Sample records for acth plasma levels
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Radioimmunoassay of ACTH in plasma
Berson, Solomon A.; Yalow, Rosalyn S.
1968-01-01
Techniques are described in detail for a radioimmunoassay of plasma adrenocorticotropin (ACTH) that is capable of detecting hormone in unextracted normal human plasma at 1:5 dilution under the conditions described. The sensitivity of the assay is at the level of 1 μμg/ml (equivalent to 0.014 mU/100 ml). In normal subjects ACTH concentrations averaged 22 μμg/ml (equivalent to 0.308 mU/100 ml) plasma at 8-10 a.m. In a smaller group the concentrations averaged 9.6 μμg/ml (equivalent to 0.134 mU/100 ml) at 10-11 p.m. Although a circadian rhythm in normal subjects was not always well marked throughout the daytime hours, plasma ACTH usually fell to its lowest value in the late evening. In hospital patients who were not acutely ill, concentrations were infrequently above 100 μμg/ml in the morning and usually fell to significantly lower levels in the late evening. Severely ill hospital patients occasionally exhibited a.m. concentrations above 200 μμg/ml. In a group of subjects showing frequent spiking of plasma 17-OHCS concentrations throughout the day parallel spiking of plasma ACTH as well was generally observed. Metyrapone produced marked increases in plasma ACTH within 24 hr in all cases and generally within 3-6 hr except when started late in the day. Dexamethasone brought about a persistent reduction in plasma ACTH in a patient under continued treatment with metyrapone. Hypoglycemia, electroshock, surgery under general anesthesia, histalog and vasopressin administration were usually followed by significant increases in plasma ACTH concentration. Prior administration of dexamethasone blocked the response to hypoglycemia. Marked elevations in plasma ACTH were observed in patients with adrenal insufficiency off steroid therapy, in Cushing's disease after adrenalectomy even in the presence of persistent hypercortisolemia, and in some untreated patients with Cushing's disease. Umbilical cord blood contained higher plasma ACTH concentrations than maternal blood at
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Srinivasan, Lakshmi; Laws, Edward R; Dodd, Robert L; Monita, Monique M; Tannenbaum, Christyn E; Kirkeby, Kjersti M; Chu, Olivia S; Harsh, Griffith R; Katznelson, Laurence
2011-12-01
Rapid assessment of adrenal function is critical following transsphenoidal surgery (TSS) for Cushing's disease (CD) in order to determine surgical efficacy. We hypothesize that there may be a role for ACTH measurement as a rapid indicator of adrenal function. Following surgery for CD, glucocorticoids were withheld and paired plasma ACTH and serum cortisol levels were measured every 6 h. Post-operative hypocortisolemia was defined as serum cortisol <2 mcg/dl or a serum cortisol <5 mcg/dl with the onset of symptoms of adrenal insufficiency within 72 h. We studied 12 subjects, all female, mean age 44.6 years (range 25-55), including 13 surgeries: nine subjects attained hypocortisolemia. Plasma ACTH levels decreased more in subjects with hypocortisolemia (0.9 pg/ml/hr, P = 0.0028) versus those with persistent disease (0 0.2 pg/ml/hr, P = 0.26) within the first 48 h after surgery. In contrast to subjects with persistent disease, all subjects with hypocortisolemia achieved a plasma ACTH <20 pg/ml by 19 h (range 1-19 h). Four of the nine subjects with hypocortisolemia achieved plasma ACTH <20 pg/ml by 13 h and the remaining five subjects by 19 h. Hypocortisolemia occurred between 3-36 h following achievement of a plasma ACTH <20 pg/ml. In CD, a reduction in postoperative plasma ACTH levels differentiates subjects with surgical remission versus subjects with persistent disease. The utility of plasma ACTH measurements in the postoperative management of CD remains to be determined.
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Stevenson, Erika T; Gese, Eric M; Neuman-Lee, Lorin A; French, Susannah S
2018-03-01
Knowledge of endocrine stress responses can be advantageous for understanding how animals respond to their environment. One tool in wildlife endocrinology is to measure the adrenocortical activity as a parameter of disturbance of animals. Fecal glucocorticoid metabolites (GCMs) provide a noninvasive assessment of adrenocortical activity. Using an adrenocorticotropic hormone (ACTH) challenge administered to 28 captive coyotes (Canis latrans), we measured the levels of plasma cortisol, and fecal cortisol and corticosterone metabolites (i.e., GCMs). Our goal was to determine the dose-response in the plasma and fecal samples following the injection and determine if there were effects of sex, age, and time of day. Specifically, animals were anesthetized for ~ 90 min with treatment animals intravenously injected with exogenous ACTH and control animals receiving saline. We collected blood samples prior to injection and at 4 different time points post-injection. We also collected fecal samples 2 days pre- and 2 days post-injection to measure fecal GCMs and determine if an endocrine stress response could be detected in fecal samples. We found a definite response in cortisol levels in the plasma for coyotes to the ACTH challenge. There was a response in fecal corticosterone 1 day post-injection, but the control males showed a similar response indicating a handling effect. Fecal cortisol levels did not indicate a response to the ACTH challenge, and were significantly lower than corticosterone concentrations. We also found significant sex, but not age or diurnal, differences in fecal GCMs. Radioimmunoassays for fecal corticosterone levels appeared to be a reliable indicator of physiological stress in coyotes.
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Gehlen, Heidrun; Bradaric, Zrinkja
2013-01-01
The evaluation of plasma ACTH and the dexamethasone suppression test are considered the methods of choice to evaluate the course of therapy of pituitary pars intermedia dysfunction (PPID). Sampling protocols as well as vacutainers for analysis differ between the laboratories. To evaluate the reproducability of plasma ACTH measurement between four different laboratories (A, B, C, D) in Germany as well as within the laboratories themselves, ten horses with previously diagnosed PPID and four healthy horses were sampled and analyzed. Each laboratory received two differently labeled samples of each horse which had been drawn at the same time (blinded samples). Sampling was performed in the morning at the same time. The sampling vacutainers (with and without addition of coagulation and proteinase inhibitors) and postage of the samples was performed according to laboratory standards. In one laboratory the influence of the time of centrifugation (immediately after taking blood versus after one hour) was determined. The samples were processed and analyzed according to laboratory protocols. Determination of ACTH levels was performed using chemiluminescence immunoassay. In total 132 blood samples were analyzed. The results of doubled blood samples of the same horse showed a standard deviation ranging from +/- 6 to +/- 27 pg/ml within the laboratories (Ø 19,29 pg/ml). The standard deviation of the repeatability of the variation coefficient was 13,48%. Blood samples of the same horse resulted in ACTH levels of 121 pg/ml in the first probe and in < 5 pg/ml in the second probe. Standard deviation of measured ACTH values between the laboratories was +/- 26,4 pg/ml (Ø 27,44 pg/ml). The standard deviation of the reproducibility of the variation coefficient was 18,36%. In a 20 year old gelding the lowest ACTH value was 60.9 pg/ml whereas the highest measured value was 108 pg/ml. Immediate centrifugation of blood samples resulted in significantly higher ACTH values at an average of
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Cortisol in saliva and plasma of cattle after ACTH administration and milking.
Negrão, J A; Porcionato, M A; de Passillé, A M; Rushen, J
2004-06-01
Interest in the measurement of salivary cortisol has increased recently because saliva can be easily collected before and after an imposed stress. This study evaluated the relationship between plasma and salivary concentrations of cortisol following ACTH administration in calves (experiment 1) and machine milking of adult cows (experiment 2). A catheter was inserted into the jugular vein of all animals 72 h before the beginning of experiments. Blood and saliva samples were collected before and after ACTH administration (0.6 IU/kg BW) in calves or before and after machine milking of cows. Using a cotton swab, each saliva sample was taken immediately following the blood sample. In general, cortisol profiles were similar in plasma and saliva and correlated in both experiments; however, plasma concentrations were significantly higher than salivary concentrations. In addition, the differences between cortisol concentrations measured in saliva and plasma within each experiment varied substantially between animals and samples. Furthermore, in experiment 2, nearly 10% of salivary samples were below limits of detection. The sharp peaks in cortisol after ACTH administration in both the plasma and saliva were reflected adrenal stimulation. In addition, increases in cortisol in response to milking in both the plasma and saliva suggest that salivary sampling is a reliable option when studying cortisol responses to normal physiological events.
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Hydrocortisone and ACTH levels in manned spaceflight
NASA Technical Reports Server (NTRS)
Leach, C. S.; Campbell, B. O.
1974-01-01
The plasma hydrocortisone, plasma ACTH, and urinary hydrocortisone values were recorded for each man of the crews of Apollo flights eight through fifteen, 30, 14, and 5 days before flight, immediately after spaceflight recovery, and on future days until the return of most variables to preflight values. The plasma and urinary preflight hydrocortisone values were significantly higher than the postflight values. This result is discussed in terms of three possible explanations: (1) the adrenal-cortical function is suppressed during spaceflight; (2) the activity in flight may amount to stressful exercise, which tests have shown can cause a decrease in plasma adrenocortical hormones; and (3) the in-flight work-rest cycles may be such as to affect the circadian periodicity of the pituitary-adrenal function.
