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Sample records for acth plasma levels

  1. Treatment of infantile spasms with high-dose ACTH: efficacy and plasma levels of ACTH and cortisol.

    PubMed

    Snead, O C; Benton, J W; Hosey, L C; Swann, J W; Spink, D; Martin, D; Rej, R

    1989-08-01

    Fifteen children with infantile spasms and a hypsarrhythmic EEG defined by EEG-videotelemetry monitoring received a regimen of high-dose (150 IU/m2/d) ACTH for their seizures. We carried out an endocrinologic evaluation before and after initiation of the ACTH and conducted a time course study of plasma ACTH and cortisol levels after ACTH dosing. Spasms were controlled and the EEG normalized in 14 of the 15 children. Prior to starting ACTH therapy all the patients had normal prolactin, insulin, cortisol, and ACTH levels in plasma and normal thyroid function. Although the pattern of rise of ACTH levels in plasma after ACTH dosing was similar in all the children, there was great individual variation in the absolute concentrations. However, both the pattern of rise and absolute level of cortisol in plasma after ACTH was highly predictable in all patients. Plasma cortisol rose rapidly within 1 hour of ACTH administration and continued a slower rise for 12 to 24 hours after the ACTH dose. High-dose ACTH therapy seems quite effective in infantile spasms, perhaps because of a sustained high level of plasma cortisol. This sustained plateau of cortisol may be more effective in controlling infantile spasms than the pulse effect expected with oral steroids or lower doses of ACTH.

  2. Effects of benzyl glucoside and chlorogenic acid from Prunus mume on adrenocorticotropic hormone (ACTH) and catecholamine levels in plasma of experimental menopausal model rats.

    PubMed

    Ina, Hiroji; Yamada, Kenji; Matsumoto, Kosai; Miyazaki, Toshio

    2004-01-01

    To investigate the effectiveness of benzyl beta-D-glucopyranoside (BG) and chlorogenic acid (CA), the constituents of the fruit of Prunus mume, for relieving tension in experimental menopausal model rats (M-rats) caused by ether stress, the effects of BG and CA on adrenocorticotropic hormone (ACTH) and catecholamine (adrenaline, noradrenaline, and dopamine) levels were examined in the plasma of M-rats. Caffeic acid, quinic acid, and rosmarinic acid, which are compounds structurally related to CA, were also examined. BG obviously recovered catecholamine levels decreased by ether stress and increased dopamine to high levels. On the other hand, CA significantly decreased the ACTH level increased by ether stress and showed the greatest effect of all compounds. These results suggest that BG and CA may contribute to relieving the tension in M-rats caused by ether stress.

  3. Plasma adrenocorticotropin (ACTH) concentrations and clinical response in horses treated for equine Cushing's disease with cyproheptadine or pergolide.

    PubMed

    Perkins, G A; Lamb, S; Erb, H N; Schanbacher, B; Nydam, D V; Divers, T J

    2002-11-01

    Plasma ACTH levels have been variable in horses with a positive clinical response for therapy for equine Cushing's Disease (ECD). Therefore, our purpose was to determine the value of monitoring plasma adrenocorticotropin (ACTH) levels during treatment of equine Cushing's disease (ECD) with either cyproheptadine (n = 32) or pergolide (n = 10). First, we validated the chemiluminescent ACTH assay (specificity, precision, accuracy, intra-assay and interassay variations) and tested methods of handling the whole blood from the time of collection to when the ACTH was assayed. The sensitivity and specificity of high plasma ACTH levels for detecting ECD was determined in a retrospective study on hospitalised horses (n = 68). Surveys were sent to veterinarians who submitted equine ACTH levels that were high initially and had at least 2 ACTH samples to determine the value of monitoring ACTH levels during therapy of ECD. The ACTH chemiluminescent assay was valid. The ACTH was stable when whole blood was collected and held in plastic tubes for 8 h before separating the plasma. The sensitivity and specificity of plasma ACTH levels for detecting ECD were 84% (n = 19,95% CI 60,97) and 78% (n = 49,95% CI 63,88), respectively. Treated horses generally showed a decrease in plasma ACTH. Plasma ACTH levels may be helpful when monitoring therapy of ECD, although improvement in clinical signs should be considered most important. There were no differences between cyproheptadine and pergolide in terms of improvements in any of the clinical signs.

  4. Effects of inhaling the vapor of Lavandula burnatii super-derived essential oil and linalool on plasma adrenocorticotropic hormone (ACTH), catecholamine and gonadotropin levels in experimental menopausal female rats.

    PubMed

    Yamada, Kenji; Mimaki, Yoshihiro; Sashida, Yutaka

    2005-02-01

    The effects of inhaling the vapor of Lavandula burnatii super-derived essential oil and one of the main components of lavender oil, linalool on plasma adrenocorticotropic hormone (ACTH), catecholamine and gonadotropin levels in menopausal model rats under ether-inhalation were studied. The increased plasma ACTH levels induced by ether-inhalation tended to decrease by pre-inhalation of Lavandula burnetii super and linalool vapor was induced the decrease of ACTH level. The decrease in adrenaline, noradrenaline and dopamine levels induced by ether-inhalation tended to recover, especially, the dopamine level significantly recovered to the normal level by the inhalation of Lavandula burnetii super and linalool vapor. However, the increased plasma gonadotropin levels in ovariectomized retired female rats (menopausal model rats) was significantly decreased by the inhalation of linalool. These results suggest that lavender oil or one of the main components, linalool may contribute to relieving tension and may be applicable to the treatment of menopausal disorders in human beings.

  5. Possible relationship between elevated plasma ACTH and tall stature in familial glucocorticoid deficiency.

    PubMed

    Imamine, Hiroki; Mizuno, Haruo; Sugiyama, Yukari; Ohro, Yoichiro; Sugiura, Tokio; Togari, Hajime

    2005-02-01

    Familial glucocorticoid deficiency (FGD) is characterized clinically by severe glucocorticoid deficiency associated with failure of adrenal responsiveness to ACTH but not with mineralcorticoid deficiency. Excessive growth was described previously in some patients with FGD, many of whom were shown to have mutations in the ACTH receptor gene. The mechanisms responsible for their excessive growth are unknown. We analyzed the ACTH receptor gene in three patients with FGD and discussed the causes of excessive growth in FGD. No mutations were detected in the coding and promoter regions of the ACTH receptor gene of one female patient who had tall stature (+ 2.41S.D.) and advanced bone age (10 years 9 months) when she was 4 years 9 months old. Her plasma ACTH level had been elevated until then (124-2,684 pg/ml). Moreover, plasma estradiol was elevated for her age (21.3 pg/ml), and it decreased in response to the dexamethasone suppression test (from 25.4 to 6.9 pg/ml). Elevated plasma estradiol was apparently related to the increase in plasma ACTH and played a major role in excessive growth in this patient. On the other hand, the genetic analysis showed that the other two patients who were siblings were homozygous for the R137W mutation. Clinically, they responded well to hydrocortisone replacement therapy with almost normal plasma ACTH levels. Although all patients with the R137W mutation reported previously were tall, our patients were of normal height. We speculate that the major causes of excessive growth in FGD are not only from ACTH receptor mutation, but also from the action of elevated plasma ACTH.

  6. Increased plasma ACTH in rats exposed to the elevated plus-maze is independent of the pineal gland.

    PubMed

    Appenrodt, E; Kröning, G; Schwarzberg, H

    1999-11-01

    The involvement of the pineal gland in activation of the hypothalamic-pituitary-adrenocortical (HPA) axis evoked by a stressful stimulus (exposure to the elevated plus-maze) was investigated. Plasma ACTH levels were measured in pinealectomized and pineal-intact rats (sham-operated and non-operated) immediately after a 5 min placement into a plus-maze. A statistically significant elevation in plasma ACTH was measured within all groups; however, no statistical differences between pinealectomized and pineal-intact rats were observed. Similarly, comparison of the plasma ACTH basal values obtained from animals only kept in their home cages did not reveal any statistical differences between pinealectomized and pineal-intact rats. From these results it can be concluded that the pineal gland is not involved in anxiety-related behavior and ACTH response.

  7. ACTH, corticosterone, and beta-endorphin in rat blood plasma after prolonged immobilization stress

    SciTech Connect

    Kiyatkin, E.A.; Amiragova, M.G.; Kushlinskii, N.E.; Polyntsev, Yu. V.

    1986-01-01

    To assess functional relations between changes in ACTH, beta-endorphin (BE), and corticosterone (CS) levels, plasma concentrations of these hormones were studied in rats during the development of prolonged immobilization stress. Plasma hormone concentrations were determined by radioimmunoassay. The results were analyzed by standard statistical methods on a microcomputer. A particular feature about the kit used to determine BE was the presence of 50% cross-reactivity of the antiserum against beta-lipotrophin. To determine CS a highly specific antiserum produced by a laboratory was used.

  8. Effect of ACTH on plasma corticosterone and cortisol in eagles and condors.

    PubMed

    Zenoble, R D; Kemppainen, R J; Young, D W; Carpenter, J W

    1985-12-01

    The effect of ACTH on plasma corticosterone and cortisol was determined in 12 eagles (Haliaeetus leucocephalus) and in 6 Andean condors (Vultur gryphus). In all raptors, the concentration of plasma corticosterone was substantially greater than that of cortisol. After ACTH administration, the eagles had a marked increase (P less than 0.001) in plasma corticosterone concentrations, but not in plasma cortisol. Administration of saline solution did not induce increased plasma corticosterone concentrations in the eagles. The condors had a smaller increase (P less than 0.002) in plasma corticosterone concentrations after ACTH administration, as compared with that of the eagles. However, administration of saline solution in 2 condors resulted in an increase in corticosterone similar to the increase after ACTH administration. In the condor, a stress-related release of endogenous ACTH may have an effect similar to that induced by exogenously administered ACTH. Plasma cortisol concentrations did not increase significantly after administration of ACTH or saline solution in either raptor species.

  9. Effect of ACTH on plasma corticosterone and cortisol in eagles and condors

    USGS Publications Warehouse

    Zenoble, R.D.; Kemppainen, R.J.; Young, D.W.; Carpenter, J.W.

    1985-01-01

    The effect of ACTH on plasma corticosterone and cortisol was determined in 12 eagles (Haliaeetus leucocephalus) and in 6 Andean condors (Vultur gryphus). In all raptors, the concentration of plasma corticosterone was substantially greater than that of cortisol. After ACTH administration, the eagles had a marked increase (P less than 0.001) in plasma corticosterone concentrations, but not in plasma cortisol. Administration of saline solution did not induce increased plasma corticosterone concentrations in the eagles. The condors had a smaller increase (P less than 0.002) in plasma corticosterone concentrations after ACTH administration, as compared with that of the eagles. However, administration of saline solution in 2 condors resulted in an increase in corticosterone similar to the increase after ACTH administration. In the condor, a stress-related release of endogenous ACTH may have an effect similar to that induced by exogenously administered ACTH. Plasma cortisol concentrations did not increase significantly after administration of ACTH or saline solution in either raptor species.

  10. Effects of ACTH on corticosteroid and progesterone levels in female baboons depending on the phase of the menstrual cycle

    SciTech Connect

    Todua, T.N.; Goncharov, N.P.; Katsiya, G.V.; Lapin, B.A.; Vorontsov, V.I.

    1986-01-01

    To study the effect of ACTH on the endocrine function of steroid producing glands depending on the level of sex hormones in the body, a comparative study of the dynamics of steroid hormones in the follicular and luteal phases of the menstrual cycle in response to a standard does of ACTH was undertaken in experiments on hamadryad baboons. Concentrations of corticosterone, 11-deoxycortisol, and progesterone were determined in duplicate samples of plasma by radioimmunoassay. It is shown that the sensitivity of the adrenals to a single injection of ACTH is independent of the phase of the menstrual cycle and the inhibitory effects of ACTH on progesterone secretion is exhibited only in the presence of an actively functioning corpus luteus of the ovary.

  11. Long-term bioeffects of 435-MHz radiofrequency radiation on selected blood-borne endpoints in cannulated rats. Volume 2. Plasma ACTH (adrenocorticotropic hormone) and plasma corticosterone. Final report, 20 August 1984-16 February 1986

    SciTech Connect

    Popovic, V.P.; Toler, J.C.; Bonasera, S.J.; Popovic, P.P.; Honeycutt, C.B.

    1987-08-01

    Two hundred adult male white rats with chronically implanted aortic cannulas were randomly divided into two groups. Animals in the first group were exposed to low-level (1.0 mW/cm2) pulsed-wave 435-MHz radiofrequency radiation (RFR) for approximately 22 h daily, 7 days each week, for 6 months. Animals in the second group were maintained under identical conditions, but were not radiated. The cannulas were used to draw microsamples (0.3 mL) of aortic blood from the unrestrained, unanesthetized rats on a cyclic schedule. Plasma adrenocorticotropic hormone (ACTH) and plasma corticosterone concentrations were determined by radioimmunoassays hormone (ACTH) and plasma corticosterone concentrations were determined by radioimmunoassays. Statistical analysis of the results did not indicate increased plasma ACTH and plasma corticosterone concentrations in exposed animals when compared to sham-exposed animals. Exposure to this low-level radiofrequency environment did not induce stresses that were manifested as an alteration in plasma hormones.

  12. Brain sites mediating corticosteroid feedback inhibition of stimulated ACTH secretion

    SciTech Connect

    Jacobson, L.

    1989-01-01

    There is substantial evidence that the brain mediates stress-induced and circadian increases in ACTH secretion and that corticosteroid concentrations which normalize basal plasma ACTH are insufficient to normalize ACTH responses to circadian or stressful stimuli in adrenalectomized rats. To identify brain sites mediating corticosteroid inhibition of stimulated ACTH secretion, two approaches were used. The first compared brain ({sup 14}C)-2-deoxyglucose uptake in rats with differential ACTH responses to stress. Relative to sham-adrenalectomized (SHAM) rats, adrenalectomized rats replaced with low, constant corticosterone levels via a subcutaneous corticosterone pellet (B-PELLET) exhibited elevated and prolonged ACTH responses to a variety of stimuli. Adrenalectomized rate given a circadian corticosterone rhythm via corticosterone in their drinking water exhibited elevated ACTH levels immediately after stress, but unlike B-PELLET rats, terminated stress induced ACTH secretion normally relative to SHAMS. Therefore, the abnormal ACTH responses to stress in B-PELLET rats were due to the lack of both circadian variations and stress-induced increases in corticosterone. Hypoxia was selected as a standardized stimulus for correlating brain ({sup 14}C)-2-deoxyglucose uptake with ACTH secretion. In intact rats, increases in plasma ACTH and decreases in arterial PO{sub 2} correlated with the severity of hypoxia at arterial PCO{sub 2} below 60 mm Hg. Hypoxia PELLET vs. SHAM rats. However, in preliminary experiments, although hypoxia increased brain 2-deoxyglucose uptake in most brain regions, plasma ACTH correlated poorly with 2-deoxyglucose uptake at 12% and 10% O{sub 2}.

  13. Validating the Novel Method of Measuring Cortisol Levels in Cetacean Skin by use of an ACTH Challenge in Bottlenose Dolphins

    DTIC Science & Technology

    2014-09-30

    Levels in Cetacean Skin by use of an ACTH Challenge in Bottlenose Dolphins 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Novel Method of Measuring Cortisol Levels in Cetacean Skin by use of an ACTH Challenge in Bottlenose Dolphins Thea Bechshoft Aarhus University...method (Bechshoft et al. Submitted) using skin samples collected from bottlenose dolphins (Tursiops truncatus). The dolphins will be sampled as part

  14. The effects of stress on plasma ACTH and corticosterone in young and aging pregnant rats and their fetuses

    SciTech Connect

    Erisman, S. ); Carnes, M. Univ. of Wisconsin, Madison ); Takahashi, L.K.; Lent, S.J. )

    1990-01-01

    Compared to younger rats, old rats exhibit prolonged elevations of plasma ACTH and corticosterone (CORT) in response to stress. In addition, CORT crosses the placenta. To investigate whether fetuses of older rats may be exposed to higher concentrations of CORT during development than fetuses of young rats, we compared the effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in young and aging pregnant rats and their 19-day-old fetuses. The plasma of the mothers and fetuses was assayed for ACTH and CORT by radioimmunoassay. Both young and aging pregnant rats showed a significant increase in plasma ACTH and CORT immediately after exposure to stress. However, aging rats had more prolonged elevation of ACTH and CORT than young rats. This suggests that, like old male rats, aging pregnant rats have an alteration in feedback inhibition of the HPA axis. Prolonged elevation of CORT was also seen in fetuses of aging mothers. These results have important implications concerning the effects of stress during pregnancy at different maternal ages, and for the potential deleterious consequences of prolonged prenatal elevation in stress hormones on the offspring of aging females.

  15. Comparison of salivary and calculated free cortisol levels during low and standard dose of ACTH stimulation tests in healthy volunteers.

    PubMed

    Elbuken, Gulsah; Tanriverdi, Fatih; Karaca, Zuleyha; Kula, Mustafa; Gokahmetoglu, Selma; Unluhizarci, Kursad; Kelestimur, Fahrettin

    2015-03-01

    Salivary cortisol (SC) has been increasingly used as a surrogate biomarker of free cortisol (FC) for the assessment of hypothalamo-pituitary-adrenal (HPA) axis, but there are not enough data regarding its use during ACTH stimulation tests. Therefore, we aimed to determine the responses of SC, calculated free cortisol (cFC) and free cortisol index (FCI) to ACTH stimulation tests in healthy adults. Forty-four healthy volunteers (24 men and 20 women) were included in the study. Low-dose (1 µg) and standard-dose (250 µg) ACTH stimulation tests were performed on two consecutive days. Basal and stimulated total cortisol (TC) and cortisol-binding globulin (CBG) levels and SC levels were measured during both doses of ACTH stimulation tests. cFC (by Coolens' equation) and FCI levels were calculated from simultaneously measured TC and CBG levels. The minimum SC, cFC, FCI levels after low-dose ACTH stimulation test were 0.21, 0.33, 16.06 µg/dL, and after standard-dose ACTH were 0.85, 0.46, 26.11 µg/dL, respectively, in healthy individuals who all had TC responses higher than 20 µg/dL. Peak CBG levels after both doses of ACTH stimulation tests were found to be higher in women than in men. So, by its effect, peak cFC and FCI levels were found to be lower in female than in male group. Neither TC nor SC levels were affected by gender. cFC and FCI levels depend on CBG levels and they are affected by gender. Cut-off levels for SC, cFC, FCI levels after both low- and standard-dose ACTH stimulation are presented. Studies including patients with adrenal insufficiency would be helpful to see the diagnostic value of these suggested cut-off levels.

  16. Long-Term Bioeffects of 435MHz Radiofrequency Radiation on Selected Blood-Borne Endpoints in Cannulated Rats. Volume 2. Plasma ACTH (adrenocorticotropic Hormone) and Plasma Corticosterone

    DTIC Science & Technology

    1987-08-01

    stress hormone concentrations. In this study , an increase in plasma corticosterone was observed after barbiturate anesthesia (Fig. 5). Plasma ACTH...C.H., and Schindler, J. In vitro and vivo adrenal corticosterone secretion following stress. Am J Physiol 196:579-582 (1959). 16. Gale, G.C...related thereto. The animals involved in this study were procured, maintained, and used in accordance with the Animal Welfare Act and the "Guide for

  17. Plasma N-POMC, ACTH and cortisol concentrations in a psychogeriatric population.

    PubMed

    Leake, A; Charlton, B G; Lowry, P J; Jackson, S; Fairbairn, A; Ferrier, I N

    1990-05-01

    Elderly patients with depression and Alzheimer-type dementia (ATD) were compared with age-matched control subjects using a protocol which measured cortisol, adrenocorticotrophic hormone (ACTH) and N-terminal pro-opiomelanocortin (N-POMC) to determine diurnal variation and the effect of dexamethasone administration. Depressed patients had significantly elevated cortisol concentrations both before and after dexamethasone administration. Basal ACTH and N-POMC concentrations were normal in depressed patients but were both elevated, compared with controls, after dexamethasone. By contrast, in ATD patients, cortisol was elevated only after dexamethasone, as was ACTH, but not N-POMC. This may imply that the pattern of secretion of POMC-derived peptides underlying increased cortisol secretion is different in ATD from that in depression.

  18. ACTH Antagonists

    PubMed Central

    Clark, Adrian John; Forfar, Rachel; Hussain, Mashal; Jerman, Jeff; McIver, Ed; Taylor, Debra; Chan, Li

    2016-01-01

    Adrenocorticotropin (ACTH) acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1) Cushing’s disease and ectopic ACTH syndrome – especially while preparing for definitive treatment of a causative tumor, or in refractory cases, or (2) congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article, we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role. PMID:27547198

  19. Bowel perforation complicating an ACTH-secreting phaeochromocytoma

    PubMed Central

    Flynn, Elise; Liu, Dorothy; Ekinci, Elif I; Farrell, Stephen; Zajac, Jeffrey D; De Luise, Mario; Seeman, Ego

    2016-01-01

    Summary ACTH-secreting phaeochromocytoma (ASP) is a rare cause of ACTH-dependent Cushing’s syndrome (CS). We report the case of a 63-year-old female presenting with CS secondary to an ASP complicated by bowel perforation. This case report highlights ASP as an uncommon but important cause of ectopic ACTH secretion (EAS). There have been 29 cases of ASP, all of which were unilateral and benign, but associated with significant complications. Patients presenting with ASP have the potential for cure with unilateral adrenalectomy. Given this promising prognosis if recognised, ASP should be considered in the diagnostic workup of ACTH-dependent CS. As this case demonstrates, gastrointestinal complications can arise from severe hypercortisolaemia associated with CS. Early medical and surgical intervention is imperative as mortality approaches 50% once bowel perforation occurs. Learning points Consider phaeochromocytoma in the diagnostic workup of ACTH-dependent CS; screen with plasma metanephrines or urinary catecholamines. Serial screening may be required if ACTH-secreting phaeochromocytoma is suspected, as absolute levels can be misleading. Early catecholamine receptor blockade and adrenal synthesis blockade may avoid the need for rescue bilateral adrenalectomy in ACTH-secreting phaeochromocytoma. Consider early medical or surgical management when gastrointestinal features are present in patients with CS, as bowel perforation due to severe hypercortisolaemia can occur and is associated with significant mortality. PMID:28203371

  20. Effect of hypotension and hyperosmolality on vasopressin and ACTH responses to hypoglycemia in conscious dogs.

    PubMed

    Raff, H; Papanek, P E; Cowley, A W

    1992-08-01

    The purpose of these studies was, first, to determine whether hypertonic saline (HS) infusion or nitroprusside (NiPr)-induced hypotension augments the vasopressin (AVP) and adrenocorticotropic hormone (ACTH) responses to insulin (Ins)-induced hypoglycemia and, second, to determine whether neurohypophysectomy could attenuate the augmentation. Conscious, male dogs (n = 8) underwent two different types of experiments. In the first, Ins was preceded by either a 30-min infusion of normal saline (control) or HS to raise plasma osmolality and AVP. HS augmented the AVP response but diminished the ACTH response to Ins. In the second group of experiments, Ins was preceded by a controlled decrease in mean arterial pressure using NiPr, which led to an increase in AVP and ACTH. The initial ACTH and AVP response to Ins was augmented by NiPr, but this early augmentation was not sustained. Neurohypophysectomy attenuated the early augmentation of the ACTH response to Ins by NiPr, but did not alter the final ACTH level achieved. We conclude that HS augmented the AVP but inhibited the ACTH response to Ins probably because of expansion of plasma volume. Concomitant hypotension led to an augmentation of the early but not sustained AVP and ACTH response to Ins. Neurohypophysectomy eliminated this augmentation, suggesting a role for AVP from the neural lobe in the early ACTH response to combined hypotension and Ins-induced hypoglycemia.

  1. Changes in plasma adrenocorticotropic hormone and cortisol levels induced by intracerebroventricular injection of histamine and its related compounds in dogs.

    PubMed

    Tsujimoto, S; Kamei, C; Yoshida, T; Tasaka, K

    1993-08-01

    Changes in plasma adrenocorticotropic hormone (ACTH) and cortisol levels induced by intracerebroventricular injection of histamine (H(i)) were studied in dogs. Intracerebroventricular administration of Hi at doses of 5 and 10 micrograms/kg caused a significant increase in plasma ACTH, while more rapid and more marked increase in plasma cortisol was noticed after Hi injection at doses of 2-10 micrograms/kg. Similar results were obtained when 2-methylhistamine was injected; remarkable increases in both plasma ACTH and cortisol levels were observed at doses of 25 and 50 micrograms/kg. However, no such effect was elicited by 4-methylhistamine even at a dose of 50 micrograms/kg. The rate of plasma cortisol increase induced by either Hi or 2-methylhistamine was significantly faster than that of plasma ACTH. Simultaneous application of pyrilamine (intracerebroventricularly) with H(i) resulted in the significant inhibition of H(i)-induced hormone secretions, but in similar administration neither ACTH nor cortisol were affected by cimetidine. In hypophysectomized dogs, a significant increase in plasma cortisol level was also observed after H(i) injection at a dose of 5 micrograms/kg. Intravenous infusion of hexamethonium continued before and after H(i) injection failed to inhibit the increase in plasma ACTH and cortisol levels induced by H(i). From these findings, it can be concluded that intracerebroventricular injection of H(i) caused an increase in plasma ACTH and cortisol levels via H1-receptor, and it is suggested that to some extent, the cortisol release elicited by H(i) is certainly produced without participation of ACTH.

  2. ACTH (cosyntropin) stimulation test

    MedlinePlus

    ... The ACTH stimulation test measures how well the adrenal glands respond to adrenocorticotropic hormone ( ACTH ). ACTH is a ... produced in the pituitary gland that stimulates the adrenal glands to release a hormone called cortisol. How the ...

  3. EDTA interference in electrochemiluminescence ACTH assay.

    PubMed

    Toprak, Burak; Yalcin, Hulya; Arı, Elif; Colak, Ayfer

    2016-11-01

    Background As plasma is the recommended sample type for Roche adrenocorticotropic hormone (ACTH) assay, we evaluated the effect of EDTA concentration on Cobas ACTH assay. Methods Samples containing twofold and fourfold higher concentrations of EDTA were prepared by adding plasma to empty K2EDTA tubes and by making under-filled EDTA tubes. All measurements were performed with four replicates. Results Increased EDTA concentration resulted in a significant decrease in ACTH concentration. Fifty-per cent-filled EDTA tube showed 19% decrease in ACTH concentration and 25% filled EDTA tube showed 50% decrease in ACTH concentration. Conclusion We recommend that inadequately filled EDTA specimens should be rejected when using Cobas ACTH assay.

  4. Effects of Chronic ACTH Excess on Human Adrenal Cortex

    PubMed Central

    Bertagna, Xavier

    2017-01-01

    Chronic ACTH excess leads to chronic cortisol excess, without escape phenomenon, resulting in Cushing’s syndrome. Excess adrenal androgens also occur: in females, they will overcompensate the gonadotrophic loss, inducing high testosterone; in males, they will not compensate it, inducing low testosterone. Chronic ACTH excess leads to chronic adrenal mineralocorticoid excess and low aldosterone levels: after an acute rise, aldosterone plasma levels resume low values after a few days when ACTH is prolonged. Two other mineralocorticoids in man, cortisol and 11 deoxycorticosterone (DOC), at the zona fasciculata, will not escape the long-term effect of chronic ACTH excess and their secretion rates will remain elevated in parallel. Over all, the concomitant rise in cortisol and 11 DOC will more than compensate the loss of aldosterone, and eventually create a state of chronic mineralocorticoid excess, best evidenced by the accompanying suppression of the renin plasma levels, a further contribution to the suppression of aldosterone secretion. Prolonged in vivo stimulation with ACTH leads to an increase in total adrenal protein and RNA synthesis. Cell proliferation is indicated by an increase in total DNA the resulting adrenocortical hyperplasia participates in the amplified response of the chronically stimulated gland, and the weight of each gland can be greatly increased. The growth-stimulatory effect of ACTH in vivo most likely proceeds through the activation of a local and complex network of autocrine growth factors and their own receptors; a number of compounds, including non-ACTH proopiomelanocortin peptides such as γ3-MSH, have been shown to exert some adrenocortical growth effect. PMID:28337175

  5. Validating the Novel Method of Measuring Cortisol Levels in Cetacean Skin by Use of an ACTH Challenge in Bottlenose Dolphins

    DTIC Science & Technology

    2013-09-30

    known as an ACTH (adrenocorticotrophic hormone ) challenge, in a group of bottlenose dolphins (Tursiops truncatus). The dolphins will be sampled as part...of an ongoing study of stress hormones conducted by Dr. Dorian Houser in collaboration with the U.S. Navy Marine Mammal Program (MMP). The ACTH

  6. Ectopic ACTH syndrome due to pheochromocytoma: case report and review of the literature.

    PubMed Central

    Forman, B. H.; Marban, E.; Kayne, R. D.; Passarelli, N. M.; Bobrow, S. N.; Livolsi, V. A.; Merino, M.; Minor, M.; Farber, L. R.

    1979-01-01

    A 51-year-old female was diagnosed preoperatively to have a pheochromocytoma producing ACTH. This diagnosis was based upon her paroxysmal hypertension, hyperpigmentation, and hypokalemia. Elevated levels of serum and urine corticosteroids, plasma ACTH, urinary VMA, and catecholamines fell after a right adrenal pheochromocytoma was removed. Subsequently this tumor was found to have a high content of ACTH. Review of the literature indicates a mortality rate of 57% for this syndrome. Proper preoperative recognition and management can result in total cure. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:222080

  7. ACTH (Adrenocorticotropic Hormone) Test

    MedlinePlus

    ... disease and ectopic ACTH from cortisol and ACTH measurement alone. A variety of other tests are often ... as any steroid, oral, inhaled, topical or eye drop may cause abnormal results. Megestrol acetate can also ...

  8. Leptin Alters Adrenal Responsiveness by Decreasing Expression of ACTH-R, StAR, and P450c21 in Hypoxemic Fetal Sheep

    PubMed Central

    Su, Yixin; Carey, Luke C.; Pulgar, Victor M.

    2012-01-01

    The late gestation increase in adrenal responsiveness to adrenocorticotropin (ACTH) is dependent upon the upregulation of the ACTH receptor (ACTH-R), steroidogenic acute regulatory protein (StAR), and steroidogenic enzymes in the fetal adrenal. Long-term hypoxia decreases the expression of these and adrenal responsiveness to ACTH in vivo. Leptin, an adipocyte-derived hormone which attenuates the peripartum increase in fetal plasma cortisol is elevated in hypoxic fetuses. Therefore, we hypothesized that increases in plasma leptin will inhibit the expression of the ACTH-R, StAR, and steroidogenic enzymes and attenuate adrenal responsiveness in hypoxic fetuses. Spontaneously hypoxemic fetal sheep (132 days of gestation, PO2 ∼15 mm Hg) were infused with recombinant human leptin (n = 8) or saline (n = 7) for 96 hours. An ACTH challenge was performed at 72 hours of infusion to assess adrenal responsiveness. Plasma cortisol and ACTH were measured daily and adrenals were collected after 96 hours infusion for messenger RNA (mRNA) and protein expression measurement. Plasma cortisol concentrations were lower in leptin- compared with saline-infused fetuses (14.8 ± 3.2 vs 42.3 ± 9.6 ng/mL, P < .05), as was the cortisol:ACTH ratio (0.9 ± 0.074 vs 46 ± 1.49, P < .05). Increases in cortisol concentrations were blunted in the leptin-treated group after ACTH1-24 challenge (F = 12.2, P < .0001). Adrenal ACTH-R, StAR, and P450c21 expression levels were reduced in leptin-treated fetuses (P < .05), whereas the expression of Ob-Ra and Ob-Rb leptin receptor isoforms remained unchanged. Our results indicate that leptin blunts adrenal responsiveness in the late gestation hypoxemic fetus, and this effect appears mediated by decreased adrenal ACTH-R, StAR, and P450c21 expression. PMID:22534336

  9. Effects of smoking on ACTH and cortisol secretion

    SciTech Connect

    Seyler, L.E. Jr.; Fertig, J.; Pomerleau, O.; Hunt, D.; Parker, K.

    1984-01-02

    The relationships among changes in plasma nicotine, ACTH, and cortisol secretion after smoking were investigated. Ten male subjects smoked cigarettes containing 2.87 mg nicotine and 0.48 mg nicotine. No rises in cortisol or ACTH were detected after smoking 0.48 mg nicotine cigarettes. Cortisol rises were significant in 11 of 15 instances after smoking 2.87 mg nicotine cigarattes, but ACTH rose significantly in only 5 of the 11 instances where cortisol increased. Each ACTH rise occurred in a subject who reported nausea and was observed to be pale, sweaty, and tachycardic. Peak plasma nicotine concentrations were not significantly different in sessions when cortisol rose with or without ACTH increases, but cortisol increases were significantly greater in nauseated than in non-nauseated smokers. This data suggest that smoking-induced nausea stimulates cortisol release by stimulating ACTH secretion and that cortisol secretion in non-nauseated smokers may occur through a non-ACTH mechanism.

  10. Effect of immobilization and concurrent exposure to a pulse-modulated microwave field on core body temperature, plasma ACTH and corticosteroid, and brain ornithine decarboxylase, Fos and Jun mRNA.

    PubMed

    Stagg, R B; Hawel, L H; Pastorian, K; Cain, C; Adey, W R; Byus, C V

    2001-04-01

    Exposure of humans and rodents to radiofrequency (RF) cell phone fields has been reported to alter a number of stress- related parameters. To study this potential relationship in more detail, tube-restrained immobilized Fischer 344 rats were exposed in the near field in a dose-dependent manner to pulse-modulated (11 packets/s) digital cell phone microwave fields at 1.6 GHz in accordance with the Iridium protocol. Core body temperatures, plasma levels of the stress-induced hormones adrenocorticotrophic hormone (ACTH) and corticosterone, and brain levels of ornithine decarboxylase (Odc), Fos and Jun mRNAs were measured as potential markers of stress responses mediated by RF radiation. We tested the effects of the loose-tube immobilization with and without prior conditioning throughout a 2-h period (required for near-field head exposure to RF fields), on core body temperature, plasma ACTH and corticosteroids. Core body temperature increased transiently (+/-0.3 degrees C) during the initial 30 min of loose-tube restraint in conditioned animals. When conditioned/tube-trained animals were followed as a function of time after immobilization, both the ACTH and corticosterone levels were increased by nearly 10-fold. For example, within 2-3 min, ACTH increased to 83.2 +/- 31.0 pg/dl, compared to 28.1 +/- 7.7 pg/dl for cage controls, reaching a maximum at 15-30 min (254.6 +/- 46.8 pg/dl) before returning to near resting levels by 120 min (31.2 +/- 10.2 pg/dl). However, when non-tube-trained animals were submitted to loose-tube immobilization, these animals demonstrated significantly higher (3-10-fold greater) hormone levels at 120 min than their tube-trained counterparts (313.5 +/- 54.8 compared to 31.2 +/- 10.2 pg/dl; corticosterone, 12.2 +/- 6.2 microg/dl compared to 37.1 +/- 6.4 microg/dl). Hormone levels in exposed animals were also compared to those in swim-stressed animals. Swimming stress also resulted in marked elevation in both ACTH and corticosterone levels, which

  11. Cortisol and ACTH levels in drug-naive adolescents with first-episode early onset schizophrenia.

    PubMed

    Şimşek, Şeref; Gençoğlan, Salih; Yüksel, Tuğba; Aktaş, Hüseyin

    2017-03-01

    The aim of this study was to investigate serum levels of cortisol and adrenocorticotropic hormone in adolescents with first-episode early onset schizophrenia. A total of 23 adolescent patients, who did not receive prior therapy and who were diagnosed with psychosis according to DSM-IV, were included. Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version, Positive and Negative Symptom Scale, and Clinical Global Impression Scale were conducted with the participants. No significant differences were found between the patients and the control subjects in serum cortisol and adrenocorticotropic hormone levels (P > .05). Our study's findings do not support the hypothesis of increased hypothalamic-pituitary-adrenal axis activity in first-episode early onset schizophrenia.

  12. Adrenocortical response to low-dose ACTH test in female patients with rheumatoid arthritis.

    PubMed

    Radikova, Zofia; Rovensky, Jozef; Vlcek, Miroslav; Penesova, Adela; Kerlik, Jana; Vigas, Milan; Imrich, Richard

    2008-12-01

    Alterations in adrenal steroid production have been suggested in females with rheumatoid arthritis (RA). The aim of the present study was to assess adrenocortical function in RA females. We examined 11 female RA patients (RA: age 30 +/- 2 years, BMI 21.0 +/- 0.7 kg/m(2)) and 10 matched healthy controls (C: age 31 +/- 1 years, BMI 21.6 +/- 0.6 kg/m(2)). Low-dose adrenocorticotropic hormone (ACTH) test (i.v. bolus of 1 microg synthetic ACTH) was performed at 10.00 h with blood sampling every 15 min for 90 min. Cortisol, 17-OH-progesterone (17OHP), androstenedione (ASD), and dehydroepiandrosterone (DHEA) were assayed in plasma. Baseline cortisol levels were higher in RA patients (RA: 385 +/- 38 versus C: 229 +/- 28 nmol/L, P= 0.007). In both study groups, ACTH administration increased all the four steroids measured (P < 0.001). Cortisol response to ACTH administration was diminished in RA patients when compared to controls (Delta(max): 284 +/- 24 in RA versus 424 +/- 31 nmol/L in C, P= 0.002). ACTH-induced maximal rise in plasma DHEA was significantly lower in RA patients when compared to controls (Delta(max): 2.59 +/- 0.68 in RA versus 5.57 +/- 1.25 ng/mL in C, P= 0.015). No significant between-groups differences were found in responses of ASD or 17OHP. The molar ratio of ASD:cortisol was significantly lower (P < 0.05) in RA patients at base line, but did not differ during ACTH test. After ACTH bolus, the cortisol:17OHP ratio decreased significantly in the RA group (P < 0.001), whereas there was no change in the control group. The present results show decreased secretion of cortisol and DHEA in RA patients in response to ACTH, suggesting a subtle HPA hypofunction at the adrenocortical level.

  13. Effects of ACTH on the last step of aldosterone biosynthesis.

    PubMed

    Cozza, E N; Ceballos, N R; Lantos, C P

    1989-12-01

    The production of tritiated aldosterone and tritiated SM (a saponifiable 18-hydroxycorticosterone derivative) by rat adrenals were studied at various incubation times in absence or presence of two concentrations of ACTH. Tritiated 18-hydroxycorticosterone or 18-deoxyaldosterone served as precursors. The lower ACTH concentration (150 pM) increased the production of tritiated aldosterone. Whereas, the higher ACTH concentration (1.5 microM) stimulated tritiated aldosterone production at shorter incubation time (30 min), while after 60 min it inhibited. This time dependency would reflect variations in the levels of endogenous steroids. On the other hand, the effects of ACTH on tritiated SM production were opposite to those on tritiated aldosterone. In effect, while 150 pM ACTH inhibited SM production, 1.5 microM ACTH stimulated it. These results suggest that ACTH promotes opposite effects on the productions of aldosterone and SM and therefore both productions would be coordinated under the regulation of ACTH.

  14. Validating the Novel Method of Measuring Cortisol Levels in Cetacean Skin by use of an ACTH Challenge in Bottlenose Dolphins

    DTIC Science & Technology

    2015-09-30

    in Cetacean Skin by use of an ACTH Challenge in Bottlenose Dolphins Thea Bechshoft Aarhus University Bioscience Roskilde Frederiksborgvej...using skin samples collected from bottlenose dolphins (Tursiops truncatus). The dolphins will be sampled as part of an ongoing out-of water stress test...N000141110436. The stress test in brief: Each dolphin is asked to perform a routine, voluntary beach into a padded beaching tray. Immediately following

  15. Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane.

    PubMed

    Malik, Sundeep; Dolan, Terrance M; Maben, Zachary J; Hinkle, Patricia M

    2015-11-13

    The melanocortin-2 (MC2) receptor is a G protein-coupled receptor that mediates responses to ACTH. The MC2 receptor acts in concert with the MC2 receptor accessory protein (MRAP) that is absolutely required for ACTH binding and signaling. MRAP has a single transmembrane domain and forms a highly unusual antiparallel homodimer that is stably associated with MC2 receptors at the plasma membrane. Despite the physiological importance of the interaction between the MC2 receptor and MRAP, there is little understanding of how the accessory protein works. The dual topology of MRAP has made it impossible to determine whether highly conserved and necessary regions of MRAP are required on the intracellular or extracellular face of the plasma membrane. The strategy used here was to fix the orientation of two antiparallel MRAP molecules and then introduce inactivating mutations on one side of the membrane or the other. This was achieved by engineering proteins containing tandem copies of MRAP fused to the amino terminus of the MC2 receptor. The data firmly establish that only the extracellular amino terminus (Nout) copy of MRAP, oriented with critical segments on the extracellular side of the membrane, is essential. The transmembrane domain of MRAP is also required in only the Nout orientation. Finally, activity of MRAP-MRAP-MC2-receptor fusion proteins with inactivating mutations in either MRAP or the receptor was rescued by co-expression of free wild-type MRAP or free wild-type receptor. These results show that the basic MRAP-MRAP-receptor signaling unit forms higher order complexes and that these multimers signal.

  16. Plasma. beta. -endorphin and stress hormone levels during adaptation and stress

    SciTech Connect

    Lishmanov, Yu.B.; Trifonova, Zh.V.; Tsibin, A.N.; Maslova, L.V.; Dement'eva, L.A.

    1987-09-01

    This paper describes a comparative study of ..beta..-endorphin and stress hormone levels in the blood plasma of rats during stress and adaptation. Immunoreactive ..beta..-endorphin in the blood plasma was assayed by means of a kit after preliminary isolation of the ..beta..-endorphin fraction by affinity chromatography on sepharose; ACTH was assayed with a kit and cortisol, insulin, thyroxine and tri-iodothyronine by means of kits from Izotop. Determination of plasma levels of ..beta..-endorphin and other opioids could evidently be an important method of assessing the state of resistance of the organism to stress.

  17. ACTH blood test

    MedlinePlus

    ... any time the skin is broken) Alternative Names Serum adrenocorticotropic hormone; Adrenocorticotropic hormone; Highly-sensitive ACTH Images Endocrine glands References Ferri FF. Cushing's disease and syndrome. In: Ferri FF, ed. Ferri's Clinical ...

  18. Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation

    NASA Technical Reports Server (NTRS)

    Brooks, V. L.; Keil, L. C.

    1992-01-01

    Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1) in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS).

  19. Analysis of the brain ACTH-immunoreactive peptide spectrum in inbred mice

    SciTech Connect

    Fedoseev, Yu.L.; Blednov, Yu.A.; Seredenin, S.B.

    1987-01-01

    Mice of the BALB/c (C) and C57BL/6 (B6) strains, characterized by high and low emotionality respectively in open field tests, have been shown to differ considerably in both the initial level and the time course of changes in the plasma ACTH concentration after exposure to stress in an open field and after administration of a benzodiazepine tranquilizer. The ACTH concentration in the pituitary gland of animals of these lines also differs. The ACTH molecule is known to contain regions with neurotropic activity. It can therefore be postulated that differences in the level of this hormone and the products of its bioconversion in the brain are an essential factor in the mechanisms of formation of the hereditary features of emotional behavior. In this first stage of this investigation, represented in this paper and undertaken to test this hypothesis, spectra of ACTH-immunoreactive peptides were studied in chromatographic fractions of an acid brain extract as well as in the blood plasma of mice belonging to B6 and C lines and their hybrids. The peptides were determined by radioimmunoassay.

  20. Possible ACTH-independent, cortisol-secreting and DHEA-secreting metastatic hepatocellular carcinoma causing Cushing's syndrome.

    PubMed

    Sacerdote, Alan; Inoue, Taiga; Thomas, Nithin; Bahtiyar, Gul

    2015-12-23

    Cortisol production by hepatocellular carcinoma (HCC) has not been previously reported and dehydroepiandrosterone (DHEA) secretion by HCC is rare. We report a case of a 53-year-old woman admitted with dyspnoea and headache. Serum cortisol by immunoassay (IA) was 42.3 μg/dL, urine free cortisol (UFC) by liquid chromatography mass spectrometry (LC/MS/MS) was 106.1 μg/24 h, serum DHEA by LC/MS/MS was 4886 ng/mL, serum DHEA-S by LC/MS/MS was 4477 ng/mL and plasma adrenocorticotrophic hormone (ACTH) by IA was 10 pg/mL. CT showed likely HCC metastatic to the left adrenal gland, brain and lungs. Liver and adrenal gland biopsies confirmed HCC. ACTH tumour staining was negative. High serum and UFC levels and high serum DHEA and DHEA-S with low-normal plasma ACTH and negative tumour ACTH staining suggested ACTH-independent ectopic Cushing's syndrome (CS); cortisol and DHEA being likely secreted by the HCC. To the best of our knowledge, this is the first reported case of HCC associated with CS.

  1. A case of isolated ACTH deficiency who developed autoimmune-mediated hypothyroidism and impaired water diuresis during glucocorticoid replacement therapy.

    PubMed

    Kageyama, Y

    2000-12-01

    A case of isolated ACTH deficiency who developed autoimmune-mediated hypothyroidism and still showed impaired water diuresis during glucocorticoid replacement therapy is reported. A 45-year-old woman was initially admitted for nausea, vomiting, and general malaise. Her serum sodium and plasma osmolality, ACTH and cortisol values were low, but her urine osmolality was high. Other pituitary hormone levels, thyroid hormone levels, and a computed tomogram of the pituitary gland were normal. The patient was treated with hydrocortisone and followed in the outpatient clinic; however, she was lost to follow up 18 months after admission. Three years later she presented with hypoglycemia and hyponatremia. Her serum or plasma ACTH, FT3, FT4, cortisol levels were low and her serum TSH level was high. Pituitary stimulation tests revealed a blunted response of ACTH to CRH and an exaggerated response of TSH to TRH. Plasma ADH was inappropriately high, and a water-loading test revealed impaired water diuresis and poor suppression of ADH. Although ADH was suppressed, impaired water diuresis was observed in the water loading test after hydrocortisone supplementation. Thyroxine supplementation completely normalized the water diuresis. Her outpatient clinic medical records revealed a gradual increase in TSH levels during follow up, indicating that she had developed hypothyroidism during glucocorticoid replacement therapy. The hyponatremia on the first admission was due to glucocorticoid deficiency, whereas the hyponatremia on the second admission was due to combined deficiencies of glucocorticoid and thyroid hormones.

  2. Metastatic Pancreatic Neuroendocrine Tumor that Progressed to Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome with Growth Hormone-releasing Hormone (GHRH) Production

    PubMed Central

    Tadokoro, Rie; Sato, Shotaro; Otsuka, Fumiko; Ueno, Makoto; Ohkawa, Shinichi; Katakami, Hideki; Taniyama, Matsuo; Nagasaka, Shoichiro

    2016-01-01

    The patient was a 61-year-old woman who had a well-differentiated pancreatic neuroendocrine tumor (PNET) with lymph node metastasis. After 15 months of octreotide treatment, glucose control deteriorated and pigmentation of the tongue and moon face developed, leading to the diagnosis of ectopic adrenocorticotropic hormone (ACTH) syndrome. An abnormal secretion of growth hormone (GH) was identified, and the plasma growth hormone-releasing hormone (GHRH) level was elevated. A tumor biopsy specimen positively immunostained for ACTH and GHRH. Ectopic hormone secretion seems to have evolved along with the progression of the PNET. PMID:27746436

  3. Metastatic Pancreatic Neuroendocrine Tumor that Progressed to Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome with Growth Hormone-releasing Hormone (GHRH) Production.

    PubMed

    Tadokoro, Rie; Sato, Shotaro; Otsuka, Fumiko; Ueno, Makoto; Ohkawa, Shinichi; Katakami, Hideki; Taniyama, Matsuo; Nagasaka, Shoichiro

    The patient was a 61-year-old woman who had a well-differentiated pancreatic neuroendocrine tumor (PNET) with lymph node metastasis. After 15 months of octreotide treatment, glucose control deteriorated and pigmentation of the tongue and moon face developed, leading to the diagnosis of ectopic adrenocorticotropic hormone (ACTH) syndrome. An abnormal secretion of growth hormone (GH) was identified, and the plasma growth hormone-releasing hormone (GHRH) level was elevated. A tumor biopsy specimen positively immunostained for ACTH and GHRH. Ectopic hormone secretion seems to have evolved along with the progression of the PNET.

  4. From Bioinactive ACTH to ACTH Antagonist: The Clinical Perspective

    PubMed Central

    Ghaddhab, Chiraz; Vuissoz, Jean-Marc; Deladoëy, Johnny

    2017-01-01

    The adrenocorticotropic hormone (ACTH) is a pituitary hormone derived from a larger peptide, the proopiomelanocortin (POMC), as are the MSHs (α-MSH, β-MSH, and γ-MSH) and the β-LPH-related polypeptides (Figure 1A). ACTH drives adrenal steroidogenesis and growth of the adrenal gland. ACTH is a 39 amino acid polypeptide that binds and activates its cognate receptor [melanocortin receptor 2 (MC2R)] through the two regions H6F7R8W9 and K15K16R17R18P19. Most POMC-derived polypeptides contain the H6F7R8W9 sequence that is conserved through evolution. This explains the difficulties in developing selective agonists or antagonists to the MCRs. In this review, we will discuss the clinical aspects of the role of ACTH in physiology and disease, and potential clinical use of selective ACTH antagonists. PMID:28228747

  5. Ectopic ACTH syndrome: clinicopathological correlations.

    PubMed Central

    Singer, W; Kovacs, K; Ryan, N; Horvath, E

    1978-01-01

    Ten out of 164 cases of bronchogenic carcinoma showed pathological evidence at necropsy of the ectopic ACTH syndrome. All occurred in association with oat-cell carcinoma, constituting 19% of that group. The pathological features consisted of adrenocortical hyperplasia confined to the zona fasciculata and Crooke's hyaline change in the pituitary. Immunoperoxidase stainable ACTH was detected in the pituitary but not in the carcinoma tissue, a surprising finding, which may be due to the different nature of ACTH present in tumour tissue. The ectopic ACTH syndrome was diagnosed ante mortem in only four out of 10 patients on the basis of hypokalaemia and metabolic alkalosis. The lack of clinical pointers in all but terminal cases is discussed as well as possible measures for earlier diagnosis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:209063

  6. Differential responses of cortisol and corticosterone to adrenocorticotropic hormone (ACTH) in a subterranean rodent (Ctenomys talarum).

    PubMed

    Vera, Federico; Zenuto, Roxana Rita; Antenucci, Carlos Daniel

    2012-03-01

    We aimed to evaluate the responses of cortisol, corticosterone, and blood glucose to adrenocorticotropic hormone (ACTH) in males and females of the subterranean rodent Ctenomys talarum and addressed interannual variations in the plasma levels of both hormones. The most important results indicate that: (1) cortisol positively responds to the ACTH signal but corticosterone does not, even though corticosterone levels were higher than cortisol concentrations, (2) plasma corticosterone concentrations in free-living animals were 20 times higher compared to values reported for the same population during previous annual periods and, as cortisol levels were similar, this resulted in much lower cortisol/corticosterone ratios, (3) cortisol and corticosterone differentiated in their relative proportions in plasma in free-living males and females. These results indicate that cortisol and corticosterone are differentially regulated in our study species and emphasize that a remarkable temporal variation in the relative proportions of these hormones may occur in natural populations. Therefore, the conclusions regarding the presence of cortisol and corticosterone in plasma of wild animals may differ substantially depending on the moment when the study is conducted. Recent data indicate that cortisol and corticosterone are not interchangeable hormones in species of free-living vertebrates. We suggest that, in addition to the classical roles of glucocorticoids (GCs), it is crucial that other physiological functions be kept in mind when interpreting GC data from wild species.

  7. Role of ACTH and Other Hormones in the Regulation of Aldosterone Production in Primary Aldosteronism

    PubMed Central

    El Ghorayeb, Nada; Bourdeau, Isabelle; Lacroix, André

    2016-01-01

    The major physiological regulators of aldosterone production from the adrenal zona glomerulosa are potassium and angiotensin II; other acute regulators include adrenocorticotropic hormone (ACTH) and serotonin. Their interactions with G-protein coupled hormone receptors activate cAMP/PKA pathway thereby regulating intracellular calcium flux and CYP11B2 transcription, which is the specific steroidogenic enzyme of aldosterone synthesis. In primary aldosteronism (PA), the increased production of aldosterone and resultant relative hypervolemia inhibits the renin and angiotensin system; aldosterone secretion is mostly independent from the suppressed renin–angiotensin system, but is not autonomous, as it is regulated by a diversity of other ligands of various eutopic or ectopic receptors, in addition to activation of calcium flux resulting from mutations of various ion channels. Among the abnormalities in various hormone receptors, an overexpression of the melanocortin type 2 receptor (MC2R) could be responsible for aldosterone hypersecretion in aldosteronomas. An exaggerated increase in plasma aldosterone concentration (PAC) is found in patients with PA secondary either to unilateral aldosteronomas or bilateral adrenal hyperplasia (BAH) following acute ACTH administration compared to normal individuals. A diurnal increase in PAC in early morning and its suppression by dexamethasone confirms the increased role of endogenous ACTH as an important aldosterone secretagogue in PA. Screening using a combination of dexamethasone and fludrocortisone test reveals a higher prevalence of PA in hypertensive populations compared to the aldosterone to renin ratio. The variable level of MC2R overexpression in each aldosteronomas or in the adjacent zona glomerulosa hyperplasia may explain the inconsistent results of adrenal vein sampling between basal levels and post ACTH administration in the determination of source of aldosterone excess. In the rare cases of glucocorticoid remediable

  8. Effect of space flights on plasma hormone levels in man and in experimental animal

    NASA Astrophysics Data System (ADS)

    Macho, L.; Kvetňanský, R.; Vigaš, M.; Németh, S.; Popova, I.; Tigranian, R. A.; Noskov, V. B.; Serova, L.; Grigoriev, I. A.

    An important increase of plasma hormone levels like insulin, TSH and aldosterone was observed in human subjects after space flights, however in the changes of plasma content of ACTH, cortisol, adrenaline and noradrenaline the individual variations were observed in relation to number and duration of space flight. For evaluation of the effects of these changes in plasma hormone levels on metabolic processes also the experiments with small animals subjected to space flights on a board of biosatellite of Cosmos series were running. An elevation of plasma levels of corticosterone, adrenaline, noradrenaline and insulin was found in rats after the space flights of duration from 7 to 20 days. It was demonstrated, that the increase of corticosterone in plasma is followed by the activation of enzymes involved in the aminoacid metabolism in rat liver (tyrosine aminotransferase, tryptophanpyrolase, alanine aminotransferase and aspartate aminotransferase). After a short recovery period (2 to 6 days) the plasma corticosterone concentration and also the activity of liver enzymes returned to control levels. The exposition of animals to stress stimuli during this recovery period showed higher response of corticosterone levels in flight rats as compared to intact controls. The increase of plasma catecholamine levels was not followed by elevation of lipolysis in adipose tissue. This is due to lower response of adipose tissue to catecholamine because a decrease of the stimulation of lipolysis by noradrenaline was observed in animals after space flight. The increase of insulin was not followed by adequate decrease of glucose concentration suggesting a disturbances in glucose utilization similarly as in cosmonauts after a long-term space flight. These results showed that changes in plasma hormone levels, observed after space flight, affected the regulation of metabolic processes in tissues.

  9. Changes in plasma melanocyte-stimulating hormone, ACTH, prolactin, GH, LH, FSH, and thyroid-stimulating hormone in response to injection of sulpiride, thyrotropin-releasing hormone, or vehicle in insulin-sensitive and -insensitive mares.

    PubMed

    Valencia, N Arana; Thompson, D L; Mitcham, P B

    2013-05-01

    Six insulin-sensitive and 6 insulin-insensitive mares were used in a replicated 3 by 3 Latin square design to determine the pituitary hormonal responses (compared with vehicle) to sulpiride and thyrotropin-releasing hormone (TRH), 2 compounds commonly used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. Mares were classified as insulin sensitive or insensitive by their previous glucose responses to direct injection of human recombinant insulin. Treatment days were February 25, 2012, and March 10 and 24, 2012. Treatments were sulpiride (racemic mixture, 0.01 mg/kg BW), TRH (0.002 mg/kg BW), and vehicle (saline, 0.01 mL/kg BW) administered intravenously. Blood samples were collected via jugular catheters at -10, 0, 5, 10, 20, 30, 45, 60, 90, and 120 min relative to treatment injection. Plasma ACTH concentrations were variable and were not affected by treatment or insulin sensitivity category. Plasma melanocyte-stimulating hormone (MSH) concentrations responded (P < 0.01) to both sulpiride and TRH injection and were greater (P < 0.05) in insulin-insensitive mares than in sensitive mares. Plasma prolactin concentrations responded (P < 0.01) to both sulpiride and TRH injection, and the response was greater (P < 0.05) for sulpiride; no effect of insulin sensitivity was observed. Plasma thyroid-stimulating hormone (TSH) concentrations responded (P < 0.01) to TRH injection only and were higher (P < 0.05) in insulin-sensitive mares in almost all time periods. Plasma LH and FSH concentrations varied with time (P < 0.05), particularly in the first week of the experiment, but were not affected by treatment or insulin sensitivity category. Plasma GH concentrations were affected (P < 0.05) only by day of treatment. The greater MSH responses to sulpiride and TRH in insulin-insensitive mares were similar to, but not as exaggerated as, those observed by others for PPID horses. In addition, the reduced TSH concentrations in insulin-insensitive mares are

  10. Fluoride absorption: independence from plasma fluoride levels

    SciTech Connect

    Whitford, G.M.; Williams, J.L.

    1986-04-01

    The concept that there are physiologic mechanisms to homeostatically regulate plasma fluoride concentrations has been supported by results in the literature suggesting an inverse relationship between plasma fluoride levels and the absorption of the ion from the gastrointestinal tract of the rat. The validity of the relationship was questioned because of possible problems in the experimental design. The present work used four different methods to evaluate the effect of plasma fluoride levels on the absorption of the ion in rats: (i) the percentage of the daily fluoride intake that was excreted in the urine; (ii) the concentration of fluoride in femur epiphyses; (iii) the net areas under the time-plasma fluoride concentration curves after intragastric fluoride doses; and (iv) the residual amounts or fluoride in the gastrointestinal tracts after the intragastric fluoride doses. None of these methods indicated that plasma fluoride levels influence the rate or the degree or fluoride absorption. It was concluded that, unless extremely high plasma fluoride levels are involved (pharmacologic or toxic doses), the absorption of the ion is independent of plasma levels. The results provide further evidence that plasma fluoride concentrations are not homeostatically regulated.

  11. Concurrent papillary thyroid cancer with pituitary ACTH-secreting tumor.

    PubMed

    Kuo, Sheng-Fong; Chen, Jeng-Yeou; Chuang, Wen-Yu; Jung, Shih-Ming; Chang, Yu-Chen; Lin, Jen-Der

    2007-04-01

    Concomitant thyroid cancer with pituitary tumor is uncommon. This study reports a case of advanced papillary thyroid carcinoma with pituitary adrenocorticotropic hormone (ACTH)-secreting tumor. A 58-year-old male patient had thyroid cancer in 1991 and presented with headache caused by pituitary tumor with apoplexy in 1993. Due to hypopituitarism, the patient underwent radioactive iodide ((131)I) for detection and treatment of metastatic thyroid cancer after the use of recombinant human thyroid-stimulating hormone (rhTSH) in 2000. During follow-up for thyroid cancer, (201)thallium scan proved to be an effective tool for detecting metastatic thyroid cancer in the patient without pituitary TSH reserve. Pituitary ACTH-secreting tumor was confirmed in 2001 based on the high serum ACTH level and positive immunohistochemical stain for ACTH. The patient had no Cushingoid features. Moreover, serum ACTH levels were 337 and 232 pg/mL with normal serum cortisol and urine-free cortisol. Although the patient underwent three operations and a total of 370 mCi (131)I therapy for recurrent thyroid cancer, the cancer continued to progress. Finally, the patient died of pneumonia with septic shock 12 years after the diagnosis of thyroid cancer.

  12. Plasma substance P levels in fibrositis.

    PubMed

    Reynolds, W J; Chiu, B; Inman, R D

    1988-12-01

    The mechanism of pain in the fibrositis syndrome is unknown. We measured plasma levels of substance P in 32 patients with fibrositis and 26 sex and age matched controls using a radioimmunoassay. The mean plasma level of substance P in the patients with fibrositis was 371 +/- 91 pg/ml and in controls 397 +/- 84 pg/ml (p = NS). We conclude that determination of plasma levels of substance P in fibrositis is of no diagnostic value. This does not exclude the possible role of substance P as a neurotransmitter in the fibrositis syndrome.

  13. Corticotropin (ACTH)-reactive immunoglobulins in adolescents in relation to antisocial behavior and stress-induced cortisol response. The TRAILS study.

    PubMed

    Schaefer, Johanna M; Fetissov, Serguei O; Legrand, Romain; Claeyssens, Sophie; Hoekstra, Pieter J; Verhulst, Frank C; Van Oort, Floor V A

    2013-12-01

    Elevated levels of corticotropin (ACTH)-reactive immunoglobulins (ACTH IgG) were found in males with conduct disorder, suggesting their involvement in the biology of antisocial behavior. We first aimed to confirm these findings in a large general population sample of adolescents. Secondly, we studied the association between ACTH IgG levels and hypothalamic-pituitary-adrenal (HPA) axis response to stress. Free and total ACTH IgG levels were measured in sera of 1230 adolescents (15-18 years). HPA axis activity was determined by measuring salivary cortisol before, during, and after a social stress test. Antisocial behavior was assessed using the Antisocial Behavior Questionnaire. ACTH peptide and IgG affinity kinetics for ACTH were assayed in a subsample of 90 adolescents selected for high or low ACTH IgG levels. In boys, higher total ACTH IgG levels were associated with higher antisocial behavior scores (β=1.05, p=0.04), especially at high levels of free ACTH IgG. In girls, antisocial behavior was associated with low free ACTH IgG levels (β=-0.20, p=0.04). Stress-induced cortisol release was associated with free ACTH IgG in boys (βareaunderthecurve=-0.67, p<0.01), and with total ACTH IgG in girls (βrecovery=0.84, p=0.05). The affinity kinetics assay showed that ACTH IgG association rates were lower in both boys and girls with high ACTH IgG levels. These data show that ACTH IgG levels are related to antisocial behavior and HPA axis response to stress in adolescents. The mechanisms behind these associations, including different ACTH binding properties of IgG in subjects with antisocial behavior, deserve further attention.

  14. Metabolic effects of chronic ACTH administration, interaction with response to stress.

    PubMed

    Armario, A; Campmany, L; Hidalgo, J

    1986-01-01

    The present experiment was undertaken to study the metabolic response to stress of single or chronic ACTH-treated male rats. It was found that chronic ACTH-treated rats showed a slight reduction in food intake and a decrease in body weight gain. This treatment increased basal serum triglyceride and insulin levels. In addition, some differences in response to stress was found in chronic ACTH-treated rats. Thus, these latter animals, unlike the other two groups, showed a decrease in circulating triglyceride and insulin levels in response to short-term stress. Moreover, 24 h after onset of stress a more marked fall in liver weight and glucose levels were found in chronic ACTH-treated rats. It suggests that chronic ACTH treatment might alter the metabolic response to prolonged acute stress what could result in lower resistance to severe stresses.

  15. Isolation of ACTH-resistant Y1 adrenal tumor cells

    SciTech Connect

    Schimmer, B.P.

    1985-01-01

    Y1 cells originate from a minimally deviated mouse adrenal tumor. When treated with ACTh or cAMP, these cells increase the rate of steroiodigenesis, stop dividing, assume a rounded morphology, and detach from the culture vessel. The ability of ACTH and cAMP to inhibit Y1 cell growth and cause cell rounding and detachment provides a basis for selection of Y1 mutants resistant to hormones and cyclic nucleotides. Newly cloned populations of Y1 cells can be treated with mutagens, such as N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) or ethyl methanesulfonate (EMS) to raise the frequency of specific mutations to detectable levels.

  16. [The binding of Semax, ACTH 4-10 heptapeptide, to plasma membranes of the rat forebrain basal nuclei and its biodegradation].

    PubMed

    Dolotov, O V; Zolotarev, Iu A; Dorokhova, E M; Andreeva, L A; Alfeeva, L Iu; Grivennikov, I A; Miasoedov, N F

    2004-01-01

    The binding characteristics of the peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) to plasma membranes of basal nuclei of the rat forebrain and the dynamics of its degradation during its incubation with these membranes were studied. Binding of the homogeneously labeled [G-3H]Semax was shown to be time-dependent, specific, and reversible. Specific binding of the heptapeptide depended on calcium ions and was characterized by the dissociation constant of the ligand-receptor complex Kd = 2.41 +/- 1.02 x 10(-9) M and by the concentration of binding sites Bmax = 33.5 +/- 7.9 x 10(-15) mol/mg of protein. A method of studying Semax biodegradation in the presence of plasma membranes of rat brain was developed. It is based on the use of the peptide homogeneously labeled with tritium and on an HPLC analysis with UV detection at 220 and 254 nm of the peptide fragments formed. The half-life of Semax in the presence of the plasma membranes was demonstrated to be longer than 1 h. Dipeptidylaminopeptidases are considered to be the main enzymes responsible for its biodegradation; they successively cleave Semax to the HFPGP pentapeptide and the PGP tripeptide. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 3; see also http://www.maik.ru.

  17. Uptake and release of adrenal ascorbic acid in the guinea pig after injection of ACTH

    SciTech Connect

    Kipp, D.E.; Rivers, J.M.

    1987-09-01

    The effect of a single injection of ACTH (3 IU/100 g body weight) on the distribution of ascorbic acid (AA) and radiolabeled AA in 20 tissues was studied in adult male guinea pigs consuming 500 mg AA/kg diet. Saline- or ACTH-injected animals were simultaneously injected with (1-/sup 14/C)AA, and killed at 0.5, 1, 2, 4 and 6 h after injection. There was no significant difference between treatments in the weight of any tissue over the 6-h experimental period. As anticipated, the concentration of AA in the adrenals of animals injected with ACTH was 33% of that of animals injected with saline at 4 h. Unexpectedly, the concentration of radiolabeled AA in the adrenals at 0.5 h after ACTH injection was 172% of that after saline injection. The concentration of radiolabeled AA in the adrenal of the saline-injected animals increased slowly over time to reach a level similar to that of ACTH-injected animals by 6 h. There was no effect of ACTH on the level of AA or uptake in any of the other tissues examined. These results demonstrate that a single dose of ACTH markedly influences the retention of AA in the adrenal gland without similarly altering retention of AA in other tissues. Furthermore, ACTH treatment causes both accelerated uptake and release of AA into the adrenals.

  18. The effect of ACTH upon faecal glucocorticoid excretion in the koala.

    PubMed

    Davies, Nicole; Gillett, Amber; McAlpine, Clive; Seabrook, Leonie; Baxter, Greg; Lunney, Daniel; Bradley, Adrian

    2013-10-01

    Environmental changes result in physiological responses of organisms, which can adversely affect population dynamics and reduce resistance to disease. These changes are expressed in chronic levels of stress. The measurement of glucocorticoid (GC) concentrations in faeces is a non-invasive method for monitoring stress in wildlife. The metabolism and excretion of steroids differ significantly between species and, as a consequence, non-invasive methods must be physiologically validated for each species. Koalas (Phascolarctos cinereus) are declining in numbers through much of their range. The role of chronic stress in koala populations has not been identified. Prior to the assessment of faecal GC concentrations in wild koala populations, the excretion timing and concentrations of GCs need to be determined. In this study, we assessed a method for identifying and measuring the concentrations of GC metabolites in faecal pellets of captive koalas following ACTH treatment. The results show that an elevation of plasma cortisol concentrations, using sustained release of ACTH, results in elevated concentrations of faecal cortisol/cortisol metabolites. Taking into account the excretion time lag, an increase in faecal cortisol metabolite concentrations corresponds to the release of GCs from the adrenal cortex as early as 36 h before faecal pellet collection. The calculations of steroid partitioning of plasma cortisol showed that the ACTH-stimulated values were significantly different from the control values for the concentrations of free, corticosteroid-binding globulin-bound and albumin-bound cortisol. This study validates the use of faecal cortisol analysis to assess the activity of the hypothalamo-pituitary-adrenocortical axis in freshly collected koala faecal pellets and indicates that the method should be suitable to assess the adrenocortical status of koalas in wild populations.

  19. Metabolic responses to adrenocorticotropic hormone (ACTH) vary with life-history stage in adult male northern elephant seals.

    PubMed

    Ensminger, David C; Somo, Derek A; Houser, Dorian S; Crocker, Daniel E

    2014-08-01

    Strong individual and life-history variation in serum glucocorticoids has been documented in many wildlife species. Less is known about variation in hypothalamic-pituitary-adrenal (HPA) axis responsiveness and its impact on metabolism. We challenged 18 free-ranging adult male northern elephant seals (NES) with an intramuscular injection of slow-release adrenocorticotropic hormone (ACTH) over 3 sample periods: early in the breeding season, after 70+ days of the breeding fast, and during peak molt. Subjects were blood sampled every 30 min for 2h post-injection. Breeding animals were recaptured and sampled at 48 h. In response to the ACTH injection, cortisol increased 4-6-fold in all groups, and remained elevated at 48 h in early breeding subjects. ACTH was a strong secretagogue for aldosterone, causing a 3-8-fold increase in concentration. Cortisol and aldosterone responses did not vary between groups but were correlated within individuals. The ACTH challenge produced elevations in plasma glucose during late breeding and molting, suppressed testosterone and thyroid hormone at 48 h in early breeding, and increased plasma non-esterified fatty acids and ketoacids during molting. These data suggest that sensitivity of the HPA axis is maintained but the metabolic impacts of cortisol and feedback inhibition of the axis vary with life history stage. Strong impacts on testosterone and thyroid hormone suggest the importance of maintaining low cortisol levels during the breeding fast. These data suggest that metabolic adaptations to extended fasting in NES include alterations in tissue responses to hormones that mitigate deleterious impacts of acute or moderately sustained stress responses.

  20. Effect of MSH/ACTH peptides on fast axonal transport in intact and regenerating sciatic nerves

    SciTech Connect

    Crescitelli, L.A.

    1985-01-01

    Fast axonal transport was examined in intact rats treated with ACTH 4-10 or ACTH 4-9 (ORG 2766), hypophysectomized rats, adrenalectomized rats, and in ACTH 4-10 treated rats with crushed regenerating sciatic nerves by injecting /sup 3/H-leucine into the ventral horn region of the spinal cord. The distance traveled by the transported activity along the sciatic nerve and the rate of fast axonal transport were not significantly altered as a result of treatment with ACTH 4-10, ACTH 4-9 (ORG 2766), hypophysectomy, or adrenalectomy. Treatment with ACTH 4-9 (ORG 2766) at concentrations of 1 ..mu..g/Kg /day and 10 ..mu..g/Kg/day caused significant reductions (62% and 64% respectively) in the crest height of the fast axonal transport curve as compared to 0.9% saline treated control animals. No significant differences were found in comparing the distance, rate, slope, or crest height of ACTH 4-10 treated animals with crushed regenerating (7 or 14d) sciatic nerves to control animals. In the group of animals in days, the amount of radiolabeled activity was significantly increased in the ACTH 4-10 treated animals as compared to control animals. The results indicate that during regeneration the peptide acts to prolong the initially high levels of synthetic activity which occur in regenerating axons.

  1. Degradation of the ACTH(4-10) analog Semax in the presence of rat basal forebrain cell cultures and plasma membranes.

    PubMed

    Zolotarev, Yu A; Dolotov, O V; Inozemtseva, L S; Dadayan, A K; Dorokhova, E M; Andreeva, L A; Alfeeva, L Yu; Grivennikov, I A; Myasoedov, N F

    2006-06-01

    Here a new approach of the elucidation of paths of proteolytic biodegradation of physiologically active peptides, based on the use of a peptide with isotopic label at all amino acid residues and the enrichment of HPLC samples with unlabeled peptide fragments in UV-detectable concentration, has been proposed. The method has been applied for the investigation of degradation dynamics of the neuroactive heptapeptide MEHFPGP (Semax) in the presence of plasma membranes, and cultures of glial and neuronal cells obtained from the rat basal forebrain. The splitting away of ME and GP, and formation of pentapeptides are the predominant processes in the presence of all tested objects, whereas the difference in patterns of resulting peptide products for glial and neuronal cells has been detected. In conclusion, the approach applied allows analyzing physiologically active peptide concentrations in biological tissues and degradation pathways of peptides in the presence of targets of their action.

