administration.

    ERIC Educational Resources Information Center

    Lombardi, Vincent L.; Hildebrand, Verna

    1981-01-01

    Suggests assignment of research duties and rotation of teaching and management roles for college administrators, to increase their effectiveness and diminish the negative effects of declining enrollments. (JD)

  11. Increased serum levels of novel T cell cytokines IL-33, IL-9 and IL-17 in subjects with type-1 diabetes.

    PubMed

    Shruthi, Sugumar; Mohan, Viswanathan; Amutha, Anandakumar; Aravindhan, Vivekanandhan

    2016-10-01

    The role of adaptive immune cytokines in the pathogenesis of type-1 Diabetes Mellitus (T1DM) is well known. Even though reports on the serum levels of both Th-1 and Th-2 cytokines are available, those on newly described T cell cytokines such as IL-17, IL-33 and IL-9 in T1DM are scarce. We therefore measured the serum levels of both T cell polarizing (IL-33 and IL-12) and T cell effector (IFN-γ, IL-4, IL-10, IL-17 and IL-9) cytokines in T1DM subjects with and without microvascular (retinopathy and nephropathy) complications (MVC). All the tested cytokines were significantly elevated in T1DM subjects except for IFN-γ (which failed to attain statistical significance) with no significant difference between those with and without MVC. From the serum cytokine analysis, no apparent Th polarization could be determined for the T1DM subjects. PMID:27442004

  12. Both serum 25-hydroxyvitamin D and calcium levels may increase the risk of incident prostate cancer in Caribbean men of African ancestry.

    PubMed

    Jackson, Maria D; Tulloch-Reid, Marshall K; Lindsay, Carole M; Smith, Garrett; Bennett, Franklyn I; McFarlane-Anderson, Norma; Aiken, William; Coard, Kathleen C M

    2015-06-01

    Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with both higher and lower risk of prostate cancer (PCa), whereas elevated levels of circulating calcium has been related to higher risks. However, there are few studies that account for effects of both calcium and 25(OH)D concentrations on incident PCa in a black population. We examined these relationships in a case-control study of men 40-80 years old with newly diagnosed, histologically confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations was higher among cases (2.32 ± 0.19 mmol/L) than controls, (2.27 ± 0.30 mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer status (cases, 33.67 ± 12.71 ng/mL; controls (32.25 ± 12.59 ng/mL). Serum calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P = 0.287). Multivariable-adjusted models showed a positive linear relationship between PCa and serum calcium (OR, 1.12; CI, 1.00-1.25 per 0.1 nmol/L). Serum 25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI, 1.01-1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was OR, 2.18; CI, 1.04-4.43 and OR, 2.47 CI, 1.20-4.90 for tertile 3 (P(trend) = 0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the strong relationship between serum calcium and vitamin D the mechanism by which each affects prostate cancer risk in men of African ancestry needs additional investigation. PMID:25858172

  13. Increased Serum Levels of Anti-Carbamylated 78-kDa Glucose-Regulated Protein Antibody in Patients with Rheumatoid Arthritis.

    PubMed

    Yu, Hui-Chun; Lai, Pei-Hsuan; Lai, Ning-Sheng; Huang, Hsien-Bin; Koo, Malcolm; Lu, Ming-Chi

    2016-01-01

    The objective of this study was to investigate the presence and titer of anti-carbamylated 78-kDa glucose-regulated protein (anti-CarGRP78) antibody in serum from controls, and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). Thirty-three RA patients, 20 SLE patients, 20 pSS patients, and 20 controls were enrolled from our outpatient clinic. GRP78 was cloned and carbamylated. Serum titers of anti- cyclic citrullinated peptides (anti-CCP), anti-GRP78, and anti-CarGRP78 were measured with an enzyme-linked immunosorbent assay. No differences in serum titers of anti-GRP78 antibody in patients with RA, SLE, or pSS compared with the controls were observed. Serum levels of anti-carGRP78 antibody in patients with RA, but not SLE or pSS, were significantly higher compared with the controls (OD405 0.15 ± 0.08 versus 0.11 ± 0.03, p = 0.033). There was a positive correlation between the serum levels of anti-GRP78 antibody, but not anti-CarGRP78 antibody, with the levels of anti-CCP antibody in patients with RA. Both anti-GRP78 and anti-carGRP78 antibodies failed to correlate with C-reactive protein levels in patients with RA. In conclusion, we demonstrated the presence of anti-CarGRP78 antibody in patients with RA. In addition, the serum titer of anti-CarGRP78 antibody was significantly elevated in patients with RA compared with the controls. Anti-CarGRP78 antibody could also be detected in patients with SLE or pSS. PMID:27618024

  14. Serum disposition of bovine lactoferrin after oral and anal administration and its proteolytic cleavage by gastric transit in rainbow trout (Oncorhynchus mykiss W.).

    PubMed

    Cecchini, Stefano; Caputo, Anna R

    2009-01-01

    Several studies have shown an immunomodulatory effect of orally administered bovine lactoferrin (LF) in fish, but the process of digestion was not characterized. In the present study, we investigated the fate of bovine LF after oral and anal administration, and studied the appearance of intact LF in the bloodstream and its proteolytic attack during the gastric transit in rainbow trout (Oncorhynchus mykiss) held at 9 degrees C and 18 degrees C. Data obtained showed the presence of intact bovine LF in the bloodstream only after anal administration in fish held at 18 degrees C and the presence of several peptides derived from bovine LF in the gastric content. Immunoblotting analysis showed that only a part of bovine LF-derived peptides reacted with the applied anti-bovine LF antibody. The concentration of intact bovine LF, after 30 min of administration, in the gastric content of fish reared at 18 degrees C, being extremely low, if any, led us to suspect that the immunoregulatory effect of dietary bovine LF shown in fish by several authors is not due to the intact form but to bioactive fragments, originated by the proteolytic attack during the gastric transit, as demonstrated in higher vertebrates. PMID:19028427

  15. Switching to a Protease Inhibitor–Containing, Nucleoside-Sparing Regimen (Lopinavir/Ritonavir Plus Efavirenz) Increases Limb Fat But Raises Serum Lipid Levels

    PubMed Central

    Tebas, Pablo; Zhang, Jiameng; Yarasheski, Kevin; Evans, Scott; Fischl, Margaret A.; Shevitz, Abby; Feinberg, Judith; Collier, Ann C.; Shikuma, Cecilia; Brizz, Barbara; Sattler, Fred