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Llompart-Pou, Juan Antonio; Raurich, Joan Maria; Ayestarán, Ignacio; Fernández-de-Castillo, Ana G; Pérez-Bárcena, Jon; Ibáñez, Jordi
2012-06-01
The use of the high-dose corticotrophin stimulation test (HDCST) as a guide to use low-dose steroid therapy in septic shock is controversial. The adrenocotropin hormone (ACTH) constitutes the immediate stimuli to produce cortisol. We evaluated the correlation of the response to the HDCST with plasma ACTH levels in patients with septic shock. This is a retrospective review of 102 patients with septic shock in which adrenal function was evaluated using the HDCST and plasma ACTH levels were measured. Patients with a δ cortisol of 9 μg/dL or less were considered as nonresponders or with subnormal response. The association between plasma ACTH levels and the response to the HDCST was investigated. Sixty-four patients (62.7%) had a subnormal response. Plasma ACTH levels were higher in patients with subnormal response (19.8 [11.7-31.4] vs 10.0 [7.0-21.2] pg/mL; P = .002). Patients in the highest quartile of plasma ACTH had lower δ cortisol (P = .014) and higher percentage of subnormal response (P = .005). The optimal cutoff point of plasma ACTH level with fewest false classifications was 10 pg/mL (sensitivity, 0.83 [95% confidence interval, 074-0.90] and specificity, 0.50 [95% confidence interval, 0.74-0.90]). Patients with septic shock with higher plasma ACTH values presented a subnormal response to the HDCST. The number of patients who failed to the HDCST was higher as plasma ACTH increased. Copyright © 2012 Elsevier Inc. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Todua, T.N.; Goncharov, N.P.; Katsiya, G.V.
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 inhibitorymore » effects of ACTH on progesterone secretion is exhibited only in the presence of an actively functioning corpus luteus of the ovary.« less
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Starkman, M N; Schteingart, D E; Schork, M A
1992-11-01
Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and beta-lipotropin/beta-endorphin (beta-LPH/beta-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean [+/- SD] depressed mood score = 0.17 +/- 0.4; modified Hamilton Depression scale score = 7.6 +/- 4.5) and five as severely depressed (mean depressed mood score = 2.4 +/- 0.5; modified Hamilton Depression scale score = 15 +/- 5.6) (p < 0.05). ACTH and beta-LPH/beta-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and beta-LPH/beta-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly depressed = 90.0 +/- 16.7; severely depressed = 34.6 +/- 8.7 (p < 0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0 mg dexamethasone administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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Reduced nocturnal ACTH-driven cortisol secretion during critical illness
Boonen, Eva; Meersseman, Philippe; Vervenne, Hilke; Meyfroidt, Geert; Guïza, Fabian; Wouters, Pieter J.; Veldhuis, Johannes D.
2014-01-01
Recently, during critical illness, cortisol metabolism was found to be reduced. We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH and cortisol secretion via feedback inhibition. To test this hypothesis, nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution analysis from plasma concentration time series in 40 matched critically ill patients and eight healthy controls, excluding diseases or drugs that affect the hypothalamic-pituitary-adrenal axis. Blood was sampled every 10 min between 2100 and 0600 to quantify plasma concentrations of ACTH and (free) cortisol. Approximate entropy, an estimation of process irregularity, cross-approximate entropy, a measure of ACTH-cortisol asynchrony, and ACTH-cortisol dose-response relationships were calculated. Total and free plasma cortisol concentrations were higher at all times in patients than in controls (all P < 0.04). Pulsatile cortisol secretion was 54% lower in patients than in controls (P = 0.005), explained by reduced cortisol burst mass (P = 0.03), whereas cortisol pulse frequency (P = 0.35) and nonpulsatile cortisol secretion (P = 0.80) were unaltered. Pulsatile ACTH secretion was 31% lower in patients than in controls (P = 0.03), again explained by a lower ACTH burst mass (P = 0.02), whereas ACTH pulse frequency (P = 0.50) and nonpulsatile ACTH secretion (P = 0.80) were unchanged. ACTH-cortisol dose response estimates were similar in patients and controls. ACTH and cortisol approximate entropy were higher in patients (P ≤ 0.03), as was ACTH-cortisol cross-approximate entropy (P ≤ 0.001). We conclude that hypercortisolism during critical illness coincided with suppressed pulsatile ACTH and cortisol secretion and a normal ACTH-cortisol dose response. Increased irregularity and asynchrony of the ACTH and cortisol time series supported non-ACTH-dependent mechanisms driving hypercortisolism during critical illness. PMID:24569590
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Suppressed pituitary ACTH response after ACTH treatment of infantile spasms.
Ross, D L
1986-01-01
Suppression of an adrenocorticotropic hormone (ACTH) response to insulin hypoglycemia has been reported in ACTH-treated adults. There are no guidelines for withdrawal of ACTH treatment in children. After observing suppressed morning cortisol in several children, insulin tolerance tests were performed in five children within 48 hours after tapered withdrawal of ACTH treatment for myoclonic seizures. ACTH response, as determined by cortisol and beta-endorphin radioimmunoassay, was adequate in four of the children. One child showed low basal levels and minimal elevation during hypoglycemia for both beta-endorphin (0 to 3 pg/ml) and cortisol (3.6 to 4.4 micrograms/dL) on initial testing, but normal responses six weeks later. Measurement of beta-endorphin response supported a central basis for suppression in the child, who had had an adrenal hemorrhage during gram-negative sepsis while on ACTH. ACTH release is transiently suppressed in some children after exogenous ACTH treatment. Tapered withdrawal and stress coverage is recommended.
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Fleseriu, Maria; Findling, James W; Koch, Christian A; Schlaffer, Sven-Martin; Buchfelder, Michael; Gross, Coleman
2014-10-01
Pituitary effects of long-term therapy with mifepristone, a glucocorticoid receptor antagonist, in Cushing's disease (CD) patients are not well understood. Our objective was to report changes in ACTH and pituitary magnetic resonance imaging (MRI) findings during long-term use of mifepristone in CD patients. The Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC) was a 24-week, open-label study of mifepristone, and its long-term extension (LTE) is a multicenter U.S. study. Forty-three CD patients (mean age 45.3 years) were enrolled in SEISMIC with 27 continuing into the LTE study. Mifepristone (300-1200 mg) was administered once daily. ACTH and pituitary MRI were assessed at baseline and at regular intervals during treatment. A ≥2-fold increase in ACTH was observed in 72% of patients treated for a median duration of 11.3 months. The mean peak increase in ACTH was 2.76 ± 1.65-fold during SEISMIC, and mean ACTH concentrations remained stable during the LTE. ACTH was directly correlated with mifepristone dose and declined to near baseline levels after mifepristone discontinuation. Tumor regressed in 2 patients and progressed in 3 patients with macroadenomas. An additional microadenoma was identified after 25 months of treatment after a baseline tumor-negative MRI. In the largest prospective study to date, long-term mifepristone treatment increased ACTH in approximately two-thirds of patients with CD. ACTH elevations were observed within the first few weeks of treatment, were dose-dependent, and generally remained stable over time. Corticotroph tumor progression and regression may occur over time, but patients may have significant increases in ACTH levels without evidence of tumor growth.
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Findling, James W.; Koch, Christian A.; Schlaffer, Sven-Martin; Buchfelder, Michael; Gross, Coleman
2014-01-01
Context: Pituitary effects of long-term therapy with mifepristone, a glucocorticoid receptor antagonist, in Cushing's disease (CD) patients are not well understood. Objective: Our objective was to report changes in ACTH and pituitary magnetic resonance imaging (MRI) findings during long-term use of mifepristone in CD patients. Design and Setting: The Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC) was a 24-week, open-label study of mifepristone, and its long-term extension (LTE) is a multicenter U.S. study. Patients: Forty-three CD patients (mean age 45.3 years) were enrolled in SEISMIC with 27 continuing into the LTE study. Interventions: Mifepristone (300–1200 mg) was administered once daily. Main Outcome Measures: ACTH and pituitary MRI were assessed at baseline and at regular intervals during treatment. Results: A ≥2-fold increase in ACTH was observed in 72% of patients treated for a median duration of 11.3 months. The mean peak increase in ACTH was 2.76 ± 1.65-fold during SEISMIC, and mean ACTH concentrations remained stable during the LTE. ACTH was directly correlated with mifepristone dose and declined to near baseline levels after mifepristone discontinuation. Tumor regressed in 2 patients and progressed in 3 patients with macroadenomas. An additional microadenoma was identified after 25 months of treatment after a baseline tumor-negative MRI. Conclusions: In the largest prospective study to date, long-term mifepristone treatment increased ACTH in approximately two-thirds of patients with CD. ACTH elevations were observed within the first few weeks of treatment, were dose-dependent, and generally remained stable over time. Corticotroph tumor progression and regression may occur over time, but patients may have significant increases in ACTH levels without evidence of tumor growth. PMID:25013998
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Alía, P; Villabona, C; Giménez, O; Sospedra, E; Soler, J; Navarro, M A
2006-09-01
No consensus exists until now about the suitable dose of tetracosactin in the ACTH stimulation test for detecting adrenal insufficiency. Our aim was to characterize both the ACTH(1-24) and the cortisol profiles after standard high-dose test (250 microg) (HDT) and low-dose test (1 microg) (LDT) in healthy subjects in order to provide a deeper knowledge about the relationship between stimulus and response. ACTH tests were performed in 10 healthy volunteers (five men, five women) with at least 1 week of difference. Plasma ACTH(1-24) and ACTH(1-39) and serum cortisol were measured before tetracosactin i.v. injection and at 5, 15, 30, 45, 60, 75 and 90 min after stimulus. Area under the curve (AUC) of ACTH(1-24) and cortisol, as well as mean residence time (MRT) for ACTH(1-24) were calculated in both tests. Elimination of ACTH(1-24) was faster in HDT than in LDT (MRTs of 0.14 vs 0.37, respectively, P = 0.008), but plasma concentrations were higher up to 60 min cortisol production in HDT reaching a higher maximum concentration (Cmax: 1144 vs 960 nmol/l) but delayed in time (75 vs 52.5 min). No significant relationship was observed between AUC or Cmax of ACTH(1-24) and AUC, Cmax and increment of cortisol in any of the tests. However, a negative correlation of basal cortisol values was observed with relative cortisol increment (HDT: r = 0.77 P = 0.009; LDT: r = 0.94 P < 0.0001), but not so with Cmax (HDT: r = 0.22 P = 0.55; LDT: r = 0.57 P = 0.09). The elimination rate of ACTH in healthy volunteers was significantly lower in LDT than in HDT, but cortisol production rate appears to be identical in both tests, so that a maximum adrenal stimulation seems to exist. The use of LDT may be more adequate, although data from patients need studying.