  2. ARH missense polymorphisms and plasma cholesterol levels.

    PubMed

    Hubacek, Jaroslav A; Hyatt, Tommy

    2004-01-01

    Mutations in a putative low-density lipoprotein (LDL) receptor adaptor protein called ARH have been recently described in patients with autosomal recessive hypercholesterolemia (ARH). ARH plays a tissue-specific role in determination of LDL receptor function. In the ARH gene three mismatched polymorphisms have been detected: Pro202Ser, Pro202His and Arg238Trp. These are of putative interest in plasma cholesterol level determination. To evaluate the effect of polymorphisms on plasma cholesterol levels, all polymorphisms were analyzed by PCR and restriction enzyme analysis by MnII, HpyCH4IV and SacII in 100 Caucasian males with high (>90%, 6.29 +/- 0.89 mmol/l), and 100 males with low (<10%, 3.60 +/- 0.57 mmol/l), total plasma cholesterol levels. No significant differences were observed in frequencies of ARH genotypes or alleles between these two extreme groups. These results suggest that ARH polymorphisms are unlikely to be important genetic determinants of plasma cholesterol levels.

  3. Aging of the rat adrenocortical cell: response to ACTH and cyclic AMP in vitro.

    PubMed

    Malamed, S; Carsia, R V

    1983-03-01

    To study intrinsic age-related changes in adrenocortical steroid production, cells isolated from rats of different ages (3 to 24 months) were used. Acute (2 hour) corticosterone production in response to stimulation by adrenocorticotrophic hormone (ACTH) and adenosine 3':5'-cyclic monophosphate (cAMP) was measured by radioimmunoassay. With age, adrenocortical cells lose much of their ability to produce corticosterone in the absence or presence of ACTH or cAMP. The loss is progressive from 6 to 24 months of age. Analysis of the data suggests that from 6 to 12 months, an intracellular steroidogenic lesion develops; in addition there may be a loss in ACTH receptors on the plasma membrane. After 12 months these defects increase and are accompanied by a decrease in receptor sensitivity to ACTH.

  4. ACTH and vasopressin responses to insulin-induced hypoglycemia in intact and neurohypophysectomized conscious dogs.

    PubMed

    Raff, H; Papanek, P E; Cowley, A W

    1991-01-01

    Factors from the neurohypophysis are important in the control of anterior pituitary function. This study evaluated the hypothesis that the neurophypophysis is an integral component of the adrenocorticotropin (ACTH) response to certain stimuli. Furthermore, we investigated the possibility that the importance of the neurohypophysis during corticotropic stimuli can be classified by the magnitude of the systemic vasopressin response induced. The ACTH response to insulin-induced hypoglycemia (INS), nitroprusside hypotension (NP), or ovine corticotropin-releasing factor (CRF) infusion (20 ng/kg/min) was measured in dogs before (intact) and greater than 2 weeks after selective transbuccal neurohypophysectomy (NHX). INS (0.2 U/kg) resulted in a significant decrease in plasma glucose from 93 +/- 1 to 33 +/- 2 mg/dl at 30 min and a significant increase in plasma ACTH from 53 +/- 10 to 306 +/- 33 pg/ml in intact dogs whereas the vasopressin (AVP) response was small (2.8 +/- 0.3 to 5.5 +/- 0.7 pg/ml). NHX had no effect on the blood glucose or ACTH response to INS. NP resulted in large increases in ACTH from 54 +/- 8 to 351 +/- 89 pg/ml and in AVP from 2.7 +/- 0.2 to 272 +/- 98 pg/ml. In contrast to INS, NHX significantly attenuated the ACTH and AVP responses to NP. The ACTH response to CRF was not attenuated by NHX, indicating normal pituitary corticotropic function. In summary, NHX attenuated the ACTH response to hypotension (large peripheral AVP response) but not to INS or CRF (small peripheral AVP response).(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Plasma level monitoring of antipsychotic drugs.

    PubMed

    Cooper, T B

    1978-01-01

    Psychotic patients treated with identical doses of antipsychotic drugs have been shown to have great interindividual differences in their steady state plasma concentration. Therefore, monitoring treatment by dosage adjustment alone is of little value. If antipsychotic blood levels can be related to clinical response then their routine measurement may well result in well defined guidelines to individualised optimal dosage. Despite the considerable effort expended in this field and the many interesting testable hypotheses generated, little substantive evidence for an acceptable plasma level monitoring guide has been reported to date. Work on metabolite level profiles, intra- and extracellular drug concentration differences, more detailed clinical rating scales, and improved experimental design, all show great promise for the future. Investigation of the pharmacokinetics and the elucidation of the often complex metabolic pathways of individual antipsychotic drugs are generating the data base required for the rational pharmacotherapy of these most severely ill patients. Until more data are available, routine monitoring of antipsychotic drug plasma levels remains of research interest.

  6. Pain sensitivity, mood and plasma endocrine levels in man following long-distance running: effects of naloxone.

    PubMed

    Janal, M N; Colt, E W; Clark, W C; Glusman, M

    1984-05-01

    The effects of intense exercise on pain perception, mood, and plasma endocrine levels in man were studied under naloxone and saline conditions. Twelve long-distance runners (mean weekly mileage = 41.5) were evaluated on thermal, ischemic, and cold pressor pain tests and on mood visual analogue scales (VAS). Blood was drawn for determination of plasma levels of beta-endorphin-like immunoreactivity (BEir), growth hormone (GH), adrenocorticotrophic hormone (ACTH), and prolactin (PRL). These procedures were undertaken before and after a 6.3 mile run at 85% of maximal aerobic capacity. Subjects participated on two occasions in a double-blind procedure counterbalanced for drug order: on one day they received 2 i.v. injections of naloxone (0.8 mg in 2 ml vehicle each) at 20 min intervals following the run; on the other day, 2 equal volume injections of normal saline (2 ml). Sensory decision theory analysis of the responses to thermal stimulation showed that discriminability, P(A), was significantly reduced post-run under the saline condition, a hypoalgesic effect; response bias, B, was unaffected. Ischemic pain reports were significantly reduced post-run on the saline day, also a hypoalgesic effect. Naloxone reversed the post-run ischemic but not thermal hypoalgesic effects. Joy, euphoria, cooperation, and conscientiousness VAS ratings were elevated post-run; naloxone attenuated the elevation of joy and euphoria ratings only. Plasma levels of BEir, ACTH, GH, and PRL were significantly increased post-run. The results show that long-distance running produces hypoalgesia and mood elevation in man. The effects of naloxone implicate endogenous opioid neural systems as mechanisms of some but not all of the run-induced alterations in mood and pain perception.

  7. Effect of high-dose total body irradiation on ACTH, corticosterone, and catecholamines in the rat.

    PubMed

    Cohen, Eric P; Bruder, Eric D; Cullinan, William E; Ziegler, Dana; Raff, Hershel

    2011-01-01

    Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic-pituitary-adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study assessed HPA axis function in rats undergoing TBI. Using a head-shielded model of TBI, we found an enhanced response to corticotropin-releasing hormone (CRH) in vitro in pituitaries from irradiated compared with nonirradiated rats at both 8 and 70 days after 10-Gy single fraction TBI. At 70, but not 8 days, plasma adrenocorticotrophic hormone (ACTH) and corticosterone levels were increased significantly in irradiated compared with nonirradiated rats. Plasma aldosterone was not affected by TBI at either time point, whereas plasma renin activity was decreased in irradiated rats at 8 days. Basal and stimulated adrenal steroid synthesis in vitro was not affected by TBI. In addition, plasma epinephrine was decreased at 70 days after TBI. The hypothalamic expression of CRH messenger RNA (mRNA) and hippocampal expression of glucocorticoid receptor mRNA were unchanged by irradiation. We conclude that the hypertension of radiation nephropathy is not aldosterone or catecholamine-dependent but that there is an abscopal activation of the HPA axis after 10 Gy TBI. This activation was attributable at least partially to enhanced pituitary ACTH production.

  8. The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome.

    PubMed

    de Keyzer, Y; Lenne, F; Auzan, C; Jégou, S; René, P; Vaudry, H; Kuhn, J M; Luton, J P; Clauser, E; Bertagna, X

    1996-03-01

    Ectopic ACTH secretion occurs in highly differentiated and rather indolent tumors like bronchial carcinoids or, in contrast, in various types of aggressive and poorly differentiated neuroendocrine tumors. We explored this phenomenon using the recently cloned human pituitary V3 vasopressin receptor as an alternate molecular marker of the corticotroph phenotype. Expression of V3 receptor, corticotrophin releasing hormone (CRH) receptor, and proopiomelanocortin (POMC) genes was examined in tumors of pituitary and nonpituitary origin. A comparative RT-PCR approach revealed signals for both V3 receptor and CHR receptor mRNAs in 17 of 18 ACTH-secreting pituitary adenomas, and 6 of 6 normal pituitaries; in six growth hormone- or prolactin-secreting adenomas, a very faint V3 receptor signal was observed in three cases, and CRH receptor signal was undetected in all. Six of eight bronchial carcinoids responsible for the ectopic ACTH syndrome had both POMC and V3 receptor signals as high as those in ACTH-secreting pituitary adenomas; in contrast, no POMC signal and only a very faint V3 receptor signal were detected in six of eight nonsecreting bronchial carcinoids. Northern blot analysis showed V3 receptor mRNA of identical size in ACTH-secreting bronchial carcinoids and pituitary tumors. Other types of nonpituitary tumors responsible for ectopic ACTH syndrome presented much lower levels of both POMC and V3 receptor gene expression than those found in ACTH-secreting bronchial carcinoids. In contrast with the V3 receptor, CRH receptor mRNA was detected in the majority of neuroendocrine tumors irrespective of their POMC status. These results show that expression of the V3 receptor gene participates in the corticotroph phenotype. Its striking association with ACTH-secreting bronchial carcinoids defines a subset of nonpituitary tumors in which ectopic POMC gene expression is but one aspect of a wider process of corticotroph cell differentiation, and opens new possibilities of

  9. Plasma adropin level in patients with pseudoexfoliation.

    PubMed

    Oğurel, Tevfik; Oğurel, Reyhan; Topuz, Mustafa; Örnek, Nurgül; Örnek, Kemal

    2016-10-01

    The aim of this study was to evaluate plasma adropin levels in patients with pseudoexfoliation (PEX). This retrospective case-control study included 35 patients with PEX and 35 individuals without PEX who served as controls. Plasma adropin levels with triglycerides, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and haemoglobin A1c (HGBA1C) concentrations were measured in both groups. The mean serum adropin levels were 3.24 ± 0.95 ng/mL (range, 1.90-7.88 ng/mL) in patients with PEX syndrome and 5.78 ± 2.85 ng/mL (range, 2.08-5.41 ng/mL) in PEX glaucoma patients. There was no statistically significant difference in mean adropin levels between PEX syndrome and PEX glaucoma patients. However, similar adropin levels were found in the PEX glaucoma patients and the control group (P > 0.05). The mean serum adropin levels were 3.34 ± 0.89 ng/mL (range, 1.90-5.39 ng/mL) in the PEX group and 5.78 ± 2.85 ng/mL (range, 3.08-11.06 ng/mL) in the control group. The mean serum adropin level of the PEX group was significantly lower than that of the control group (P < 0.001). There were no significant differences between the two groups in terms of serum glucose, total cholesterol, LDL, HDL, HGBA1C, triglycerides levels, or body mass index (all P > 0.05). Adropin level is lower in patients with PEX.

  10. Cushing Syndrome Due to ACTH-Secreting Pheochromocytoma, Aggravated by Glucocorticoid-Driven Positive-Feedback Loop

    PubMed Central

    Sakuma, Ikki; Higuchi, Seiichiro; Fujimoto, Masanori; Takiguchi, Tomoko; Nakayama, Akitoshi; Tamura, Ai; Kohno, Takashi; Komai, Eri; Shiga, Akina; Nagano, Hidekazu; Hashimoto, Naoko; Suzuki, Sawako; Mayama, Takafumi; Koide, Hisashi; Ono, Katsuhiko; Sasano, Hironobu; Tatsuno, Ichiro; Yokote, Koutaro

    2016-01-01

    Context: Pheochromocytoma is a catecholamine-producing tumor that originates from adrenal chromaffin cells and is capable of secreting various hormones, including ACTH. Case Description: A 56-year-old female presented with Cushingoid appearance and diabetic ketoacidosis. Endocrinological examinations demonstrated ectopic ACTH production with hypercortisolemia and excess urinary cortisol accompanied by elevated plasma and urine catecholamines. Computed tomography revealed a large left adrenal tumor with bilateral adrenal enlargement. Metaiodobenzylguanidine scintigraphy revealed abnormal accumulation in the tumor, which was eventually diagnosed as pheochromocytoma with ectopic ACTH secretion with subsequent manifestation of Cushing's syndrome. Ectopic ACTH secretion and catecholamine production were blocked by metyrapone treatment, whereas dexamethasone paradoxically increased ACTH secretion. Left adrenalectomy resulted in complete remission of Cushing's syndrome and pheochromocytoma. In Vitro Studies: Immunohistological analysis revealed that the tumor contained two functionally distinct chromaffin-like cell types. The majority of tumor cells stained positive for tyrosine hydroxylase (TH), whereas a minor population of ACTH-positive tumor cells was negative for TH. Furthermore, gene expression and in vitro functional analyses using primary tumor tissue cultures demonstrated that dexamethasone facilitated ACTH as well as catecholamine secretion with parallel induction of proopiomelanocortin (POMC), TH, and phenylethanolamine N-methyltransferase mRNA, supporting a glucocorticoid-dependent positive-feedback loop of ACTH secretion in vivo. DNA methylation analysis revealed that the POMC promoter of this tumor, particularly the E2F binding site, was hypomethylated. Conclusion: We present a case of ectopic ACTH syndrome associated with pheochromocytoma. ACTH up-regulation with paradoxical response to glucocorticoid, possibly through the hypomethylation of the POMC

  11. Testosterone, estradiol, ACTH and musical, spatial and verbal performance.

    PubMed

    Hassler, M; Gupta, D; Wollmann, H

    1992-01-01

    Testosterone, estradiol, and ACTH were determined in blood serum of 26 healthy males aged 19.16 and of 25 healthy females aged 18.77 years on average, and results were correlated with test scores of three spatial tests, a verbal fluency measure, and a test measuring general musical ability. In addition, hemispheric lateralization for verbal material and handedness was assessed. While testosterone and estradiol alone were not significantly related to any of the cognitive or musical tests, testosterone/estradiol ratio was significantly negatively correlated with spatial tests, and ACTH was significantly positively correlated with spatial and musical tests. Correlations were stronger in females than in males. The laterality index was significantly negatively correlated with testosterone in males indicating that right hemisphere involvement in verbal processing was associated with high testosterone levels.

  12. ACTH Action on Messenger RNA Stability Mechanisms

    PubMed Central

    Desroches-Castan, Agnès; Feige, Jean-Jacques; Cherradi, Nadia

    2017-01-01

    The regulation of mRNA stability has emerged as a critical control step in dynamic gene expression. This process occurs in response to modifications of the cellular environment, including hormonal variations, and regulates the expression of subsets of proteins whose levels need to be rapidly adjusted. Modulation of messenger RNA stability is usually mediated by stabilizing or destabilizing RNA-binding proteins (RNA-BP) that bind to the 3′-untranslated region regulatory motifs, such as AU-rich elements (AREs). Destabilizing ARE-binding proteins enhance the decay of their target transcripts by recruiting the mRNA decay machineries. Failure of such mechanisms, in particular misexpression of RNA-BP, has been linked to several human diseases. In the adrenal cortex, the expression and activity of mRNA stability regulatory proteins are still understudied. However, ACTH- or cAMP-elicited changes in the expression/phosphorylation status of the major mRNA-destabilizing protein TIS11b/BRF1 or in the subcellular localization of the stabilizing protein Human antigen R have been reported. They suggest that this level of regulation of gene expression is also important in endocrinology. PMID:28163695

  13. GH-releasing peptide (GHRP-6)-induced ACTH release in patients with addison's disease: effect of glucocorticoid withdrawal.

    PubMed

    Martins, M R A; Pinto, A C A R; Brunner, E; Silva, M R D; Lengyel, A M J

    2003-02-01

    GH releasing peptide (GHRP-6) is a synthetic hexapeptide with potent GH releasing activity both in man and in animals. This peptide is also able to stimulate ACTH and cortisol (F) release. It has been suggested that the ACTH responsiveness to GHRP-6 is modulated by circulating glucocorticoid levels. To further clarify this hypothesis, we studied the effect of GHRP-6 (1 ug/kg, iv) on ACTH and F release in patients with Addison's disease (no.=6) during replacement therapy and after 72 h of glucocorticoid withdrawal. Seven controls were also submitted to a single GHRP-6 test. In control subjects, ACTH values (pmol/l; mean +/- SE) increased from 2.9 +/- 0.8 to 4.7 +/- 1.4 (peak). AUC (pmol.min/l) values were 170.3 +/- 48.8. F (nmol/l) values increased from 257.0 +/- 42.9 to 367.0 +/- 50.8. In patients with Addison's disease there was an increase in ACTH levels from 38.1 +/- 17.1 to 174.9 +/- 79.4 after GHRP-6 administration. AUC values were 5490.4 +/- 2269.1. After 72 h withdrawal of glucocorticoid, there was an increase in basal ACTH values (191.2 +/- 97.3), and a trend toward an increase in ACTH levels after GHRP-6 (p=0.053). Patients with Addison's disease on therapy showed a significantly higher ACTH response to GHRP-6 when compared to controls. Our results show that in patients with Addison's disease on replacement there is an increased ACTH release after GHRP-6 administration, compared to controls. After 72 h glucocorticoid withdrawal, this enhanced responsiveness is not maintained. Our data suggest that circulating glucocorticoids modulate GHRP-6-induced ACTH release and that multiple mechanisms may be involved in this process.

  14. Ectopic ACTH secretion due to a bronchopulmonary carcinoid localized by somatostatin receptor scintigraphy.

    PubMed

    Iser, G; Pfohl, M; Dörr, U; Weiss, E M; Seif, F J

    1994-11-01

    We present the case of a 65-year-old woman with an adrenocorticotropic hormone (ACTH) secreting bronchopulmonary carcinoid. This patient showed the typical long history of Cushing's syndrome, including hypokaliemia, impaired glucose tolerance, high levels of ACTH and beta-endorphin, and coproduction of other peptides. At the onset of clinical symptoms in 1979 an adrenal adenoma was suspected, and left-sided adrenalectomy was performed. The symptoms soon recurred, and the diagnosis of ACTH-dependent Cushing's syndrome was made. As no ACTH-secreting tumor was found, the right adrenal was resected, and the patient was followed up regularly. Fourteen years later chest roentgenography and computed tomography revealed a para-aortic pulmonary lesion, which was suspicious for a bronchopulmonary carcinoid. ACTH and beta-endorphin were excessively, pancreatic polypeptide slightly elevated at that time. The final diagnosis was made using somatostatin receptor scintigraphy which confirmed the hormonal activity of the suspicious lesion; no additional focus was found. This method turned out to be not only a useful additional localization technique but also a promising tool for characterization and staging of a suspected ACTH-producing carcinoid. The tumor was resected curatively, and the diagnosis was confirmed histologically.

  15. Ghrelin and GHRP-6-induced ACTH and cortisol release in thyrotoxicosis.

    PubMed

    Nascif, Sergio Oliva; Molica, Patrícia; Correa-Silva, Silvia Regina; Silva, Marcos Roberto; Lengyel, Ana-Maria Judith

    2009-01-01

    Thyrotoxicosis might alter the hypothalamic-pituitary-adrenal (HPA) axis. We evaluated the effects of ghrelin and GHRP-6 on the HPA axis in 20 hyperthyroid patients and in 9 controls. Mean basal cortisol (microg/dl) and ACTH (pg/ml) levels were higher in hyperthyroidism (cortisol: 10.7 +/- 0.7; ACTH: 21.5 +/- 2.9) compared to controls (cortisol: 8.1 +/- 0.7; ACTH: 13.5 +/- 1.8). In thyrotoxicosis Delta AUC cortisol values (microg/dl.90 min) after ghrelin (484 +/- 80) and GHRP-6 (115 +/- 63) were similar to controls (ghrelin: 524 +/- 107; GHRP-6: 192 +/- 73). A significant increase in Delta AUC ACTH (pg/ml x 90 min) after ghrelin was observed in thyrotoxicosis (4,189 +/- 1,202) compared to controls (1,499 +/- 338). Delta AUC ACTH values after GHRP-6 were also higher, although not significantly (patients: 927 +/- 330; controls: 539 +/- 237). In summary, our results suggest that ghrelin-mediated pathways of ACTH release might be activated by thyroid hormone excess, but adrenocortical reserve is maintained.

  16. The corticotropin-releasing hormone test in normal short children: comparison of plasma adrenocorticotropin and cortisol responses to human corticotropin-releasing hormone and insulin-induced hypoglycemia.

    PubMed

    Goji, K

    1989-03-01

    The human corticotropin-releasing hormone (hCRH) tests were performed in twelve normal short children, and the responses of plasma ACTH and cortisol to iv administration of 1 micrograms/kg hCRH were compared with those to insulin-induced hypoglycemia. After administration of hCRH, the mean plasma ACTH level rose from a basal value of 3.3 +/- 0.4 pmol/l (mean +/- SEM) to a peak value of 9.2 +/- 0.8 pmol/l at 30 min, and the mean plasma cortisol level rose from a basal value of 231 +/- 25 nmol/l to a peak value of 546 +/- 30 nmol/l at 30 min. The ACTH response after insulin-induced hypoglycemia was greater than that after hCRH administration; the mean peak level (P less than 0.01), the percent maximum increment (P less than 0.01), and the area under the ACTH response curve (P less than 0.01) were all significantly greater after insulin-induced hypoglycemia than those after hCRH administration. Although the mean peak cortisol level after insulin-induced hypoglycemia was about 1.3-fold higher than that after hCRH administration (P less than 0.01), neither the percent maximum increment in plasma cortisol nor the area under the cortisol response curve after insulin-induced hypoglycemia was significantly different from that after hCRH administration. Consequently, the acute increases in plasma ACTH after the administration of 1 microgram/kg hCRH stimulated the adrenal gland to almost the same cortisol response as that obtained with a much greater increase in plasma ACTH after insulin-induced hypoglycemia. These results suggest that a plasma ACTH peak of 9-11 pmol/l produces near maximum acute stimulation of adrenal steroidogenesis.

  17. ACTH adenomas transforming their clinical expression: report of 5 cases.

    PubMed

    Zoli, Matteo; Faustini-Fustini, Marco; Mazzatenta, Diego; Marucci, Gianluca; De Carlo, Eugenio; Bacci, Antonella; Pasquini, Ernesto; Lanzino, Giuseppe; Frank, Giorgio

    2015-02-01

    resolution of Cushing disease. This patient again developed hypercortisolism, which finally resolved spontaneously. In this series, the transformation occurred after a mean of 3.5 years (range 6 months to 7 years). The shift from an ACTH-silent to a functioning adenoma was observed in 9% of the ACTH-silent adenomas in this series (4 of 44 cases), and the spontaneous remission of Cushing disease to a silent corticotroph cell adenoma occurred in 1.5% of cases of this series (2 of 132 functioning ACTH adenomas). At follow-up (mean 107 months; range 60-177 months), cortisol levels were within normal limits in all 5 cases. However, 1 patient required Gamma Knife radiosurgery and eventually adrenalectomy for disease control to be achieved. CONCLUSIONS The ability of silent ACTH adenomas to transform their secretion pattern poses a challenge for neurosurgeons and endocrinologists. Because the transformation is often unexpected, the clinical and biochemical data can be underestimated. Furthermore, this bizarre and unpredictable postoperative tumor behavior can lead to misinterpretation of clinical and endocrinological outcomes. Even if these cases are very rare, they are not anecdotal in large series. Thus, ACTH adenomas require careful biohumoral and neuroradiological follow-up to detect possible transformations.

  18. The effect of ACTH on suckling rats.

    PubMed

    Sato, Y

    1984-01-01

    In the present study, the causes of brain shrinkage induced by synthetic ACTH treatment in epileptic children were investigated using suckling rats. Synthetic ACTH was injected subcutaneously once a day for 5 days into suckling rats aged 15 days. Saline was injected into control subjects in the same way. Rats were sacrificed before the injection, immediately after the repeated injections, and 5 and 14 days from the end of the course of repeated injections. The weight, volume and water content of the brains were measured and the protein, DNA, sodium and potassium contents of the brains were also determined. The mean weight and volume of the brains after 5-day injection of ACTH were slightly smaller compared to those of control rats. No natural increase in brain protein with growth was found from the start of ACTH injections to 14 days after finishing the course of repeated injections. The DNA, sodium and potassium contents of the brains significantly increased immediately after the repeated injections of 5 days. It was suggested that the brain shrinkage of epileptics induced by ACTH treatment might be caused by decreased water content and not cellular degradation.

  19. Motion sickness susceptibility related to ACTH, ADH and TSH

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.; Leach, C.; Homick, J. L.; Larochelle, F. T.

    1983-01-01

    The hypothesis that endogenous levels of certain hormones might be indicative of an individual's susceptibility to stressful motion is tested in a comparison of subjects classified as less prone to motion sickness with those of higher susceptibility. The levels of ACTH and vasopressin measured before exposure to stressful motion were twice as high in the less-suceptible group. No significant differences were noted in the levels of angiotensin, aldosterone, or TSH. The differences between the two groups were greater for a given hormone than for any of the changes induced by exposure to stressful motion.

  20. ACTH and prednisone in childhood seizure disorders.

    PubMed

    Snead, O C; Benton, J W; Myers, G J

    1983-08-01

    We treated 116 children with ACTH or prednisone. Fifty-two had infantile spasms with hypsarhythmia, and 64 had other types of intractable seizures. ACTH completely controlled seizures in all patients with infantile spasms and hypsarhythmia and 74% of those with other types of seizures. Prednisone controlled 51% of patients with infantile spasms and none with other seizures. Serious side effects were minimal for both drugs, and recurrent seizures occurred in 40 to 50% of patients within 4 to 14 months after completion of therapy.

  1. Proopiomelanocortin, glucocorticoid, and CRH receptor expression in human ACTH-secreting pituitary adenomas.

    PubMed

    Cassarino, Maria Francesca; Sesta, Antonella; Pagliardini, Luca; Losa, Marco; Lasio, Giovanni; Cavagnini, Francesco; Pecori Giraldi, Francesca

    2017-03-01

    ACTH-secreting pituitary tumors are by definition partially autonomous, i.e., secrete ACTH independent of physiological control. However, only few, small-sized studies on proopiomelanocortin (POMC) and its regulation by corticotropin-releasing hormone (CRH) or glucocorticoids are available. Objective of the present study was to report on constitutive and CRH- and dexamethasone-regulated POMC, CRH (CRH-R1), and glucocorticoid receptor (NR3C1) gene expression in a large series of human corticotrope adenomas. Fifty-three ACTH-secreting adenomas were incubated with 10 nM CRH or 10 nM dexamethasone for 24 h. POMC, CRH-R1, NR3C1, and its alpha and beta isoforms were quantified and medium ACTH measured. Constitutive POMC expression proved extremely variable, with macroadenomas exhibiting higher levels than microadenomas. POMC increased during CRH in most specimens; conversely, changes induced by dexamethasone were varied, ranging from decrease to paradoxical increase. No correlation between POMC and ACTH was detected in any experimental condition. CRH-R1 expression was not linked to the response to CRH while NR3C1 was expressed at greater levels in specimens who failed to inhibit during dexamethasone; glucocorticoid receptor α was the more abundant isoform and subject to down-regulation by dexamethasone. Our results demonstrate a considerable variability in POMC expression among tumors and no correlation between POMC and ACTH, suggesting that POMC peptide processing/transport plays a major role in modulating ACTH secretion. Further, CRH-R1 and NR3C1 expression were not linked to the expected ligand-induced outcome, indicating that receptor signaling rather than abundance determines corticotrope responses. Our findings pave the way to new avenues of research into Cushing's disease pathophysiology.

  2. Low levels of dehydroepiandrosterone sulphate in plasma, and reduced sympathoadrenal response to hypoglycaemia in premenopausal women with rheumatoid arthritis

    PubMed Central

    Imrich, R; Rovensky, J; Malis, F; Zlnay, M; Killinger, Z; Kvetnansky, R; Huckova, M; Vigas, M; Macho, L; Koska, J

    2005-01-01

    Objectives: To evaluate the function of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in premenopausal women with rheumatoid arthritis (RA). Methods: Insulin-induced hypoglycaemia (0.1 IU/kg) was produced in 15 glucocorticoid-naive patients with long term RA with low disease activity and in 14 healthy women matched for age and body mass index. Concentrations of glucose, adrenocorticotropic hormone (ACTH), cortisol, Δ4-androstenedione (ASD), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 17α-hydroxyprogesterone (17OHP), epinephrine (EPI), norepinephrine (NE), interleukin 6 (IL6), and tumour necrosis factor α (TNFα) were analysed in plasma. Results: Patients had comparable responses of glucose, cortisol, ACTH, ASD, and 17OHP to hypoglycaemia, without any signs of hypothalamic insufficiency. Patients had lower basal DHEAS than controls (3.03 (0.37) µmol/l v 5.1 (0.9) µmol/l, respectively; p<0.05); borderline lower basal DHEA levels (p = 0.067); while the response of DHEA to hypoglycaemia was comparable to that of controls. Patients with RA had lower EPI (p = 0.005) and NE (p<0.001) responses to hypoglycaemia. TNFα and IL6 were higher (p<0.05) in patients with RA (TNFα 8 (2.8) pg/ml in RA v 1.1 (0.5) pg/ml in controls and IL6 15.1 (6.7) pg/ml v 1.4 (0.7) pg/ml). Conclusions: Lower basal DHEAS levels, without concomitant differences or changes in DHEA, ASD, 17OHP, and cortisol responses to hypoglycaemia in patients with RA, indicate an isolated decrease in adrenal androgen production. Significantly lower responses of EPI and NE to hypoglycaemia may suggest sympathoadrenal hyporeactivity in patients with RA. PMID:15647427

  3. ACTH-secreting 'apudoma' of gallbladder.

    PubMed Central

    Spence, R W; Burns-Cox, C J

    1975-01-01

    The case of a 44-year-old woman is reported. The diagnosis after the appropriate tests and laparotomy was ACTH-secreting 'apudoma' of the gallbladder. This is a rare tumour and this case is believed to be the first reported of an ectopic hormone producing tumour from this side. Images Fig 1 Fig 2 PMID:168130

  4. The Role of ACTH and Corticosteroids for Sepsis and Septic Shock: An Update

    PubMed Central

    Annane, Djillali

    2016-01-01

    Sepsis is a common disorder associated with high morbidity and mortality. It is now defined as an abnormal host response to infection, resulting in life-threatening dysfunction of organs. There is evidence from in vitro and in vivo experiments in various animal models and in patients that endotoxin or sepsis may directly and indirectly alter the hypothalamic–pituitary–adrenal response to severe infection. These alterations may include necrosis or hemorrhage or inflammatory mediator-mediated decreased ACTH synthesis, steroidogenesis, cortisol delivery to tissues, clearance from plasma, and decreased sensitivity of tissues to cortisol. Disruption of the hypothalamic–pituitary–adrenal axis may translate in patients with sepsis into cardiovascular and other organ dysfunction, and eventually an increase in the risk of death. Exogenous administration of corticosteroids at moderate dose, i.e., <400 mg of hydrocortisone or equivalent for >96 h, may help reversing sepsis-associated shock and organ dysfunction. Corticosteroids may also shorten the duration of stay in the ICU. Except for increased blood glucose and sodium levels, treatment with corticosteroids was rather well tolerated in the context of clinical trials. The benefit of treatment on survival remains controversial. Based on available randomized controlled trials, the likelihood of survival benefit is greater in septic shock versus sepsis patients, in sepsis with acute respiratory distress syndrome or with community-acquired pneumonia versus patients without these conditions, and in patients with a blunted cortisol response to 250 μg of ACTH test versus those with normal response. PMID:27379022

  5. Acromegaly and Cushing's syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6.

    PubMed

    Jansson, J O; Svensson, J; Bengtsson, B A; Frohman, L A; Ahlman, H; Wängberg, B; Nilsson, O; Nilsson, M

    1998-02-01

    A 50-year-old male presented with diabetes mellitus and Cushing's syndrome associated with a large mediastinal mass. The levels of serum cortisol were high (1500-1800 nmol/l) without diurnal variation. Plasma ACTH levels (200-250 ng/l) and urinary excretion of cortisol were also increased. The levels of these hormones did not change in response to stimulation with corticotrophin releasing hormone (CRH) or suppression with high doses of dexamethasone. The patient had an elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH-releasing hormone (GHRH) in eight plasma samples were markedly increased (600-1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY) were also increased. Computer-assisted tomography and octreotide scintigraphy revealed a large mediastinal tumour and metastases in the left supraclavicular fossa. During treatment with octreotide, the baseline GH level was decreased (to 4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of the tumour tissue resulted in a further decrease in the baseline serum GH level to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height and mean GH were affected to a lesser extent. Postoperatively, circulating levels of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement. Histological examination showed a neuroendocrine tumour with characteristics consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH and NPY, but not immunoreactive GH, were detected in 80-90% of the tumour cells and the three peptides appeared to be co-localized. In primary culture, cells from this tumour displayed calcium influx in response to GHRH or GH releasing peptide-6 (GHRP-6), while there were not such responses by cells from another carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells were responsive

  6. Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions

    PubMed Central

    Lefebvre, Hervé; Thomas, Michaël; Duparc, Céline; Bertherat, Jérôme; Louiset, Estelle

    2016-01-01

    In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions. PMID:27489549

  7. Acylated ghrelin as provocative test for the diagnosis of ACTH deficiency in patients with hypothalamus-pituitary disease.

    PubMed

    Gasco, Valentina; Berton, Alessandro; Caprino, Mirko Parasiliti; Karamouzis, Ioannis; Maccario, Mauro; Ghigo, Ezio; Grottoli, Silvia

    2015-11-01

    The insulin tolerance test (ITT) is the gold standard to evaluate adrenocorticotropic hormone (ACTH) insufficiency. However, alternative tests have been proposed such as metyrapone, glucagon, and ACTH stimulation test. We determined the diagnostic reliability of testing with ghrelin, the natural GH secretagogue that is a potent stimulus exploring the integrity of hypothalamic-pituitary-adrenal axis. We studied the ACTH and cortisol response to acylated ghrelin in 49 patients with history of pituitary disease. The best cortisol and ACTH cut offs to ghrelin test, defined as those with the best sensitivity (SE) and specificity (SP), were identified using the ROC analysis. We also compared accuracy of ghrelin test with that of a simple and cheap test like basal cortisol and ACTH levels. The best cortisol and ACTH cut offs to ghrelin test were ≤11.6 µg/dl (SE 86.4%, SP 77.8%) and ≤32.5 pg/ml (SE 72.7%, SP 51.9%), respectively; the best basal cortisol and ACTH cut offs were ≤10.7 µg/dl (SE 90.9%, SP 70.4%) and ≤25.0 pg/ml (SE 85%, SP 37%), respectively. The diagnostic accuracy was 81.6, 60.9, 79.6, and 57.4%, respectively. A comparison between ROC AUC showed a great diagnostic power for cortisol, both stimulated and basal, versus ACTH, both stimulated and basal, but no difference between stimulated and basal cortisol evaluation. Our data show that testing with acylated ghrelin is not a useful diagnostic tool for the diagnosis of central hypocortisolism; particularly ghrelin test adds no more information that basal cortisol evaluation in the diagnosis of ACTH deficiency in patients with hypothalamus-pituitary disease.

  8. Effect of Novel Melanocortin Type 2 Receptor Antagonists on the Corticosterone Response to ACTH in the Neonatal Rat Adrenal Gland In Vivo and In Vitro

    PubMed Central

    Nensey, Nasha K.; Bodager, Jonathan; Gehrand, Ashley L.; Raff, Hershel

    2016-01-01

    Stress-induced increases in neonatal corticosterone demonstrate a unique shift from ACTH independence to ACTH dependence between postnatal day 2 (PD2) and day 8 (PD8) in newborn rats. This shift could be due to the binding of a bioactive, non-­immunoreactive plasma ligand to the adrenocortical melanocortin 2 receptor (MC2R) (ACTH receptor). A potent MC2R antagonist would be useful to evaluate this phenomenon in the neonate. Therefore, we investigated the acute corticosterone response to ACTH(1–39) injection in rat pups pretreated with newly developed MC2R antagonists (GPS1573 and GPS1574), which have not been tested in vivo. The doses used in vivo were based on their in vitro potency, with GP1573 being more potent than GPS1574. GPS1573 (PD2 and PD8), GPS1574 (PD2 only), or vehicle were injected intraperitoneally (ip) 10 min before baseline sampling. Then, 0.001 mg/kg of ACTH(1–39) was injected ip, and subsequent blood samples obtained for the measurement of plasma corticosterone. Pretreatment of PD2 pups with GPS1573 demonstrated augmentation, rather than inhibition, of the corticosterone response to ACTH. In PD8 pups, pretreatment with 0.1 mg/kg GPS1573, but not 4 mg/kg, augmented the corticosterone response to ACTH. Pretreatment with GPS1574 attenuated the plasma corticosterone response to ACTH at 30 min in PD2 pups. The activity of these two compounds in vivo do not match their potency in vitro, with GPS1573 leading to a small augmentation of the corticosterone response to ACTH in vivo while GPS1574 resulted in inhibition. PMID:27047449

  9. Plasma cortisol levels and illness appraisal in deficit syndrome schizophrenia.

    PubMed

    White, Ross G; Lysaker, Paul; Gumley, Andrew I; McLeod, Hamish; McCleery, Muriel; O'Neill, Donnacha; MacBeth, Angus; Giurgi-Oncu, Catalina; Mulholland, Ciaran C

    2014-12-30

    Research investigating the association between negative symptoms and plasma cortisol levels in individuals with schizophrenia has produced inconsistent findings. This study investigated whether deficit syndrome schizophrenia (characterized by high levels of primary negative symptoms) is associated with comparatively high morning plasma cortisol levels, more negative appraisals about illness and higher levels of depression. Participants were 85 individuals diagnosed with schizophrenia and 85 individuals with no history of contact with psychiatric services matched for age and gender. All participants provided fasting 9.00a.m. plasma cortisol samples. There were no significant differences between the schizophrenia and control participants in plasma cortisol levels. The Proximal Deficit Syndrome method was used to identify individuals with deficit syndrome schizophrenia. Contrary to what had been hypothesized, participants with deficit syndrome schizophrenia had significantly lower plasma cortisol levels than both non-deficit syndrome participants and control participants. Participants with the deficit syndrome reported significantly less negative appraisals about illness (assessed by PBIQ) and lower levels of depression (assessed by BDI-II). Differences in cortisol levels continued to trend toward significance when levels of depression were controlled for. The patterns of illness-related appraisals and plasma cortisol levels raise the possibility that the deficit syndrome could be a form of adaptation syndrome.

  10. The plasma cyclic-AMP response to noise in humans and rats—short-term exposure to various noise levels

    NASA Astrophysics Data System (ADS)

    Iwamoto, M.; Dodo, H.; Ishii, F.; Yoneda, J.; Yamazaki, S.; Goto, H.

    1988-12-01

    Rats were exposed to short-term noise which was found to activate the hypothalamohypophyseal-adrenal system and result in a decrease of adrenal ascorbic acid (AAA) and an increase of serum corticosterone (SCS). The threshold limit value lay between 60 and 70 dB(A). To characterize better the effect of noise on the human hypothalamo-hypophyseal-adrenal system, a large group of subjects was exposed to short-term noise at 85 dB(A) and higher, and tested for levels of adrenocortical steroid (cortisol) and anterior pituitary hormones such as ACTH, growth hormone (GH) and prolactin (PRL). Results in humans showed hyperfunction of the hypothalamo-pituitary system. However, as the responses in rats and humans differed, a further experiment was performed using C-AMP, a second messenger mediating many of the effects of a variety of hormones. Plasma C-AMP in humans and rats increased significantly after exposure to noise greater than 70 dB(A). We suggest that plasma C-AMP could be useful as a sensitive index for noise-related stress in the daily living environment of humans and rats.

  11. Rapid Glucocorticoid Feedback Inhibition of ACTH Secretion Involves Ligand-Dependent Membrane Association of Glucocorticoid Receptors

    PubMed Central

    Deng, Qiong; Riquelme, Denise; Trinh, Loc; Low, Malcolm J.; Tomić, Melanija; Stojilkovic, Stanko

    2015-01-01

    The hypothesis that rapid glucocorticoid inhibition of pituitary ACTH secretion mediates a feedforward/feedback mechanism responsible for the hourly glucocorticoid pulsatility was tested in cultured pituitary cells. Perifusion with 30 pM CRH caused sustained the elevation of ACTH secretion. Superimposed corticosterone pulses inhibited CRH-stimulated ACTH release, depending on prior glucocorticoid clearance. When CRH perifusion started after 2 hours of glucocorticoid-free medium, corticosterone levels in the stress range (1 μM) caused a delayed (25 min) and prolonged inhibition of CRH-stimulated ACTH secretion, up to 60 minutes after corticosterone withdrawal. In contrast, after 6 hours of glucocorticoid-free medium, basal corticosterone levels inhibited CRH-stimulated ACTH within 5 minutes, after rapid recovery 5 minutes after corticosterone withdrawal. The latter effect was insensitive to actinomycin D but was prevented by the glucocorticoid receptor antagonist, RU486, suggesting nongenomic effects of the classical glucocorticoid receptor. In hypothalamic-derived 4B cells, 10 nM corticosterone increased immunoreactive glucocorticoid receptor content in membrane fractions, with association and clearance rates paralleling the effects on ACTH secretion from corticotrophs. Corticosterone did not affect CRH-stimulated calcium influx, but in AtT-20 cells, it had biphasic effects on CRH-stimulated Src phosphorylation, with early inhibition and late stimulation, suggesting a role for Src phosphorylation on the rapid glucocorticoid feedback. The data suggest that the nongenomic/membrane effects of classical GR mediate rapid and reversible glucocorticoid feedback inhibition at the pituitary corticotrophs downstream of calcium influx. The sensitivity and kinetics of these effects is consistent with the hypothesis that pituitary glucocorticoid feedback is part of the mechanism for adrenocortical ultradian pulse generation. PMID:26121342

  12. Adrenocorticotrophic Hormone Levels in Ground Based Studies

    NASA Technical Reports Server (NTRS)

    Campbell, B. O.

    1972-01-01

    Baseline values of immunoreactive ACTH were established in the normal healthy adult. Normal levels of ACTH secretion were determined for both the male and the female in circulating plasma and serum. The data obtained in these studies are particularly significant in that the sampling was carefully controlled; only healthy employed individuals of both sexes were tested in a routine work situation that would not be considered conducive to stress. It has been found that alterations in the classically described circadian rhythm of ACTH secretion can occur when activities (such as work/rest cycles) are imposed on the individual studied. These changes can be demonstrated even when there is no appreciable change noted in the rhythm of hydrocortisone secretion.

  13. GHRP-6 is able to stimulate cortisol and ACTH release in patients with Cushing's disease: comparison with DDAVP.

    PubMed

    Oliveira, J H A; Vieira, J G H; Abucham, J; Lengyel, A M J

    2003-03-01

    It has been shown that hexarelin stimulates ACTH and cortisol secretion in patients with Cushing's disease. The ACTH release induced by this peptide is 7-fold greater than that obtained by hCRH. The mechanism of action of hexarelin on the hypothalamic-pituitary-adrenal axis has not been fully elucidated. Although controversial, there is evidence that it might be mediated by arginine vasopressin (AVP). The aim of this study was to evaluate the ACTH and cortisol releasing effects of GHRP-6 in patients with Cushing's disease and to compare them with those obtained with DDAVP administration. We studied 10 patients with Cushing's disease (8 female, 2 male; age: 36.7 +/- 4.2 yr), 9 with microadenomas, who were submitted to both GHRP-6 (2 microg/kg iv) and DDAVP (10 micro g i.v.) in bolus administration on 2 separate occasions. ACTH was measured by immunochemiluminometric assay and cortisol by radioimmunoassay. The sensitivities of the assays are 0.2 pmol/l for ACTH, and 11 nmol/l for cortisol. GHRP-6 was able to increase significantly both ACTH (pmol/l, mean +/- SE; basal: 15.5 +/- 1.7 vs peak: 45.1 +/- 9.3) and cortisol values (nmol/l, basal: 583.0 +/- 90.8 vs peak: 1013.4 +/- 194.6). ACTH AUC (pmol/l min(-1)) and cortisol AUC (nmol/l min(-1)) values were 1235.4 and 20577.2, respectively. After DDAVP administration there was a significant increase in ACTH (basal: 13.0 +/- 1.4 vs peak: 50.5 +/- 16.2) and cortisol levels (basal: 572.5 +/- 112.7 vs peak: 860.5 +/- 102.8. AUC values for ACTH and cortisol were 1627.6 +/- 639.8 and 18364.7 +/- 5661.4, respectively. ACTH and cortisol responses to GHRP-6 and DDAVP did not differ significantly (peak: 45.1 +/- 9.3 vs 50.5 +/- 16.2; AUC: 1235.4 +/- 424.8 vs 1627.6 +/- 639.8). There was a significant positive correlation between peak cortisol values after GHRP-6 and DDAVP administration (r = 0.87, p = 0.001). Our results show that GHRP-6 is able to stimulate ACTH and cortisol release in patients with Cushing's disease. These

  14. ACTH- and Cortisol-Associated Neutrophil Modulation in Coronary Artery Disease Patients Undergoing Stent Implantation

    PubMed Central

    Keresztes, Margit; Horváth, Tamás; Ocsovszki, Imre; Földesi, Imre; Serfőző, Gyöngyi; Boda, Krisztina; Ungi, Imre

    2013-01-01

    Background Psychosocial stress and activation of neutrophil granulocytes are increasingly recognized as major risk factors of coronary artery disease (CAD), but the possible relationship of these two factors in CAD patients is largely unexplored. Activation of neutrophils was reported to be associated with stenting; however, the issue of neutrophil state in connection with percutaneous coronary intervention (PCI) is incompletely understood from the aspect of stress and its hypothalamic-pituitary-adrenal axis (HPA) background. Thus, we aimed to study cortisol- and ACTH-associated changes in granulocyte activation in patients undergoing PCI. Methodology/Principal Findings Blood samples of 21 stable angina pectoris (SAP) and 20 acute coronary syndrome (ACS) patients were collected directly before (pre-PCI), after (post-PCI) and on the following day of PCI (1d-PCI). Granulocyte surface L-selectin, CD15 and (neutrophil-specific) lactoferrin were analysed by flow cytometry. Plasma cortisol, ACTH, and lactoferrin, IL-6 were also assayed. In both groups, pre- and post-PCI ratios of lactoferrin-bearing neutrophils were relatively high, these percentages decreased substantially next day; similarly, 1d-PCI plasma lactoferrin was about half of the post-PCI value (all p≤0.0001). Post-PCI ACTH was reduced markedly next day, especially in ACS group (SAP: p<0.01, ACS: p≤0.0001). In ACS, elevated pre-PCI cortisol decreased considerably a day after stenting (p<0.01); in pre-PCI samples, cortisol correlated with plasma lactoferrin (r∼0.5, p<0.05). In 1d-PCI samples of both groups, ACTH showed negative associations with the ratio of lactoferrin-bearing neutrophils (SAP: r = −0.601, p<0.005; ACS: r = −0.541, p<0.05) and with plasma lactoferrin (SAP: r = −0.435, p<0.05; ACS: r = −0.609, p<0.005). Conclusions/Significance Pre- and post-PCI states were associated with increased percentage of activated/degranulated neutrophils indicated by elevated lactoferrin

  15. Plasma levels of heat shock protein 72 (HSP72) and beta-endorphin as indicators of stress, pain and prognosis in horses with colic.

    PubMed

    Niinistö, Kati E; Korolainen, Raija V; Raekallio, Marja R; Mykkänen, Anna K; Koho, Ninna M; Ruohoniemi, Mirja O; Leppäluoto, Juhani; Pösö, A Reeta

    2010-04-01

    A prospective observational study was performed to evaluate whether the plasma concentration of heat shock protein 72 (HSP72) or beta-endorphin is related to clinical signs, blood chemistry, or severity of pain of colic. Seventy-seven horses with colic and 15 clinically healthy controls were studied. The horses were divided into four groups which reflected increasing severity of colic, from normal control horses to horses with mild, moderate and severe colic. Blood samples were collected before any treatment. Packed cell volume (PCV) and plasma HSP72, beta-endorphin, cortisol, adrenocorticotropic hormone (ACTH) and lactate concentrations were measured. Plasma beta-endorphin was related with severity of colic and survival, as well as with plasma cortisol, ACTH and lactate concentrations, heart rate, PCV and pain score. High plasma HSP72 concentration may indicate circulatory deficits, but was not associated with clinical signs of colic. Plasma lactate still seemed to be the most useful single prognostic parameter in horses with colic.

  16. ACTH protects against glucocorticoid-induced osteonecrosis of bone.

    PubMed

    Zaidi, Mone; Sun, Li; Robinson, Lisa J; Tourkova, Irina L; Liu, Li; Wang, Yujuan; Zhu, Ling-Ling; Liu, Xuan; Li, Jianhua; Peng, Yuanzhen; Yang, Guozhe; Shi, Xingming; Levine, Alice; Iqbal, Jameel; Yaroslavskiy, Beatrice B; Isales, Carlos; Blair, Harry C

    2010-05-11

    We report that adrenocorticotropic hormone (ACTH) protects against osteonecrosis of the femoral head induced by depot methylprednisolone acetate (depomedrol). This therapeutic response likely arises from enhanced osteoblastic support and the stimulation of VEGF by ACTH; the latter is largely responsible for maintaining the fine vascular network that surrounds highly remodeling bone. We suggest examining the efficacy of ACTH in preventing human osteonecrosis, a devastating complication of glucocorticoid therapy.

  17. Serotonin transporter genotype modulates HPA axis output during stress: effect of stress, dexamethasone test and ACTH challenge

    PubMed Central

    Sorenson, Andrea N.; Sullivan, Erin C.; Mendoza, Sally P.; Capitanio, John P.; Higley, J. Dee

    2014-01-01

    Background Studies show that the hypothalamic–pituitary–adrenal (HPA) axis is dysregulated in depression. Some studies suggest that variation in the serotonin transporter genotype (hereafter 5HTT) modulates both risk for depression and psychopathological HPA axis responsiveness. Rhesus monkeys are well suited to model such relationships. Rhesus macaque models of human psychopathology have assessed the effect of the serotonin transporter (rh5HTT) on levels of cortisol in stressed subjects. These studies show that that under conditions of stress, heterozygous females (Ls) reared under adversity exhibit high levels of cortisol. Studies have not to our knowledge, however, assessed the potential additive effect on the cortisol response in a number of macaque subjects homozygous for the serotonin transporter short allele (ss). Moreover, little is known about the level of the central or peripheral nervous system at which the 5HTT genotype acts to modulate the cortisol response. Methods This study assesses a relatively large number of subjects homozygous and heterozygous for the rh5HTT short and long alleles (a) during stress; (b) following a dexamethasone suppression test; and (c) following an adrenocorticotropic hormone (ACTH) challenge. Subjects included 190 infant rhesus macaques (Macaca mulatta – 84 males and 106 females; 118 LL, 60 Ls, and 12 ss subjects), obtaining two blood plasma samples during the stress of separation from their mothers. Then on the following day, we obtained a blood sample following a dexamethasone test, and later that day we obtained a blood sample after an ACTH challenge test. Subjects ranged in age between 90 and 128 days, with a mean age of 107 days. Results Subjects homozygous for the short allele had significantly higher levels of cortisol across all test conditions, when compared to those homozygous for the long allele, or those heterozygous with Ls alleles. Subsequent analyses showed a high correlation between individual cortisol

  18. Chemotherapy and plasma adipokines level in patients with colorectal cancer.

    PubMed

    Słomian, Grzegorz; Świętochowska, Elżbieta; Nowak, Grzegorz; Pawlas, Krystyna; Żelazko, Aleksandra; Nowak, Przemysław

    2017-04-12

    Adipokines are molecules produced and secreted by adipose tissue and are linked to multiple malignancies. Adipokines can suppress or promote particular cell behaviors in different types of cancer. The aim of this study was to investigate the impact of chemotherapy on select adipokines in patients with colorectal cancer (CRC). Blood samples were collected from 42 patients with pathologically documented advanced CRC, who required palliative chemotherapy. Leptin, adiponectin, resistin and visfatin levels were measured by ELISA before and 3 months after the administration of chemotherapy. Among the 42 patients evaluated, 18 achieved a partial response (PR), 16 achieved stable disease (SD) and 8 patients experienced disease progression (PD). We found that 5-fluorouracil-based chemotherapy regimens significantly increased plasma levels of leptin and adiponectin and decreased plasma levels of resistin and visfatin in PR and SD patients, whereas the plasma levels of these molecules were not affected in PD patients. Furthermore, the mean plasma levels of leptin were significantly lower, and the mean plasma levels of resistin and visfatin were significantly greater in patients with PD compared with PR and SD both before and after chemotherapy treatment. We conclude that palliative chemotherapy in CRC patients, in addition to providing clinical benefits, positively affects cytokine production and secretion in PR and SD patients. Specifically, we found that palliative chemotherapy increased plasma levels of the anti-inflammatory adipokine adiponectin and decreased the plasma levels of visfatin and resistin, molecules known to promote angiogenesis and cancer cell proliferation in PR and SD patients. Moreover, the baseline values of leptin, visfatin and resistin might serve as prognostic indicators of a poor response to chemotherapy.

  19. Plasma obestatin levels in normal weight, obese and anorectic women.

    PubMed

    Zamrazilová, H; Hainer, V; Sedlácková, D; Papezová, H; Kunesová, M; Bellisle, F; Hill, M; Nedvídková, J

    2008-01-01

    Obestatin is a recently discovered peptide produced in the stomach, which was originally described to suppress food intake and decrease body weight in experimental animals. We investigated fasting plasma obestatin levels in normal weight, obese and anorectic women and associations of plasma obestatin levels with anthropometric and hormonal parameters. Hormonal (obestatin, ghrelin, leptin, insulin) and anthropometric parameters and body composition were examined in 15 normal weight, 21 obese and 15 anorectic women. Fasting obestatin levels were significantly lower in obese than in normal weight and anorectic women, whereas ghrelin to obestatin ratio was increased in anorectic women. Compared to leptin, only minor differences in plasma obestatin levels were observed in women who greatly differed in the amount of fat stores. However, a negative correlation of fasting obestatin level with body fat indexes might suggest a certain role of obestatin in the regulation of energy homeostasis. A significant relationship between plasma obestatin and ghrelin levels, independent of anthropometric parameters, supports simultaneous secretion of both hormones from the common precursor. Lower plasma obestatin levels in obese women compared to normal weight and anorectic women as well as increased ghrelin to obestatin ratio in anorectic women might play a role in body weight regulation in these pathologies.

  20. Clinical significance of plasma metastin level in pancreatic cancer patients.

    PubMed

    Katagiri, Fumihiko; Nagai, Kazuyuki; Kida, Atsushi; Tomita, Kenji; Oishi, Shinya; Takeyama, Masaharu; Doi, Ryuichiro; Fujii, Nobutaka

    2009-03-01

    Metastin, which is a 54-residue peptide coded by KiSS-1 gene, is an endogenous ligand to a G-protein-coupled receptor GPR54. Metastin suppresses a malignant tumor to metastasize and regulates secretion of gonadotropine releasing hormone. Physiological action of metastin has been focused on in oncology. It is reported that less KiSS-1 gene and more hOT7T175 gene which codes GPR54 are expressed in pancreatic cancers than in normal pancreatic tissues; however, there is no study that investigates the relationship between clinicopathological characteristics and plasma metastin concentration in pancreatic cancer patients. The purpose of this study was to investigate the relationship between plasma metastin-like immunoreactive substance (LI) levels and clinical characteristics in pancreatic cancer patients. Thirty-three patients with pathologically confirmed pancreatic cancer before or just after treatments and 24 healthy volunteers were included in the study. Patients were grouped according to the International Union Against Cancer TNM classification. Plasma metastin-LI was measured by enzyme immunoassay. The plasma metastin-LI levels of cancer patients were significantly higher when compared with healthy volunteers. Significant relationship was not found between the plasma metastin-LI levels and the clinicopathological factors such as tumor size, invasion, lymph node metastasis and distant metastasis. The plasma metastin levels may be a significant biomarker to predict the presence of pancreatic cancer and could be used in pancreatic cancer screening.

  1. Excess nicotinamide increases plasma serotonin and histamine levels.

    PubMed

    Tian, Yan-Jie; Li, Da; Ma, Qiang; Gu, Xin-Yi; Guo, Ming; Lun, Yong-Zhi; Sun, Wu-Ping; Wang, Xin-Yuan; Cao, Yu; Zhou, Shi-Sheng

    2013-02-25

    Methylation, a methyl group-consuming reaction, plays a key role in the degradation (i.e., inactivation) of monoamine neurotransmitters, including catecholamines, serotonin and histamine. Without labile methyl groups, the methylation-mediated degradation cannot take place. Although high niacin (nicotinic acid and nicotinamide) intake, which is very common nowadays, is known to deplete the body's methyl-group pool, its effect on monoamine-neurotransmitter degradation is not well understood. The aim of this article was to investigate the effect of excess nicotinamide on the levels of plasma serotonin and histamine in healthy subjects. Urine and venous blood samples were collected from nine healthy male volunteers before and after oral loading with 100 mg nicotinamide. Plasma N(1)-methylnicotinamide, urinary N(1)-methyl-2-pyridone-5-carboxamide (2-Py), and plasma betaine levels were measured by using high-performance liquid chromatography (HPLC). Plasma concentrations of choline, serotonin and histamine were measured using commercial kits. The results showed that the plasma N(1)-methylnicotinamide level and the urinary excretion of 2-Py significantly increased after oral loading with 100 mg nicotinamide, which was accompanied with a decrease in the methyl-group donor betaine. Compared with those before nicotinamide load, five-hour postload plasma serotonin and histamine levels significantly increased. These results suggest that excess nicotinamide can disturb monoamine-neurotransmitter metabolism. These findings may be of significance in understanding the etiology of monoamine-related mental diseases, such as schizophrenia and autism (a neurodevelopmental disorder).

  2. Association of plasma manganese levels with chronic renal failure.

    PubMed

    Sánchez-González, Cristina; López-Chaves, Carlos; Gómez-Aracena, Jorge; Galindo, Pilar; Aranda, Pilar; Llopis, Juan

    2015-01-01

    Manganese (Mn) is an essential trace element involved in the formation of bone and in amino acid, lipid and carbohydrate metabolism. Mn excess may be neurotoxic to humans, affecting specific areas of the central nervous system. However, relatively little is known about its physiological and/or toxicological effects, and very few data are available concerning the role of Mn in chronic renal failure (CRF). This paper describes a 12-month study of the evolution of plasma Mn levels in predialysis patients with CRF and the relationship with energy and macronutrient intake. The participants in this trial were 64 patients with CRF in predialysis and 62 healthy controls. Plasma levels of creatinine, urea, uric acid, total protein and Mn were measured. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault index. The CRF patients had higher plasma levels of creatinine, urea, uric acid and Mn and a lower GFR than the controls. Plasma Mn was positively correlated with creatinine, plasma urea and plasma uric acid and was negatively correlated with the GFR and the intake of energy and macronutrients. In conclusion, CRF in predialysis patients is associated with increases in circulating levels of Mn.

  3. [Relationship between clozapine plasma levels and withdrawal symptoms].

    PubMed

    Berecz, R; de la Rubia Martínez, A; Norberto Gamero, M J; Gutiérrez Casares, J R; Glaub, T; Degrell, I; Llerena, A

    2002-01-01

    Discontinuation of clozapine and an attempt to change his medication to sertindol has led to serious psychotic and somatic symptoms in an schizophrenic patient treated with clozapine for five years, however after readministration of clozapine these symptoms rapidly disappeared. To further analyse the case we have developed an HPLC method for the measurement of plasma levels of clozapine and its main metabolite N-desmethyl clozapine in order to monitor the plasma levels of clozapine and to correlate with the clinical symptoms. The present results confirmed that after discontinuation of clozapine no measurable amount of drug or its main metabolite were present in the plasma of the patient. The correlation between the plasma levels of clozapine and the changes in the clinical state of the patient confirmed that the patient's severe psychotic and somatic symptoms were the result of discontinuation of clozapine treatment. The clozapine plasma concentration of the patient reported here was low (100 ng/ml) compared to the generally accepted plasma levels for antipsychotic action of clozapine (350 ng/ml), however the somatic and psychotic clozapine withdrawal symptoms rapidly and completely disappeared.

  4. ACTH Action on StAR Biology.

    PubMed

    Clark, Barbara J

    2016-01-01

    Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies.

  5. ACTH Action on StAR Biology

    PubMed Central

    Clark, Barbara J.

    2016-01-01

    Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies. PMID:27999527

  6. Adrenal hemorrhage complicating ACTH therapy in Crohn's disease.

    PubMed

    Levin, T L; Morton, E

    1993-01-01

    Huge dose ACTH therapy is used in some severely ill patients with inflammatory bowel disease. We report a teenage girl with Crohn's disease who developed an acute abdomen following ACTH therapy. CT revealed the mass to be a hemorrhagic adrenal gland; the opposite adrenal gland was hypertrophied but without signs of hemorrhage.

  7. Acute effects of ACTH on dissociated adrenocortical cells: quantitative changes in mitochondria and lipid droplets.

    PubMed

    Zoller, L C; Malamed, S

    1975-08-01

    To study the role of certain organelles in steroidogenesis, dissociated rat adrenocortical cells were incubated for two hours with ACTH at a concentration that induces a high level of steroid production. Sections of ACTH treated and untreated cells were photographed in the electron microscope, and morphometric analysis was undertaken to assess possible ACTH-induced changes in total cell volume, volume density and numerical denisty of lipid droplets and mitochondria. There was no change in total cell volume. Lipid droplet volume density and numerical density decreased. Mitochondrial volume density did not change, but numerical density increased. The decrease in lipid droplet volume density indicates a rapid depletion of cholesterol for steroid production. This depletion is almost entirely due to the disappearance of lipid droplets, rather than to an overall diminution in their size, as shown by the decrease in lipid droplet numerical density. The mitochondrial data suggest that the adrenocortical cell has an adedquate mitochondrial apparatus to respond to acute ACTH stimulation with increased steroid output without an increase inmitochondrial volume.

  8. Relationship between plasma and saliva quinine levels in humans.

    PubMed

    Babalola, C P; Bolaji, O O; Ogunbona, F A; Dixon, P A

    1996-02-01

    The relationship between saliva and plasma levels of quinine was studied in four healthy volunteers. After a single oral dose of quinine sulfate (600 mg) to the volunteers, quinine was determined in both saliva and plasma simultaneously over a 48-h period by an ion pair reverse-phase high performance liquid chromatography method. The tmax (4.3 +/- 0.5 h) and elimination half-life (11.8 +/- 2.9 h) of quinine derived from saliva levels were comparable with those obtained from plasma levels (tmax = 2.8 +/- 0.2 h, t1/2 = 12.9 +/- 2.3 h). A significant correlation existed between the plasma and saliva concentrations of the drug (r = 0.93, n = 20, p < 0.001). The mean saliva/plasma quinine concentration ratio was 0.24 +/- 0.02. The results suggest that quinine is passively secreted into saliva and that saliva level determination may be useful as a noninvasive method in the evaluation of pharmacokinetic parameters and therapeutic drug monitoring of quinine.

  9. Plasma amino acid response to graded levels of escape protein.

    PubMed

    Gibb, D J; Klopfenstein, T J; Britton, R A; Lewis, A J

    1992-09-01

    A trial was conducted to examine the potential of using plasma amino acid responses to graded levels of escape protein to determine limiting amino acids in cattle. Growing calves (n = 120; mean BW = 220 +/- 21 kg) were fed a basal diet of corncob:sorghum silage (61:39) and were individually supplemented with distillers' dried grains (DDG), heat-damaged DDG (H-DDG), feather meal (FTH), or urea. The urea supplement was mixed with DDG and H-DDG to allow 0, 20, 35, 50, 65, or 80% of the supplemental CP to come from distillers' protein and maintain an 11.5% CP diet. Urea supplement was mixed with FTH to allow 0, 22, 39, 56, 73, or 90% of the supplemental CP to come from FTH. Dietary CP ranged from 11.5% at the 0% level to 17.3% at the 90% level. Plasma concentration of most essential plasma amino acids responded (P less than .10) linearly and(or) quadratically to increased escape protein. The broken-line response of plasma methionine at low DDG intake suggested that methionine was limiting at low levels of escape protein. An initial decrease followed by a plateau fit by a broken line indicated that histidine became limiting in FTH diets, and lysine eventually became limiting for DDG, H-DDG, and FTH diets before maximum BW gain was reached. Results indicate that plasma amino acid responses may identify amino acids that become limiting with increasing escape protein.

  10. Relationship of blood cadmium level to hypertension and plasma norepinephrine level: a Romanian study (41159)

    SciTech Connect

    Revis, N.W.; Zinsmeister, A.R.

    1981-06-01

    The associations of blood cadmium levels with hypertension and plasma norepinephrine concentrations were determined in normotensive and hypertensive nonsmokers and smokers. Statistical analysis showed that after adjustment for age alone, the estimated mean values of blood cadmium and plasma norepinephrine in nonsmokers were significantly lower than in smokers. However, after adjustment for age and blood cadmium, the estimated mean values for plasma norepinephrine were not significantly different between nonsmokers and smokers or normotensives and hypertensives. In contrast the estimated mean value for blood cadmium as a function of blood pressure and smoking habit was still significant after adjustment for age and plasma norepinephrine. We suggest that smoking and blood pressure affect the level of blood cadmium, and through this change in blood cadmium the level of plasma norepinephrine is affected.

  11. The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin.

    PubMed

    Larzul, C; Terenina, E; Foury, A; Billon, Y; Louveau, I; Merlot, E; Mormede, P

    2015-12-01

    In the search for biological basis of robustness, this study aimed (i) at the determination of the heritability of the cortisol response to ACTH in juvenile pigs, using restricted maximum likelihood methodology applied to a multiple trait animal model, and (ii) at the study of the relationships between basal and stimulated cortisol levels with corticosteroid-binding globulin (CBG), IGF-I and haptoglobin, all important players in glucose metabolism and production traits. At 6 weeks of age, 298 intact male and female piglets from 30 litters (30 dams and 30 boars) were injected with 250 µg ACTH(1-24) (Synacthen). Blood was taken before ACTH injection to measure basal levels of cortisol, glucose, CBG, IGF-I and haptoglobin, and 60 min later to measure stimulated cortisol levels and glucose. Cortisol increased 2.8-fold after ACTH injection, with a high correlation between basal and stimulated levels (phenotypic correlation, r p=0.539; genetic correlation, r g=0.938). Post-ACTH cortisol levels were highly heritable (h 2=0.684) and could therefore be used for genetic selection of animals with a more reactive hypothalamic-pituitary-adrenocortical axis. CBG binding capacity correlated with cortisol levels measured in basal conditions in males only. No correlation was found between CBG binding capacity and post-ACTH cortisol levels. Basal IGF-I concentration was positively correlated with BW at birth and weaning, and showed a high correlation with CBG binding capacity with a strong sexual dimorphism, the correlation being much higher in males than in females. Basal haptoglobin concentrations were negatively correlated with CBG binding capacity and IGF-I concentrations. Complex relationships were also found between circulating glucose levels and these different variables that have been shown to be related to glucose resistance in humans. These data are therefore valuable for the genetic selection of animals to explore the consequences on production and robustness traits, but

  12. Plasma separation: physical separation at the molecular level

    NASA Astrophysics Data System (ADS)

    Gueroult, Renaud; Rax, Jean-Marcel; Fisch, Nathaniel J.

    2016-09-01

    Separation techniques are usually divided in two categories depending on the nature of the discriminating property: chemical or physical. Further to this difference, physical and chemical techniques differ in that chemical separation typically occurs at the molecular level, while physical separation techniques commonly operate at the macroscopic scale. Separation based on physical properties can in principle be realized at the molecular or even atomic scale by ionizing the mixture. This is in essence plasma based separation. Due to this fundamental difference, plasma based separation stands out from other separation techniques, and features unique properties. In particular, plasma separation allows separating different elements or chemical compounds based on physical properties. This could prove extremely valuable to separate macroscopically homogeneous mixtures made of substances of similar chemical formulation. Yet, the realization of plasma separation techniques' full potential requires identifying and controlling basic mechanisms in complex plasmas which exhibit suitable separation properties. In this paper, we uncover the potential of plasma separation for various applications, and identify the key physics mechanisms upon which hinges the development of these techniques.

  13. Modulation of Human Plasma Fibronectin Levels Following Exercise,

    DTIC Science & Technology

    1988-01-01

    increased under conditions of pathology, such as in obesity (6). cancer (3). proteinuria (4). diabetic retinopathy (5). and preeclampsia (27). in the absence...Res. 1977: 22:709-716. 27. Stubbs. T.M.. Lazarchick. J.. and Horger. E.O. Plasma fibronectin levels in preeclampsia : A possible biochemical marker

  14. Progesterone and estradiol plasma levels in neonatally irradiated cycling rats

    SciTech Connect

    Freud, A.; Sod-Moriah, U.A. )

    1990-01-01

    Female rats which were exposed to a single low dose of gamma irradiation (6R or 15R) at the age of 8 days produce smaller litters when mature than untreated controls. The possibility that the impaired fertility resulted from altered ovarian activity as reflected by changes in plasma levels of progesterone or estardiol was investigated. Plasma levels of both steroids were determined throughout the day of proestrus. Progesterone level was also determined in 6R animals on the day of weaning. The maturity of such irradiated rats was assessed by observing the time of vaginal opening. The results indicated that the preovulatory peak of progesterone was delayed in the 6R rats whereas in the 15R group its levels were significantly lower. On the other hand no differences in estradiol plasma levels were noticed between the groups. The higher level of progesterone in the 6R animals was not evident on the day of weaning and was even in both groups, but vaginal opening in the irradiated rats was significantly delayed. The elevated level of progesterone might be responsible, among other endocrine changes, for the lower fertility of neonatally irradiated mature female rats.

  15. Plasma lipid levels in preterm neonates receiving parenteral fat emulsions.

    PubMed Central

    Hilliard, J L; Shannon, D L; Hunter, M A; Brans, Y W

    1983-01-01

    Concentrations of various plasma lipid fractions were determined during 96 hours of continuous parenteral infusions of lipid emulsions in 10 normally-grown neonates whose birth-weights ranged from 960 to 1760 g and whose gestational ages ranged from 26 to 32 weeks. Total lipid, triglyceride, free glycerol, and free fatty acid concentrations were measured. During lipid infusions, mean plasma concentrations of all lipid fractions increased above the mean preinfusion values if 2 g/kg a day or more of lipid emulsion was used. There were no further significant increases in mean plasma lipid levels if the infused dosage was increased to 3 or 4 g/kg a day. At these higher infusion rates however, there were considerable individual variations. The only neonate less than 27 weeks of gestation had plasma lipid levels severalfold higher than any of his peers, his plasma was frankly creamy on visual inspection, and the study had to be stopped. Further investigations are needed to determine the optimal modalities of parenteral nutrition with fat emulsions. PMID:6402989

  16. Plasma ghrelin levels in patients with Familial Mediterranean Fever.

    PubMed

    Keskin, Göksal; Inal, Ali; Ilikçi, Rahşan; Baysal, Ozan

    2009-01-01

    Familial mediterranean fever (FMF) is a familial disease characterized by recurrent episodes of febrile serositis, peritonitis, arthritis and pleuritis. Many studies have been performed is an attempt to understand the basis of the inflammatory attacts in FMF. Ghrelin, a recently described orexigene peptide is predominantly produced by stomach. Ghrelin also exerts multiple regulatory effects on immune system. It has reported that grelin has anti-inflammatory effects. There is currently no published evidence demonstrating a role for anti-inflammatory effects of ghrelin in FMF. For this reason, we investigated the role of plasma ghrelin levels in patients with FMF. Thirty seven patients with FMF and 10 healthy controls (5 female, 5 male; mean age 35.4 +/- 5.6 years) were enrolled in this study. Twenty-one patients were in active stage (10 female, 11 male, mean age; 31.0 +/- 5.4 years, mean disease duration 7.2 +/- 3.3 years) and 16 patients were in inactive stage (7 female,9 male, mean age; 33.0 +/- 6.0 years, mean disease duration; 8.7 +/- 3.2 years). Plasma ghrelin levels were determined by EIA. The mean plasma ghrelin levels were 158.4 +/- 52.9 pg/ml in patients with FMF and 56.7 +/- 7.5 pg/ml in healthy controls. The mean plasma ghrelin levels were 190.5 +/- 49.4 pg/ml in the active patients and 116.2 +/- 11.7 pg/ml in the inactive patients. Plasma ghrelin levels were significantly high in patients with FMF compared to healthy controls (p<0.001). Plasma ghrelin levels were significantly high in the active patients compared to in the inactive patients and healthy controls (p<0.001 and p<0.001 respectively). There was significantly difference between in active and inactive patients with FMF (p<0.001). As a results; Plasma ghrelin levels were high both in active and inactive patients with FMF. It is showed that ghrelin may play significant role of the pathogenesis of FMF.