    2015-01-01

    Background Subcutaneous limb fat loss continues to be one the most troubling side effects of long-term antiretroviral regimens. Nucleoside analogues and protease inhibitors (PIs) have been linked to the development of this complication. Methods We evaluated the effects of nucleoside-sparing and PI-sparing regimens on fat distribution, bone mineral density, and metabolic parameters in 62 subjects, who were not selected for lipoatrophy, with advanced HIV (nadir CD4 count ≤200 cells/mm3 or HIV RNA level ≥80,000 copies/mL) and an undetectable HIV viral load. Participants were randomized to switch their initial successful antiretroviral regimen to open-label lopinavir/ritonavir (LPV/r) at a dose of 533/133 mg twice a day and efavirenz (EFV) at a dose of 600 mg/d (the nucleoside-sparing arm) versus EFV and 2 nucleoside analogues (the PI-sparing arm). Findings At week 48, the median change in limb fat in the nucleoside-sparing arm was 562 g (6%, interquartile range [IQR]: −218–1186 g) versus a loss of −242 g (−4%, IQR: −539–452 g) in the nucleoside-containing PI-sparing arm (P = 0.086). At the time of last observation (median = 102 weeks, IQR: 73–152 weeks), a median gain of 782 g (10%, IQR: −380–1168 g) of limb fat was noted in the nonnucleoside arm (n = 22) versus a loss of 850 g (−15%, IQR: −1270 to −526 g) in the nucleoside-containing arm (n = 25; P = 0.002). Interpretation The switch to a nucleoside-sparing combination antiretroviral regimen (LPV/r + EFV) was associated with significant improvement in limb fat. These results provide additional evidence that nucleoside analogues are important in the progressive limb fat loss that characterizes antiretroviral treatment and that switching medications can significantly improve this complication. This option has to be carefully balanced with the potential to increase serum lipid levels and the trend to increase virologic failure. PMID:17527093

  16. Body condition loss and increased serum levels of nonesterified fatty acids enhance progesterone levels at estrus and reduce estrous activity and insemination rates in postpartum dairy cows.

    PubMed

    Lüttgenau, J; Purschke, S; Tsousis, G; Bruckmaier, R M; Bollwein, H

    2016-03-01

    Data from 96 Holstein Friesian cows on a commercial dairy farm were used to investigate whether body condition and serum levels of nonesterified fatty acids (NEFAs) postpartum (pp) affect progesterone (P4) levels, estrous activity, and fertility in dairy cows. The examination period started 14 days before the expected calving date and ended either when a cow was inseminated or at a maximum of 90 days pp. Body condition score (BCS; 1-5 scale) and backfat thickness (BFT) were determined every 2 weeks. Blood for analysis of NEFA and P4 concentrations was sampled weekly during the first 35 days pp and then every 48 hours until an ovulation was observed. Transrectal ultrasonography of the ovaries started at 21 days pp and was performed after blood sampling. If cows were not inseminated because of silent ovulation, sampling and ultrasonography continued on Days 7, 14, and 18 after ovulation and again every 48 hours until the next ovulation. Estrous activity was continuously measured with the Heatime estrus detection system. Pregnancy controls were performed ultrasonographically 28 and 42 days after AI. Cows with increased NEFA levels at 28 days pp had an increased risk of maintaining minimum P4 levels above 0.4 ng/mL at first recognized estrus (P = 0.03). Higher NEFA levels at Day 7 were associated with lower probability for a cow to have elevated P4 levels (≥2 ng/mL) by Day 35 pp, indicating delayed commencement of luteal activity (C-LA). Estrous activity was not influenced (P > 0.10) by minimum P4 concentrations at estrus, but more animals with C-LA until Day 35 pp showed estrous activity compared to cows without C-LA throughout this period (P = 0.006). Estrous activity was lower in cows with a low BCS 14 days pp (P = 0.02) and with a low BFT 42 days pp (P = 0.03). Moreover, the probability to exhibit estrus was reduced with higher NEFA levels at 21 days pp (P = 0.01). Eighty-five cows were inseminated and 37 (44%) got pregnant after insemination. Higher NEFA levels

  17. A Cross-Sectional Study Demonstrating Increased Serum Amyloid A Related Inflammation in High-Density Lipoproteins from Subjects with Type 1 Diabetes Mellitus and How This Association Was Augmented by Poor Glycaemic Control

    PubMed Central

    McEneny, Jane; Daniels, Jane-Ann; McGowan, Anne; Gunness, Anjuli; Moore, Kevin; Stevenson, Michael; Young, Ian S.; Gibney, James

    2015-01-01

    Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM). Normally high-density lipoproteins (HDL) protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA-) related inflammation this property may be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matched control subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-, and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly in serum (P = 0.088), and significantly in HDL2(P = 0.003) and HDL3(P = 0.005). When the T1DM group were separated according to mean HbA1c (8.34%), serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c ≥ 8.34%, compared to when HbA1c was <8.34% (P < 0.05). Furthermore, regression analysis illustrated, that for every 1%-unit increase in HbA1c, SAA increased by 20% and 23% in HDL2 and HDL3, respectively, independent of BMI. HsCRP did not differ between groups (P > 0.05). This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poor glycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increased atherosclerosis risk. PMID:26557720

  18. Administration of orexin receptor 1 antagonist into the rostral ventromedial medulla increased swim stress-induced antinociception in rat

    PubMed Central

    Soliemani, Neda; Moslem, Alireza; Shamsizadeh, Ali; Azhdari-Zarmehri, Hassan

    2016-01-01

    Objective(s): Intracerebroventricular injection of orexin-A (hypocretin-1) antagonist has been shown to inhibit stress-induced analgesia. However the locations of central sites that may mediate these effects have not been totally demonstrated. This study was performed to investigate the role of rostral ventromedial medulla (RVM) orexin receptor 1 in stress-induced analgesia (SIA). Materials and Methods: Forced swim stress in water was employed to adult male rats (200-250 g). Nociceptive responses were measured by formalin test (50 µl injection of formalin 2% subcutaneously into hind paw) and, pain related behaviors were monitored for 90 min following intra-microinjection of SB-334867 (orexin receptor 1 antagonist) into RVM. Results: Exposure to swimming stress test after administration of SB-334867 into RVM significantly reduces the formalin-induced nociceptive behaviors in phase1, interphase, and phase 2 in rats. Conclusion: The result demonstrated the involvement of OXR1 in antinociceptive behaviors induced by swim stress in RVM. PMID:27403261

  19. In vitamin B12 deficiency, higher serum folate is assoicated with increased total homocysteine (tHcy) and methlmalonic acid (MMA) concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In a recent study of older participants (age >/= 60 y) in the 1999-2002 National Health and Nutrition Examination Survey (NHANES), we showed that a combination of high serum folate and low vitamin B-12 status was associated with higher prevalence of cognitive impairment and anemia than other combina...

  20. Growing steers grazing high versus low endophyte (Neotyphodium coenophialum)-infected tall fescue have reduced serum enzymes increased hepatic glucogenic enzymes and reduced liver and carcass mass

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is well established that grazing Neotyphodium coenophialum-infected forages results in reduced weight gain and serum prolactin levels of cattle. The objective of this study was to determine the potential effects of toxic endophyte-infected tall fescue consumption on carcass characteristics, bloo...