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UTILITY OF A SINGLE LATE-NIGHT PLASMA CORTISOL AND ACTH FOR THE DIAGNOSIS OF CUSHING SYNDROME.
Jarial, Kush Dev Singh; Bhansali, Anil; Mukherjee, Kanchan K; Pal, Rimesh; Sharma, Akhilesh; Vashishtha, Rakesh K; Sukumar, Suja P; Sachdeva, Naresh; Walia, Rama
2018-02-01
To evaluate the diagnostic efficacy of various screening tests for the diagnosis of Cushing syndrome (CS). Thirty-five patients with CS and 16 patients of pseudo-CS were enrolled. Assessment of 24-h urinary free cortisol (UFC), late-night salivary cortisol (LNSC), overnight dexamethasone suppression test (ONDST), late-night plasma cortisol (LNPC), and adrenocorticotropic hormone (ACTH) on outpatient basis, and during sleep as well as in awake state after 48 hours of hospital admission. We found that 24-h UFC performed the best among the screening tests with sensitivity, specificity and areas under the curve (AUCs) of 96.0%, 99%, and 0.988, respectively, at a cut-off of 144.6 μg/24 h. A cut-off of 10.5 nmol/L for LNSC had sensitivity 85.7%, specificity 88.2%, and an AUC of 0.897. A cut-off of 412.4 nmol/L for LNPC on outpatient basis had sensitivity 88.2%, specificity 91.2%, and an AUC of 0.957. Cut-offs of 215 and 243.3 nmol/L for LNPC during sleep and awake states after acclimatization had sensitivity, specificity, and an AUC of 94.1%, 88.2%, and 0.958, respectively. An ONDST cut-off of 94.6 nmol/L provided sensitivity, specificity, and an AUC of 96.0%, 99.03% and 0.995, respectively. A cut-off of 30.3 pg/mL for late-night ACTH on outpatient basis had sensitivity 67.6%, specificity 99.9%, and an AUC 0.796.A cut-off of 22.6 pg/mL for ACTH during sleep state after acclimatization had sensitivity, specificity, and an AUC of 73.5%, 99.2%, and 0.827, respectively. UFC is the best screening test for CS. Furthermore, single measurements of LNPC and ACTH help to establish the diagnosis and ACTH dependency of CS in the majority of patients with CS. ACTH = adrenocorticotropic hormone AUC = area under the curve CRH = corticotropin-releasing hormone CS = Cushing syndrome ECLIA = electrochemiluminescence immuno-assay LDDST = low-dose dexamethasone suppression test LNPC = late-night plasma cortisol LNSC = late-night salivary cortisol ONDST = overnight dexamethasone suppression
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Ectopic ACTH syndrome due to pheochromocytoma: case report and review of the literature.
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
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ACTH releasing activity of KP-102 (GHRP-2) in rats is mediated mainly by release of CRF.
Hirotani, Chiharu; Oki, Yutaka; Ukai, Kiyoharu; Okuno, Tadashi; Kurasaki, Shigeru; Ohyama, Tadashi; Doi, Naomi; Sasaki, Ken; Ase, Katsuhiko
2005-01-01
KP-102 (GHRP-2: pralmorelin) is a synthetic growth hormone releasing peptide (GHRP) that powerfully stimulates the release of GH by acting (i.v.) at both hypothalamic and pituitary sites. Intravenous (i.v.) administration of KP-102 also elicits slight but significant release of adrenocorticotropic hormone (ACTH) in both animals and humans, as is seen with other GHRPs. GHRPs are thought to stimulate the hypothalamic-pituitary-adrenal axis by releasing endogenous ACTH secretagogues such as arginine vasopressin (AVP) and/or corticotropin releasing factor (CRF), though neither AVP nor CRF has been shown clearly to be involved significantly in GHRP-evoked ACTH release. In the present study, we investigated the effects of KP-102 on ACTH release in conscious rats under improved experimental conditions that minimized the influence of stress. Administration of KP-102 i.v. increased plasma ACTH significantly, but did not stimulate ACTH release from rat primary pituitary cells. Administration of KP-102 together with either AVP or CRF elicited significantly greater increases in plasma ACTH levels than any of the agonists alone. Notably, the combination of KP-102 and AVP produced a much greater increase in ACTH than KP-102 plus CRF, indicating that KP-102 augments the effect of exogenous CRF only weakly. Conversely, a CRF antagonist markedly inhibited KP-102-induced ACTH release in conscious rats, whereas an AVP antagonist or anti-AVP antiserum did not. Taken together, these findings suggest that KP-102 acts via the hypothalamus to stimulate ACTH release in rats, and that these effects are mediated mainly by the release of CRF.
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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).
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Chronic inhibition of nitric oxide synthase augments the ACTH response to exercise
Jankord, Ryan; McAllister, Richard M.; Ganjam, Venkataseshu K.; Laughlin, M. Harold
2009-01-01
Exercise can activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and regular exercise training can impact how the HPA axis responds to stress. The mechanism by which acute exercise induces HPA activity is unclear. Therefore, the purpose of this study was to test the hypothesis that nitric oxide modulates the neuroendocrine component of the HPA axis during exercise. Female Yucatan miniature swine were treated with N-nitro-l-arginine methyl ester (l-NAME) to test the effect of chronic nitric oxide synthase (NOS) inhibition on the ACTH response to exercise. In addition, we tested the effect of NOS inhibition on blood flow to tissues of the HPA axis and report the effects of handling and treadmill exercise on the plasma concentrations of ACTH and cortisol. Chronic NOS inhibition decreased plasma NOx levels by 44%, increased mean arterial blood pressure by 46%, and increased expression of neuronal NOS in carotid arteries. Vascular conductance was decreased in the frontal cortex, the hypothalamus, and the adrenal gland. Chronic NOS inhibition exaggerated the ACTH response to exercise. In contrast, chronic NOS inhibition decreased the ACTH response to restraint, suggesting that the role of NO in modulating HPA activity is stressor dependent. These results demonstrate that NOS activity modulates the response of the neuroendocrine component of the HPA axis during exercise stress. PMID:19144752
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Chronic inhibition of nitric oxide synthase augments the ACTH response to exercise.
Jankord, Ryan; McAllister, Richard M; Ganjam, Venkataseshu K; Laughlin, M Harold
2009-03-01
Exercise can activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and regular exercise training can impact how the HPA axis responds to stress. The mechanism by which acute exercise induces HPA activity is unclear. Therefore, the purpose of this study was to test the hypothesis that nitric oxide modulates the neuroendocrine component of the HPA axis during exercise. Female Yucatan miniature swine were treated with N-nitro-l-arginine methyl ester (l-NAME) to test the effect of chronic nitric oxide synthase (NOS) inhibition on the ACTH response to exercise. In addition, we tested the effect of NOS inhibition on blood flow to tissues of the HPA axis and report the effects of handling and treadmill exercise on the plasma concentrations of ACTH and cortisol. Chronic NOS inhibition decreased plasma NO(x) levels by 44%, increased mean arterial blood pressure by 46%, and increased expression of neuronal NOS in carotid arteries. Vascular conductance was decreased in the frontal cortex, the hypothalamus, and the adrenal gland. Chronic NOS inhibition exaggerated the ACTH response to exercise. In contrast, chronic NOS inhibition decreased the ACTH response to restraint, suggesting that the role of NO in modulating HPA activity is stressor dependent. These results demonstrate that NOS activity modulates the response of the neuroendocrine component of the HPA axis during exercise stress.
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Hong, A Ram; Kim, Jung Hee; Hong, Eun Shil; Kim, I Kyeong; Park, Kyeong Seon; Ahn, Chang Ho; Kim, Sang Wan; Shin, Chan Soo; Kim, Seong Yeon
2015-09-01
Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively. Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.
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Diagnostic value of ACTH stimulation test in determining the subtypes of primary aldosteronism.
Jiang, Yiran; Zhang, Cui; Wang, Weiqing; Su, Tingwei; Zhou, Weiwei; Jiang, Lei; Zhu, Wei; Xie, Jing; Ning, Guang
2015-05-01
Adrenal venous sampling is recommended as the golden standard for subtyping primary aldosteronism (PA). However, it is invasive and inconvenient, and seeking a better way to make differential diagnosis of PA is necessary. The objective of the study was to evaluate the diagnostic value of ACTH stimulation test under 1 mg dexamethasone suppression test (DST) in determining the subtypes of PA. Ninety-five patients with PA confirmed by saline infusion test were included in this study. According to adrenal venous sampling and histopathology, 39 patients were diagnosed as bilateral adrenal hyperplasia (BAH), 37 as aldosterone-producing adenoma (APA), and 19 as unilateral adrenal hyperplasia (UAH). An ACTH stimulation test under 1 mg DST was performed in all patients. Plasma aldosterone and cortisol levels were measured every 30 minutes until 120 minutes after the iv injection of 50 IU ACTH. During the ACTH stimulation test, aldosterone levels in APA and UAH were similar (P > .05) but higher than those in BAH (P < .001). Furthermore, stimulated aldosterone levels of unilateral PA (APA and UAH) were significantly higher than bilateral PA (BAH) (P < .001). Receiver-operated characteristics curve analyses showed the aldosterone after ACTH stimulation was effective for distinguishing between unilateral PA and bilateral PA. The diagnostic accuracy was highest at 120 minutes after ACTH stimulation, and the optimal cutoff value of the aldosterone was 77.90 ng/dL, with a sensitivity of 76.8%, a specificity of 87.2%, a positive predictive value of 89.6%, and a negative predictive value of 72.3%. The ACTH stimulation test under 1 mg DST is useful to determine the subtypes of PA, especially in unilateral and bilateral PA, and may guide further treatment in PA patients.