  17. Human traumatic brain injury alters plasma microRNA levels.

    PubMed

    Redell, John B; Moore, Anthony N; Ward, Norman H; Hergenroeder, Georgene W; Dash, Pramod K

    2010-12-01

    Circulating microRNAs (miRNAs) present in the serum/plasma are characteristically altered in many pathological conditions, and have been employed as diagnostic markers for specific diseases. We examined if plasma miRNA levels are altered in patients with traumatic brain injury (TBI) relative to matched healthy volunteers, and explored their potential for use as diagnostic TBI biomarkers. The plasma miRNA profiles from severe TBI patients (Glasgow Coma Scale [GCS] score ≤8) and age-, gender-, and race-matched healthy volunteers were compared by microarray analysis. Of the 108 miRNAs identified in healthy volunteer plasma, 52 were altered after severe TBI, including 33 with decreased and 19 with increased relative abundance. An additional 8 miRNAs were detected only in the TBI plasma. We used quantitative RT-PCR to determine if plasma miRNAs could identify TBI patients within the first 24 h post-injury. Receiver operating characteristic curve analysis indicated that miR-16, miR-92a, and miR-765 were good markers of severe TBI (0.89, 0.82, and 0.86 AUC values, respectively). Multiple logistic regression analysis revealed that combining these miRNAs markedly increased diagnostic accuracy (100% specificity and 100% sensitivity), compared to either healthy volunteers or orthopedic injury patients. In mild TBI patients (GCS score > 12), miR-765 levels were unchanged, while the plasma levels of miR-92a and miR-16 were significantly increased within the first 24 h of injury compared to healthy volunteers, and had AUC values of 0.78 and 0.82, respectively. Our results demonstrate that circulating miRNA levels are altered after TBI, providing a rich new source of potential molecular biomarkers. Plasma-derived miRNA biomarkers, used in combination with established clinical practices such as imaging, neurocognitive, and motor examinations, have the potential to improve TBI patient classification and possibly management.

  18. Smoking, COPD and 3-Nitrotyrosine Levels of Plasma Proteins

    SciTech Connect

    Jin, Hongjun; Webb-Robertson, Bobbie-Jo M.; Peterson, Elena S.; Tan, Ruimin; Bigelow, Diana J.; Scholand, Mary Beth; Hoidal, John R.; Pounds, Joel G.; Zangar, Richard C.

    2011-09-01

    BACKGROUND: Nitric oxide is a physiologically regulator of endothelial function and hemodynamics. Oxidized products of nitric oxide can form nitrotyrosine, which is a marker of nitrative stress. Cigarette smoking decreases exhaled nitric oxide, and the underlying mechanism may be important in the cardiovascular toxicity of cigarette smoke, although it is not clear if this effect results from decreased nitric oxide production or oxidation of nitric oxide to reactive, nitrating, species. These processes would be expected to have opposite effects on nitrotyrosine levels, a marker of nitrative stress. OBJECTIVE: In this study, we determine the effects of smoking and chronic obstructive pulmonary disease (COPD) on circulating levels of nitrotyrosine, and thereby gain insight into the processes regulating nitrotyrosine formation. METHODS: A custom antibody microarray platform was used to analyze the levels of 3-nitrotyrosine modifications on 24 proteins in plasma. Plasma samples from 458 individuals were analyzed. RESULTS: Nitrotyrosine levels in circulating proteins were uniformly reduced in smokers but increased in COPD patients. We also observed a persistent suppression of nitrotyrosine in former smokers. CONCLUSIONS: Smoking broadly suppresses the levels of 3-nitrotyrosine in plasma proteins, suggesting that cigarette smoke suppresses endothelial nitric oxide production. In contrast, the increase in nitrotyrosine levels in COPD patients most likely results from inflammatory processes. This study provides the first evidence that smoking has irreversible effects on endothelial production of nitric oxide, and provides insight into how smoking could induce a loss of elasticity in the vasculature and a long-term increase in the risk of cardiovascular disease.

  19. Plasma folate levels in men with type 2 diabetes.

    PubMed

    Sakuta, Hidenari; Suzuki, Takashi; Yasuda, Hiroko; Ito, Teizo

    2005-09-01

    Limited data suggest that folate levels are higher in patients with type 2 diabetes than in subjects with normal glucose tolerance (NGT). We compared the fasting plasma folate, glucose (FPG), body mass index (BMI), and supplementary vitamin use among male subjects with NGT, those with impaired glucose tolerance (IGT), those with newly diagnosed type 2 diabetes, and those with previously diagnosed type 2 diabetes. Plasma folate of patients with newly diagnosed diabetes and that of patients with previously diagnosed diabetes was significantly higher than that of NGT subjects (p < 0.001). Prevalence of vitamin use was lower in newly diagnosed or previously diagnosed diabetic patients compared with non-diabetic subjects. Self-rated vegetable intake was similar among the four groups. FPG, BMI, triglycerides, and systolic blood pressure correlated with plasma folate levels independently of lifestyle factors studied. These results suggest that plasma folate levels are elevated in male diabetic patients independently of health-conscious behavior that is recommended for diabetic people.

  20. Long-term ACTH and corticosteroid therapy in two siblings with polyneuropathy due to acute intermittent porphyria.

    PubMed

    Jusić, A; Sostarko, M; Majić, D

    1976-01-01

    The influence of long-term corticosteroid and ACTH therapy in two sisters was followed up. The periods of observation were 4 and 2 years. The high levels of corticosteroids obviously reversed the fatal progress of the disease. The relapses in the elder sister occurred during longer periods of discontinued corticosteroid therapy. In the younger the therapy was continuous. There was no relapse except for a short one appearing after the tooth extraction and discontinuation of the therapy for 10 days. Some correlation between neurological signs and symptoms and porphobilinogen androporphyrin levels were found. The question arises how it is possible to influence the genetically determined disease by corticosteroids or ACTH.

  1. Changes in plasma taurine levels after different endurance events.

    PubMed

    Ward, R J; Francaux, M; Cuisinier, C; Sturbois, X; De Witte, P

    1999-01-01

    The sulphonated amino acid taurine increased significantly in the plasma of trained athletes after three endurance exercises of different duration and intensity, a 90 min run on a treadmill at 75% of an individual's VO2 peak, a Marathon, 42.2 km and a 100 km run, by 19%, 77% and 36%, respectively. Such results indicated that the speed at which the exercise is performed, referred to as the intensity, rather than the duration of the exercise, correlated with the elevated taurine levels possibly indicating its release from muscle fibres. The plasma amino acid pool decreased significantly in relationship with the duration of the exercise, caused by their utilisation for glucogenesis. The possible sources of the increased plasma taurine are discussed.

  2. Plasma immunoreactive relaxin levels in pregnant and nonpregnant women.

    PubMed

    O'Byrne, E M; Carriere, B T; Sorensen, L; Segaloff, A; Schwabe, C; Steinetz, B G

    1978-11-01

    Immunoreactive relaxin was measured in plasma samples obtained from human volunteers utilizing the RIA procedure of Sherwood et al., as modified by O'Byrne and Steinetz for heterologous plasma samples. Immunoreactive hormone was not detected in samples obtained from men, and only rarely in plasma of nonpregnant women. Immunoreactive relaxin was present as early as the fourth week of pregnancy and was detectable throughout the course of gestation. Immunoreactive relaxin tended to be higher early in pregnancy, and there was no peak just before parturition as occurs in many other species. Our results are at variance with those of Bryant and coworkers, who reported high levels of immunoreactive relaxin in men and nonpregnant as well as pregnant women. The possible reasons for this discrepancy are presented.

  3. Plasma levels of S100A4 in portopulmonary hypertension.

    PubMed

    Peng, Tien; Zamanian, Roham; Krowka, Michael J; Benza, Raymond L; Roberts, Kari E; Taichman, Darren B; Rybak, Debbie; Trotter, James F; Brown, Robert S; Fallon, Michael B; Kawut, Steven M

    2009-05-01

    We previously showed that a single nucleotide polymorphism in S100A4 was associated with portopulmonary hypertension (PPHTN) in patients with advanced liver disease. We aimed to determine the association between plasma levels of S100A4 and PPHTN. We performed a case-control study of patients with advanced liver disease. Cases with PPHTN had mean pulmonary artery pressure >25 mmHg, pulmonary vascular resistance >240 dynes s cm(-5) and pulmonary capillary wedge pressure Plasma samples were assayed for S100A4. The study sample included 14 cases with PPHTN and 32 controls with liver disease. There was no difference in mean age between cases and controls (p = 0.52). Seventy-nine percent of cases were female compared with 44% of controls (p = 0.03). There was no difference in S100A4 levels between cases and controls (p = 0.58). Both groups had significantly higher S100A4 levels than healthy volunteers (p <0.05). There was no significant difference in plasma levels of S100A4 between PPHTN patients and controls with liver disease, although liver disease itself was associated with increased S100A4 levels.

  4. Plasma Levels of S100A4 in Portopulmonary Hypertension

    PubMed Central

    Peng, Tien; Zamanian, Roham; Krowka, Michael J.; Benza, Raymond L.; Roberts, Kari E.; Taichman, Darren B.; Rybak, Debbie; Trotter, James F.; Brown, Robert S.; Fallon, Michael B.; Kawut, Steven M.

    2010-01-01

    We previously showed that a single nucleotide polymorphism in S100A4 was associated with developing portopulmonary hypertension (PPHTN) in patients with advanced liver disease. We aimed to determine the association between plasma levels of S100A4 and PPHTN. We performed a case-control study of patients with advanced liver disease. Cases with PPHTN had mean pulmonary artery pressure > 25 mm Hg, pulmonary vascular resistance > 240 dynes-sec · cm−5, and pulmonary capillary wedge pressure ≤15 mm Hg. Controls with liver disease had right ventricular systolic pressure < 40 mm Hg and normal right atrial and ventricular morphology by echocardiography. Plasma samples were assayed for S100A4. The study sample included 14 cases with PPHTN and 32 liver disease controls. The mean age for both cases and controls was 52 ± 9 yrs. Eighty percent of cases were female compared to 42% of controls (p = 0.02). There was no difference in S100A4 levels between cases and controls (p = 0.53). Both groups had significantly higher S100A4 levels than healthy volunteers (p < 0.05). There was no significant difference in plasma levels of S100A4 between PPHTN patients and controls with liver disease, although liver disease itself was associated with increased S100A4 levels. PMID:19399660

  5. Neuropeptide Y administration reverses tricyclic antidepressant treatment-resistant depression induced by ACTH in mice.

    PubMed

    Antunes, Michelle S; Ruff, Jossana Rodrigues; de Oliveira Espinosa, Dieniffer; Piegas, Manuela Bastos; de Brito, Maicon Lenon Otenio; Rocha, Kellen Athaíde; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Souza, Leandro Cattelan; Donato, Franciele; Boeira, Silvana Peterini; Jesse, Cristiano R

    2015-07-01

    Depression is one of the most common mental disorders and a primary cause of disability. To better treat patients suffering this illness, elucidation of the underlying psychopathological and neurobiological mechanisms is urgently needed. Based on the above-mentioned evidence, we sought to investigate the effects of neuropeptide Y (NPY) treatment in tricyclic antidepressant treatment-resistant depression induced by adrenocorticotropic hormone (ACTH) administration. Mice were treated with NPY (5.84, 11.7 or 23.4mmol/μl) intracerebroventricularly (i.c.v.) for one or five days. The levels of serum corticosterone, tryptophan (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and indoleamine 2,3-dioxygenase (IDO) activity in the hippocampus were analyzed. The behavioral parameters (depressive-like and locomotor activity) were also verified. This study demonstrated that ACTH administration increased serum corticosterone levels, KYN, 5-HIAA levels, IDO activity (hippocampus), immobility in the forced swimming test (FST) and the latency to feed in the novelty suppressed feeding test (NSFT). In addition, ACTH administration decreased the BDNF and NGF levels in the hippocampus of mice. NPY treatment was effective in preventing these hormonal, neurochemical and behavioral alterations. It is suggested that the main target of NPY is the modulation of corticosterone and neuronal plasticity protein levels, which may be closely linked with pharmacological action in a model of tricyclic antidepressant treatment-resistant depression. Thus, this study demonstrated a protective effect of NPY on the alterations induced by ACTH administration in mice, indicating that it could be useful as a therapy for the treatment of tricyclic antidepressant treatment-resistant depression.

  6. Low and intermediate level radioactive waste processing in plasma reactor

    SciTech Connect

    Sauchyn, V.; Khvedchyn, I.; Van Oost, G.

    2013-07-01

    Methods of low and intermediate level radioactive waste processing comprise: cementation, bituminization, curing in polymer matrices, combustion and pyrolysis. All these methods are limited in their application in the field of chemical, morphological, and aggregate composition of material to be processed. The thermal plasma method is one of the universal methods of RAW processing. The use of electric-arc plasma with mean temperatures 2000 - 8000 K can effectively carry out the destruction of organic compounds into atoms and ions with very high speeds and high degree of conversion. Destruction of complex substances without oxygen leads to a decrease of the volume of exhaust gases and dimension of gas cleaning system. This paper presents the plasma reactor for thermal processing of low and intermediate level radioactive waste of mixed morphology. The equipment realizes plasma-pyrolytic conversion of wastes and results in a conditioned product in a single stage. As a result, the volume of conditioned waste is significantly reduced (more than 10 times). Waste is converted into an environmentally friendly form that suits long-term storage. The leaching rate of macro-components from the vitrified compound is less than 1.10{sup -7} g/(cm{sup 2}.day). (authors)

  7. Plasma Leptin Levels in Children Hospitalized with Cholera in Bangladesh.

    PubMed

    Falkard, Brie; Uddin, Taher; Rahman, M Arifur; Franke, Molly F; Aktar, Amena; Uddin, Muhammad Ikhtear; Bhuiyan, Taufiqur Rahman; Leung, Daniel T; Charles, Richelle C; Larocque, Regina C; Harris, Jason B; Calderwood, Stephen B; Qadri, Firdausi; Ryan, Edward T

    2015-08-01

    Vibrio cholerae, the cause of cholera, induces both innate and adaptive immune responses in infected humans. Leptin is a hormone that plays a role in both metabolism and mediating immune responses. We characterized leptin levels in 11 children with cholera in Bangladesh, assessing leptin levels on days 2, 7, 30, and 180 following cholera. We found that patients at the acute stage of cholera had significantly lower plasma leptin levels than matched controls, and compared with levels in late convalescence. We then assessed immune responses to V. cholerae antigens in 74 children with cholera, correlating these responses to plasma leptin levels on day 2 of illness. In multivariate analysis, we found an association between day 2 leptin levels and development of later anti-cholera toxin B subunit (CtxB) responses. This finding appeared to be limited to children with better nutritional status. Interestingly, we found no association between leptin levels and antibody responses to V. cholerae lipopolysaccharide, a T cell-independent antigen. Our results suggest that leptin levels may be associated with cholera, including the development of immune responses to T cell-dependent antigens.

  8. Elevated plasma tricyclic levels with therapeutic doses of imipramine.

    PubMed

    Garvey, M J; Tuason, V B; Johnson, R A; Valentine, R H; Cooper, T B

    1984-07-01

    Nine (15%) of 59 patients treated with imipramine at doses of 150 to 300 mg/day had steady-state plasma levels greater than 500 ng/ml. Low capacity for hydroxylation was found in all six patients for whom hydroxy metabolites were measured. Maximum tricyclic levels in the nine study patients were comparable to levels found in tricyclic antidepressant overdoses (651-2439 ng/ml). No study patient experienced any adverse effects: QRS durations were all less than 100 msec, and a mildly dry mouth was the most commonly reported side effect (five of nine patients). Depressive symptoms recurred in three patients when their imipramine dose was decreased.

  9. Injected phytosterols/stanols suppress plasma cholesterol levels in hamsters.

    PubMed

    Vanstone, C A.; Raeini-Sarjaz, M; Jones, P J.H.

    2001-10-01

    Although plant sterols are known to suppress intestinal cholesterol absorption, whether plasma and hepatic lipid levels are influenced through non-gut related internal mechanisms has not been established. To examine this question 50 male hamsters were divided into 5 groups and fed semi-purified diets containing 20% energy as fat and 0.25% (w/w) cholesterol ad libitum for 60 days. The control group (i) received diet alone, while four additional groups consumed the diet plus one of four equivalent phytosterol mixtures (5 mg/kg/day) given either as (ii) tall oil phytosterols/stanols mixed with diet (oralSA), (iii) tall oil phytosterols/stanols subcutaneously injected (subSA), (iv) soybean oil phytosterols alone mixed with diet (oralSE), or (v) soybean oil subcutaneous injected phytosterols alone (subSE). The control group and both orally supplemented groups also received placebo subcutaneous sham injections. Neither food consumption, body weight, nor liver weight differed across treatment groups. Subcutaneous administration of SA and SE decreased plasma total cholesterol levels by 21% and 23% (p < 0.0001) and non-apolipoprotein-A cholesterol concentrations by 22% and 15% (p < 0.0002), respectively, compared to control. HDL cholesterol and TG concentrations remained unchanged across all groups, except for a decline of 25% (p < 0.0001) in HDL concentration in the subSE group versus control. Plasma campesterol levels were lower (p < 0.05) in the subSA group relative to all other groups. Plasma campesterol:cholesterol and campesterol:sitosterol ratios were, however, higher (p < 0.0001) for both the oral and subSE groups. Hepatic cholesterol levels were higher (p < 0.0001) in the oral and subSE phytosterol groups by 30% and 31%, respectively, relative to control. We conclude that low doses of subcutaneously administered plant sterols reduce circulating cholesterol levels through mechanisms other than inhibiting intestinal cholesterol absorption.

  10. ACTH stimulation test in the captive cheetah (Acinonyx jubatus).

    PubMed

    Köster, L S; Schoeman, J P; Meltzer, D G A

    2007-09-01

    Serum cortisol response was assessed in 8 captive cheetahs, of varying ages, after the intravenous administration of 500 microg of tetracosactide (Synacthen Depot, Novartis, Kempton Park) while maintained under general anaesthesia. In addition, 8 cheetahs were anaesthetised and given an equal volume of saline in order to establish baseline cortisol concentrations at similar stages of anaesthesia. A significant difference in the median cortisol concentration measured over time was found following ACTH administration in the ACTH group (P < 0.001). There was no difference between the median cortisol concentrations in the ACTH group at time-points 120, 150 and 180 min after ACTH stimulation (P = 0.867). Thus it appears appropriate to collect serum 120 to 180 min after tetracosactide administration to assess maximal stimulation of the adrenal in the cheetah. No statistically significant rise was seen in the anaesthetised control group following the injection of saline (P = 0.238).

  11. The regulation of plasma relaxin levels during human pregnancy.

    PubMed

    Johnson, M R; Abbas, A A; Allman, A C; Nicolaides, K H; Lightman, S L

    1994-08-01

    The factors that determine the circulating levels of relaxin during pregnancy have been investigated by comparing the plasma levels of relaxin throughout pregnancy in women who became pregnant spontaneously (singleton, n = 240) or following superovulation (singleton and multifetal pregnancies (two to ten conceptuses), n = 83). Some of the women with multifetal pregnancies underwent selective fetal reduction to twin pregnancies. Relaxin levels were higher at 7-34 weeks of gestation in singleton pregnancies achieved following superovulation when compared with levels in spontaneously conceived singleton pregnancies (p < 0.05-0.001). In samples obtained between 10 and 12 weeks of gestation (before fetal reduction for the multifetal pregnancies), plasma relaxin levels correlated with fetal number (r = 0.526, P = 0.0001). Reduction in fetal number to a twin pregnancy did not alter relaxin levels. These data suggest that the circulating levels of relaxin throughout pregnancy are determined during the cycle of conception by gonadotrophin stimulation, and within the first 10 weeks of pregnancy by the luteotrophic stimulus from the conceptus. Furthermore, once corpus luteum synthesis of relaxin is established, then reduction in the luteotrophic stimulus does not appear to affect it.

  12. Neonatal isolated ACTH deficiency (IAD): a potentially life-threatening but treatable cause of neonatal cholestasis

    PubMed Central

    Alsaleem, Mahdi; Saadeh, Lina; Misra, Amrit; Madani, Shailender

    2016-01-01

    Isolated ACTH deficiency (IAD) is a rare cause of neonatal cholestasis and hypoglycaemia. This diagnosis has a 20% mortality potential if unrecognised. We describe a case of an infant presenting with cholestatic jaundice and hypoglycaemia. The patient had laboratory findings suggestive of IAD, which was later confirmed with molecular genetic testing. One of the mutations this patient had is a new finding. The patient was started on glucocorticoid replacement therapy after which his bilirubin and glucose levels normalised. PMID:27535729

  13. [Preoperative digitalization. Measurement of digoxin plasma levels (author's transl)].

    PubMed

    Geiger, H J; Rietbrock, N

    1976-09-01

    In a study of 233 patients from the department of surgery and anesthesiology taking digoxin preparations 64, per cent exhibit digoxin levels in the therapeutic range (0.6--1.5 ng/ml), 19 per cent had subtoxic concentrations ranged from 1.6--2.0 ng/ml and 7 per cent were in the toxic range (greater than 2 ng/ml). In patients treated with digoxin before admission to hospital subtherapeutic levels were most frequent. An average loading dose of digoxin 1 mg or more on one day may result in subtoxic and toxic digoxin levels on the second day, in patients receiving less than 1 mg digoxin daily an increasing frequency of plasma digoxin concentrations of 1.5 ng/ml or higher values was present on the third day. Averaged plasma digoxin concentrations were correlated with daily maintenance dose. There was, however, a wide individual variation in digoxin plasma concentrations. A low incidence of toxic digoxin plasma levels was observed in patients receiving a daily oral maintenance dose of 0.375 mg digoxin (Lanicor). For prophylactic digitalization of patients with normal renal and thyroid function the following schedules or statistical guidlines are proposed: Lanicor (bioavailability 60%): oral loading dose of 0.75 mg over two days, and then daily oral maintenance dose of 0.375 mg; Novodigal (bioavailability 80%): oral loading dose of 0.6 mg over two days and then daily oral maintenance dose of 0.3 mg; Digoxin i.v.: intravenous loading dose of 0.5 (0.4) mg over two days and then 0.25 (0.2) mg daily intravenous maintenance dose. For any patient needing treatment with digitalis glycosides therapy must be individual and dynamic. The reasons for toxic concentrations were frequently attributed to wrong dosage.

  14. Decreased Plasma BDNF Levels of Patients with Somatization Disorder

    PubMed Central

    Kang, Nam-In; Park, Jong-Il

    2016-01-01

    Objective Brain-derived neurotrophic factor (BDNF), one of the most abundant and important neurotrophins, is known to be involved in the development, survival, maintenance, and plasticity of neurons in the nervous system. Some studies have suggested that BDNF may play a role in the pathophysiology of several psychiatric illnesses such as depression and schizophrenia. Similarly, it is likely that the alteration of BDNF may be associated with the neuro-modulation that contributes to the development of somatization disorder. Methods The purpose of this study was to determine whether there is an abnormality of plasma BDNF levels in patients with somatization disorder, and to analyze the nature of the alteration after pharmacotherapy using an enzyme-linked immunosorbent assay (ELISA). Results The plasma BDNF levels of the patients with a somatization disorder were significantly lower compared with those of the control volunteers (83.61±89.97 pg/mL vs. 771.36±562.14 pg/mL); moreover, the plasma BDNF levels of those patients who received an antidepressant were significantly increased after the treatment (118.13±91.45 pg/mL vs. 72.92±88.21 pg/mL). Conclusion These results suggest that BDNF may play a role in the pathophysiology of somatization disorder. PMID:27757131

  15. Early-onset severe obesity with ACTH deficiency and red hair in a boy: the POMC deficiency.

    PubMed

    Ozen, S; Aldemir, O

    2012-01-01

    The patient is a 2.8 years old male who is extremely obese and severe hyperphagic from birth. He had seizures attacks and apnea from the second week of his life. He has red hair and serum cortisol and ACTH levels are very low. We examined our patient as a hypocortisolism due to ACTH deficiency and central hypothyrodism. After the corticosteroid replacement therapy hair color changed to brown. We performed molecular genetic analysis at the Institue for Experimental Pediatric Endocrinology laboratory in Berlin, Germany by Krude H. and found compound heterozygous mutations. As a result the case is diagnosed as POMC deficiency.

  16. Effects of ACTH, capture, and short term confinement on glucocorticoid concentrations in harlequin ducks (Histrionicus histrionicus)

    USGS Publications Warehouse

    Nilsson, P.B.; Hollmén, Tuula E.; Atkinson, S.; Mashburn, K.L.; Tuomi, P.A.; Esler, Daniel; Mulcahy, D.M.; Rizzolo, D.J.

    2008-01-01

    Little is known about baseline concentrations of adrenal hormones and hormonal responses to stress in sea ducks, although significant population declines documented in several species suggest that sea ducks are exposed to increased levels of environmental stress. Such declines have been observed in geographically distinct harlequin duck populations. We performed an adrenocorticotropic hormone (ACTH) challenge to evaluate adrenal function and characterize corticosterone concentrations in captive harlequin ducks and investigated the effects of capture, surgery, and short term confinement on corticosterone concentrations in wild harlequin ducks. Harlequin ducks responded to the ACTH challenge with an average three-fold increase in serum corticosterone concentration approximately 90??min post injection, and a four- to five-fold increase in fecal glucocorticoid concentration 2 to 4??h post injection. Serum corticosterone concentrations in wild harlequin ducks increased within min of capture and elevated levels were found for several hours post capture, indicating that surgery and confinement maintain elevated corticosterone concentrations in this species. Mean corticosterone concentrations in wild harlequin ducks held in temporary captivity were similar to the maximum response levels during the ACTH challenge in captive birds. However, large variation among individuals was observed in responses of wild birds, and we found additional evidence suggesting that corticosterone responses varied between hatch year and after hatch year birds. ?? 2008.

  17. FABP4 plasma levels are increased in familial combined hyperlipidemia

    PubMed Central

    Cabré, Anna; Lázaro, Iolanda; Cofán, Montserrat; Jarauta, Estibaliz; Plana, Núria; Garcia-Otín, Angel L.; Ascaso, Juan F.; Ferré, Raimón; Civeira, Fernando; Ros, Emilio; Masana, Lluís

    2010-01-01

    The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) μg/l and 19.2 (9.2) μg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and homeostasis model assessment (HOMA) index (all P< 0.05), but not to lipid levels, whereas in obese patients, FABP4 correlated to triglyceride levels (r = 0.303, P= 0.014) and very low density lipoprotein size (r = 0.502, P = 0.001), as determined by nuclear magnetic resonance. Associations of FABP4 with BMI and waist circumference, but not with insulin levels, persisted in this subgroup. Plasma FABP4 does not influence the lipid phenotype of FCHL. In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance. These results support a hyperlipidemic mechanism of FCHL different from similar metabolic conditions where fat mass is strongly related to FABP4 and hypertriglyceridemia. PMID:20388924

  18. Hip Osteonecrosis Is Associated with Increased Plasma IL-33 Level

    PubMed Central

    Ma, Jinhui; Guo, Wanshou; Li, Zirong; Li, Shirui; Wang, Peng

    2017-01-01

    The recently discovered IL-33 as an IL-1 cytokine family member has been proved to be specifically released from osteonecrotic bones. We aimed to investigate the potential role of IL-33 in the development of osteonecrosis of femoral head (ONFH). Forty patients diagnosed with ONFH and forty age-, sex-, and body mass index- (BMI-) matched healthy subjects were included in this prospective study between March 2016 and September 2016. A commercially available ELISA kit was used to test the level of plasma IL-33. The IL-33 levels were compared among different ARCO stages, CJFH types, and etiology groups. Plasma IL-33 levels were significantly higher in the ONFH patients than that in the control subjects. The levels of IL-33 did not differ significantly among the ONFH patients with different ARCO stages. The IL-33 levels of patients with CJFH type L3 were significantly higher than that of patients with types L1 and L2. No significant differences were observed in IL-33 levels between steroid-induced, alcohol-induced, and idiopathic patients. Our findings seem to indicate that IL-33 effects may be detrimental during ONFH, which appeared to be associated with the prognosis of ONFH. The IL-33 deserves particular attention in the pathogenesis of ONFH. PMID:28167850

  19. Plasma-cortisol levels in experimental heatstroke in dogs

    NASA Astrophysics Data System (ADS)

    Assia, Ehud; Epstein, Yoram; Magazanik, Avraham; Shapiro, Yair; Sohar, Ezra

    1989-06-01

    The effect of external heat-load, exercise and dehydration on dynamic changes in plasma cortisol during the development of heatstroke was investigated. Thirty-three unanesthetized dogs were tested under two sets of climatic conditions: comfort conditions and hot-dry climatic conditions, half of them while exercising. Half of the dogs in each group were rehydrated. None of the dogs that were investigated at room temperature suffered heatstroke. Of the dogs exposed to high ambient temperature, all of the exercising, as well as five out of six non-hydrated dogs and one rehydrated non-exercising dog suffered heatstroke. Significant dehydration (6% 7% of body weight), occurred only under hgh ambient temperature. Plasma cortisol levels of all dogs that suffered heatstroke rose conspicuously for at least 5 h and returned to normal levels 24 h later. Cortisol levels of dogs who did not experience heatstroke remained within the normal range. Cortisol levels correlated with the severity of the stress leading to heatstroke. High and rising levels of cortisol, several hours after body temperature returns to normal, may support the diagnosis of heatstroke.

  20. Hyperglycemia may determine fibrinopeptide A plasma level increase in humans.

    PubMed

    Ceriello, A; Giugliano, D; Quatraro, A; Dello Russo, P; Marchi, E; Torella, R

    1989-12-01

    The effects of hyperglycemia on plasma fibrinopeptide A (FPA) levels in normal subjects are reported. An increase of FPA concentration parallel to sustained hyperglycemia was observed; when the glycemia returned to basal values, FPA showed values in normal range. Heparin infusion was able to significantly decrease the hyperglycemia-induced augment of FPA levels. Isovolumic-isotonic NaCl solution infusion produced a slight (NS) increase in FPA levels; however, mild hyperglycemia, achieved by glucagon, was also able to produce a significant increase in FPA concentration. These data demonstrate the direct role of hyperglycemia in conditioning FPA level, and suggest that hyperglycemia, by itself, is a sufficient stimulus to produce thrombin activation in humans.

  1. A Novel Medical Treatment of Cushing's Due to Ectopic ACTH in a Patient With Neurofibromatosis Type 1

    PubMed Central

    Bano, Gul; Mir, Farheen; Beharry, Nigel; Wilson, Philip; Hodgson, Shirley; Schey, Stephen

    2012-01-01

    A 64-year-old male presented with neurofibromatosis 1 and Cushing’s syndrome. Clinically he was over weight, depressed with extensive skin bruising and hypertension. His 24 hours urinary metanephrines, urinary 5HIAA, gut peptides and chromgranin levels were normal. His renal function and renal MRI scan was also normal. His cortisol failed to suppress on overnight dexamethsone suppression test. His low dose dexamethasone suppression with CRH stimulation showed failure of suppression of cortisol to < 50 nmol/L and ACTH was measurable at 10 ng/L on day 3. There was no response of ACTH or cortisol to CRH stimulation. His ACTH precursors were high at 126 pmol/L consistent with defective pro-opiomelanocortin (POMC) processing suggesting an ectopic source of ACTH production. The MRI scan of his pituitary and CT scan of the adrenal glands was normal. His octreotide scan was negative. The source of his ectopic ACTH was most likely a large retroperitoneal plexiform neurofibroma seen on CT abdomen that had undergone malignant peripheral nerve sheath tumour transformation on histology. He was a poor surgical risk for tumour debulking procedure. In view of the available literature and role of c-kit signalling in neurofibromatosis, he was treated with Imitinib. Four months after the treatment his Cushings had resolved on biochemical testing. After a year his plexiform neurofibroma has not increased in size. To our knowledge, this is the first case of NF1 associated with clinical and biochemical features of Cushing’s secondary to ectopic ACTH due to MPNST in a plexiform neurofibroma and its resolution on treatment with imatinib. PMID:23853621

  2. A Novel Medical Treatment of Cushing's Due to Ectopic ACTH in a Patient With Neurofibromatosis Type 1.

    PubMed

    Bano, Gul; Mir, Farheen; Beharry, Nigel; Wilson, Philip; Hodgson, Shirley; Schey, Stephen

    2013-01-01

    A 64-year-old male presented with neurofibromatosis 1 and Cushing's syndrome. Clinically he was over weight, depressed with extensive skin bruising and hypertension. His 24 hours urinary metanephrines, urinary 5HIAA, gut peptides and chromgranin levels were normal. His renal function and renal MRI scan was also normal. His cortisol failed to suppress on overnight dexamethsone suppression test. His low dose dexamethasone suppression with CRH stimulation showed failure of suppression of cortisol to < 50 nmol/L and ACTH was measurable at 10 ng/L on day 3. There was no response of ACTH or cortisol to CRH stimulation. His ACTH precursors were high at 126 pmol/L consistent with defective pro-opiomelanocortin (POMC) processing suggesting an ectopic source of ACTH production. The MRI scan of his pituitary and CT scan of the adrenal glands was normal. His octreotide scan was negative. The source of his ectopic ACTH was most likely a large retroperitoneal plexiform neurofibroma seen on CT abdomen that had undergone malignant peripheral nerve sheath tumour transformation on histology. He was a poor surgical risk for tumour debulking procedure. In view of the available literature and role of c-kit signalling in neurofibromatosis, he was treated with Imitinib. Four months after the treatment his Cushings had resolved on biochemical testing. After a year his plexiform neurofibroma has not increased in size. To our knowledge, this is the first case of NF1 associated with clinical and biochemical features of Cushing's secondary to ectopic ACTH due to MPNST in a plexiform neurofibroma and its resolution on treatment with imatinib.

  3. Plasma matrix metalloproteinase 2 levels and breast cancer risk.

    PubMed

    Aroner, Sarah A; Rosner, Bernard A; Tamimi, Rulla M; Tworoger, Shelley S; Baur, Nadja; Joos, Thomas O; Hankinson, Susan E

    2015-06-01

    Matrix metalloproteinase 2 (MMP2) is an enzyme with important functions in breast cancer invasion and metastasis. However, it is unclear whether circulating MMP2 levels may predict breast cancer risk. We conducted a prospective nested case-control analysis in the Nurses' Health Study among 1136 cases who were diagnosed with invasive breast cancer between 1992 and 2004 and 1136 matched controls. All participants provided blood samples in 1989-1990, and a subset (170 cases, 170 controls) contributed an additional sample in 2000-2002. Pre-diagnostic plasma MMP2 levels were measured via immunoassay, and conditional logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for breast cancer risk factors. No association was observed between plasma MMP2 levels and risk of total invasive breast cancer (top vs. bottom quartile, OR=1.0; 95% CI: 0.7, 1.2; p-trend=0.89). Findings did not vary significantly by time since blood draw, body mass index, postmenopausal hormone use, or menopausal status at either blood draw or breast cancer diagnosis. MMP2 was associated with a greater risk of nodal metastases at diagnosis (top vs. bottom quartile, OR=1.5; 95% CI: 1.0, 2.2; p-heterogeneity, any vs. no lymph nodes=0.002), but no significant associations were observed with other tumor characteristics or with recurrent or fatal cancers. Plasma MMP2 levels do not appear to be predictive of total invasive breast cancer risk, although associations with aggressive disease warrant further study.

  4. Glucagon-like peptide-2 but not imipramine exhibits antidepressant-like effects in ACTH-treated mice.

    PubMed

    Iwai, Takashi; Ohnuki, Tomoko; Sasaki-Hamada, Sachie; Saitoh, Akiyoshi; Sugiyama, Azusa; Oka, Jun-Ichiro

    2013-04-15

    We investigated the effectiveness of glucagon-like peptide-2 (GLP-2) against refractory depression in adrenocorticotropic hormone (ACTH)-treated mice as a model of tricyclic antidepressant (TCA)-resistant depression. Chronic ACTH treatment (0.45 mg/kg, s.c., 14 days) weakened the antidepressant-like effects of imipramine (20 mg/kg, i.p., 6 days) in the forced-swim test (FST). Conversely, GLP-2 (3 μg/mice, i.c.v., 6 days) induced antidepressant-like effects in the ACTH-treated mice in the FST. ACTH-treatment increased basal serum corticosterone levels, with an additional increase induced by the FST. Imipramine or GLP-2 had no effect on the basal corticosterone level, but GLP-2 attenuated the additional increase caused by the FST. Moreover, GLP-2 increased 5-HT levels, but not 5-HIAA. These results suggest that GLP-2 induced antidepressant-like effects under imipramine-resistant conditions through increase in 5-HT levels.

  5. [Effect of dalargin on the content of endorphins, leucine-enkephalin ACTH and corticosterone of the blood of stressed rats].

    PubMed

    Bobkov, A I; Polonskiĭ, V M; Vinogradov, V A; Demina, D G; Smagin, V G

    1985-12-01

    Stress caused by acute cysteamine duodenal ulcer was induced in Wistar male rats. All the endogenous opioides under study were involved in the stress-reaction mechanism. Protective dalargin (synthetic enkephalin analogue) administration revealed a tendency towards normalization of endorphin, L-enkephalin and ACTH blood levels.

  6. Multi-level molecular modelling for plasma medicine

    NASA Astrophysics Data System (ADS)

    Bogaerts, Annemie; Khosravian, Narjes; Van der Paal, Jonas; Verlackt, Christof C. W.; Yusupov, Maksudbek; Kamaraj, Balu; Neyts, Erik C.

    2016-02-01

    Modelling at the molecular or atomic scale can be very useful for obtaining a better insight in plasma medicine. This paper gives an overview of different atomic/molecular scale modelling approaches that can be used to study the direct interaction of plasma species with biomolecules or the consequences of these interactions for the biomolecules on a somewhat longer time-scale. These approaches include density functional theory (DFT), density functional based tight binding (DFTB), classical reactive and non-reactive molecular dynamics (MD) and united-atom or coarse-grained MD, as well as hybrid quantum mechanics/molecular mechanics (QM/MM) methods. Specific examples will be given for three important types of biomolecules, present in human cells, i.e. proteins, DNA and phospholipids found in the cell membrane. The results show that each of these modelling approaches has its specific strengths and limitations, and is particularly useful for certain applications. A multi-level approach is therefore most suitable for obtaining a global picture of the plasma-biomolecule interactions.

  7. ATRAZINE DOES NOT INDUCE GASTROINTESTINAL DISCOMFORT (PICA) IN RATS AT DOSES THAT INCREASE ACTH ANDCORTICOSTERONE RELEASE AND CAUSE CONDITIONED TASTE AVERSION.

    EPA Science Inventory

    Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT), with a LOEL of 12.5mg/kg. The mechanism for these effects is unk...

  8. Plasma bupivacaine levels associated with extradural anaesthesia for caesarean section.

    PubMed

    Thompson, E M; Wilson, C M; Moore, J; McClean, E

    1985-05-01

    Plasma bupivacaine levels were measured in 47 women undergoing extradural Caesarean delivery. They were divided into four groups according to the following dose regimens using 0.5% bupivacaine. Group A were given a bolus of 20 ml with increment after 20 minutes. Groups B and C were given 10 ml initially with further increments if required at 10 minutes (group B) and 20 minutes (group C); Group D consisted of patients who had an extradural block extended for emergency Caesarean delivery. In the elective groups the highest and most rapidly achieved values were associated with group A and the lowest levels found in group C. The highest levels of all were found in the emergency group. The investigation indicates that slow controlled induction of extradural anaesthesia for Caesarean section greatly reduces the risk of local anaesthetic toxicity.

  9. CRH stimulation of corticosteroids production in melanocytes is mediated by ACTH.

    PubMed

    Slominski, Andrzej; Zbytek, Blazej; Szczesniewski, Andrzej; Semak, Igor; Kaminski, Jan; Sweatman, Trevor; Wortsman, Jacobo

    2005-04-01

    The response to systemic stress is organized along the hypothalamic-pituitary-adrenal axis (HPA), whereas the response to a peripheral stress (solar radiation) is mediated by epidermal melanocytes (cells of neural crest origin) responsible for the pigmentary reaction. Melanocytes express proopiomelanocortin (POMC), corticotropin-releasing hormone (CRH), and CRH receptor-1 (CRH-R1) and can produce corticosterone. In the present study, incubation of normal epidermal melanocytes with CRH was found to trigger a functional cascade structured hierarchically and arranged along the same algorithm as in the HPA axis: CRH activation of CRH-R1 stimulated cAMP accumulation and increased POMC gene expression and production of ACTH. CRH and ACTH also enhanced production of cortisol and corticosterone, and cortisol production was also stimulated by progesterone. The chemical identity of the cortisol was confirmed by liquid chromatography-mass spectrometry (LC/MS2) with [corrected] mass spectrometry-mass spectrometry analyses. POMC gene silencing abolished the stimulatory effect of CRH on corticosteroid synthesis, indicating that this is indirect and mediated via production of ACTH. Thus the melanocyte response to CRH is highly organized along the same functional hierarchy as the HPA axis. This pattern demonstrates the fractal nature of the response to stress with similar activation sequence at the single-cell and whole body levels.

  10. Antimullerian Hormone Level and Endometrioma Ablation Using Plasma Energy

    PubMed Central

    Bubenheim, Michael; Auber, Mathieu; Marpeau, Loïc; Puscasiu, Lucian

    2014-01-01

    Objective: To investigate the impact of ovarian endometrioma vaporization using plasma energy on antimullerian hormone (AMH) level. Method: We report a prospective, noncomparative series (NCT01596985). Twenty-two patients with unilateral ovarian endometriomas ≥30 mm, with no surgical antecedent and no ongoing pregnancy, underwent vaporization of ovarian endometriomas using plasma energy during the period of November 29, 2010 to November 28, 2012. We assessed AMH levels before surgery, 3 months postoperatively, and at the end of follow-up. Results: The mean length of postoperative follow-up was 18.2 ± 8 months. AMH level significantly varied through the 3 assessments performed in the study, as the mean values ± SD were 3.9 ± 2.6 ng/mL before the surgery, 2.3 ± 1.1 ng/mL at 3 months, and 3.1 ± 2.2 ng/mL at the end of the follow-up (P = .001). There was a significant increase from 3 months postoperatively to the end of follow-up (median change 0.7 ng/mL, P = .01). Seventy-one percent of patients had an AMH level >2 ng/mL at the end of the follow-up versus 76% before the surgery (P = 1). During the postoperative follow-up, 11 patients tried to conceive, of whom 8 (73%) became pregnant. Conclusions: The ablation of unilateral endometriomas is followed in a majority of cases by a significant decrease in AMH level 3 months after surgery. In subsequent months, this level progressively increases, raising questions about the real factors that impact postoperative ovarian AMH production. PMID:25392649

  11. The increase of serum Bcl-2 concentration in moderate head injury outcome: The role of ACTH4-10Pro8-Gly9-Pro10

    PubMed Central

    Indharty, Rr Suzy

    2013-01-01

    Background: Traumatic brain injury (TBI) is one of the major causes of death and disability. Apoptosis after TBI contributes significantly to the final extent of tissue damage. The Bcl-2 family proteins are important apoptosis modulators which increased in injured neurons. Bcl-2 has shown an antiapoptotic effect in rats and mice. ACTH4-10Pro8-Gly9-Pro10 is a synthetic short fragment of ACTH devoid of hormonal effects and has neuromodulatory properties. ACTH4-10Pro8-Gly9-Pro10 has been shown to increase levels of Bcl-2 and BDNF in vitro as well as in vivo. It has been postulated that ACTH4-10Pro8-Gly9-Pro10 will result in improved clinical outcome and reduce hospital length of stay. The goal of this study is to compare the effect of standard therapy only with standard therapy and ACTH4-10Pro8-Gly9-Pro10, the increase of Bcl-2, and clinical outcome with reduction of hospital stay. Materials and Methods: Subjects of moderate head injury (MHI) with no indication of surgery were taken consecutively (n = 40) and separated into two groups: standard treatment only and standard treatment combined with ACTH4-10Pro8-Gly9-Pro10. Blood samples were taken on day 1 and day 5 from each subject for measurements of Bcl-2 concentration. Barthel Index and MMSE were measured, at discharge and hospital length of stay was noted. Results: Forty subjects have been involved in this study, three subjects died in the standard therapy group, and one subject in ACTH4-10Pro8-Gly9-Pro10 group. Bcl-2 serum level in standard therapy was 1.39 ± 0.75 ng/mL on day 1 and 1.48 ± 0.77 ng/mL on day 5. After treatment with ACTH4-10Pro8-Gly9-Pro10, Bcl-2 level was 1.39 ± 0.70 ng/mL on day 1 and 3.70 ± 1.02 ng/mL on day 5. The serum Bcl-2 concentration was significantly increased with ACTH4-10Pro8-Gly9-Pro10 therapy with shorter hospital length of stay (P < 0.05). Conclusion: ACTH4-10Pro8-Gly9-Pro10 increased serum Bcl-2 levels and reduced hospital length of stay significantly compared with standard

  12. Steroidogenic acute regulatory protein in eels: cDNA cloning and effects of ACTH and seawater transfer on its mRNA expression.

    PubMed

    Li, Yuan-You; Inoue, Koji; Takei, Yoshio

    2003-02-01

    Steroidogenic acute regulatory protein (StAR) is a key molecule for steroid production by translocating cholesterol from the outer to inner mitochondrial membrane. Two cDNAs of different length encoding StAR was cloned from the head kidney of the eel (Anguilla japonica). In the 3'-untranslated region (UTR) of the longer cDNA, two putative polyadenylation signals were found. The shorter one differed from the longer one solely by the lack of middle of 3'-UTR including the first polyadenylation signal. Reverse transcription-polymerase chain reaction (RT-PCR) that differentiates the two mRNAs showed that the ratio of the two was highly variable among individuals, and no preferential expression was detected between freshwater and seawater eels. The predicted protein consists of 285 amino acid residues with 64-83% identity to other StARs thus far obtained. RT-PCR analyses revealed that eel StAR mRNA was expressed abundantly in the head kidney and gonad, and faintly in the brain; but no expression was detected in the gill, heart, liver, intestine, kidney and skeletal muscle. Plasma cortisol concentration increased, but StAR mRNA content in the head kidney did not change, 3 and 24 h after transfer of freshwater eels to seawater, indicating that the transcriptional regulation of StAR may not be involved in cortisol production after seawater transfer. However, ACTH elevated both plasma cortisol and StAR mRNA levels in the head kidney 1.5 and 4.5 h after injection. Thus, the steroidogenic effect of ACTH is mediated by increased StAR production as observed in mammals.

  13. Nocturnal oscillations of plasma aldosterone in relation to sleep stages.

    PubMed

    Krauth, M O; Saini, J; Follenius, M; Brandenberger, G

    1990-10-01

    This study examined the relationship between aldosterone secretion and sleep stages in conjunction with two aldosterone regulating hormone systems, the renin-angiotensin system (RAS) and adrenocorticotropin (ACTH), and also K+. Nocturnal plasma patterns of aldosterone, plasma renin activity (PRA), ACTH and K+ were established in blood collected at 10-min intervals in two groups of 6 subjects. Both groups underwent two 9 hour overnight-studies, consisting of one control night and one experimental night. The first group was maintained on a low Na diet and the other was given a beta-blocker, atenolol. Polygraphic recordings of sleep were scored according to established criteria. For the control night, REM sleep usually began at peak level or in the descending phase of aldosterone oscillations. As previously described, PRA reflected REM-NREM sleep alteration, levels increased in NREM and decreased during REM sleep. ACTH fluctuations did not oscillate with sleep stages, but levels were very seldom in the ascending phase at REM sleep onset. Plasma K+ remained almost constant throughout the night. The relative importance of the ACTH and the RAS on nocturnal aldosterone secretion and the relationship between aldosterone oscillations and sleep stages remained unclear. Modulating renin levels by either consuming a low Na diet or administration of a beta-blocker enabled this relationship to be clarified. The RAS dominated aldosterone secretion when stimulated by a low sodium diet. Aldosterone oscillations then reflected PRA oscillations with a delay of about 20 min and the relationship of aldosterone to sleep stages was dependent on the relationship of PRA with sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. AB191. Laparoscopic subcutaneous transposition of a pedicled adrenal for ACTH-independent bilateral macronodular adrenal hyperplasia

    PubMed Central

    Zhang, Weixing; Zhang, Tianbiao

    2016-01-01

    Objective Bilateral adrenalectomy or unilateral adrenalectomy and contralateral partial adrenalectomy are indicated for the treatment of ACTH-independent macronodular adrenal hyperplasia. Independent of the surgical procedure, the prognosis is poor. This paper discusses a new treatment method and its efficacy for treating nodular adrenal hyperplasia. Methods We performed a retrospective review of the medical records of 12 patients operated on between January 2008 and October 2014 at the First Affiliated Hospital of Zhengzhou University. All patients were treated by laparoscopic subcutaneous transposition of a pedicled adrenal. We performed postoperative monitoring of patients including clinical symptoms and 24-hour levels of serum free and urinary free cortisol. Results All twelve patients were pathologically confirmed to have nodular adrenal hyperplasia, and were followed for an average of 45.5 months (range, 24–60 months). The clinical symptoms of all patients disappeared, and the 24-hour plasma free cortisol and urinary free cortisol levels were within the normal range. Conclusions Laparoscopic subcutaneous transposition of a pedicled adrenal is a new and effective method for treating bilateral macronodular adrenal hyperplasia, and can achieve long-term remission of Cushing’s syndrome.

  15. Decreased GH secretion and enhanced ACTH and cortisol release after ghrelin administration in Cushing's disease: comparison with GH-releasing peptide-6 (GHRP-6) and GHRH.

    PubMed

    Correa-Silva, Silvia Regina; Nascif, Sérgio Oliva; Lengyel, Ana-Maria Judith

    2006-01-01

    GH responsiveness to GH secretagogues (GHS) is blunted in Cushing's disease (CD), while ACTH/cortisol responses are enhanced, by mechanisms still unclear. Ghrelin, the endogenous ligand for GHS-receptors (GHS-R), increases GH, ACTH, cortisol and glucose levels in humans. This study evaluated the GH, ACTH, cortisol and glucose-releasing effects of ghrelin in CD in comparison with GHRP-6. GHRH-induced GH release was also studied. Ten patients with CD (BMI 26.9+/-1.0 kg/m(2)) and ten controls (BMI 24.4+/-1.1 kg/m(2)) received ghrelin (1 microg/kg), GHRP-6 (1 microg/kg) and GHRH (100 microg) separately. GH, ACTH, cortisol and glucose levels were measured. In CD ghrelin-induced GH (microg/L; mean +/- SE) release (peak: 7.2+/-3.0) was higher than seen with GHRP-6 (2.7+/-1.0) and GHRH (0.7+/-0.2), but lower than in controls (ghrelin: 58.3+/-12.1; GHRP-6: 22.9+/-4.8; GHRH: 11.3+/-3.7). In controls ACTH (pg/mL) release after ghrelin (79.2+/-26.8) was higher than after GHRP-6 (23.6+/-5.7). In CD these responses (ghrelin: 192+/-43; GHRP-6: 185+/-56) were similar, and enhanced compared to controls. The same was observed with cortisol. Glucose levels failed to increase after ghrelin in CD, differently than in controls. Our data suggests that hypothalamic and pituitary pathways of GH release activated by ghrelin, GHRP-6 and GHRH are deranged in chronic hypercortisolism. The increased ACTH/cortisol responses to ghrelin and GHRP-6 in CD could be mediated by overexpression of GHS-R in ACTH-secreting adenomas. Hypercortisolism apparently impairs the ability of ghrelin to increase glucose levels.

  16. [Levels of plasma cholinesterase in Colombian working-class populations].

    PubMed

    Carmona-Fonseca, Jaime

    2003-12-01

    Levels of plasma cholinesterase in Colombian working-class populations Reference values for plasma cholinesterase (EC 3.1.1.8) are not available for Colombian populations. A representative sample of a working-class population was used to establish these values to provide reference data for use by the social security system. Two working-class populations were sampled from the Aburrá Valley (Aburrá) and eastern Antioquia (Oriente). Cholinesterase activity was measured in 827 workers, with ages spanning 18-49 years, 415 from Aburrá and 412 people from Oriente. Three methods were used to measure cholinesterase: Michel, EQM and Monotest The average values by Michel and EQM were not statistically different between regions (Michel: Aburrá, 1.11, and East, 1.13 deltas pH/hora; EQM: Aburrá, 2.55, and Oriente, 2.48 U/ml). By the Monotest, the enzyme average was statistically higher in Aburra than in Oriente (5,743 and 5,459 U/L respectively; p = 0 .012). By region and technique, men had significantly higher enzymatic levels than women. Within both regions and sexes, no statistically significant difference among the three aged groups was noted. Our obtained Colombian values differed significantly from foreign reference values: Michel and Monotest levels were higher and EQM levels were lower. For making clinical and epidemiologic decisions in Colombia related to these data, the values obtained for the Colombian populations are preferred over values derived from external sources.

  17. Brain shrinkage and subdural effusion associated with ACTH administration.

    PubMed

    Satoh, J; Takeshige, H; Hara, H; Fukuyama, Y

    1982-01-01

    Sequential computed tomographic (CT) studies of 11 patients (aged five months to seven years) with intractable epilepsy treated with synthetic ACTH-Z showed brain shrinkage in all cases. Brain shrinkage started to appear on daily ACTH injections for seven days, reached the maximum within four weeks of administration (14 injections every day and then 7 injections every other day), and almost returned to the original status in seven out of nine cases which were followed up for one to three months after the therapy. The subjects aged less than two years showed more remarkable brain shrinkage than did those aged more than five years. Furthermore, two other cases were complicated by subdural effusion after ACTH therapy. It is the authors' assumption that both of these phenomena are caused by the high concentration of corticosteroid through a change of the water and electrolyte contents in the brain.

  18. DETERMINANTS OF PLASMA PARATHYROID HORMONE LEVELS IN YOUNG WOMEN

    PubMed Central

    Paik, Julie M.; Curhan, Gary C.; Forman, John P.; Taylor, Eric N.

    2011-01-01

    Purpose While the effects of calcium, phosphorus intake, and vitamin D on parathyroid hormone (PTH) have been well studied, less is known about other factors that impact PTH. Our goal was to delineate associations between demographic, dietary, and plasma factors and PTH. Methods We conducted a cross-sectional study of intact PTH among 1,288 non-black women in the Nurses Health Study II aged 33–53 with BMI < 30kg/m2 and eGFR ≥60 ml/min/1.73m2. Results Median PTH was 30.7pg/ml. After adjusting for 25-hydroxyvitamin D and other factors, PTH was 4.1pg/ml lower (95% CI −7.7 to −0.5) in women who smoked 1–14 cigarettes/day and 6.4pg/ml lower (95% CI −11.2 to −1.7) in women who smoked >15 cigarettes/day compared to non-smokers. After multivariate adjustment, women whose BMI was 27–29 kg/m2 had PTH levels 2.0pg/ml higher (95% CI 0.2–3.9) compared to BMI of 21–22 kg/m2, and women in the highest quartile of plasma phosphorus had PTH levels 4.1pg/ml lower (95% CI −5.8 to −2.4) than women in the lowest quartile. Higher vitamin A intake was independently associated with lower PTH whereas lower calcium intake, lower plasma calcium, lower plasma 25-hydroxyvitamin D, and winter blood draw were associated with higher PTH. Intakes of phosphorus, animal protein, magnesium, alcohol, and caffeine were not associated with PTH. Conclusions Factors not classically associated with calcium-phosphorus metabolism impact PTH. Additional research is needed to elucidate the mechanisms whereby smoking, vitamin A, and phosphorus affect PTH and to examine how body size and season may affect PTH independent of 25(OH)D. PMID:20631996

  19. Mid-gut ACTH-secreting neuroendocrine tumor unmasked with 18F-dihydroxyphenylalanine-positron emission tomography

    PubMed Central

    Gomez, Fulgencio; Prior, John O; Boubaker, Ariane; Matter, Maurice; Monti, Matteo; Pu, Yan; Pitteloud, Nelly; Portmann, Luc

    2015-01-01

    Summary Ectopic ACTH Cushing's syndrome (EAS) is often caused by neuroendocrine tumors (NETs) of lungs, pancreas, thymus, and other less frequent locations. Localizing the source of ACTH can be challenging. A 64-year-old man presented with rapidly progressing fatigue, muscular weakness, and dyspnea. He was in poor condition and showed facial redness, proximal amyotrophy, and bruises. Laboratory disclosed hypokalemia, metabolic alkalosis, and markedly elevated ACTH and cortisol levels. Pituitary was normal on magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus blood sampling with corticotropin-releasing hormone stimulation showed no significant central-to-periphery gradient of ACTH. Head and neck, thoracic and abdominal computerized tomography (CT), MRI, somatostatin receptor scintigraphy (SSRS), and 18F-deoxyglucose-positron emission tomography (FDG-PET) failed to identify the primary tumor. 18F-dihydroxyphenylalanine (F-DOPA)-PET/CT unveiled a 20-mm nodule in the jejunum and a metastatic lymph node. Segmental jejunum resection showed two adjacent NETs, measuring 2.0 and 0.5 cm with a peritoneal metastasis. The largest tumor expressed ACTH in 30% of cells. Following surgery, after a transient adrenal insufficiency, ACTH and cortisol levels returned to normal values and remain normal over a follow-up of 26 months. Small mid-gut NETs are difficult to localize on CT or MRI, and require metabolic imaging. Owing to low mitotic activity, NETs are generally poor candidates for FDG-PET, whereas SSRS shows poor sensitivity in EAS due to intrinsically low tumor concentration of type-2 somatostatin receptors (SST2) or to receptor down regulation by excess cortisol. However, F-DOPA-PET, which is related to amine precursor uptake by NETs, has been reported to have high positive predictive value for occult EAS despite low sensitivity, and constitutes a useful alternative to more conventional methods of tumor localization. Learning points Uncontrolled high

  20. Ketamine Inhibits Fetal ACTH Responses to Cerebral Hypoperfusion

    PubMed Central

    Powers, Melanie J.; Wood, Charles E.

    2009-01-01

    The present study tested the effect of ketamine on the fetal reflex responses of late-gestation sheep to brachiocephalic occlusion (BCO), a stimulus that mimics the reduction in cerebral blood flow that results from severe fetal hypotension. Ketamine, a dissociative anesthetic and known non-competitive antagonist of N-methyl D-aspartate (NMDA) receptors, has previously been shown to impair chemoreceptor responsiveness. Studies from this laboratory suggest that fetal reflex ACTH responses to hypotension are largely mediated by chemoreceptors; therefore we hypothesized that ketamine would inhibit the reflex hormonal response to BCO. Chronically catheterized fetal sheep were subjected to acute cerebral hypoperfusion through occlusion of the brachiocephalic artery. Fetal blood pressure and heart rate were continuously recorded and fetal blood samples drawn during the experiment were analyzed with specific hormone assays. Our results demonstrate that ketamine attenuates hemodynamic responses to cerebral hypoperfusion and is a potent inhibitor of adrenocorticotropin (ACTH) and proopiomelanocortin (POMC) / pro-ACTH release. These data support the hypothesis that fetal reflex responses hypotension are chemoreceptor mediated. Given the potency with which ketamine inhibits ACTH response to fetal hypotension, we suggest that the use of ketamine, or other anesthetic or analgesic drugs that block or otherwise interact with the NMDA-glutamate pathways, in late pregnancy or in pre-term newborns be reconsidered. PMID:17158270

  1. ACTH and. cap alpha. -melanotropin in central temperature control

    SciTech Connect

    Lipton, J.M.; Glyn, J.R.; Zimmer, J.A.

    1981-11-01

    Adrenocorticotropin (ACTH) and ..cap alpha..-melanotropin (..cap alpha..-MSH) occur in brain tissue known to be important to temperature control. These peptides cause hypothermia if they are injected centrally in sufficient doses, but they do not act on the central set point of temperature control. Instead they appear to inhibit central pathways for heat conservation and production. In addition to their hypothermic capability, these peptides are antipyretic when given centrally in doses that have no effect on normal body temperature. ACTH has previously been associated with fever reduction in both clinical and experimental studies, and it may be that endogenous central ACTH is important for limitation of maximal fever. The hypothermic and antipyretic effects of ACTH do not depend on stimulation of the adrenal cortex because they are also observed in adrenalectomized rabbits. Nor is the antipyretic effect limited to the rabbit inasmuch as a comparable effect has been demonstrated in the squirrel monkey. The two peptides may be involved in central mediation of normal thermoregulation and fever, perhaps limiting the febrile response and other rises in body temperature by acting as neurotransmitters or neuromodulators in central thermoregulatory pathways.

  2. Impact of ACTH Signaling on Transcriptional Regulation of Steroidogenic Genes

    PubMed Central

    Ruggiero, Carmen; Lalli, Enzo

    2016-01-01

    The trophic peptide hormone adrenocorticotropic (ACTH) stimulates steroid hormone biosynthesis evoking both a rapid, acute response and a long-term, chronic response, via the activation of cAMP/protein kinase A (PKA) signaling. The acute response is initiated by the mobilization of cholesterol from lipid stores and its delivery to the inner mitochondrial membrane, a process that is mediated by the steroidogenic acute regulatory protein. The chronic response results in the increased coordinated transcription of genes encoding steroidogenic enzymes. ACTH binding to its cognate receptor, melanocortin 2 receptor (MC2R), stimulates adenylyl cyclase, thus inducing cAMP production, PKA activation, and phosphorylation of specific nuclear factors, which bind to target promoters and facilitate coactivator protein recruitment to direct steroidogenic gene transcription. This review provides a general view of the transcriptional control exerted by the ACTH/cAMP system on the expression of genes encoding for steroidogenic enzymes in the adrenal cortex. Special emphasis will be given to the transcription factors required to mediate ACTH-dependent transcription of steroidogenic genes. PMID:27065945

  3. 21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Adrenocorticotropic hormone (ACTH) test system. 862.1025 Section 862.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  4. 21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Adrenocorticotropic hormone (ACTH) test system. 862.1025 Section 862.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  5. 21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Adrenocorticotropic hormone (ACTH) test system. 862.1025 Section 862.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  6. 21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Adrenocorticotropic hormone (ACTH) test system. 862.1025 Section 862.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  7. 21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Adrenocorticotropic hormone (ACTH) test system. 862.1025 Section 862.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  8. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats

    PubMed Central

    Bjørndal, Bodil; Ramsvik, Marie S.; Lindquist, Carine; Nordrehaug, Jan E.; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and γ-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and γ-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC’s content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis. PMID:26371012

  9. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats.

    PubMed

    Bjørndal, Bodil; Ramsvik, Marie S; Lindquist, Carine; Nordrehaug, Jan E; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K

    2015-09-08

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and γ-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and γ-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC's content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis.

  10. Plasma Cytokine Levels in Astronauts Before and after Spaceflight

    NASA Technical Reports Server (NTRS)

    Mehta, Satish K.; Aggarwal, Barat B.; Feiveson, Alan H.; Hammond, Dinne K.; Castro, Victoria A.; Stowe, Raymond; Pierson Duane L.

    2008-01-01

    Space flight is a unique experience and results in adverse effects on human physiology. Changes have been reported in various physiological systems, including musculoskeletal, neurovestibular, cardiovascular, endocrine, immunity and increased latent viral reactivation as well as others. The potential mechanisms behind these changes are not fully understood. Various cytokines such as IL-1, IL-6, TNF and chemokines have been linked to several of these changes, like muscle loss, bone loss, fatigue, sleep deprivation and viral reactivation. Eighteen astronauts (15 M and 3 F) from 8 spaceflights and 10 healthy age-matched adults (6 M, 4 F) were included in the present study. A panel of 21 plasma cytokines was analyzed with the Luminex 100 to measure the cytokines in these subjects 10 days before the flight (L-10), 2-3 hour after landing (R+0), 3 days after landing (R+3), and at their annual medical exam (AME). IL-10, IL-1, IFN-alpha, MCP-1 and IP-10 increased significantly at L-10 as compared with AME levels. IL-6 and IFN-alpha showed significant increases at R + 0 (P less than .05) over their baseline levels (AME). Cytokine levels at R+3 were not significantly different from R+0. IL-10 and IL-6 have been reported to increase in during viral reactivation. These data show that there was a shift from TH1 to TH2 cytokines L-10 and R+0. We also studied viral reactivation in 10 of the 18 subjects included in the present study before, during, and after space flight. Increased salivary varicella zoster virus (VZV) shedding in these subjects was found either during or after the mission. VZV shedding correlated with the increased levels of cytokines especially IL-10 and IL-6. Overall, our data suggests that cytokines may play an important role in regulating adverse changes in astronauts, and further studies are needed to fully understand the mechanism.

  11. Brief Report: Plasma Beta-Endorphin and Cortisol Levels in Autistic Patients.

    ERIC Educational Resources Information Center

    Sandman, Curt A.; And Others

    1991-01-01

    Comparison of plasma levels of beta-endorphin (BE) found that levels in 8 adult autistic patients were lower than levels in 17 healthy controls, for both morning and evening measurements. Plasma BE concentrations were also significantly lower for 13 developmentally disabled patients than levels for normal controls. (JDD)

  12. Reintoxication: the release of fat-stored Δ9-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure

    PubMed Central

    Gunasekaran, N; Long, LE; Dawson, BL; Hansen, GH; Richardson, DP; Li, KM; Arnold, JC; McGregor, IS

    2009-01-01

    Background and purpose: Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in adipose tissue where it is stored for long periods of time. Here we investigated whether conditions that promote lipolysis can liberate THC from adipocytes to yield increased blood levels of THC. Experimental approach: In vitro studies involved freshly isolated rat adipocytes that were incubated with THC before exposure to the lipolytic agent adrenocorticotrophic hormone (ACTH). A complementary in vivo approach examined the effects of both food deprivation and ACTH on blood levels of THC in rats that had been repeatedly injected with THC (10 mg·kg−1) for 10 consecutive days. Lipolysis promoted by ACTH or food deprivation was indexed by measurement of glycerol levels. Key results: ACTH increased THC levels in the medium of THC-pretreated adipocytes in vitro. ACTH also enhanced THC release from adipocytes in vitro when taken from rats repeatedly pretreated with THC in vivo. Finally, in vivo ACTH exposure and 24 h food deprivation both enhanced the levels of THC and its metabolite, (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in the blood of rats that had been pre-exposed to repeated THC injections. Conclusions and implications: The present study shows that lipolysis enhances the release of THC from fat stores back into blood. This suggests the likelihood of ‘reintoxication’ whereby food deprivation or stress may raise blood THC levels in animals chronically exposed to the drug. Further research will need to confirm whether this can lead to functional effects, such as impaired cognitive function or ‘flashbacks’. PMID:19681888

  13. Current-level triggered plasma-opening switch

    DOEpatents

    Mendel, C.W.

    1987-06-29

    An opening switch for very high power electrical pulses uses a slow magnetic field to confine a plasma across a gap between two electrodes. The plasma conducts the electric pulse across the gap while the switch is closed. A magnetic field generated by the pulse repels the slow magnetic field from the negative electrode to push the plasma from the electrode, opening the switch. A plurality of radial vanes may be used to enhance the slow magnetic field. 5 figs.

  14. Current-level triggered plasma-opening switch

    DOEpatents

    Mendel, Clifford W.

    1989-01-01

    An opening switch for very high power electrical pulses uses a slow magnetic field to confine a plasma across a gap between two electrodes. The plasma conducts the electric pulse across the gap while the switch is closed. A magnetic field generated by the pulse repels the slow magnetic field from the negative electrode to push the plasma from the electrode, opening the switch. A plurality of radial vanes may be used to enhance the slow magnetic field.

  15. Associations between dietary acrylamide intake and plasma sex hormone levels

    PubMed Central

    Hogervorst, Janneke G.; Fortner, Renee T.; Mucci, Lorelei A.; Tworoger, Shelley S.; Eliassen, A. Heather; Hankinson, Susan E.; Wilson, Kathryn M.

    2013-01-01

    Background The rodent carcinogen acrylamide was discovered in 2002 in commonly consumed foods. Epidemiological studies have observed positive associations between acrylamide intake and endometrial, ovarian and breast cancer risks, which suggests that acrylamide may have sex-hormonal effects. Methods We cross-sectionally investigated the relationship between acrylamide intake and plasma levels of sex hormones and SHBG among 687 postmenopausal and 1300 premenopausal controls from nested case-control studies within the Nurses’ Health Studies. Results There were no associations between acrylamide and sex hormones or SHBG among premenopausal women overall or among never-smokers. Among normal-weight premenopausal women, acrylamide intake was statistically significantly positively associated with luteal total and free estradiol levels. Among postmenopausal women overall and among never-smokers, acrylamide was borderline statistically significantly associated with lower estrone sulfate levels but not with other estrogens, androgens, prolactin or SHBG. Among normal weight women, (borderline) statistically significant inverse associations were noted for estrone, free estradiol, estrone sulfate, DHEA, and prolactin, while statistically significant positive associations for testosterone and androstenedione were observed among overweight women. Conclusions Overall, this study did not show conclusive associations between acrylamide intake and sex hormones that would lend unequivocal biological plausibility to the observed increased risks of endometrial, ovarian and breast cancer. The association between acrylamide and sex hormones may differ by menopausal and overweight status. We recommend other studies investigate the relationship between acrylamide and sex hormones in women, specifically using acrylamide biomarkers. Impact The present study showed some interesting associations between acrylamide intake and sex hormones that urgently need confirmation. PMID:23983241

  16. Decrease in plasma high-density lipoprotein cholesterol levels at puberty in boys with delayed adolescence: correlation with plasma testosterone levels

    SciTech Connect

    Kirkland, R.T.; Keenan, B.S.; Probstfield, J.L.; Patsch, W.; Lin, T.L.; Clayton, G.W.; Insull, W. Jr.

    1987-01-23

    A three-phase study tested the hypothesis that the decrease in the high-density lipoprotein cholesterol (HDL-C) level observed in boys at puberty is related to an increase in the plasma testosterone concentration. In phase I, 57 boys aged 10 to 17 years were categorized into four pubertal stages based on clinical parameters and plasma testosterone levels. These four groups showed increasing plasma testosterone values and decreasing HDL-C levels. In phase II, 14 boys with delayed adolescence were treated with testosterone enanthate. Plasma testosterone levels during therapy were in the adult male range. Levels of HDL-C decreased by a mean of 7.4 mg/dL (0.20 mmol/L) and 13.7 mg/dL (0.35 mmol/L), respectively, after the first two doses. In phase III, 13 boys with delayed adolescence demonstrated increasing plasma testosterone levels and decreasing HDL-C levels during spontaneous puberty. Levels of HDL-C and apolipoprotein A-1 were correlated during induced and spontaneous puberty. Testosterone should be considered a significant determinant of plasma HDL-C levels during pubertal development.

  17. Caffeine suppresses amyloid-beta levels in plasma and brain of Alzheimer's disease transgenic mice.

    PubMed

    Cao, Chuanhai; Cirrito, John R; Lin, Xiaoyang; Wang, Li; Wang, Lilly; Verges, Deborah K; Dickson, Alexander; Mamcarz, Malgorzata; Zhang, Chi; Mori, Takashi; Arendash, Gary W; Holtzman, David M; Potter, Huntington

    2009-01-01

    Recent epidemiologic studies suggest that caffeine may be protective against Alzheimer's disease (AD). Supportive of this premise, our previous studies have shown that moderate caffeine administration protects/restores cognitive function and suppresses brain amyloid-beta (Abeta) production in AD transgenic mice. In the present study, we report that acute caffeine administration to both young adult and aged AD transgenic mice rapidly reduces Abeta levels in both brain interstitial fluid and plasma without affecting Abeta elimination. Long-term oral caffeine treatment to aged AD mice provided not only sustained reductions in plasma Abeta, but also decreases in both soluble and deposited Abeta in hippocampus and cortex. Irrespective of caffeine treatment, plasma Abeta levels did not correlate with brain Abeta levels or with cognitive performance in individual aged AD mice. Although higher plasma caffeine levels were strongly associated with lower plasma Abeta1-40 levels in aged AD mice, plasma caffeine levels were also not linked to cognitive performance. Plasma caffeine and theophylline levels were tightly correlated, both being associated with reduced inflammatory cytokine levels in hippocampus. Our conclusion is two-fold: first, that both plasma and brain Abeta levels are reduced by acute or chronic caffeine administration in several AD transgenic lines and ages, indicating a therapeutic value of caffeine against AD; and second, that plasma Abeta levels are not an accurate index of brain Abeta levels/deposition or cognitive performance in aged AD mice.

  18. Plasma Cytokine Levels During Long-Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Zwart, Sara R.; Quiriarte, Heather A.; Smith, Scott M.; Sams, Clarence F.