  1. Characterization of a cytotoxic factor induced in murine serum after the intravenous administration of dehydrogenation polymers of phenylpropenoids (a class of synthetic lignins).

    PubMed

    Shimizu, N; Kohara, A; Kawazoe, Y

    1997-08-01

    A cytotoxic factor (CF) appeared in murine serum after the intravenous injection of the dehydrogenation polymers (DHPs) of p-coumaric acid (DHP-pCA), caffeic acid (DHP-CA), and ferulic acid (DHP-FA), which are categorized as a class of synthetic lignins. The highest CF activity was observed 15 min after the i.v. injection of DHP-pCA. CF is likely to be cytocidal through an apoptotic mechanism accompanied by nucleosome-sized DNA fragmentation. CF is extractable with aqueous ethanol and highly stable against heat, proteases, and acid/alkali treatments. The ethanol extract showed cytotoxicity toward various cultured cell lines and also ascites carcinoma cells in vivo. The parent molecules DHPs did not show any appreciable cytotoxicity. After the induction of CF activity, the activity quickly diminished and completely disappeared from the blood stream within an hour or so. The cytotoxicity was observed only when the target cells were exposed to CF for longer than 10 h. PMID:9300127

  2. Increased Prevalance of the −211 T Allele of Follicle Stimulating Hormone (FSH) β Subunit Promoter Polymorphism and Lower Serum FSH in Infertile Men

    PubMed Central

    Grigorova, Marina; Punab, Margus; Poolamets, Olev; Kelgo, Piret; Ausmees, Kristo; Korrovits, Paul; Vihljajev, Vladimir; Laan, Maris

    2010-01-01

    Context: The human FSHB promoter polymorphism (rs10835638; −211 G/T) has been associated with serum FSH in a cohort of young Estonian men. The minor allele carriers had reduced serum FSH (15.7% in GT heterozygotes; 40% in TT homozygotes) compared with GG homozygotes. Objective: Because FSH is essential for normal spermatogenesis and fertility, we speculated that abnormalities in FSH action could contribute to male infertility. We sought to study whether genetically inherited constitutively reduced FSH levels may affect male reproduction and replicate the association between rs10835638 and serum FSH among infertile male patients. Design: Genotyping of rs10835638 in a cohort of infertile men (n = 1029; Andrology Center of the Tartu University Clinics, Estonia), including idiopathic infertility cases (IIFC; n = 750). Patients: Patients included male partners (sperm concentration <20 × 106/ml) of infertile couples failing to conceive a child for 12 months or longer. Results: A significant excess of TT homozygotes (1.1 vs. 2.4%) as well as GT heterozygotes (22.4 vs. 25.1%) was detected among infertile men compared with the young male cohort (χ2 test, P < 0.05). The T allele of rs10835638 was associated with reduced serum FSH (analysis of covariance; full cohort: P = 1.20 × 10−6, F = 13.8; IIFC: P = 7.70 × 10−7, F = 14.3) as well as with low FSH to LH ratio (full cohort: P = 1.52 × 10−11, F = 25.6; IIFC: P = 3.25 × 10−9, F = 20.4). The median serum FSH levels differed between the GG and TT carriers by 48.5%. All IIFC with TT genotype exhibited low (<1.8) FSH to LH ratio. Conclusions: In perspective, this genetic marker may have clinical significance in molecular diagnostics of male reproductive success and a potential to identify positive responders to FSH treatment. PMID:19897680

  3. Does postmenopausal estrogen administration increase the risk of breast cancer? Contributions of animal, biochemical, and clinical investigative studies to a resolution of the controversy.

    PubMed

    Zumoff, B

    1998-01-01

    Despite nearly six decades of epidemiological studies, meta-analyses, and reviews, there is still considerable controversy in the literature about the question, does postmenopausal estrogen administration increase the risk of breast cancer? In an effort to resolve the controversy, a number of animal, biochemical, and clinical investigative studies in this field have been reviewed. The following summary formulation is proposed: 1. Administration of estrogen is inherently capable of promoting the growth of breast cancer, and therefore of increasing the incidence of clinical breast cancer. 2. Human response to estrogen is like that of the low-cancer-incidence strains of mice studied by Lacassagne, in that large doses and prolonged administration are required to induce clinical breast cancer. 3. The blood levels of estradiol produced by the usual doses of postmenopausal estrogen are relatively low, equivalent to those of the follicular phase of the menstrual cycle. These levels may be near the threshold for producing breast-cancer-promoting effects; therefore, the tumor response will vary greatly in different populations, depending on genetic susceptibility factors: a. The prevalence of a family history of premenopausal breast cancer in a first-degree relative. b. The prevalence of abnormal BRCA1, BRCA2, and p53 genes. c. The prevalence of increased 16 alpha-hydroxylation of estradiol. d. The prevalence of smokers who are slow acetylators. 4. Consumption of alcohol (5 grams or more daily) along with the postmenopausal estrogen administration results in elevation of blood estradiol levels to values equivalent to those of the periovulatory peak of the menstrual cycle, which may be well above the threshold for producing breast-cancer-promoting effects in all women. The risk for cancer will therefore be uniformly increased in women who use alcohol and take estrogen. 5. Increased risk of breast cancer from postmenopausal estrogen administration can be eliminated by taking

  4. Increased Risk for ESBL-Producing Bacteria from Co-administration of Loperamide and Antimicrobial Drugs for Travelers’ Diarrhea1

    PubMed Central

    Mero, Sointu; Kirveskari, Juha; Lääveri, Tinja

    2016-01-01

    Antimicrobial drug treatment of travelers’ diarrhea is known to increase the risk for colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae. Among 288 travelers with travelers’ diarrhea, the colonization rate without medications was 21%. For treatment with loperamide only, the rate was 20%; with antimicrobial drugs alone, 40%; and with loperamide and antimicrobial drugs, 71%. PMID:26691898

  5. Increased Risk for ESBL-Producing Bacteria from Co-administration of Loperamide and Antimicrobial Drugs for Travelers' Diarrhea.