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A rare cause of Cushing's syndrome: an ACTH-secreting phaeochromocytoma.
Folkestad, Lars; Andersen, Marianne Skovsager; Nielsen, Anne Lerberg; Glintborg, Dorte
2014-10-08
Excess glucocorticoid levels cause Cushing's syndrome (CS) and may be due to pituitary, adrenal or ectopic tumours. Adrenocorticotropic hormone (ACTH) levels are useful in identifying adrenal tumours. In rare cases, ACTH-producing phaeochromocytomas are the cause of CS. We present two cases of ACTH-secreting phaeochromocytoma as the underlying cause of CS. In both cases, female patients presented with the classical clinical signs of CS and an adrenal mass. High ACTH levels raised the suspicion of an ACTH-secreting phaeochromocytoma. The diagnosis was confirmed by urinary catecholamine levels and positive fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) CT (Case 1) and fluorodeoxyglucose PET-CT (Case 2). Both patients were treated with an α-blocker prior to surgical intervention. The two cases underline the importance of thorough diagnostic workup in patients with CS. An ACTH-secreting phaeochromocytoma should be checked for in patients with an adrenal mass and elevated ACTH levels. 2014 BMJ Publishing Group Ltd.
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A rare cause of Cushing's syndrome: an ACTH-secreting phaeochromocytoma
Folkestad, Lars; Andersen, Marianne Skovsager; Nielsen, Anne Lerberg; Glintborg, Dorte
2014-01-01
Excess glucocorticoid levels cause Cushing's syndrome (CS) and may be due to pituitary, adrenal or ectopic tumours. Adrenocorticotropic hormone (ACTH) levels are useful in identifying adrenal tumours. In rare cases, ACTH-producing phaeochromocytomas are the cause of CS. We present two cases of ACTH-secreting phaeochromocytoma as the underlying cause of CS. In both cases, female patients presented with the classical clinical signs of CS and an adrenal mass. High ACTH levels raised the suspicion of an ACTH-secreting phaeochromocytoma. The diagnosis was confirmed by urinary catecholamine levels and positive fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) CT (Case 1) and fluorodeoxyglucose PET-CT (Case 2). Both patients were treated with an α-blocker prior to surgical intervention. The two cases underline the importance of thorough diagnostic workup in patients with CS. An ACTH-secreting phaeochromocytoma should be checked for in patients with an adrenal mass and elevated ACTH levels. PMID:25297883
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Katagiri, Fumihiko; Shiga, Toru; Inoue, Shin; Sato, Yuhki; Itoh, Hiroki; Takeyama, Masaharu
2006-01-01
Itopride hydrochloride (itopride), a gastrokinetic drug, has recently been evaluated for its clinical usefulness in functional dyspepsia. We investigated effects of itopride on human plasma gastrin-, somatostatin-, motilin-, and cholecystokinin (CCK)-like immunoreactive substances (IS); adrenocorticotropic hormone (ACTH)-immunoreactive substances (IS), and cortisol under stress conditions in healthy subjects. A single administration of itopride caused significant increases in plasma somatostatin- and motilin-IS levels compared to placebo. Itopride significantly decreased plasma CCK-IS, and suppressed the ACTH-IS level compared to placebo. We hypothesize that itopride may have an accelerating gastric emptying effect, and a modulatory effect on the hypothalamo-pituitary-adrenal axis and autonomic nervous functions. These effects might be beneficial in stress-related diseases, suggesting that itopride has clinicopharmacological activities.
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Kapritsou, Maria; Papathanassoglou, Elizabeth D; Bozas, Evangelos; Korkolis, Dimitrios P; Konstantinou, Evangelos A; Kaklamanos, Ioannis; Giannakopoulou, Margarita
2017-03-01
Fast-track (FT) postoperative protocol in oncological patients after major abdominal surgery reduces complications and length of postoperative stay compared to the conventional (CON) protocol. However, stress and pain responses have not been compared between the two protocols. To compare stress, pain, and related neuropeptidic responses (adrenocorticotropic hormone [ACTH], cortisol, and neuropeptide Y [NPY]) between FT and CON protocols. A clinical trial with repeated measurements was conducted (May 2012 to May 2014) with a sample of 63 hepatectomized or pancreatectomized patients randomized into two groups: FT ( n = 29) or CON ( n = 34). Demographic and clinical data were collected, and pain (Visual Analog Scale [VAS] and Behavioral Pain Scale [BPS]) and stress responses (3 self-report questions) assessed. NPY, ACTH, and cortisol plasma levels were measured at T1 = day of admission, T2 = day of surgery, and T3 = prior to discharge. ACTH T1 and ACTH T2 levels were positively correlated with self-reported stress levels (ρ = .43 and ρ = .45, respectively, p < .05) in the FT group. NPY levels in the FT group were higher than those in the CON group at all time points ( p ≤ .004); this difference remained significant after adjusting for T1 levels through analysis of covariance for age, gender, and body mass index ( F = .003, F = .149, F = .015, respectively, p > .05). Neuropeptidic levels were higher in the FT group. Future research should evaluate this association further, as these biomarkers might serve as objective indicators of postoperative pain and stress.
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An unusual case of ectopic ACTH syndrome.
Willhauck, M J; Pöpperl, G; Rachinger, W; Giese, A; Auernhammer, C J; Spitzweg, C
2012-02-01
Ectopic ACTH-syndrome is a rare cause of Cushing's disease. Despite extensive diagnostic procedures the source of ACTH secretion often remains occult. This case describes a 45-year old woman with an ectopic Cushing's syndrome. Extensive imaging procedures including CT scan of chest and abdomen, octreotide scan and MRI of the chest and pituitary did not reveal the source of ACTH secretion. In consideration of an occult source of ACTH secretion we started a therapeutic trial with cabergoline (0.5 mg/d), a dopamine receptor agonist, which has been shown to be effective in ectopic Cushing's syndrome. 2 months after cabergoline treatment had been initiated, ACTH and cortisol levels normalized in association with significant improvement of the clinical symptoms. During follow-up a [(68)Ga-DOTA-dPhe(1), Tyr(3)]-octreotate ([(68)Ga-DOTA]-TATE) PET-CT was performed revealing a somatostatin receptor positive lesion in the right sphenoidal sinus suggesting the source of ACTH secretion. The patient was cured by transnasal resection of the polypoid lesion, which was immunohistochemically characterized as an ACTH-positive neuroendocrine tumor. This case report demonstrates the management of ectopic ACTH-syndrome by molecularly -targeted therapy with dopamine receptor -agonists as well as improved detection of the ectopic ACTH source by novel imaging modalities, such as [(68)Ga-DOTA]-TATE PET specifically targeting somatostatin receptor subtype-2 with high affinity. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.
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Iranmanesh, Ali; Veldhuis, Johannes D
2008-11-01
ACTH secretion is under hypothalamic stimulatory (feedforward) and adrenal inhibitory (feedback) control. Assessment of overnight ACTH secretion during a hypocortisolemic clamp will permit the estimation of changing feedforward and feedback. Seven healthy men. An oral dose of placebo (PLAC), metyrapone (METY, 3 g), or ketoconazole (KTCZ, 1.2 g) was given at midnight (MN) to block glucocorticoid synthesis. Plasma ACTH was sampled every 10 min (MN to 0800 h). Variable-waveform deconvolution analysis of ACTH secretion and approximate entropy (ApEn) analysis of pattern regularity. Compared with PLAC, administration of METY and KTCZ reduced morning cortisol concentrations by >or=77 and 54% respectively (P<0.001). Hypocortisolemia elevated pulsatile ACTH secretion by 8.2- (METY) and 5.3-fold (KTCZ; both P<0.001). Basal ACTH secretion rose by 3.4-fold under METY-induced cortisol depletion (P=0.020). ACTH secretory-burst shape and half-life were stable. ApEn of ACTH release declined overnight (P=0.021) and with the drug (P=0.001), denoting enhanced feedforward coordination. The combined data predict overnight amplification and coordination of hypothalamic feedforward drive onto ACTH release. Therefore, disruption of either mechanism might contribute to clinical pathophysiology, such as late-day elevations of cortisol output in fasting, alcoholism, depression, or aging.