    2012-01-01

    Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation. Specific measurements include leukocyte distribution, T cell function, cytokine production profiles (mRNA, intracellular, secreted, plasma), virus-specific T cell number/function, latent herpesvirus reactivation, stress hormone levels. Determine the clinical risk related to immune dysregulation for exploration class spaceflight, as well as an appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures. Specific Study Objectives: Determine the nutritional status of astronauts before, during, and after spaceflight ensure adequate intake of energy, protein, and vitamins during missions. The Clinical Nutritional Status Assessment measures dietary intake, body composition, protein, bone, iron, mineral, vitamin, and antioxidant status (60 total analytes). Currently, it is a medical requirement for U.S. crewmembers on-board the ISS. The results of data analysis are used both to understand the connections between nutrition and human health during space flight, and to develop effective dietary strategies to reduce adverse health impacts (including bone loss, loss of important vitamins and minerals, and increased genetic damage from radiation).

  19. Biperiden and haloperidol plasma levels and extrapyramidal side effects in schizophrenic patients.

    PubMed

    Meszaros, K; Lenzinger, E; Hornik, K; Schönbeck, G; Hatzinger, R; Langer, G; Sieghart, W; Aschauer, H N

    1997-01-01

    Anticholinergic drugs such as biperiden are used for the treatment of extrapyramidal side effects (EPS) induced by neuroleptics such as haloperidol. The effects of biperiden and haloperidol plasma levels on EPS were studied in 29 chronically ill schizophrenics. The results show relationships between biperiden dose and biperiden plasma levels (BPL), and between BPL and haloperidol plasma levels (HPL). Neither BPL nor HPL seem to influence EPS.

  20. Plasma Potassium Levels in Healthy Prehypertension Subjects and the Role of A High Potassium Drink.

    PubMed

    Farapti, Farapti; Sayogo, Savitri; Siregar, Parlindungan

    2017-02-24

    Most populations around the world consume less than the recommended levels of potassium. Long term low potassium intake could lead to decreased plasma potassium levels and induce hypokalemia. The increasing of plasma potassium levels 0,2-0,4 mmol/L by improving potassium intake decreased significantly blood pressure (BP). Assessing plasma potassium levels in healthy people related to potassium intake have not been studied. In this study, we analysed plasma potassium levels in prehypertension (PHT) subjects and to evaluate the effect of tender coconut water (TCW) as a high potassium drink on plasma potassium levels in PHT adults. Thirthy-two female aged 25-44 years were randomly allocated to 14 days on TCW or water in a parallel randomized clinical trial . The treatment (T) group received TCW 300 ml twice daily and the control (C) group received water 300 ml twice daily too. At baseline, plasma potassium levels was 3.71±0.41 mmol/L, and 22.58% were categorized as hypokalemia. After 14 days treatment, potassium plasma level between T and C groups were not significantly different (p=0,247). The change of plasma potassium levels in both groups showed tendency to increase but not statistically significant (p=0.166). In healthy prehypertension women, the low levels of potassium plasma may be caused by low potassium intake for long time and intervension with TCW 300 ml twice daily for 14 consecutive days has not proven yet to increase plasma potassium levels. It is necessary to give higher dose and longer time to increase potassium plasma in low potassium plasma level subjects.

  1. Metabonomics of Pig Blood Plasma Following Whole Body Exposure to Low Levels of Gb Vapor

    DTIC Science & Technology

    2005-10-01

    METABONOMICS OF PIG BLOOD PLASMA FOLLOWING WHOLE BODY EXPOSURE TO LOW LEVELS OF GB VAPOR Vicky L. H. Bevilacqua▲, Terrence G...DATES COVERED - 4. TITLE AND SUBTITLE Metabonomics Of Pig Blood Plasma Following Whole Body Exposure To Low Levels Of Gb Vapor 5a. CONTRACT...analysis of minipig blood plasma by high field NMR after low-level exposure to GB by whole body inhalation. EXPERIMENTAL METHODS 1. SARIN

  2. Plasma Lactate Dehydrogenase Levels Predict Mortality in Acute Aortic Syndromes

    PubMed Central

    Morello, Fulvio; Ravetti, Anna; Nazerian, Peiman; Liedl, Giovanni; Veglio, Maria Grazia; Battista, Stefania; Vanni, Simone; Pivetta, Emanuele; Montrucchio, Giuseppe; Mengozzi, Giulio; Rinaldi, Mauro; Moiraghi, Corrado; Lupia, Enrico

    2016-01-01

    Abstract In acute aortic syndromes (AAS), organ malperfusion represents a key event impacting both on diagnosis and outcome. Increased levels of plasma lactate dehydrogenase (LDH), a biomarker of malperfusion, have been reported in AAS, but the performance of LDH for the diagnosis of AAS and the relation of LDH with outcome in AAS have not been evaluated so far. This was a bi-centric prospective diagnostic accuracy study and a cohort outcome study. From 2008 to 2014, patients from 2 Emergency Departments suspected of having AAS underwent LDH assay at presentation. A final diagnosis was obtained by aortic imaging. Patients diagnosed with AAS were followed-up for in-hospital mortality. One thousand five hundred seventy-eight consecutive patients were clinically eligible, and 999 patients were included in the study. The final diagnosis was AAS in 201 (20.1%) patients. Median LDH was 424 U/L (interquartile range [IQR] 367–557) in patients with AAS and 383 U/L (IQR 331–460) in patients with alternative diagnoses (P < 0.001). Using a cutoff of 450 U/L, the sensitivity of LDH for AAS was 44% (95% confidence interval [CI] 37–51) and the specificity was 73% (95% CI 69–76). Overall in-hospital mortality for AAS was 23.8%. Mortality was 32.6% in patients with LDH ≥ 450 U/L and 16.8% in patients with LDH < 450 U/L (P = 0.006). Following stratification according to LDH quartiles, in-hospital mortality was 12% in the first (lowest) quartile, 18.4% in the second quartile, 23.5% in the third quartile, and 38% in the fourth (highest) quartile (P = 0.01). LDH ≥ 450 U/L was further identified as an independent predictor of death in AAS both in univariate and in stepwise logistic regression analyses (odds ratio 2.28, 95% CI 1.11–4.66; P = 0.025), in addition to well-established risk markers such as advanced age and hypotension. Subgroup analysis showed excess mortality in association with LDH ≥ 450 U/L in elderly, hemodynamically stable

  3. Effects of imipramine and bupropion on the duration of immobility of ACTH-treated rats in the forced swim test: involvement of the expression of 5-HT2A receptor mRNA.

    PubMed

    Kitamura, Yoshihisa; Fujitani, Yoshika; Kitagawa, Kouhei; Miyazaki, Toshiaki; Sagara, Hidenori; Kawasaki, Hiromu; Shibata, Kazuhiko; Sendo, Toshiaki; Gomita, Yutaka

    2008-02-01

    We examined the effect of chronic administration of imipramine and bupropion, monoamine reuptake inhibitors, on the duration of immobility in the forced swim test and serotonin (5-HT)(2A) receptor function in the form of 5-HT(2A) receptor mRNA levels in rats chronically treated with adrenocorticotropic hormone (ACTH). The immobility-decreasing effect of bupropion without imipramine did not influence the chronic ACTH treatment. The effect on the expression of 5-HT(2A) receptor mRNA of chronic ACTH treatment was decreased by bupropion, but not imipramine. These results suggest that bupropion has the effect of reducing immobility time in the forced swim test in the tricyclic antidepressant-resistant depressive model induced by chronic ACTH treatment in rats, and that decreased 5-HT(2A) receptor mRNA levels may be involved in this phenomenon.

  4. ACTH Receptor (MC2R) Specificity: What Do We Know About Underlying Molecular Mechanisms?

    PubMed

    Fridmanis, Davids; Roga, Ance; Klovins, Janis

    2017-01-01

    Coincidentally, the release of this Research Topic in Frontiers in Endocrinology takes place 25 years after the discovery of the adrenocorticotropic hormone receptor (ACTHR) by Mountjoy and colleagues. In subsequent years, following the discovery of other types of mammalian melanocortin receptors (MCRs), ACTHR also became known as melanocortin type 2 receptor (MC2R). At present, five types of MCRs have been reported, all of which share significant sequence similarity at the amino acid level, and all of which specifically bind melanocortins (MCs)-a group of biologically active peptides generated by proteolysis of the proopiomelanocortin precursor. All MCs share an identical -H-F-R-W- pharmacophore sequence. α-Melanocyte-stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH) are the most extensively studied MCs and are derived from the same region. Essentially, α-MSH is formed from the first 13 amino acid residues of ACTH. ACTHR is unique among MCRs because it binds one sole ligand-ACTH, which makes it a very attractive research object for molecular pharmacologists. However, much research has failed, and functional studies of this receptor are lagging behind other MCRs. The reason for these difficulties has already been outlined by Mountjoy and colleagues in their publication on ACTHR coding sequence discovery where the Cloudman S91 melanoma cell line was used for receptor expression because it was a "more sensitive assay system." Subsequent work showed that ACTHR could be successfully expressed only in endogenous MCR-expressing cell lines, since in other cell lines it is retained within the endoplasmic reticulum. The resolution of this methodological problem came in 2005 with the discovery of melanocortin receptor accessory protein, which is required for the formation of functionally active ACTHR. The decade that followed this discovery was filled with exciting research that provided insight into the molecular mechanisms underlying the action of

  5. Effects of RXR Agonists on Cell Proliferation/Apoptosis and ACTH Secretion/Pomc Expression

    PubMed Central

    Saito-Hakoda, Akiko; Uruno, Akira; Yokoyama, Atsushi; Shimizu, Kyoko; Parvin, Rehana; Kudo, Masataka; Saito-Ito, Takako; Sato, Ikuko; Kogure, Naotaka; Suzuki, Dai; Shimada, Hiroki; Yoshikawa, Takeo; Fujiwara, Ikuma; Kagechika, Hiroyuki; Iwasaki, Yasumasa; Kure, Shigeo; Ito, Sadayoshi; Sugawara, Akira

    2015-01-01

    Various retinoid X receptor (RXR) agonists have recently been developed, and some of them have shown anti-tumor effects both in vivo and in vitro. However, there has been no report showing the effects of RXR agonists on Cushing’s disease, which is caused by excessive ACTH secretion in a corticotroph tumor of the pituitary gland. Therefore, we examined the effects of synthetic RXR pan-agonists HX630 and PA024 on the proliferation, apoptosis, ACTH secretion, and pro-opiomelanocortin (Pomc) gene expression of murine pituitary corticotroph tumor AtT20 cells. We demonstrated that both RXR agonists induced apoptosis dose-dependently in AtT20 cells, and inhibited their proliferation at their higher doses. Microarray analysis identified a significant gene network associated with caspase 3 induced by high dose HX630. On the other hand, HX630, but not PA024, inhibited Pomc transcription, Pomc mRNA expression, and ACTH secretion dose-dependently. Furthermore, we provide new evidence that HX630 negatively regulates the Pomc promoter activity at the transcriptional level due to the suppression of the transcription factor Nur77 and Nurr1 mRNA expression and the reduction of Nur77/Nurr1 heterodimer recruiting to the Pomc promoter region. We also demonstrated that the HX630-mediated suppression of the Pomc gene expression was exerted via RXRα. Furthermore, HX630 inhibited tumor growth and decreased Pomc mRNA expression in corticotroph tumor cells in female nude mice in vivo. Thus, these results indicate that RXR agonists, especially HX630, could be a new therapeutic candidate for Cushing’s disease. PMID:26714014

  6. ACTH-Independent Cushing’s Syndrome with Bilateral Micronodular Adrenal Hyperplasia and Ectopic Adrenocortical Adenoma

    PubMed Central

    Louiset, Estelle; Gobet, Françoise; Libé, Rossella; Horvath, Anelia; Renouf, Sylvie; Cariou, Juliette; Rothenbuhler, Anya; Bertherat, Jérôme; Clauser, Eric; Grise, Philippe; Stratakis, Constantine A.; Kuhn, Jean-Marc; Lefebvre, Hervé

    2010-01-01

    Context: Bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing’s syndrome. Objective: The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma. Design and Setting: In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories. Intervention: Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies. Main Outcome Measure: Detection of 17α-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes. Results: Histological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17α-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway. Conclusion: This case suggests that unknown molecular defects can favor both micronodular adrenal hyperplasia and ectopic adrenocortical adenoma associated with Cushing’s syndrome. PMID:19915020

  7. Validated HPLC method for determination of caffeine level in human plasma using synthetic plasma: application to bioavailability studies.

    PubMed

    Alvi, Syed N; Hammami, Muhammad M

    2011-04-01

    Several high-performance liquid chromatography (HPLC) methods have been described for the determination of caffeine in human plasma. However, none have been cross validated using synthetic plasma. The present study describes a simple and reliable HPLC method for the determination of the caffeine level in human plasma. Synthetic plasma was used to construct calibration curves and quality control samples to avoid interference by caffeine commonly present in donor's human plasma. After deproteination of plasma samples with perchloric acid, caffeine and antipyrine (internal standard, IS) were separated on a Waters Atlantis C18 column using a mobile phase of 15 mM potassium phosphate (pH 3.5) and acetonitrile (83:17, v/v), and monitored by photodiode array detector, with the wavelength set at 274 nm. The relationship between caffeine concentrations and peak area ratio (caffeine-IS) was linear over the range of 0.05-20 μg/mL. Inter-run coefficient of variation was ≤ 5.4% and ≤ 6.0% and bias was ≤ 3% and ≤ 7% using human and synthetic plasma, respectively. Mean extraction recovery from human plasma of caffeine and the IS was 91% and 86%, respectively. Caffeine in human plasma was stable for at least 24 h at room temperature or 12 weeks at -20 °C, and after three freeze-thaw cycles. The method was successfully applied to monitor caffeine levels in healthy volunteers with correction of caffeine levels using the mean ratio of the slopes of the calibration's curves constructed using human and synthetic plasma.

  8. Regulation of plasma histamine levels by the mast cell clock and its modulation by stress

    PubMed Central

    Nakamura, Yuki; Ishimaru, Kayoko; Shibata, Shigenobu; Nakao, Atsuhito

    2017-01-01

    At steady state, plasma histamine levels exhibit circadian variations with nocturnal peaks, which is implicated in the nighttime exacerbation of allergic symptoms. However, the regulatory mechanisms are largely unexplored. This study determined how steady-state plasma histamine levels are regulated and affected by environmental factors. We found that plasma histamine levels decreased in mast cell–deficient mice and their circadian variations were lost in mast cell–deficient mice reconstituted with bone marrow–derived mast cells (BMMCs) harboring a mutation in the circadian gene Clock. Clock temporally regulates expression of organic cation transporter 3 (OCT3), which is involved in histamine transport, in mast cells; OCT inhibition abolished circadian variations in plasma histamine levels. Mice housed under aberrant light/dark conditions or suffering from restraint stress exhibited de-synchronization of the mast cell clockwork, concomitant with the loss of circadian variations in OCT3 expression and plasma histamine levels. The degree of compound 48/80–induced plasma extravasation in mice was correlated with plasma histamine levels. Collectively, the mast cell clock mediates circadian regulation of plasma histamine levels at steady state, in part by controlling OCT3 expression, which can be modulated by stress. Additionally, we propose that plasma histamine levels potentiate mast cell–mediated allergic reactions. PMID:28074918

  9. Physical activity affects plasma coenzyme Q10 levels differently in young and old humans.

    PubMed

    Del Pozo-Cruz, Jesús; Rodríguez-Bies, Elisabet; Ballesteros-Simarro, Manuel; Navas-Enamorado, Ignacio; Tung, Bui Thanh; Navas, Plácido; López-Lluch, Guillermo

    2014-04-01

    Coenzyme Q (Q) is a key lipidic compound for cell bioenergetics and membrane antioxidant activities. It has been shown that also has a central role in the prevention of oxidation of plasma lipoproteins. Q has been associated with the prevention of cholesterol oxidation and several aging-related diseases. However, to date no clear data on the levels of plasma Q during aging are available. We have measured the levels of plasmatic Q10 and cholesterol in young and old individuals showing different degrees of physical activity. Our results indicate that plasma Q10 levels in old people are higher that the levels found in young people. Our analysis also indicates that there is no a relationship between the degree of physical activity and Q10 levels when the general population is studied. However, very interestingly, we have found a different tendency between Q10 levels and physical activity depending on the age of individuals. In young people, higher activity correlates with lower Q10 levels in plasma whereas in older adults this ratio changes and higher activity is related to higher plasma Q10 levels and higher Q10/Chol ratios. Higher Q10 levels in plasma are related to lower lipoperoxidation and oxidized LDL levels in elderly people. Our results highlight the importance of life habits in the analysis of Q10 in plasma and indicate that the practice of physical activity at old age can improve antioxidant capacity in plasma and help to prevent cardiovascular diseases.

  10. Correlation between plasma D-dimer levels and the severity of patients with chronic urticaria

    PubMed Central

    Triwongwaranat, Daranporn; Chularojanamontri, Leena; Pinkaew, Samruay

    2013-01-01

    Background Beside autoimmunity, coagulation pathway is also involved in the pathogenesis of chronic urticaria (CU). Previous studies showed that plasma D-dimer levels paralleled the severity of the disease. To date, there are no data concerning D-dimer level in Thai patients with CU. Objective This study aimed to find the relationship between plasma D-dimer levels and the disease severity of Thai CU patients. The secondary objective is to analyze plasma D-dimer level in each group of patients who performed autologous plasma skin testing (APST) and autologous serum skin testing (ASST). Methods We retrospectively reviewed case record forms of chronic idiopathic urticaria (CIU) patients aged at least 18 years in Skin Allergy Clinic, Siriraj Hospital Mahidol University, Bangkok, during June 2008 to June 2011. Results Of 120 patients, plasma D-dimer level was abnormal in 58 patients (48.3%). The study showed statistically significant positive correlation between disease severity and plasma D-dimer level (p < 0.05, r = 0.537). There was no statistically significant difference in plasma D-dimer level between APST positive and negative groups, and also between ASST positive and negative groups. In APST negative group, plasma D-dimer level was elevated in 29 patients (47.5%) and correlated with disease severity. Conclusion This study showed elevated plasma D-dimer levels in nearly half of Thai patients with CIU. There was a positive correlation between plasma D-dimer levels and the severity of disease activity. Investigation for plasma D-dimer level may be an alternative way to evaluate disease severity in patients with CIU. PMID:23667833

  11. Hormone (ACTH, T3) content of immunophenotyped lymphocyte subpopulations.

    PubMed

    Pállinger, Éva; Kiss, Gergely Attila; Csaba, György

    2016-12-01

    Cells of the immune system synthesize, store, and secrete polypeptide and amino acid type hormones, which also influence their functions, having receptors for different hormones. In the present experiment immunophenotyped immune cells isolated from bone marrow, thymus, and peritoneal fluid of mice were used for demonstrating the adrenocorticotropic hormone (ACTH) and triiodothyronine (T3) hormone production of differentiating immune cells. Both hormones were found in each cell type, and in each maturation state, which means that all cells are participating in the hormonal function of the immune system. The lineage-independent presence of ACTH and T3 in differentiating hematopoietic cells denotes that their expression ubiquitous during lymphocyte development. Higher ACTH and T3 content of B cells shows that these cells are the most hormonally active and suggests that the hormones may have an autocrine regulatory role in B cell development. Developing T cells showed heterogeneous hormone production which was associated with their maturation state. Differences in the hormone contents of immune cells isolated from different organs indicate that their hormone production is defined by their differentiation or maturation state, however, possibly also by the local microenvironment.

  12. ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia

    NASA Technical Reports Server (NTRS)

    Heybach, J. P.; Vernikos, J.

    1981-01-01

    The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors.

  13. The effect of intracarotid vasopressin infusion on ACTH release in neurohypophysectomized, conscious dogs.

    PubMed

    Raff, H; Papanek, P E; Liard, J F; Cowley, A W

    1994-09-01

    Neurohypophysectomy (NHX) attenuates the adrenocorticotropic hormone (ACTH) response to arterial hypotension but not corticotropin-releasing hormone (CRH) or insulin-induced hypoglycemia in conscious dogs. The purpose of the present study was to determine if increasing vasopressin (AVP) in the cephalic circulation by carotid infusion normalizes the ACTH response to hypotension attenuated by NHX. Five male, conditioned dogs underwent controlled, acute decreases in arterial pressure (by approximately 25 mmHg) by infusion of sodium nitroprusside (NP) before and > 4 wk after selective NHX. ACTH increased from 40 +/- 3 to 242 +/- 79 pg/ml during NP in the intact state. This response was greatly attenuated after NHX (peak ACTH 81 +/- 15 pg/ml). Simultaneous intravenous infusion of AVP (12.5 ng/min) had a small, augmenting effect on the ACTH response to NP (peak ACTH 120 +/- 27 pg/ml). Intracarotid AVP (12.5 ng/min) greatly augmented the ACTH response to NP (peak ACTH 202 +/- 26 pg/ml) such that it was no longer different from the intact response. Neither intravenous nor intracarotid AVP infusion per se had a great effect on ACTH. A normal ACTH response to hypotension requires an intact neurohypophysis and is mediated by a cephalic action of magnocellular AVP.

  14. Inactivation of the DMH selectively inhibits the ACTH and corticosterone responses to hypoglycemia.

    PubMed

    Evans, Scott B; Wilkinson, Charles W; Gronbeck, Pam; Bennett, Jennifer L; Zavosh, Aryana; Taborsky, Gerald J; Figlewicz, Dianne P

    2004-01-01

    We have previously reported that repeated bouts of insulin-induced hypoglycemia (IIH) in the rat result in blunted activation of the paraventricular, arcuate, and dorsomedial hypothalamic (DMH) nuclei. Because DMH activation has been implicated in the sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to stressors, we hypothesized that its blunted activation may play a role in the impaired counterregulatory response that is also observed with repeated bouts of IIH. In the present study, we evaluated the role of normal DMH activation in the counterregulatory response to a single bout of IIH. Local infusion of lidocaine (n = 8) to inactivate the DMH during a 2-h bout of IIH resulted in a significant overall decrease of the ACTH response and a delay of onset of the corticosterone response compared with vehicle-infused controls (n = 9). We observed suppression of the ACTH response at time (t) = 90 and 120 min (50 +/- 12 and 63 +/- 6%, respectively, of control levels) and early suppression of the corticosterone response at t = 30 min (59 +/- 13% of the control level). The epinephrine, norepinephrine, and glucagon responses were not altered by DMH inactivation. Our finding suggests that DMH inactivation may play a specific role in decreasing the HPA axis response after repeated bouts of IIH.

  15. Plasma levels of immunoreactive atrial natriuretic factor in healthy subjects and in patients with edema.

    PubMed Central

    Shenker, Y; Sider, R S; Ostafin, E A; Grekin, R J

    1985-01-01

    Atrial natriuretic factor (ANF), a recently sequenced cardiac peptide, has been shown to have potent natriuretic, diuretic, and vasodilating effects in several species. We have developed a radioimmunoassay to measure the levels of immunoreactive ANF in human plasma. Plasma levels of ANF in healthy volunteers on a low sodium diet were 9.8 +/- 1.4 pmol/liter and increased to 21.9 +/- 3.0 on a high sodium diet. The levels of atrial natriuretic factor correlated directly with urinary sodium and inversely with plasma renin activity and plasma aldosterone levels. Patients with marked edema due to congestive heart failure had plasma levels of atrial natriuretic factor five times higher than normal (P less than 0.05), whereas patients with cirrhosis and edema had levels that were not different from normal. These results suggest that atrial natriuretic factor plays an important role in the adaptation to increased sodium intake. PMID:2932471

  16. [Long-lasting behavioral effects of chronic neonatal treatment with ACTH (4-10) analogue semax in white rat pups].

    PubMed

    Sebentsova, E A; Denisenko, A V; Levitskaia, N G; Andreeva, L A; Kamenskiĭ, A A; Miasoedov, N F

    2005-01-01

    It is well known that ACTH/MSH-like peptides (melanocortins) have neurotrophic and neuroprotective effects on the central and peripheral nervous systems in the early postnatal life. The aim of present work was to study consequences of the ACTH (4-10) analogue Semax influence on the developing brain. The work was carried out in white rat pups. The peptide (0.05 mg/kg, i/p) was injected daily on the 8th-21st postnatal days. Delayed long-lasting effects of such treatment on animal behavior were revealed. At the age of four to eight weeks, Semax-treated rats displayed elevated exploratory activity, decreased anxiety level and improved passive avoidance conditioning. The results suggest that neonatal Semax administration modulates the development of the central nervous system.

  17. Differences in bisphenol A and estrogen levels in the plasma and seminal plasma of men with different degrees of infertility.

    PubMed

    Vitku, J; Sosvorova, L; Chlupacova, T; Hampl, R; Hill, M; Sobotka, V; Heracek, J; Bicikova, M; Starka, L

    2015-01-01

    The general population is potentially exposed to many chemicals that can affect the endocrine system. These substances are called endocrine disruptors (EDs), and among them bisphenol A (BPA) is one of the most widely used and well studied. Nonetheless, there are still no data on simultaneous measurements of various EDs along with steroids directly in the seminal fluid, where deleterious effects of EDs on spermatogenesis and steroidogenesis are assumed. We determined levels of BPA and 3 estrogens using LC-MS/MS in the plasma and seminal plasma of 174 men with different degrees of infertility. These men were divided according their spermiogram values into 4 groups: (1) healthy men, and (2) slightly, (3) moderate, and (4) severely infertile men. Estradiol levels differed across the groups and body fluids. Slightly infertile men have significantly higher BPA plasma and seminal plasma levels in comparison with healthy men (p<0.05 and p<0.01, respectively). Furthermore, seminal BPA, but not plasma BPA, was negatively associated with sperm concentration and total sperm count (-0.27; p<0.001 and -0.24; p<0.01, respectively). These findings point to the importance of seminal plasma in BPA research. Overall, a disruption of estrogen metabolism was observed together with a weak but significant impact of BPA on sperm count and concentration.

  18. Plasma steroid profiling and response to trophins to illustrate intra-adrenal dynamics.

    PubMed

    McManus, F; Fraser, R; Davies, E; Connell, J M C; Freel, E M

    2015-02-01

    The importance of corticosteroids in cardiovascular and other chronic disease is recognised. In addition, plasma steroid precursor-to-product ratios are useful and convenient indirect indicators of efficiency of key steroidogenic enzymes (aldosterone synthase, 11β-hydroxylase and 17α-hydroxylase). The use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) has enabled measurement of numerous corticosteroid compounds simultaneously. However, normal responses to trophins and variation in salt intake are not well described. This study examined these parameters in a large group of healthy volunteers. Sixty normotensive volunteers were recruited and underwent infusion of angiotensin II (AngII) and ACTH, following low- and high-salt diet. Measurement of plasma steroids at baseline and 30 min after infusion of trophin was carried out by LC-MS. As expected, plasma mineralocorticoid levels increased in response to salt restriction and were suppressed with salt loading; ACTH infusion increased all corticosteroids, while AngII increased mineralocorticoids and suppressed glucocorticoid production. ACTH increased S:F but decreased DOC:B, thus the S:F ratio is a more appropriate index of 11β-hydroxylase efficiency. The B:F ratio increased following ACTH treatment and salt restriction. A larger proportion of plasma B than generally accepted may be derived from the zona glomerulosa and this ratio may be most informative of 17α-hydroxylase activity in salt-replete subjects. Although DOC:aldosterone, B:aldosterone and 18-hydroxyB:aldosterone should provide indices of aldosterone synthase efficiency, responses of individual compounds to trophins suggest that none of them accurately reflect this. Based on these data, aldosterone synthase activity is most accurately reflected by aldosterone concentration alone.

  19. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels.

    PubMed

    Rasmussen, D D; Boldt, B M; Wilkinson, C W; Yellon, S M; Matsumoto, A M

    1999-02-01

    Human and rat pineal melatonin secretion decline with aging, whereas visceral fat and plasma insulin levels increase. Melatonin modulates fat metabolism in some mammalian species, so these aging-associated melatonin, fat and insulin changes could be functionally related. Accordingly, we investigated the effects of daily melatonin supplementation to male Sprague-Dawley rats, starting at middle age (10 months) and continuing into old age (22 months). Melatonin was added to the drinking water (92% of which was consumed at night) at a dosage (4 microg/ml) previously reported to attenuate the aging-associated decrease in survival rate in male rats, as well as at a 10-fold lower dosage. The higher dosage produced nocturnal plasma melatonin levels in middle-aged rats which were 15-fold higher than in young (4 months) rats; nocturnal plasma melatonin levels in middle-aged rats receiving the lower dosage were not significantly different from young or middle-aged controls. Relative (% of body wt) retroperitoneal and epididymal fat, as well as plasma insulin and leptin levels, were all significantly increased at middle age when compared to young rats. All were restored within 10 weeks to youthful (4 month) levels in response to both dosages of melatonin. Continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) levels were not significantly altered by aging or melatonin treatment. Plasma testosterone, insulin-like growth factor I (IGF-I) and total triiodothyronine (T3) decreased by middle age; these aging-associated decreases were not significantly altered by melatonin treatment. Thus, visceral fat, insulin and leptin responses to melatonin administration may be independent of marked changes in gonadal, thyroid, adrenal or somatotropin regulation. Since increased visceral fat is associated with increased insulin resistance, diabetes, and cardiovascular disease, these results

  20. Corticotropin (ACTH) regulates alternative RNA splicing in Y1 mouse adrenocortical tumor cells.

    PubMed

    Schimmer, Bernard P; Cordova, Martha

    2015-06-15

    The stimulatory effect of ACTH on gene expression is well documented and is thought to be a major mechanism by which ACTH maintains the functional and structural integrity of the gland. Previously, we showed that ACTH regulates the accumulation of over 1200 transcripts in Y1 adrenal cells, including a cluster with functions in alternative splicing of RNA. On this basis, we postulated that some of the effects of ACTH on the transcription landscape of Y1 cells are mediated by alternative splicing. In this study, we demonstrate that ACTH regulates the alternative splicing of four transcripts - Gnas, Cd151, Dab2 and Tia1. Inasmuch as alternative splicing potentially affects transcripts from more than two-thirds of the mouse genome, we suggest that these findings are representative of a genome-wide effect of ACTH that impacts on the mRNA and protein composition of the adrenal cortex.

  1. Clinical features of congenital adrenal insufficiency including growth patterns and significance of ACTH stimulation test.

    PubMed

    Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook; Yu, Jeesuk

    2013-11-01

    Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.

  2. Clinical Features of Congenital Adrenal Insufficiency Including Growth Patterns and Significance of ACTH Stimulation Test

    PubMed Central

    Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook

    2013-01-01

    Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency. PMID:24265530

  3. ACTH and Polymorphisms at Steroidogenic Loci as Determinants of Aldosterone Secretion and Blood Pressure

    PubMed Central

    MacKenzie, Scott M.; Freel, E. Marie; Connell, John M.; Fraser, Robert; Davies, Eleanor

    2017-01-01

    The majority of genes contributing to the heritable component of blood pressure remain unidentified, but there is substantial evidence to suggest that common polymorphisms at loci involved in the biosynthesis of the corticosteroids aldosterone and cortisol are important. This view is supported by data from genome-wide association studies that consistently link the CYP17A1 locus to blood pressure. In this review article, we describe common polymorphisms at three steroidogenic loci (CYP11B2, CYP11B1 and CYP17A1) that alter gene transcription efficiency and levels of key steroids, including aldosterone. However, the mechanism by which this occurs remains unclear. While the renin angiotensin system is rightly regarded as the major driver of aldosterone secretion, there is increasing evidence that the contribution of corticotropin (ACTH) is also significant. In light of this, we propose that the differential response of variant CYP11B2, CYP11B1 and CYP17A1 genes to ACTH is an important determinant of blood pressure, tending to predispose individuals with an unfavourable genotype to hypertension. PMID:28272372

  4. Cushing's storm secondary to a rare case of ectopic ACTH secreting metastatic breast cancer

    PubMed Central

    Bucciarelli, Maura; Lee, Ya-Yu

    2015-01-01

    Summary Ectopic ACTH secretion from breast cancer is extremely rare. We report a case of a 30-year-old woman with a history of breast cancer, who presented with psychosis and paranoid behaviour. CT of the head showed white matter disease consistent with posterior reversible encephalopathy syndrome (PRES). Despite using mifepristone with multiple antihypertensives including lisinopril, spironolactone and metoprolol, she was hypertensive. Transaminitis did not allow mifepristone dose escalation and ketoconazole utilization. Etomidate infusion at a non-sedating dose in the intensive care unit controlled her hypertension and cortisol levels. She was transitioned to metyrapone and spironolactone. She was discharged from the hospital on metyrapone with spironolactone and underwent chemotherapy. She died 9 months later after she rapidly redeveloped Cushing's syndrome and had progressive metastatic breast cancer involving multiple bones, liver and lungs causing respiratory failure. Learning points Cushing's syndrome from ectopic ACTH secreting breast cancer is extremely rare.Cushing's syndrome causing psychosis could be multifactorial including hypercortisolism and PRES.Etomidate at non-sedating doses in intensive care setting can be effective to reduce cortisol production followed by transition to oral metyrapone. PMID:26525183

  5. Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

    PubMed

    Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

    2013-01-01

    Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

  6. Plasma Levels of Nitrite and Nitrate in Early and Recent Classes of Fish

    PubMed Central

    Williams, Donna A; Flood, Mary H; Lewis, Debra A; Miller, Virginia M; Krause, William J

    2008-01-01

    The stable metabolite of nitric oxide in plasma is NOx, the sum of nitrite plus nitrate. Measures of plasma NOx may provide information about the nitric oxide tonus of the entire endothelium including capillary microvessels. Although data are available for mammalian species, plasma NOx measurements in early vertebrate species are scarce. The purpose of this study was to test the hypothesis that plasma NOx would be similar to the NOx in the water environment for fish in early classes (Agnatha and Chondrichthye) and would exceed water NOx levels in the known nitrite-sensitive fish (Osteichthye). Plasma samples were obtained from 18 species of adult fish (n = 167) and from their housing or natural water environment. NOx was measured by using chemiluminescence. Plasma NOx was detected in all species and ranged from 0.5 nmol/ml (skate) to 453.9 nmol/ml (shortnose gar). Average plasma NOx was significantly higher in sea lamprey than in Atlantic hagfish whereas that of little skate was 3-fold lower than in spiny dogfish shark. Plasma NOx differed significantly among early bony fish (paddlefish, pallid sturgeon, gar) yet was similar among modern bony fish, with the exception of rainbow trout. Plasma NOx reflected water NOx in only 2 species (hagfish and shark), and levels did not coincide with nitrite sensitivity. This study provides an expanded comparative view of plasma NOx levels across 3 groups of early fish. The data obtained suggest a nitric oxide system in early and modern fish. PMID:19004368

  7. Tobacco use is associated with increased plasma BDNF levels in depressed patients.

    PubMed

    Colle, Romain; Trabado, Séverine; Rotenberg, Samuel; Brailly-Tabard, Sylvie; Benyamina, Amine; Aubin, Henri-Jean; Hardy, Patrick; Falissard, Bruno; Becquemont, Laurent; Verstuyft, Céline; Fève, Bruno; Corruble, Emmanuelle

    2016-12-30

    Since serum Brain Derived Neurotrophic Factor (BDNF) levels are higher in tobacco smokers than in non-smokers and since Major Depressive Disorder (MDD) is associated with a 2-fold increased risk of smoking, we assessed the association of smoking and plasma BDNF levels in 359 depressed MDD patients. Plasma BDNF levels were positively correlated with the magnitude of tobacco consumption (current number of cigarettes/day and number of packs/year). Accordingly, current tobacco users had significantly higher plasma BDNF levels than non-users. In further studies of MDD, peripheral measures of BDNF should take into account tobacco use.

  8. Nicotine, cotinine, and trans-3-hydroxycotinine levels in seminal plasma of smokers: effects on sperm parameters.

    PubMed

    Pacifici, R; Altieri, I; Gandini, L; Lenzi, A; Pichini, S; Rosa, M; Zuccaro, P; Dondero, F

    1993-10-01

    Sperm samples from 44 cigarette smokers and 50 nonsmokers attending an infertility clinic were examined by high-performance liquid chromatography (HPLC) assay and HPLC-mass spectrometry for the presence of nicotine (NIC), cotinine (COT), and trans-3'-hydroxycotinine (THOC) in seminal plasma. Smokers were found to have levels of COT and THOC in seminal plasma that were similar to those found in serum. The level of NIC was significantly increased in seminal plasma compared to serum. Total motility of spermatozoa was significantly and negatively correlated to COT and THOC levels in seminal plasma. Forward motility of spermatozoa was correlated only with cotinine semen levels. On the basis of these results, we suggest that the presence of tobacco smoke constituents in seminal plasma could provide a warning of the adverse effects of cigarette smoke on the physiology of reproduction.

  9. Transient brain shrinkage in infantile spasms after ACTH treatment. Report of two cases.

    PubMed

    Maekawa, K; Ohta, H; Tamai, I

    1980-02-01

    This is the report of two cases of infantile spasms, manifesting transient brain shrinkage in computerized tomography (CT) after ACTH treatment. ACTH was given for 8 weeks to a 8-months-old Japanese girl with infantile spasms. First CT performed at 2 weeks after the final ACTH injection, displayed moderate brain shrinkage. Second CT at 4 months showed marked diminution of the shrinkage. ACTH was also given for 8 weeks to a 14 months old Japanese boy with infantile spasms. First CT, just before ACTH treatment, showed mild cortical atrophy, the second at 7 days after the final ACTH injection revealed marked brain shrinkage and moderate ventricular dilatation, and the third at 2 months, disclosed mild improvement of the shrinkage. ACTH or corticoateroid has widespread effects on the developing nervous system. In animal experiments, ACTH or steroids interfere with brain growth of young rats. CT findings of transient brain shrinkage in a child with infantile spasms might suggest that intensive treatment with ACTH or steroids in infancy interferes with brain growth as seen in the results of animal experiments.

  10. Comparative study of analgesic potency of ACTH4-10 fragment and its analog semax.

    PubMed

    Ivanova, D M; Levitskaya, N G; Andreeva, L A; Kamenskii, A A; Myasoedov, N F

    2007-01-01

    The effects of ACTH4-10 fragment and its analog semax on nociception were examined on various animal models. ACTH4-10 in a dose of 0.5 mg/kg decreased nociception in rats during hindpaw compression test and in mice subjected to acetic acid writhing test. Lower doses of ACTH4-10 produced no analgesic effect. Semax (0.015-0.500 mg/kg) decreased pain sensitivity in all experimental models. Hence, the substitution of three C-terminal amino acid residues in ACTH4-10 for Pro-Gly-Pro sequence augmented the analgesic potency of the peptide after its peripheral injection.

  11. Naloxone inhibits and morphine potentiates. The adrenal steroidogenic response to ACTH

    NASA Technical Reports Server (NTRS)

    Heybach, J. P.; Vernikos, J.

    1980-01-01

    The adrenal actions were stereospecific since neither the positve stereoisomer of morphine, nor that of naloxone, had any effect on the adrenal response to exogenous adrenocorticotrophic hormone (ACTH). The administration of human beta endorphin to phyophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone secreting cells of the adrenal cortex.

  12. Chloramphenicol in children: dose, plasma levels and clinical effects.

    PubMed

    Ismail, R; Teh, L K; Choo, E K

    1998-06-01

    Despite concerns about adverse effects, chloramphenicol (CMC) continues to be used in certain situations and, due to its low therapeutic index and variable pharmacokinetics, therapeutic drug monitoring (TDM) is often recommended. At our centre, CMC finds applications in typhoid and meningitis and TDM is routinely performed. Elsewhere in Malaysia, however, CMC is used without TDM. We therefore decided to evaluate our TDM for CMC in relation to its roles in CMC therapy in children, who constitute most of our patients. Our objective was also to develop strategies to improve our TDM for CMC use. Data were collected from 168 children given CMC for various indications and monitored by the TDM service. Plasma CMC was determined by HPLC and used to adjust doses to maintain concentrations within a range of 10-25 micrograms/ml. Outcomes measured included daily temperatures and haematological indices. Daily doses and plasma CMC varied greatly. Doses averaged 40.5 mg/kg for neonates and 75.5 for older children. Average peak concentrations were therapeutic in 60% and trough in 42%. Average duration of fever was 6.3 days and it was unaffected by plasma CMC. Typhoid was eradicated in 97% but nine children with other diagnoses died. Side-effects were confined to mild reversible haematological abnormalities which developed in 11% of children at plasma concentrations which tended to be high. We conclude that CMC remains useful in children with typhoid. Its use for other indications, however, should be reviewed. Routine TDM for CMC is probably not warranted, at least until a clearer role is defined by well designed prospective studies.

  13. Multiple Levels of Degradation Diminish Hemostatic Potential of Thawed Plasma

    PubMed Central

    Matijevic, Nena; Kostousov, Vadim; Wang, Yao-Wei W.; Wade, Charles E.; Wang, Weiwei; Letourneau, Phillip; Hartwell, Elizabeth; Kozar, Rosemary; Ko, Tien; Holcomb, John B.

    2011-01-01

    Background Severe bleeding after injury requires transfusion of blood products, including fresh frozen plasma (FFP). Many centers are keeping thawed plasma (TP) ready for massively transfused patients. According to the American Association of Blood Banks Standards, TP is approved for transfusion up to 5 days after thawing, when stored at 1°C to 6°C. However, there are no clinical data analyzing the effects of the approved 5-day storage on plasma. We hypothesize that the hemostatic potential (HP) of freshly thawed (FFP-0) was superior to plasma stored for 5 days (FFP-5). Methods FFP from 30 single donors were thawed at 37°C and kept at 1°C to 6°C for 5 days. HP was evaluated at day 0 and 5 by measuring kinetics of thrombin generation (TG), kinetics of clot formation by thromboelastography, clotting factors and inhibitors, and cell-derived microparticles (MPs) by flow cytometry. Results When comparing FFP-5 to FFP-0, FFP-5 exhibited only 40% of the potential of FFP-0 for TG (6.2 nM/min vs. 14.3 nM/min, p < 0.0001), a slower clotting response via thromboelastography (reaction time: 4.3 minutes vs. 3.2 minutes, p < 0.0001) and a longer delay in reaching maximum thrombus generation (5.7 minutes vs. 4.6 minutes, p < 0.01). Diminished HP was accompanied by a significant decline in multiple coagulation proteins, including FV, VII, VIII, von Willebrand factor, and free Protein S, by up to 30%, and a decrease of 50% in MP counts. Conclusion The HP and clot forming ability of TP significantly declined with storage. Hence, freshly TP may have a greater ability to restore hemostasis and correct coagulopathy compared with FFP-5. The clinical consequences for transfused patients deserve further exploration. PMID:21217484

  14. Clinical Implication of Plasma Hydrogen Sulfide Levels in Japanese Patients with Type 2 Diabetes

    PubMed Central

    Suzuki, Kunihiro; Sagara, Masaaki; Aoki, Chie; Tanaka, Seiichi; Aso, Yoshimasa

    2017-01-01

    Objective The goal of the present study was to investigate the plasma hydrogen sulfide (H2S) levels in patients with type 2 diabetes, as the plasma H2S levels in Japanese patients with type 2 diabetes remain unclear. Methods The plasma H2S levels were measured in 154 outpatients with type 2 diabetes and 66 outpatients without diabetes. All blood samples were collected in the outpatient department from 09:00 to 10:00. The patients had fasted from 21:00 the previous evening and had not consumed alcohol or caffeine or smoked until sample collection. The plasma H2S levels were measured using the methylene blue assay. The plasma H2S levels were determined in triplicate, and the average concentrations were calculated against a calibration curve of sodium sulfide. Results The patients with type 2 diabetes showed a progressive reduction in the plasma H2S levels (45.1±15.5 μM versus 54.0±26.4 μM, p<0.05), which paralleled poor glycemic control. There was a significant correlation between a reduction in the plasma H2S levels and the HbA1c levels (β=-0.505, p<0.01), Furthermore, a reduction in the plasma H2S levels was found to be related to a history of cardiovascular diseases in patients with type 2 diabetes (39.9±13.8 μM versus 47.5±15.9 μM, p<0.01). Conclusion Collectively, the plasma H2S levels were reduced in patients with type 2 diabetes, which may have implications in the pathophysiology of cardiovascular disease in diabetic patients. The trial was registered with the University Hospital Medical Information Network (UMIN no. #000020549). PMID:28049995

  15. Correlation between plasma component levels of cultured fish and resistance to bacterial infection

    USGS Publications Warehouse

    Maita, M.; Satoh, K.-I.; Fukuda, Y.; Lee, H.-K.; Winton, J.R.; Okamoto, N.

    1998-01-01

    Mortalities of yellowtail Seriola quinqueradiata artificially infected with Lactococcus garvieae and of rainbow trout Oncorhynchus mykiss artificially infected with Vibrio anguillarum were compared with the levels of plasma components measured prior to challenge. The levels of plasma total cholesterol, free cholesterol and phospholipid of fish surviving infection were significantly higher in both yellowtail and rainbow trout than those of fish which died during the challenge test. Mortality of yellowtail with plasma total cholesterol levels lower than 250 mg/100 ml was significantly higher than that of fish which had cholesterol levels higher than 275 mg/100 ml (p < 0.05). Rainbow trout whose cholesterol was lower than 520 mg/100 ml suffered a significantly higher mortality due to vibriosis than fish having cholesterol levels higher than 560 mg/100 ml (p < 0.005). These results indicate that low levels of plasma lipid components may be an indicator of lowered disease resistance in cultured fish.

  16. Effects of ACTH and cAMP on steroidogenic acute regulatory protein and P450 11beta-hydroxylase messenger RNAs in rainbow trout interrenal cells: relationship with in vitro cortisol production.

    PubMed

    Hagen, I Julie; Kusakabe, Makoto; Young, Graham

    2006-02-01

    Steroidogenic acute regulatory protein (StAR) transfers cholesterol over the inner mitochondrial membrane, thereby making the molecule available for cholesterol side-chain cleavage enzyme, which carries out the first conversion in the steroidogenic pathway. In mammals, StAR controls this rate limiting step in steroidogenesis, and both StAR protein and StAR mRNA levels become rapidly elevated in response to tropic hormone stimulation. The relationship between StAR gene expression and steroid production in fish has not yet been well explored. We investigated the relationship between adrenocorticotropic hormone (ACTH)- and cAMP-stimulated cortisol production in vitro and levels of StAR transcripts in interrenal cells of rainbow trout. To assess the effect of ACTH on mRNA levels of a downstream steroidogenic enzyme, we also investigated the effects of ACTH on transcripts encoding 11beta hydroxylase (P450 11beta). In a series of experiments, juvenile rainbow trout head kidney tissue containing interrenal cells was incubated with either ACTH or dibutyryl cyclic AMP (dbcAMP). Cortisol in incubation media were measured by radioimmunoassay and total RNA was isolated from the tissue for Northern analysis or for quantitative real-time PCR. Incubation of tissue with 150 ng/mL ACTH for 1-18 h induced a progressive increase in cortisol accumulation in media, but StAR mRNA levels increased modestly and mostly insignificantly over 18 h, irrespective of treatment. Exposure of tissue for 18 h to 5, 150, 500 or 1,500 ng ACTH/mL resulted in a strong increase in cortisol production, with a peak response (15-fold increase over controls) achieved with 150 ng/mL ACTH. Although there was a trend towards a dose-response effect, mean StAR mRNA levels were only significantly affected by the highest concentration of ACTH used (1,500 ng/mL), which induced a less than 2-fold increase in StAR transcripts. However, there was a significant linear relationship between StAR mRNA levels and ACTH

  17. Effects of aging on the plasma levels of nesfatin-1 and adiponectin

    PubMed Central

    LI, JIANG-BO; NISHIDA, MIYUKI; KAIMOTO, KAORI; ASAKAWA, AKIHIRO; CHAOLU, HUHE; CHENG, KAI-CHUN; LI, YING-XIAO; TERASHI, MUTSUMI; KOYAMA, KEN ICHIRO; AMITANI, HARUKA; SAKOGUCHI, TAKEO; USHIKAI, MIHARU; IKEDA, SATOSHI; AOYAMA, KOHJI; HORIUCHI, MASAHISA; LI, JIAN-ZHONG; INUI, AKIO

    2014-01-01

    Gastric and adipose tissue secrete a number of hormones that are involved in energy metabolism. The biological functions of these hormones, including their effects on aging, are currently under investigation. Adiponectin was shown to be directly involved in appetite and the control of body weight. However, the effects of aging of nesfatin-1, an appetite-suppressing peptide that was recently identified, have not yet been fully elucidated. The aim of this study was to determine the effects of aging on the plasma levels of nesfatin-1 and adiponectin. Our results demonstrated no significant differences in the nesfatin-1 plasma levels among three age groups (2, 6 and 24 months) of female BALB/c mice. The plasma nesfatin-1 levels/visceral fat (VF) ratio in the 24-month-old mice was significantly lower compared to that in the 2- and 6-month-old mice. In addition, there were no significant differences in the plasma adiponectin levels among the three age groups. The plasma adiponectin levels/VF ratio in the 24-month-old mice was significantly lower compared to that in the 2- and 6-month-old mice. In conclusion, there were no age-related changes in the plasma levels of nesfatin-1 and adiponectin, although the ratio of plasma levels of nesfatin-1 and adiponectin per VF was decreased with advancing age. Our results indicated that nesfatin-1 and adiponectin may be involved in controlling energy balance during aging. PMID:24649088

  18. The effect of different alcoholic beverages on blood alcohol levels, plasma insulin and plasma glucose in humans.

    PubMed

    Nogueira, L C; Couri, S; Trugo, N F; Lollo, P C B

    2014-09-01

    In the present work we studied the effects of four alcoholic beverages on blood alcohol levels, plasma insulin concentrations and plasma glucose concentrations in men and women. The volunteers were healthy non-smokers and they were divided according to sex into two groups of ten individuals. The alcoholic beverages used in the study were beer, red wine, whisky and "cachaça". In men, ingestion of the distilled drinks promoted a spike in blood alcohol levels more quickly than ingestion of the fermented drinks. In women, beer promoted the lowest blood alcohol levels over the 6h of the experiment. Whisky promoted highest blood alcohol levels in both sexes. The ingestion of wine promoted a significant difference in relation to the blood alcohol concentration (BAC) as a function of gender. The ingestion of cachaça by women produced BAC levels significantly smaller than those obtained for wine.

  19. Elevated plasma levels of F2 alpha isoprostane in cystic fibrosis.

    PubMed

    Collins, C E; Quaggiotto, P; Wood, L; O'Loughlin, E V; Henry, R L; Garg, M L

    1999-06-01

    Cystic fibrosis (CF) is associated with chronic lung infection, inflammation, and elevated indices of oxidative stress. Recently, isoprostanes were shown to be a reliable in vivo marker of oxidant injury with 8-iso-PGF2 alpha, shown to cause airflow obstruction and plasma exudation in guinea pig lung. The present study was designed to examine the relationship between 8-iso-PGF2 alpha levels, plasma antioxidants, and clinical status in CF. We hypothesized that plasma 8-iso-PGF2 alpha levels would be higher in subjects with CF compared to healthy controls. Plasma 8-iso-PGF2 alpha levels were prospectively measured in 22 subjects with CF and nine healthy controls using an 8-isoprostane enzyme immunoassay kit along with plasma vitamins A, E, and beta-carotene. Plasma 8-iso-PGF2 alpha levels were shown to be significantly elevated in the CF subjects compared to controls (319.6 +/- 52.6 vs. 145.0 +/- 21.0 pg/mL, P = 0.005). Plasma levels of antioxidants were significantly lower for the CF subjects compared to the controls (vitamin A, P < 0.003; vitamin E, P < 0.001; and beta-carotene, P < 0.01). This study confirms significantly elevated lipid peroxidation in CF using 8-iso-PGF2 alpha levels.

  20. Plasma B-Endorphin Levels in Patients with Self-Injurious Behavior and Stereotypy.

    ERIC Educational Resources Information Center

    Sandman, Curt A.; And Others

    1990-01-01

    B-endorphin and cortisol concentrations were examined in the plasma of mentally retarded adults who displayed symptoms of self-injurious behavior (SIB) (N=9), stereotypy (N=17), or SIB plus stereotypy (N=14). Compared to matched controls, patients with SIB plus stereotypy had elevated b-endorphin plasma, while cortisol levels were identical for…

  1. Plasma selenium levels and nonalcoholic fatty liver disease in Chinese adults: a cross-sectional analysis

    PubMed Central

    Yang, Zhen; Yan, Chonghuai; Liu, Gang; Niu, Yixin; Zhang, Weiwei; Lu, Shuai; Li, Xiaoyong; Zhang, Hongmei; Ning, Guang; Fan, Jiangao; Qin, Li; Su, Qing

    2016-01-01

    Selenium exposure can induce liver insulin resistance and increased liver triglyceride concentrations in animals, which may link to an increased risk of nonalcoholic fatty liver disease (NAFLD). However, epidemiological studies investigating the association between elevated plasma selenium levels and NAFLD were not available. We aimed to investigate the association of selenium levels with the prevalence of NAFLD in Chinese adults. This was a cross-sectional study of 8550 Chinese adults aged 40 yr or older in Shanghai, China. A questionnaire, anthropometric measurements, and laboratory tests were conducted. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. Plasma selenium concentration was assessed by inductively coupled plasma mass spectroscopy. The median concentration of plasma selenium was 213.0 μg/L. Elevated plasma selenium levels were associated with higher triglycerides, LDL-cholesterol, fasting plasma glucose, post-loading plasma glucose, A1c, HOMA-IR, as well as ALT, AST and γ-GT (all P < 0.05). The odds ratios were substantially higher for NAFLD (OR = 1.54, 95% CI 1.13–2.18) in the highest selenium quartile compared with those in the lowest quartile, after adjustment for potential cofounder. The results of this study provided epidemiological evidence that increased plasma selenium level is associated with elevated prevalence of NAFLD. PMID:27853246

  2. BLOOD PLASMA LEVELS AND ELIMINATION OF SALTS OF 2-PAM IN MAN AFTER ORAL ADMINISTRATION,

    DTIC Science & Technology

    salts of 2-PAM in varying amounts. A measurable amount of oxime was found in blood plasma within about 15 minutes; the concentration rose rapidly...level of oxime 3.5 fold. The biological half-life in man of the 2-PAM salts given orally, calculated from blood plasma values and urinary excretion rates

  3. Plasma homocysteine levels in Taiwanese vegetarians are higher than those of omnivores.

    PubMed

    Hung, Chien-Jung; Huang, Po-Chao; Lu, Shao-Chun; Li, Yi-Hwei; Huang, Hsien-Bin; Lin, Bi-Fong; Chang, Sue-Joan; Chou, Hsu-Fang

    2002-02-01

    Mild hyperhomocysteinemia is an independent risk factor for cardiovascular disease and may result from a deficiency of folate, vitamin B-6 or vitamin B-12. Because vitamin B-12 deficiency is often associated with vegetarianism, this study was designed to examine the effect of Taiwanese vegetarian diets on B-vitamin status and plasma homocysteine levels. Female Buddhist lacto-vegetarians (n = 45; 31-45 y) and matched omnivores (n = 45) recruited in Hualien, Taiwan, were investigated. Taiwanese vegetarians consumed normal amount of folate, but only 21% of Taiwan Recommended Daily Nutrient Allowances (RDNA) values of vitamin B-12. Compared with the omnivores, the vegetarians had significantly higher levels of plasma folate (14.79 +/- 7.70 vs. 11.98 +/- 8.29 nmol/L), but lower levels of vitamin B-12 (207.7 +/- 127.1 vs. 403.5 +/- 138.9 pmol/L). Fasting plasma homocysteine levels were significantly higher in vegetarians than in omnivores (mean: 11.20 +/- 4.27 vs. 8.64 +/- 2.06 micromol/L; median: 10.5 vs. 8.5 micromol/L). Fasting plasma homocysteine was inversely correlated with plasma folate and vitamin B-12 in the vegetarian group. Multiple regression analysis revealed that plasma folate, vitamin B-12 and creatinine were independent determinants of homocysteine variation and contributed to 38.6% of homocysteine variation in the vegetarians. Compared with the omnivores, vegetarians also had significantly lower serum levels of valine, isoleucine, leucine, lysine, alanine and arginine, but higher levels of glycine. In the vegetarian group, fasting plasma homocysteine correlated negatively with serum threonine, lysine, histidine, arginine and cystine, and these amino acids contributed to 38.7% of homocysteine variation. In conclusion, the Buddhist nuns who consumed a lacto-vegetarian diet had mildly elevated fasting plasma homocysteine levels presumably due to lower levels of plasma vitamin B-12.

  4. Alterations in plasma vascular endothelial growth factor levels in patients with schizophrenia before and after treatment.

    PubMed

    Lee, Bun-Hee; Hong, Jin-Pyo; Hwang, Jung-A; Ham, Byung-Joo; Na, Kyoung-Sae; Kim, Won-Joong; Trigo, Jose; Kim, Yong-Ku

    2015-07-30

    Vascular endothelial growth factor (VEGF), a potent angiogenetic factor, is a known neurotrophic factor. In this study, we examined plasma levels of VEGF in 50 patients with schizophrenia (SPR) and 50 healthy control subjects. We also explored any changes in plasma VEGF levels after 6-week treatment with antipsychotic agents in patients with schizophrenia. All subjects with schizophrenia were either medication-naïve or medication-free for at least 4 weeks before assessment. Plasma VEGF levels in all subjects were significantly correlated with smoking duration, which was considered to be a significant covariate. Pre-treatment plasma VEGF levels in patients with schizophrenia were significantly lower than those in healthy controls. Post-treatment VEGF levels were significantly increased in patients with schizophrenia. Plasma VEGF levels in patients with schizophrenia did not exhibit significant correlation with the total or subscale scores of the Positive and Negative Syndrome Scale (PANSS) either at baseline or at the end of the 6-week treatment. In conclusion, our findings reveal that plasma VEGF levels before treatment were lower in patients with schizophrenia and that their VEGF levels increased after treatment. Thus, VEGF may have a neuroprotective role in the improvement of schizophrenia or in the treatment effects of antipsychotics.

  5. Potential Role of Plasma Myeloperoxidase Level in Predicting Long-Term Outcome of Acute Myocardial Infarction

    PubMed Central

    Kaya, Mehmet Gungor; Yalcin, Ridvan; Okyay, Kaan; Poyraz, Fatih; Bayraktar, Nilufer; Pasaoglu, Hatice; Boyaci, Bulent; Cengel, Atiye

    2012-01-01

    We investigated the prognostic importance of plasma myeloperoxidase levels in patients with ST-elevation myocardial infarction (STEMI) at long-term follow-up, and we analyzed the correlations between plasma myeloperoxidase levels and other biochemical values. We evaluated 73 consecutive patients (56 men; mean age, 56 ±11 yr) diagnosed with acute STEMI and 46 age- and sex-matched healthy control participants. Patients were divided into 2 groups according to the median myeloperoxidase level (Group 1: plasma myeloperoxidase ≤68 ng/mL; and Group 2: plasma myeloperoxidase >68 ng/mL). Patients were monitored for the occurrence of major adverse cardiovascular events (MACE), which were defined as cardiac death; reinfarction; new hospital admission for angina; heart failure; and revascularization procedures. The mean follow-up period was 25 ± 16 months. Plasma myeloperoxidase levels were higher in STEMI patients than in control participants (82 ± 34 vs 20 ±12 ng/mL; P=0.001). Composite MACE occurred in 12 patients with high myeloperoxidase levels (33%) and in 4 patients with low myeloperoxidase levels (11%) (P=0.02). The incidences of nonfatal recurrent myocardial infarction and verified cardiac death were higher in the high-mye-loperoxidase group. In multivariate analysis, high plasma myeloperoxidase levels were independent predictors of MACE (odds ratio = 3.843; <95% confidence interval, 1.625–6.563; P=0.003). High plasma myeloperoxidase levels identify patients with a worse prognosis after acute STEMI at 2-year follow-up. Evaluation of plasma myeloperoxidase levels might be useful in determining patients at high risk of death and MACE who can benefit from further aggressive treatment and closer follow-up. PMID:22949765

  6. Potential role of plasma myeloperoxidase level in predicting long-term outcome of acute myocardial infarction.

    PubMed

    Kaya, Mehmet Gungor; Yalcin, Ridvan; Okyay, Kaan; Poyraz, Fatih; Bayraktar, Nilufer; Pasaoglu, Hatice; Boyaci, Bulent; Cengel, Atiye

    2012-01-01

    We investigated the prognostic importance of plasma myeloperoxidase levels in patients with ST-elevation myocardial infarction (STEMI) at long-term follow-up, and we analyzed the correlations between plasma myeloperoxidase levels and other biochemical values. We evaluated 73 consecutive patients (56 men; mean age, 56 ± 11 yr) diagnosed with acute STEMI and 46 age- and sex-matched healthy control participants. Patients were divided into 2 groups according to the median myeloperoxidase level (Group 1: plasma myeloperoxidase ≤ 68 ng/mL; and Group 2: plasma myeloperoxidase > 68 ng/mL). Patients were monitored for the occurrence of major adverse cardiovascular events (MACE), which were defined as cardiac death; reinfarction; new hospital admission for angina; heart failure; and revascularization procedures. The mean follow-up period was 25 ± 16 months. Plasma myeloperoxidase levels were higher in STEMI patients than in control participants (82 ± 34 vs 20 ± 12 ng/mL; P = 0.001). Composite MACE occurred in 12 patients with high myeloperoxidase levels (33%) and in 4 patients with low myeloperoxidase levels (11%) (P = 0.02). The incidences of nonfatal recurrent myocardial infarction and verified cardiac death were higher in the high-myeloperoxidase group. In multivariate analysis, high plasma myeloperoxidase levels were independent predictors of MACE (odds ratio = 3.843; <95% confidence interval, 1.625-6.563; P = 0.003). High plasma myeloperoxidase levels identify patients with a worse prognosis after acute STEMI at 2-year follow-up. Evaluation of plasma myeloperoxidase levels might be useful in determining patients at high risk of death and MACE who can benefit from further aggressive treatment and closer follow-up.

  7. Increased FGF21 plasma levels in humans with sepsis and SIRS.

    PubMed

    Gariani, Karim; Drifte, Geneviève; Dunn-Siegrist, Irène; Pugin, Jérôme; Jornayvaz, François R

    2013-01-01

    Fibroblast growth factor 21 (FGF21) is a key regulator in glucose and lipid metabolism and its plasma levels have been shown to be increased not only in humans in different situations such as type 2 diabetes, obesity, and nonalcoholic fatty liver disease but also in animal models of sepsis and pancreatitis. FGF21 is considered as a pharmacological candidate in conditions associated with insulin resistance. The aim of this study was to compare FGF21 plasma levels in patients with sepsis, in patients with systemic inflammatory response syndrome (SIRS), and in healthy controls. We measured FGF21 plasma concentrations in 22 patients with established sepsis, in 11 with SIRS, and in 12 healthy volunteers. Here, we show that FGF21 levels were significantly higher in plasma obtained from patients with sepsis and SIRS in comparison with healthy controls. Also, FGF21 levels were significantly higher in patients with sepsis than in those with noninfectious SIRS. FGF21 plasma levels measured at study entry correlated positively with the APACHE II score, but not with procalcitonin levels, nor with C-reactive protein, classical markers of sepsis. Plasma concentrations of FGF21 peaked near the onset of shock and rapidly decreased with clinical improvement. Taken together, these results indicate that circulating levels of FGF21 are increased in patients presenting with sepsis and SIRS, and suggest a role for FGF21 in inflammation. Further studies are needed to explore the potential role of FGF21 in sepsis as a potential therapeutic target.

  8. Plasma Levels of Folates, Riboflavin, Vitamin B6, and Ascorbate in Severely Disturbed Children.

    ERIC Educational Resources Information Center

    Sankar, D. V. Siva

    1979-01-01

    The plasma levels of folic acid, ascorbic acid, pyridoxine, and riboflavin were studied in 125 severely emotionally disturbed children (ages 5-16 years) to determine whether they had overt vitamin deficiencies. (Author/DLS)

  9. Tartary buckwheat sprout powder lowers plasma cholesterol level in rats.

    PubMed

    Kuwabara, Tomoko; Han, Kyu-Ho; Hashimoto, Naoto; Yamauchi, Hiroaki; Shimada, Ken-Ichiro; Sekikawa, Mitsuo; Fukushima, Michihiro

    2007-12-01

    We examined the effects of different types of buckwheat sprouts on the plasma cholesterol concentration, fecal steroid excretion and hepatic mRNA expression related to cholesterol metabolism in rats. Rats were fed a cholesterol-free diet with 5 g of Kitawasesoba common buckwheat sprout powder (KS)/100 g, 5 g of Hokkai T no. 8 tartary buckwheat sprout powder (HS-8)/100 g or 5 g of Hokkai T no. 9 tartary buckwheat sprout powder (HS-9)/100 g of diet for 4 wk. Control rats were fed a diet with alpha-cornstarch instead of sprout powder for 4 wk. There were no significant differences in food intake, body weight, liver weight or cecal contents among the groups. Plasma total cholesterol concentrations in the HS-8 and HS-9 groups were significantly lower than in the control group, whereas there was no significant difference between the KS and control groups. Fecal bile acid excretion and cecal short-chain fatty acid concentrations in the KS, HS-8 and HS-9 groups were significantly greater than in the control group. Furthermore, fecal matter excretion in the KS, HS-8 and HS-9 groups tended to be increased compared to the control group, with that in the HS-8 group being significantly higher than in the control group. Hepatic cholesterol 7alpha-hydroxylase mRNA expression in the KS, HS-8 and HS-9 groups and hepatic HMG-CoA reductase mRNA expression in the HS-9 group were significantly higher than in the control group. The results suggest that tartary buckwheat sprout powder has a serum cholesterol-lowering function by enhancing fecal bile acid excretion through increased fecal matter excretion or the upregulation of hepatic cholesterol 7alpha-hydroxylase mRNA expression in rats.

  10. The effects of ACTH on steroid metabolomic profiles in human adrenal cells.

    PubMed

    Xing, Yewei; Edwards, Michael A; Ahlem, Clarence; Kennedy, Mike; Cohen, Anthony; Gomez-Sanchez, Celso E; Rainey, William E

    2011-06-01

    The adrenal glands are the primary source of mineralocorticoids, glucocorticoids, and the so-called adrenal androgens. Under physiological conditions, cortisol and adrenal androgen synthesis are controlled primarily by ACTH. Although it is well established that ACTH can stimulate steroidogenesis in the human adrenal gland, the effect of ACTH on overall production of different classes of steroid hormones has not been defined. In this study, we examined the effect of ACTH on the production of 23 steroid hormones in adult adrenal primary cultures and 20 steroids in the adrenal cell line, H295R. Liquid chromatography/tandem mass spectrometry analysis revealed that, in primary adrenal cell cultures, cortisol and corticosterone were the two most abundant steroid hormones produced with or without ACTH treatment (48  h). Cortisol production responded the most to ACTH treatment, with a 64-fold increase. Interestingly, the production of two androgens, androstenedione and 11β-hydroxyandrostenedione (11OHA), that were also produced in large amounts under basal conditions significantly increased after ACTH incubation. In H295R cells, 11-deoxycortisol and androstenedione were the major products under basal conditions. Treatment with forskolin increased the percentage of 11β-hydroxylated products, including cortisol and 11OHA. This study illustrates that adrenal cells respond to ACTH through the secretion of a variety of steroid hormones, thus supporting the role of adrenal cells as a source of both corticosteroids and androgens.

  11. Can ACTH therapy improve the long-term outcome of drug-resistant frontal lobe epilepsy?

    PubMed

    Gobbi, Giuseppe; Loiacono, Giulia; Boni, Antonella; Marangio, Lucia; Verrotti, Alberto

    2014-06-01

    Frontal lobe epilepsy is a common focal epilepsy in children and is often difficult to treat. Adrenocorticotropic hormone (ACTH) or steroids have been used for patients with several forms of medically intractable epilepsy. We evaluated the short, medium, and long-term evolution of patients with frontal lobe epilepsy and secondary bilateral synchrony on the EEG, who received ACTH treatment. Patients were recruited for an add-on trial during clinical practice, and data was retrospectively analysed. The study group comprised 6 patients treated with ACTH. The effects of ACTH were assessed in the short term (at the end of a 6-week period of ACTH treatment), medium term (at 6 months after the end of treatment), and long term (at 12 months after the end of treatment). At short-term follow-up, ACTH treatment was effective for all types of seizures in 5 of 6 patients and ineffective in 1 patient. All patients who were seizure-free at the end of ACTH treatment maintained an excellent outcome, remaining seizure-free at the end of follow-up. Our study demonstrates that ACTH may represent an effective treatment for frontal lobe epilepsy with secondary bilateral synchrony. Further double-blind prospective studies are required to confirm our initial findings.

  12. Plasma Tau Levels in Cognitively Normal Middle-Aged and Older Adults

    PubMed Central

    Chiu, Ming-Jang; Fan, Ling-Yun; Chen, Ta-Fu; Chen, Ya-Fang; Chieh, Jen-Jei; Horng, Herng-Er

    2017-01-01

    Using an ultra-sensitive technique, an immunomagnetic reduction assay, the plasma tau level can be measured to a limit of quantification of pg/ml. In total 126 cognitively normal middle-aged and older adults (45–95 years old) were recruited. The plasma tau levels were significantly higher in the older group (aged 65–95 years) 18.14 ± 7.33 pg/ml than those in the middle-aged group (aged 45–64 years) 14.35 ± 6.49 pg/ml when controlled gender and ApoEε4 carrier status (F = 3.102, P = 0.029). The ApoEε4 carriers had higher plasma tau levels than the non-carriers when controlled age and gender (F = 6.149, P = 0.001). Men had higher plasma tau levels than their women counterparts when controlled ApoEε4 carrier status and gender (F = 6.149, P = 0.001). The plasma tau levels were found to be positively associated with their ages (r = 0.359, P < 0.001). Regression analysis showed that age explained approximately 13% of the variance in the plasma tau levels, and explained more than 10% of the variance in the volumes of the hippocampus and white matter hypodensity (R2 change 0.123~0.167, all P < 0.001), and explained less than 10% of the variance in the volume of the amygdala, and central part of the corpus callosum (R2 change 0.085~0.097, all P = 0.001). However, the plasma tau levels do not further explain any residual variance in the volume of brain structures. In conclusion, the effect of age on the plasma tau levels should always be considered in clinical applications of this surrogate biomarker to middle-aged and elderly subjects. PMID:28321189

  13. Plasma NOV/CCN3 Levels Are Closely Associated with Obesity in Patients with Metabolic Disorders

    PubMed Central

    Pakradouni, Jihane; Le Goff, Wilfried; Calmel, Claire; Antoine, Bénédicte; Villard, Elise; Frisdal, Eric; Abifadel, Marianne; Tordjman, Joan; Poitou, Christine; Bonnefont-Rousselot, Dominique; Bittar, Randa; Bruckert, Eric; Clément, Karine; Fève, Bruno; Martinerie, Cécile; Guérin, Maryse

    2013-01-01

    Objective Evidence points to a founder of the multifunctional CCN family, NOV/CCN3, as a circulating molecule involved in cardiac development, vascular homeostasis and inflammation. No data are available on the relationship between plasma NOV/CCN3 levels and cardiovascular risk factors in humans. This study investigated the possible relationship between plasma NOV levels and cardiovascular risk factors in humans. Methods NOV levels were measured in the plasma from 594 adults with a hyperlipidemia history and/or with lipid-lowering therapy and/or a body mass index (BMI) >30 kg/m2. Correlations were measured between NOV plasma levels and various parameters, including BMI, fat mass, and plasma triglycerides, cholesterol, glucose, and C-reactive protein. NOV expression was also evaluated in adipose tissue from obese patients and rodents and in primary cultures of adipocytes and macrophages. Results After full multivariate adjustment, we detected a strong positive correlation between plasma NOV and BMI (r = 0.36 p<0.0001) and fat mass (r = 0.33 p<0.0005). According to quintiles, this relationship appeared to be linear. NOV levels were also positively correlated with C-reactive protein but not with total cholesterol, LDL-C or blood glucose. In patients with drastic weight loss induced by Roux-en-Y bariatric surgery, circulating NOV levels decreased by 28% (p<0.02) and 48% (p<0.0001) after 3 and 6 months, respectively, following surgery. In adipose tissue from obese patients, and in human primary cultures NOV protein was detected in adipocytes and macrophages. In mice fed a high fat diet NOV plasma levels and its expression in adipose tissue were also significantly increased compared to controls fed a standard diet. Conclusion Our results strongly suggest that in obese humans and mice plasma NOV levels positively correlated with NOV expression in adipose tissue, and support a possible contribution of NOV to obesity-related inflammation. PMID:23785511

  14. Plasma Tau Levels in Cognitively Normal Middle-Aged and Older Adults.

    PubMed

    Chiu, Ming-Jang; Fan, Ling-Yun; Chen, Ta-Fu; Chen, Ya-Fang; Chieh, Jen-Jei; Horng, Herng-Er

    2017-01-01

    Using an ultra-sensitive technique, an immunomagnetic reduction assay, the plasma tau level can be measured to a limit of quantification of pg/ml. In total 126 cognitively normal middle-aged and older adults (45-95 years old) were recruited. The plasma tau levels were significantly higher in the older group (aged 65-95 years) 18.14 ± 7.33 pg/ml than those in the middle-aged group (aged 45-64 years) 14.35 ± 6.49 pg/ml when controlled gender and ApoEε4 carrier status (F = 3.102, P = 0.029). The ApoEε4 carriers had higher plasma tau levels than the non-carriers when controlled age and gender (F = 6.149, P = 0.001). Men had higher plasma tau levels than their women counterparts when controlled ApoEε4 carrier status and gender (F = 6.149, P = 0.001). The plasma tau levels were found to be positively associated with their ages (r = 0.359, P < 0.001). Regression analysis showed that age explained approximately 13% of the variance in the plasma tau levels, and explained more than 10% of the variance in the volumes of the hippocampus and white matter hypodensity (R(2) change 0.123~0.167, all P < 0.001), and explained less than 10% of the variance in the volume of the amygdala, and central part of the corpus callosum (R(2) change 0.085~0.097, all P = 0.001). However, the plasma tau levels do not further explain any residual variance in the volume of brain structures. In conclusion, the effect of age on the plasma tau levels should always be considered in clinical applications of this surrogate biomarker to middle-aged and elderly subjects.