    PubMed

    Kantele, Anu; Mero, Sointu; Kirveskari, Juha; Lääveri, Tinja

    2016-01-01

    Antimicrobial drug treatment of travelers' diarrhea is known to increase the risk for colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae. Among 288 travelers with travelers' diarrhea, the colonization rate without medications was 21%. For treatment with loperamide only, the rate was 20%; with antimicrobial drugs alone, 40%; and with loperamide and antimicrobial drugs, 71%. PMID:26691898

  6. Both serum 25-hydroxyvitamin D and calcium levels may increase the risk of incident prostate cancer in Caribbean men of African ancestry

    PubMed Central

    Jackson, Maria D; Tulloch-Reid, Marshall K; Lindsay, Carole M; Smith, Garrett; Bennett, Franklyn I; McFarlane-Anderson, Norma; Aiken, William; Coard, Kathleen C M

    2015-01-01

    Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with both higher and lower risk of prostate cancer (PCa), whereas elevated levels of circulating calcium has been related to higher risks. However, there are few studies that account for effects of both calcium and 25(OH)D concentrations on incident PCa in a black population. We examined these relationships in a case–control study of men 40–80 years old with newly diagnosed, histologically confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations was higher among cases (2.32 ± 0.19 mmol/L) than controls, (2.27 ± 0.30 mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer status (cases, 33.67 ± 12.71 ng/mL; controls (32.25 ± 12.59 ng/mL). Serum calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P = 0.287). Multivariable-adjusted models showed a positive linear relationship between PCa and serum calcium (OR, 1.12; CI, 1.00–1.25 per 0.1 nmol/L). Serum 25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI, 1.01–1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was OR, 2.18; CI, 1.04–4.43 and OR, 2.47 CI, 1.20–4.90 for tertile 3 (Ptrend = 0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the strong relationship between serum calcium and vitamin D the mechanism by which each affects prostate cancer risk in men of African ancestry needs additional investigation. PMID:25858172

  7. Effect of sodium valproate on phenobarbital serum levels in children and adults.

    PubMed

    Fernandez de Gatta, M R; Alonso Gonzalez, A C; Garcia Sanchez, M J; Dominguez-Gil Hurle, A; Santos Borbujo, J; Monzon Corral, L

    1986-01-01

    The influence of sodium valproate on serum levels of phenobarbital during combination treatment was studied in 29 children and 50 adults with epilepsy. Steady-state drug levels in serum were determined immediately prior to drug administration using immunoenzymatic analysis. The serum level/dose ratio of phenobarbital increased significantly (p less than 0.001) when sodium valproate was added to the treatment. The increase had a mean value of 50.9% in adults and 112.5% in children, suggesting marked interindividual variability in the intensity of the interaction. Almost half of the patients required a decrease in the dose of phenobarbital prescribed. The interaction was more pronounced in patients with high serum levels of phenobarbital, while the dose of phenobarbital and the serum levels and dose of sodium valproate did not seem to affect the extent of the interaction. Close monitoring of the serum levels of phenobarbital is recommended during simultaneous treatment with sodium valproate. PMID:3103264

  8. Chronic Aldosterone Administration Causes NOX2-Mediated Increases In Reactive Oxygen Species Production and Endothelial Dysfunction in the Cerebral Circulation

    PubMed Central

    CHRISSOBOLIS, Sophocles; DRUMMOND, Grant R.; FARACI, Frank M.; SOBEY, Christopher G.

    2014-01-01

    Objective An elevated plasma aldosterone level is an independent cardiovascular risk factor. Although excess aldosterone promotes cardiovascular disease, no studies have examined the effect of increased plasma aldosterone on the cerebral circulation. A major source of vascular reactive oxygen species (ROS) during cardiovascular disease is the NADPH oxidases. Because NOX2-containing NADPH oxidase (NOX2 oxidase) is highly expressed in cerebral endothelium, we postulated that it might contribute to ROS generation and vascular dysfunction in response to aldosterone. Here we examined the effect of aldosterone and NOX2 oxidase on ROS production and endothelial dysfunction in the cerebral circulation, and whether the effects of aldosterone are exacerbated in aged mice. Methods and Results In adult (average age ~24–25 wk) wild-type (WT) and Nox2-deficient (Nox2−/y) mice, neither vehicle nor aldosterone (0.28 mg/kg/day for 14 days) affected blood pressure (measured using tail-cuff). By contrast, aldosterone treatment reduced dilation of the basilar artery (measured using myography) to the endothelium-dependent agonist acetylcholine in WT mice (P<0.05), but had no such effect in NOX2−/y mice (P>0.05). Aldosterone increased basal and phorbol-dibutyrate stimulated superoxide production (measured using L-012-enhanced chemiluminesence) in cerebral arteries from WT but not Nox2−/y mice. In aged WT mice (average age ~70 wk), aldosterone treatment increased blood pressure, but had a similar effect on cerebral artery superoxide levels as in adult WT mice. Conclusions These data indicate that NOX2 oxidase mediates aldosterone-induced increases in ROS production and endothelial dysfunction in cerebral arteries from adult mice independently of blood pressure changes. Aldosterone-induced hypertension is augmented during aging. PMID:24991871

  9. Increased susceptibility to hyperoxic lung injury and alveolar simplification in newborn rats by prenatal administration of benzo[a]pyrene

    PubMed Central

    Thakur, Vijay S.; Liang, Yanhong W.; Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Barrios, Roberto; Zhou, Guodong; Guntupalli, Bharath; Shivanna, Binoy; Maturu, Paramahamsa; Welty, Stephen E.; Moorthy, Bhagavatula; Couroucli, Xanthi I.

    2014-01-01

    Maternal smoking is one of the risk factors for preterm birth and for the development of bronchopulmonary dysplasia (BPD). In this study, we tested the hypothesis that prenatal exposure of rats to benzo[a]pyrene (BP), a component of cigarette smoke, will result in increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification, and that cytochrome P450 (CYP)1A and 1B1 enzymes and oxidative stress mechanistically contribute to this phenomenon. Timed pregnant Fisher 344 rats were administered BP (25 mg/Kg) or the vehicle corn oil (CO) on gestational days 18, 19 and 20, and newborn were either maintained in room air or exposed to hyperoxia (85% O2) for 7 or 14 days. Hyperoxic newborn rats prenatally exposed to the vehicle CO showed lung injury and alveolar simplification, and inflammation, and these effects were potentiated in rats that were prenatally exposed to BP. Prenatal exposure to BP, followed by hyperoxia, also resulted in significant modulation of hepatic and pulmonary cytochrome P450 (CYP)1A and 1B1 enzymes at PND 7-14. These rats displayed significant oxidative stress in lungs at postnatal day (PND) 14, as evidenced by increased levels of the F2-isoprostane 8-iso-PGF2α. Furthermore, these animals showed BP-derived DNA adducts and oxidative DNA adducts in the lung. In conclusion, our results show increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification following maternal exposure to BP, and our results suggest that modulation of CYP1A/1B1 enzymes, increases in oxidative stress, and BP-DNA adducts contributed to this phenomenon. PMID:24657529

  10. A recommendation to perform a blood culture before the administration of intravenous antibiotics increased the detection of Staphylococcus aureus bacteremia.