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El Asmar, Nadine; Rajpal, Aman; Selman, Warren R; Arafah, Baha M
2018-02-01
Despite the development of hypocortisolemia after corticotroph surgical adenomectomy, 15% to 20% patients have recurrence of Cushing disease (CD). In this study, we investigated the effect of tumor size and the value of perioperative assessment of corticotropin (ACTH) and adrenal steroid levels in predicting recurrence. Perioperatively, no glucocorticoids were administered until the serum cortisol was ≤3 μg/dL. Blood samples were obtained before and repeatedly after adenomectomy in 79 patients with CD. Of these, 66 had a nadir serum cortisol of ≤3.0 μg/dL and clinical and biochemical remissions. During a median follow-up of 131 months, 11 of 66 had disease recurrence (REC), whereas 55 of 66 did not (NO-REC). Preoperative hormone levels in the REC and NO-REC groups were similar. After adenomectomy, a brief and similar increase in ACTH, cortisol, and dehydroepiandrosterone (DHEA) levels was observed in both groups followed by gradual decline in those levels. Although REC and NO-REC patients had similar cortisol levels (3.4 ± 1.7 μg/dL vs 2.9 ± 2.2 μg/dL) at the 36th postoperative hour, their respective ACTH (33 ± 7.1 ng/L vs 12.1 ± 5.4 ng/L; P < 0.0001), DHEA (3.8 ± 1.7 ng/mL vs 1.2 ± 1.1 ng/mL; P = 0.005), and dehydroepiandrosterone sulphate (DHEA-S) (143.9 ± 45.2 μg/dL vs 48.9 ± 38.2 μg/dL; P < 0.0001) were higher. At nadir hypocortisolemia, perioperative ACTH levels were >20 in all REC patients and <20 ng/L in the NO-REC group. Patients with REC had larger tumors than those with NO-REC. Recurrent CD is characterized by persistent perioperative ACTH secretion after adenomectomy. Higher perioperative levels of ACTH, DHEA, and DHEA-S are highly predictive of future disease recurrence, particularly in those with profound hypocortisolemia. Copyright © 2017 Endocrine Society
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Iranmanesh, Ali; Veldhuis, Johannes D
2009-01-01
Background ACTH secretion is under hypothalamic stimulatory (feedforward) and adrenal inhibitory (feedback) control. Hypothesis Assessment of overnight ACTH secretion during a hypocortisolemic clamp will permit the estimation of changing feedforward and feedback. Subjects Seven healthy men. Interventions An oral dose of placebo (PLAC), metyrapone (METY, 3 g), or ketoconazole (KTCZ, 1.2 g) was given at midnight (MN) to block glucocorticoid synthesis. Plasma ACTH was sampled every 10 min (MN to 0800 h). Analysis Variable-waveform deconvolution analysis of ACTH secretion and approximate entropy (ApEn) analysis of pattern regularity. Results Compared with PLAC, administration of METY and KTCZ reduced morning cortisol concentrations by ≥77 and 54% respectively (P<0.001). Hypocortisolemia elevated pulsatile ACTH secretion by 8.2- (METY) and 5.3-fold (KTCZ; both P<0.001). Basal ACTH secretion rose by 3.4-fold under METY-induced cortisol depletion (P = 0.020). ACTH secretory-burst shape and half-life were stable. ApEn of ACTH release declined overnight (P = 0.021) and with the drug (P = 0.001), denoting enhanced feedforward coordination. Conclusion The combined data predict overnight amplification and coordination of hypothalamic feedforward drive onto ACTH release. Therefore, disruption of either mechanism might contribute to clinical pathophysiology, such as late-day elevations of cortisol output in fasting, alcoholism, depression, or aging. PMID:18713842
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Measurement of salivary aldosterone: validation by low-dose ACTH test and gender differences.
Hlavacova, N; Kerlik, J; Radikova, Z; Izakova, L; Jezova, D
2013-10-01
The aim of the present study was to validate the feasibility of measurement of the salivary aldosterone concentrations by performing a low-dose adrenocorticotropic hormone (ACTH) test. Moreover, the presence of gender differences in salivary aldosterone, considering the phase of the menstrual cycle in women, was verified. The sample consisted of 107 volunteers (60 men, 21 women in the follicular phase and 26 women in the luteal phase of the menstrual cycle). Saliva samples were taken by the subjects themselves around 08:00 AM, at least 60 min after awaking. A separate group of female subjects in the follicular phase underwent low-dose ACTH test (1µg synthetic ACTH i.v.) performed at 08:30 AM with blood and saliva sampling every 30 min for 120 min. Modification of the commercial aldosterone radioimmunoassay methodology for the salivary aldosterone measurement was performed. Salivary aldosterone concentrations rose in response to low-dose ACTH test and positive significant correlation in aldosterone concentrations between plasma and saliva was found. The results showed that women in the luteal phase of the menstrual cycle exhibited significantly higher morning concentrations in salivary aldosterone than men and women in the follicular phase. This study clearly demonstrates suitability of measurement of salivary aldosterone concentrations in the low-dose ACTH test and reveals gender differences in salivary aldosterone levels. The results show high validity of the presented method and its usefulness for assessment of the aldosterone concentrations in saliva.
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Rocco, Antonio; Martocchia, Antonio; Frugoni, Patrizia; Baldini, Rossella; Sani, Gabriele; Di Simone Di Giuseppe, Barbara; Vairano, Andrea; Girardi, Paolo; Monaco, Edoardo; Tatarelli, Roberto; Falaschi, Paolo
2007-10-01
Evidence in the literature suggests stress-related changes of hypothalamus-pituitary-adrenal (HPA) axis in mobbing. We investigated the association between HPA activity and psychological profiles in mobbing, using a multidisciplinary approach. Forty-eight victims of mobbing were evaluated by a working group of the Departments of Occupational Medicine, Psychiatry and Internal Medicine. After an informed consent, a detailed occupational history, a psychiatric interview with Minnesota Multiphasic Personality Inventory 2 (MMPI-2) administration and a blood sample (8:00 AM) for the determination of basal adrenocorticotropin (ACTH), cortisol and dehydroepiandrosterone sulphate (DHEAS) plasma levels were collected. Twenty-six patients received an overnight dexamethasone (dex) test. Mean ACTH, cortisol and DHEAS levels were within normal ranges. The dex-test response was normal, with a significant hormone suppression (ACTH p<0.001, cortisol p<0.001, DHEAS p<0.001). The correlations between basal hormones and the psychometric scales of MMPI-2 revealed that cortisol was significantly and negatively related to Psychasthenia (Pt, p=0.003) and Depression (D, p=0.006), while DHEAS showed a significant negative correlation to Hysteria (Hy, p=0.008). Basal ACTH levels were not significantly related to psychometric scales. A significant inverse correlation between morning plasma cortisol levels and psychometric parameters in victims of mobbing with adjustment disorders was observed. A larger group of patients is necessary to identify and validate a cut-off cortisol level that may become an innovative biological parameter for the diagnosis and follow-up in victims of mobbing.
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Birkenhäger, J C; Upton, G V; Seldenrath, H J; Krieger, D T; Tashjian, A H
1976-10-01
A 45-year-old women had medullary tyroid carcinoma associated with Cushing's syndrome and galactorrhoea. Elevated plasma immunoreactive ACTH and cortisol were partially suppressed by intravenous dexamethasone, appreciably raised by lysine vasopressin, and urinary excretion of 17-oxogenic steroids slightly elevated by metyrapone. A large arterio-venous increase in plasma corticotrophin releasing factor-like activity across the thyroid gland was observed and tumour tissue contained corticotrophin releasing factor-like activity. Biologically active ACTH was not detected in tumour extracts before incubation with trypsin, but after trypsinization a value of 3.2 mU per gram was obtained. Arterial plasma contained biologically active ACTH (1.5 mU/100 ml) prior to trypsinization. Venous effluent from the thyroid gland contained biologically active (9.6 mU/100 ml) and immunoreactive ACTH (970 pg/ml) before trypsinization. Tumour extracts also contained prolactin production-stimulating activity. These findings can explain the Cushing's syndrome and the galactorrhoea both of which disappeared completely after thyroidectomy.
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1987-08-01
B.- and Soutas. Dpmptrio; I 13a. TYPE OF REPORT 13b. TIME COVERED 114. DATE OF REPORT (Year, Month, Day) S. PAGE COUNT Final FROM84/8/20 TO 86/2/16...cages and placed in sampling boxes. At this moment a first 0.2 mL sample of blood was withdrawn. At 0 time (20 min later) another 0.2 mL sample of blood...concentration data scatter diagram (exposure group) ............. . . . . . . . . . . . . . . . 18 10. Mean plasma ACTH concentrations versus time ....... 19
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Fleischer, Norman; Abe, Kaoru; Liddle, Grant W.; Orth, David N.; Nicholson, Wendell E.
1967-01-01
Six patients who had experienced prolonged steroid-induced pituitary-adrenal suppression were treated with 100 U of depot procine ACTH every 2 to 4 days for several months. Such treatment did not hasten the recovery of normal pituitary-adrenal function compared with the rate of recovery of a group of similarly suppressed patients who received no depot ACTH. Eight of nine patients who received prolonged courses of depot porcine ACTH developed antibodies to ACTH that cross-reacted with endogenous ACTH, binding it in the circulation in inactive form and retarding its removal from the circulation. The presence of such antibodies did not in itself grossly alter pituitary-adrenal interrelationships. Images PMID:4289551
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Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat
Bruder, Eric D.; Taylor, Jennifer K.; Kamer, Kimberli J.; Raff, Hershel
2008-01-01
Acute episodes of severe hypoxia are among the most common stressors in neonates. An understanding of the development of the physiological response to acute hypoxia will help improve clinical interventions. The present study measured ACTH and corticosterone responses to acute, severe hypoxia (8% inspired O2 for 4 h) in neonatal rats at postnatal days (PD) 2, 5, and 8. Expression of specific hypothalamic, anterior pituitary, and adrenocortical mRNAs was assessed by real-time PCR, and expression of specific proteins in isolated adrenal mitochondria from adrenal zona fascisulata/reticularis was assessed by immunoblot analyses. Oxygen saturation, heart rate, and body temperature were also measured. Exposure to 8% O2 for as little as 1 h elicited an increase in plasma corticosterone in all age groups studied, with PD2 pups showing the greatest response (∼3 times greater than PD8 pups). Interestingly, the ACTH response to hypoxia was absent in PD2 pups, while plasma ACTH nearly tripled in PD8 pups. Analysis of adrenal mRNA expression revealed a hypoxia-induced increase in Ldlr mRNA at PD2, while both Ldlr and Star mRNA were increased at PD8. Acute hypoxia decreased arterial O2 saturation (SPo2) to ∼80% and also decreased body temperature by 5–6°C. The hypoxic thermal response may contribute to the ACTH and corticosterone response to decreases in oxygen. The present data describe a developmentally regulated, differential corticosterone response to acute hypoxia, shifting from ACTH independence in early life (PD2) to ACTH dependence less than 1 wk later (PD8). PMID:18703410
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Ritzel, Katrin; Beuschlein, Felix; Berr, Christina; Osswald, Andrea; Reisch, Nicole; Bidlingmaier, Martin; Schneider, Harald; Honegger, Jürgen; Geyer, Lucas L; Schopohl, Jochen; Reincke, Martin
2015-08-01
The aim of the present study was to validate criteria of corticotropin-releasing hormone (CRH) stimulation and 8 mg dexamethasone suppression (high-dose dexamethasone suppression, HDDS) to distinguish the etiology of ACTH-dependent Cushing's syndrome. We retrospectively analyzed cortisol and ACTH after the injection of 100 μg human CRH in confirmed Cushing's disease (CD, n=78) and confirmed ectopic Cushing's syndrome (ECS, n=18). Cortisol and ACTH increase (in percentage above basal (%B)) at each time point, maximal increase (Δmax %B), and area under the curve (AUC %B) were analyzed using receiver operator characteristics (ROC) curve analyses. Cortisol suppression (%B) after 8 mg of dexamethasone was evaluated as a supplementary criterion. An increase in ACTH of ≥ 43%B at 15 min after CRH was the strongest predictor of CD, with a positive likelihood ratio of 14.0, a sensitivity of 83%, a specificity of 94%, a positive predictive value of 98% and a negative predictive value of 58%. All of the other criteria of stimulated ACTH and cortisol levels were not superior in predicting CD in response to CRH injection. The addition of cortisol suppression by dexamethasone did not increase the discriminatory power. However, the combination of a positive ACTH response at 15 min and a positive HDDS test excluded ECS in all cases. The present findings support the use of plasma ACTH levels 15 min after the injection of human CRH as a response criterion for distinguishing between CD and ECS. The addition of the HDDS test is helpful for excluding ECS when both tests are positive. © 2015 European Society of Endocrinology.