  15. Iron Supplementation in Suckling Piglets: How to Correct Iron Deficiency Anemia without Affecting Plasma Hepcidin Levels

    PubMed Central

    Starzyński, Rafał R.; Laarakkers, Coby M. M.; Tjalsma, Harold; Swinkels, Dorine W.; Pieszka, Marek; Styś, Agnieszka; Mickiewicz, Michał; Lipiński, Paweł

    2013-01-01

    The aim of the study was to establish an optimized protocol of iron dextran administration to pig neonates, which better meets the iron demand for erythropoiesis. Here, we monitored development of red blood cell indices, plasma iron parameters during a 28-day period after birth (till the weaning), following intramuscular administration of different concentrations of iron dextran to suckling piglets. To better assess the iron status we developed a novel mass spectrometry assay to quantify pig plasma levels of the iron-regulatory peptide hormone hepcidin-25. This hormone is predominantly secreted by the liver and acts as a negative regulator of iron absorption and reutilization. The routinely used protocol with high amount of iron resulted in the recovery of piglets from iron deficiency but also in strongly elevated plasma hepcidin-25 levels. A similar protocol with reduced amounts of iron improved hematological status of piglets to the same level while plasma hepcidin-25 levels remained low. These data show that plasma hepcidin-25 levels can guide optimal dosing of iron treatment and pave the way for mixed supplementation of piglets starting with intramuscular injection of iron dextran followed by dietary supplementation, which could be efficient under condition of very low plasma hepcidin-25 level. PMID:23737963

  16. Iron supplementation in suckling piglets: how to correct iron deficiency anemia without affecting plasma hepcidin levels.

    PubMed

    Starzyński, Rafał R; Laarakkers, Coby M M; Tjalsma, Harold; Swinkels, Dorine W; Pieszka, Marek; Styś, Agnieszka; Mickiewicz, Michał; Lipiński, Paweł

    2013-01-01

    The aim of the study was to establish an optimized protocol of iron dextran administration to pig neonates, which better meets the iron demand for erythropoiesis. Here, we monitored development of red blood cell indices, plasma iron parameters during a 28-day period after birth (till the weaning), following intramuscular administration of different concentrations of iron dextran to suckling piglets. To better assess the iron status we developed a novel mass spectrometry assay to quantify pig plasma levels of the iron-regulatory peptide hormone hepcidin-25. This hormone is predominantly secreted by the liver and acts as a negative regulator of iron absorption and reutilization. The routinely used protocol with high amount of iron resulted in the recovery of piglets from iron deficiency but also in strongly elevated plasma hepcidin-25 levels. A similar protocol with reduced amounts of iron improved hematological status of piglets to the same level while plasma hepcidin-25 levels remained low. These data show that plasma hepcidin-25 levels can guide optimal dosing of iron treatment and pave the way for mixed supplementation of piglets starting with intramuscular injection of iron dextran followed by dietary supplementation, which could be efficient under condition of very low plasma hepcidin-25 level.

  17. Elevated pretreatment plasma D-dimer levels and platelet counts predict poor prognosis in pancreatic adenocarcinoma.

    PubMed

    Liu, Peng; Zhu, Yuan; Liu, Luying

    2015-01-01

    This retrospective study was conducted to evaluate the prognostic significance of the preoperative plasma D-dimer levels and platelet counts in patients with pancreatic adenocarcinoma. A total of 168 consecutive locally advanced pancreatic adenocarcinoma patients who underwent intensity modulated radiation therapy with or without chemotherapy were enrolled in this study. Plasma D-dimer levels were measured by a latex-enhanced immunoturbidimetric assay. Of the 168 patients enrolled, 106 patients were males and 62 patients were females. There was significant difference between plasma D-dimer levels and clinical responses (P=0.001). The 1-year, 2-year, and 3-year cumulative overall survival rates were 50.6%, 15.0%, and 4.9%, respectively. Plasma D-dimer levels (P<0.001) and platelet counts (P=0.010) were significantly related with overall survival in univariate analysis. The Cox proportional hazards regression indicated that plasma D-dimer levels (P=0.028), platelet counts (P=0.004), and treatment response (P<0.001) were independent prognostic factors for overall survival. Elevated pretreatment plasma D-dimer levels and platelet counts predict poor prognosis in pancreatic adenocarcinoma.

  18. [Measurement and correlation analysis of plasma VEGF level in the patients of hyperthyroidism].

    PubMed

    Zhao, Xiaoni; Wang, Guangrong; You, Jinhui

    2013-04-01

    Vascular endothelial growth factor (VEGF) is a glycoprotein that promotes endothelial regeneration, stimulates formation of collateral blood vessels and increases vascular permeability. The purpose of this study was to measure the peripheral blood plasma level of VEGF and FT3, FT4, TSH and to analyze the correlation of the level of VEGF and TSH, FT3, FT4, age and gender in the patients of hyperthyroidism. The relationship between hyperthyroidism and VEGF was investigated as well. The plasma level of VEGF in 45 hyperthyroidism patients and 27 healthy persons were measured by enzyme-linked immunosorbent assay (ELISA), while plasma FT3, FT4, TSH were detected by chemiluminescence. The result showed that the plasma level of VEGF in hyperthyroidism patients [(92.53 +/- 62.38) pg/mL] was significantly lower than that in the control group [(158.28 +/- 77.15) pg/mL] (P < 0.01). The plasma level of VEGF correlated with age, and that of those over 40Y was significantly higher than that of 40Y or younger (P < 0.05) in healthy group. Whereas there was no correlation among VEGF, TSH, FT3, FT4, age and gender in hyperthyroidism patients (P > 0.05). These results suggested that the peripheral blood plasma level of VEGF in hyperthyroidism patients was significantly lower than that in the control group. Further experimental investigations are needed to estimate the relationship between VEGF and hyperthyroidism.

  19. Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia.

    PubMed

    de Miguel, Valeria; Redal, María Ana; Viale, María Lorena; Kahan, Mariano; Glerean, Mariela; Beskow, Axel; Fainstein Day, Patricia

    2010-01-01

    Adrenocorticotropin (ACTH) independent bilateral macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein-coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing's syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal) and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon) tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide) was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient's adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing's syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.

  20. Effects of bupropion on the forced swim test and release of dopamine in the nucleus accumbens in ACTH-treated rats.

    PubMed

    Kitamura, Yoshihisa; Yagi, Takahiko; Kitagawa, Kouhei; Shinomiya, Kazuaki; Kawasaki, Hiromu; Asanuma, Masato; Gomita, Yutaka

    2010-08-01

    The dopamine reuptake inhibitor bupropion has clinically been proven to improve depression and treatment-resistant depression. We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which bupropion acts in this model was explored specifically in relation to the site of action through the use of microinjections into the medial prefrontal cortex and nucleus accumbens. Bupropion significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by D2 and D3 receptor antagonists in normal rats. Furthermore, infusions of bupropion into the nucleus accumbens, but not medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Bupropion treatment plus repeated ACTH treatment significantly increased the extracellular dopamine concentration. These findings suggest the antidepressant-like effect of bupropion to be related to levels of dopamine in the rat nucleus accumbens.

  1. ACTH acts via an anterior ventral third ventricular site to elicit grooming behavior.

    PubMed

    Dunn, A J; Hurd, R W

    1986-01-01

    Intracerebroventricular but not parenteral application of ACTH has been shown to elicit excessive grooming behavior in rats and mice. This behavior is elicited by administration of ACTH into the lateral, third, or fourth ventricles. Plugging of the cerebral aqueduct with cold cream fails to prevent grooming in response to lateral ventricle injection of ACTH. However, cold cream plugs in the third ventricle can prevent the subsequent induction of grooming behavior by lateral ventricle injection of ACTH, but only when the plugs are located in the anterior ventral third ventricle in the region of the organum vasculosum laminae terminalis (OVLT) and median eminence. These data suggest the anterior ventral third ventricle as the periventricular site of action of ACTH in eliciting excessive grooming, although it is possible that peptides taken up in this area are transported to other regions to elicit the behavioral response.

  2. Disturbances of the hypothalamic-pituitary-adrenal axis and plasma electrolytes during experimental sepsis

    PubMed Central

    2011-01-01

    Background Sepsis continues to be a poorly understood syndrome with a high mortality rate. While we are beginning to decipher the intricate interplay of the inflammatory response during sepsis, the precise regulation of the hypothalamic-pituitary-adrenal (HPA) axis and its impact on electrolyte homeostasis during sepsis remains incompletely understood. Methods Sepsis was induced in adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). Plasma samples were obtained as a function of time (6-48 hrs) after CLP and compared with healthy animals (neg ctrl). Samples were analyzed for adrenocorticotropin (ACTH), corticosterone, and aldosterone levels, as well as concentrations of sodium (Na+), potassium (K+), chloride (Cl-), and magnesium (Mg2+). Results ACTH levels were found to be significantly reduced 6-24 hrs after CLP in comparison to baseline levels and displayed gradual recovery during the later course (24-48 hrs) of sepsis. Plasma corticosterone concentrations exhibited a bell-shaped response, peaking between 6 and 12 hrs followed by rapid decline and concentrations below negative control levels 48 hrs after injury. Aldosterone levels in septic animals were continuously elevated between 6 and 48 hrs. Whereas plasma Na+ levels were found to be persistently elevated following CLP, levels of K+, Cl- and Mg2+ were significantly reduced as a function of time and gradually recovered during the later course of sepsis. Conclusions CLP-induced sepsis resulted in dynamic changes of ACTH, corticosterone, and aldosterone levels. In addition, electrolyte levels showed significant disturbances after CLP. These electrolyte perturbations might be evoked by a downstream effect or a dysfunctional HPA-axis response during sepsis and contribute to severe complications during sepsis. PMID:22208725

  3. Plasma agouti-related protein levels in women with anorexia nervosa.

    PubMed

    Moriya, Junko; Takimoto, Yoshiyuki; Yoshiuchi, Kazuhiro; Shimosawa, Tatsuo; Akabayashi, Akira

    2006-10-01

    Agouti-related protein (AGRP) is the competitive antagonist of alpha-melanocyte stimulating hormone (alpha-MSH) located at melanocortin receptors 3 and 4 (MC3R and MC4R), and also acts as an MC4R inverse agonist. Hypothalamic AGRP controls food intake and body weight in rodents. It has also been found in human plasma. To study the possibility of disturbances in melanocortin receptor-related peptides in eating disorders, plasma AGRP, alpha-MSH, and leptin levels were measured in 18 female patients with anorexia nervosa (AN) (age, 23.5+/-7.1 yr; body mass index (BMI) 14.5+/-1.8 kg/m(2)) and 17 age-matched female controls (age, 25.8+/-3.9 yr; BMI 20.2+/-1.6 kg/m(2)). Blood samples were collected after overnight fasting, and plasma peptides levels were measured using ELISA. Plasma AGRP levels increased significantly in AN patients when compared with controls (P<0.01) while plasma alpha-MSH levels were not significantly different. Plasma leptin levels decreased significantly in AN patients when compared with controls (P<0.001). In addition, plasma AGRP levels were negatively correlated with leptin (r=-0.41, P<0.01) and BMI (r=-0.40, P<0.05) in all subjects. In conclusion, plasma AGRP elevation may be related to energy homeostasis disturbance in AN, and in addition to leptin, peripheral AGRP levels could be used as a nutritional marker in AN patients.

  4. ACTH Receptor (MC2R) Specificity: What Do We Know About Underlying Molecular Mechanisms?

    PubMed Central

    Fridmanis, Davids; Roga, Ance; Klovins, Janis

    2017-01-01

    Coincidentally, the release of this Research Topic in Frontiers in Endocrinology takes place 25 years after the discovery of the adrenocorticotropic hormone receptor (ACTHR) by Mountjoy and colleagues. In subsequent years, following the discovery of other types of mammalian melanocortin receptors (MCRs), ACTHR also became known as melanocortin type 2 receptor (MC2R). At present, five types of MCRs have been reported, all of which share significant sequence similarity at the amino acid level, and all of which specifically bind melanocortins (MCs)—a group of biologically active peptides generated by proteolysis of the proopiomelanocortin precursor. All MCs share an identical –H–F–R–W– pharmacophore sequence. α-Melanocyte-stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH) are the most extensively studied MCs and are derived from the same region. Essentially, α-MSH is formed from the first 13 amino acid residues of ACTH. ACTHR is unique among MCRs because it binds one sole ligand—ACTH, which makes it a very attractive research object for molecular pharmacologists. However, much research has failed, and functional studies of this receptor are lagging behind other MCRs. The reason for these difficulties has already been outlined by Mountjoy and colleagues in their publication on ACTHR coding sequence discovery where the Cloudman S91 melanoma cell line was used for receptor expression because it was a “more sensitive assay system.” Subsequent work showed that ACTHR could be successfully expressed only in endogenous MCR-expressing cell lines, since in other cell lines it is retained within the endoplasmic reticulum. The resolution of this methodological problem came in 2005 with the discovery of melanocortin receptor accessory protein, which is required for the formation of functionally active ACTHR. The decade that followed this discovery was filled with exciting research that provided insight into the molecular mechanisms underlying

  5. The physiological consequences of crib-biting in horses in response to an ACTH challenge test.

    PubMed

    Briefer Freymond, S; Bardou, D; Briefer, E F; Bruckmaier, R; Fouché, N; Fleury, J; Maigrot, A-L; Ramseyer, A; Zuberbühler, K; Bachmann, I

    2015-11-01

    Stereotypies are repetitive and relatively invariant patterns of behavior, which are observed in a wide range of species in captivity. Stereotypic behavior occurs when environmental demands produce a physiological response that, if sustained for an extended period, exceeds the natural physiological regulatory capacity of the organism, particularly in situations that include unpredictability and uncontrollability. One hypothesis is that stereotypic behavior functions to cope with stressful environments, but the existing evidence is contradictory. To address the coping hypothesis of stereotypies, we triggered physiological reactions in 22 horses affected by stereotypic behavior (crib-biters) and 21 non-crib-biters (controls), using an ACTH challenge test. Following administration of an ACTH injection, we measured saliva cortisol every 30 min and heart rate (HR) continuously for a period of 3h. We did not find any differences in HR or HR variability between the two groups, but crib-biters (Group CB) had significantly higher cortisol responses than controls (Group C; mean ± SD: CB, 5.84 ± 2.62 ng/ml, C, 4.76 ± 3.04 ng/ml). Moreover, crib-biters that did not perform the stereotypic behavior during the 3-hour test period (Group B) had significantly higher cortisol levels than controls, which was not the case of crib-biters showing stereotypic behavior (Group A) (B, 6.44 ± 2.38 ng/ml A, 5.58 ± 2.69 ng/ml). Our results suggest that crib-biting is a coping strategy that helps stereotypic individuals to reduce cortisol levels caused by stressful situations. We conclude that preventing stereotypic horses from crib-biting could be an inappropriate strategy to control this abnormal behavior, as it prevents individuals from coping with situations that they perceive as stressful.

  6. Plasma ficolin levels and risk of nephritis in Danish patients with systemic lupus erythematosus.

    PubMed

    Tanha, Nima; Pilely, Katrine; Faurschou, Mikkel; Garred, Peter; Jacobsen, Søren

    2017-02-01

    Given the scavenging properties of ficolins, we hypothesized that variation in the plasma concentrations of the three ficolins may be associated with development of lupus nephritis (LN), type of LN, end-stage renal disease (ESRD), and/or mortality among patients with systemic lupus erythematosus (SLE). SLE patients attending a Danish tertiary rheumatology referral center were included. Plasma concentrations of ficolin-1, ficolin-2, and ficolin-3 were determined and dichotomized by the median into high and low. LN was defined by clinical criteria; type of LN by renal biopsy; ESRD follow-up time was defined as time from onset of LN to the development of ESRD or censoring at the end of follow-up. The study included 112 SLE patients with median disease duration of 8 years of which 53 (47%) had LN at the time of inclusion. During a median follow-up of 10 years, five patients developed ESRD. Sixteen patients died. Odds ratios (ORs) of LN were 1.2 (95% CI: 0.6-2.7), 4.1 (95% CI: 1.7-9.7), and 0.9 (95% CI: 0.4-2.0) for patients with low ficolin-1, ficolin-2, and ficolin-3 plasma levels, respectively. The distribution of histological classes differed between patients with high and low plasma levels of ficolin-1 (p = 0.009). Patients with high ficolin-1 plasma levels had an increased risk of ESRD. There was no association between the levels of the analyzed plasma ficolins and mortality. Low plasma ficolin-2 levels were associated with an increased risk of having LN. High plasma levels of ficolin-1 were associated with the histological subtype of LN and development of ESRD.

  7. Binding energy levels of a slowly moving ion in dusty plasmas

    NASA Astrophysics Data System (ADS)

    Hu, Hongwei; Li, Fuli

    2013-02-01

    The near field electric potential of a slowly moving ion in complex plasmas is studied. We find that the potential consists of the Debye-Hückel potential, the wake potential, and the potential associated with charge fluctuations. The binding energy levels of the ion are calculated by use of the Ritz variation method. The results show that the binding energy levels are related to the magnetic quantum number m. The binding energy levels are affected by speed of the ion and dust grain number density. In contract to isolated ion or static ion in plasmas, the binding energy levels of the ion are pushed up and even become unbounded.

  8. Plasma and urine nitric oxide levels in healthy Turkish children.

    PubMed

    Elli, Murat; Söylemezoglu, Oguz; Erbas, Deniz; Bakkaloglu, Sevcan A; Buyan, Necla; Ozkaya, Ozan; Hasanoglu, Enver

    2005-11-01

    Nitric oxide (NO) is an important messenger molecule with a wide range of actions in virtually all cell systems and organs. In kidneys it participates in glomerular and medullary hemodynamics, tubuloglomerular feed-back, renin secretion, and extracellular fluid balance. Although the role of NO in regulating renal function in adults is well-established, it has recently been suggested that NO has a more critical role in maintaining basal renal blood flow and glomerular filtration rate (GFR) in the developing kidney. NO is rapidly metabolized to the stable end products nitrite and nitrate, which are more slowly excreted into the urine. Thus these metabolites can be recommended as useful markers of endogenous NO synthase activity, despite limited data about age-related changes in in-vivo NO production. The aims of this study were to determine age-related normal reference values of serum and urinary NO metabolites and to assess the probable relationship between these metabolites and the GFR. Normal levels of NO end products in blood and urine of 296 healthy children (117 female, 179 male) between the ages of 0 and 16 were investigated, as was whether these values change with age. Serum and urinary nitrate levels did not differ according to sex. Serum nitrate levels are higher in younger children, especially in the newborn period, and decrease with age. Nitrate levels in urine are higher in younger children with a peak in infancy (1 month to 1 year) and decrease with age. It was demonstrated that this decrease in serum and urinary nitrate levels with age parallels the increase in GFR. In conclusion, urinary NO products may be an indirect marker of serum NO levels and NO might have an important regulatory function both in the maintenance of renal function and in the maturation of the developing kidneys.

  9. Relationship Between Brain and Plasma Carbaryl Levels and Cholinesterase Inhibition

    EPA Science Inventory

    Carbaryl is a N-methylcarbamate pesticide and, like others in this class, is a reversible inhibitor of cholinesterase (ChE) enzymes. Although studied for many years, there is a surprising lack of information relating tissue levels of carbaryl with ChE activity in the same animals...

  10. Elevated plasma midkine and pleiotrophin levels in patients with systemic lupus erythematosus.

    PubMed

    Wu, Guo-Cui; Yuan, Hui; Pan, Hai-Feng; Ye, Dong-Qing

    2016-11-26

    Emerging evidence suggests that two heparin-binding growth factor, midkine and pleiotrophin are implicated in the pathogenesis of autoimmune diseases including SLE. To investigate the plasma midkine and pleiotrophin levels in SLE patients, as well as their correlation with major clinical parameters and interleukin-17 (IL-17) level in SLE, 83 SLE patients and 123 controls including 20 rheumatoid arthritis (RA) patients, 21 Sjögren's syndrome (SS) patients and 82 healthy controls (HCs) were recruited. Plasma midkine, pleiotrophin and IL-17 levels were detected by ELISA. Midkine and pleiotrophin levels were significantly higher in SLE, RA and SS patients compared with HCs (all P < 0.05). There were significantly lower midkine and pleiotrophin levels in SLE compared to SS (P < 0.05 and P < 0.01, respectively). No significant differences in midkine and pleiotrophin levels were found between SLE and RA (P = 0.240 and P = 0.074, respectively). Both plasma midkine and pleiotrophin levels were associated with rash and anti-SSA in SLE. In addition, both midkine and pleiotrophin levels were positively associated with IL-17 level in SLE (both P < 0.001). Area under curve (AUC) of the receiver operating characteristic (ROC) curve for midkine and pleiotrophin were 0.606 (0.527-0.681) and 0.605 (0.526-0.680) respectively. In conclusion, elevated plasma midkine and pleiotrophin levels and their associations with rash, anti-SSA and IL-17 in SLE patients suggest their involvement in this disease.

  11. Factors associated with plasma IL-33 levels in patients with chronic obstructive pulmonary disease

    PubMed Central

    Kim, Sei Won; Rhee, Chin Kook; Kim, Ki Uk; Lee, Sang Haak; Hwang, Hun Gyu; Kim, Yu Il; Kim, Deog Kyeom; Lee, Sang Do; Oh, Yeon-Mok; Yoon, Hyoung Kyu

    2017-01-01

    Background Interleukin (IL)-33 promotes T helper (Th)2 immunity and systemic inflammation. The role of IL-33 in asthma has been widely investigated. IL-33 has also been suggested to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study investigated the clinical significance and usefulness of plasma IL-33 level in patients with COPD. Methods A total of 307 patients with stable COPD from 15 centers, who were in the Korean Obstructive Lung Disease cohort, were enrolled in this study. Plasma IL-33 levels were measured by enzyme-linked immunosorbent assay. We analyzed the association between IL-33 level and other clinical characteristics related to COPD. We also examined the features of patients with COPD who exhibited high IL-33 levels. Results IL-33 levels varied, but were very low in most patients. Eosinophil count was significantly correlated with a plasma IL-33 level. In addition, old age and current smoking were related to a low IL-33 level. Significantly more patients with a higher IL-33 level had chronic bronchitis compared with those with a low IL-33 level. Conclusion Plasma IL-33 level in patients with stable COPD was related to eosinophil count and chronic bronchitis phenotype. Further studies are needed to identify the precise mechanisms of IL-33/ST2 pathway in patients with COPD. PMID:28176939

  12. Increased plasma neopterin and hs-CRP levels in patients with endemic fluorosis.

    PubMed

    Varol, Ercan; Aksoy, Fatih; Icli, Atilla; Arslan, Akif; Yuksel, Ozlem; Ersoy, I Hakki; Varol, Simge; Dogan, Abdullah

    2012-11-01

    Although fluoride induced inflammatory reactions have been shown in animals and in vitro humans, there are few studies about fluoride induced inflammatory reactions in human beings at clinical setting. We aimed to measure the plasma neopterin, a marker of activation of the monocyte/macrophage system, and high sensitivity C-reactive protein (hs-CRP) levels in patients with endemic fluorosis to investigate the possible role of inflammatory processes (monocyte/macrophage activity) in the underlying pathophysiology of fluoride toxicity at clinical level. Plasma neopterin and hs-CRP levels were determined in endemic fluorosis patients and control subjects. Plasma neopterin levels were significantly higher among patients with endemic fluorosis when compared with control group (2.40 ± 0.66 vs. 1.63 ± 0.27 ng/mL respectively; p < 0.001) and plasma hs-CRP levels were also significantly higher among patients with endemic fluorosis when compared with control group (2.41 ± 1.23 vs. 1.93 ± 0.64 mg/L respectively; p < 0.001). Plasma neopterin levels were positively correlated with urine fluoride levels (r = 0.67, p < 0.001) and serum hs-CRP levels were positively correlated with urine fluoride levels (r = 0.36, p < 0.001). We have found that plasma neopterin and hs-CRP levels are increased in patients with endemic fluorosis. We have concluded that inflammation play an important role in the pathophysiology of fluoride toxicity in patients with endemic fluorosis.

  13. Short-term treatment with rivastigmine and plasma levels of Abeta peptides in Alzheimer's disease.

    PubMed

    Sobow, Tomasz; Kloszewska, Iwona

    2005-01-01

    Deregulation of APP metabolism is considered to be a key pathogenic event in Alzheimer's disease. Data from cell cultures indicate that the secretion of Abeta1-42 might be inhibited by cholinesterase inhibitors, possibly via M1 receptors stimulation. Treatment with tacrine, a dual acetyl- and butyrylcholinesterase inhibitor, had no significant effect on mean plasma Abeta species concentrations. However, a correlation was observed between higher drug concentrations and lower Abeta levels that might indicate an effect on APP metabolism with an increased alpha-cleavage. Abeta1-40 and Abeta1-42 levels were measured in the plasma of 28 AD subjects by means of a commercially available ELISA before rivastigmine treatment and at week 2 after the first dose of the drug (3 mg/day) had been administered. Treatment with rivastigmine exhibited a significant effect on mean plasma concentrations of Abeta1-42 (mean difference 7.8+/-8.4, t=-4.9, pmean difference 7.8+/-8.4, t=-4.9, p<0.001) with a negative correlation with the patients age (Pearson's R=-0.40, p=0.035). No significant effect on plasma Abeta1-40 was observed. The observed increase of mean levels of plasma Abeta1-42 after rivastigmine treatment might indicate an effect of the drug on Abeta metabolism, mobilization of Abeta1-42 from deposits in the affected brain areas and a consecutive Ab1-42 brain-to-plasma efflux. The negative correlation between Abeta1-42 plasma levels changes and age may be a sign of impairment of this process in the older patients. A large individual variation of the observed response, however, excludes drawing definite conclusions. Whether those subjects who respond to rivastigmine in terms of Abeta1-42 plasma levels changes also respond clinically needs to be established.

  14. Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels

    SciTech Connect

    Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.; Krauss, Ronald M.; Rubin, Edward M.; Cohen, Jonathan C.

    2002-09-16

    The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in {approx}16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n 1/4 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12 percent of Caucasians, 14 percent of African-Americans and 28 percent of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 50 percent of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

  15. ACTH TREATMENT OF INFANTILE SPASMS: MECHANISMS OF ITS EFFECTS IN MODULATION OF NEURONAL EXCITABILITY

    PubMed Central

    Brunson, K. L.; Avishai-Eliner, S.; Baram, T. Z.

    2011-01-01

    The efficacy of ACTH, particularly in high doses, for rapid and complete elimination of infantile spasms (IS) has been demonstrated in prospective controlled studies. However, the mechanisms for this efficacy remain unknown. ACTH promotes the release of adrenal steroids (glucocorticoids), and most ACTH effects on the central nervous system have been attributed to activation of glucocorticoid receptors. The manner in which activation of these receptors improves IS and the basis for the enhanced therapeutic effects of ACTH — compared with steroids — for this disorder are the focus of this chapter. First, a possible “common excitatory pathway,” which is consistent with the many etiologies of IS and explains the confinement of this disorder to infancy, is proposed. This notion is based on the fact that all of the entities provoking IS activate the native “stress system” of the brain. This involves increased synthesis and release of the stress-activated neuropeptide, corticotropin-releasing hormone (CRH), in limbic, seizure-prone brain regions. CRH causes severe seizures in developing experimental animals, as well as limbic neuronal injury. Steroids, given as therapy or secreted from the adrenal gland upon treatment with ACTH, decrease the production and release of CRH in certain brain regions. Second, the hypothesis that ACTH directly influences limbic neurons via the recently characterized melanocortin receptors is considered, focusing on the effects of ACTH on the expression of CRH. Experimental data showing that ACTH potently reduces CRH expression in amygdala neurons is presented. This downregulation was not abolished by experimental elimination of steroids or by blocking their receptors and was reproduced by a centrally administered ACTH fragment that does not promote steroid release. Importantly, selective blocking of melanocortin receptors prevented ACTH-induced downregulation of CRH expression, providing direct evidence for the involvement of these

  16. Comparing Azole Plasma Trough Levels in Lung Transplant Recipients: Percentage of Therapeutic Levels and Intrapatient Variability

    PubMed Central

    Weber, Alexandra; Ihle, Franziska; Matthes, Sandhya; Ceelen, Felix; Zimmermann, Gregor; Kneidinger, Nikolaus; Schramm, Rene; Winter, Hauke; Zoller, Michael; Vogeser, Michael; Behr, Juergen; Neurohr, Claus

    2017-01-01

    Background: This study compared therapeutic azole plasma trough levels (APL) of the azole antimycotics itraconazole (ITR), voriconazole (VOR), and posaconazole (POS) in lung transplant recipients and analyzed the influencing factors. In addition, intrapatient variability for each azole was determined. Methods: From July 2012 to July 2015, 806 APL of ITR, VOR, posaconazole liquid (POS-Liq), and posaconazole tablets (POS-Tab) were measured in 173 patients of the Munich Lung Transplantation Program. Therapeutic APL were defined as follows: ITR, ≥700 ng/mL; VOR, 1000–5500 ng/mL; and POS, ≥700 ng/mL (prophylaxis) and ≥1000 ng/mL (therapy). Results: VOR and POS-Tab reached the highest number of therapeutic APL, whereas POS-Liq showed the lowest percentage (therapy: ITR 50%, VOR 70%, POS-Liq 38%, and POS-Tab 82%; prophylaxis: ITR 62%, VOR 85%, POS-Liq 49%, and POS-Tab 76%). Risk factors for subtherapeutic APL of all azoles were the azole dose (ITR, P < 0.001; VOR, P = 0.002; POS-Liq, P = 0.006) and age over 60 years (ITR, P = 0.003; VOR, P = 0.002; POS-Liq, P = 0.039; POS-Tab, P < 0.001). Cystic fibrosis was a significant risk factor for subtherapeutic APL for VOR and POS-Tab (VOR, P = 0.002; POS-Tab, P = 0.005). Double lung transplantation (LTx) was significantly associated with less therapeutic APL for VOR and POS-Liq (VOR, P = 0.030; POS-Liq, P < 0.001). Concomitant therapy with 80 mg pantoprazole led to significantly fewer therapeutic POS APL as compared to 40 mg (POS-Liq, P = 0.015; POS-Tab, P < 0.001). VOR displayed the greatest intrapatient variability (46%), whereas POS-Tab showed the lowest (32%). Conclusions: Our study showed that VOR and POS-Tab achieve the highest percentage of therapeutic APL in patients with LTx; POS-Tab showed the lowest intrapatient variability. APL are significantly influenced by azole dose, age, cystic fibrosis, type of LTx, and comedication with proton-pump inhibitors. Considering the high number of subtherapeutic APL

  17. Impact of bone lead and bone resorption on plasma and whole blood lead levels during pregnancy.

    PubMed

    Téllez-Rojo, Martha María; Hernández-Avila, Mauricio; Lamadrid-Figueroa, Héctor; Smith, Donald; Hernández-Cadena, Leticia; Mercado, Adriana; Aro, Antonio; Schwartz, Joel; Hu, Howard

    2004-10-01

    The authors tested the hypotheses that maternal bone lead burden is associated with increasing maternal whole blood and plasma lead levels over the course of pregnancy and that this association is modified by rates of maternal bone resorption. A total of 193 Mexican women were evaluated (1997-1999) in the first, second, and third trimesters of pregnancy. Whole blood lead and plasma lead levels were measured in each trimester. Urine was analyzed for cross-linked N-telopeptides (NTx) of type I collagen, a biomarker of bone resorption. Patella and tibia lead levels were measured at 4 weeks postpartum. The relation between whole blood, plasma, and bone lead and NTx was assessed using mixed models. Plasma lead concentrations followed a U-shape, while NTx levels increased significantly during pregnancy. In a multivariate model, the authors observed a significant and positive interaction between NTx and bone lead when plasma lead was used as the outcome variable. Dietary calcium intake was inversely associated with plasma lead. Results for whole blood lead were similar but less pronounced. These results confirm previous evidence that bone resorption increases during pregnancy, with a consequential significant release of lead from bone, constituting an endogenous source of prenatal exposure. They also provide a rationale for testing strategies (e.g., nutritional supplementation with calcium) aimed at decreasing prenatal lead exposure.

  18. Seminal plasma zinc level may be associated with the effect of cigarette smoking on sperm parameters.

    PubMed

    Liu, R-Z; Gao, J-C; Zhang, H-G; Wang, R-X; Zhang, Z-H; Liu, X-Y

    2010-01-01

    The aim of this study was to investigate the effect of cigarette smoking on seminal plasma zinc levels and sperm parameters, and to examine the role of seminal plasma zinc. Semen samples from 79 non-smokers and 68 smokers were obtained. There was a significant decrease in seminal plasma zinc in smokers and a clear correlation between seminal plasma zinc levels and the extent of smoking. Sperm parameters (concentration, motility and morphology) among smokers were significantly lower in comparison to non-smokers. These parameters were also significantly decreased among smokers with abnormal zinc levels, while there was no significant difference between non-smokers with normal zinc and non-smokers with abnormal zinc levels. As previous studies have shown that seminal plasma zinc is associated with a decrease of anti-oxidant defences, seminal plasma zinc could be a contributor to the effects of cigarette smoking on sperm parameters. In conclusion, cigarette smoking can affect sperm parameters and this study may help towards providing a mechanistic explanation.

  19. Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers

    PubMed Central

    Meeter, Lieke H.H.; Patzke, Holger; Loewen, Gordon; Dopper, Elise G.P.; Pijnenburg, Yolande A.L.; van Minkelen, Rick; van Swieten, John C.

    2016-01-01

    Background Pathogenic mutations in the granulin gene (GRN) are causative in 5-10% of patients with frontotemporal dementia (FTD), mostly leading to reduced progranulin protein (PGRN) levels. Upcoming therapeutic trials focus on enhancing PGRN levels. Methods Fluctuations in plasma PGRN (n = 41) and its relationship with cerebrospinal fluid (CSF, n = 32) and specific single nucleotide polymorphisms were investigated in pre- and symptomatic GRN mutation carriers and controls. Results Plasma PGRN levels were lower in carriers than in controls and showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02), plasma only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622 genotypes only partly explained the variability of PGRN levels between subjects. Conclusions Plasma PGRN is relatively stable over 1 week and therefore seems suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN only moderately correlated with CSF PGRN, CSF sampling will additionally be needed in therapeutic trials. PMID:27703466

  20. Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels

    PubMed Central

    Bershad, Anya K.; Kirkpatrick, Matthew G.; Seiden, Jacob A.; de Wit, Harriet

    2015-01-01

    Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”), appears to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of two other “social” drugs on plasma oxytocin levels: methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin. In Study 1, 11 healthy adult volunteers attended three sessions during which they received methamphetamine (10mg or 20mg) or placebo under double blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin were measured at regular intervals throughout the sessions. In Study 2, 8 healthy adult volunteers attended a single session during which they received one beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither drug increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified. PMID:25853370

  1. Seminal plasma HIV-1 RNA concentration is strongly associated with altered levels of seminal plasma interferon-γ, interleukin-17, and interleukin-5.

    PubMed

    Hoffman, Jennifer C; Anton, Peter A; Baldwin, Gayle Cocita; Elliott, Julie; Anisman-Posner, Deborah; Tanner, Karen; Grogan, Tristan; Elashoff, David; Sugar, Catherine; Yang, Otto O; Hoffman, Risa M

    2014-11-01

    Seminal plasma HIV-1 RNA level is an important determinant of the risk of HIV-1 sexual transmission. We investigated potential associations between seminal plasma cytokine levels and viral concentration in the seminal plasma of HIV-1-infected men. This was a prospective, observational study of paired blood and semen samples from 18 HIV-1 chronically infected men off antiretroviral therapy. HIV-1 RNA levels and cytokine levels in seminal plasma and blood plasma were measured and analyzed using simple linear regressions to screen for associations between cytokines and seminal plasma HIV-1 levels. Forward stepwise regression was performed to construct the final multivariate model. The median HIV-1 RNA concentrations were 4.42 log10 copies/ml (IQR 2.98, 4.70) and 2.96 log10 copies/ml (IQR 2, 4.18) in blood and seminal plasma, respectively. In stepwise multivariate linear regression analysis, blood HIV-1 RNA level (p<0.0001) was most strongly associated with seminal plasma HIV-1 RNA level. After controlling for blood HIV-1 RNA level, seminal plasma HIV-1 RNA level was positively associated with interferon (IFN)-γ (p=0.03) and interleukin (IL)-17 (p=0.03) and negatively associated with IL-5 (p=0.0007) in seminal plasma. In addition to blood HIV-1 RNA level, cytokine profiles in the male genital tract are associated with HIV-1 RNA levels in semen. The Th1 and Th17 cytokines IFN-γ and IL-17 are associated with increased seminal plasma HIV-1 RNA, while the Th2 cytokine IL-5 is associated with decreased seminal plasma HIV-1 RNA. These results support the importance of genital tract immunomodulation in HIV-1 transmission.

  2. Plasma D-lactate levels in diagnosis of appendicitis.

    PubMed

    Cağlayan, Fatma; Cakmak, Murat; Cağlayan, Osman; Cavuşoglu, Turgut

    2003-01-01

    We investigated the possible use of D-lactate as a predictor in the diagnosis of appendicitis. C-reactive protein level (CRP) and leukocyte counts were also evaluated. Venous blood D-lactate, CRP, and leukocyte counts were measured preoperatively in 53 patients undergoing surgery for appendicitis, as well as in 20 healthy subjects. Levels of all three parameters in the surgical patients were significantly higher than in the control group (p <.05). Previous studies have shown that venous D-lactate is more specific to the intestine than CPR or leukocyte count. Based on our data, venous D-lactate, which had the lowest false-negative rate among these laboratory parameters, may be a useful diagnostic marker for appendicitis. None of these parameters were helpful in identifying the type of the appendicitis.

  3. Neural correlates of plasma acylated ghrelin level in individuals with major depressive disorder.

    PubMed

    Matsuo, Koji; Nakano, Masayuki; Nakashima, Mami; Watanuki, Toshio; Egashira, Kazuteru; Matsubara, Toshio; Watanabe, Yoshifumi

    2012-09-14

    Anhedonic symptoms, which include loss of pleasure, appetite and motivation, are key symptoms of major depressive disorder (MDD) and are thought to depend on a neural circuit of the mesolimbic system. The neuropeptide ghrelin plays a crucial role in appetite and reward. Little is known, however, about the role of ghrelin in MDD. We examined the association between morphometric change and plasma ghrelin levels in patients with MDD. Twenty-four patients with MDD and 24 healthy control subjects were studied. Plasma concentration of acylated ghrelin was measured after a period of fasting. Using voxel-based morphometry, we found a main effect of ghrelin on the volume of several brain regions. We then compared these regional volumes in patients with MDD versus healthy subjects. We also compared brain volumes between the two groups, controlling for ghrelin level. There was no significant difference in plasma acylated ghrelin level between patients with MDD and healthy subjects. In the MDD group, ghrelin levels positively correlated with the severity of reduced appetite. Ghrelin levels negatively correlated with gray matter volume of the ventral tegmental area (VTA) in the total sample. The patients with MDD showed significantly smaller VTA gray matter volume compared to healthy subjects. Controlling for the plasma acylated ghrelin level, patients with MDD showed significantly smaller gray matter volume of right substantia nigra compared to healthy subjects. Our findings suggest that plasma acylated ghrelin is associated with neural abnormalities of the pleasure/reward system and may be involved in the pathophysiology of MDD.

  4. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1.

    PubMed

    Meltzer, Mirjam E; Lisman, Ton; de Groot, Philip G; Meijers, Joost C M; le Cessie, Saskia; Doggen, Carine J M; Rosendaal, Frits R

    2010-07-08

    Elevated plasma clot lysis time (CLT) increases risk of venous and arterial thrombosis. It is unclear which fibrinolytic factors contribute to thrombosis risk. In 743 healthy control subjects we investigated determinants of CLT. By comparison with 770 thrombosis patients, we assessed plasma levels of fibrinolytic proteins as risk factors for a first thrombosis. Plasminogen activator inhibitor-1 (PAI-1) levels were the main determinants of CLT, followed by plasminogen, thrombin-activatable fibrinolysis inhibitor (TAFI), prothrombin, and alpha2-antiplasmin. Fibrinogen, factor VII, X, and XI contributed minimally. These proteins explained 77% of variation in CLT. Levels of the fibrinolytic factors were associated with thrombosis risk (odds ratios, highest quartile vs lowest, adjusted for age, sex, and body mass index: 1.6 for plasminogen, 1.2 for alpha2-antiplasmin, 1.6 for TAFI, 1.6 for PAI-1, and 1.8 for tissue plasminogen activator [t-PA]). Adjusting for acute-phase proteins attenuated the risk associated with elevated plasminogen levels. The risk associated with increased t-PA nearly disappeared after adjusting for acute-phase proteins and endothelial activation. TAFI and PAI-1 remained associated with thrombosis after extensive adjustment. In conclusion, CLT reflects levels of all fibrinolytic factors except t-PA. Plasminogen, TAFI, PAI-1, and t-PA are associated with venous thrombosis. However, plasminogen and t-PA levels may reflect underlying risk factors.

  5. The effect of glycemic index on plasma glucose and lactate levels during incremental exercise.

    PubMed

    Stannard, S R; Constantini, N W; Miller, J C

    2000-03-01

    Consumption of low glycemic index (GI) foods before submaximal endurance exercise may be beneficial to performance. To test whether this may also be true for high intensity exercise, 10 trained cyclists began an incremental exercise test to exhaustion 65 min after consuming equal carbohydrate portions of glucose (HGI), pasta (LGI), and a noncarbohydrate control (PL). Time to fatigue did not differ significantly (p = 0.05) between treatments. Plasma glucose concentration was significantly lower after LGI vs. HGI from 15 to 45 min of rest postprandial. During exercise, plasma glucose concentration was significantly lower after HGI vs. LGI from 200 W until exhaustion. Plasma lactate concentration following HGI was significantly higher than PL from 30 min of rest postprandial through to the end of the 200-W workload. Plasma lactate concentration following LGI was significantly lower than after HGI from 45 min of rest postprandial through to the end of the 100-W workload. At higher exercise intensities, there was no significant difference in plasma lactate levels between treatments. These findings suggest that a high GI carbohydrate meal (1 g/kg body wt) 65 min prior to exercise decreases plasma glucose and increases plasma lactate levels compared to a low GI meal, but not enough to be detrimental to incremental exercise performance.

  6. Genetic effects of an air discharge plasma on Staphylococcus aureus at the gene transcription level

    NASA Astrophysics Data System (ADS)

    Xu, Zimu; Wei, Jun; Shen, Jie; Liu, Yuan; Ma, Ronghua; Zhang, Zelong; Qian, Shulou; Ma, Jie; Lan, Yan; Zhang, Hao; Zhao, Ying; Xia, Weidong; Sun, Qiang; Cheng, Cheng; Chu, Paul K.

    2015-05-01

    The dynamics of gene expression regulation (at transcription level) in Staphylococcus aureus after different doses of atmospheric-pressure room-temperature air plasma treatments are investigated by monitoring the quantitative real-time polymerase chain reaction. The plasma treatment influences the transcription of genes which are associated with several important bio-molecular processes related to the environmental stress resistance of the bacteria, including oxidative stress response, biofilm formation, antibiotics resistance, and DNA damage protection/repair. The reactive species generated by the plasma discharge in the gas phase and/or induced in the liquid phase may account for these gene expression changes.

  7. Gonadal Development, Spawning and Plasma Sex Steroid Levels of the Indoor Cultured Grunt, Hapalogenys nitens

    PubMed Central

    Kang, Hee Woong; Cho, Jae-Kwon; Son, Maeng-Hyun; Park, Jong Youn; Hong, Chang Gi; Chung, Jae Seung; Chung, Ee-Yung

    2015-01-01

    The gonadosomatic index (GSI), gonadal development and changes in hormones in plasma level of the indoor cultured grunt (Hapalogenys nitens) were investigated by histological study from August 2011 to October 2012. The GSI showed similar trends with gonad developmental stages during the culture periods. Changes in plasma level of estradiol-17β of female H. nitens reached the highest value before the spawning period, and seasonal changes in plasma level of estradiol-17β were similar in trends of oocyte developments and GSI changes. Testosterone levels of male H. nitens reached the highest value before and after the spent stage. Ovarian developmental stages of H. nitens could be classified into early growing stage, late growing stage, mature stage, ripe and spawning stage, recovery and resting stage. The testicular developmental stages could be divided into growing stage, mature stage, ripe and spent stage, and recovery and resting stage. PMID:25949208

  8. Influences of ACTH 4-10 on event-related potentials reflecting attention in man.

    PubMed

    Born, J; Fehm-Wolfsdorf, G; Voigt, K H; Fehm, H L

    1987-01-01

    The present paper is concerned with effects of the 4-10 sequence of the endogenous ACTH on electrophysiological measures of attention in humans. It was attempted to replicate previous findings of an impaired selective attention following administration of an analog of ACTH 4-9. The effect of this analog had been found to dominate in the beginning of the blocks of an attention task, but to fade away with time on task. In the present study, fourteen male students were tested in a dichotic listening paradigm, 40 min after intranasal application of either 0.4 mg ACTH 4-10, or placebo. Averaged auditory evoked potentials (AEPs) to attended and inattended tone pips, EEG power spectra, heart rate and blood pressure, and behavioral performance were measured during task performance. ACTH 4-10 appeared to slightly impair selective attention as indicated by AEP responses. In particular, the positive shift of the AEP waveforms to inattended stimuli was reduced at the beginning of each block of tone pips under ACTH 4-10. The pattern of actions resembled the effects observed after administration of the more potent synthetic analog of ACTH 4-9 in the previous experiment. Effects of ACTH 4-10 on the AEPs to inattended stimuli, however, differed from influences of the synthetic analog in that they did not affect a rather wide latency range but concentrated on the latency range of the P200 component.

  9. Naloxone inhibits and morphine potentiates the adrenal steroidogenic response to ACTH

    NASA Technical Reports Server (NTRS)

    Heybach, J. P.; Vernikos, J.

    1981-01-01

    The administration of morphine to hypophysectomized rats potentiated the steroidogenic response of the adrenal cortex to exogenous adrenocorticotrophic hormone (ACTH) in a dose-dependent fashion. Conversely, the opiate antagonist naloxone inhibited the adrenal response to ACTH. Naloxone pretreatment also antagonized the potentiating effect of morphine on ACTH-induced steroidogenesis in a dose-dependent manner. Neither morphine nor naloxone, administered to hypophysectomized rats, had any direct effect on adrenal steroidogenesis. These adrenal actions were stereospecific since neither the (+)-stereoisomer of morphine, nor that or naloxone, had any effect on the adrenal response to ACTH. The administration of human beta-endorphin to hypophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose-dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone-secreting cells of the adrenal cortex.

  10. [Malondialdehyde and ceruloplasmin levels in plasma of patients with alimentary toxic infection].

    PubMed

    Nagoev, B S; Marzhokhova, M Iu

    2004-07-01

    The content of malonic dialdehyde and of ceruloplasmin in blood plasma was studied, as an indicator of the prooxidant-antioxidant system, in 84 patients, aged 21 to 63, with alimentary toxicoinfection. A higher level of malonic dialdehyde and a lower level of ceruloplasmin were detected, which depended on a disease stage and on a severity of the clinical course and pathologic progression.

  11. Preliminary results on plasma progesterone levels during pregnancy and superfetation in the hare, Lepus Europaeus.

    PubMed

    Caillol, M; Martinet, L

    1976-01-01

    Peripheral plasma progesterone levels were studied in pregnant hares. A rise occurred at the beginning of pregnancy, followed by a plateau from Days 10 to 35, and then a drop during the days just before parturition. No significant differences were noted between progesterone levels in pregnancies initiated at the pre-partum oestrus and those from other oestrous periods.

  12. Plasma Amino Acid Levels in Children with Autism and Their Families.

    ERIC Educational Resources Information Center

    Aldred, Sarah; Moore, Kieran M.; Fitzgerald, Michael; Waring, Rosemary H.

    2003-01-01

    Plasma amino acid levels were measured in autistic (n=12), Asperger syndrome (n=11) patients, their parents and siblings. Patients with autism or Asperger syndrome and their siblings and parents all had raised glutamic acid, phenyalanine, asparagine, tyrosine, alanine, and lysine levels than age-matched controls. Results suggest dysregulated amino…

  13. Plasma BDNF Levels Vary in Relation to Body Weight in Females

    PubMed Central

    Pillai, Anilkumar; Bruno, Davide; Sarreal, Antero S.; Hernando, Raymundo T.; Saint-Louis, Leslie A.; Nierenberg, Jay; Ginsberg, Stephen D.; Pomara, Nunzio; Mehta, Pankaj D.; Zetterberg, Henrik; Blennow, Kaj; Buckley, Peter F.

    2012-01-01

    Brain derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression as well as neuropsychiatric and neurodegenerative disorders. Recent studies show a role of BDNF in energy metabolism and body weight regulation. We examined BDNF levels in plasma and cerebrospinal fluid (CSF) samples from age matched elderly depressed and control subjects. Also, the association of BDNF levels with age, gender, body weight, body mass index (BMI), and cognitive performance was evaluated. We did not find any significant differences in plasma and CSF BDNF levels between depressed and control subjects. Plasma BDNF levels were negatively correlated with age (but not with BMI and body weight), when analyses were performed including both depressed and control subjects. A significant reduction in plasma BDNF levels was observed in females as compared to male subjects, and the change in BDNF levels were significantly and positively related to body weight in females. Furthermore, significant increases in Total Recall and Delayed Recall values were found in females as compared to males. In conclusion, the lower BDNF levels observed in females suggest that changes in peripheral BDNF levels are likely secondary to an altered energy balance. However, further studies using larger sample size are warranted. PMID:22768299

  14. Effect of Streptozotocin on Plasma Insulin Levels of Rats and Mice: A Meta-analysis Study

    PubMed Central

    Koksal, Burcu

    2015-01-01

    BACKGROUND: In the studies focusing on diabetic organisms, Streprozotocine (STZ) is a frequently used agent to induce diabetes in rats and mice. However the current studies do not represent practical importance of their statistical findings. For showing practical importance of the differences in plasma insulin levels of diabetic rats and mice induced by STZ, there should be a statistical synthesis regarding statistical findings of the studies. AIM: The purpose of this study is to make a meta-analysis of the studies on the effect of STZ on plasma insulin levels in diabetic rats and mice. MATERIALS AND METHODS: In this study 39 effect sizes (37 studies) about levels of plasma insulin were analyzed by calculating individual effect sizes (d) and mean effect size. RESULTS: The effect sizes were between -13.7 and +65.3 and the mean effect size value (+9.33) represented a large effect indicating that STZ was an effective agent to significantly decrease plasma insulin levels of diabetic rats and mice. CONCLUSION: It can be said that the differences in plasma insulin levels between STZ-applied and no application groups has a practical importance in making animal model of diabetes. PMID:27275254

  15. Effect of Bu-zhong-yi-qi-tang on seminal plasma cytokine levels in patients with idiopathic male infertility.

    PubMed

    Furuya, Y; Akashi, T; Fuse, H

    2004-01-01

    Twenty-two idiopathic infertile patients were treated with Oriental herbal medicine, Bu-zhong-yi-qi-tang (Hochu-ekki-to). Seminal plasma sFas level elevated significantly after herb administration. There was an inverse correlation between seminal plasma IL-6 level and sperm concentration before treatment. After the administration of herb seminal plasma, sFas levels significantly correlated with sperm concentration. Seminal plasma IL-8 level did not change. Certain kinds of cytokine in the seminal plasma might play some role in improving semen quality with treatment.

  16. Plasma Folate and Vitamin B12 Levels in Patients with Hepatocellular Carcinoma.

    PubMed

    Cui, Lian-Hua; Quan, Zhen-Yu; Piao, Jin-Mei; Zhang, Ting-Ting; Jiang, Meng-Hui; Shin, Min-Ho; Choi, Jin-Su

    2016-06-30

    Folate and vitamin B12 involved in the one-carbon metabolism may play a key role in carcinogenesis and progression of hepatocellular carcinoma (HCC) through influencing DNA integrity. The purpose of this study is to evaluate the association of plasma folate and vitamin B12 levels with HCC in a case-control study on 312 HCC patients and 325 cancer-free controls. Plasma concentrations of folate and vitamin B12 in all the subjects were measured by electrochemiluminescence immunoassay. Meanwhile, the information of HCC patients' clinical characteristics including tumor-node-metastasis (TNM) stage, tumor size and tumor markers were collected. The patients of HCC had significantly lower folate levels than those of controls; there was no significant difference in the mean of plasma vitamin B12 levels. We also observed an inverse association between the levels of plasma folate and HCC: the adjusted odds ratios (OR) (95% confidence intervals (CI)) of HCC from the highest to lowest quartile of folate were 0.30 (0.15-0.60), 0.33 (0.17-0.65), and 0.19 (0.09-0.38). Compared to the subjects in the lowest quartile of plasma vitamin B12, only the subjects in the highest quartile of vitamin B12 exhibited a significant positive relationship with HCC, the adjusted OR was 2.01 (95% CI, 1.02-3.98). HCC patients with Stage III and IV or bigger tumor size had lower folate and higher vitamin B12 levels. There was no significant difference in the mean plasma folate levels of the HCC cases in tumor markers status (AFP, CEA and CA19-9 levels), whereas patients with higher CEA or CA19-9 levels retained significantly more plasma vitamin B12 than those with normal-CEA or CA19-9 level. In conclusion, plasma folate and vitamin B12 levels could be associated with HCC, and might be used as predictors of clinical characteristics of HCC patients. However, further prospective studies are essential to confirm the observed results.

  17. The role of ACTH and glucocorticoids in nonenzymatic fibrinolysis during immobilization stress in animals

    NASA Technical Reports Server (NTRS)

    Kudryashov, B. A.; Shapiro, F. B.; Lomovskaya, E. G.; Lyapina, L. A.

    1980-01-01

    The role of the altered hormonal status of an organism in the activation of the anticoagulative system during stress is investigated. The 30 minute immobilization stress was shown to raise significantly the nonenzymatic fibrinolytic activity of blood in rats. Combined with adrenocorticotropin (ACTH) the effect is still greater. Intravenous administration of 0.2 m1 0.01 percent solution of protamine sulphate prevented the nonenzymatic fibrinolysis induced by the stress. Administration of ACTH after protomine sulphate again raised the fibrinolysis. This suggests that ACTH stimulates the release of heparin.

  18. Macadamia nut consumption lowers plasma total and LDL cholesterol levels in hypercholesterolemic men.

    PubMed

    Garg, Manohar L; Blake, Robert J; Wills, Ron B H

    2003-04-01

    This study was conducted to assess the cholesterol-lowering potential of macadamia nuts. Seventeen hypercholesterolemic men (mean age 54 y) were given macadamia nuts (40-90 g/d), equivalent to 15% energy intake, for 4 wk. Plasma total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and homocysteine concentrations and the fatty acid composition of plasma lipids were determined before and after treatment. Plasma MUFA 16:1(n-7), 18:1(n-7) and 20:1(n-9) were elevated after intervention with macadamia nuts. Plasma (n-6) and (n-3) PUFA concentrations were unaffected by macadamia nut consumption. Plasma total cholesterol and LDL cholesterol concentrations decreased by 3.0 and 5.3%, respectively, and HDL cholesterol levels increased by 7.9% in hypercholesterolemic men after macadamia nut consumption. Plasma triglyceride and homocysteine concentrations were not affected by treatment. Macadamia nut consumption was associated with a significant increase in the relative intake of MUFA and a reduced relative intake of saturated fatty acids and PUFA. This study demonstrates that macadamia nut consumption as part of a healthy diet favorably modifies the plasma lipid profile in hypercholesterolemic men despite their diet being high in fat.

  19. The effect of rapeseed meal and methimazole on levels of plasma hormones in growing broiler cockerels.

    PubMed

    Chiasson, R B; Sharp, P J; Klandorf, H; Scanes, C G; Harvey, S

    1979-11-01

    The effects of feeding a heat treated rapeseed meal, which has goitrogenic properties, on the concentrations of plasma pituitary and thyroid gland hormones was investigated in broiler cockerels of between 3 and 10 weeks of age. For purposes of comparison, two other groups were included in the study; one was fed the goitrogen, methimazole, and the other a normal control diet. The hormones measured were thyroxine (T4), triiodothyronine (T3), growth hormone (GH), prolactin, and luteinizing hormone (LH). In birds fed methimazole the thyroid glands were greatly enlarged, the concentrations of plasma T4 and T3 were depressed and the concentrations of growth hormone, prolactin, and LH were elevated. The high level of plasma LH in the birds fed methimazole was not due to the absence of sufficient concentrations of plasma testosterone to exert a negative feedback effect. Although the inclusion of rapeseed meal in the diet caused the thyroid glands to enlarge, the concentrations of all the hormones studied, with the exception of T3, were similar to those in the control birds. However, there was a tendency, which was more pronounced in birds of between 3 and 5 weeks of age, for rapeseed meal to depress the concentrations of plasma T4, GH, and LH and to increase the concentration of plasma prolactin. The most significant observation was that between 3 and 5 weeks of age the inclusion of rapeseed meal in the diet significantly (P less than .001) depressed the concentration of plasma T3.

  20. Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men.

    PubMed

    Colagar, Abasalt Hosseinzadeh; Marzony, Eisa Tahmasbpour; Chaichi, Mohammad Javad

    2009-02-01

    Zinc has antioxidative properties and plays an important role in scavenging reactive oxygen species. We hypothesized that in the absence of Zn, the possibility of increased oxidative damage exists that would contribute to poor sperm quality. Therefore, measurement of seminal Zn in the seminal plasma of males with a history of subfertility or idiopathic infertility is necessary and can be helpful in fertility assessment. The primary objective of the present study was to assess the relationship between Zn levels in seminal plasma with sperm quality in fertile and infertile men. Semen samples were provided by fertile (smoker [n = 17], nonsmoker [n = 19]) and infertile men (smoker [n = 15], nonsmoker [n = 21]). After semen analysis, concentrations of Zn, Mg, Ca, Na, and K in the seminal plasma of all groups were determined by atomic absorption spectroscopy. Element concentrations in seminal plasma of all groups were in the order Na > K > Ca > Zn > Mg. Fertile subjects, smoker or not, demonstrated significantly higher seminal Zn levels than any infertile group (P < .001). A trend was observed for a lower Zn levels in seminal plasma of smokers compared with nonsmokers. Seminal Zn in fertile and infertile (smokers or nonsmokers) males correlated significantly with sperm count (P < .01) and normal morphology of sperm (P < .001). There was a significantly positive correlation between seminal Zn with Ca (P < .01) and K (P < .01) levels in all specimens. In conclusion, poor Zn nutrition may be an important risk factor for low quality of sperm and idiopathic male infertility.

  1. Inverse association of plasma vanadium levels with newly diagnosed type 2 diabetes in a Chinese population.

    PubMed

    Wang, Xia; Sun, Taoping; Liu, Jun; Shan, Zhilei; Jin, Yilin; Chen, Sijing; Bao, Wei; Hu, Frank B; Liu, Liegang

    2014-08-15

    Vanadium compounds have been proposed to have beneficial effects on the pathogenesis and complications of type 2 diabetes. Our objective was to evaluate the association between plasma vanadium levels and type 2 diabetes. We performed a case-control study involving 1,598 Chinese subjects with or without newly diagnosed type 2 diabetes (December 2004-December 2007). Cases and controls were frequency-matched by age and sex. Plasma vanadium concentrations were measured and compared between groups. Analyses showed that plasma vanadium concentrations were significantly lower in cases with newly diagnosed type 2 diabetes than in controls (P = 0.001). Mean plasma vanadium levels in participants with and without diabetes were 1.0 μg/L and 1.2 μg/L, respectively. Participants in the highest quartile of plasma vanadium concentration had a notably lower risk of newly diagnosed type 2 diabetes (odds ratio = 0.26, 95% confidence interval: 0.19, 0.35; P < 0.001), compared with persons in the lowest quartile. The trend remained significant after adjustment for known risk factors and in further stratification analyses. Our results suggested that plasma vanadium concentrations were inversely associated with newly diagnosed type 2 diabetes in this Chinese population.

  2. Assessing plasma levels of selenium, copper, iron and zinc in patients of Parkinson's disease.

    PubMed

    Zhao, Hai-Wen; Lin, Jie; Wang, Xue-Bao; Cheng, Xing; Wang, Jian-Yong; Hu, Bei-Lei; Zhang, Yan; Zhang, Xiong; Zhu, Jian-Hong

    2013-01-01

    Trace elements have been recognized to play an important role in the development of Parkinson's disease (PD). However, it is difficult to precisely identify the relationship between these elements and the progression of PD because of an insufficient number of patients. In this study, quantifications of selenium (Se), copper (Cu), iron (Fe) and zinc (Zn) by atomic absorption spectrophotometry were performed in plasma from 238 PD patients and 302 controls recruited from eastern China, which is so far the largest cohort of PD patients and controls for measuring plasma levels of these elements. We found that plasma Se and Fe concentrations were significantly increased whereas Cu and Zn concentrations decreased in PD patients as compared with controls. Meanwhile, these four elements displayed differential changes with regard to age. Linear and logistic regression analyses revealed that both Fe and Zn were negatively correlated with age in PD patients. Association analysis suggests that lower plasma Se and Fe levels may reduce the risk for PD, whereas lower plasma Zn is probably a PD risk factor. Finally, a model was generated to predict PD patients based on the plasma concentrations of these four trace elements as well as other features such as sex and age, which achieved an accuracy of 80.97±1.34% using 10-fold cross-validation. In summary, our data provide new insights into the roles of Se, Cu, Fe and Zn in PD progression.

  3. Effects of cytostatic drugs on plasma level and renal excretion of beta-acetyldigoxin.

    PubMed

    Kuhlmann, J; Zilly, W; Wilke, J

    1981-10-01

    Mucosal defects decrease digoxin absorption in patients with malabsorption syndromes. Since the intestinal mucosa can be damaged by cytostatic drugs, we investigated their effects on digoxin plasma levels and urinary digoxin excretion. In six patients with malignant lymphoma who received 0.8 mg beta-acetyldigoxin before and 24 hr after treatment with a combination of cyclophosphamide, oncovin, procarbazine, and prednisone (COPP) or cyclophosphamide, oncovin, and prednisone (COP), plasma digoxin concentrations were measured 0 to 8 hr after the dose and areas under the plasma concentration-time curves were calculated. In 15 patients on 0.3 mg of beta-acetyldigoxin daily, plasma glycoside concentrations and renal excretion were measured daily before and after COPP, COP, cyclophosphamide, oncovin, cytosine-arabinosine, and prednisone (COAP), or adriamycin, bleomycin, and prednisone (ABP) treatment schemes. The diminished steady-state glycoside plasma concentrations and daily renal glycoside excretion during the 24 to 168 hr after the cytostatic drug established reversible impairment of digoxin absorption. The delayed time to peak after a single dose of digoxin during cytostatic drug therapy shows that extent and rate of digoxin absorption are reduced. To maintain adequate control of digoxin therapy in patients treated with cytostatic drugs, plasma levels should be monitored.

  4. Plasma and urine DNA levels are related to microscopic hematuria in patients with bladder urothelial carcinoma.

    PubMed

    de Almeida, Eduardo Ferreira Pedroso; Abdalla, Tomás Elias; Arrym, Tiago Pedromonico; de Oliveira Delgado, Pamela; Wroclawski, Marcelo Langer; da Costa Aguiar Alves, Beatriz; de S Gehrke, Flávia; Azzalis, Ligia Ajaime; Alves, Sarah; Tobias-Machado, Marcos; de Lima Pompeo, Antonio Carlos; Fonseca, Fernando Luiz Affonso

    2016-11-01

    a) Objective: An increase in cell-free DNA was observed in the plasma of many cancer patients. This major biomarker can be used to differentiate patients with malignant neoplasms from those with benign neoplasms or healthy patients. Depending on the characteristic of the tumor, there are qualitative variations in the circulating cell-free DNA. Today, studies on the concentration of fragments of circulating cell-free DNA and their respective sizes in patients with bladder cancer are not plentiful in the literature. A 100% effective plasma tumor marker, which would help in the diagnosis and follow-up of bladder cancer, is yet to be developed; therefore, cell-free DNA levels in the plasma may represent a valuable biomarker for the diagnosis, prognosis and follow-up of patients with this type of tumor. b) Design and methods: In this study we analyze the kinetics of plasma and urine DNA concentrations in patients with bladder cancer, relating them to the other clinical laboratory variables. c) Results: Patients with hematuria showed a positive correlation with urine DNA. d) Conclusion: An increase in plasma and urine DNA was unprecedentedly reported over time, a fact that may come in handy in the prognosis of patients. Furthermore, microscopic haematuria is correlated with plasma and urinary DNA levels.

  5. Significance of plasma lead levels in normal and lead-intoxicated children.

    PubMed

    Rosen, J F; Trinidad, E E

    1974-05-01

    Plasma lead (Pb) levels have been measured in normal and lead-intoxicated children, newborns, and children with sickle cell disease. The results in all groups were contant over a wide range of red cell Pb concentration. These results support the thesis that the red cell represents a large repository for Pb, maintaining plasma Pb concentration within closely defined limits, and that methods other than measurements of plasma Pb will be necessary to uncover a presumably dynamic transport system between red cell and plasma. Indeed, we have demonstrated in vitro that ionized calcium (Ca(2+)) lowers red cell Pb content according to a linear dose-response curve. Ca(2+) may thereby control Pb transport from red cell to plasma, and fluctuations in the concentration of Ca(2+) in serum and extracellular fluid may influence the toxic activities of Pb. In bone organ culture, changes in the concentration of Ca(2+) and phosphate in the medium alter the release of previously incorporated (210)Pb from fetal rat bones in response to parathyroid hormone (PTH). Therefore, both PTH and the ionic milieu of the medium apparently regulate bone Pb metabolism.We would expect that understanding further the dynamics of Pb transport in plasma and bone may lead to a more exact definition of the real hazards of low level Pb toxicity in children.

  6. Plasma fibrinogen levels are correlated with postoperative distant metastasis and prognosis in esophageal squamous cell carcinoma.

    PubMed

    Zhang, Danhong; Zhou, Xia; Bao, Wuan; Chen, Ying; Cheng, Lei; Qiu, Guoqin; Sheng, Liming; Ji, Yongling; Du, Xianghui

    2015-11-10

    This study investigated the correlation of preoperative plasma fibrinogen level with distant metastasis and prognosis in esophageal squamous cell carcinoma (ESCC). A total of 255 patients with ESCC who underwent surgery in Zhejiang cancer hospital (Hangzhou, China), between October 2006 and December 2009, were evaluated in this retrospective study. Population controls were selected from a pool of cancer-free subjects in the same region. Each patient and cancer-free people provided 3-mL pretreatment blood. Plasma fibrinogen level was measured by the Clauss method. The effects of hyperfibrinogenemia on locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were assessed using Kaplan-Meier analysis. Independent prognostic factors were identified in the multivariate Cox analysis. The proportion of hyperfibrinogenemia was higher in ESCC patients than those in controls (40.4% vs 13.6%). Subjects with hyperfibrinogenemia had a significantly higher risk of ESCC than those with normal plasma fibrinogen level (adjust OR = 4.61; 95% CI = 3.02-7.01, P < 0.001) after adjusted for age, sex and smoking status. The Kaplan-Meier curves showed that patients with hyperfibrinogenemia had worse DMFS, RFS and OS (P < 0.001). Tumor length, lymph node metastasis and plasma fibrinogen level were independent prognostic factors of ESCC (P < 0.05). Increased plasma fibrinogen level was significantly associated with elevated risk of ESCC. Preoperative plasma fibrinogen level was a predictor of distant metastasis and independently associated with prognosis of patients with ESCC.

  7. Effects of Caffeine Supplementation on Plasma and Blood Mononuclear Cell Interleukin-10 Levels After Exercise.

    PubMed

    Tauler, Pedro; Martinez, Sonia; Martinez, Pau; Lozano, Leticia; Moreno, Carlos; Aguiló, Antoni

    2016-02-01

    This study compared the response of interleukin (IL)-10, and also of IL-6 and IL-12 p40, to exercise and caffeine supplementation between plasma and blood mononuclear cells (BMNCs). Participants in the study (n = 28) were randomly allocated in a double-blind fashion to either caffeine (n = 14) or placebo (n = 14) treatments. One hour before completing a 15-km run competition, athletes took 6 mg/kg body mass of caffeine or a placebo. Plasma and BMNCs were purified from blood samples taken before and after competition. Concentrations of interleukins (IL-10, IL-6, and IL-12 p40), cyclic adenosine monophosphate (cAMP), caffeine, adrenaline, and cortisol were measured in plasma. IL-10, IL-6, and IL-12 p40 and cAMP levels were also determined in BMNCs. Exercise induced significant increases in IL-6 and IL-10 plasma levels, with higher increases in the caffeine-supplemented group. After 2-hr recovery, these levels returned to almost preexercise values. However, no effect of caffeine on BMNC cytokines was observed. IL-10, IL-6, and IL-12 p40 levels in BMNCs increased mainly at 2 hr postexercise. cAMP levels increased postexercise in plasma and after recovery in BMNCs, but no effects of caffeine were observed. In conclusion, caffeine did not modify cytokine levels in BMNCs in response to exercise. However, higher increases of IL-10 were observed in plasma after exercise in the supplemented participants, which could suppose an enhancement of the anti-inflammatory properties of exercise.

  8. Plasma D-lactic acid level: a useful marker to distinguish perforated from acute simple appendicitis.

    PubMed

    Demircan, Mehmet; Cetin, Selma; Uguralp, Sema; Sezgin, Nurzen; Karaman, Abdurrahman; Gozukara, Engin M

    2004-10-01

    Early diagnosis of perforated appendicitis is important for reducing morbidity rates. The aim of this study was to determine the value and utility of plasma D-lactic acid levels in identifying the type of appendicitis. In this clinical study, plasma D-lactic acid levels were assessed in 44 consecutive paediatric patients (23 with acute appendicitis, 21 with perforated appendicitis) before laparotomy. D-lactic acid levels were determined by an enzymatic spectrophotometric technique using a D-lactic acid dehydrogenase kit. Patients with perforated appendicitis had higher D-lactic acid levels (3.970 +/- 0.687 mg/dL) than patients in the control group (0.478 +/- 0.149 mg/dL) and patients with acute appendicitis (1.409 +/- 0.324 mg/dL; p < 0.05). For a plasma D-lactic acid level greater than 2.5 mg/dL, the sensitivity and specificity of the D-lactic acid assay were 96% and 87%, respectively. The positive predictive value was 87%, the negative predictive value was 96%, and the diagnostic value was 91%. These results suggest that the measurement of plasma D-lactic acid levels may be a useful adjunct to clinical and radiological findings in distinguishing perforated from acute non-perforated appendicitis in children.

  9. Diurnal Variation in Oral Glucose Tolerance: Blood Sugar and Plasma Insulin Levels Morning, Afternoon, and Evening

    PubMed Central

    Jarrett, R. J.; Baker, I. A.; Keen, H.; Oakley, N. W.

    1972-01-01

    Twenty-four subjects received three oral glucose tolerance tests, in the morning, afternoon, and evening of separate days. The mean blood sugar levels in the afternoon and evening tests were similar, and they were both significantly higher than those in the morning test. Plasma immunoreactive insulin levels, however, were highest in the morning test. The pattern of insulin levels during the afternoon and evening tests resembled that described as typical of maturity-onset diabetes. PMID:5058728

  10. Assays to measure nanomolar levels of the renin inhibitor CGP 38 560 in plasma

    SciTech Connect

    Cumin, F.; de Gasparo, M.; Wood, J.M.; Schnell, C.; Frueh, F.; Graf, P. )

    1989-10-01

    A radioinhibitor binding assay and an enzyme inhibition assay have been developed to measure plasma levels of CGP 38 560, a potent human renin inhibitor. The detection limit of the assays was between 0.5 and 1 pmol/ml. There was a good correlation (r = 0.989) between the two assays for the measurement of human plasma spiked with CGP 38 560 in concentrations from 1.9 nM to 12 microM. Intra-assay variability was 6.1-17.3% and 4.4-27.2% for the radioinhibitor binding assay and the enzyme inhibition assay, respectively. Interassay variability was 6.0-28.2% and 3.8-28.4% for the radioinhibitor binding assay and the enzyme inhibition assay, respectively. Blood samples were collected during a pharmacological study performed in normotensive human volunteers on an unrestricted diet who were infused during a 30-minute period with CGP 38 560 A (50 micrograms/kg). Similar values for the concentrations of renin inhibitor in plasma were obtained with the radioinhibitor binding assay and the enzyme inhibitor assay, and there was a significant correlation between values obtained with the two different methodologies (r = 0.94). The plasma levels of renin inhibitor reached a maximum at the end of infusion and then decreased rapidly, indicating a short plasma half-life. The changes in biochemical parameters, plasma renin activity, and plasma concentration of active renin could be related to the concentrations of CGP 38 560 measured in the plasma.