    PubMed

    Jogenfors, A; Stark, L; Svefors, J; Löfgren, S; Malmvall, B-E; Matussek, A

    2014-05-01

    In 2004, the Surviving Sepsis Campaign was launched to increase awareness and improve the outcome of severe sepsis. Accordingly, in Jönköping County, Sweden, a strong recommendation to perform a blood culture before the start of intravenous antibiotic treatment was introduced in 2007. Moreover, a reminder was included in the laboratory report to consult an infectious disease specialist when Staphylococcus aureus was isolated from a blood culture. Retrospectively, patients with at least one blood culture growing S. aureus during 2002 through 2003 (pre intervention n = 58) or during 2008 through 2009 (post intervention n = 100) were included. Medical records were evaluated regarding clinical data and outcome. Blood culture isolates were characterized by antibiotic susceptibility testing (AST) and S. aureus protein A (spa) gene typing. The annual incidence of S. aureus bacteremia (SAB) increased from 28 per 100,000 inhabitants at the pre intervention period to 45 per 100,000 at the post intervention period (p = 0.046). During post intervention, the SAB incidence was significantly higher in men (p = 0.009). The mortality rate during hospital stay was 14 % during pre intervention and 18 % during post intervention (p = 0.47). The most common spa types were t012 and t084. The Surviving Sepsis Campaign resulted in an increased number of detected cases of SAB. The mortality rate was the same before and after the intervention, and no spa type correlated to certain clinical manifestations or mortality. PMID:24249284

  11. A high-fat meal, or intraperitoneal administration of a fat emulsion, increases extracellular dopamine in the nucleus accumbens.

    PubMed

    Rada, Pedro; Avena, Nicole M; Barson, Jessica R; Hoebel, Bartley G; Leibowitz, Sarah F

    2012-01-01

    Evidence links dopamine (DA) in the nucleus accumbens (NAc) shell to the ingestion of palatable diets. Less is known, however, about the specific relation of DA to dietary fat and circulating triglycerides (TG), which are stimulated by fat intake and promote overeating. The present experiments tested in Sprague-Dawley rats whether extracellular levels of NAc DA increase in response to acute access to fat-rich food or peripheral injection of a fat emulsion and, if so, whether this is related to caloric intake or elevated circulating lipids. When rats consumed more calories of a high-fat meal compared with a low-fat meal, there was a significant increase in extracellular accumbens DA (155% vs. 119%). Systemic injection of a fat emulsion, which like a high-fat diet raises circulating TG but eliminates the factor of taste and allows for the control of caloric intake, also significantly increased extracellular levels of DA (127%) compared to an equicaloric glucose solution (70%) and saline (85%). Together, this suggests that a rise in circulating TG may contribute to the stimulatory effect of a high-fat diet on NAc DA. PMID:24962774

  12. A High-Fat Meal, or Intraperitoneal Administration of a Fat Emulsion, Increases Extracellular Dopamine in the Nucleus Accumbens

    PubMed Central

    Rada, Pedro; Avena, Nicole M.; Barson, Jessica R.; Hoebel, Bartley G.; Leibowitz, Sarah F.

    2012-01-01

    Evidence links dopamine (DA) in the nucleus accumbens (NAc) shell to the ingestion of palatable diets. Less is known, however, about the specific relation of DA to dietary fat and circulating triglycerides (TG), which are stimulated by fat intake and promote overeating. The present experiments tested in Sprague-Dawley rats whether extracellular levels of NAc DA increase in response to acute access to fat-rich food or peripheral injection of a fat emulsion and, if so, whether this is related to caloric intake or elevated circulating lipids. When rats consumed more calories of a high-fat meal compared with a low-fat meal, there was a significant increase in extracellular accumbens DA (155% vs. 119%). Systemic injection of a fat emulsion, which like a high-fat diet raises circulating TG but eliminates the factor of taste and allows for the control of caloric intake, also significantly increased extracellular levels of DA (127%) compared to an equicaloric glucose solution (70%) and saline (85%). Together, this suggests that a rise in circulating TG may contribute to the stimulatory effect of a high-fat diet on NAc DA. PMID:24962774

  13. Repeated methylphenidate administration during lactation reduces maternal behavior, induces maternal tolerance, and increases anxiety-like behavior in pups in adulthood.

    PubMed

    Ponchio, R A; Teodorov, E; Kirsten, T B; Coelho, C P; Oshiro, A; Florio, J C; Bernardi, M M

    2015-01-01

    Methylphenidate (MPD) is a dopamine uptake inhibitor and the most commonly prescribed drug for the treatment of attention-deficit/hyperactivity disorder in children. Several studies have shown that such stimulants as cocaine and amphetamine that are administered during gestation and lactation may disrupt maternal behavior. Also, MPD is used in lactation. Repeated MPD administration can induce either sensitization or tolerance. The aim of the present study was to investigate whether repeated MPD administration alters maternal behavior and promotes tolerance or sensitization in these females. The effects in adult offspring were also examined in models of anxiety. Methylphenidate (5mg/kg) was administered from lactation day 2 to 4, and maternal pup retrieval behavior was assessed. This treatment was continued until lactation day 7. At weaning, the dams received a challenge dose of MPD, and general activity was evaluated in the open field. Striatal monoamine and metabolite levels were also measured to determine whether this treatment promotes behavioral or biochemical plasticity. The long-term behavioral effects of MPD exposure were evaluated in pups in adulthood. The results showed an increase in the latency to retrieve the first, second, and third pups and a decrease in the number of dams that retrieved all pups. After a challenge dose of MPD, the dams exhibited a decrease in locomotion frequency, an increase in immobility duration in the open field, and a decrease in striatal serotonin levels. In pups, anxiety-like behavior increased in the light/dark box test. These results indicate that repeated MPD administration during early lactation impairs maternal behavior, likely by decreasing maternal motivation. Repeated MPD administration induced maternal tolerance at weaning after a challenge dose of MPD, suggesting the development of central nervous system plasticity. In pups, maternal exposure to MPD during early lactation induced long-term effects and increased

  14. Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use

    NASA Technical Reports Server (NTRS)

    Cheung, E. V.; Tidball, J. G.

    2003-01-01

    OBJECTIVE: To test the hypothesis that ibuprofen administration during modified muscle use reduces muscle necrosis and invasion by select myeloid cell populations. METHODS: Rats were subjected to hindlimb unloading for 10 days, after which they experienced muscle reloading by normal weight-bearing to induce muscle inflammation and necrosis. Some animals received ibuprofen by intraperitoneal injection 8 h prior to the onset of muscle reloading, and then again at 8 and 16 h following the onset of reloading. Other animals received buffer injection at 8 h prior to reloading and then ibuprofen at 8 and 16 h following the onset of reloading. Control animals received buffer only at each time point. Quantitative immunohistochemical analysis was used to assess the presence of necrotic muscle fibers, total inflammatory infiltrate, neutrophils, ED1+ macrophages and ED2+ macrophages at 24 h following the onset of reloading. RESULT: Administration of ibuprofen beginning 8 h prior to reloading caused significant reduction in the concentration of necrotic fibers, but increased the concentration of inflammatory cells in muscle. The increase in inflammatory cells was attributable to a 2.6-fold increase in the concentration of ED2+ macrophages. Animals treated with ibuprofen 8 h following the onset of reloading showed no decrease in muscle necrosis or increase in ED2+ macrophage concentrations. CONCLUSION: Administration of ibuprofen prior to increased muscle loading reduces muscle damage, but increases the concentration of macrophages that express the ED2 antigen. The increase in ED2+ macrophage concentration and decrease in necrosis may be mechanistically related because ED2+ macrophages have been associated with muscle regeneration and repair.