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Robaczyk, Maciej G
2002-01-01
The discovery of leptin (LEP) shed new light on mechanisms regulating body fat mass (BFM). In this aspect, interactions between LEP and glucocorticoids at hypothalamic level may be of great importance. Factors that influence plasma LEP levels have not been fully recognized and available data on LEP levels are often inconsistent. The aim of this study was to evaluate absolute and BFM-corrected plasma LEP levels and their diurnal variation, as well as to assess the relationship between LEP levels, body fat distribution, and hormones influencing body fat in subjects with various levels of endogenous cortisol and different nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9-37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do 63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose (G) concentration was determined with an enzymatic method. Adiposity-corrected LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin resistance index (FIRI) was also calculated. Higher BFM and %BF values were found in the OTY group as compared with CUS KON and AD groups. BFM distribution did not differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation of fat in the trunk
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Second-line tests in the differential diagnosis of ACTH-dependent Cushing's syndrome.
Barbot, Mattia; Trementino, Laura; Zilio, Marialuisa; Ceccato, Filippo; Albiger, Nora; Daniele, Andrea; Frigo, Anna Chiara; Mardari, Rodica; Rolma, Giuseppe; Boscaro, Marco; Arnaldi, Giorgio; Scaroni, Carla
2016-10-01
Diagnosing Cushing's syndrome (CS) can be a challenge, especially in ACTH-dependent CS, when it comes to detecting the origin of ACTH secretion. Retrospective data were collected on 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two endocrinology units, focusing on three non-invasive tests: dexamethasone 8 mg overnight challenge (HDDST); corticotrophin-releasing hormone (CRH) assay and the desmopressin (DDAVP) test. Patients with EAS were slightly older and had higher ACTH, serum and urinary cortisol levels than patients with CD (p < 0.01). CD patients had a stronger ACTH and cortisol response after CRH injection (p < 0.0001), and a more pronounced reduction in cortisol levels after HDDST (p < 0.0001). A threshold percentage ACTH increase after CRH stimulation of 72.4 % was able to identify CD with a sensitivity (SE) of 76 % (95 % CI 68-83) and a specificity (SP) of 100 % (95 % CI 83-100). As for HDDST, a cortisol suppression >52.7 % below the basal level suggested a pituitary origin with a SE of 88 % (95 % CI 81-93) and a SP of 90 % (95 % CI 68-99). There were no cases of EAS with positive responses to both these tests. Increases in ACTH and cortisol levels after the DDAVP test were also higher in CD than in EAS (p < 0.01), though the SE and SP were lower. Patients with CD showed a stronger response to HDDST and CRH, and the adopted cut-offs showed a good SE and SP in discriminating them from patients with EAS. Concordant tests indicated CD when positive, whereas no response to either test was highly suggestive of EAS. The DDAVP test was of limited utility in the diagnostic phase. In conclusion, the choice of tests may play an important part in the differential diagnosis of ACTH-dependent CS.
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Lavrnja, Irena; Trifunovic, Svetlana; Ajdzanovic, Vladimir; Pekovic, Sanja; Bjelobaba, Ivana; Stojiljkovic, Mirjana; Milosevic, Verica
2014-02-10
Traumatic brain injury (TBI) represents a serious event with far reaching complications, including pituitary dysfunction. Pars distalis corticotropes (ACTH cells), that represent the active module of hypothalamo-pituitary-adrenocortical axis, seem to be affected as well. Since pituitary failure after TBI has been associated with neurobehavioral impairments the aim of this study was to evaluate the effects of TBI on recovery of motor functions, morphology and secretory activity of ACTH cells in the pituitary of adult rats. Wistar male rats, initially exposed to sensorimotor cortex ablation (SCA), were sacrificed at the 2nd, 7th, 14th and 30th days post-surgery (dps). A beam walking test was used to evaluate the recovery of motor functions. Pituitary glands and blood were collected for morphological and hormonal analyses. During the first two weeks post-injury increased recovery of locomotor function was detected, reaching almost the control value at day 30. SCA induces significant increase of pituitary weights compared to their time-matched controls. The volume of ACTH-immunopositive cells was reduced at the 7th dps, while at the 14th dps their volume was enlarged, in comparison to corresponding sham controls. Volume density of ACTH cells was increased only at 14th dps, while at day 30 this increase was insignificant. The plasma level of ACTH transiently increased after the injury. The most pronounced changes were observed at the 7th and 14th dps, and were followed by decrease toward control levels at the 30th dps. Thus, temporal changes in the hypothalamic-pituitary-adrenal axis after traumatic brain injury appear to correlate with the recovery process. Copyright © 2013 Elsevier Inc. All rights reserved.
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ACTH is a novel regulator of bone mass.
Isales, Carlos M; Zaidi, Mone; Blair, Harry C
2010-03-01
Adrenocorticotropin (ACTH) is one of several peptide hormones derived from a larger molecule, proopiomelanocortin (POMC). ACTH is a classic endocrine hormone, processed and secreted from the pituitary to stimulate cortisol production from the fasciculata cells in the adrenal gland. However, ACTH is also produced by other cells, including macrophages, at many sites in the body. ACTH binds to a specific member of the melanocortin receptor family, the MC2R. MC2R is expressed in osteoblastic cells in vivo, as shown by in situ hybridization. MC2R expression is strongest at sites of active bone deposition, and thus ACTH response probably varies with osteoblastic activity or stage of osteoblast differentiation. In vitro ACTH stimulates proliferation of osteoblasts in a dose-dependent manner. ACTH at 10 nM increases collagen I mRNA in the osteoblastic cell line SaOs2, although at lower concentrations ACTH may oppose osteoblast differentiation. ACTH is thus, at high concentrations, anabolic for the osteoblast, and it is highly likely that the hormone has concentration-dependent effects on bone metabolism in vivo.
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Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies.
Baker, Peter R; Nanduri, Priyaanka; Gottlieb, Peter A; Yu, Liping; Klingensmith, Georgeanna J; Eisenbarth, George S; Barker, Jennifer M
2012-05-01
Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality. To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH-AA+ individuals. Individuals were screened for 21OH-AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH-AA (n = 87) were tested, and the majority prospectively followed for the development of Addison's disease, including seven diagnosed with AD upon 21OH-AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors. Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH-AA were measured at various time points relative to diagnosis of AD or last AD-free follow-up. Compared with nonprogressors, in the time period 2 months-2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11-22 pM, P < 1E-4), with no significant differences in mean PRA (P = 0·07) or baseline cortisol (P = 0·08), and significant but less distinct differences seen with 21OH-AA levels (P < 1E-4) and poststimulation cortisol levels (P = 6E-3). Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH-AA, PRA or peak cortisol, in the 2 months-2 years preceding the onset of AD. © 2012 Blackwell Publishing Ltd.
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Katznelson, Laurence
2013-05-01
Nelson's syndrome refers to aggressive pituitary corticotroph adenoma growth after bilateral adrenalectomy for treatment of Cushing's disease (CD). Pasireotide, a novel somatostatin analog, has been effective in treating CD. Here, the first case report of a patient with Nelson's syndrome treated with pasireotide is presented. A 55-year-old female was diagnosed with CD in 1973 at age 15 years and underwent bilateral adrenalectomy 1 year later. She subsequently developed Nelson's syndrome and underwent multiple surgeries and radiotherapy for adenoma growth. After presentation with ocular pain, third cranial nerve palsy, and a finding of suprasellar tumor enlargement with hemorrhage, she began pasireotide long-acting release 60 mg/28 days im. At baseline, fasting plasma ACTH was 42 710 pg/mL (normal, 5-27 pg/mL), and fasting plasma glucose was 98 mg/dL. After 1 month, ACTH declined to 4272 pg/mL, and it has remained stable over 19 months of follow-up. Hyperpigmentation progressively improved. Magnetic resonance imaging scans show reduction in the suprasellar component. Fasting plasma glucose increased to 124 mg/dL, and the patient underwent diabetes management. In this clinical case seminar, the current understanding of the treatment of Nelson's syndrome and the use of pasireotide in CD are summarized. A case of Nelson's syndrome with clinically significant and dramatic biochemical and clinical responses to pasireotide administration is reported. Hyperglycemia was noted after pasireotide administration. Pasireotide may represent a useful tool in the medical management of Nelson's syndrome. Further study of the potential benefits and risks of pasireotide in this population is necessary.