  11. Experimental relationships between levels of corticosterone in plasma and feathers in a free-living bird.

    PubMed

    Fairhurst, Graham D; Marchant, Tracy A; Soos, Catherine; Machin, Karen L; Clark, Robert G

    2013-11-01

    Integrated measures of corticosterone (CORT), such as from feathers (CORTf), have intuitive appeal because they incorporate both the duration and amplitude of glucocorticoid secretion. An association between CORTf and plasma CORT has never been shown in wild birds, and it is unclear as to when and whether these measures should be correlated, given that they are fundamentally different yet related measures of physiology. We hypothesized that CORTf should correlate with instantaneous measurements of plasma CORT when the latter reflect sustained changes in the activity of the hypothalamic-pituitary-adrenal (HPA) axis. To test this, we experimentally manipulated levels of plasma CORT in wild nestling tree swallows (Tachycineta bicolor) using 5 day time-release CORT pellets, and measured plasma CORT and growth parameters before, during and at the end of hormone manipulation (days 7, 9 and 11 post-hatch, respectively). CORTf and plasma CORT were significantly positively related only when the latter was at its highest and most variable among individuals (day 9). A similar relationship was expected at day 11, but plasma CORT had returned to near-original levels. Nestlings with higher CORTf were smaller, lighter and less likely to fledge, but we did not detect seasonal effects on CORTf. Our results clearly demonstrate that CORTf from free-living birds can reflect plasma CORT, but correlations may not always be expected, especially if elevations in plasma CORT are relatively modest and of short duration. Our work suggests that CORTf is best used to study the activity of the HPA axis over relatively long time frames and can be used effectively to advance avian ecology.

  12. Plasma Levels of Soluble Interleukin 1 Receptor Accessory Protein Are Reduced in Obesity

    PubMed Central

    Attard, Chantal; Kulkarni, Hemant; Cummings, Nik; Diego, Vincent P.; Carless, Melanie A.; Shields, Katherine A.; Johnson, Matthew P.; Kowlessur, Sudhir; Dyer, Thomas D.; Comuzzie, Anthony G.; Almasy, Laura; Zimmet, Paul; Moses, Eric K.; Göring, Harald H. H.; Curran, Joanne E.; Blangero, John; Jowett, Jeremy B. M.

    2014-01-01

    Context: Adipokines actuate chronic, low-grade inflammation through a complex network of immune markers, but the current understanding of these networks is incomplete. The soluble isoform of the IL-1 receptor accessory protein (sIL1RAP) occupies an important position in the inflammatory pathways involved in obesity. The pathogenetic and clinical influences of sIL1RAP are unknown. Objective: The objective of the study was to elucidate whether plasma levels of sIL1RAP are reduced in obesity, using affluent clinical, biochemical, and genetic data from two diverse cohorts. Design, Setting, and Participants: The study was conducted in two cohorts: the San Antonio Family Heart Study (n = 1397 individuals from 42 families) and South Asians living in Mauritius, n = 230). Main Outcome Measures: Plasma sIL1RAP levels were measured using an ELISA. The genetic basis of sIL1RAP levels were investigated using both a large-scale gene expression profiling study and a genome-wide association study. Results: A significant decrease in plasma sIL1RAP levels were observed in obese subjects, even after adjustment for age and sex. The sIL1RAP levels demonstrated a strong inverse association with obesity measures in both populations. All associations were more significant in females. Plasma sIL1RAP levels were significantly heritable, correlated with IL1RAP transcript levels (NM_134470), showed evidence for shared genetic influences with obesity measures and were significantly associated with the rs2885373 single-nucleotide polymorphism (P = 6.7 × 10−23) within the IL1RAP gene. Conclusions: Plasma sIL1RAP levels are reduced in obesity and can potentially act as biomarkers of obesity. Mechanistic studies are required to understand the exact contribution of sIL1RAP to the pathogenesis of obesity. PMID:24915116

  13. PLASMA OXYTOCIN LEVELS PREDICT SOCIAL CUE RECOGNITION IN INDIVIDUALS WITH SCHIZOPHRENIA

    PubMed Central

    Strauss, Gregory P.; Keller, William R.; Koenig, James I.; Gold, James M.; Frost, Katherine H.; Buchanan, Robert W.

    2015-01-01

    Lower endogenous levels of the neuropeptide oxytocin may be an important biological predictor of social cognition impairments in schizophrenia (SZ). Prior studies have demonstrated that lower-level social cognitive processes (e.g., facial affect perception) are significantly associated with reduced plasma oxytocin levels in SZ; however, it is unclear whether higher-level social cognition, which requires inferential processes and knowledge not directly presented in the stimulus, is associated with endogenous oxytocin. The current study explored the association between endogenous oxytocin levels and lower- and higher-level social cognition in 40 individuals diagnosed with SZ and 22 demographically matched healthy controls (CN). All participants received the Social Cue Recognition Test (SCRT), which presents participants with videotaped interpersonal vignettes and subsequent true/false questions related to concrete or abstract aspects of social interactions in the vignettes. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ and CN did not differ on SCRT hits, but SZ had more false positives and lower sensitivity scores than CN. Higher plasma oxytocin levels were associated with better sensitivity scores for abstract items in CN and fewer false positives for concrete items in individuals with SZ. Findings indicate that endogenous oxytocin levels predict accurate encoding of lower-level socially relevant information in SZ. PMID:25673435

  14. Plasma miRNA levels correlate with sensitivity to bone mineral density in postmenopausal osteoporosis patients.

    PubMed

    Li, Hongqiu; Wang, Zhe; Fu, Qin; Zhang, Jing

    2014-11-01

    In our study, we detect the levels of three micro-RNAs (miRNAs; miR-21, miR-133a and miR-146a) in the plasma of 120 Chinese postmenopausal women who were divided into three groups (normal, osteopenia and osteoporosis) according to the T-scores. Downregulation of miR-21, as well as upregulation of miR-133a, was validated in the plasma of osteoporosis and osteopenia patients versus the normal group. The difference in expression regarding the miR-146a level in plasma among the three groups was not significant (p > 0.01). The circulating miRNA expression levels and bone mineral density (BMD) were examined during a multiple correlation analysis as a dependent variable after adjusting for age, weight and height. We have demonstrated that specific miRNAs species are significantly changed in the plasma of osteoporosis and osteopenia patients and correlated with the BMD. Our study suggested a potential use of miR-21 and miR-133a as sensitive and plasma biomarkers for postmenopausal osteoporosis.

  15. Genetic variants in ABCA1 promoter affect transcription activity and plasma HDL level in pigs.

    PubMed

    Dang, Xiao-yong; Chu, Wei-wei; Shi, Heng-chuan; Yu, Shi-gang; Han, Hai-yin; Gu, Shu-Hua; Chen, Jie

    2015-01-25

    Excess accumulation of cholesterol in plasma may result in coronary artery disease. Numerous studies have demonstrated that ATP-binding cassette protein A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to apolipoproteins, a process necessary for plasma high density lipoprotein (HDL) formation. Higher plasma levels of HDL are associated with lower risk for cardiovascular disease. Studies of human disease and animal models had shown that an increased hepatic ABCA1 activity relates to an enhanced plasma HDL level. In this study, we hypothesized that functional mutations in the ABCA1 promoter in pigs may affect gene transcription activity, and consequently the HDL level in plasma. The promoter region of ABCA1 was comparatively scanned by direct sequencing with pool DNA of high- and low-HDL groups (n=30 for each group). Two polymorphisms, c. - 608A>G and c. - 418T>A, were revealed with reverse allele distribution in the two groups. The two polymorphisms were completely linked and formed only G-A or A-T haplotypes when genotyped in a larger population (n=526). Furthermore, we found that the G-A/G-A genotype was associated with higher HDL and ABCA1 mRNA level than A-T/A-T genotype. Luciferase assay also revealed that G-A haplotype promoter had higher activity than A-T haplotype. Single-nucleotide mutant assay showed that c.-418T>A was the causal mutation for ABCA1 transcription activity alteration. Conclusively, we identified two completely linked SNPs in porcine ABCA1 promoter region which have influence on the plasma HDL level by altering ABCA1 gene transcriptional activity.

  16. Coenzyme Q10, carotenoid, tocopherol, and retinol levels in cord plasma from multiethnic subjects in Hawaii.

    PubMed

    Franke, A A; Lai, J F; Morrison, C M; Pagano, I; Li, X; Halm, B M; Soon, R; Custer, L J

    2013-09-01

    Coenzyme Q10 (Q10), carotenoids, tocopherols, and retinol are the major circulating lipid-phase micronutrients (LPM) known to help mitigate oxidative damage and prevent chronic diseases. However, the functions of these compounds in newborns are little understood. This is due, in part, to the paucity of studies reporting their concentrations in this population. We measured Q10, carotenoids, tocopherols, and retinol in cord plasma from 100 multiethnic subjects living in Hawaii using HPLC with diode array and electrochemical detection. Appropriate internal standards were used including, for the first time, custom designed oxidized (UN10) and reduced (UL10) Q10 analogues. These compounds reflected the oxidation of UL10 to UN10 that occurred during sample processing and analysis and thus permitted accurate adjustments of natively circulating Q10 levels. All LPM measured were much lower in cord than in peripheral plasma. Cord plasma levels of total carotenoids, tocopherols, and retinol were approximately 10-fold, 3- to 5-fold and 1.5- to 3-fold lower than those in children or women. Cord plasma levels of total Q10 (TQ10; median, 113 ng/mL) were approximately 2-fold or 7- to 9-fold lower than peripheral plasma levels of neonates or children and adults, respectively. In contrast, the UN10/TQ10 ratio was substantially higher in cord (24%) than in peripheral plasma of children (3-4%) or adults (9%). Among the 5 ethnic groups in our cohort, no differences were observed in the levels of UN10, UL10, or TQ10. However, significant differences in many of the LPM were observed between ethnicities. More research is needed to explain these phenomena.

  17. Infantile Refsum Disease: Influence of Dietary Treatment on Plasma Phytanic Acid Levels.

    PubMed

    Sá, Maria João Nabais; Rocha, Júlio C; Almeida, Manuela F; Carmona, Carla; Martins, Esmeralda; Miranda, Vasco; Coutinho, Miguel; Ferreira, Rita; Pacheco, Sara; Laranjeira, Francisco; Ribeiro, Isaura; Fortuna, Ana Maria; Lacerda, Lúcia

    2016-01-01

    Infantile Refsum disease (IRD) is one of the less severe of Zellweger spectrum disorders (ZSDs), a group of peroxisomal biogenesis disorders resulting from a generalized peroxisomal function impairment. Increased plasma levels of very long chain fatty acids (VLCFA) and phytanic acid are biomarkers used in IRD diagnosis. Furthermore, an increased plasma level of phytanic acid is known to be associated with neurologic damage. Treatment of IRD is symptomatic and multidisciplinary.The authors report a 3-year-old child, born from consanguineous parents, who presented with developmental delay, retinitis pigmentosa, sensorineural deafness and craniofacial dysmorphisms. While the relative level of plasma C26:0 was slightly increased, other VLCFA were normal. Thus, a detailed characterization of the phenotype was essential to point to a ZSD. Repeatedly increased levels of plasma VLCFA, along with phytanic acid and pristanic acid, deficient dihydroxyacetone phosphate acyltransferase activity in fibroblasts and identification of the homozygous pathogenic mutation c.2528G>A (p.Gly843Asp) in the PEX1 gene, confirmed this diagnosis. Nutritional advice and follow-up was proposed aiming phytanic acid dietary intake reduction. During dietary treatment, plasma levels of phytanic acid decreased to normal, and the patient's development evaluation showed slow progressive acquisition of new competences.This case report highlights the relevance of considering a ZSD in any child with developmental delay who manifests hearing and visual impairment and of performing a systematic biochemical investigation, when plasma VLCFA are mildly increased. During dietary intervention, a biochemical improvement was observed, and the long-term clinical effect of this approach needs to be evaluated.

  18. The adrenocortical response of greater sage grouse (Centrocercus urophasianus) to capture, ACTH injection, and confinement, as measured in fecal samples

    USGS Publications Warehouse

    Jankowski, M.D.; Wittwer, D.J.; Heisey, D.M.; Franson, J. Christian; Hofmeister, Erik K.

    2009-01-01

    Investigators of wildlife populations often utilize demographic indicators to understand the relationship between habitat characteristics and population viability. Assessments of corticosterone may enable earlier detection of populations at risk of decline because physiological adjustments to habitat disturbance occur before reproductive diminutions. Noninvasive methods to accomplish these assesments are important in species of concern, such as the greater sage grouse (GRSG). Therefore, we validated a radioimmunoassay that measures immunoreactive corticosterone metabolites (ICM) in fecal samples and used it to characterize the adrenocortical response of 15 GRSG exposed to capture, intravenous injection of 50 IU/kg adrenocorticotrophic hormone (ACTH) or saline, and 22 h of confinement. Those animals injected with ACTH exhibited a more sustained (P = 0.0139) and less variable (P = 0.0012) response than those injected with saline, indicating different levels of adrenocortical activity. We also found that potential field-collection protocols of fecal samples did not alter ICM concentrations: samples held at 4??C for up to 16 h contained similar levels of ICM as those frozen (-20??C) immediately. This study demonstrates a multiphasic adrenocortical response that varied with the level of stimulation and indicates that the assay used to measure this phenomenon is applicable for studies of wild GRSG. ?? 2009 by The University of Chicago. All rights reserved.

  19. Association Between Seminal Plasma Copper and Magnesium Levels with Oxidative Stress in Iraqi Infertile Men

    PubMed Central

    Abdul-Rasheed, Omar F.

    2010-01-01

    Objectives To study the association between copper, magnesium and malondialdehyde levels in seminal plasma of oligozoospermic, azoospermic in relation to normozoospermic men. Methods The present study was conducted at the Chemistry and Biochemistry department, College of Medicine, Al-Nahrain University, Baghdad-Iraq during September 2007 to February 2008 after obtaining approval from the research and ethics committee and obtaining written consent, 78 infertile men (age range 33.01±4.20 years) were recruited at the institute of embryo research and infertility treatment, Al-Kadhimiya teaching hospital, Iraq and were categorized according to their seminal fluid parameters to oligozoospermia (n=43) and azoospermia (n=35). 41 fertile men (age range 30.29±2.30 years) were selected as controls. Seminal plasma copper and magnesium were measured by atomic absorption spectrophotometry. Malondialdehyde was measured calorimetrically using thiobarbituric acid assay which detects thiobarbituric acid reactive substances. Results Seminal plasma copper level was decreased significantly (p=0.000) in the azoospermic group compared to the control group. Whereas, the level decreased non-significantly in the oligozoospermic group. Seminal plasma magnesium levels were decreased significantly (p=0.000) in all the infertility groups studied. On the other hand, malondialdehyde levels which is an end product of lipid peroxidation were significantly elevated (p=0.000) in all the infertility groups studied. Conclusion Copper and magnesium work in different ways in order to maintain normal environment for spermatozoa for normal fertilization to occur. PMID:22043332

  20. Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs

    SciTech Connect

    Adams, M.L.; Morris, D.L.; Dewey, W.L.

    1986-03-05

    ..beta..-endorphin, (met)enkephalin, and (leu)enkephalin were quantitated in canine plasma by radioimmunoassay (RIA) after extraction of the peptides on Sep Pak C18 cartridges. Plasma samples were taken one hour after a 10 mg/kg s.c. injection of (-)-morphine SO/sub 4/ or (+)-morphine HBr. Antinociception, measured by a dog tail-flick test, and morphine-induced emesis, salivation, diarrhea, and ataxia were quantitated before sampling. Control levels for each dog were taken one week earlier at the same time of day after saline injections. Antinociception, morphine signs, and opioid peptide levels in plasma were significantly increased by (-)-morphine. Antinociception increased from zero to 83.54 +/- 11.0%. The number of morphine signs increased from zero to 2.9 +/- 0.28 per dog. ..beta..-endorphin levels increased from 44.52 +/- 4.25 to 90.6 +/- 7.38 pg/ml; (met)enkephalin levels increased from 253.56 +/- 22.04 to 497.1 +/- 58.12 pg/ml; (leu)-enkephalin increased from 141.65 +/- 12.9 to 313.24 +/- 35.95 pg/ml. None of these effects were observed in the dogs that received (+)-morphine. The conclude that morphine stereospecifically inhibits nociception, induces observable signs, and increases plasma opioid peptide levels in dogs.

  1. Lack of association between plasma leptin levels and appetite in children with iron deficiency.

    PubMed

    Topaloglu, A K; Hallioglu, O; Canim, A; Duzovali, O; Yilgor, E

    2001-01-01

    A negative correlation between leptin and appetite or food intake has been shown in healthy individuals. However, the role of leptin in clinical conditions characterized by anorexia has not been established. One of the well-known clinical features of iron-deficiency anemia is poor appetite. We examined the changes in plasma leptin levels in relation to expected improvement in appetite with iron treatment in children with iron deficiency. In 24 infants and small children (mean age +/- standard deviation = 19.6 +/- 7.7 months) with iron deficiency, we studied plasma leptin levels before and after iron therapy. After 15.0 +/- 2.4 wk of iron treatment, serum ferritin levels improved significantly, with accompanying increases in their subjective appetite scores and food intakes. However, as their mean age and plasma leptin levels adjusted their body mass indexes were unchanged. Serum ferritin correlated significantly with appetite score (r = 0.680, P < 0.001) and food intake (r = 0.480, P < 0.01). Leptin correlated only with body mass index (r = 0.405, P < 0.01). Lack of association between plasma leptin levels and degree of appetite in iron-deficient children treated with iron suggests a leptin-independent mechanism for the observed increase in appetite.

  2. [Acute pancreatitis after bilateral laparoscopic adrenalectomy in patients with ectopic ACTH syndrome].

    PubMed

    Cougard, P; Peix, J L; Peschaud, F; Goudet, P

    2001-05-01

    Two cases of acute necrotizing pancreatitis after bilateral laparoscopic adrenalectomy were observed in patients with an ectopic ACTH syndrome. Two reasons may be suspected: the difficulty of dissection in such patients and the specific morbidity in relation to hypercorticism.

  3. Higher plasma level of STIM1, OPG are correlated with stent restenosis after PCI

    PubMed Central

    Li, Haibin; Jiang, Zhian; Liu, Xiangdong; Yang, Zhihui

    2015-01-01

    Object: Percutaneous Coronary Intervention (PCI) is one of the most effective treatments for Coronary Heart Disease (CHD), but the high rate of In Stent Restenosis (ISR) has plagued clinicians after PCI. We aim to investigate the correlation of plasma Stromal Interaction Molecular 1 (STIM1) and Osteoprotegerin (OPG) level with stent restenosis after PCI. Methods: A total of 100 consecutive patients with Coronary Heart Disease (CHD) received PCI procedure were recruited. Coronary angiography was performed 8 months after their PCI. Then patients were divided into 2 groups: observation group was composed by patients who existing postoperative stenosis after intervention; Control group was composed by patients with no postoperative stenosis. The plasma levels of STIM, OPG in all patients were tested before and after intervention. Pearson correlation and multiple linear regression analysis were performed to analysis the correlation between STIM, OPG level and postoperative stenosis. Results: 35 cases were divided into observation group and other 65 were divided into control group. The plasma levels of STIM, OPG have no statistical difference before their PCI procedure, but we observed higher level of High-sensitivity C-reactive protein (Hs-CRP) existed in observation group. We observed higher level of plasma STIM, OPG in observation group when compared with control group after PCI procedure (P < 0.05). Regression analysis demonstrated that Hs-CRP, STIM1, OPG are independent risk factors for ISR. Conclusion: Elevated levels of plasma STIM1, OPG are independent risk factors for ISR in patients received PCI, which could provide useful information for the restenosis control after PCI. PMID:26885040

  4. [Plasma concentration of C-reactive protein in patients with high estrogen levels].

    PubMed

    Ricoux, R; Pontet, M; Tresca, J P; Engler, R

    1994-01-01

    The monitoring of inflammatory activity in patients with a high level of estrogen is controversial because the significance of a raised estradiol level on C-reactive protein (CRP) concentrations is a debated question. This prompted us to assay CRP by a sensitive Elisa in a sample of 30 patients with ovarian stimulation for in vitro fertilization, thus with high levels of estradiol. For 15 of these women, six to nine plasma samples were analyzed allowing a kinetic study of plasma levels of CRP, estradiol and sex steroid-binding plasma protein (SBP). No significant correlation was found between the concentrations of estradiol and CRP for the 30 patients. In the kinetic study, as mean estradiol levels rose exponentially from 50 to 1400 ng/l between day 5 and 14, the CRP level tended to vary markedly from one patient to another and sometimes from day to day, but there was never any relation with estradiol level. Furthermore, CRP did not significantly modify the slope of the regression line between estradiol concentration and the day of the menstrual cycle. In contrast, the effect of estradiol on SBP was clear, which supports the absence of estradiol effect on CRP level.

  5. Determinants of plasma glucose level and diabetic status in a northern Canadian Indian population.

    PubMed Central

    Young, T K; Sevenhuysen, G P; Ling, N; Moffatt, M E

    1990-01-01

    We conducted a cross-sectional survey of 704 Indians aged 20 to 64 years in six remote communities in northern Ontario and Manitoba to determine the factors associated with the fasting plasma glucose and glycosylated hemoglobin levels and diabetic status, defined by past history and current fasting plasma glucose level. Multivariate analyses for the 671 subjects with complete data showed that triglyceride level, age and body mass index (BMI) were significant predictors of the log fasting plasma glucose level and the log glycosylated hemoglobin level; for the latter, waist/hip ratio, history of diabetes mellitus among first-degree relatives and low level of education were additional predictors. Significant risk factors for diabetes as a dichotomous variable included triglyceride level, age, BMI and family history of diabetes. Although energy intake per unit of body weight was lower among subjects with diabetes than those without diabetes, possibly reflecting the lower physical activity level of diabetic subjects, the former consumed significantly more "calorie-adjusted" protein and less carbohydrate than the latter. The findings are consistent with studies in other populations. Further study is needed to determine the natural history of diabetes and its metabolic consequences and to assess the effect of dietary alteration and promotion of physical activity on the incidence of the disease. PMID:2322914

  6. Major Abdominal Surgery Increases Plasma Levels of Vascular Endothelial Growth Factor

    PubMed Central

    Belizon, Avraham; Balik, Emre; Feingold, Daniel L.; Bessler, Marc; Arnell, Tracey D.; Forde, Kenneth A.; Horst, Patrick K.; Jain, Suvinit; Cekic, Vesna; Kirman, Irena; Whelan, Richard L.

    2006-01-01

    Introduction: Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis that is necessary for wound healing and also promotes tumor growth. It is anticipated that plasma levels would increase after major surgery and that such elevations may facilitate tumor growth. This study's purpose was to determine plasma VEGF levels before and early after major open and minimally invasive abdominal surgery. Methods: Colorectal resection for cancer (n = 139) or benign pathology (n = 48) and gastric bypass for morbid obesity (n = 40) were assessed. Similar numbers of open and laparoscopic patients were studied for each indication. Plasma samples were obtained preoperatively and on postoperative days (POD) 1 and 3. VEGF levels were determined via ELISA. The following statistical methods were used: Fisher exact test, unmatched Student t test, Wilcoxon's matched pairs test, and the Mann Whitney U Test with P < 0.05 considered significant. Results: The mean preoperative VEGF level of the cancer patients was significantly higher than baseline level of benign colon patients. Regardless of indication or surgical method, on POD3, significantly elevated mean VEGF levels were noted for each subgroup. In addition, on POD1, open surgery patients for all 3 indications had significantly elevated VEGF levels; no POD1 differences were noted for the closed surgery patients. At each postoperative time point for each procedure and indication, the open group's VEGF levels were significantly higher than that of the matching laparoscopic group. VEGF elevations correlated with incision length for each indication. Conclusion: As a group colon cancer patients prior to surgery have significantly higher mean VEGF levels than patients without tumors. Also, both open and closed colorectal resection and gastric bypass are associated with significantly elevated plasma VEGF levels early after surgery. This elevation is significantly greater and occurs earlier in open surgery patients. The

  7. Purification of swine carbonic anhydrase isoenzyme III and measurement of its levels in tissues and plasma.

    PubMed

    Nishita, T; Harada, T; Sakanoue, H; Arai, S; Itoh, S; Orito, K; Arishima, K

    2014-02-01

    The changes in the levels of carbonic anhydrase isozyme III (CA-III) in swine plasma and urine have not been previously determined or reported. CA-III is relatively specific to skeletal muscles, and should therefore be a useful diagnostic marker for muscle diseases. We isolated CA-III from swine muscle tissues and determined CA-III levels in the plasma and urine from both healthy and diseased pigs. The levels of CA-III in the tissues of female swine (age, 3 months) and plasma of young swine (age, 1-5 months) and adult female pigs (age, 2-3 years) were determined using the ELISA system for swine CA-III. The mean (± SD) levels of CA-III in the skeletal muscles were 3.8 ± 3.2 mg/g (wet tissue), and in the plasma, 230 ± 193 ng/ml at 1 month, 189 ± 208 ng/ml at 2 months, 141 ± 148 ng/ml at 3 months, 78 ± 142 ng/ml at 4 months and 53 ± 99 ng/ml at 5 months. The mean level of CA-III in the plasma samples from 2- to 3-year-old pigs was 18 ± 60 ng/ml. CA-III in the plasma samples was found to decrease from 1 month until 3 years of age (p < 0.01). We performed far-western blotting to clarify the cause of the observed decrease in CA-III in plasma. Our results demonstrated that CA-III is bound to the transferrin and albumin. In addition, we determined that the levels of CA-III in plasma and urine samples were higher in diseased swine compared with the healthy pigs.

  8. Isolated ACTH deficiency in a patient with empty sella as revealed by severe hyponatremia.

    PubMed

    Doroftei, Nicoleta Alina; de Rudder, Catherine; de Visscher, Nathalie; Hanon, Francois

    2016-12-01

    Hyponatremia due to isolated adrenocorticotropic hormone (ACTH) deficiency is difficult to diagnose as it is usually indistinguishable from non-endocrine syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present a case secondary to empty sella. Most patients with empty sella remain asymptomatic throughout life and require no treatment; however, in cases involving the development of isolated ACTH deficiency, corticosteroid treatment should be enforced to avoid fatal consequences.

  9. Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone.

    PubMed

    van den Beukel, Johanna C; Grefhorst, Aldo; Quarta, Carmelo; Steenbergen, Jacobie; Mastroberardino, Pier G; Lombès, Marc; Delhanty, Patric J; Mazza, Roberta; Pagotto, Uberto; van der Lely, Aart Jan; Themmen, Axel P N

    2014-11-01

    Brown adipose tissue (BAT) and brown-like cells in white adipose tissue (WAT) can dissipate energy through thermogenesis, a process mediated by uncoupling protein 1 (UCP1). We investigated whether stress hormones ACTH and corticosterone contribute to BAT activation and browning of WAT. ACTH and corticosterone were studied in male mice exposed to 4 or 23°C for 24 h. Direct effects were studied in T37i mouse brown adipocytes and primary cultured murine BAT and inguinal WAT (iWAT) cells. In vivo effects were studied using (18)F-deoxyglucose positron emission tomography. Cold exposure doubled serum ACTH concentrations (P=0.03) and fecal corticosterone excretion (P=0.008). In T37i cells, ACTH dose-dependently increased Ucp1 mRNA (EC50=1.8 nM) but also induced Ucp1 protein content 88% (P=0.02), glycerol release 32% (P=0.03) and uncoupled respiration 40% (P=0.003). In cultured BAT and iWAT, ACTH elevated Ucp1 mRNA by 3-fold (P=0.03) and 3.7-fold (P=0.01), respectively. In T37i cells, corticosterone prevented induction of Ucp1 mRNA and Ucp1 protein by both ACTH and norepinephrine in a glucocorticoid receptor (GR)-dependent fashion. ACTH and GR antagonist RU486 independently doubled BAT (18)F-deoxyglucose uptake (P=0.0003 and P=0.004, respectively) in vivo. Our results show that ACTH activates BAT and browning of WAT while corticosterone counteracts this.

  10. Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate.

    PubMed

    Tiwari, Priya; Thomas, M K; Pathania, Subha; Dhawan, Deepa; Gupta, Y K; Vishnubhatla, Sreenivas; Bakhshi, Sameer

    2015-01-01

    Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Δ creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Δ creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Δ creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Δ creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Δ creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Δ creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance.

  11. Plasma hepcidin levels and anemia in old age. The Leiden 85-Plus Study.

    PubMed

    den Elzen, Wendy P J; de Craen, Anton J M; Wiegerinck, Erwin T; Westendorp, Rudi G J; Swinkels, Dorine W; Gussekloo, Jacobijn

    2013-03-01

    Hepcidin, an important regulator of iron homeostasis, is suggested to be causally related to anemia of inflammation. The aim of this study was to explore the role of plasma hepcidin in anemia among older persons from the general population. The Leiden 85-Plus Study is a population-based study of 85-year olds in Leiden, the Netherlands. Eighty-five-year old inhabitants of Leiden were enrolled between September 1997 and September 1999. At the age of 86, plasma hepcidin was determined with time of flight mass spectrometry in 490 participants [160 (32.7%) male, 114 (23.3%) with anemia]. Anemia was defined according to criteria of the World Health Organization (hemoglobin level <13 g/dL for men and hemoglobin <12 g/dL for women). The median plasma hepcidin level was 3.0 nM [interquartile range (IQR) 1.8-4.9]. We found strong correlations between plasma hepcidin and body iron status, C-reactive protein and erythropoietin levels. Significantly higher hepcidin levels were found in participants with anemia of inflammation (P<0.01), in participants with anemia of kidney disease (P=0.01), and in participants with unexplained anemia (P=0.01) than in participants without anemia. Participants with iron-deficiency anemia had significantly lower plasma hepcidin levels than participants without anemia (P<0.01). In conclusion, older persons with anemia of inflammation have higher hepcidin levels than their counterparts without anemia. The potential clinical value of hepcidin in future diagnostic algorithms for anemia has to be explored.

  12. Decrease of N-acetylaspartate after ACTH therapy in patients with infantile spasms.

    PubMed

    Maeda, H; Furune, S; Nomura, K; Kitou, O; Ando, Y; Negoro, T; Watanabe, K

    1997-10-01

    Apparent brain atrophy has been frequently observed at CT and MRI after ACTH therapy in patients with infantile spasms. There are several hypotheses to explain ACTH-induced brain shrinkage: 1) a catabolic effect of ACTH on brain tissue, 2) a mineralocorticoid effect resulting in a loss of water and 3) an increase in cerebrospinal fluid (CSF) pressure compressing the brain. An average of 0.21 +/- 0.03 mg/kg of ACTH was administered to nine patients over a period of 14 to 17 days. Water content and concentrations of N-acetylaspartate (NAA), creatine and phosphocreatine (Cr + PCr), and choline (Cho) were measured before, immediately after, and several months after the ACTH therapy by using in-vivo 1H magnetic resonance spectroscopy (MRS). Only NAA concentration exhibited a significant change during the study (6.6 +/- 1.5 mmol/kg, 5.4 +/- 1.1, and 7.0 +/- 1.5, p = 0.017). There was no significant change in Cr + PCr, in Cho, or in water content. These data suggest catabolic effects of ACTH on brain tissue, such as cell loss, decrease in NAA synthesis in mitochondria, and leakage of NAA from cell membrane.

  13. ACTH Modulates PTP-PEST Activity and Promotes Its Interaction With Paxillin.

    PubMed

    Gorostizaga, Alejandra Beatriz; Mori Sequeiros Garcia, M Mercedes; Acquier, Andrea B; Lopez-Costa, Juan J; Mendez, Carlos F; Maloberti, Paula M; Paz, Cristina

    2016-09-01

    Adrenocorticotropic hormone (ACTH) treatment has been proven to promote paxillin dephosphorylation and increase soluble protein tyrosine phosphatase (PTP) activity in rat adrenal zona fasciculata (ZF). Also, in-gel PTP assays have shown the activation of a 115-kDa PTP (PTP115) by ACTH. In this context, the current work presents evidence that PTP115 is PTP-PEST, a PTP that recognizes paxillin as substrate. PTP115 was partially purified from rat adrenal ZF and PTP-PEST was detected through Western blot in bioactive samples taken in each purification step. Immunohistochemical and RT-PCR studies revealed PTP-PEST expression in rat ZF and Y1 adrenocortical cells. Moreover, a PTP-PEST siRNA decreased the expression of this phosphatase. PKA phosphorylation of purified PTP115 isolated from non-ACTH-treated rats increased KM and VM . Finally, in-gel PTP assays of immunoprecipitated paxillin from control and ACTH-treated rats suggested a hormone-mediated increase in paxillin-PTP115 interaction, while PTP-PEST and paxillin co-localize in Y1 cells. Taken together, these data demonstrate PTP-PEST expression in adrenal ZF and its regulation by ACTH/PKA and also suggest an ACTH-induced PTP-PEST-paxillin interaction. J. Cell. Biochem. 117: 2170-2181, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

  14. The ACTH cells in the pituitary gland of the nine-spined stickleback, Pungitius pungitius L.

    PubMed Central

    Benjamin, M

    1982-01-01

    The ACTH cells form a layer 1-8 cells thick, dorsal to the prolactin cells in the rostral pars distalis. They react only mildly with a variety of stains including PAS-lead haematoxylin. Their nuclear diameters vary seasonally in a manner that closely parallels that of the prolactin cells. The relative volumes of the ACTH and prolactin cell zones are remarkably constant in animals of different sizes. It is suggested that the two hormones may act synergistically at various body sites and that this accounts for the related morphological features of the ACTH and prolactin cells. There are no changes in the surface density of the ACTH zone with increasing animal size. Consequently, the ACTH/neurohypophysial border is highly convoluted in large animals. The proximity of the neurohypophysis also influences cell ultrastructure, as small processes, packed with secretory granules are more numerous near the basal lamina separating the adeno- and neurohypophyses. A morphometric analysis of ACTH cells provides base-line ultrastructural data for experimental studies and for comparisons with other teleosts. The cells have small, secretory granules, 100-300 nm in diameter, and of variable electron density. There is little rough endoplasmic reticulum and a small Golgi apparatus. There is no evidence of granule release by exocytosis and various explanations for this are suggested. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:6290440

  15. Effect of Antiepileptic drugs on plasma lipoprotein (a) and other lipid levels in childhood.

    PubMed

    Aynaci, F M; Orhan, F; Orem, A; Yildirmis, S; Gedik, Y

    2001-05-01

    Antiepileptic drugs may alter plasma lipid status in epileptic patients. We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on plasma levels of lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A, and apolipoprotein B in 22 epileptic children. The children were separated as group 1, seven children, mean age 1.6+/-0.2 years, treated with phenobarbital, 5 mg/kg/day, twice daily; group 2, seven children, mean age 9.8+/-1.2 years, treated with carbamazepine, 20 mg/kg/day, twice daily; and group 3, eight children, mean age 6.8+/-0.6 years, treated with valproate, 20 mg/kg/day, twice daily. Plasma lipoprotein (a) and other lipid levels were studied before (pretreatment) and at 3 and 6 months of treatment. Friedman two-way analysis of variance and Wilcoxon's signed-rank test were used for statistical analysis, and the results were expressed as the mean and standard error of the mean. The mean age of children in group 1 was significantly low, compared with groups 2 and, 3 (P < .001). The mean pretreatment lipid levels between the groups were not significant. The increase in lipoprotein (a) at 3 and 6 months and high-density lipoprotein cholesterol at 6 months was statistically significant in group 1 (P < .025). We suggest a careful monitoring of plasma levels of lipoprotein (a) and other lipids in epileptic children treated with antiepileptic drugs.

  16. Marihuana attenuates the rise in plasma ethanol levels in human subjects.

    PubMed

    Lukas, S E; Benedikt, R; Mendelson, J H; Kouri, E; Sholar, M; Amass, L

    1992-08-01

    This study was conducted to determine if plasma ethanol levels are altered as a result of smoking marihuana. Fifteen healthy adult male volunteers who used ethanol and marihuana on a casual basis participated in this study. Subjects were randomly assigned to one of three groups: placebo, low-dose, or high-dose marihuana. The marihuana dose was held constant and each subject drank three different doses of ethanol on 3 separate days spaced at least 1 week apart. Subjects drank either placebo or ethanol at doses of 0.35 g/kg (7.60 mmol/kg) or 0.70 g/kg (15.19 mmol/kg). Thirty minutes after drinking they smoked either a placebo marihuana cigarette, or one containing either 1.26% or 2.53% delta 9-tetrahydrocannabinol. Plasma ethanol levels rose sharply after the 0.7 g/kg dose and peaked at 50 minutes after drinking began (78.25 +/- 4.95 mg/dl). When subjects smoked the high-dose marihuana cigarettes after the 0.7 g/kg dose of ethanol, peak plasma ethanols levels were only 54.80 +/- 8.32 mg/dl at 105 minutes after drinking began. These alterations in plasma ethanol levels paralleled a reduction in the duration of ethanol- and marihuana-induced subjective effects after high doses of both drugs. These data suggest that marihuana may alter ethanol bioavailability.

  17. Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

    PubMed Central

    Ates, Orhan; Bilen, Habip; Keles, Sadullah; Alp, H. Hakan; Keleş, Mevlüt Sait; Yıldırım, Kenan; Öndaş, Osman; Pınar, L. Can; Civelekler, Mustafa; Baykal, Orhan

    2013-01-01

    AIM To determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration. METHODS Patients with type 2 diabetes and PDRP were determined to be the case group (n=50). The control group was consist of healthy individuals (n=50). Plasma CoQ10 and malondialdehyde (MDA) levels were measured in both groups. RESULTS Ubiquinone-10 (Coenzyme Q10) levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively. CONCLUSION The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy. PMID:24195048

  18. Effect of frequency of dosing of plant sterols on plasma cholesterol levels and synthesis rate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to compare the effects of plant sterols (PS) consumed as a single dose (single) at breakfast or as three doses consumed with breakfast, lunch and dinner (divided) on plasma lipoprotien levels and cholesterol endogenous fractional synthesis rate (FSR). A randomized, placebo-controll...

  19. Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients

    PubMed Central

    Qundos, Ulrika; Drobin, Kimi; Mattsson, Cecilia; Hong, Mun‐Gwan; Sjöberg, Ronald; Forsström, Björn; Solomon, David; Uhlén, Mathias; Nilsson, Peter; Michaëlsson, Karl

    2015-01-01

    Purpose Affinity proteomic approaches by antibody bead arrays enable multiplexed analysis of proteins in body fluids. In the presented study, we investigated blood plasma within osteoporosis to discovery differential protein profiles and to propose novel biomarkers candidates for subsequent studies. Experimental design Starting with 4608 antibodies and plasma samples from 22 women for an untargeted screening, a set of 72 proteins were suggested for further analysis. Complementing these with targets from literature and other studies, a targeted bead array of 180 antibodies was built to profile for 92 proteins in plasma samples of 180 women from two independent population‐based studies. Results Differential profiles between osteoporosis patients and matched controls were discovered for 12 proteins in at least one of the two study sets. Among these targets, the levels of autocrine motility factor receptor (AMFR) were concordantly lower in plasma of female osteoporosis patients. Subsequently, verification of anti‐AMFR antibody selectivity was conducted using high‐density peptide and protein arrays, and Western blotting. Conclusions and clinical relevance Further validation in additional study sets will be needed to determine the clinical value of the observed decrease in AMFR plasma levels in osteoporosis patients, but AMFR may aid our understanding of disease mechanisms and could support existing tools for diagnosis and monitoring of patient mobility within osteoporosis. PMID:25689831

  20. Plasma Ghrelin Levels Are Associated with Anorexia but Not Cachexia in Patients with NSCLC

    PubMed Central

    Blauwhoff-Buskermolen, Susanne; Langius, Jacqueline A. E.; Heijboer, Annemieke C.; Becker, Annemarie; de van der Schueren, Marian A. E.; Verheul, Henk M. W.

    2017-01-01

    Background and Aims: The ghrelin receptor is one of the new therapeutic targets in the cancer anorexia-cachexia syndrome. Previous studies revealed that plasma ghrelin levels were high in patients with anorexia nervosa and low in obese subjects. We studied to what extent ghrelin levels are related with anorexia and cachexia in patients with cancer. Materials and Methods: Fasted ghrelin levels were determined as well as anorexia and cachexia in patients with stage III/IV non-small cell lung cancer before chemotherapy. Total plasma ghrelin was measured by radioimmunoassay. Anorexia was measured with the FAACT-A/CS questionnaire (cut-off value ≤ 37). Cachexia was determined as >5% weight loss (WL) in 6 months or >2% WL in 6 months in combination with low BMI or low muscle mass. The Kruskal-Wallis test was performed to assess differences in plasma ghrelin levels between four groups: patients with (+) or without (−) anorexia (A) or cachexia (C). Multiple regression analyses were performed to assess differences in plasma ghrelin levels between patients C+ and C− and patients with A+ and A− (adjusted for age and sex). Results: Forty patients with stage III (33%) or stage IV (68%) were recruited, of which 50% was male. Mean age was 59.6 ± 10.3 years. Sixteen patients had no anorexia or cachexia (A−C−), seven patients had both anorexia and cachexia (A+C+), ten patients had anorexia without cachexia (A+C−) and seven patients had cachexia without anorexia (A−C+). The levels of total plasma ghrelin were significantly different between the four groups of patients with or without anorexia or cachexia (p = 0.032): the A+C− patients had significantly higher ghrelin levels [median (IQR): 1,754 (1,404–2,142) compared to the A−C+ patients 1,026 (952–1,357), p = 0.003]. A+ patients had significantly higher ghrelin levels compared A− patients (C+ and C− combined, β: 304, p = 0.020). Plasma ghrelin levels were not significantly different in C+ patients

  1. Plasma zinc alpha2-glycoprotein levels correlate positively with frailty severity in female elders

    PubMed Central

    Lee, Ya-Ping; Chang, Chin-Hao; Liu, Heng-Hsiu; Chen, Chin-Ying; Chen, Ching-Yu; Hsu, Chih-Cheng; Chang, Ching-I; Lin, Yen-Ting; Lee, Chung-Sheng; Tsai, Jaw-Shiun

    2016-01-01

    Abstract Frailty is a geriatric syndrome associated with adiposity. Zinc alpha2-glycoprotein (ZAG), a novel adipokine, is a modulator of body fat mass and positively correlates with age. This observational study aims to investigate the relationship between plasma ZAG levels and frailty in the elderly. We enrolled 189 elder participants from a hospital-based comprehensive geriatric assessment program in Taiwan from January 2007 to June 2008. The demographic data, body weight, body mass index, appendicular skeletal muscle mass index (ASMI), body fat mass percentage, metabolic and inflammatory parameters including plasma tumor-necrosis factor alpha, C-reactive protein and ZAG levels, were assessed. The frailty score was assessed by Fried Frailty Index. The mean age of all participants (91 [48.1%] men and 98 [51.9%] women) was 77.19 ± 6.12 years. Judged by the FFI score, 46 (24.34%) elders were robust, 106 (56.08%) were pre-frail, and 37 (19.58%) were frail. Older men showed greater ASMI and lower fat mass percentage in comparison to older women (P < 0.0001). The log-transformed mean plasma ZAG (μg/mL) level of overall was 1.82 ± 0.11, and it was higher in men than in women (1.85 ± 0.12 vs 1.79 ± 0.1, P = 0.0006). Plasma ZAG levels were different among the robust, pre-frail and frail subgroups (1.78 ± 0.09, 1.83 ± 0.12, 1.83 ± 1.10, respectively, P = 0.028), and the differences were more significant in woman elders (P = 0.005). Further multiple linear regression analysis showed plasma ZAG levels positively correlated with frailty severity in women (P for trend = 0.0435). Plasma ZAG levels positively correlated with frailty severity in woman elders. The difference between sexes suggests certain sex-specific mechanisms may exist to affect the association between plasma ZAG levels and frailty. PMID:27583927

  2. [Blood plasma level of endothelin in miners of a deep coal mine].

    PubMed

    Plotkin, V Ia; Rebrov, B A; Nikitina, I V

    2000-09-01

    In 60 miners working in a deep coal mine the blood plasma level of endoteline-1 (E-1) was measured by the immunoenzyme technique immediately after working shift. Those in the mining where the working conditions are especially harsh were found to have the highest level of E-1 exceeding the control values. In studying the age-related content of E-1 in blood plasma of coal miners the highest levels of E-1 were recordable in workers 20 to 30 years old, declining and differing in age groups 20-30 and 41-50 years old. The level of E-1 was at its greatest in those workers with minimum length of service in the underground conditions, declining with the service more than 10 years in duration.

  3. Effect of one month ketoconazole treatment on GH, cortisol and ACTH release after ghrelin, GHRP-6 and GHRH administration in patients with Cushing's disease.

    PubMed

    Correa-Silva, Silvia R; Nascif, Sérgio O; Silva, Marcos R; Molica, Patrícia; Lengyel, Ana-Maria J

    2007-10-01

    GH responses to ghrelin, GHRP-6, and GHRH in Cushing's disease (CD) are markedly blunted. There is no data about the effect of reduction of cortisol levels with steroidogenesis inhibitors, like ketoconazole, on GH secretion in CD. ACTH levels during ketoconazole treatment are controversial. The aims of this study were to compare the GH response to ghrelin, GHRP-6, and GHRH, and the ACTH and cortisol responses to ghrelin and GHRP-6 before and after one month of ketoconazole treatment in 6 untreated patients with CD. Before treatment peak GH (microg/L; mean +/- SEM) after ghrelin, GHRP-6, and GHRH administration was 10.0 +/- 4.5; 3.8 +/- 1.6, and 0.6 +/- 0.2, respectively. After one month of ketoconazole there was a significant decrease in urinary cortisol values (mean reduction: 75%), but GH responses did not change (7.0 +/- 2.0; 3.1 +/- 0.8; 0.9 +/- 0.2, respectively). After treatment, there was a significant reduction in cortisol (microg/dL) responses to ghrelin (before: 30.6 +/- 5.2; after: 24.2 +/- 5.1). No significant changes in ACTH (pg/mL) responses before (ghrelin: 210.9 +/- 69.9; GHRP-6: 199.8 +/- 88.8) and after treatment (ghrelin: 159.7 +/- 40.3; GHRP-6: 227 +/- 127.2) were observed. In conclusion, after short-term ketoconazole treatment there are no changes in GH or ACTH responses, despite a major decrease of cortisol levels. A longer period of treatment might be necessary for the recovery of pituitary function.

  4. Genetic and Environmental Determinants of Plasma Total Homocysteine Levels: Impact of Population-wide Folate Fortification

    PubMed Central

    Nagele, Peter; Meissner, Konrad; Francis, Amber; Födinger, Manuela; Saccone, Nancy L.

    2011-01-01

    Objectives Folate metabolism is an important target for drug therapy. Drug-induced inhibition of folate metabolism often causes an elevation of plasma total homocysteine (tHcy). Plasma tHcy levels are influenced by several non-genetic (e.g., folate intake, age, smoking) as well as genetic factors. Over the last decade, several countries have implemented a nation-wide folate fortification program of all grain products. This investigation sought to determine the impact of folate fortification on the relative contribution of environmental and genetic factors to the variability of plasma tHcy. Methods Two cohorts were compared in this study, one from the U.S. (with folate fortification, n=281), and one from Austria (without folate fortification, n=139). Several environmental factors as well as previously identified gene variants important for tHcy levels (MTHFR C677T, MTHFR A1298C, MTRR A66G) were examined for their ability to predict plasma tHcy in a multiple linear regression model. Results Non-genetic, environmental factors had a comparable influence on plasma tHcy between the two cohorts (R2 ~ 0.19). However, after adjusting for other covariates, the tested gene variants had a substantially smaller impact among patients from the folate fortified cohort (R2= 0.021) compared to the non-folate fortified cohort (R2= 0.095). The MTHFR C677T polymorphism was the single most important genetic factor. Male gender, smoking and folate levels were important predictors for non-folate fortified patients; age for folate fortified. Conclusions Population-wide folate fortification had a significant effect on the variability of plasma tHcy and reduced the influence of genetic factors, most importantly the MTHFR 677TT genotype, and may be an important confounder for a personalized drug therapy. PMID:21597397

  5. The relation between serum sex steroid levels and plasma cell infiltrates in endometritis.

    PubMed

    Punnonen, R; Lehtinen, M; Teisala, K; Aine, R; Rantala, I; Heinonen, P K; Miettinen, A; Laine, S; Paavonen, J

    1989-01-01

    We measured serum levels of progesterone and estradiol among 35 patients with endometritis confirmed by endometrial biopsy. The onset of symptoms took place predominantly in the proliferative phase of the cycle. A negative correlation was found between the serum progesterone levels and the histopathologic severity of plasma cell endometritis. Our results suggest that the hormonal status contributes to the immune response and susceptibility to endometrial infection.

  6. Plasma adrenocorticotropin responses to opioid blockade with naloxone: generating a dose-response curve in a single session.

    PubMed

    Mangold, D; McCaul, M E; Ali, M; Wand, G S

    2000-08-15

    We examined two methods of generating a dose-response curve to the opioid receptor antagonist naloxone. In 15 healthy male subjects (18-25 years) plasma adrenocorticotropin (ACTH) responses to five doses of naloxone studied over 5 separate days were compared to plasma ACTH responses to five incremental doses of naloxone studied within a single session. There was a statistically significant positive correlation in ACTH responses (area under the curve and peak) between dosing methods. Furthermore, the doses of naloxone that produced half-maximal and maximal ACTH response were similar. The comparability of ACTH responses between the two naloxone dosing techniques, combined with the safety and ease associated with the single-session methodology, underscores the usefulness of the single-session technique for future investigations.

  7. Plasma soluble thrombomodulin levels are associated with mortality in the acute respiratory distress syndrome

    PubMed Central

    Calfee, Carolyn S.; Liu, Kathleen D.; Kangelaris, Kirsten; Hansen, Helen; Pawlikowska, Ludmila; Ware, Lorraine B.; Alkhouli, Mustafa F.; Abbot, Jason; Matthay, Michael A.

    2015-01-01

    Objective Thombomodulin (TM) is an activator of protein C and a biomarker for endothelial injury. We hypothesized that (1) elevated plasma levels would be associated with clinical outcomes and (2) polymorphisms in the TM gene would be associated with plasma levels. Patients We studied 449 patients enrolled in the Fluid and Catheter Treatment Trial (FACTT) for whom both plasma and DNA were available. We used logistic regression and receiver operator curves (ROC) to test for associations between soluble TM (sTM) and mortality at 60 days. Measurements and results Plasma sTM levels were higher in non-survivors than survivors at baseline [median 147 (IQR, 95–218) vs. 89 (56–129) ng/mL, p < 0.0001] and on day 3 after study enrollment [205 (146–302) vs. 127 (85–189), p < 0.0001]. The odds of death increased by 2.4 (95 %CI 1.5–3.8, p < 0.001), and by 2.8 (1.7–4.7, P < 0.001) for every log increase in baseline and day 3 sTM levels, respectively, after adjustment for age, race, gender, severity of illness, fluid management strategy, baseline creatinine, and non-pulmonary sepsis as the primary cause of ARDS. By ROC analysis, plasma sTM levels discriminated between non-survivors and survivors [AUC = 72 % (66–78 %) vs. AUC = 54 % for severity based on Berlin criteria). Addition of sTM improved discrimination based on APACHE III from 77 to 80 % (P < 0.03). sTM levels at baseline were not statistically different among subjects stratified by genotypes of tag SNPs in the TM gene. Conclusions Higher plasma sTM levels are associated with increased mortality in ARDS. The lack of association between the sTM levels and genetic variants suggests that the increased levels of sTM may reflect severity of endothelial damage rather than genetic heterogeneity. These findings underscore the importance of endothelial injury in ARDS pathogenesis and suggest that, in combination with clinical markers, sTM could contribute to risk stratification. PMID:25643902

  8. Plasma 25-hydroxyvitamin D2 and D3 levels and incidence of postoperative atrial fibrillation.

    PubMed

    Skuladottir, G V; Cohen, A; Arnar, D O; Hougaard, D M; Torfason, B; Palsson, R; Indridason, O S

    2016-01-01

    Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography-tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P < 0·05) and the incidence of POAF increased significantly with each higher quartile of preoperative plasma levels of 25(OH)D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P < 0·05) on the third postoperative day compared with preoperatively. Our findings demonstrate that higher plasma levels of 25(OH)D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study.

  9. Decreased Endothelin-1 Plasma Levels in Multiple Sclerosis Patients: A Possible Factor of Vascular Dysregulation?

    PubMed Central

    Jankowska-Lech, Irmina; Terelak-Borys, Barbara; Grabska-Liberek, Iwona; Palasik, Witold; Bik, Wojciech; Wolińska-Witort, Ewa

    2015-01-01

    Background Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system with possible involvement of vascular dysregulation secondary to endothelial dysfunction caused by destruction of the vessel wall. Vascular dysregulation leads to excessive vasoconstriction or insufficient vasodilatation, resulting in vasospasm mediated by endothelin-1 (ET-1), the most potent and long-lasting mediator. Vascular dysregulation can play an important role in the pathogenesis of some eye disorders and it has been hypothesized that it is a vascular risk factor for glaucomatous optic neuropathy. The aim of this study was to estimate endothelin-1 (ET-1) plasma levels in patients with MS. Material/Methods The MS group consisted of 39 patients (9 males, 30 females), mean age: 38.8±10.02 years, range: 22–62. The control group consisted of 27 healthy volunteers (3 males and 24 females), mean age: 37.4±10.88 years, range: 20–62; clinically, in a non-active stage of the disease. ET-1 plasma levels were measured using the Endothelin-1 ELISA Kit (Immuno-Biological Laboratories Co., Japan). Statistical analysis was performed with the nonparametric Mann-Whitney U test for independent groups. Results Endothelin-1 (ET-1) plasma levels were significantly lower in MS patients compared to healthy controls: mean value 0.55±0.44 pg/ml (146.05±118.27 fmol/ml) vs. 0.95±0.48 pg/ml (252.83±127.16 fmol/ml); P=0.012. Conclusions Significantly decreased ET-1 plasma levels in the MS patients could reflect the non-active disease at the time of ET-1 measurements or the effects of immunomodulatory treatment, but it cannot be excluded that decreased ET-1 plasma levels in these patients might result from vascular dysregulation. PMID:25864450

  10. Gene-diet interactions on plasma lipid levels in the Inuit population.

    PubMed

    Rudkowska, Iwona; Dewailly, Eric; Hegele, Robert A; Boiteau, Véronique; Dubé-Linteau, Ariane; Abdous, Belkacem; Giguere, Yves; Chateau-Degat, Marie-Ludivine; Vohl, Marie-Claude

    2013-03-14

    The Inuit population is often described as being protected against CVD due to their traditional dietary patterns and their unique genetic background. The objective of the present study was to examine gene-diet interaction effects on plasma lipid levels in the Inuit population. Data from the Qanuippitaa Nunavik Health Survey (n 553) were analysed via regression models which included the following: genotypes for thirty-five known polymorphisms (SNP) from twenty genes related to lipid metabolism; dietary fat intake including total fat (TotFat) and saturated fat (SatFat) estimated from a FFQ; plasma lipid levels, namely total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and TAG. The results demonstrate that allele frequencies were different in the Inuit population compared with the Caucasian population. Further, seven SNP (APOA1 - 75G/A (rs670), APOB XbAI (rs693), AGT M235T (rs699), LIPC 480C/T (rs1800588), APOA1 84T/C (rs5070), PPARG2 - 618C/G (rs10865710) and APOE 219G/T (rs405509)) in interaction with TotFat and SatFat were significantly associated with one or two plasma lipid parameters. Another four SNP (APOC3 3238C>G (rs5128), CETP I405V (rs5882), CYP1A1 A4889G (rs1048943) and ABCA1 Arg219Lys (rs2230806)) in interaction with either TotFat or SatFat intake were significantly associated with one plasma lipid variable. Further, an additive effect of these SNP in interaction with TotFat or SatFat intake was significantly associated with higher TC, LDL-C or TAG levels, as well as with lower HDL-C levels. In conclusion, the present study supports the notion that gene-diet interactions play an important role in modifying plasma lipid levels in the Inuit population.

  11. Simvastatin Effect on Calcium and Silicon Plasma Levels in Postmenopausal Women with Osteoarthritis.

    PubMed

    Horecka, Anna; Hordyjewska, Anna; Blicharski, Tomasz; Kocot, Joanna; Żelazowska, Renata; Lewandowska, Anna; Kurzepa, Jacek

    2016-05-01

    Postmenopausal women more often suffered from knee osteoarthritis and its pathogenesis still remains unclear. Calcium and silicon are significant elements involved in bone and joint metabolism, especially in older people. Cardiovascular diseases are common worldwide and simvastatin is the most prescribed drug in such population of patients. The purpose of this study was to evaluate the effect of simvastatin administration on calcium and silicon concentration in the plasma of postmenopausal women with osteoarthritis. Sixty postmenopausal mild hypercholesterolemic women (mean age 61.4 years, range 54-68) were enrolled. Thirty patients received simvastatin (20 or 40 mg/day) for at least 1 year before being enrolled (simvastatin "+" group). Control group consists of remaining 30 women (simvastatin "-"group). Silicon and calcium concentrations were measured spectrophotometrically. Plasma simvastatin level was determined 3 h after the drug administration using HPLC-UV-Vis. Calcium but not silicon level was significantly lower in patients receiving simvastatin in comparison with non-statin group (1.91 ± 0.32 vs. 2.33 ± 0.19 mmol/l, p < 0.05). A weak but significant positive correlation between plasma silicon and simvastatin levels (r = 0.3, p < 0.05) was observed; this may be due to the fact that simvastatin contains silicon dioxide as an inactive ingredient. The mean simvastatin concentration was 9.02 ng/ml. All hypotheses were verified at the significance level of p < 0.05. A statistically significant decrease in the plasma calcium concentration of postmenopausal women, treated with simvastatin suggests that simvastatin may play a role in calcium metabolism in postmenopausal women with osteoarthritis. Positive correlation of simvastatin concentration with silicon level in the plasma suggests that both might prompt the positive effect of osteoarthritis treatment.

  12. Development of a label-free immunosensor system for detecting plasma cortisol levels in fish.

    PubMed

    Wu, Haiyun; Ohnuki, Hitoshi; Hibi, Kyoko; Ren, Huifeng; Endo, Hideaki

    2016-02-01

    Fishes display a wide variation in their physiological responses to stress, which is clearly evident in the plasma corticosteroid changes, chiefly cortisol levels in fish. In the present study, we describe a novel label-free immunosensor for detecting plasma cortisol levels. The method is based on immunologic reactions and amperometric measurement using cyclic voltammetry. For the immobilization of the antibody on the surface of sensing electrode, we used a self-assembled monolayer of thiol-containing compounds. Using this electrode, we detect the CV signal change caused by the generation of antigen-antibody complex. The immunosensor showed a response to cortisol levels, and the anodic peak value linearly decreased with a correlation coefficient of 0.990 in diluted plasma. The specificity of the label-free immunosensor system was investigated using other steroid hormones, such as 17α, 20β-dihydroxy-4-pregnen-3-one, progesterone, estriol, estradiol, and testosterone. The specific detection of cortisol was suggested by a minimal change from -0.32 to 0.51 μA in the anodic peak value of the other steroid hormones. The sensor system was used to determine the plasma cortisol levels in Nile tilapia (Oreochromis niloticus), and the results were compared with those of the same samples determined using the conventional method (ELISA). A good correlation was obtained between values determined using both methods (correlation coefficient 0.993). These findings suggest that the proposed label-free immunosensor could be useful for rapid and convenient analysis of cortisol levels in fish plasma samples.

  13. Cognitive style, alprazolam plasma levels, and treatment response in panic disorder.

    PubMed

    Uhlenhuth, E H; Starcevic, Vladan; Qualls, Clifford; Antal, Edward J; Matuzas, William; Javaid, Javaid I; Barnhill, Jamie

    2008-01-01

    This study investigated an anxiety-prone cognitive style (measured by the Anxious Thoughts and Tendencies Questionnaire, AT&T) as a predictor of the acute response to increasing alprazolam plasma levels in panic disorder. Panic disorder patients (n=26) were treated with escalating doses of alprazolam for 4 weeks, then a fixed dose of 1 mg four times a day for 4 weeks. At 0, 1, 2, 3, 4, 6, and 8 weeks, trough alprazolam plasma levels; clinical, self-report, and performance measures; and vital signs were assessed. Panic attack data were from daily diaries. The repeated response measures were analyzed in relation to alprazolam plasma levels using SAS GENMOD, with patients classified as high or low on the baseline AT&T. Panic attacks, anticipatory anxiety, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, and clinicians' global ratings improved with increasing alprazolam plasma levels. Hopkins Symptom Checklist-90 Anger-Hostility; Profile of Mood States Vigor, Confusion, and Friendliness; and speed and accuracy of performance worsened. Patients with high AT&T scores were worse throughout the study on situational panics, fear, avoidance, overall agoraphobia, the Hamilton Anxiety Rating Scale, the Hamilton Rating Scale for Depression, and Clinical Global Improvement; most Hopkins Symptom Checklist-90 clusters; Profile of Mood States Anxiety, Depression, and Confusion; and Continuous Performance Task omissions. We conclude that in panic disorder: (1) alprazolam has a broad spectrum of clinical activity related to plasma levels in individual patients; (2) sedation, disinhibition, and performance deficits may persist for at least a month after dose escalation ends; (3) marked anxiety-prone cognitions predict more symptoms throughout treatment, but do not modify the response to alprazolam and therefore should not influence the choice of alprazolam as treatment.

  14. High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age.

    PubMed

    Mangialasche, Francesca; Kivipelto, Miia; Mecocci, Patrizia; Rizzuto, Debora; Palmer, Katie; Winblad, Bengt; Fratiglioni, Laura

    2010-01-01

    In this study we investigated the association between plasma levels of eight forms of vitamin E and incidence of Alzheimer's disease (AD) among oldest-old individuals in a population-based setting. A dementia-free sample of 232 subjects aged 80+ years, derived from the Kungsholmen Project, was followed-up to 6 years to detect incident AD. Plasma levels of vitamin E (alpha-, beta-, gamma, and delta-tocopherol; alpha-, beta-, gamma-, and delta-tocotrienol) were measured at baseline. Vitamin E forms-AD association was analyzed with Cox proportional hazard model after adjustment for several potential confounders. Subjects with plasma levels of total tocopherols, total tocotrienols, or total vitamin E in the highest tertile had a reduced risk of developing AD in comparison to persons in the lowest tertile. Multi-adjusted hazard ratios (HRs) and 95% confidence interval (CI) were 0.55 (0.32-0.94) for total tocopherols, 0.46 (0.23-0.92) for total tocotrienols, and 0.55 (0.32-0.94) for total vitamin E. When considering each vitamin E form, the risk of developing AD was reduced only in association with high plasma levels of beta-tocopherol (HR: 0.62, 95% CI 0.39-0.99), whereas alpha-tocopherol, alpha- tocotrienol, and beta-tocotrienol showed only a marginally significant effect in the multiadjusted model [HR (95% CI): alpha-tocopherol: 0.72 (0.48-1.09); alpha-tocotrienol: 0.70 (0.44-1.11); beta-tocotrienol: 0.69 (0.45-1.06)]. In conclusion, high plasma levels of vitamin E are associated with a reduced risk of AD in advanced age. The neuroprotective effect of vitamin E seems to be related to the combination of different forms, rather than to alpha-tocopherol alone, whose efficacy in interventions against AD is currently debated.

  15. Increased plasma levels of competing amino acids, rather than lowered plasma tryptophan levels, are associated with a non-response to treatment in major depression.

    PubMed

    Ormstad, Heidi; Dahl, Johan; Verkerk, Robert; Andreassen, Ole A; Maes, Michael

    2016-08-01

    Lowered plasma tryptophan (TRP) and TRP/competing amino acid (CAA) ratio may be involved in the pathophysiology of major depression (MDD). Increased cortisol and immune-inflammatory mediators in MDD may affect the availability of TRP to the brain. We investigated whether baseline or post-treatment TRP, CAAs and TRP/CAA ratio are associated with a treatment response in MDD and whether these effects may be mediated by cortisol or immune biomarkers. We included 50 medication-free MDD patients with a depressive episode (DSM diagnosis) and assessed symptom severity with the Inventory of Depressive Symptomatology (IDS) before and after treatment as usual for 12 weeks (endpoint). Plasma levels of TRP, CAAs, the ratio, cortisol, CRP and 6 selected cytokines were assayed. The primary outcome was a 50% reduction in the IDS, while the secondary was a remission of the depressive episode. In IDS non-responders, CAAs increased and the TRP/CAA ratio decreased, while in IDS responders CAAs decreased and the TRP/CAA ratio increased from baseline to endpoint. In patients who were still depressed at endpoint TRP and CAAs levels had increased from baseline, while in remitted patients no such effects were found. Increases in CAAs were inversely correlated with changes in interleukin-1 receptor antagonist levels. The results show that increased CAA levels from baseline to endpoint are associated with a non-response to treatment in MDD patients. This suggests that the mechanism underpinning the CAA-related treatment resistance may be related to changes in immune pathways. CAA levels and amino acid metabolism may be new drug targets in depression.

  16. Follow-up measurements of Nevirapine plasma levels over a prolonged period.

    PubMed

    Sienz, M; Zilly, M; Ebigbo, A; Knipper, A; Winzer, R; Klinker, H; Langmann, Peter

    2004-08-31

    Over a period of more than four years of treatment, 177 Nevirapine plasma levels were taken from 27 patients. The values showed a high inter-patient variability and a lower intra-patient variability. Differences in body weight turned out to be the main reason for inter-patient variability. Treatment over a prolonged period did not result in any change in plasma concentrations. Adjusting dosage by means of therapeutic drug monitoring would appear to be a reasonable way of maximising patient benefit from treatment.

  17. Cyclic GMP levels in the rat brain and plasma during clinical death and after resuscitation.

    PubMed

    Kapuściński, A

    1993-01-01

    Changes of cGMP content in the rat brain and plasma have been evaluated by means of the radioimmunologic method after 5-min clinical death and up to 2 hours after resuscitation. Ischemia produced a decrease of cGMP in the brain, however, at the 15th min after resuscitation a reversible significant rise of nucleotide concentration was noted. In plasma at the end of ischemia and in the postischemic period a significant decrease of cGMP level was observed. The mechanisms of cGMP regulation in the central nervous system and the significance of the obtained results are discussed.

  18. Alterations in the levels of plasma amino acids in polycystic ovary syndrome- A pilot study

    PubMed Central

    Unni, C. Sumithra N.; Lakshman, Lakshmi R.; Vaidyanathan, Kannan; Subhakumari, K.N.; Menon, N. Leela

    2015-01-01

    Background & objectives: Plasma amino acid levels are known to be altered in conditions like sepsis and burns which are situations of metabolic stress. Polycystic ovary syndrome (PCOS), a condition which affects a woman throughout her life, is said to be associated with metabolic stress. This study was undertaken to assess if there were significant alterations in the levels of plasma amino acids in women with PCOS. Methods: Sixty five women with PCOS along with the similar number of age matched normal controls were included in this study. Levels of 14 amino acids were determined using reverse phase high performance liquid chromatography. Results: The levels of methionine, cystine, isoleucine, phenylalanine, valine, tyrosine, proline, glycine, lysine and histidine were found to be significantly (P<0.001) lower in cases than in controls. Arginine and alanine levels were found to be significantly (P<0.001) higher in cases compared with controls. Interpretation & conclusions: Our findings showed significant derangement in the levels of plasma amino acids in women with PCOS which might be due to the oxidative and metabolic stress associated with it. Further studies need to be done to confirm the findings. PMID:26658589

  19. Utility of Plasma Osteopontin Levels in Management of Community-Acquired Pneumonia

    PubMed Central

    Chang, Jer-Hwa; Hung, Wen-Yueh; Bai, Kuan-Jen; Yang, Shun-Fa; Chien, Ming-Hsien

    2016-01-01

    Osteopontin (OPN) is an essential cytokine involved in immune cell recruitment and an important regulator of inflammation. The purpose of this study was to examine differences in OPN plasma levels between before and after antibiotic treatment in hospitalized adult patients with community-acquired pneumonia (CAP). OPN levels were measured in 93 patients with CAP and 54 healthy controls using a commercial enzyme-linked immunosorbent assay (ELISA). The CURB-65, Pneumonia Severity Index (PSI), and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were used to determine the CAP severity in patients upon initial hospitalization. A decline in the number of white blood cells (WBCs) and neutrophils, and decreases in the levels of OPN and C-reactive protein (CRP) were observed after antibiotic treatment. Only the plasma level of OPN, but not CRP, was correlated with the severity of CAP based on the PSI (r = 0.514, p < 0.001), CURB-65 (r = 0.396, p < 0.001), and APACHE II scores (r = 0.473, p < 0.001). The OPN level also showed a significant correlation with the length of hospital stay (r = 0.210, p = 0.044). In conclusion, plasma level of OPN may act as diagnostic adjuvant biomarkers for CAP and further play a role in clinical assessment of the severity of CAP, which could potentially guide the development of treatment strategies. PMID:27647996

  20. Reduction in plasma vasopressin levels of dehydrated rats following acute stress

    NASA Technical Reports Server (NTRS)

    Keil, L. C.; Severs, W. B.

    1977-01-01

    Results are presented for an investigation directed to substantiate and extend preliminary findings of stress-induced reduction in plasma arginine vasopressin (pAVP). Since normally hydrated rats have very low levels of pAVP, it is difficult to measure reliably any decrease in pAVP that may result from stress. To overcome this problem, the pAVP levels of the tested rats were raised by dehydration prior to application of stress. A radioimmunoassay for pAVP is described and used to determine the levels of vasopressin in the plasma of nondehydrated and dehydrated rats after exposure to ether or acceleration stress. Plasma pAVP is also determined in rats following nicotine administration. It is shown that exposure of nondehydrated rats to ether or acceleration stress does not elicit any significant alterations in circulating pAVP levels while nicotine injections stimulate a marked increase. In particular, ether and acceleration stress produce a rapid reduction in the pAVP level of dehydrated rats, the decrease being observed in both large and small animals. The mechanism for this reduction in pAVP level following stress is yet unknown.

  1. Circularly polarized, sinusoidal, 50 Hz magnetic field exposure does not influence plasma testosterone levels of rats.

    PubMed

    Kato, M; Honma, K; Shigemitsu, T; Shiga, Y

    1994-01-01

    We exposed rats to circularly polarized 50 Hz magnetic fields to determine if plasma testosterone concentration was affected. Previous experiments indicate that magnetic fields suppress the nighttime rise in melatonin, suggesting that other neuroendocrine changes might occur as well. Male Wistar-King rats were exposed almost continuously for 6 weeks to magnetic flux densities of 1, 5, or 50 microT. Blood samples were obtained by decapitation at 12:00 h and 24:00 h. Plasma testosterone concentration showed a significant day-night difference, with a higher level at 12:00 h when studied in July and December, but night difference, with a higher level at 12:00 h when studied in July and December, but the day-night difference disappeared when concentrations were studied in April. In three experiments, magnetic field exposure had no statistically significant effect on plasma testosterone levels compared with the sham-exposed groups. These findings indicate that 6 weeks of nearly continuous exposure to circularly polarized, 50 Hz magnetic fields did not change plasma testosterone concentration in rats.

  2. Taste acuity, plasma zinc levels, and weight loss during radiotherapy: a study of relationships

    SciTech Connect

    Bolze, M.S.; Fosmire, G.J.; Stryker, J.A.; Chung, C.K.; Flipse, B.G.

    1982-07-01

    Thirty-five patients who were to undergo radiotherapy and 13 normal subjects were evaluated with taste questionnaires, taste acuity tests, and plasma zinc analyses. The studies were repeated on the patients in the fifth week of radiotherapy. The mean taste thresholds for NaCl (salt), sucrose (sweet), HCl (sour), and urea (bitter) were elevated and the plasma zinc levels were lower (77.2 +/- 11.8 vs. 94.6 +/- 30.1 g/100 ml, p = 0.055) for the patients than for the controls. However, there was not a significant correlation between the taste thresholds and plasma zinc levels at any time. The mean weight loss experienced by the 14 patients who reported subjective taste alteration in the fifth week was 3.1 kg versus 0.1 kg (p = 0.005) for those who did not report taste alteration. The data suggest that alterations in taste acuity, but not plasma zinc levels, are associated with weight loss during radiotherapy.