  15. Association of Opioids and Sedatives with Increased Risk of In-Hospital Cardiopulmonary Arrest from an Administrative Database

    PubMed Central

    Overdyk, Frank J.; Dowling, Oonagh; Marino, Joseph; Qiu, Jiejing; Chien, Hung-Lun; Erslon, Mary; Morrison, Neil; Harrison, Brooke; Dahan, Albert; Gan, Tong J.

    2016-01-01

    Background While opioid use confers a known risk for respiratory depression, the incremental risk of in-hospital cardiopulmonary arrest, respiratory arrest, or cardiopulmonary resuscitation (CPRA) has not been studied. Our aim was to investigate the prevalence, outcomes, and risk profile of in-hospital CPRA for patients receiving opioids and medications with central nervous system sedating side effects (sedatives). Methods A retrospective analysis of adult inpatient discharges from 2008–2012 reported in the Premier Database. Patients were grouped into four mutually exclusive categories: (1) opioids and sedatives, (2) opioids only, (3) sedatives only, and (4) neither opioids nor sedatives. Results Among 21,276,691 inpatient discharges, 53% received opioids with or without sedatives. A total of 96,554 patients suffered CPRA (0.92 per 1000 hospital bed-days). Patients who received opioids and sedatives had an adjusted odds ratio for CPRA of 3.47 (95% CI: 3.40–3.54; p<0.0001) compared with patients not receiving opioids or sedatives. Opioids alone and sedatives alone were associated with a 1.81-fold and a 1.82-fold (p<0.0001 for both) increase in the odds of CPRA, respectively. In opioid patients, locations of CPRA were intensive care (54%), general care floor (25%), and stepdown units (15%). Only 42% of patients survived CPRA and only 22% were discharged home. Opioid patients with CPRA had mean increased hospital lengths of stay of 7.57 days and mean increased total hospital costs of $27,569. Conclusions Opioids and sedatives are independent and additive risk factors for in-hospital CPRA. The impact of opioid sparing analgesia, reduced sedative use, and better monitoring on CPRA incidence deserves further study. PMID:26913753

  16. Low body weight gain, low white blood cell count and high serum ferritin as markers of poor nutrition and increased risk for preterm delivery.

    PubMed

    Hsu, Wen-Yin; Wu, Cheng-Hsuan; Hsieh, Charles Tsung-Che; Lo, Hui-Chen; Lin, Jen-Shiou; Kao, Mei-Ding

    2013-01-01

    This study determined factors of preterm delivery in Taiwan. Healthy women (n=520, age 29.1±4.2 y) at 8-12 weeks of pregnancy were recruited from prenatal clinics. Background information, anthropometrics, biochemical parameters, and dietary intake, collected by 24 h-recall were obtained from the first, second, and third trimesters to delivery. Clinical outcomes of neonates were also collected. The results show that 53.7% of women were primiparous and that the incidence of preterm delivery was 6.2%. Body weight gains in the first trimester and throughout pregnancy were significantly lower in mothers with preterm delivery (preterm group) than in mothers with term delivery (term group, p<0.05). Maternal cholesterol intake, circulating white blood cell counts (WBC) and serum albumin were significantly lower and that serum magnesium and ferritin were significantly higher in the preterm group than in the term group. Maternal weight gain was positively correlated with caloric and nutrient intake (p<0.05). Neonatal birth weight was positively correlated with maternal weight gain and intakes of protein and phosphate during pregnancy; with intakes of calories, vitamin B-1 and B-2 in the first trimester; and with intakes of calcium, magnesium, iron and zinc, as well as circulating WBC in the third trimester. However, neonatal birth weight was negatively correlated with serum iron in the third trimester and with serum iron and ferritin at the time of delivery. In conclusion, maternal weight gain in early pregnancy and WBC, mineral intake and iron status in late pregnancy seem to be major factors affecting delivery and neonatal outcomes. PMID:23353616

  17. May the Evaluation of Nitrosative Stress Through Selective Increase of 3-Nitrotyrosine Proteins Other Than Nitroalbumin and Dominant Tyrosine-125/136 Nitrosylation of Serum α-Synuclein Serve for Diagnosis of Sporadic Parkinson's Disease?

    PubMed Central

    García-Moreno, José-Manuel; Martín de Pablos, Angel; Chacón, José

    2013-01-01

    Abstract Nitrosative stress, where nitrosylation of tyrosine (Tyr) leading to 3-nitrotyrosine proteins or free 3-nitrotyrosine is the most prominent change, has been proposed as a pathogenic mechanism in Parkinson's disease (PD). Levels of 3-nitrotyrosine proteins in serum and cerebrospinal fluid (CSF) of patients with PD have not been studied. Nitrosative stress-induced protein changes in serum and CSF were analyzed in patients with PD (n=54) and controls (n=40). Herein, we demonstrate the presence of nitrosative stress in serum and CSF of patients with early PD leading to selective increase of 3-nitrotyrosine proteins other than nitroalbumin, without free 3-nitrotyrosine (Hoehn-Yahr stage 1, p<0.05; stage 2, p<0.01). Among 3-nitrotyrosine proteins, nitro-α-synuclein (N-αSyn) was detected in serum, not CSF, and the sites of Tyr nitrosylation were observed to be modified in patients with early PD. Thus, the intensity of nitrosylation of Tyr125/136 residues is enhanced (stage 1, p<0.05; stage 2, p<0.01), and that of the Tyr39 site is reduced (stage 1, p<0.05), and the ratio between both parameters (α-synuclein with nitrosylated tyrosines 125 and 136 [N-αSyn-Tyr125/136]:α-synuclein with nitrosylated tyrosine 39 [N-αSyn-Tyr39] ratio) is significantly higher in patients with early PD (p<0.01). These observations lead to the hypothesis that evaluating nitrosative stress through enhanced levels of 3-nitrotyrosine proteins in serum and CSF without changes in nitroalbumin, together with the profile of tyrosine nitrosylation of serum αSyn characterized by dominant nitrosylation of Tyr125/136, could serve for the diagnosis of sporadic PD. Antioxid. Redox Signal. 19, 912–918. PMID:23418747

  18. May the evaluation of nitrosative stress through selective increase of 3-nitrotyrosine proteins other than nitroalbumin and dominant tyrosine-125/136 nitrosylation of serum α-synuclein serve for diagnosis of sporadic Parkinson's disease?