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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
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Androgen Responses to ACTH Infusion among Individual Women with Polycystic Ovary Syndrome
Maas, Kevin H.; Chuan, Sandy; Harrison, Evan; Cook-Andersen, Heidi; Duleba, Antoni J; Chang, R. Jeffrey
2016-01-01
Objective To compare androgen responses during ACTH infusion among women with PCOS and normal women. Design Cross-sectional study. Setting Research center at an academic medical center. Participants Women with PCOS (n=13) and normal controls (n=15). Interventions Blood samples were obtained frequently during a 6-hour dose-response ACTH infusion. Main Outcome Measures Comparison of basal and stimulated levels of 17-OHP, androgens, and cortisol during ACTH infusion with those following hCG injection within individual subjects. Results In women with PCOS increased 17-OHP, A4, and DHEA responses during ACTH infusion were comparable to those observed in normal controls. The magnitude of responses was highly variable among PCOS women. Within individual women with PCOS adrenal responses to ACTH and ovarian responses to hCG were significantly correlated. Cortisol responses to ACTH were similar in PCOS and normal controls. Conclusion Within individual women with PCOS, enhanced androgen responses to ACTH are accompanied by comparable androgen responsiveness to hCG. These findings suggest that dysregulated steroidogenesis leading to hyperandrogenemia in this disorder is likely present in both adrenal and ovarian tissues. PMID:27473350
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Peytremann, Andre; Nicholson, Wendell E.; Brown, Ronald D.; Liddle, Grant W.; Hardman, Joel G.
1973-01-01
The comparative effects of angiotensin II and adrenocorticotropic hormone (ACTH) on cyclic AMP and steroidogenesis were investigated employing isolated bovine adrenal cells from the zona fasciculata. Like ACTH, angiotensin produced a prompt increase in cyclic AMP which preceded the increase in corticosteroid production. Although this increase in cyclic AMP was small when compared to that induced by ACTH, it correlated with the amount of steroidogenesis. This observation is consistent with the view that cyclic AMP is the intracellular mediator of the steroidogenic action of angiotensin. Angiotensin acted synergistically with ACTH on cyclic AMP levels. This synergism was not explained by inhibition of phosphodiesterase activity. Unlike ACTH, angiotensin failed to stimulate adenylate cyclase in broken cell preparations. The observations suggest that more than one mechanism may be involved in effects of ACTH and angiotensin on cyclic AMP levels. PMID:4348344
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EGFR as a therapeutic target for human, canine, and mouse ACTH-secreting pituitary adenomas
Fukuoka, Hidenori; Cooper, Odelia; Ben-Shlomo, Anat; Mamelak, Adam; Ren, Song-Guang; Bruyette, Dave; Melmed, Shlomo
2011-01-01
Cushing disease is a condition in which the pituitary gland releases excessive adrenocorticotropic hormone (ACTH) as a result of an adenoma arising from the ACTH-secreting cells in the anterior pituitary. ACTH-secreting pituitary adenomas lead to hypercortisolemia and cause significant morbidity and mortality. Pituitary-directed medications are mostly ineffective, and new treatment options are needed. As these tumors express EGFR, we tested whether EGFR might provide a therapeutic target for Cushing disease. Here, we show that in surgically resected human and canine corticotroph cultured tumors, blocking EGFR suppressed expression of proopiomelanocortin (POMC), the ACTH precursor. In mouse corticotroph EGFR transfectants, ACTH secretion was enhanced, and EGF increased Pomc promoter activity, an effect that was dependent on MAPK. Blocking EGFR activity with gefitinib, an EGFR tyrosine kinase inhibitor, attenuated Pomc expression, inhibited corticotroph tumor cell proliferation, and induced apoptosis. As predominantly nuclear EGFR expression was observed in canine and human corticotroph tumors, we preferentially targeted EGFR to mouse corticotroph cell nuclei, which resulted in higher Pomc expression and ACTH secretion, both of which were inhibited by gefitinib. In athymic nude mice, EGFR overexpression enhanced the growth of explanted ACTH-secreting tumors and further elevated serum corticosterone levels. Gefitinib treatment decreased both tumor size and corticosterone levels; it also reversed signs of hypercortisolemia, including elevated glucose levels and excess omental fat. These results indicate that inhibiting EGFR signaling may be a novel strategy for treating Cushing disease. PMID:22105169
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Lennartsson, Anna-Karin; Sjörs, Anna; Währborg, Peter; Ljung, Thomas; Jonsdottir, Ingibjörg H
2015-01-01
Common consequences of long-term psychosocial stress are fatigue and burnout. It has been suggested that burnout could be associated with hypocortisolism, thus, inability to produce sufficient amounts of cortisol. This study aimed to investigate whether patients with clinical burnout exhibit aberrant ACTH and cortisol responses under acute psychosocial stress compared with healthy individuals. Nineteen patients (9 men and 10 women) and 37 healthy subjects (20 men and 17 women), underwent the Trier Social Stress Test. Blood samples and saliva samples were collected before, after, and during the stress test for measurements of plasma ACTH, serum cortisol, and salivary cortisol. Several statistical analyses were conducted to compare the responses between patients and controls. In addition, in order to investigate the possibility that burnout patients with more severe symptoms would respond differently, sub-groups of patients reporting higher and lower burnout scores were compared. In both patients and healthy controls, we observed elevated levels of ACTH and cortisol after exposure to the stressor. There were no differences in responses of ACTH, serum cortisol, or salivary cortisol between patients and controls. Patients reporting higher burnout scores had lower salivary cortisol responses than controls, indicating that patients with more severe burnout symptoms may be suffering from hypocortisolism. In addition, patients with more severe burnout symptoms tended to have smaller ACTH responses than the other patients. However, there was no corresponding difference in serum cortisol. This study indicates that hypocortisolism is not present in a clinical burnout patient group as a whole but may be present in the patients with more severe burnout symptoms.
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[Bronchopulmonary ACTH-producing tumors].
Pikunov, M Iu; Kuznetsov, N S; Latkina, N V; Dobreva, E A; Remizov, O V
2014-01-01
Neuroendocrine tumors have the ability to produce the hormones and vasoactive peptides. Excess of these hormones leads to different symptoms and syndromes because of organs' injuries. Detection of ACTH origin by using of modern diagnostic methods is not always possible. Lungs and bronchi are one of the most frequent localization of ACTH-producing tumors. It is considered that carcinoids with bronchopulmonary localization like a benign tumors in the clinical course. But at the same time carcinoid tends to metastasize, so timely diagnostics and treatment improve quality of life significant and increase the life expectancy of patients. The modern state of diagnostics and surgical treatment problem of ACTH-producing tumors with bronchopulmonary localization is presented in the article. It was described the brief historical background, clinical symptoms, instrumental and biochemical methods of diagnosis. The principles of surgical treatment are presented in the article.
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Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies
Baker, Peter R.; Nanduri, Priyaanka; Gottlieb, Peter A.; Yu, Liping; Klingensmith, Georgeanna J.; Eisenbarth, George S.; Barker, Jennifer M.
2016-01-01
Summary Context Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality. Objective To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH-AA+ individuals. Design, Setting and Participants Individuals were screened for 21OH-AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH-AA (n = 87) were tested, and the majority prospectively followed for the development of Addison's disease, including seven diagnosed with AD upon 21OH-AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors. Main Outcome Measured Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH-AA were measured at various time points relative to diagnosis of AD or last AD-free follow-up. Results Compared with nonprogressors, in the time period 2 months–2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11–22 pm, P < 1E-4), with no significant differences in mean PRA (P = 0·07) or baseline cortisol (P = 0·08), and significant but less distinct differences seen with 21OH-AA levels (P < 1E-4) and poststimulation cortisol levels (P = 6E-3). Conclusion Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH-AA, PRA or peak cortisol, in the 2 months–2 years preceding the onset of AD. PMID:22066755
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Different activation of ACTH and corticosterone release in response to various stressors in rats.
Djordjević, J; Cvijić, G; Davidović, V
2003-01-01
The aim of this study was to investigate the reaction of the hypothalamo-pituitary-adrenocortical (HPA) system to various stressors (fasting, crowding, cold and heat) by measuring blood ACTH and corticosterone (CORT) concentration as well as the cholesterol (CHOL) content in the adrenals. To examine the effects of stress termination, the rats were returned and kept under control conditions for the same period as that of stress duration (supposed recovery period). According to our results HPA system was activated by all the stressors applied. Heat seems to be the strongest stressor since the exposure of animals to a high ambient temperature resulted in the greatest rise of plasma ACTH concentration as well as CORT synthesis and secretion. These values remained elevated after the stress termination i.e. after the rats had been returned to room temperature. Fasting seems to be the weakest stressor given because it causes the smallest increase in blood ACTH and CORT concentrations. Moreover, in refed rats the HPA function was fully recovered. In conclusion, the various stressors applied seem to induce a different response of the HPA system as judged by quantitative changes in ACTH and CORT release.