  3. Taste acuity, plasma zinc levels, and weight loss during radiotherapy: a study of relationships

    SciTech Connect

    Bolze, M.S.; Fosmire, G.J.; Stryker, J.A.; Chung, C.K.; Flipse, B.G.

    1982-07-01

    Thirty-five patients who were to undergo radiotherapy and 13 normal subjects were evaluated with taste questionnaires, taste acuity tests, and plasma zinc analyses. The studies were repeated on the patients in the fifth week of radiotherapy. The mean taste thresholds for NaCl (salt), sucrose (sweet), HCl (sour), and urea (bitter) were elevated and the plasma zinc levels were lower (77.2 +/- 11.8 vs. 94.6 +/- 30.1 g/100 ml, p . 0.055) for the patients than for the controls. However, there was not a significant correlation between the taste thresholds and plasma zinc levels at any time. The mean weight loss experienced by the 14 patients who reported subjective taste alteration in the fifth week was 3.1 kg versus 0.1 kg (p . 0.005) for those who did not report taste alteration. The data suggest that alterations in taste acuity, but not plasma zinc levels, are associated with weight loss during radiotherapy.

  4. Relationship of drinking water disinfectants to plasma cholesterol and thyroid hormone levels in experimental studies

    SciTech Connect

    Revis, N.W.; McCauley, P.; Bull, R.; Holdsworth, G.

    1986-03-01

    The effects of drinking water containing 2 or 15 ppm chlorine (pH 6.5 and 8.5), chlorine dioxide, and monochloramine on thyroid function and plasma cholesterol were studied because previous investigators have reported cardiovascular abnormalities in experimental animals exposed to chlorinated water. Plasma thyroxine (T4) levels, as compared to controls, were significantly decreased in pigeons fed a normal or high-cholesterol diet and drinking water containing these drinking water disinfectants at a concentration of 15 ppm (the exception was chlorine at pH 6.5) for 3 months. In most of the treatment groups, T4 levels were significantly lower following the exposure to drinking water containing the 2 ppm dose. Increase in plasma cholesterol were frequently observed in the groups with lower T4 levels. This association was most evident in pigeons fed the high-cholesterol diet and exposed to these disinfectants at a dose of 15 ppm. The factor(s) associated with the effect of these disinfectants on plasma T4 and cholesterol is not known. The authors suggest however that these effects are probably mediated by products formed when these disinfectants react with organic matter in the upper gastrointestinal tract.

  5. Programming of the hypothalamic-pituitary-adrenal axis by neonatal intermittent hypoxia: effects on adult male ACTH and corticosterone responses are stress specific.

    PubMed

    Chintamaneni, Kathan; Bruder, Eric D; Raff, Hershel

    2014-05-01

    Intermittent hypoxia (IH) is an animal model of apnea-induced hypoxia, a common stressor in the premature neonate. Neonatal stressors may have long-term programming effects in the adult. We hypothesized that neonatal exposure to IH leads to significant changes in basal and stress-induced hypothalamic-pituitary-adrenal (HPA) axis function in the adult male rat. Rat pups were exposed to normoxia (control) or 6 approximately 30-second cycles of IH (5% or 10% inspired O₂) daily on postnatal days 2-6. At approximately 100 days of age, we assessed the diurnal rhythm of plasma corticosterone and stress-induced plasma ACTH and corticosterone responses, as well as mRNA expression of pertinent genes within the HPA axis. Basal diurnal rhythm of plasma corticosterone concentrations in the adult rat were not affected by prior exposure to neonatal IH. Adults exposed to 10% IH as neonates exhibited an augmented peak ACTH response and a prolonged corticosterone response to restraint stress; however, HPA axis responses to insulin-induced hypoglycemia were not augmented in adults exposed to neonatal IH. Pituitary Pomc, Crhr1, Nr3c1, Nr3c2, Avpr1b, and Hif1a mRNA expression was decreased in adults exposed to neonatal 10% IH. Expression of pertinent hypothalamic and adrenal mRNAs was not affected by neonatal IH. We conclude that exposure to neonatal 10% IH programs the adult HPA axis to hyperrespond to acute stimuli in a stressor-specific manner.

  6. Corticotropin releasing hormone- and adreno-corticotropin-like immunoreactivity in human placenta, peripheral and uterine vein plasma.

    PubMed

    Schulte, H M; Healy, D L

    1987-01-01

    The presence of corticotropin releasing hormone (CRH)-like immunoreactivity (IR) in human placenta and maternal peripheral blood has been reported by many investigators. However, its physiological role has not yet been defined. We investigated plasma and placental tissue from women at different times of pregnancy and performed peripheral and uterine vein sampling during caesarean section before and after removal of the placenta. Beside IR-CRH, IR-GRF and -GnRH as well as -ACTH and cortisol were measured. The highest content of CRH was found in placental extracts from end term (40 weeks) pregnancies and lower levels at an earlier stage (10 weeks). Plasma CRH from peripheral blood could be detected in some samples and was higher as pregnancy advanced. Thirty minutes after removal of the placenta CRH levels dropped in peripheral plasma and could not be detected in uterine vein samples. IR-ACTH plasma levels were within the range of normals, cortisol was elevated. Gel- and HPLC-chromatographie revealed that placental extracts coeluted with synthetic human CRH. The material from endterm placenta showed full bioactivity in the rat pituitary bio-assay. IR-GRF could only be detected in 10 weeks placental tissue and no IR-GnRH was measured. We conclude that CRH from the placenta is biologically active, however, cannot stimulate the maternal pituitary-adrenal-axis.

  7. Effect of 14 days of bed rest on urine metabolite excretion and plasma enzyme levels

    NASA Technical Reports Server (NTRS)

    Pace, N.; Grunbaum, B. W.; Kodama, A. M.; Rahlmann, D. F.; Newsom, B. D.

    1974-01-01

    After 1 week of ambulatory base-line measurement, a group of 8 men 19-26 years of age remained continuously recumbent for 14 days. Studies were continued for 1 week following the prolonged recumbency. Urine excretion rates for a number of constituents were determined 2 days before bed rest, on day 14 of bed rest, and day 6 after bed rest. Blood plasma samples were also obtained at these times, and analyzed for several enzymes. On day 14 of bed rest significant increases were observed in urine excretion of total osmotically-active substances, magnesium, calcium, phosphate, creatinine, hydroxyproline, and 17-OH corticosteroids. A decrease occurred in urinary glucose excretion. Plasma levels of alkaline phosphatase and LDH-3 were depressed, while plasma GPT was elevated. Many of these changes persisted on day 6 after bed rest, and are interpreted as concomitants of the disuse atrophy of the musculoskeletal system that characterizes prolonged bed rest and weightlessness.

  8. Plasma levels of TGF-β1 in homeostasis of the inflammation in sickle cell disease.

    PubMed

    Torres, Lidiane de Souza; Okumura, Jéssika Viviani; da Silva, Danilo Grünig Humberto; Belini Júnior, Édis; de Oliveira, Renan Garcia; Mimura, Kallyne Kioko Oliveira; Lobo, Clarisse Lopes de Castro; Oliani, Sonia Maria; Bonini Domingos, Claudia Regina

    2016-04-01

    Sickle cell disease (SCD) represents a chronic inflammatory condition with complications triggered by the polymerization of hemoglobin S (Hb S), resulting in a series of cellular interactions mediated by inflammatory cytokines, as the transforming growth factor beta (TGF-β), which plays an important role in inflammation resolution. This study assessed the relation between SCD inflammation and the plasma concentration of TGF-β1, and also checked the influence of the presence of -509C/T polymorphism in TGFB1 gene on TGF-β1 plasma values. The plasma levels of TGF-β1 were quantified by ELISA in 115 patients with SCD (genotypes SS, SD-Los Angeles, Sβ-thalassemia and SC) and in 58 individuals with no hemoglobinopathies (Hb AA), as the control group. The -509C/T polymorphism in TGFB1 gene was screened by PCR-RFLP. The correlation between TGF-β1 plasma levels and the inflammation was based on its association with the count of platelets, total white blood cells (WBC) and neutrophils in the peripheral blood. Patients with SCD showed plasma levels of TGF-β1 higher than the control group, especially the Hb SS genotype, followed by the group with Hb SD. Polymorphism investigation showed no interference in the values obtained for the cytokine in the groups evaluated. All SCD groups showed TGF-β1 levels positively correlated to the platelets and WBC counts. The original data obtained in this study for SCD support the involvement of TGF-β1 in regulating of the inflammatory response and suggest that this marker possibly may become a potential therapeutic target in the treatment of the disease.

  9. In vivo evidence that Agxt2 can regulate plasma levels of dimethylarginines in mice.

    PubMed

    Kittel, Anja; Maas, Renke; König, Jörg; Mieth, Maren; Weiss, Norbert; Jarzebska, Natalia; Hohenstein, Bernd; Martens-Lobenhoffer, Jens; Bode-Böger, Stefanie M; Rodionov, Roman N

    2013-01-04

    Elevated plasma concentrations of the asymmetric (ADMA) and symmetric (SDMA) dimethylarginine have repeatedly been linked to adverse cardiovascular clinical outcomes. Both dimethylarginines can be degraded by alanine-glyoxylate aminotransferase 2 (Agxt2), which is also the key enzyme responsible for the degradation of endogenously formed β-aminoisobutyrate (BAIB). In the present study we wanted to investigate the effect of BAIB on Agxt2 expression and Agxt2-mediated metabolism of dimethylarginines. We infused BAIB or saline intraperitoneally for 7days in C57/BL6 mice via minipumps. Expression of Agxt2 was determined in liver and kidney. The concentrations of BAIB, dimethylarginines and the Agxt2-specific ADMA metabolite α-keto-δ-(N(G),N(G)-dimethylguanidino)valeric acid (DMGV) was determined by LC-MS/MS in plasma and urine. As compared to controls systemic administration of BAIB increased plasma and urine BAIB levels by a factor of 26.5 (p<0.001) and 25.8 (p<0.01), respectively. BAIB infusion resulted in an increase of the plasma ADMA and SDMA concentrations of 27% and 31%, respectively, (both p<0.05) and a 24% decrease of plasma DMGV levels (p<0.05), while expression of Agxt2 was not different. Our data demonstrate that BAIB can inhibit Agxt2-mediated metabolism of dimethylarginines and show for the first time that endogenous Agxt2 is involved in the regulation of systemic ADMA, SDMA and DMGV levels. The effect of BAIB excess on endogenous dimethylarginine levels may have direct clinical implications for humans with the relatively common genetic trait of hyper-β-aminoisobutyric aciduria.

  10. Serial changes in plasma annexin A1 and cortisol levels in sepsis patients.

    PubMed

    Tsai, Wen-Hui; Li, I-Ting; Yu, Yuan-Bin; Hsu, Hui-Chi; Shih, Chung-Hung

    2014-02-28

    Annexin A1 (AnxA1), originally identified as a glucocorticoid-regulated protein, is an impor- tant endogenous anti-inflammatory mediator during the resolution phase of inflammation, and its cir- culating level has been rarely studied in sepsis patients. Glucocorticoid has been extensively used in treating patients with sepsis. However, it is unclear whether endogenous cortisol or exogenous glucocor- ticoid contributes to the regulation of AnxA1 levels in peripheral blood of sepsis patients. The aim of this study was to investigate: [1] serial changes over time in the plasma levels of AnxA1 and cortisol in sepsis patients; and [2] prognostic value of AnxA1 level in the survival of sepsis patients. Fifty-eight adult sepsis patients admitted to an intensive care unit (ICU) were enrolled. The plasma levels of cortisol and AnxA1 were determined by specific enzyme-link immunosorbent assay. Results show that the median daily levels of cortisol at the 1st, 3rd, 5th and 7th day after admission to ICU were signifi- cantly elevated over the cortisol level of the control subjects. However, the AnxA1 level was elevated in only thirty-three patients (56%) over the observation period. There was no significant correlation between cortisol levels and AnxA1 levels. Further analysis indicated that steroid treatment resulted in significant elevation of the cortisol level over time, but did not affect the AnxA1 level. AnxA1 levels were also not statistically different between surviving and non-surviving patients. In conclusions, the circu- lating level of AnxA1 is elevated in a subgroup of sepsis patients, and the AnxA1 level does not correlate with the cortisol level in the peripheral blood of sepsis patients.

  11. Bone morphogenetic protein 4 and bone morphogenetic protein receptor expression in the pituitary gland of adult dogs in healthy condition and with ACTH-secreting pituitary adenoma.

    PubMed

    Sato, A; Ochi, H; Harada, Y; Yogo, T; Kanno, N; Hara, Y

    2017-01-01

    The purpose of this study was to investigate the expression of bone morphogenetic protein 4 (BMP4) and its receptors, bone morphogenetic protein receptor I (BMPRI) and BMPRII, in the pituitary gland of healthy adult dogs and in those with ACTH-secreting pituitary adenoma. Quantitative polymerase chain reaction analysis showed that the BMP4 messenger RNA expression level in the ACTH-secreting pituitary adenoma samples was significantly lower than that in the normal pituitary gland samples (P = 0.03). However, there were no statistically significant differences between samples with respect to the messenger RNA expression levels of the receptors BMPRIA, BMPRIB, and BMPRII. Double-immunofluorescence analysis of the normal canine pituitary showed that BMP4 was localized in the thyrotroph (51.3 ± 7.3%) and not the corticotroph cells. By contrast, BMPRII was widely expressed in the thyrotroph (19.9 ± 5.2%) and somatotroph cells (94.7 ± 3.6%) but not in the corticotroph cells (P < 0.001, thyrotroph cells vs somatotroph cells). Similarly, in ACTH-secreting pituitary adenoma, BMP4 and BMPRII were not expressed in the corticotroph cells. Moreover, the percentage of BMP4-positive cells was also significantly reduced in the thyrotroph cells of the surrounding normal pituitary tissue obtained from the resected ACTH-secreting pituitary adenoma (8.3 ± 7.9%) compared with that in normal canine pituitary (P < 0.001). BMP4 has been reported to be expressed in corticotroph cells in the human pituitary gland. Therefore, the results of this study reveal a difference in the cellular pattern of BMP4-positive staining in the pituitary gland between humans and dogs and further revealed the pattern of BMPRII-positive staining in the dog pituitary gland. These species-specific differences regarding BMP4 should be considered when using dogs as an animal model for Cushing's disease.

  12. Ectopic ACTH-secreting pituitary adenoma of the sphenoid sinus: case report of endoscopic endonasal resection and systematic review of the literature.

    PubMed

    Seltzer, Justin; Lucas, Joshua; Commins, Deborah; Lerner, Olga; Lerner, Alexander; Carmichael, John D; Zada, Gabriel

    2015-02-01

    Ectopic pituitary adenomas are exceedingly rare entities that are often misdiagnosed. The resulting delay in diagnosis may be particularly concerning in the case of Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Although the total resection of ectopic adenomas results in rapid and durable remission, persistent Cushing syndrome is often associated with permanently damaging invasive procedures and significantly higher risk of mortality. The authors report the case of a 48-year-old man with ACTH-dependent Cushing syndrome. On the morning before surgery, his serum cortisol measured 51 μg/dl, his ACTH level was 195.7 pg/ml, and his urinary free cortisol level was 2109 μg/day. Serum cortisol was not suppressed with the administration of high-dose dexamethasone. Imaging showed separate masses in both the sphenoid sinus and the pituitary gland, complicating the diagnostic process and requiring pathological assessment of both masses. No other abnormalities were found on thoracic, abdominal, or pelvic scans. Gross-total resection of both lesions was accomplished via an endoscopic endonasal transsphenoidal approach. Pathology confirmed an ectopic ACTH pituitary adenoma of the sphenoid sinus and a Crooke hyaline change of the pituitary gland. The patient achieved stable hormonal remission without significant postoperative complications, returned to full activity within 3 months, and remained disease free nearly 1 year after tumor resection. In a systematic literature review, the authors identified 41 cases of ectopic ACTH-secreting pituitary adenomas, including 18 arising in the sphenoid sinus without direct involvement of the sella. Including the case described here, the total number of ectopic ACTH pituitary adenomas arising in the sphenoid sinus was 19, and the total number of ectopic ACTH pituitary adenomas without regard to location was 42. For the 19 patients with adenomas found in the sphenoid sinus, ages ranged

  13. Delta(9)-tetrahydrocannabinol enhances an increase of plasma corticosterone levels induced by forced swim-stress.

    PubMed

    Sano, Kazunori; Koushi, Emi; Irie, Keiichi; Higuchi, Sei; Tsuchihashi, Ryota; Kinjo, Junei; Egashira, Nobuaki; Oishi, Ryozo; Uchida, Naoki; Nagai, Hiroshi; Nishimura, Ryoji; Tanaka, Hiroyuki; Morimoto, Satoshi; Mishima, Kenichi; Iwasaki, Katsunori; Fujiwara, Michihiro

    2009-12-01

    The present study was designed to determine the effect of delta(9)-tetrahydrocannabinol (THC) on susceptibility to stress. We reported that THC significantly prolonged the immobility time during the forced swim-stress. The selective cannabinoid CB(1) receptor antagonist O-2050 significantly reduced the enhancement of immobility by THC. We investigated the effect of THC on levels of stress hormone corticosterone under non-stress and forced swim-stress conditions. THC did not affect plasma corticosterone levels under non-stress conditions. However, THC, together with forced swim-stress, significantly increased plasma corticosterone levels. This effect was inhibited by O-2050. This evidence suggests that THC, under stressful conditions, enhances the susceptibility of the hypothalamus-pituitary-adrenal-axis to stress via the CB(1) receptor, thereby increasing the risk of depression.

  14. Levels of plasma soluble complement receptor 1 (sCR1) in normal Indian adult population.

    PubMed

    Sivasankar, B; Raju, K R; Anand, V; Malu, S; Padmanabhan, S; Tiwari, S C; Das, N; Srivastava, L M

    1999-07-01

    A decrease in the membrane anchored erythrocyte complement receptor 1 (CR1) is reported as an acquired phenomenon in a number of inflammatory and autoimmune diseases with concomitant rise in soluble CR1 (sCR1) levels in plasma. There is a need to establish the normal range of sCR1 in Indian adults to assess the function and disease association of this protein. The plasma sCR1 levels of 50 healthy individuals have been estimated by an indigenously developed sandwich ELISA. sCR1 levels from 26 patients suffering from nephropathies had also been assayed which was much higher than the normal controls. This observation suggests sCR1 as a potential market for the assessment of disease activity in nephropathies.

  15. Correlation between Saliva and Plasma Levels of Endothelin Isoforms ET-1, ET-2, and ET-3.

    PubMed

    Gurusankar, Roma; Kumarathasan, Prem; Saravanamuthu, Anusha; Thomson, Errol M; Vincent, Renaud

    2015-01-01

    Although saliva endothelins are emerging as valuable noninvasive cardiovascular biomarkers, reports on the relationship between isoforms in saliva and plasma remain scarce. We measured endothelins in concurrent saliva and plasma samples (n = 30 males; age 18-63) by HPLC-fluorescence. Results revealed statistically significant positive correlations among all isoforms between saliva and plasma: big endothelin-1 (BET-1, 0.55 ± 0.27 versus 3.35 ± 1.28 pmol/mL; r = 0.38, p = 0.041), endothelin-1 (ET-1, 0.52 ± 0.21 versus 3.45 ± 1.28 pmol/mL; r = 0.53, p = 0.003), endothelin-2 (ET-2, 0.21 ± 0.07 versus 1.63 ± 0.66 pmol/mL; r = 0.51, p = 0.004), and endothelin-3 (ET-3, 0.39 ± 0.19 versus 2.32 ± 1.44 pmol/mL; r = 0.75, p < 0.001). Correlations of BET-1, ET-1, and ET-3 within each compartment were positive in both plasma (p < 0.05) and saliva (p ≤ 0.1), whereas ET-2 was not significantly correlated with other isoforms in either plasma or saliva. For all isoforms, concentrations varied on average fivefold between individuals (90th/10th percentiles); individuals with high plasma endothelin levels generally had high saliva endothelin levels. Our results reveal that salivary ET isoform profiles portray the plasmatic profiles and support the view of coordinated regulation of ET-1 and ET-3, but distinct regulatory pathways for ET-2.

  16. Plasma brain-derived neurotrophic factor levels in patients suffering from post-traumatic stress disorder.

    PubMed

    Su, Shanshan; Xiao, Zeping; Lin, Zhiguang; Qiu, Yongming; Jin, Yichao; Wang, Zhen

    2015-09-30

    A number of studies have been done to investigate the role of brain-derived neurotrophic factor (BDNF) in patients with post-traumatic stress disorder (PTSD). In this study we aimed to test the relationship between plasma BDNF levels and PTSD. We solicited 65 subjects having recently experienced road traffic accidents (RTA) conforming to screening criteria. They were given follow-up examinations after one month, three months, and six months. PTSD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-R-TR, American Psychiatric Association, 2000) using the Mini International Neuropsychiatric Interview (MINI). All participants were divided into two groups: a group with PTSD and a group without PTSD. There were no significant differences in plasma BDNF levels between the two groups at either the 48h or six-month examination. Within the PTSD group, no significant differences were found in plasma BDNF levels between the two examinations. BDNF levels in those without PTSD showed a higher trend over time after trauma. Higher BDNF levels may be an important protective factor for the prevention of traumatized subjects from developing PTSD.

  17. Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians.

    PubMed

    Kim, Sungeun; Nho, Kwangsik; Ramanan, Vijay K; Lai, Dongbing; Foroud, Tatiana M; Lane, Katie; Murrell, Jill R; Gao, Sujuan; Hall, Kathleen S; Unverzagt, Frederick W; Baiyewu, Olusegun; Ogunniyi, Adesola; Gureje, Oye; Kling, Mitchel A; Doraiswamy, P Murali; Kaddurah-Daouk, Rima; Hendrie, Hugh C; Saykin, Andrew J

    2016-01-01

    Plasma homocysteine, a metabolite involved in key cellular methylation processes seems to be implicated in cognitive functions and cardiovascular health with its high levels representing a potential modifiable risk factor for Alzheimer's disease (AD) and other dementias. A better understanding of the genetic factors regulating homocysteine levels, particularly in non-white populations, may help in risk stratification analyses of existing clinical trials and may point to novel targets for homocysteine-lowering therapy. To identify genetic influences on plasma homocysteine levels in individuals with African ancestry, we performed a targeted gene and pathway-based analysis using a priori biological information and then to identify new association performed a genome-wide association study. All analyses used combined data from the African American and Yoruba cohorts from the Indianapolis-Ibadan Dementia Project. Targeted analyses demonstrated significant associations of homocysteine and variants within the CBS (Cystathionine beta-Synthase) gene. We identified a novel genome-wide significant association of the AD risk gene CD2AP (CD2-associated protein) with plasma homocysteine levels in both cohorts. Minor allele (T) carriers of identified CD2AP variant (rs6940729) exhibited decreased homocysteine level. Pathway enrichment analysis identified several interesting pathways including the GABA receptor activation pathway. This is noteworthy given the known antagonistic effect of homocysteine on GABA receptors. These findings identify several new targets warranting further investigation in relation to the role of homocysteine in neurodegeneration.

  18. Impact of restraint and disinhibition on PYY plasma levels and subjective feelings of appetite.

    PubMed

    Martins, C; Robertson, M D; Morgan, L M

    2010-10-01

    The impact of eating behaviours on circulating levels of appetite-regulating hormones remains largely unknown. The aims of this study were to assess the role of restraint and disinhibition on fasting/postprandial peptide YY (PYY) plasma levels and subjective feelings of appetite in normal-weight individuals and to determine whether the effect was energy load dependent. 33 participants (12 men) were classified as restrained/unrestrained and low/high in disinhibition based on Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour Questionnaire. The impact of restraint/disinhibition on PYY plasma levels and feelings of appetite was measured, after a 500kcal and 1000kcal breakfast, using a randomised crossover design. Restraint did not impact on either fasting or postprandial PYY plasma levels, but participants with high disinhibition had a tendency towards a blunted postprandial PYY response. Moreover, restrained eaters reported lower ratings of prospective food consumption postprandially, and a tendency towards higher fullness/lower hunger. In conclusion, circulating PYY is unaffected by restrained eating behaviour, despite being associated with increased fullness and reduced hunger in the fed state. High levels of disinhibition tend to be associated with a blunted PYY response and this may contribute towards the susceptibility to overconsumption and increased risk of weight gain characteristic of this trait.

  19. Increased Levels of Sphingosylphosphorylcholine (SPC) in Plasma of Metabolic Syndrome Patients

    PubMed Central

    El-Najjar, Nahed; Orsó, Evelyn; Wallner, Stefan; Liebisch, Gerhard; Schmitz, Gerd

    2015-01-01

    Recent developments in lipid mass spectrometry enable extensive lipid class and species analysis in metabolic disorders such as diabesity and metabolic syndrome. The minor plasma lipid class sphingosylphosphorylcholine (SPC) was identified as a ligand for lipid sensitive G-protein coupled receptors playing a key role in cell growth, differentiation, motility, calcium signaling, tissue remodeling, vascular diseases and cancer. However, information about its role in diabesity patients is sparse. In this study, we analyzed plasma lipid species in patients at risk for diabesity and the metabolic syndrome and compared them with healthy controls. Our data show that SPC is significantly increased in plasma samples from metabolic syndrome patients but not in plasma from patients at risk for diabesity. Detailed SPC species analysis showed that the observed increase is due to a significant increase in all detected SPC subspecies. Moreover, a strong positive correlation is observed between total SPC and individual SPC species with both body mass index and the acute phase low grade inflammation marker soluble CD163 (sCD163). Collectively, our study provides new information on SPC plasma levels in metabolic syndrome and suggests new avenues for investigation. PMID:26466367

  20. Elevated plasma homocysteine level is possibly associated with skin sclerosis in a series of Japanese patients with systemic sclerosis.

    PubMed

    Motegi, Sei-Ichiro; Toki, Sayaka; Yamada, Kazuya; Uchiyama, Akihiko; Ishikawa, Osamu

    2014-11-01

    Homocysteine is a sulfhydryl-containing amino acid that is derived from dietary methionine, and there has been increasing evidence that elevated plasma homocysteine levels are associated with increased risk of cardiovascular diseases, including carotid, coronary and peripheral arterial disease (PAD). The association of plasma homocysteine levels with peripheral vascular involvements, such as Raynaud phenomenon (RP), digital ulcers (DU) in systemic sclerosis (SSc) patients has not been well studied. The objective of this study was to examine plasma homocysteine levels and their clinical associations in patients with SSc. Plasma homocysteine levels in 151 Japanese patients with SSc and 20 healthy controls were examined. No significant differences were observed in plasma homocysteine levels between SSc patients and healthy individuals. Demographic and clinical features of the SSc patients revealed that severe skin sclerosis, anti-topoisomerase I antibody positivity, complications of DU, acro-osteolysis (AO) and interstitial lung disease (ILD) were significantly more prevalent among the patients with elevated plasma homocysteine levels. The plasma homocysteine levels were positively correlated with modified Rodnan total skin score. The plasma homocysteine levels in the SSc patients with DU, AO and ILD were significantly higher than those in the SSc without DU, AO and ILD, respectively. Plasma homocysteine levels did not correlate with either the mean or max intima-media thickness (IMT) or plaque score, suggesting that plasma homocysteine levels might not be associated with carotid artery atherosclerosis in SSc patients. The measurement of plasma homocysteine levels in SSc patients might be useful for the risk stratifications of severe skin sclerosis, DU and AO.

  1. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men.

    PubMed

    Berge, Kjetil; Piscitelli, Fabiana; Hoem, Nils; Silvestri, Cristoforo; Meyer, Ingo; Banni, Sebastiano; Di Marzo, Vincenzo

    2013-05-27

    We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m², age of 42.6 years and plasma triglycerides of 192.5 ± 96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome.

  2. Human plasma levels of POPs, and diet among native people from Uelen, Chukotka.

    PubMed

    Sandanger, Torkjel M; Brustad, Magritt; Odland, Jon Oyvind; Doudarev, Alexey A; Miretsky, Georgy I; Chaschin, Valery; Burkow, Ivan C; Lund, Eiliv

    2003-08-01

    Some of the people living in the Chukotka Peninsula of Russia depend heavily on marine mammals, but little is known of the exact dietary patterns and plasma levels of POPs among these populations. In this study, POPs levels in plasma from 50 participants from the isolated community of Uelen (Bering Strait) were determined and related to dietary information obtained through a food frequency questionnaire. The intake of marine mammals was high and the combined intake of blubber from walrus, seal and whale was a significant predictor (p < 0.01) of plasma concentrations of sum PCBs and borderline for sum CDs (p = 0.02) and sum DDTs (p = 0.04). There was a significant gender difference in the levels of POPs, and among women there was a significant increase with age. Extensive breastfeeding and lower blubber intake among women could be possible explanations for this gender difference. Despite the high intake of blubber the plasma levels of PCBs and DDTs were lower than some of those reported for the East Coast of Greenland. The geometric mean values for sum PCBs (17 congeners) and sum DDTs were 1316 ng g(-1) lipids and 563 ng g(-1) lipids, respectively. PCB 163, which partly co-eluted with PCB 138, was found in high concentrations (40% of PCB 138). This raises questions regarding the validity of using PCB 138 and PCB 153 to calculate the level of Arochlor 1260. The geometric mean of sum CDs was 518 ng g(-1) lipids. Concentrations of beta-HCH (geometric mean; 410 ng g(-1) lipids) were higher than observed for other native populations depending on marine mammals. Transportation of beta-HCH by ocean currents through the Bering Strait into the Arctic Ocean or regional point sources might explain these elevated levels.

  3. Effects of light on plasma somatolactin levels in red drum (Sciaenops ocellatus).

    PubMed

    Zhu, Y; Thomas, P

    1998-07-01

    The effects of illumination on circulating somatolactin (SL) levels were studied in red drum sampled at various times during a 24-h light-dark cycle (l2L:l2D) and during a 24-h period of constant light. Plasma SL concentrations were low in red drum sampled during the light phase (0.6 +/- 0.05-1.1 +/- 0.2 ng/ml). The levels were significantly elevated during the early-dark phase (5.8 +/- 1.0 ng/ml) and declined during the late-dark phase (0.39 +/- 0.05 ng/ml). In contrast, plasma SL levels remained low. (0.4 +/- 0.1-1.3 +/- 0.4 ng/ml) in fish sampled through a 24-h constant light period following a 1-week exposure to the light-dark cycle. Circulating SL levels were also significantly elevated during the early-dark phase in fish maintained under a reversed light-dark cycle. The role of the eyes in mediation the SL response to light was evaluated by comparing circulating SL levels in optic-tract sectioned and enucleated fish with those of intact (control) fish. Plasma SL concentrations were significantly higher in optic-tract sectioned and enucleated fish (6.5 +/- 0.9-13.8 +/- 1.5 ng/ml) than in control fish (0.6 +/- 0.05-3.9 +/- 0.7 ng/ml) during both the early-dark phase and the early-light phase of the 24-h light-dark cycle. The absence of significant changes in plasma SL levels between the light and dark phases in optic-tract sectioned and enucleated fish appears to be due to a loss of light perception in these fish. Moreover, intact and sham-operated red drum maintained in constant darkness had dramatically increased plasma SL levels (18.8 +/- 2.0-24.8 +/- 1.8 ng/ml). The present results are consistent with our earlier findings that plasma SL levels are elevated in fish kept in constant darkness and in a dark-background tank (reduction in overall light levels) during the light phase. Taken together, these results suggest that plasma SL levels are elevated in red drum in the absence of light and in response to low illumination. Interestingly, the integument of the

  4. Plasma ghrelin and obestatin levels are increased in spontaneously hypertensive rats.

    PubMed

    Li, Zhao-Feng; Guo, Zhi-Fu; Cao, Jiang; Hu, Jian-Qiang; Zhao, Xian-Xian; Xu, Rong-Liang; Huang, Xin-Miao; Qin, Yong-Wen; Zheng, Xing

    2010-02-01

    Obestatin, encoded by the same gene as ghrelin, was first described as a physiological opponent of ghrelin. We investigated fasting plasma ghrelin and obestatin levels in spontaneously hypertensive rats and Wistar-Kyoto rats. We found that ghrelin levels, obestatin levels and the ratio of ghrelin to obestatin were significantly higher in spontaneously hypertensive rats than Wistar-Kyoto rats. Systolic blood pressure and diastolic blood pressure were positively correlated; however, heart period and baroreflex sensitivity were negatively correlated with ghrelin levels. Systolic blood pressure was positively correlated, whereas baroreflex sensitivity was negatively correlated with obestatin levels. In addition, systolic blood pressure was a significantly independent variable of ghrelin levels, obestatin levels, and the ghrelin to obestatin ratio in a multiple regression analysis. Our data suggests that there is a disturbance of ghrelin and obestatin in the circulation of spontaneously hypertensive rats and the ghrelin/obestatin system might play a role in blood pressure regulation.

  5. Interleukin-7 Plasma Levels in Human Differentiate Anorexia Nervosa, Constitutional Thinness and Healthy Obesity

    PubMed Central

    Germain, Natacha; Viltart, Odile; Loyens, Anne; Bruchet, Céline; Nadin, Katia; Wolowczuk, Isabelle; Estour, Bruno; Galusca, Bogdan

    2016-01-01

    Introduction Interleukin-7 (IL-7) is a cytokine involved in energy homeostasis as demonstrated in rodents. Anorexia nervosa is characterized by restrained eating behavior despite adaptive orexigenic regulation profile including high ghrelin plasma levels. Constitutional thinness is a physiological condition of resistance to weight gain with physiological anorexigenic profile including high Peptide YY plasma level. Healthy obesity can be considered as a physiological state of resistance to weight loss with opposite appetite regulating profile to constitutional thinness including low Peptide YY plasma level. No studies in IL-7 are yet available in those populations. Therefore we evaluated circadian plasma levels of IL-7 in anorexia nervosa compared to constitutional thinness, healthy obese and control females. Materials and Methods 10 restrictive-type anorexia nervosa women, 5 bingeing/purging anorexia nervosa woman, 5 recovered restrictive anorexia nervosa women, 4 bulimic females, 10 constitutional thinness women, 7 healthy obese females, and 10 normal weight women controls were enrolled in this cross-sectional study, performed in endocrinology unit and academic laboratory. Twelve-point circadian profiles of plasma IL-7 levels were measured in each subject. Results 24h mean IL-7 plasma levels (pg/ml, mean±SEM) were decreased in restrictive-type anorexia nervosa (123.4±14.4, p<0.0037), bingeing/purging anorexia nervosa (24.2±5.6, p<0.001), recovered restrictive anorexia nervosa (64.2±16.1, p = 0.01) and healthy obese patients (51±3.2, p<0.001) compared to controls (187.7±28.6). Bulimic patients (197.4±42.7) and constitutional thinness patients (264.3±35.8) were similar to controls. Conclusions Low IL-7 is part of the adaptive profile in restrictive-type anorexia nervosa, confirming its difference with constitutional thinness. Healthy obesity, with low IL-7, is once again in mirror image of constitutional thinness with normal high IL-7. PMID:27611669

  6. Variation in dose and plasma level of lamotrigine in patients discharged from a mental health trust

    PubMed Central

    Douglas-Hall, Petrina; Dzahini, Olubanke; Gaughran, Fiona; Bile, Ahmed; Taylor, David

    2016-01-01

    Background: The objectives of this study were to investigate the dose of lamotrigine when prescribed with an enzyme inhibitor or enzyme inducer in patients discharged from a mental health trust and to determine the corresponding lamotrigine plasma concentrations and the factors that may affect these. Methods: All patients discharged on lamotrigine between October 2007 and September 2012 were identified using the pharmacy dispensing database. We recorded demographic details, lamotrigine dose and plasma levels and coprescribed medication. Results: During the designated period, 187 patients were discharged on lamotrigine of whom 117 had their plasma levels recorded. The mean lamotrigine daily dose was 226.1 mg (range 12.5–800 mg) and the mean plasma level 5.9 mg/l (range 0.8–18.1 mg/l). Gender, ethnicity, diagnosis and smoking status had no significant effect on dose or plasma levels. Patients taking an enzyme-inducing drug (n = 6) had significantly lower plasma levels [mean (SD) 3.40 (1.54) mg/l] than those not taking enzyme inducers [n = 111; 6.03 (3.13) mg/l; p = 0.043]. Patients taking an enzyme-inhibiting drug (n = 23) had significantly higher levels [7.47 (3.99) mg/l] than those not taking an inhibitor [n = 94; 5.52 (2.75) mg/l; p = 0.035]. No significant difference was found between the doses of lamotrigine in patients taking an enzyme inhibitor and those not taking one (p = 0.376). No significant difference was found between the doses of lamotrigine in patients taking an enzyme-inducing drug and those not taking any (p = 0.574). Conclusions: Current dosing recommendations indicate that lamotrigine doses should be halved in individuals taking enzyme inhibitors and doubled in those on enzyme inducers. In our survey these recommendations were rarely followed with the consequence that patients received too high or too low a dose of lamotrigine, respectively. PMID:28101320

  7. The significance of ACTH for the process of formation of complex heparin compounds in the blood during immobilization stress

    NASA Technical Reports Server (NTRS)

    Kudryashov, B. A.; Shapiro, F. B.; Lomovskaya, F. B.; Lyapina, L. A.

    1979-01-01

    Adrenocorticotropin (ACTH) was administered to rats at different times following adrenalectomy. Adrenocorticotropin caused a significant increase in the formation of heparin complexes even in the absence of stress factor. When ACTH secretion is blocked, immobilization stress is not accompanied by an increase in the process of complex formation. The effect of ACTH on the formation of heparin complexes was mediated through its stimulation of the adrenal cortex.

  8. Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms.

    PubMed

    Zhang, Hong-Feng; Dai, Yu-Chuan; Wu, Jing; Jia, Mei-Xiang; Zhang, Ji-Shui; Shou, Xiao-Jing; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng

    2016-10-01

    Autism spectrum disorder (ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The "twin" nonapeptides oxytocin (OXT) and arginine-vasopressin (AVP) are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children. As expected, children with ASD had lower plasma OXT levels than gender-matched controls (P = 0.028). No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication (Rho = -0.22, P = 0.076), while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects (Rho = -0.231, P = 0.079). Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children (P = 0.072). In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.

  9. Increased plasma levels of CK-18 as potential cell death biomarker in patients with HELLP syndrome.

    PubMed

    John, K; Wielgosz, S; Schulze-Osthoff, K; Bantel, H; Hass, R

    2013-10-24

    HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome represents a life-threatening pregnancy disorder with high fetal and maternal mortality, but its underlying molecular mechanisms remain unknown. Although apoptosis has been implicated in HELLP syndrome, its pathogenic role remains largely unclear. In the present study, we investigated whether the detection of apoptosis by novel plasma biomarkers is of diagnostic value in HELLP patients. For this purpose, we analyzed two biomarkers that specifically detect apoptosis or overall cell death of epithelial cells, such as hepatocytes or placental trophoblasts, through the release of caspase-cleaved or total (caspase-cleaved and uncleaved) cytokeratin-18 (CK-18) in plasma of HELLP patients compared with pregnant as well as non-pregnant healthy women. In addition, caspase activation and cell death were determined in placental tissues of HELLP patients and individuals with normal pregnancy. In contrast to pregnant or non-pregnant healthy controls, we observed significantly increased levels of both caspase-cleaved and total CK-18 in plasma of HELLP patients. Following delivery, CK-18 levels rapidly decreased in HELLP patients. Caspase activation and cell death were also elevated in placental tissues from HELLP patients compared with healthy pregnant women. These data demonstrate not only that apoptosis is increased in HELLP syndrome, but also that caspase-cleaved or total CK-18 are promising plasma biomarkers to identify patients with HELLP syndrome. Thus, further studies are warranted to evaluate the utility of these biomarkers for monitoring disease activity in HELLP syndrome.

  10. Comparison of plasma bismuth levels after oral dosing with basic bismuth carbonate or tripotassium dicitrato bismuthate.

    PubMed

    Madaus, S; Schulte-Frohlinde, E; Scherer, C; Kämmereit, A; Schusdziarra, V; Classen, M

    1992-04-01

    In 20 healthy subjects plasma bismuth concentration was measured after single oral doses of basic bismuth carbonate or tripotassium dicitrato bismuthate. The drugs were administered in the fasted state or immediately after ingestion of a standard breakfast. After basic bismuth carbonate, plasma bismuth rose to concentrations between 0.7 and 2.6 micrograms/L in the fasted state, while after the meal the maximal level was only 1.3 micrograms/L. In contrast to these very low levels after basic bismuth carbonate, the administration of tripotassium dicitrato bismuthate was paralleled by an increase of plasma bismuth to concentrations between 15 and 232 micrograms/L with a mean peak value of 64 +/- 15.3 (S.E.M.) micrograms/L in the fasted state. Postprandial ingestion of tripotassium dicitrato bismuthate attenuated the peak concentrations to 10.9 +/- 6.3 micrograms/L. One subject, however, had a value of 120 micrograms/L. This study demonstrates that basic bismuth carbonate leads to very low plasma bismuth concentrations, which are far below the critical range that might eventually be associated with bismuth neurotoxicity. Therefore this compound can be considered potentially useful for bismuth therapy of gastrointestinal disorders.

  11. [Efavirenz and nevirapine plasma levels in HIV-infected patients with hemophilia].

    PubMed

    Martorell, Marta; López, Rosa M; Ribera, Esteban; Ruiz, Isabel; Tural, Cristina; Puig, Lluís; Monterde, Josep

    2005-01-01

    The aim of this study was to evaluate efavirenz and nevirapine plasma levels in HIV-infected hemophilic patients seen in two hospitals in Barcelona. Plasma levels of these drugs were determined by high-performance liquid chromatography (HPLC) at four-month intervals, together with viral load and CD4 cell count. Nineteen patients treated with efavirenz and 8 with nevirapine were included, and 68 efavirenz and 31 nevirapine determinations were performed. Mean study time was 12 months. Median efavirenz plasma concentration was 2.95 .g/ml (interval: 1.54-5.26 .g/ml) in patients with favorable virological response and 1.86 .g/ml (0.82-4.88 .g/ml) in patients with detectable viral load (p = 0.32). Nevirapine plasma concentrations were 4.41 .g/ml (3.50-6.72 .g/ml) and 3.12 .g/ml (2.44-3.80 .g/ml) respectively (p = 0.18).

  12. Cardiotrophin-1 plasma levels are associated with the severity of hypertrophy in hypertrophic cardiomyopathy

    PubMed Central

    Monserrat, Lorenzo; López, Begoña; González, Arantxa; Hermida, Manuel; Fernández, Xusto; Ortiz, Martín; Barriales-Villa, Roberto; Castro-Beiras, Alfonso; Díez, Javier

    2011-01-01

    Aims Cardiotrophin-1 (CT-1) is a cytokine that induces hypertrophy in cardiomyocytes and is associated with left ventricular hypertrophy (LVH) in hypertensive patients. The objective of this study was to evaluate whether plasma CT-1 is associated with hypertrophic cardiomyopathy (HCM). Methods and results The study was performed in 124 patients with HCM. All patients underwent a full clinical evaluation and an echocardiogram. Left ventricular hypertrophy was evaluated by the measurement of the maximal LV wall thickness and the Spirito's LVH score. Plasma CT-1 was measured by an enzyme-linked immunosorbent assay. Compared with controls, patients with HCM exhibited higher (P < 0.001) plasma CT-1 levels. Significant correlations were found between CT-1 and maximal LV wall thickness (r = 0.284, P = 0.001) and the Spirito's LVH score (r = 0.287, P = 0.006) in HCM patients. In addition, the levels of CT-1 were higher (P = 0.02) in patients with severe LVH (maximal LV wall thickness ≥30 mm) than in patients with mild or moderate LVH (maximal LV wall thickness <30 mm). Conclusions These findings show that plasma CT-1 is associated with the severity of LVH in patients with HCM. Further studies are required to ascertain whether CT-1 is a diagnostic biomarker of this cardiomyopathy. PMID:21059734

  13. Cytostatic drugs are without significant effect on digitoxin plasma level and renal excretion.

    PubMed

    Kuhlmann, J; Wilke, J; Rietbrock, N

    1982-11-01

    In three patients with malignant lymphoma who received 0.5 mg digitoxin before and 24 hr after combination therapy with cyclophosphamide, Oncovin, procarbazine, and prednisone (COPP) or cyclophosphamide, Oncovin, and prednisone (COP), plasma glycoside concentrations and renal excretion were measured 0 to 168 hr after digitoxin and the areas under plasma concentration-time curves *(AUCs) were calculated. In 10 patients receiving 0.1 mg digitoxin, daily plasma glycoside concentration and daily renal excretion were measured before and after COPP, COP, or cyclophosphamide, Oncovin, cytosine-arabinoside, and prednisone (COAP) treatment schemes. In contrast to previous reports on digoxin, cytostatic drug therapy does not lead to a reduction in steady-state digitoxin plasma levels and daily renal excretion. During cytostatic therapy attainment of peak digitoxin level was delayed after a single dose, showing that the rate of digitoxin absorption was reduced, but that the AUCs and renal excretion of digitoxin (parameters of the extent of digitoxin absorption) were not diminished. Since the absorption rate is not clinically relevant in patients on long-term glycoside therapy, our results indicate that digitoxin is preferable to digoxin in such patients.

  14. Long term efficacy of paroxetine in major depression: A study with plasma levels.

    PubMed

    Mauri, M C; Laini, V; Bitetto, A; Boscati, L; Scalvini, M; Mapelli, L; Rudelli, R

    1999-01-01

    Depressive disorders can be regarded as recurrent and chronic conditions that may reduce the quality of life and work output of patients. Data on the long-term efficacy of paroxetine appear to indicate that it is an effective maintenance treatment. Our aim was to measure paroxetine concentrations in plasma in order to optimize its clinical efficacy and tolerability during long-term treatment. We studied 35 patients aged 23-70 years, suffering from Major Depressive Disorder (recurrent). These patients received 10-50 mg of paroxetine once a day for one year; they were evaluated at baseline, after 2 weeks and then after 1,2,6,9 and 12 months by BPRS, HRS-D and HRS-A rating scales, and at the same time, any side-effects were assessed and samples for paroxetine plasma determination were also collected. Results confirmed the efficacy and tolerability of paroxetine for long-term treatment. We observed a curvilinear relationship between plasma paroxetine levels and improvement on the HRS-D with greater clinical amelioration at plasma levels between 20 and 70 ng/ml.

  15. New level-resolved collision data for neutral argon, benchmarked against the ALEXIS plasma experiment

    NASA Astrophysics Data System (ADS)

    Arnold, Nicholas; Loch, Stuart; Ballance, Connor; Thomas, Ed

    2016-10-01

    Performing spectroscopic measurements of emission lines in low temperature laboratory plasmas is challenging because the plasma is often neutral-dominated and not in thermal equilibrium. The densities and temperatures are such that coronal models do not apply; meaning that generalized collisional-radiative (GCR) methods must be employed to theoretically analyze atomic processes. However, for most noble gases, detailed, level-resolved atomic data for neutral and low-charge states does not exist in the literature. We report on a new project, where we use existing atomic physics codes to calculate level-resolved atomic data for neutral and low charge states of argon and compare with previously published, term-resolved theoretical results. In addition, we use the Atomic Structure and Data Analysis (ADAS) suite of codes to calculate a GCR model for low temperature neutral argon, which we compare to published measurements of argon optical emission cross sections. Finally, we compare synthetic spectra generated from our data with observations taken from the Auburn Linear Experiment for Instability Studies (ALEXIS) in an attempt to develop new optical plasma diagnostics for electron temperature and plasma density measurements. This project is supported by the U.S. Department of Energy. Grant Number: DE-FG02-00ER54476.

  16. Acute psychological stress increases plasma levels of cortisol, prolactin and TSH.

    PubMed

    Schedlowski, M; Wiechert, D; Wagner, T O; Tewes, U

    1992-01-01

    The effects of acute stress during a parachute jump on hormonal responses were studied in 12 experienced and 11 inexperienced military parachutists. Each subject performed two jumps. Prior to and immediately after each jump blood samples were drawn and analysed for plasma levels of cortisol, prolactin, thyrotropin (TSH), somatotropin (STH), and luteinizing hormone (LH). While there was a significant increase in cortisol, prolactin and TSH levels after both jumps, no alterations could be observed in STH and LH levels. Stress-induced hormonal responses were not affected by jump experience. There was also no association between the endocrine variables and anxiety scores.

  17. Effects of plasma microfields on radiative transitions from atomic levels above the ionization threshold

    NASA Technical Reports Server (NTRS)

    Davis, J.; Jacobs, V. L.

    1975-01-01

    The effects of plasma electric microfields on line-like optical features arising from atomic levels above the ionization threshold are investigated within the framework of the quasi-static and single-frequency dynamic-field theories of spectral-line broadening. The 2p(23)P to 1s2p(3)P and 2s2p(3)P to 1s2s(3)S transitions in helium and helium-like ions are treated as examples. The mixing of the doubly excited levels in the perturbing microfields produces Stark broadening of the emission lines and induces autoionization of the 2p(23)P level, which, unlike the 2s2p(3)P level, is metastable against autoionization in the field-free environment. Determination of the complete Stark-broadening profiles in thermal plasmas is complicated by the need to include the effects of both the (quasi-static) ion and the (dynamic) electron fields. Under nonequilibrium conditions, where electric fields from either electron or ion plasma waves can far exceed nearby particle fields, the calculation and interpretation of the line shapes may be simplified and could provide a diagnostic probe of the wave-field properties.

  18. Plasma metabolite levels predict bird growth rates: A field test of model predictive ability.

    PubMed

    Albano, Noelia; Masero, José A; Villegas, Auxiliadora; Abad-Gómez, José María; Sánchez-Guzmán, Juan M

    2011-09-01

    Bird growth rates are usually derived from nonlinear relationships between age and some morphological structure, but this procedure may be limited by several factors. To date, nothing is known about the capacity of plasma metabolite profiling to predict chick growth rates. Based on laboratory-trials, we here develop predictive logistic models of body mass, and tarsus and wing length growth rates in Gull-billed Tern Gelochelidon nilotica chicks from measurements of plasma metabolite levels at different developmental stages. The predictive model obtained during the fastest growth period (at the age of 12 days) explained 65-68% of the chicks' growth rates, with fasting triglyceride level explaining most of the variation in growth rate. At the end of pre-fledging period, β-hydroxybutyrate level was also a good predictor of growth rates. Finally, we carried out a field test to check the predictive capacity of the models in two colonies of wild Gull-billed Tern, comparing field-measured and model-predicted growth rates between groups. Both, measured and predicted growth rates, matched statistically. Plasma metabolite levels can thus be applied in comparative studies of chick growth rates when semi-precocial birds can be captured only once.

  19. Effect of sodium intake on gene expression and plasma levels of ANF in rats

    SciTech Connect

    Lattion, A.L.; Aubert, J.F.; Flueckiger, J.P.; Nussberger, J.; Waeber, B.; Brunner, H.R. )

    1988-08-01

    The effect of short- and long-term sodium loading and sodium restriction on the gene expression as well as on circulating plasma levels of atrial natriuretic factor (ANF) was evaluated in normotensive Wistar rats. These rats were fed either a low-, a regular-, or a high-sodium diet (regular diet and 1% saline as drinking fluid) and studied after 1 and 3 wk. The ANF mRNA was determined in pooled atria and ventricles of the different groups of rats, using the dot-blot technique. Plasma ANF levels were measured with a radioimmunoassay. After 1 wk on the high-sodium diet, ANF mRNA was increased in right atria and ventricles together with circulating ANF levels when compared with animals maintained for the same period on a low-sodium diet. After 3 wk on the various diets, the differences in cardiac ANF mRNA and in plasma ANF levels had disappeared. Gene expression of ANF was also looked for in different areas of the brain, lung, thyroid, adrenals, and the kidney; no hybridization was detected in any of these organs. These data suggest that in rats, the transcription of the ANF gene and peptide release is enhanced only during short-term adaptation to dietary sodium loading.

  20. Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans

    PubMed Central

    Graham, Mark J.; Viney, Nick; Crooke, Rosanne M.; Tsimikas, Sotirios

    2016-01-01

    Epidemiological, genetic association, and Mendelian randomization studies have provided strong evidence that lipoprotein (a) [Lp(a)] is an independent causal risk factor for CVD, including myocardial infarction, stroke, peripheral arterial disease, and calcific aortic valve stenosis. Lp(a) levels >50 mg/dl are highly prevalent (20% of the general population) and are overrepresented in patients with CVD and aortic stenosis. These data support the notion that Lp(a) should be a target of therapy for CVD event reduction and to reduce progression of aortic stenosis. However, effective therapies to specifically reduce plasma Lp(a) levels are lacking. Recent animal and human studies have shown that Lp(a) can be specifically targeted with second generation antisense oligonucleotides (ASOs) that inhibit apo(a) mRNA translation. In apo(a) transgenic mice, an apo(a) ASO reduced plasma apo(a)/Lp(a) levels and their associated oxidized phospholipid (OxPL) levels by 86 and 93%, respectively. In cynomolgus monkeys, a second generation apo(a) ASO, ISIS-APO(a)Rx, significantly reduced hepatic apo(a) mRNA expression and plasma Lp(a) levels by >80%. Finally, in a phase I study in normal volunteers, ISIS-APO(a)Rx ASO reduced Lp(a) levels and their associated OxPL levels up to 89 and 93%, respectively, with minimal effects on other lipoproteins. ISIS-APO(a)Rx represents the first specific and potent drug in clinical development to lower Lp(a) levels and may be beneficial in reducing CVD events and progression of calcific aortic valve stenosis. PMID:26538546

  1. Changes in plasma levels of BDNF and NGF reveal a gender-selective vulnerability to early adversity in rhesus macaques

    PubMed Central

    Cirulli, Francesca; Francia, Nadia; Branchi, Igor; Antonucci, Maria Teresa; Aloe, Luigi; Suomi, Stephen J.; Alleva, Enrico

    2009-01-01

    Summary Early stressful events can increase vulnerability for psychopathology, although knowledge on the effectors is still limited. Here we tested the hypothesis that peripheral levels of Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF), which are involved in the response to stress and in the pathophysiology of anxiety and depression, might be affected in a non-human primate model of adverse rearing. Males and females rhesus macaques reared with their mothers (MR) or in peer-only groups (PR) were used as experimental subjects. BDNF, NGF, adrenocorticotropic hormone (ACTH), cortisol and growth hormone (GH) were determined at baseline on postnatal days (PND) 14, 30 and 60 by means of specific ELISA and RIA procedures. In addition, behavior was assessed on PND 7, 14, 21, 30 (Brazelton test) and 60 (home cage observation). Data indicate gender differences in basal levels of BDNF throughout development. Peer-rearing increased significantly BDNF levels only in females. In addition, while all peer-reared subjects showed high levels of stereotypies and self-directed behaviors, behavioral passivity was selectively increased in females. By contrast, NGF levels were increased in response to peer rearing only in males, and correlated positively with other “classic” endocrine responses to stress, such as cortisol and growth hormone. Our data identify BDNF and NGF as neuroendocrine markers underlying differential responses to maternal deprivation in males and females rhesus macaques. The selective changes in BDNF levels in females could help explain the greater vulnerability to mood disorders of this gender reported in humans. PMID:18849121

  2. Social context-dependent relationships between mouse dominance rank and plasma hormone levels.

    PubMed

    Williamson, Cait M; Lee, Won; Romeo, Russell D; Curley, James P

    2017-03-15

    The associations between social status and endogenous testosterone and corticosterone have been well-studied across taxa, including rodents. Dominant social status is typically associated with higher levels of circulating testosterone and lower levels of circulating corticosterone but findings are mixed and depend upon numerous contextual factors. Here, we determine that the social environment is a key modulator of these relationships in Mus musculus. In groups of outbred CD-1 mice living in stable dominance hierarchies, we found no evidence of simple linear associations between social rank and corticosterone or testosterone plasma levels. However, in social hierarchies with highly despotic alpha males that socially suppress other group members, testosterone levels in subordinate males were significantly lower than in alpha males. In less despotic hierarchies, where all animals engage in high rates of competitive interactions, subordinate males had significantly elevated testosterone compared to agonistically inhibited subordinates from despotic hierarchies. Subordinate males from highly despotic hierarchies also had elevated levels of corticosterone compared to alpha males. In pair-housed animals, the relationship was the opposite, with alpha males exhibiting elevated levels of corticosterone compared to subordinate males. Notably, subordinate males living in social hierarchies had significantly higher levels of plasma corticosterone than pair-housed subordinate males, suggesting that living in a large group is a more socially stressful experience for less dominant individuals. Our findings demonstrate the importance of considering social context when analyzing physiological data related to social behavior and using ethologically relevant behavioral paradigms to study the complex relationship between hormones and social behavior.

  3. Prospective multicentre study of the effect of voluntary plasmapheresis on plasma cholesterol levels in donors

    PubMed Central

    Rosa-Bray, M; Wisdom, C; Wada, S; Johnson, BR; Grifols-Roura, V; Grifols-Lucas, V

    2013-01-01

    Background and Objectives LDL apheresis is used to treat patients with familial hypercholesterolaemia, and low-volume plasmapheresis for plasma donation may similarly lower cholesterol levels in some donors. This study was designed to assess the effect of plasmapheresis on total, LDL and HDL cholesterol levels in a plasma donor population. Materials and Methods This was a prospective, unblinded longitudinal cohort study in which a blood sample was obtained for analysis before each donation. Data from 663 donors were analysed using a multivariable repeated measures regression model with a general estimating equations approach with changes in cholesterol as the primary outcome measure. Results The model predicted a significant decrease in total and LDL cholesterol for both genders and all baseline cholesterol levels (P < 0·01). The greatest total cholesterol decreases (women, −46·8 mg/dL; men, −32·2 mg/dL) were associated with high baseline levels and 2–4 days between donations. Small but statistically significant increases (P ≤ 0·01) in HDL cholesterol were predicted for donors with low baseline levels. Conclusions These results suggest that, in donors with elevated baseline cholesterol levels, total and LDL cholesterol levels may decrease during routine voluntary plasmapheresis. PMID:23517282

  4. Plasma C-Reactive Protein Levels Are Associated With Improved Outcome in ARDS

    PubMed Central

    Bajwa, Ednan K.; Khan, Uzma A.; Januzzi, James L.; Gong, Michelle N.; Thompson, B. Taylor; Christiani, David C.

    2009-01-01

    Background: C-reactive protein (CRP) has been studied as a marker of systemic inflammation and outcome in a number of diseases, but little is known about its characteristics in ARDS. We sought to examine plasma levels of CRP in patients with ARDS and their relationship to outcome and measures of illness severity. Methods: We measured CRP levels in 177 patients within 48 h of disease onset and tested the association of protein level with 60-day mortality, 28-day daily organ dysfunction scores, and number of ventilator-free days. Results: We found that CRP levels were significantly lower in nonsurvivors when compared with survivors (p = 0.02). Mortality rate decreased with increasing CRP decile (p = 0.02). An increasing CRP level was associated with a significantly higher probability of survival at 60 days (p = 0.005). This difference persisted after adjustment for age and severity of illness in a multivariable model (p = 0.009). Multivariable models were also used to show that patients in the group with higher CRP levels had significantly lower organ dysfunction scores (p = 0.001) and more ventilator-free days (p = 0.02). Conclusions: Increasing plasma levels of CRP within 48 h of ARDS onset are associated with improved survival, lower organ failure scores, and fewer days of mechanical ventilation. These data appear to be contrary to the established view that CRP is solely a marker of systemic inflammation. PMID:19411291

  5. Low SGK1 Expression in Human Adrenocortical Tumors Is Associated with ACTH-Independent Glucocorticoid Secretion and Poor Prognosis

    PubMed Central

    Sbiera, Silviu; Leich, Ellen; Tissier, Frédérique; Steinhauer, Sonja; Deutschbein, Timo; Fassnacht, Martin; Allolio, Bruno

    2012-01-01

    Context: Using single-nucleotide polymorphism analysis, we observed allelic loss of the gene for serum glucocorticoid (GC) kinase 1 (SGK1), a GC-responsive kinase involved in multiple cellular functions, in a subset of cortisol-secreting adenomas. Objective: Our objective was to analyze SGK1 expression in adrenocortical tumors and to further characterize its role in ACTH-independent cortisol secretion, tumor progression, and prognosis. Design and Setting: Gene expression levels of SGK1, SGK3, and CTNNB1 (coding for β-catenin) and protein expression levels of SGK1, nuclear β-catenin, and phosphorylated AKT were determined in adrenocortical tumors and normal adrenal glands. Patients: A total of 227 adrenocortical tumors (40 adenomas and 187 carcinomas) and 25 normal adrenal tissues were included. Among them, 62 frozen tumor samples were used for mRNA analysis and 203 tumors were investigated on tissue microarrays or full standard slides by immunohistochemistry. Main Outcome Measures: We evaluated the relationship between SGK1 mRNA and/or protein levels and clinical parameters. Results: SGK1 mRNA levels were lower in cortisol-secreting than in nonsecreting tumors (P < 0.005). Nonsecreting neoplasias showed a significant correlation between SGK1 and CTNNB1 mRNA levels (P < 0.001; r = 0.57). Low SGK1 protein levels, but not nuclear β-catenin and phosphorylated AKT, were associated with poor overall survival in patients with adrenocortical carcinoma (P < 0.005; hazard ratio = 2.0; 95% confidence interval = 1.24–3.24), independent of tumor stage and GC secretion. Conclusion: Low SGK1 expression is related to ACTH-independent cortisol secretion in adrenocortical tumors and is a new prognostic factor in adrenocortical carcinoma. PMID:23055545

  6. Preoperative plasma leptin levels predict delirium in elderly patients after hip fracture surgery.

    PubMed

    Chen, Xue-Wu; Shi, Jun-Wu; Yang, Ping-Shan; Wu, Zhu-Qi

    2014-07-01

    Leptin is considered to be a modulator of the immune response. Hypoleptinemia increases the risk for Alzheimer's disease and vascular dementia. The present study aimed to investigate the ability of plasma leptin level to predict delirium in elderly patients after hip fracture surgery. Postoperative delirium (pod) was evaluated using the Confusion Assessment Method. Prolonged postoperative delirium (ppod) was defined as delirium lasting more than 4 weeks. Plasma leptin levels of 186 elderly patients and 186 elderly controls were measured by an enzyme-linked immunosorbent assay. Plasma leptin level was substantially lower in patients than in controls (4.6±2.2ng/ml vs. 7.5±1.8ng/ml, P<0.001). It was identified as an independent predictor for pod [odds ratio, 0.385; 95% confidence interval (CI), 0.286-0.517; P<0.001] and ppod (odds ratio, 0.283; 95% CI, 0.152-0.527; P<0.001) using a multivariate analysis, and had high area under receiver operating characteristic curve for pod [area under curve (AUC), 0.850; 95% CI, 0.790-0.898] and ppod (AUC, 0.890; 95% CI, 0.836-0.931). The predictive value of leptin was markedly bigger than that of age for pod (AUC, 0.705; 95% CI, 0.634-0.770; P=0.002) and ppod (AUC, 0.713; 95% CI, 0.642-0.777; P=0.019). In a combined logistic-regression model, leptin improved the AUC of age to 0.890 (95% CI, 0.836-0.931) (P<0.001) for pod and 0.910 (95% CI, 0.860-0.947) (P=0.005) for ppod. Thus, preoperative plasma leptin level may be a useful, complementary tool to predict delirium and also prolonged delirium in elderly patients after hip fracture surgery.

  7. Serotonin (5-HT) receptor 5A sequence variants affect human plasma triglyceride levels

    PubMed Central

    Zhang, Y.; Smith, E. M.; Baye, T. M.; Eckert, J. V.; Abraham, L. J.; Moses, E. K.; Kissebah, A. H.; Martin, L. J.

    2010-01-01

    Neurotransmitters such as serotonin (5-hydroxytryptamine, 5-HT) work closely with leptin and insulin to fine-tune the metabolic and neuroendocrine responses to dietary intake. Losing the sensitivity to excess food intake can lead to obesity, diabetes, and a multitude of behavioral disorders. It is largely unclear how different serotonin receptor subtypes respond to and integrate metabolic signals and which genetic variations in these receptor genes lead to individual differences in susceptibility to metabolic disorders. In an obese cohort of families of Northern European descent (n = 2,209), the serotonin type 5A receptor gene, HTR5A, was identified as a prominent factor affecting plasma levels of triglycerides (TG), supported by our data from both genome-wide linkage and targeted association analyses using 28 publicly available and 12 newly discovered single nucleotide polymorphisms (SNPs), of which 3 were strongly associated with plasma TG levels (P < 0.00125). Bayesian quantitative trait nucleotide (BQTN) analysis identified a putative causal promoter SNP (rs3734967) with substantial posterior probability (P = 0.59). Functional analysis of rs3734967 by electrophoretic mobility shift assay (EMSA) showed distinct binding patterns of the two alleles of this SNP with nuclear proteins from glioma cell lines. In conclusion, sequence variants in HTR5A are strongly associated with high plasma levels of TG in a Northern European population, suggesting a novel role of the serotonin receptor system in humans. This suggests a potential brain-specific regulation of plasma TG levels, possibly by alteration of the expression of HTR5A. PMID:20388841

  8. Bothrops jararaca Venom Metalloproteinases Are Essential for Coagulopathy and Increase Plasma Tissue Factor Levels during Envenomation

    PubMed Central

    Yamashita, Karine M.; Alves, André F.; Barbaro, Katia C.; Santoro, Marcelo L.

    2014-01-01

    Background/Aims Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF), resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a) whether TF and protein disulfide isomerase (PDI), an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b) the involvement and significance of snake venom metalloproteinases (SVMP) and serine proteinases (SVSP) to hemostatic disturbances. Methods/Principal Findings Crude Bothrops jararaca venom (BjV) was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. Conclusions SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in engendering

  9. [Effect of the treatment on hemodynamic indicators and plasma testosterone level in patients with juvenile hypertension].

    PubMed

    Zanozdra, N S; Chernoguz, L S; Kupchinskaia, E G; Krishchuk, A A; Savitskiĭ, S Iu; Popova, L I

    1990-07-01

    The effect of anapriline, corinfar and reserpine on parameters of hemodynamics and plasma testosterone was evaluated in 60 juvenile hypertension patients who achieved pronounced hypotensive response. It was established that the level of sex hormones tended to diminution by the end of the treatment month 1 or 2, this drop being more noticeable in reserpine administration. Basing on this evidence it would be beneficial for patients suffering from juvenile hypertension in need of chemotherapy to take courses of the above drugs.

  10. Elevated levels of angiogenic cytokines in the plasma of cancer patients.

    PubMed

    Fuhrmann-Benzakein, E; Ma, M N; Rubbia-Brandt, L; Mentha, G; Ruefenacht, D; Sappino, A P; Pepper, M S

    2000-01-01

    Although in the normal healthy organism angiogenesis is a tightly regulated process, under a variety of circumstances it may contribute to disease states. These include the growth of solid tumors, the hematogenous spread of tumor cells and the growth of metastasis. Our aim was to measure the levels of 5 angiogenic cytokines in the plasma of patients with a variety of cancers, to establish a plasmatic angiogenic profile. We prospectively obtained blood samples in citrated tubes from 40 healthy individuals and 75 patients with a variety of solid tumors. Patients who had received any form of treatment in the preceeding 6 months were excluded from the study. Plasma levels of the following 5 cytokines were determined by ELISA: vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), basic fibroblast growth factor, transforming growth factor-beta and tumor necrosis factor-alpha. In some cases, additional samples were taken 4 and 15 days after surgical removal of the tumor. Our findings demonstrate, that firstly, compared to the tumor group VEGF was almost always undetectable or present at very low levels in healthy individuals; secondly, a threshold value for HGF was found to exist between the 2 groups (healthy vs. tumor); and thirdly, there was a clear relationship between plasma levels of VEGF and HGF and extension of disease (i.e., without or with metastases). The timing of blood sampling in the post-operative period was found to be critical, particularly with regard to VEGF and HGF. The existence of a systemic angiogenic profile in the plasma of cancer patients may be useful as a diagnostic and prognostic tool and may help in the future to monitor the responses of individual patients to anti-tumor and, particularly, anti-angiogenic therapy.

  11. Elevated plasma homocysteine levels in patients with multiple sclerosis are associated with male gender.

    PubMed

    Zoccolella, Stefano; Tortorella, Carla; Iaffaldano, Pietro; Direnzo, Vita; D'Onghia, Mariangela; Paolicelli, Damiano; Livrea, Paolo; Trojano, Maria

    2012-10-01

    Elevated homocysteine (Hcy) levels exert several neurotoxic actions and vascular dysfunctions that may be involved in pathogenesis and progression of multiple sclerosis (MS). The effective role of Hcy in MS however remains to be determined. The aim of this work was to compare plasma Hcy levels in MS patients and neurological disease controls (NDC) and to evaluate their relationships with clinical and demographic variables. In this cross-sectional study, we examined plasma Hcy levels in 217 patients with MS [53 clinically isolated syndromes (CIS) suggestive of MS, 134 relapsing remitting (RR), 23 secondary progressive (SP) and seven primary progressive (PP) MS], recruited among patients attending a tertiary clinical center in southern Italy and in 219 age/sex-matched controls. Median Hcy levels were slightly higher in MS patients compared to NDC (9.1 μmol/l; range, 3.4-35.9 vs. 8.6, range 3.5-27.4; p = 0.02). Median Hcy concentrations were increased in males more than in females in the MS population (10.4 vs. 8.4; p < 0.0001), whereas no differences across genders were found in NDC (9.1 vs. 8.5). Hcy levels were higher in male MS patients compared to the male NDC patients (p = 0.001). Patients with CIS had lower Hcy (7.5 μmol/l; p = 0.004) compared to patients with RR (9.5 μmol/l), SP (10.1 μmol/l) and PP (9.9 μmol/l). Median Hcy concentration was higher in patients with disease duration longer than 22 months (9.7 vs. 8.6 μmol/l; p = 0.02). Plasma Hcy levels are increased in patients with definite MS. Higher Hcy levels are associated with male sex, suggesting a role of Hcy in neurodegenerative processes of MS, which are prominent in male patients.

  12. Photoperiod regulation of plasma growth hormone levels during induced smoltification of underyearling Atlantic salmon.

    PubMed

    Björnsson, B T; Hemre, G I; Bjørnevik, M; Hansen, T

    2000-07-01

    Earlier studies have established that increased daylength increases plasma growth hormone (GH) levels during spring smoltification of yearling Atlantic salmon. Recently, the Atlantic salmon aquaculture industry has started the production of underyearling ("summer") smolts. This involves fast juvenile growth on continuous light (24L), the transfer of juveniles over 8 cm in length to short day (12L) for 6 weeks in the summer, followed by transfer to 24L for another 6 weeks before transfer to seawater in late October. Three groups were studied in fresh water from July to the following May in order to elucidate the GH response to this photoperiod manipulation: one group was kept on 24L throughout (long-day group), while the other two groups were exposed to short day from July 15th. Of these, one was brought back onto long day on September 1st (winter group) while the other was kept on short day (short-day group). Plasma GH levels of the long-day group were around 1.6 ng/ml throughout the study. The short-day transfer suppressed GH levels to 0.7 ng/ml within 2 weeks (short-day and winter groups). The long-day transfer (winter group) increased GH levels to 11 ng/ml within 3 weeks, and this elevation of GH levels was sustained for about 3 months, before declining to pretreatment levels. The study demonstrates that underyearling Atlantic salmon react to increased daylength in a way similar to traditional yearling smolts. It also demonstrates for the first time that decreased daylength can suppress plasma GH levels in fish. It is concluded that winter photoperiod manipulation causes an out-of-season initiation and completion of the parr-smolt transformation of underyearling Atlantic salmon and that growth hormone plays a major role in this process.