    PubMed

    Fernández, Emilio; García-Moreno, José-Manuel; Martín de Pablos, Angel; Chacón, José

    2013-09-20

    Nitrosative stress, where nitrosylation of tyrosine (Tyr) leading to 3-nitrotyrosine proteins or free 3-nitrotyrosine is the most prominent change, has been proposed as a pathogenic mechanism in Parkinson's disease (PD). Levels of 3-nitrotyrosine proteins in serum and cerebrospinal fluid (CSF) of patients with PD have not been studied. Nitrosative stress-induced protein changes in serum and CSF were analyzed in patients with PD (n=54) and controls (n=40). Herein, we demonstrate the presence of nitrosative stress in serum and CSF of patients with early PD leading to selective increase of 3-nitrotyrosine proteins other than nitroalbumin, without free 3-nitrotyrosine (Hoehn-Yahr stage 1, p<0.05; stage 2, p<0.01). Among 3-nitrotyrosine proteins, nitro-α-synuclein (N-αSyn) was detected in serum, not CSF, and the sites of Tyr nitrosylation were observed to be modified in patients with early PD. Thus, the intensity of nitrosylation of Tyr125/136 residues is enhanced (stage 1, p<0.05; stage 2, p<0.01), and that of the Tyr39 site is reduced (stage 1, p<0.05), and the ratio between both parameters (α-synuclein with nitrosylated tyrosines 125 and 136 [N-αSyn-Tyr125/136]:α-synuclein with nitrosylated tyrosine 39 [N-αSyn-Tyr39] ratio) is significantly higher in patients with early PD (p<0.01). These observations lead to the hypothesis that evaluating nitrosative stress through enhanced levels of 3-nitrotyrosine proteins in serum and CSF without changes in nitroalbumin, together with the profile of tyrosine nitrosylation of serum αSyn characterized by dominant nitrosylation of Tyr125/136, could serve for the diagnosis of sporadic PD. PMID:23418747

  19. A prebiotic fiber increases the formation and subsequent absorption of compound K following oral administration of ginseng in rats

    PubMed Central

    Kim, Kyung-Ah; Yoo, Hye Hyun; Gu, Wan; Yu, Dae-Hyung; Jin, Ming Ji; Choi, Hae-Lim; Yuan, Kathy; Guerin-Deremaux, Laetitia; Kim, Dong-Hyun

    2014-01-01

    Background Gut microflora play a crucial role in the biotransformation of ginsenosides to compound K (CK), which may affect the pharmacological effects of ginseng. Prebiotics, such as NUTRIOSE, could enhance the formation and consequent absorption of CK through the modulation of gut microbial metabolic activities. In this study, the effect of a prebiotic fiber (NUTRIOSE) on the pharmacokinetics of ginsenoside CK, a bioactive metabolite of ginsenosides, and its mechanism of action were investigated. Methods Male Sprague–Dawley rats were given control or NUTRIOSE-containing diets (control diet + NUTRIOSE) for 2 wk, and ginseng extract or vehicle was then orally administered. Blood samples were collected to investigate the pharmacokinetics of CK using liquid chromatography–tandem mass spectrometry. Fecal activities that metabolize ginsenoside Rb1 to CK were assayed with fecal specimens or bacteria cultures. Results When ginseng extract was orally administered to rats fed with 2.5%, 5%, or 10% NUTRIOSE containing diets, the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve values of CK significantly increased in a NUTRIOSE content-dependent manner. NUTRIOSE intake increased glycosidase activity and CK formation in rat intestinal contents. The CK-forming activities of intestinal microbiota cultured in vitro were significantly induced by NUTRIOSE. Conclusion These results show that prebiotic diets, such as NUTRIOSE, may promote the metabolic conversion of ginsenosides to CK and the subsequent absorption of CK in the gastrointestinal tract and may potentiate the pharmacological effects of ginseng. PMID:26045693

  20. Intracerebroventricular administration of leptin increase physical activity but has no effect on thermogenesis in cold-acclimated rats

    PubMed Central

    Tang, Gang-Bin; Tang, Xiang-Fang; Li, Kui; Wang, De-Hua

    2015-01-01

    Most small homotherms display low leptin level in response to chronic cold exposure. Cold-induced hypoleptinemia was proved to induce hyperphagia. However, it is still not clear whether hypoleptinemia regulates energy expenditure in cold condition. We try to answer this question in chronic cold-acclimated rats. Results showed that 5-day intracerebroventricular(ICV) infusion of leptin (5 μg/day) had no effects on basal and adaptive thermogenesis and uncoupling protein 1 expression. Physical activity was increased by leptin treatment. We further determined whether ghrelin could reverse the increasing effect of leptin on physical activity. Coadministration of ghrelin (1.2 μg/day) completely reversed the effect of leptin on physical activity. Collectively, this study indicated the regulation of leptin on energy expenditure during cold acclimation may be mainly mediated by physical activity but not by thermogenesis. Our study outlined behavioral role of leptin during the adaptation to cold, which adds some new knowledge to promote our understanding of cold-induced metabolic adaptation. PMID:26053156

  1. 3'-5' cyclic-guanosine monophosphate increase in rat brain hippocampus after gamma-hydroxybutyrate administration. Prevention by valproate and naloxone

    SciTech Connect

    Vayer, P.; Gobaille, S.; Mandel, P.; Maitre, M.

    1987-08-03

    An increase (123%) of cyclic GMP (cGMP) was observed in the hippocampus of the rat killed by microwave irradiation 45 min after administration of 500 mg/kg el-hydroxybutyrate (GHB) IP. This increase is time and dose dependent. No modification in cyclic nucleotide content was observed in striatum and in cerebellum. As the role of GHB has been implicated in neurotransmission, the fact that this compound increases cyclic GMP accumulation in hippocampus in vivo may represent a mechanism by which the actions of GHB are mediated at the cellular level. Valproate (400 mg/kg) or naloxone (10 mg/kg) pretreatment completely abolish the cGMP increase due to GHB. A GABAergic and/or opiate phenomenon may be involved in the mechanism of GHB induced increase of cGMP. 34 references, 4 figures.

  2. Increased Dendrite Branching in AβPP/PS1 Mice and Elongation of Dendrite Arbors by Fasudil Administration

    PubMed Central

    Couch, Brian A.; DeMarco, George J.; Gourley, Shannon L.; Koleske, Anthony J.