  13. Myoglobin plasma level related to muscle mass and fiber composition: a clinical marker of muscle wasting?

    PubMed

    Weber, Marc-André; Kinscherf, Ralf; Krakowski-Roosen, Holger; Aulmann, Michael; Renk, Hanna; Künkele, Annette; Edler, Lutz; Kauczor, Hans-Ulrich; Hildebrandt, Wulf

    2007-08-01

    Progressive muscle wasting is a central feature of cancer-related cachexia and has been recognized as a determinant of poor prognosis and quality of life. However, until now, no easily assessable clinical marker exists that allows to predict or to track muscle wasting. The present study evaluated the potential of myoglobin (MG) plasma levels to indicate wasting of large locomotor muscles and, moreover, to reflect the loss of MG-rich fiber types, which are most relevant for daily performance. In 17 cancer-cachectic patients (weight loss 22%) and 27 age- and gender-matched healthy controls, we determined plasma levels of MG and creatine kinase (CK), maximal quadriceps muscle cross-sectional area (CSA) by magnetic resonance imaging, muscle morphology and fiber composition in biopsies from the vastus lateralis muscle, body cell mass (BCM) by impedance technique as well as maximal oxygen uptake (VO(2)max). In cachectic patients, plasma MG, muscle CSA, BCM, and VO(2)max were 30-35% below control levels. MG showed a significant positive correlation to total muscle CSA (r = 0.65, p < 0.001) and to the CSA fraction formed by type 1 and 2a fibers (r = 0.80, p < 0.001). However, when adjusted for body height and age by multiple regression, MG yielded a largely improved prediction of total CSA (multiple r = 0.83, p < 0.001) and of fiber type 1 and 2a CSA (multiple r = 0.89, p < 0.001). The correlations between CK and these muscle parameters were weaker, and elevated CK values were observed in 20% of control subjects despite a prior abstinence from exercise for 5 days. In conclusion, plasma MG, when adjusted for anthropometric parameters unaffected by weight, may be considered as a novel marker of muscle mass (CSA) indicating best the mass of MG-rich type 1 and 2a fibers as well as VO(2)max as an important functional readout. CK plasma levels appear to be less reliable because prolonged increases are observed in even subclinical myopathies or after exercise. Notably, cancer

  14. Characterization of a novel ACTH inducible cytochrome P-450 from rat adrenal microsomes

    SciTech Connect

    Otto, S.A.; Marcus, C.M.; Jefcoate, C.R. )

    1990-02-26

    In rat adrenal cortex 7,12 dimethylbenz(a)anthracene (DMBA) causes massive necrosis that is dependent of ACTH. This is related to an ACTH inducible adrenal microsomal cytochrome P-450 that catalyzes hydrocarbon metabolism. Rat adrenal microsomes, catalyze the formation of DMBA 3,4 diol a precursor of the bay region reactive electrophile DMBA 3,4 diol 1,2 oxide. Both DMBA metabolism and a 57Kd protein have disappeared from microsomes 30 days after hypophysectomy, but are restored by 14 days treatment with ACTH. Dexamethasone which fully suppresses ACTH only partially suppresses this activity. The 57 Kd protein was partially purified to a single major band in one step from solubilized microsomes by h.p.l.c. chromatography using detergent elution from a novel column that mimics phospholipid membranes. This preparation exhibits a specific content of 2 nm P-450/mg protein and a turnover number of 1,500pm DMBA/nm P-450/minutes. A polyclonal antisera raised against this preparation provides a single western blot corresponding to the 57Kd ACTH sensitive protein. This antibody did not blot microsomal P-450 c21, nor did selected antibodies from known families react with this adrenal P-450 protein, suggesting substantial sequence differences from known P-450's.

  15. ACTH-producing neuroendocrine tumor of the pancreas: a case report and literature review

    PubMed Central

    Byun, Justin; Kim, Sung Hyun; Jeong, Hyang Sook; Rhee, Yumie; Lee, Woo Jung

    2017-01-01

    Tumors that arise from the endocrine pancreas, or the islets of pancreas, are called pancreatic neuroendocrine tumors (NETs). Pancreatic NET have an incidence of <0.1 per one million persons, and can lead to secretion of ectopic adrenocorticotropic hormone (ACTH). Herein, we presented a case of patient with Cushing's syndrome as a result of ACTH-producing pancreatic NET, who underwent successful laparoscopic distal pancreatosplenectomy. A 40-year-old Korean female patient with ophthalmologic discomfort, osteoporosis, and unexplained hypokalemia was admitted to our hospital. Under the suspicion of ACTH producing pancreatic NET after the diagnostic workup, we decided to perform surgical resection. Laparoscopic distal pancreatosplenectomy was performed; and the pathological examination revealed a 1.5 cm-sized grade 2 neuroendocrine tumor of the pancreas, which was encapsulated within the pancreatic parenchyma. After the operation, the patient no longer displayed cushingoid features. ACTH-producing pancreatic NET is rare, but can be one of the causes of Cushing's syndrome. Surgical resection is a feasible option in treating ACTH-producing pancreatic NET. PMID:28317048

  16. Association between arsenic exposure from drinking water and plasma levels of cardiovascular markers.

    PubMed

    Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G; Liu, Mengling; Wójcik, Oktawia; Parvez, Faruque; Rahaman, Ronald; Roy, Shantanu; Paul-Brutus, Rachelle; Segers, Stephanie; Slavkovich, Vesna; Islam, Tariqul; Levy, Diane; Mey, Jacob L; van Geen, Alexander; Graziano, Joseph H; Ahsan, Habibul; Chen, Yu

    2012-06-15

    The authors conducted a cross-sectional study to assess the relation between arsenic exposure from drinking water and plasma levels of markers of systemic inflammation and endothelial dysfunction (matrix metalloproteinase-9, myeloperoxidase, plasminogen activator inhibitor-1, soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble vascular adhesion molecule-1 (VCAM-1)) using baseline data from 668 participants (age, >30 years) in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2007-2008). Both well water arsenic and urinary arsenic were positively associated with plasma levels of soluble VCAM-1. For every 1-unit increase in log-transformed well water arsenic (ln μg/L) and urinary arsenic (ln μg/g creatinine), plasma soluble VCAM-1 was 1.02 (95% confidence interval: 1.01, 1.03) and 1.04 (95% confidence interval: 1.01, 1.07) times greater, respectively. There was a significant interaction between arsenic exposure and higher body mass index, such that the increased levels of plasminogen activator inhibitor-1 and soluble VCAM-1 associated with arsenic exposure were stronger among people with higher body mass index. The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation and endothelial dysfunction that could be modified by body mass index and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease.

  17. Decrease in NTproBNP plasma levels indicates clinical improvement of acute decompensated heart failure.

    PubMed

    Di Somma, Salvatore; Magrini, Laura; Mazzone, Marinella; De Leva, Raffaella; Tabacco, Fabio; Marino, Rossella; Talucci, Veronica; Ferri, Enrico; Forte, Paola; Cardelli, Patrizia; Gentiloni, Nicola; Pittoni, Valerio

    2007-03-01

    Thirty-seven consecutive patients with acute decompensated heart failure (ADHF) admitted to emergency departments for acute dyspnea were investigated. Ten patients with acute exacerbation of chronic obstructive pulmonary disease and 10 patients with hypertension crisis were also included as controls. For each patient, a plasma amino-terminal pro-B-type natriuretic peptide (NTproBNP) concentration measurement was performed at admission, 4, 12, and 24 hours later, and on the day of discharge. In patients with ADHF, the observation of a progressive reduction to a complete relief of symptoms of heart failure was accompanied by a reduction of 58% of NTproBNP plasma levels on the day of discharge. Amelioration of symptoms was accompanied by improvement of physiologic parameters and New York Heart Association functional class. In the control population (chronic obstructive pulmonary disease and hypertension crisis patients), no significant variation of NTproBNP levels in comparison with those at admission was found at each time point. In conclusion, a plasma profile obtained with sequential measurements indicates that a significant decrease in NTproBNP levels is associated with the clinical improvement of patients with ADHF at the time of discharge.

  18. Lower Oxytocin Plasma Levels in Borderline Patients with Unresolved Attachment Representations.

    PubMed

    Jobst, Andrea; Padberg, Frank; Mauer, Maria-Christine; Daltrozzo, Tanja; Bauriedl-Schmidt, Christine; Sabass, Lena; Sarubin, Nina; Falkai, Peter; Renneberg, Babette; Zill, Peter; Gander, Manuela; Buchheim, Anna

    2016-01-01

    Interpersonal problems and affective dysregulation are core characteristics of borderline personality disorder (BPD). BPD patients predominantly show unresolved attachment representations. The oxytocin (OT) system is associated with human social attachment and affiliative behavior, and OT dysregulation may be related to distinct attachment characteristics. Here, we investigated whether attachment representations are related to peripheral OT levels in BPD patients. Twenty-one female BPD patients and 20 age-, gender-, and education-matched healthy controls (HCs) were assessed with clinical scales and measures of interpersonal and attachment-related characteristics, including the Adult Attachment Projective Picture System (AAP). Plasma OT concentrations were measured prior to and during social exclusion in a virtual ball tossing game (Cyberball). The majority of BPD patients (63.2%) but no HCs showed unresolved (disorganized) attachment representations. In this subgroup of patients, baseline OT plasma levels were significantly lower than in BPD patients with organized attachment representations. This pilot study extends previous findings of altered OT regulation in BPD as a putative key mechanism underlying interpersonal dysregulation. Our results provide first evidence that altered OT plasma levels are related to disorganized attachment representations in BPD patients.

  19. Changes in salivary and plasma cortisol levels in Purebred Arabian horses during race training session.

    PubMed

    Kędzierski, Witold; Cywińska, Anna; Strzelec, Katarzyna; Kowalik, Sylwester

    2014-03-01

    Physical activity and stress both cause an increase in cortisol release ratio. The aim of this study was to evaluate the use of saliva samples for the determination of cortisol concentrations indicating the work-load level in horses during race training. Twelve Purebred Arabian horses aged 3-5 years were studied during the routine training session. After the warm-up, the horses galloped on the 800 m sand track at a speed of 12.8 m/s. Three saliva samples, and three blood samples were collected from each horse. Both types of samples were taken at rest, immediately after return from the track and after 30 min restitution. The concentrations of blood lactic acid (LA), and cortisol in saliva and plasma samples were measured and analyzed. Blood LA, plasma and salivary cortisol levels increased significantly after exercise (P < 0.05). Salivary cortisol concentration determined 30 min after the exercise correlated significantly with plasma cortisol level obtained immediately after exercise (P < 0.05) as well as measured 30 min after the end of exercise (P < 0.05). The determination of cortisol concentration in saliva samples taken from racehorses 30 min after the end of exercise can be recommended to use in field conditions to estimate the work-load in racehorses.

  20. Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F2α Metabolite Levels

    PubMed Central

    Hagman, R; Kindahl, H; Lagerstedt, A-S

    2006-01-01

    Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2α metabolite 15-ketodihydro-PGF2α (PG-metabolite), progesterone and oestradiol (E2-17β) levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The γ-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra. PMID:16722306

  1. Lower Oxytocin Plasma Levels in Borderline Patients with Unresolved Attachment Representations

    PubMed Central

    Jobst, Andrea; Padberg, Frank; Mauer, Maria-Christine; Daltrozzo, Tanja; Bauriedl-Schmidt, Christine; Sabass, Lena; Sarubin, Nina; Falkai, Peter; Renneberg, Babette; Zill, Peter; Gander, Manuela; Buchheim, Anna

    2016-01-01

    Interpersonal problems and affective dysregulation are core characteristics of borderline personality disorder (BPD). BPD patients predominantly show unresolved attachment representations. The oxytocin (OT) system is associated with human social attachment and affiliative behavior, and OT dysregulation may be related to distinct attachment characteristics. Here, we investigated whether attachment representations are related to peripheral OT levels in BPD patients. Twenty-one female BPD patients and 20 age-, gender-, and education-matched healthy controls (HCs) were assessed with clinical scales and measures of interpersonal and attachment-related characteristics, including the Adult Attachment Projective Picture System (AAP). Plasma OT concentrations were measured prior to and during social exclusion in a virtual ball tossing game (Cyberball). The majority of BPD patients (63.2%) but no HCs showed unresolved (disorganized) attachment representations. In this subgroup of patients, baseline OT plasma levels were significantly lower than in BPD patients with organized attachment representations. This pilot study extends previous findings of altered OT regulation in BPD as a putative key mechanism underlying interpersonal dysregulation. Our results provide first evidence that altered OT plasma levels are related to disorganized attachment representations in BPD patients. PMID:27064696

  2. Pyometra in bitches induces elevated plasma endotoxin and prostaglandin F2alpha metabolite levels.

    PubMed

    Hagman, R; Kindahl, H; Lagerstedt, A S

    2006-01-01

    Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2alpha metabolite 15-ketodihydro-PGF2alpha (PG-metabolite), progesterone and oestradiol (E2-17beta) levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The gamma-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra.

  3. Plasma and urine renalase levels and activity during the recovery of renal function in kidney transplant recipients.

    PubMed

    Quelhas-Santos, Janete; Soares-Silva, Isabel; Fernandes-Cerqueira, Cátia; Simões-Silva, Liliana; Ferreira, Inês; Carvalho, Catarina; Coentrão, Luís; Vaz, Raquel; Sampaio-Maia, Benedita; Pestana, Manuel

    2014-04-01

    Renalase is a recently described enzyme secreted by the kidney into both plasma and urine, where it was suggested to degrade catecholamines contributing to blood pressure control. While there is a controversy regarding the relationship between renal function and plasma renalase levels, there is virtually no data in humans on plasma renalase activity as well as on both urine renalase levels and activity. We prospectively examined the time course of plasma and urine renalase levels and activity in 26 end-stage renal disease (ESRD) patients receiving a cadaver kidney transplant (cadaver kidney recipients [CKR]) before surgery and during the recovery of renal function up to day 90 post transplant. The relationship with sympathetic and renal dopaminergic activities was also evaluated. The recovery of renal function in CKR closely predicted decreases in plasma renalase levels (r = 0.88; P < 0.0001), urine renalase levels (r = 0.75; P < 0.0001) and urine renalase activity (r = 0.56; P < 0.03), but did not predict changes in plasma renalase activity (r = -0.02; NS). Plasma norepinephrine levels positively correlated with plasma renalase levels (r = 0.64, P < 0.002) as well as with urine renalase levels and activity (r = 0.47 P < 0.02; r = 0.71, P < 0.0005, respectively) and negatively correlated with plasma renalase activity (r = -0.57, P < 0.002). By contrast, plasma epinephrine levels positively correlated with plasma renalase activity (r = 0.67, P < 0.0001) and negatively correlated with plasma renalase levels (r = -0.62, P < 0.003). A significant negative relationship was observed between urine dopamine output and urine renalase levels (r = -0.48; P < 0.03) but not with urine renalase activity (r = -0.33, NS). We conclude that plasma and urine renalase levels closely depend on renal function and sympathetic nervous system activity. It is suggested that epinephrine-mediated activation of circulating renalase may occur in renal transplant recipients with good recovery of

  4. Plasma homocysteine level is a risk factor for osteoporotic fractures in elderly patients

    PubMed Central

    Zhu, Yuefeng; Shen, Jie; Cheng, Qun; Fan, Yongqian; Lin, Weilong

    2016-01-01

    Objective To study the relationship of plasma homocysteine (Hcy), bone turnover biomarkers (BTB), and bone mineral density (BMD) with osteoporotic fracture (OPF) in elderly people. Methods Eighty-two patients (aged 65 years or older) admitted to our orthopedics department between October 2014 and May 2015 were randomly divided into three groups: 1) OPF group: 39 cases with the mean age 81.82±5.49 years, which included 24 females and 15 males; 2) high-energy fracture (HEF) group: 22 cases with the mean age 78.88±5.75 years, which included 16 females and six males; 3) non-bone-fracture group: 21 cases with mean age 79.75±5.47 years without bone fracture, which included 14 females and seven males. Plasma Hcy, BTB, and BMD were measured. Analysis of variance and multiple regression analysis were used in the statistical analysis. Results There was no significant difference in either age or sex among the three groups. There were significant differences in plasma Hcy and hip BMD between the OPF and HEF groups; there was also significant difference in plasma Hcy, 25-(OH) Vit D, and hip BMD between the OPF and non-fracture groups. There was no difference in lumbar spine BMD between the OPF group and the other two groups. There was no significant difference in plasma Hcy, 25-(OH) Vit D, hip or lumbar spine BMD between the HEF and non-fracture group. There was no significant difference in procollagen type I N-propeptide of type I collagen, serum C-terminal cross-linking telopeptide of type I collagen, and parathyroid hormone among the three groups. Plasma Hcy was linearly correlated with age and serum C-terminal cross-linking telopeptide of type I collagen, but not correlated with either hip or lumbar spine BMD or any other BTBs. Conclusion In this study, we found that the plasma Hcy level in elderly patients with OPF is higher than that of nonosteoporotic patients. It is not correlated with BMD, but positively correlated with bone resorption markers. An increased Hcy

  5. Relationship between plasma matrix metalloproteinase levels, pulmonary function, bronchodilator response, and emphysema severity

    PubMed Central

    Koo, Hyeon-Kyoung; Hong, Yoonki; Lim, Myoung Nam; Yim, Jae-Joon; Kim, Woo Jin

    2016-01-01

    Objective Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airway and lung. A protease–antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. We evaluated the relationship between matrix metalloproteinase (MMP) levels and COPD severity. Methods Plasma levels of MMP-1, MMP-8, MMP-9, and MMP-12 were measured in 57 COPD patients and 36 normal controls. The relationship between MMP levels and lung function, emphysema index, bronchial wall thickness, pulmonary artery pressure, and quality of life was examined using general linear regression analyses. Results There were significant associations of MMP-1 with bronchodilator reversibility and of MMP-8 and MMP-9 with lung function. Also, MMP-1, MMP-8, and MMP-9 levels were correlated with the emphysema index, independent of lung function. However, MMP-12 was not associated with lung function or emphysema severity. Associations between MMP levels and bronchial wall thickness, pulmonary artery pressure, and quality of life were not statistically significant. Conclusion Plasma levels of MMP-1, MMP-8, and MMP-9 are associated with COPD severity and can be used as a biomarker to better understand the characteristics of COPD patients. PMID:27313452

  6. Dose, Plasma Level, and Treatment Outcome Among Methadone Patients in Shanghai, China.

    PubMed

    Jiang, Haifeng; Hillhouse, Maureen; Du, Jiang; Pan, Shujun; Alfonso, Ang; Wang, Jun; Zhou, Zhirong; Yuan, Weijun; Ling, Walter; Zhao, Min

    2016-12-01

    The purpose of this study was to investigate the blood levels of methadone in participants receiving methadone for the treatment of opioid dependence. After stabilization on methadone for four weeks, blood samples from 95 participants were collected between treatment weeks 4 and 12, before and after receiving doses of methadone, and its blood levels were measured. A multiple linear regression model was used to examine the association between methadone blood levels and the outcomes of methadone maintenance treatment (MMT). Outcome differences between participants who had high (≥2) or low (<2) peak-to-trough ratios were also compared using an independent sample t-test. The blood level of methadone was not correlated with the clinical outcome of MMT with the moderate range of doses given. However, the retention of patients who had a free peak-to-trough ratio >2 was significantly poorer than those whose ratio was <2. Thus, monitoring plasma methadone levels is unlikely to be effective for guiding dosing decisions in situations where compliance with MMT is already very high or when the methadone dose is no longer the dominant factor in determining the clinical outcome. However, monitoring plasma methadone levels is still helpful for guiding the dosage for patients with a rapid metabolism.

  7. Association between seminal plasma zinc level and asthenozoospermia: a meta-analysis study.

    PubMed

    Taravati, A; Tohidi, F

    2016-08-01

    Zinc is proposed to have an important role in the morphology, viability and motility of spermatozoa. There are inconsistent reports on the association between seminal plasma zinc concentration and male infertility. For this purpose, papers reporting the level of seminal zinc among asthenozoospermic groups were selected and used for further analysis. This meta-analysis of previous published studies was performed to obtain more precise information on the association between seminal plasma zinc and asthenozoospermia. Relevant studies for inclusion were identified after preliminary investigation of research papers published on electronic databases up to February 2015. Eight reports and 475 subjects were finally included in the meta-analysis. In the overall analysis, a statistically significant reduction in seminal plasma zinc concentrations was observed in asthenozoospermic infertile men. Random-effects method was used to evaluate the summary effect size due to the presence of significant heterogeneity. The effect of zinc on asthenozoospermia was significant (Hedge's G effect size = -0.506, 95% confidence interval (95% CI): -0.998 to -0.014, P = 0.044). Taken together, despite of significant statistical heterogeneity between studies, our findings were indicative of significant association between zinc concentration and asthenozoospermia. In conclusion, the meta-analysis suggests that seminal plasma zinc concentration is negatively associated with male infertility.

  8. Changes in plasma catecholamines levels as preclinical biomarkers in experimental models of Parkinson's disease.

    PubMed

    Kim, A R; Ugryumov, M V

    2015-01-01

    The goal of this study was to investigate the changes in the concentrations of blood plasma catecholamines as possible biomarkers of Parkinson's disease (PD) in the mouse experimental model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A significant decrease was detected in the levels of dopamine and L-DOPA in the PD preclinical stage model as a result of the catecholamines systemic metabolism disfunction. In the PD early clinical stage models, the level of L-DOPA and dihydroxyphenylacetic acid decreased, which is consistent with the results of blood tests in untreated patients.

  9. Prolactin plasma levels and D2-dopamine receptor occupancy measured with IBZM-SPECT.

    PubMed

    Schlegel, S; Schlösser, R; Hiemke, C; Nickel, O; Bockisch, A; Hahn, K

    1996-04-01

    By the application of 123([123I]IBZM), an iodine-labelled dopamine D2-receptor antagonist, brain D2 receptors in humans can be visualized with single photon emission computed tomography (SPECT). The ratio of IBZM binding to striatal regions versus binding to frontal cortex (ST/FC ratio) provided a semiquantitative measurement of D2 receptor binding in the striatum. This study investigated the relationship between receptor occupancy and plasma prolactin levels in 12 male patients treated with haloperidol, benperidol or clozapine. Prolactin levels were positively correlated with D2 receptor occupancy, reflecting at least in part a comparable dopamine receptor antagonism in different dopaminergic pathways.

  10. Plasma Levels of Tumor Necrosis Factor-Alpha and Interleukin-6 in Obsessive Compulsive Disorder

    PubMed Central

    Konuk, N.; Tekın, I. O.; Ozturk, U.; Atik, L.; Atasoy, N.; Bektas, S.; Erdogan, A.

    2007-01-01

    Aim. Recent research implicated place of an immune mechanism in the pathophysiology of obsessive-compulsive disorder (OCD). Despite increasing evidence involvement of cytokine release in OCD, results of the studies are inconsistent. The aim of this study was to evaluate the plasma levels of the cytokines; tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in OCD patients. Methods. Plasma concentrations of TNF-α and IL-6 were measured in 31 drug-free outpatients with OCD, and 31-year age and sex-matched healthy controls. TNF-α and IL-6 concentrations in blood were determined by enzyme-linked immunosorbent assay (ELISA). Results. Both TNF-α and IL-6 levels showed statistically significant increases in OCD patients compared to controls (P < .000, P < .001, resp.). In addition, the age of onset was negatively correlated with TNF-α level (r = −.402, P = .025) and duration of illness was weakly correlated with IL-6 levels (r : .357; P : .048) in patients group. Conclusion. OCD patients showed increases in TNF-α and IL-6 levels compared to the healthy controls. This study provides evidence for alterations in the proinflamatory cytokines which suggest the involvement of the immune system in the pathophysiology of OCD. PMID:17497035

  11. Plasma progesterone levels in the pregnant female rat-kangaroo (Bettongia gaimardi).

    PubMed

    Jones, S M; Rose, R W

    1992-08-01

    Plasma progesterone levels were measured in female bettongs (small macropodid marsupials) under two natural regimes: (1) during "delayed" gestation (initiated by removal of pouch young, RPY) and (2) during the pregnancy prior to pouch vacation when a young still occupies the pouch (i.e., during lactation). Basal levels of progesterone were 0.15-0.5 ng/ml. There was a transient peak of progesterone (0.7 ng/ml) early in gestation at Day 4 RPY. After Day 6 RPY, progesterone levels remained elevated (1.2-1.5 ng/ml) until they dropped sharply to basal levels on the day of birth. This pattern of progesterone secretion during delayed gestation is similar to that seen in other marsupials, such as the tammar wallaby. There was no significant difference between the progesterone profiles of the two experimental groups. We deduce, then, that lactation had no effect on corpus luteum function (as assessed by plasma progesterone levels) in the pregnant bettong.

  12. Effects of different fixatives on demonstrating epinephrine and ACTH hormones in Tetrahymena.

    PubMed

    Csaba, G; Kovács, P; Pállinger, E

    2009-12-01

    The unicellular Tetrahymena produces, contains, and secretes many hormones characteristic of higher animals. We tested three fixatives, formaldehyde, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC), and glutaraldehyde for suitability for immunocytochemical demonstration of epinephrine and adrenocorticotropic harmone (ACTH) in Tetrahymena. Using flow cytometric immunocytochemistry, staining of ACTH was highest after EDAC fixation and that of epinephrine after glutaraldehyde fixation. Using laser scanning confocal microscopy, formaldehyde fixation prevented staining. Glutaraldehyde fixation produced high autofluorescence, which obscured specific staining. After EDAC fixation, ACTH was localized in the ciliary row; however, demonstration of epinephrine was not improved. Our results show that there is no "fixative for any hormone." Different fixatives are needed to demonstrate different hormones in Tetrahymena.

  13. Investigation of the Plasma Nitrite Levels and Oxidant–Antioxidant Status in Obstructive Sleep Apnea Syndrome

    PubMed Central

    BOZKURT, Hakan; NEYAL, Abdurrahman; GEYİK, Sırma; TAYSI, Seyithan; ANARAT, Rüksan; BULUT, Mesut; NEYAL, Ayşe Münife

    2015-01-01

    Introduction Obstructive sleep apnea (OSA) is one of the most prevalent sleep disorders. In the present study, we assessed the nitrite level, which is an indirect indicator of nitric oxide (NO), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI), which may be associated with endotel dysfunction. We investigated the difference between the groups and the relationship among the severity of comorbid conditions. Methods This study was conducted in 39 OSA patients confirmed by polysomnography and 40 healthy subjects (controls). The OSA group consisted of 10 women and 29 men and the control group consisted of 20 women and 20 men. Polysomnographic revealed mild OSA in two, moderate in 7 and severe in 30 cases. We measured plasma TAS, TOS and nitrite levels from venous blood. The OSI value was obtained by dividing the TOS and TAS values. Values were compared with the control group and between patient groups. Results A high body mass index (BMI), cardiovasculer diseases (CVD) and the use of medication for co-morbid diseases were more prevalent in the OSA group (p=.001, p=.029 and p=.006, respectively). The median plasma TOS level and OSI in the obstructive sleep apnea syndrome (OUA) group were significantly higher than those in the control group (p=.001 and p=.001, respectively). The plasma median nitrite level and TAS did not show any significant difference between the OSA and the control groups. None of the parameters revealed a significant difference between severe and moderate OSA cases. Conclusion Our findings in the present study revealed that the oxidant–antioxidant balance shifted toward the oxidant side in OSA cases; however, the NO level did not change. These findings together may point out that some molecules other than NO may have a role in the pathophysiology of endothelial dysfunction and also in the disturbed oxidant–antioxidant balance in OSA.

  14. Plasma levels of zinc, copper, and ceruloplasmin in patients after undergoing laparoscopic adjustable gastric banding.

    PubMed

    Böyük, Abdullah; Banlı, Oktay; Gümüş, Metehan; Evliyaoğlu, Osman; Demirelli, Salih

    2011-12-01

    Laparoscopic adjustable gastric banding (LAGB) causes significant weight loss in morbidly obese adults. However, its consequences on nutritional status still remain unclear. There are a few studies determining the nutritional status after LAGB and none have focused on the serum levels of zinc (Zn), copper (Cu), and ceruloplasmin (CP). We aimed to investigate the effects of LAGB surgery on plasma Zn, Cu, and CP levels. Thirty patients with LAGB with morbid obesity were included. Blood samples were collected preooperatively and in the postoperative third month to determine plasma Zn, Cu, and CP levels. The mean preoperative and postoperative body mass indexes (BMI) were 44.9 ± 7.4 kg/m(2) and 44.1 ± 6.5 kg/m(2), respectively. The mean weight loss was 12.9 ± 3.3 kg at the postoperative third month. The postoperative Zn (500 ± 130 ng/ml), Cu (280 ± 80 ng/ml), and CP (23.9 ± 8.8 mg/dl) values were statistically significantly lower than the preooperative Zn (740 ± 230 ng/ml), Cu (370 ± 80 ng/ml) and CP (33.3 ± 15.7 mg/dl) levels (p < 0.05). Decreases in the plasma levels of Zn, Cu, and CP were seen postoperatively following LAGB surgery. The nutritional status of LAGB-applied patients should be monitored and mineral supplementation may be considered.

  15. Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk.

    PubMed

    Blanco-Colio, Luis M; Martín-Ventura, Jose L; Gómez-Guerrero, Carmen; Masramon, Xavier; de Teresa, Eduardo; Farsang, Csaba; Gaw, Allan; Gensini, GianFranco; Leiter, Lawrence A; Langer, Anatoly; Egido, Jesús

    2008-05-31

    Adiponectin can suppress atherogenesis by inhibiting the adherence of monocytes, reducing their phagocytic activity, and suppressing the accumulation of modified lipoproteins in the vascular wall. Contradictory data have been reported about the effect of statins on adiponectin plasma levels. In this work, adiponectin plasma levels were measured in 102 statin-free subjects from the Spanish population of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study, a 12-week, prospective, multi-centre, open-label trial which enrolled subjects with coronary heart disease, coronary heart disease-equivalent or a 10-year coronary heart disease risk >20%. Subjects were assigned to atorvastatin (10-80 mg/day) based on low-density lipoprotein (LDL)-cholesterol concentration at screening. For comparison, age and gender-matched blood donors (N=40) were used as controls. Control subjects did not present hypertension, hypercholesterolemia, diabetes, metabolic syndrome and history of cardiovascular diseases. Adiponectin levels were diminished in patients at high cardiovascular risk compared with control subjects [4166 (3661-4740) vs 5806 (4764-7075) ng/ml respectively; geometric mean (95% CI); P<0.0001]. In the whole population, atorvastatin treatment increased adiponectin levels [9.7 (3.2-16.7);% Change (95% CI); P=0.003]. This increment was in a dose-dependent manner; maximal effect observed with atorvastatin 80 mg/d [24.7 (5.7-47.1); P=0.01]. Adiponectin concentrations were positively correlated with high-density lipoprotein-cholesterol both before and after atorvastatin treatment. No association was observed between adiponectin and LDL-cholesterol before and after atorvastatin treatment. In conclusion, atorvastatin increased adiponectin plasma levels in subjects at high cardiovascular risk, revealing a novel anti-inflammatory effect of this drug.

  16. Subclinical sleep apnoea and plasma levels of endothelin-1 among young and healthy adults

    PubMed Central

    Schoen, Tobias; Aeschbacher, Stefanie; Leuppi, Joerg D; Miedinger, David; Werthmüller, Ursina; Estis, Joel; Todd, John; Risch, Martin; Risch, Lorenz; Conen, David

    2017-01-01

    Objective Obstructive sleep apnoea (OSA) is a risk factor for vascular disease and other adverse outcomes. These associations may be at least partly due to early endothelin-1 (ET-1)-mediated endothelial dysfunction (ED). Therefore, we assessed the relationships between subclinical sleep apnoea and plasma levels of ET-1. Methods We performed a population-based study among 1255 young and healthy adults aged 25–41 years. Cardiovascular disease, diabetes or a body mass index >35 kg/m2 were exclusion criteria. Plasma levels of ET-1 were measured using a high-sensitivity, single-molecule counting technology. The relationships between subclinical sleep apnoea (OSA indices: respiratory event index (REI), oxygen desaturation index (ODI), mean night-time blood oxygen saturation (SpO2)) and ET-1 levels were assessed by multivariable linear regression analysis. Results Median age of the cohort was 35 years. Median ET-1 levels were 2.9 (IQR 2.4–3.6) and 2.5 pg/mL (IQR 2.1–3.0) among patients with (n=105; 8%) and without subclinical sleep apnoea (REI 5–14), respectively. After multivariable adjustment, subclinical sleep apnoea remained significantly associated with plasma levels of ET-1 (β=0.13 (95% CI 0.06 to 0.20) p=0.0002 for a REI 5–14; β=0.10 (95% CI 0.03 to 0.16) p=0.003 for an ODI≥5). Every 1% decrease in mean night-time SpO2 increased ET-1 levels by 0.1 pg/mL, an association that remained significant after multivariable adjustment (β=0.02 (95% CI 0.003 to 0.033) p=0.02). Conclusions In this study of young and healthy adults, we found that participants with subclinical sleep apnoea had elevated plasma ET-1 levels, an association that was due to night-time hypoxaemia. Our results suggest that ED may already be an important consequence of subclinical sleep apnoea.

  17. Aromatase inhibitors in obese breast cancer patients are not associated with increased plasma estradiol levels.

    PubMed

    Diorio, Caroline; Lemieux, Julie; Provencher, Louise; Hogue, Jean-Charles; Vachon, Eric

    2012-11-01

    Obesity, in postmenopausal women, has been associated to a higher breast cancer incidence and worst prognosis. Some studies suggested a decrease in aromatase inhibitors (AI) efficacy in obese postmenopausal breast cancer patients, although estradiol levels were not measured. The purpose of the present study was to verify if estradiol levels are measurable in postmenopausal women under AI. If achievable, the goal is to compare the estradiol levels in lean versus obese postmenopausal women under AI treatment for non-metastatic breast cancer. Postmenopausal women were recruited in accordance to one of these four groups: lean [body mass index (BMI) of 18-25 kg/m(2)] under AI (n = 30), obese (BMI ≥ 30 kg/m(2)) under AI (n = 30), lean AI-naïve (n = 10), and obese AI-naïve (n = 10). Lean and obese women were matched according to their age. Estradiol levels were measured in plasma using an ELISA. The Wilcoxon signed-rank test was used to assess the significance of the differences between the groups. Estradiol levels in postmenopausal women under AI varied from 0 to 94.65 pg/ml with a median value of 0.98 pg/ml. Obese AI-naïve women had higher estradiol levels than lean AI-naïve women (p = 0.03). There was no difference in estradiol levels between lean and obese women under AI (p = 0.76). Despite very low plasma levels, it is possible to measure the estradiol levels in postmenopausal women under AI treatment. Our results suggest that the known impact of obesity on recurrence risk in women under AI treatment may not be due to incomplete aromatase inhibition. Further works are needed to examine closely the aromatase-independent pathways that are linking obesity to breast cancer risk and recurrence.

  18. Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde.

    PubMed

    Ridpath, John R; Nakamura, Ayumi; Tano, Keizo; Luke, April M; Sonoda, Eiichiro; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Gillespie, David A F; Sale, Julian E; Yamazoe, Mitsuyoshi; Bishop, Douglas K; Takata, Minoru; Takeda, Shunichi; Watanabe, Masami; Swenberg, James A; Nakamura, Jun

    2007-12-01

    Formaldehyde is an aliphatic monoaldehyde and is a highly reactive environmental human carcinogen. Whereas humans are continuously exposed to exogenous formaldehyde, this reactive aldehyde is a naturally occurring biological compound that is present in human plasma at concentrations ranging from 13 to 97 micromol/L. It has been well documented that DNA-protein crosslinks (DPC) likely play an important role with regard to the genotoxicity and carcinogenicity of formaldehyde. However, little is known about which DNA damage response pathways are essential for cells to counteract formaldehyde. In the present study, we first assessed the DNA damage response to plasma levels of formaldehyde using chicken DT40 cells with targeted mutations in various DNA repair genes. Here, we show that the hypersensitivity to formaldehyde is detected in DT40 mutants deficient in the BRCA/FANC pathway, homologous recombination, or translesion DNA synthesis. In addition, FANCD2-deficient DT40 cells are hypersensitive to acetaldehyde, but not to acrolein, crotonaldehyde, glyoxal, and methylglyoxal. Human cells deficient in FANCC and FANCG are also hypersensitive to plasma levels of formaldehyde. These results indicate that the BRCA/FANC pathway is essential to counteract DPCs caused by aliphatic monoaldehydes. Based on the results obtained in the present study, we are currently proposing that endogenous formaldehyde might have an effect on highly proliferating cells, such as bone marrow cells, as well as an etiology of cancer in Fanconi anemia patients.

  19. Aircraft noise exposure affects rat behavior, plasma norepinephrine levels, and cell morphology of the temporal lobe.

    PubMed

    Di, Guo-Qing; Zhou, Bing; Li, Zheng-Guang; Lin, Qi-Li

    2011-12-01

    In order to investigate the physiological effects of airport noise exposure on organisms, in this study, we exposed Sprague-Dawley rats in soundproof chambers to previously recorded aircraft-related noise for 65 d. For comparison, we also used unexposed control rats. Noise was arranged according to aircraft flight schedules and was adjusted to its weighted equivalent continuous perceived noise levels (L(WECPN)) of 75 and 80 dB for the two experimental groups. We examined rat behaviors through an open field test and measured the concentrations of plasma norepinephrine (NE) by high performance liquid chromatography-fluorimetric detection (HPLC-FLD). We also examined the morphologies of neurons and synapses in the temporal lobe by transmission electron microscopy (TEM). Our results showed that rats exposed to airport noise of 80 dB had significantly lower line crossing number (P<0.05) and significantly longer center area duration (P<0.05) than control animals. After 29 d of airport noise exposure, the concentration of plasma NE of exposed rats was significantly higher than that of the control group (P<0.05). We also determined that the neuron and synapsis of the temporal lobe of rats showed signs of damage after aircraft noise of 80 dB exposure for 65 d. In conclusion, exposing rats to long-term aircraft noise affects their behaviors, plasma NE levels, and cell morphology of the temporal lobe.

  20. Effect of fluoridated water on plasma insulin levels and glucose homeostasis in rats with renal deficiency.

    PubMed

    Lupo, Maela; Buzalaf, Marília Afonso Rabelo; Rigalli, Alfredo

    2011-05-01

    Glucose intolerance in fluorosis areas and when fluoride is administered for the treatment of osteoporosis has been reported. Controlled fluoridation of drinking water is regarded as a safe and effective measure to control dental caries. However, the effect on glucose homeostasis was not studied so far. The aim of this study was to evaluate the effect of the intake of fluoridated water supply on glucose metabolism in rats with normal and deficient renal function. Male Sprague-Dawley rats were divided into eight groups of four rats. Renal insufficiency was induced in four groups (NX) which received drinking water containing 0, 1, 5, and 15 ppm F (NaF) for 60 days. Four groups with simulated surgery acted as controls. There were no differences in plasma glucose concentration after a glucose tolerance test between controls and NX rats and among rats with different intakes of fluoride. However, plasma insulin level increased as a function of fluoride concentration in drinking water, both in controls and in NX rats. It is concluded that the consumption of fluoridated water from water supply did not affect plasma glucose levels even in cases of animals with renal disease. However, a resistance to insulin action was demonstrated.

  1. Aircraft noise exposure affects rat behavior, plasma norepinephrine levels, and cell morphology of the temporal lobe*

    PubMed Central

    Di, Guo-qing; Zhou, Bing; Li, Zheng-guang; Lin, Qi-li

    2011-01-01

    In order to investigate the physiological effects of airport noise exposure on organisms, in this study, we exposed Sprague-Dawley rats in soundproof chambers to previously recorded aircraft-related noise for 65 d. For comparison, we also used unexposed control rats. Noise was arranged according to aircraft flight schedules and was adjusted to its weighted equivalent continuous perceived noise levels (L WECPN) of 75 and 80 dB for the two experimental groups. We examined rat behaviors through an open field test and measured the concentrations of plasma norepinephrine (NE) by high performance liquid chromatography-fluorimetric detection (HPLC-FLD). We also examined the morphologies of neurons and synapses in the temporal lobe by transmission electron microscopy (TEM). Our results showed that rats exposed to airport noise of 80 dB had significantly lower line crossing number (P<0.05) and significantly longer center area duration (P<0.05) than control animals. After 29 d of airport noise exposure, the concentration of plasma NE of exposed rats was significantly higher than that of the control group (P<0.05). We also determined that the neuron and synapsis of the temporal lobe of rats showed signs of damage after aircraft noise of 80 dB exposure for 65 d. In conclusion, exposing rats to long-term aircraft noise affects their behaviors, plasma NE levels, and cell morphology of the temporal lobe. PMID:22135145

  2. Fluctuating plasma phosphorus level by changes in dietary phosphorus intake induces endothelial dysfunction.

    PubMed

    Watari, Eriko; Taketani, Yutaka; Kitamura, Tomoyo; Tanaka, Terumi; Ohminami, Hirokazu; Abuduli, Maerjianghan; Harada, Nagakatsu; Yamanaka-Okumura, Hisami; Yamamoto, Hironori; Takeda, Eiji

    2015-01-01

    High serum phosphorus (P) impairs endothelial function by increasing oxidative stress and decreasing nitric oxide production. Serum P levels fluctuate due to circadian rhythms or dietary P intake in healthy people and due to dialysis in end-stage chronic kidney disease patients. Here we examined whether fluctuating plasma P caused by changes in dietary P intake may be involved in endothelial dysfunction, resulting in increased cardiovascular risk. Rats were fed a diet containing 0.6% P for 16 days (control group), or a diet alternating between 0.02% P and 1.2% P (LH group) or between 1.2% P and 0.02% P (HL group) every 2 days; the total amount of P intake among the groups during the feeding period was similar. In the LH and HL groups, endothelial-dependent vasodilation significantly decreased plasma 8-(OH)dG level significantly increased, and the expression of inflammatory factors such as MCP-1 increased in the endothelium as compared with the control group. These data indicate that repetitive fluctuations of plasma P caused by varying dietary P intake can impair endothelial function via increased oxidative stress and inflammatory response. Taken together, these results suggest that habitual fluctuation of dietary P intake might be a cause of cardiovascular disease through endothelial dysfunction, especially in chronic kidney disease patients.

  3. Effects of controlled exposure of sunlight on plasma and skin levels of beta-carotene.

    PubMed

    Biesalski, H K; Hemmes, C; Hopfenmuller, W; Schmid, C; Gollnick, H P

    1996-03-01

    We conducted a randomized placebo-controlled double-blind study in 20 healthy young female students (skin type II + III, body mass index 18-22) in order to evaluate the efficacy of 10 weeks of moderate dose (30 mg/d) beta-carotene (BC) on plasma and skin beta-carotene levels during 12 days of time and intensity controlled sunlight exposure at sea level (30 degrees latitude, Red Sea, Eilath, Israel). After 12 days of controlled sun exposure (total UV dose of about 10.000J/cm2), plasma beta-carotene decreased in the placebo (p < 0.01) and beta-carotene group (not significant). In addition cutaneous beta-carotene decreased significantly in both groups. Plasma alpha-tocopherol decreased significantly (p < 0.01) during exposure time in both groups. In the supplemented group, however, the decrease of a-tocopherol was significantly greater (p < 0.01) than in the placebo group. We conclude that sunlight influences the beta-carotene and alpha-tocopherol content of blood and tissues.

  4. Direct measurement of the precursors of adrenocorticotropin in human plasma by two-site immunoradiometric assay

    SciTech Connect

    Crosby, S.R.; Stewart, M.F.; Ratcliffe, J.G.; White, A.

    1988-12-01

    An immunoradiometric assay (IRMA) for the direct measurement of the precursors of ACTH in unextracted human plasma has been developed and evaluated clinically in normal subjects and patients with disorders of the hypothalamic-pituitary-adrenal axis. The IRMA is based on an iodinated monoclonal antibody to ACTH and a monoclonal antibody to gamma MSH coupled to Sephacryl S300. The assay detects only peptides containing both epitopes, i.e. POMC (31K) and pro-ACTH (22K). The reference standard was partially purified POMC from culture medium of human corticotroph adenoma cells. The detection limit (greater than +2.5SD of the 0 standard) was 2.0 pmol/L and the within-assay coefficient of variation was less than 10% between 29 and 2600 pmol/L. Plasma concentrations of ACTH precursor peptides in 11 normal subjects sampled at 0930 h ranged from 5-34 pmol/L. The concentrations in the patient groups studied were: 260-2300 pmol/L in 5 patients with the ectopic ACTH syndrome associated with small cell lung cancer, less than 2.0-104 pmol/L in 10 patients with pituitary-dependent Cushing's disease, 23 pmol/L in a patient with Nelson's syndrome, and 3.0-230 pmol/L in 5 patients with Addison's disease. We conclude that this IRMA offers a simple and reliable method for measuring ACTH precursors in unextracted plasma. The proportionately greater elevation of ACTH precursors compared to ACTH in patients with the ectopic ACTH syndrome associated with small cell lung cancer but not in pituitary-dependent Cushing's syndrome, suggests that this assay may be clinically useful.

  5. Gender differences in plasma levels of lipoprotein (a) in patients with angiographically proven coronary artery disease.

    PubMed

    Frohlich, J; Dobiásová, M; Adler, L; Francis, M

    2004-01-01

    The objective of the study was to assess the association between plasma levels of lipoprotein(a) [Lp(a)] and the presence of angiographically defined coronary artery disease (aCAD). Patients (346 men and 184 women) undergoing selective coronary angiography (SCA) were classified into groups with positive [aCAD(+)] and negative [aCAD(-)] findings and their age, body mass index (BMI), waist circumference, blood pressure, smoking, plasma total, LDL-, HDL-cholesterol (TC, LDL-C, HDL-C), triglycerides (TG), apolipoprotein B (apoB), Log(TG/HDL-C) and TC/HDL-C were determined. Concentration of plasma Lp(a) was estimated using the commercial solid phase two-side immunoradiometric assay of apolipoprotein apo(a). The plasma Lp(a) was significantly higher in both women and men with aCAD(+) compared to those with aCAD(-). While there was no significant difference in the Lp(a) level between men and women with aCAD(-) (median 138 vs. 145 units/l), the women with aCAD(+) had almost twice as high Lp(a) levels as men (median 442 vs. 274 units/l, p<0.001). Women with aCAD(+) had also significantly lower HDL cholesterol levels (1.09 vs. 1.20 mmol/l, p<0.05), higher triglycerides (1.82 vs. 1.46 mmol/l, p<0.05) and Log(TG/HDL-C) than women with aCAD(-). The differences in Lp(a) between positive and negative findings remained highly significant (p<0.001 in women, p<0.05 in men) after the adjustment for age, plasma HDL- and LDL-cholesterol and triglycerides in logistic regression analyses. In logistic regression model the Lp(a) and Log(TG/HDL-C) and smoking in women but smoking and age in men were the most powerful predictors of positive aCAD findings. Our findings suggest that Lp(a) is more strongly associated with aCAD+ in women than in men.

  6. Plasma Glucose Levels for Red Drum Sciaenops Ocellatus in a Florida Estuarine Fisheries Reserve

    NASA Technical Reports Server (NTRS)

    Bourtis, Carla M.; Francis-Floyd, Ruth; Boggs, Ashley S P.; Reyier, Eric A.; Stolen, Eric D.; Yanong, Roy P.; Guillette, Louis J., Jr.

    2015-01-01

    Despite the significant value of the southeastern United States' red drum (Sciaenops ocellatus) fishery, there is a lack of clinical blood chemistry data. This was the first study to assess plasma glucose values as an indicator of stress response to evaluate variation and the effect of reproductive activity for wild adult red drum in Florida. Red drum (n=126) were collected from NASA's Kennedy Space Center waters during three reproductive periods in 2011. Samples were obtained from the branchial vessels of the gill arch. Plasma glucose levels were significantly different among reproductive periods, with the highest mean values recorded during the spawning period, September- October (38.23 mg / dL +/- 10.0). The glucose range was 17 - 69 mg / dL. Glucose values were lower during all three periods than previous values recorded for cultured or captive red drum studies. This may indicate that fish from this population were under less stress than other populations previously sampled.

  7. Soft mean spherical approximation for dusty plasma liquids: Level of accuracy and analytic expressions

    SciTech Connect

    Tolias, P.; Ratynskaia, S.; Angelis, U. de

    2015-08-15

    The soft mean spherical approximation is employed for the study of the thermodynamics of dusty plasma liquids, the latter treated as Yukawa one-component plasmas. Within this integral theory method, the only input necessary for the calculation of the reduced excess energy stems from the solution of a single non-linear algebraic equation. Consequently, thermodynamic quantities can be routinely computed without the need to determine the pair correlation function or the structure factor. The level of accuracy of the approach is quantified after an extensive comparison with numerical simulation results. The approach is solved over a million times with input spanning the whole parameter space and reliable analytic expressions are obtained for the basic thermodynamic quantities.

  8. Comparison of the blood plasma catecholamines level in thoroughbred and Arabian horses during the same-intensity exercise.

    PubMed

    Podolak, M; Kedzierski, W; Bergero, D

    2006-01-01

    The aim of this study was to compare changes in epinephrine (E), norepinephrine (NE) and dopamine (DA) levels in blood plasma of two racehorses breeds: Arabian and Thoroughbred during moderate intensity exercise performed in the same conditions. The increase in plasma E level just after exercise was higher in Thoroughbreds than in Arabians. During the whole test, the Arabians showed the higher levels of NE and DA as compared to those found in Thoroughbreds.

  9. Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test

    PubMed Central

    Rodríguez-Gutiérrez, René; Rendon, Adrian; Barrera-Sánchez, Maximiliano; Carlos-Reyna, Kevin Erick Gabriel; Álvarez-Villalobos, Neri Alejandro; González-Saldivar, Gloria; González-González, José Gerardo

    2016-01-01

    Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients' health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg) ACTH stimulation test at baseline and at 6–12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2 ± 3.6 months) adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or

  10. Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test.

    PubMed

    Rodríguez-Gutiérrez, René; Rendon, Adrian; Barrera-Sánchez, Maximiliano; Carlos-Reyna, Kevin Erick Gabriel; Álvarez-Villalobos, Neri Alejandro; González-Saldivar, Gloria; González-González, José Gerardo

    2016-01-01

    Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients' health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg) ACTH stimulation test at baseline and at 6-12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2 ± 3.6 months) adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or treat

  11. Association of Plasma ADMA Levels with MRI Markers of Vascular Brain Injury: The Framingham Offspring Study

    PubMed Central

    Pikula, Aleksandra; Böger, Rainer H.; Beiser, Alexa S.; Maas, Renke; DeCarli, Charles; Schwedhelm, Edzard; Himali, Jayandra J.; Schulze, Friedrich; Au, Rhoda; Kelly-Hayes, Margaret; Kase, Carlos S.; Vasan, Ramachandran S.; Wolf, Philip A.; Seshadri, Sudha

    2009-01-01

    Background and Purpose Asymmetric dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase, is a marker of endothelial dysfunction. Elevated circulating ADMA concentrations have been associated with systemic and carotid atherosclerosis, an elevated risk of developing stroke and with MRI white matter hyperintensities (WMH). The relation of plasma ADMA to subclinical vascular brain injury has not been previously studied in a middle-aged, community-based sample. Methods In 2013 stroke-free Framingham Offspring (mean age 58±9.5yrs, 53% women) we related baseline plasma ADMA levels (1995–98) to subsequent brain MRI (1999–2004) measures of subclinical vascular injury: presence of silent brain infarcts (SBI) and large white matter hyperintensity volume (LWMH; defined as >1SD above age-specific mean). Results Prevalence of SBI and LWMH were 10.7% and 12.6%, respectively. In multivariable analyses adjusting for age-, sex- and traditional stroke risk factors, higher ADMA levels were associated with an increased risk of prevalent SBI (OR per SD increase in ADMA: 1.16, 95%CI: 1.01–1.33, p= 0.04).We observed that participants in the upper three age-specific quartiles of plasma ADMA had an increased prevalence of SBI (OR for Q2–4 versus Q1:1.43, 95%CI: 1.00–2.04, p<0.05). Prevalence of SBI in Q1and Q2–4 was 8.3% and 11.6%, respectively. Prevalence of LWMH did not differ according to ADMA concentrations. Conclusion Higher plasma ADMA was associated with increased prevalence of SBI after adjustment for traditional stroke risk factors. Thus, ADMA may be a potentially useful new biomarker of subclinical vascular brain injury, which is an important correlate of vascular cognitive impairment and risk of stroke. PMID:19644064

  12. Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure.

    PubMed

    Bell, David; Gordon, Brian J; Lavery, Anita; Megaw, Katie; Kinney, Michael O; Harbinson, Mark T

    2016-02-01

    Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD(25-56) and preproIMD(57-92), were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin(45-92) (MRproAM(45-92)) in 19 patients with systolic heart failure (LVEF<45%). In healthy subjects, plasma levels (mean+SE) of IMD (6.3+0.6 pg ml(-1)) were lower than, but correlated with those of AM (25.8+1.8 pg ml(-1); r=0.49, p<0.001). Plasma preproIMD(25-56) (39.6+3.1 pg ml(-1)), preproIMD(57-92) (25.9+3.8 pg ml(-1)) and MRproAM(45-92) (200.2+6.7 pg ml(-1)) were greater than their respective bioactive peptides. IMD levels correlated positively with BMI but not age, and were elevated in heart failure (9.8+1.3 pg ml(-1), p<0.05), similarly to MRproAM(45-92) (329.5+41.9 pg ml(-1), p<0.001) and AM (56.8+10.9 pg ml(-1), p<0.01). IMD levels were greater in heart failure patients with concomitant renal impairment (11.3+1.8 pg ml(-1)) than those without (6.5+1.0 pg ml(-1); p<0.05). IMD and AM were greater in patients receiving submaximal compared with maximal heart failure drug therapy and were decreased after 6 months of cardiac resynchronization therapy. In conclusion, IMD is present in the plasma of healthy subjects less abundantly than AM, but is similarly correlated weakly with BMI. IMD levels are elevated in heart failure, especially with concomitant renal impairment, and tend to be reduced by high intensity drug or pacing therapy.

  13. Trend analysis of plasma insulin level around parturition in relation to parity in Saanen goats.

    PubMed

    Magistrelli, D; Rosi, F

    2014-06-01

    The present study investigated the effect of parity on plasma insulin level around parturition in Saanen goats. On d -14, -7, 0, 3, 7, 10, and 14 from parturition, plasma glucose, NEFA, free AA, cortisol, and insulin concentrations were analyzed in 10 primiparous and 10 multiparous goats. At parturition, BW of primiparous goats was about 75% of that of multiparous ones (P < 0.001) and then their milk production was lower than that of multiparous ones (P < 0.001). At parturition, glucose increased (P < 0.01) in both primiparous and multiparous goats and then decreased (P < 0.01) on d 3 of lactation, remaining higher (P < 0.01) in primiparous than multiparous goats until the end of the study period. In both groups, free AA decreased (P < 0.01) at parturition, returning to prepartum levels (P < 0.01) on d 3 of lactation without difference between groups. Only in multiparous goats, plasma NEFA increased at parturition (P < 0.01), returning to prepartum levels on d 14 (P < 0.01). Changes in glucose and AA could have been caused by cortisol, which increased (P < 0.01) at parturition in both primiparous and multiparous goats, returning to prepartum levels (P < 0.01) on d 7 of lactation, without difference between the parity groups. In multiparous goats, insulin decreased soon after parturition (P < 0.05), remaining at low levels until the end of the study period, whereas in primiparous goats, insulin did not vary until d 14 of lactation, when it decreased (P < 0.05) also in this group. Therefore, between d 3 and 14 of lactation, insulin was higher in primiparous than multiparous goats (P < 0.05). Only in primiparous goats, at kidding, insulin was negatively correlated to BW (P < 0.01), and after parturition it was negatively correlated with milk yield (P < 0.05) and plasma NEFA (P < 0.05). We hypothesize that higher insulin levels in primiparous Saanen goats, which are still immature at their first breeding season, acted to limit both the mobilization of bodily reserves

  14. Lipoprotein(a) plasma levels and the risk of cancer: the PRIME study.

    PubMed

    Marrer, Émilie; Wagner, Aline; Montaye, Michèle; Luc, Gérald; Amouyel, Philippe; Dallongeville, Jean; Ducimetiere, Pierre; Bingham, Annie; Arveiler, Dominique; Velten, Michel

    2013-05-01

    Although experimental studies have shown lipoprotein(a) antiangiogenic and antitumoral effects, the association of lipoprotein(a) levels with cancer in population studies remains elusive and poorly documented. The aim of this study was to analyse the relationship between lipoprotein(a) plasma levels and the incidence of cancer over 10 years of follow-up. Data from two French centres of the PRIME cohort were used, representing 5237 men aged 50-59 years and free from a history of cancer at baseline. Data on medical history, socioeconomic and lifestyle factors were obtained by questionnaire. Lipoprotein(a) plasma levels were analysed from fasting blood samples collected at baseline. The relationship between lipoprotein(a) levels and first incident cancer was studied using the multivariate Cox proportional hazards models for all-site and the main-site-specific cancers, adjusted for various potential confounders including age, centre, smoking status and alcohol consumption. During follow-up, 456 new cancers were identified. No significant association was found between lipoprotein(a) and the all-site or main-site-specific cancers (hazard ratios for quartiles 2-4 vs. 1, respectively: 1.24, 1.11, 1.29, P=0.23). However, a higher risk seemed to be observed for highest lipoprotein(a) levels in all sites, lung, colorectal or tobacco/alcohol-related cancers. For prostate cancer, the lowest risk was observed for the highest levels of lipoprotein(a) (P=0.12). In conclusion, no evident association was found between the lipoprotein(a) levels and the incidence of cancer. Nevertheless, a higher cancer risk seemed to be observed for the highest lipoprotein(a) levels. Further research focusing on the lipoprotein(a) qualitative structure, that is, apolipoprotein(a) polymorphism could help clarify this highly complex relation.

  15. [1H-NMR studies of the ACTH-like immunoregulatory peptides].

    PubMed

    Khristoforov, V S; Kutyshenko, V P; Abramov, V M; Zav'ialov, V P

    1997-01-01

    A comparative study of the conformational and dynamics properties of the ACTH-like linear peptides, sequences of which correspond to amino acid residues 11-20 of the heavy chain of human immunoglobulin G1 Eu, residues 78-85 of human pro-interleukin-1 alpha and site 10-18 of human ACTH, was performed in aqueous solution and dimethylsulfoxide by 1H-NMR spectroscopy at 400 MHz. The peptides were shown to possess an unordered unfolded flexible conformation in aqueous solution. The revealed structural and dynamic features of the peptides are discussed together with biological activity of this class of compounds.

  16. Loss of sensitivity to ACTH of adrenocortical cells isolated from maturing domestic fowl.

    PubMed

    Carsia, R V; Scanes, C G; Malamed, S

    1985-07-01

    Maturation of domestic fowl corticosteroidogenesis was evaluated using purified adrenocortical cells. Basal corticosterone production decreased steadily from 2 days to 26 weeks after hatching. However, maximally stimulated corticosterone production was not changed. In contrast, the half-maximal steroidogenic concentrations (ED50 values or effective doses for 50% maximal effect) of ACTH analogs increased approximately 40 times by 26 weeks, but the ED50 values of 8-bromo-cyclic AMP and pregnenolone were not changed. This suggests that adrenocortical cell sensitivity to ACTH decreases with maturation of the domestic fowl.

  17. [Neurophysiologic analysis of the effect of ACTH and hydrocortisone on conditioned reflex behavior in cats].

    PubMed

    Sever'ianova, L A

    1977-01-01

    In defensive behaviour of cats, ACTH eliminated extinction delay, evoked by electrical stimulation (with constant parameters) of the midbrain reticular formation, and enhanced the activating influence of the thalamus reticular zone. Hydrocortisone produced opposite effects. In alimentary behaviour, the adaptive hormones enhanced the facilitating effect on extinction, induced by stimulation of non-specific structures and the hypothalamus. However, during hydrocortisone action, encephalographic signs of the reflex remained for a long time after extinction of effector manifestations. Thus, ACTH and hydrocortizone, by changing the interaction between brain structures, exert certain influences on the behavioral processes. The hormonal effects, in turn, depend on the initial co-excitation of the centres.

  18. Basal Plasma Levels of Copeptin are Elevated in Inactive Inflammatory Bowel Disease after Bowel Resection

    PubMed Central

    Ohlsson, Bodil; Melander, Olle

    2015-01-01

    Evidence of interactions between the enteric nervous system, neuropeptides, and the immune system is growing. The aim of this study was to examine basal plasma levels of a variety of peptide precursors in patients with inflammatory bowel disease (IBD). In two middle-aged cohorts, Malmö Preventive Medicine (n = 5,415) and Malmö Diet and Cost Study (n = 6,103), individuals with the diagnosis of IBD were identified. Medical records were scrutinized. Three controls were matched for each patient. Copeptin, midregional fragments of adrenomedullin, pro-atrial natriuretic peptide, and proenkephalin A, as well as N-terminal protachykinin A and proneurotensin were analyzed in the plasma. Sixty-two IBD patients were identified. The only difference between patients and controls was higher copeptin levels in the patients compared with controls (P = 0.006), with higher copeptin levels in resected than unresected patients (P = 0.020). There was no difference in any precursor levels between Crohn’s disease and ulcerative colitis, between different distributions of disease lesions, or between different treatments. PMID:26244009

  19. Nerve growth factor plasma levels and ventricular repolarization in Rett syndrome.

    PubMed

    Guideri, F; Acampa, M; Calamandrei, G; Aloe, L; Zappella, M; Hayek, Y

    2004-01-01

    Rett syndrome is a severe neurological developmental disorder. In this syndrome, the high incidence of sudden death is correlated with an alteration of ventricular repolarization. The purpose of this study was to evaluate plasmatic levels of nerve growth factor (NGF) in Rett patients with prolonged corrected QT (QTc) interval in comparison with those of Rett patients with normal QTc. We observed 23 female Rett patients (9.9+/-4.7 years). NGF plasma levels and QTc interval were measured in all patients. Student t-test was performed for statistical analysis. NGF plasma levels were significantly lower in Rett patients with QTc interval prolongation (QTc > 0.44 sec) in comparison with Rett patients with a normal QTc interval (4.5+/-4.5 vs 11+/-8.3 pg/ml, p = 0.02). The alteration of NGF levels, observed in Rett patients with a long QTc interval, may explain the presence of an altered ventricular repolarization associated with a higher risk of cardiac arrhythmias.

  20. Acute gastric pH changes alter intraluminal but not plasma peptide levels.

    PubMed

    Mueller, C R; Ure, T; O'Dorisio, T M; Barrie, R J; Woltering, E A

    1991-12-01

    Gastric acidity is influenced by systemic and local peptide effects. Previous work by others has shown that intraluminally secreted peptides may have a role in local control of gastric acidity; however, the response of these peptides to acute changes in gastric pH is unknown. To determine the effects of acute changes in pH on systemic and intraluminal peptide levels, 14 normal volunteers underwent placement of a nasogastric tube after an overnight fast. Blood and gastric fluid were analyzed on a control day, 2 hours after completion of 24 hours of aluminum-magnesium antacid therapy and after 24 hours of H2 blockade. Plasma and acid-alcohol-extracted gastric peptide levels were measured with specific radioimmunoassays. Specimens were subdivided into two groups: 28 gastric fluid specimens with a pH less than 4 and 10 specimens with a pH greater than 4. In the patients with a pH greater than 4, the luminal peptides, motilin, neurotensin, pancreatic polypeptide, somatostatin, substance P, and gastrin, were decreased by 50% to 90% and gastrin-releasing peptide was decreased by 36% compared with specimens with a pH less than 4. Conversely, intraluminal vasoactive intestinal polypeptide and calcitonin levels were elevated by 60% and 27%, respectively, in the samples with a pH greater than 4. Intraluminal peptide concentrations are responsive to changes in intragastric pH; however, this response was not seen in plasma peptide levels.

  1. Alteration in plasma testosterone levels in male mice lacking soluble epoxide hydrolase.

    PubMed

    Luria, Ayala; Morisseau, Christophe; Tsai, Hsing-Ju; Yang, Jun; Inceoglu, Bora; De Taeye, Bart; Watkins, Steven M; Wiest, Michelle M; German, J Bruce; Hammock, Bruce D

    2009-08-01

    Soluble epoxide hydrolase (Ephx2, sEH) is a bifunctional enzyme with COOH-terminal hydrolase and NH(2)-terminal phosphatase activities. sEH converts epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), and the phosphatase activity is suggested to be involved in cholesterol metabolism. EETs participate in a wide range of biological functions, including regulation of vascular tone, renal tubular transport, cardiac contractility, and inflammation. Inhibition of sEH is a potential approach for enhancing the biological activity of EETs. Therefore, disruption of sEH activity is becoming an attractive therapeutic target for both cardiovascular and inflammatory diseases. To define the physiological role of sEH, we characterized a knockout mouse colony lacking expression of the Ephx2 gene. Lack of sEH enzyme is characterized by elevation of EET to DHET ratios in both the linoleate and arachidonate series in plasma and tissues of both female and male mice. In male mice, this lack of expression was also associated with decreased plasma testosterone levels, sperm count, and testicular size. However, this genotype was still able to sire litters. Plasma cholesterol levels also declined in this genotype. Behavior tests such as anxiety-like behavior and hedonic response were also examined in Ephx2-null and WT mice, as all can be related to hormonal changes. Null mice showed a level of anxiety with a decreased hedonic response. In conclusion, this study provides a broad biochemical, physiological, and behavioral characterization of the Ephx2-null mouse colony and suggests a mechanism by which sEH and its substrates may regulate circulating levels of testosterone through cholesterol biosynthesis and metabolism.

  2. Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels

    PubMed Central

    Jiang, Xian-cheng; Bruce, Can; Mar, Jefferson; Lin, Min; Ji, Yong; Francone, Omar L.; Tall, Alan R.

    1999-01-01

    It has been proposed that the plasma phospholipid transfer protein (PLTP) facilitates the transfer of phospholipids and cholesterol from triglyceride-rich lipoproteins (TRL) into high-density lipoproteins (HDL). To evaluate the in vivo role of PLTP in lipoprotein metabolism, we used homologous recombination in embryonic stem cells and produced mice with no PLTP gene expression. Analysis of plasma of F2 homozygous PLTP–/– mice showed complete loss of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, and partial loss of free cholesterol transfer activities. Moreover, the in vivo transfer of [3H]phosphatidylcholine ether from very-low-density proteins (VLDL) to HDL was abolished in PLTP–/– mice. On a chow diet, PLTP–/– mice showed marked decreases in HDL phospholipid (60%), cholesterol (65%), and apo AI (85%), but no significant change in non-HDL lipid or apo B levels, compared with wild-type littermates. On a high-fat diet, HDL levels were similarly decreased, but there was also an increase in VLDL and LDL phospholipids (210%), free cholesterol (60%), and cholesteryl ester (40%) without change in apo B levels, suggesting accumulation of surface components of TRL. Vesicular lipoproteins were shown by negative-stain electron microscopy of the free cholesterol– and phospholipid-enriched IDL/LDL fraction. Thus, PLTP is the major factor facilitating transfer of VLDL phospholipid into HDL. Reduced plasma PLTP activity causes markedly decreased HDL lipid and apoprotein, demonstrating the importance of transfer of surface components of TRL in the maintenance of HDL levels. Vesicular lipoproteins accumulating in PLTP–/– mice on a high-fat diet could influence the development of atherosclerosis. PMID:10079112

  3. Increased plasma chemokine levels in children with Prader-Willi syndrome.

    PubMed

    Butler, Merlin G; Hossain, Waheeda; Sulsona, Carlos; Driscoll, Daniel J; Manzardo, Ann M

    2015-03-01

    Prader-Willi syndrome (PWS) is caused by loss of paternally expressed genes from the 15q11-q13 region and reportedly rearranged as a cause of autism. Additionally, increased inflammatory markers and features of autism are reported in PWS. Cytokines encoded by genes involved with inflammation, cell proliferation, migration, and adhesion play a role in neurodevelopment and could be disturbed in PWS as abnormal plasma cytokine levels are reported in autism. We analyzed 41 plasma cytokines in a cohort of well-characterized children with PWS between 5 and 11 years of age and unaffected unrelated siblings using multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Data were analyzed using ANOVA testing for effects of diagnosis, gender, body mass index (BMI) and age on the 24 cytokines meeting laboratory criteria for inclusion. No significant effects were observed for age, gender or BMI. The log-transformed levels of the 24 analyzable cytokines were examined simultaneously using MANOVA adjusting for age and gender and a main effect of diagnosis was found (P-value <0.03). Four of 24 plasma cytokine levels (MCP1, MDC, Eotaxin, RANTES) were significantly higher in children with PWS compared with controls and classified as bioinflammatory chemokines supporting a disturbed immune response unrelated to obesity status. BMI was not statistically different in the two subject groups (PWS or unaffected unrelated siblings) and chemokine levels were not correlated with percentage of total body fat. Additional studies are required to identify whether possible early immunological disturbances and chemokine inflammatory processes found in PWS may contribute to neurodevelopment and behavioral features.

  4. Maternal intake of antioxidant vitamins in pregnancy in relation to maternal and fetal plasma levels at delivery.

    PubMed

    Scaife, Alison R; McNeill, Geraldine; Campbell, Doris M; Martindale, Sheelagh; Devereux, Graham; Seaton, Anthony

    2006-04-01

    The aim of the present study was to test the hypothesis that maternal intake of antioxidant vitamins is associated with maternal and cord plasma levels at delivery. Women were recruited in early pregnancy in Aberdeen Maternity Hospital and habitual diet during pregnancy was assessed by a food-frequency questionnaire mailed at 34 weeks gestation. Blood samples were taken at recruitment (n 1149) and maternal (n 1149) and cord blood samples (n 747) taken at delivery for analyses of vitamins A, C, E and beta-carotene. Maternal plasma levels of vitamin E and beta-carotene at delivery were significantly higher than levels in early pregnancy while levels of vitamins A and C were significantly lower. Positive correlations were observed for maternal levels of all the vitamins between early pregnancy and delivery. At delivery, maternal plasma concentrations of vitamins A, E and beta-carotene were significantly higher than cord levels, while maternal levels of vitamin C were significantly lower. There were significant correlations between maternal and cord plasma concentrations for beta-carotene and vitamin C but not for vitamins A or E. Maternal dietary intakes were positively correlated with maternal plasma levels of vitamins C, E and beta-carotene in early pregnancy, with maternal plasma levels of beta-carotene and vitamin C at delivery and with cord plasma levels of beta-carotene and vitamin C. The results from the present study show that, in this population, maternal diet influences cord plasma levels of beta-carotene and vitamin C, but not vitamins A and E.

  5. Adrenocortical steroid response to ACTH in different phenotypes of non-obese polycystic ovary syndrome

    PubMed Central

    2012-01-01

    Background Adrenal androgen excess is frequently observed in PCOS. The aim of the study was to determine whether adrenal gland function varies among PCOS phenotypes, women with hyperandrogenism (H) only and healthy women. Methods The study included 119 non-obese patients with PCOS (age: 22.2 ± 4.1y, BMI:22.5 ± 3.1 kg/m2), 24 women with H only and 39 age and BMI- matched controls. Among women with PCOS, 50 had H, oligo-anovulation (O), and polycystic ovaries (P) (PHO), 32 had O and H (OH), 23 had P and H (PH), and 14 had P and O (PO). Total testosterone (T), SHBG and DHEAS levels at basal and serum 17-hydroxprogesterone (17-OHP), androstenedione (A4), DHEA and cortisol levels after ACTH stimulation were measured. Results T, FAI and DHEAS, and basal and AUC values for 17-OHP and A4 were significantly and similarly higher in PCOS and H groups than controls (p < 0.05 for all) whereas three groups did not differ for basal or AUC values of DHEA and cortisol. Three hyperandrogenic subphenotypes (PHO, OH, and PH) compared to non-hyperandrogenic subphenotype (PO) had significantly and similarly higher T, FAI, DHEAS and AUC values for 17-OHP, A4 and DHEA (p < 0.05). All subphenotypes had similar basal and AUC values for cortisol. Conclusion PCOS patients and women with H only have similar and higher basal and stimulated adrenal androgen levels than controls. All three hyperandrogenic subphenotypes of PCOS exhibit similar and higher basal and stimulated adrenal androgen secretion patterns compared to non-hyperandrogenic subphenotype. PMID:23216997

  6. Influence of dietary lipids on hepatic mRNA levels of proteins regulating plasma lipoproteins in baboons with high and low levels of large high density lipoproteins.

    PubMed

    Kushwaha, R S; McMahan, C A; Mott, G E; Carey, K D; Reardon, C A; Getz, G S; McGill, H C

    1991-12-01

    Selective breeding of baboons has produced families with increased plasma levels of large high density lipoproteins (HDL1) and very low (VLDL) and low (LDL) density lipoproteins when the animals consume a diet enriched in cholesterol and saturated fat. High HDL1 baboons have a slower cholesteryl ester transfer, which may account for the accumulation of HDL1, but not of VLDL and LDL. To investigate the mechanism of accumulation of VLDL + LDL in plasma of the high HDL1 phenotype, we selected eight half-sib pairs of baboons, one member of each pair with high HDL1, the other member with little or no HDL1 on the same high cholesterol, saturated fat diet. Baboons were fed a chow diet and four experimental diets consisting of high and low cholesterol with corn oil, and high and low cholesterol with lard, each for 6 weeks, in a crossover design. Plasma lipids and lipoproteins and hepatic mRNA levels were measured on each diet. HDL1 phenotype, type of dietary fat, and dietary cholesterol affected plasma cholesterol and apolipoprotein (apo) B concentrations, whereas dietary fat alone affected plasma triglyceride and apoA-I concentrations. HDL1 phenotype and dietary cholesterol alone did not influence hepatic mRNA levels, whereas dietary lard, compared to corn oil, significantly increased hepatic apoE mRNA levels and decreased hepatic LDL receptor and HMG-CoA synthase mRNA levels. Hepatic apoA-I message was associated with cholesterol concentration in HDL fractions as well as with apoA-I concentrations in the plasma or HDL. However, hepatic apoB message level was not associated with plasma or LDL apoB levels. Total plasma cholesterol, including HDL, was negatively associated with hepatic LDL receptor and HMG-CoA synthase mRNA levels. However, compared with low H