    2011-01-01

    Amyloid-β (Aβ) overproduction and dendrite arbor atrophy are hallmarks of Alzheimer’s disease. The RhoA GTPase (Rho) signals through Rho kinase (ROCK) to control cytoskeletal dynamics and regulate neuron structure. Hyperactive Rho signaling destabilizes neurons leading to dendritic regression that can be rescued by genetic or pharmacological reduction of ROCK signaling. To understand what effect reduced ROCK signaling has on the dendrite arbors of mice that overproduce Aβ, we administered the ROCK inhibitor fasudil to AβPP/PS1 transgenic mice. We report that increased dendrite branching occurs in AβPP/PS1 mice and that fasudil promotes lengthening of the dendrite arbors of CA1 pyramidal neurons. PMID:20413901

  3. Post-Injury Administration of Mitochondrial Uncouplers Increases Tissue Sparing and Improves Behavioral Outcome following Traumatic Brain Injury in Rodents.

    PubMed

    Pandya, Jignesh D; Pauly, James R; Nukala, Vidya N; Sebastian, Andrea H; Day, Kristen M; Korde, Amit S; Maragos, William F; Hall, Edward D; Sullivan, Patrick G

    2007-05-01

    Following experimental traumatic brain injury (TBI), a rapid and significant necrosis occurs at the site of injury which coincides with significant mitochondrial dysfunction. The present study is driven by the hypothesis that TBI-induced glutamate release increases mitochondrial Ca(2+)cycling/overload, ultimately leading to mitochondrial dysfunction. Based on this premise, mitochondrial uncoupling during the acute phases of TBI-induced excitotoxicity should reduce mitochondrial Ca(2+) uptake (cycling) and reactive oxygen species (ROS) production since both are mitochondrial membrane potential dependent. In the present study, we utilized a cortical impact model of TBI to assess the potential use of mitochondrial uncouplers (2,4-DNP, FCCP) as a neuroprotective therapy. Young adult male rats were intraperitoneally administered vehicle (DMSO), 2,4-DNP (5 mg/kg), or FCCP (2.5 mg/kg) at 5 min post-injury. All animals treated with the uncouplers demonstrated a significant reduction in the amount of cortical damage and behavioral improvement following TBI. In addition, mitochondria isolated from the injured cortex at 3 or 6 h post-injury demonstrated that treatment with the uncouplers significantly improved several parameters of mitochondrial bioenergetics. These results demonstrate that post-injury treatment with mitochondrial uncouplers significantly (p < 0.01) increases cortical tissue sparing ( approximately 12%) and significantly (p< 0.01) improves behavioral outcome following TBI. The mechanism of neuroprotection most likely involves the maintenance of mitochondrial homeostasis by reducing mitochondrial Ca(2+) loading and subsequent mitochondrial dysfunction. These results further implicate mitochondrial dysfunction as an early event in the pathophysiology of TBI and that targeting acute mitochondrial events can result in long-term neuroprotection and improve behavioral outcome following brain injury. PMID:17518535

  4. Antifungal serum concentration monitoring: an update.

    PubMed

    Goodwin, Megan L; Drew, Richard H

    2008-01-01

    Invasive fungal infections (IFIs) are occurring with increasing incidence and are associated with significant morbidity and mortality. Understanding the relationship between the pharmacokinetic and pharmacodynamic properties of antifungals is essential to optimize the potential for favourable clinical and microbiological outcomes while minimizing risks of treatment-related toxicity. Antifungal serum concentrations may aid in the determination of appropriate dosing in select circumstances. The polyene and echinocandin classes of antifungals lack sufficient data to justify serum concentration monitoring in routine clinical practice. In contrast, serum concentration monitoring of flucytosine may help to reduce the risk of treatment-related haematological toxicity. Determination of itraconazole serum concentrations is advised in situations where the drug is used for prolonged periods to treat serious IFIs (such as invasive aspergillosis or histoplasmosis) because of variability in absorption following oral administration (most notable for the capsule formulation). The use of serum concentration monitoring during therapy with the extended-spectrum triazoles (i.e. voriconazole and posaconazole) is still evolving, due primarily to inter-patient variability in drug exposure combined with sparse data regarding relationships with efficacy (posaconazole) and both safety and efficacy (voriconazole). PMID:17999982

  5. Increased epidermal cell proliferation in normal human skin in vivo following local administration of interferon-gamma.

    PubMed Central

    Barker, J. N.; Goodlad, J. R.; Ross, E. L.; Yu, C. C.; Groves, R. W.; MacDonald, D. M.

    1993-01-01

    Recombinant human interferon-gamma was administered intradermally (10 micrograms in 0.1 ml) to healthy adult human volunteers from day 1 to day 3, and epidermal cell proliferation was measured on whole skin biopsies at day 6. Three independent parameters were assessed, namely, a) epidermal keratin-16 expression, b) keratinocyte proliferating cell nuclear antigen expression, and c) keratinocyte silver nucleolar organizer region counts. Significantly increased scores for each parameter were observed after interferon-gamma injection (P < 0.01 in each case) compared to site-matched controls. Keratin-16 expression was confined to suprabasal epidermis, whereas proliferating cell nuclear antigen and silver nucleolar organizer region counts were particularly elevated in the basal epidermis. Taken together with previous findings, these studies indicate both proinflammatory and growth regulatory roles for interferon-gamma in human skin. These data are likely to be of particular importance to pathophysiological mechanisms of psoriasis and related cutaneous inflammatory diseases. Images Figure 1 Figure 2 Figure 3 PMID:7682760

  6. Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

    PubMed Central

    DiGirolamo, Douglas J.; Singhal, Vandana; Chang, Xiaoli; Lee, Se-Jin; Germain-Lee, Emily L.

    2015-01-01

    Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system. PMID:26161291

  7. Perioperative use of anti-rheumatic agents does not increase early postoperative infection risks: a Veteran Affairs' administrative database study.

    PubMed

    Abou Zahr, Zaki; Spiegelman, Andrew; Cantu, Maria; Ng, Bernard

    2015-02-01

    The aim of this study was to validate a novel technique that predicts stopping of disease-modifying anti-rheumatic drugs (DMARDs) and biologic agents (BA) from the Veterans Affairs (VA) database and compare infection risks of rheumatoid arthritis patients who stopped versus continued DMARDs/BA perioperatively. We identified 6,024 patients on 1 DMARD or BA in the perioperative period between 1999 and 2009. Time gap between medication stop date and the next start date predicted drug stoppage (X). Time gap between surgery date and stop date predicted whether stoppage was before surgery (Y). Chart review from Houston VA was used for validation. ROC analyses were performed on chart review data to obtain X and Y cutoffs. The primary endpoints were wound infections and other infections within 30 days. ROC analyses found X ≥ 33 (AUC = 0.954) and Y ≥ -11 (AUC = 0.846). Risk of postoperative infections was not different when stopping and continuing DMARDs/BA preoperatively. Stopping BA after surgery was associated with higher odds of postoperative wound (OR 14.15, 95 % CI 1.76-113.76) and general infection (OR 9.2, 95 % CI 1.99-42.60) compared to not stopping. Stopping DMARDs after surgery was associated with increased risk of postope