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Erfe, J Mark; Perry, Avital; McClaskey, John; Inzucchi, Silvio E; James, Whitney Sheen; Eid, Tore; Bronen, Richard A; Mahajan, Amit; Huttner, Anita; Santos, Florecita; Spencer, Dennis
2017-10-13
OBJECTIVE Cushing disease is caused by a pituitary micro- or macroadenoma that hypersecretes adrenocorticotropic hormone (ACTH), resulting in hypercortisolemia. For decades, transsphenoidal resection (TSR) has been an efficacious treatment but with certain limitations, namely precise tumor localization and complete excision. The authors evaluated the novel use of a double-antibody sandwich assay for the real-time quantitation of ACTH in resected pituitary specimens with the goals of augmenting pathological diagnosis and ultimately improving long-term patient outcome. METHODS This study involved a retrospective review of records and an analysis of assay values, pathology slides, and MRI studies of patients with Cushing disease who had undergone TSR in the period from 2009 to 2014 and had at least 1 year of follow-up in coordination with an endocrinologist. In the operating room, biopsy specimens from the patients had been analyzed for tissue ACTH concentration. Additional samples were simultaneously sent for frozen-section pathological analysis. The ACTH assay performance was compared against pathology assessments of surgical tumor samples using receiver operating characteristic (ROC) analysis and against pre- and postoperative MRI studies. RESULTS Fourteen patients underwent TSR with guidance by ACTH-antibody assay and pathological assessment of 127 biopsy samples and were followed up for an average of 3 years. The ACTH threshold for discriminating adenomatous from normal tissue was 290,000 pg/mg of tissue, based on jointly maximized sensitivity (95.0%) and specificity (71.3%). Lateralization discordance between preoperative MRI studies and surgical visualization was noted in 3 patients, confirming the impression that MRI alone may not achieve optimal localization. A majority of the patients (85.7%) attained long-term disease remission based on urinary free cortisol levels, plasma cortisol levels, and long-term corticosteroid therapy. Comparisons of patient
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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.
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Kenyon, C J; Fraser, R; Birnie, G G; Connell, J M; Lever, A F
1986-01-01
Isolated bovine adrenocortical cells were incubated with and without 3 ng/ml ACTH, with various concentrations (10-1000 micrograms/ml) of either cimetidine or ranitidine. Cortisol, corticosterone, and deoxycorticosterone outputs were measured. Cimetidine and ranitidine at 320 and 1000 micrograms/ml inhibited ACTH-stimulated corticosterone and cortisol synthesis and cimetidine decreased basal cortisol synthesis. The inhibitory effects of cimetidine on cortisol synthesis were approximately 10 times greater than those of ranitidine. Cimetidine (1000 micrograms/ml), but not ranitidine increased deoxycorticosterone synthesis by ACTH-stimulated cells, indicating inhibition of 11 beta-hydroxylation in the adrenal steroidogenic pathway. Although doses of cimetidine and ranitidine which produce these in vitro effects are much greater than plasma concentrations in normal clinical use, they might be important in acutely ill patients given intravenous bolus injections of cimetidine, or if either antagonist were accumulated by the adrenal to produce high intracellular concentrations. PMID:3023203
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Luque, R M; Ibáñez-Costa, A; López-Sánchez, L M; Jiménez-Reina, L; Venegas-Moreno, E; Gálvez, M A; Villa-Osaba, A; Madrazo-Atutxa, A M; Japón, M A; de la Riva, A; Cano, D A; Benito-López, P; Soto-Moreno, A; Gahete, M D; Leal-Cerro, A; Castaño, J P
2013-10-01
Desmopressin is a synthetic agonist of vasopressin receptors (AVPRs). The desmopressin stimulation test is used in the diagnosis and postsurgery prognosis of Cushing disease (CD). However, the cellular and molecular mechanisms underlying the desmopressin-induced ACTH increase in patients with CD are poorly understood. The objectives of this study were to determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release and to elucidate the cellular and molecular mechanisms involved in desmopressin-induced ACTH increase in CD. A total of 8 normal pituitaries (NPs), 23 corticotropinomas, 14 nonfunctioning pituitary adenomas, 17 somatotropinomas, and 3 prolactinomas were analyzed for AVPR expression by quantitative real-time RT-PCR. Primary cultures derived from corticotropinomas, nonfunctioning pituitary adenomas, somatotropinomas, prolactinomas, and NPs were treated with desmopressin, and ACTH secretion/expression, [Ca(2+)]i kinetics, and AVPR expression and/or proliferative response were evaluated. The relationship between AVPR expression and plasma adrenocorticotropin/cortisol levels obtained from desmopressin tests was assessed. Desmopressin affects all functional parameters evaluated in corticotropinoma cells but not in NPs or other pituitary adenomas cells. These effects might be due to the dramatic elevation of AVPR1b expression levels found in corticotropinomas. In line with this notion, the use of an AVPR1b antagonist completely blocked desmopressin stimulatory effects. Remarkably, only AVPR1b expression was positively correlated with elevated plasma adrenocorticotropin levels in corticotropinomas. The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and postsurgery prognosis of CD. Furthermore, our data indicate that AVPR1b is responsible for the direct
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Influence of estradiol and androstenedione on ACTH and cortisol secretion in the ovine fetus.
Wood, C E; Saoud, C J
1997-01-01
To test the hypothesis that physiologic increases in fetal plasma 17 beta-estradiol and androstenedione modulate the activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis. Seventeen pregnant ewes and their fetuses were chronically catheterized. At the time of surgery, the fetuses received implants that released 17 beta-estradiol (n = 5) alone or 17 beta-estradiol and androstenedione (n = 6), each at a rate of approximately 250 micrograms/day for each steroid. The control group (n = 6) received either no pellet (n = 2) or a "placebo" pellet, which contained no steroid (n = 4). Fetal blood samples were drawn for hormone and blood gas analysis at 1-3-day intervals until the time of spontaneous parturition. Fetal plasma ACTH and cortisol concentrations were fit to semilogarithmic equations and analyzed by stepwise multiple linear regression analysis for statistically significant effects of 17 beta-estradiol and androstenedione. Estradiol significantly increased and androstenedione significantly decreased the ACTH and cortisol concentrations. Treatment with both 17 beta-estradiol and androstenedione resulted in parturition approximately 4 days earlier than in the other groups (P < .05). Physiologic increases in fetal plasma estradiol and androstenedione modify the activity of the HPA axis.
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Refractory Cushing's disease caused by multinodular ACTH-cell hyperplasia.
McKeever, P E; Koppelman, M C; Metcalf, D; Quindlen, E; Kornblith, P L; Strott, C A; Howard, R; Smith, B H
1982-09-01
A patient with pituitary-dependent hypercortisolism, unresponsive to resection of nodules in the anterior lobe, is described. Histochemical stains of the nodules showed multiple, focal, cellular expansions of the fibrovascular stroma. Transitions between normal and expanded adenohypophysial acini were present. Immunoperoxidase stains for ACTH and other pituitary hormones revealed that these multiple foci contained an excess of ACTH-positive cells. Less than 10% of the cells in these foci were negative for ACTH and positive for other hormones. Serial sections showed that these foci of predominantly ACTH-producing acini were not connected. Clinical, morphological, and immunohistochemical data indicated that ACTH-cell hyperplasia caused Crushing's disease in this patient. Pathologic study of individual cases should concentrate on determining whether hyperplasia or adenoma exist at the time of surgical exploration of the pituitary gland, since this determination is important to proper treatment. Tentative criteria to recognize ACTH-cell hyperplasia are: 1. Multiple foci of ACTH laden cells. 2. A minor subpopulation of cells of alternate hormone series. 3. Expansion without destruction of acini in the adenohypophysis.
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Araya, A V; Rojas, P; Fritsch, R; Rojas, R; Herrera, L; Rojas, G; Gatica, H; Silva, H; Fiedler, J L
2006-12-01
A link between stressful life events and development or exacerbation of depression has been established via a large body of evidence. An alteration in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression has also been associated with an increase in cortisol secretion. As arginine-vasopressin (AVP) plays an important role in the activation of HPA axis during stress, the present study investigated ACTH and cortisol secretory response induced by an AVP-related peptide desmopressin (ddAVP) in patients with major depression. Prior to antidepressant treatment, endocrinological parameters were evaluated and correlated with the clinical response to venlafaxine treatment, which offers a dual antidepressant action. Depressive patients with no other psychiatric pathology were evaluated with 17-item Hamilton Depression Scale (HAM-D) in order to follow-up the response to venlafaxine. After 1 wk of treatment, 60% of patients reduced their initial HAM-D score to at least 25%; this group was classified as early responders. The other group (40%) started to reduce significantly their HAM-D score after 3 wk of treatment and was classified as late responders. After 6 wk of treatment both groups have reduced HAM-D score to at least 25% of the baseline score. Prior to the pharmacological treatment, both early and late responders showed salivary cortisol rhythm and urinary free cortisol (UFC) in 24-h similar to healthy subjects. However, we did observe differences in basal ACTH secretion, showing that the late responder group had higher basal ACTH than both early responders and controls. The ddAVP challenge promoted a robust secretion of ACTH only in late responders, suggesting a different sensitivity of pituitary vasopressin receptor. The differences in clinical response to venlafaxine among depressive patients seem to be related to endocrinological parameters.
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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. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
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Severe Cushing's syndrome and bilateral pulmonary nodules: beyond ectopic ACTH.
Tavares Bello, Carlos; van der Poest Clement, Emma; Feelders, Richard
2017-01-01
Cushing's syndrome is a rare disease that results from prolonged exposure to supraphysiological levels of glucocorticoids. Severe and rapidly progressive cases are often, but not exclusively, attributable to ectopic ACTH secretion. Extreme hypercortisolism usually has florid metabolic consequences and is associated with an increased infectious and thrombotic risk. The authors report on a case of a 51-year-old male that presented with severe Cushing's syndrome secondary to an ACTH-secreting pituitary macroadenoma, whose diagnostic workup was affected by concurrent subclinical multifocal pulmonary infectious nodules. The case is noteworthy for the atypically severe presentation of Cushing's disease, and it should remind the clinician of the possible infectious and thrombotic complications associated with Cushing's syndrome. Severe Cushing's syndrome is not always caused by ectopic ACTH secretion.Hypercortisolism is a state of immunosuppression, being associated with an increased risk for opportunistic infections.Infectious pulmonary infiltrates may lead to imaging diagnostic dilemmas when investigating a suspected ectopic ACTH secretion.Cushing's syndrome carries an increased thromboembolic risk that may even persist after successful surgical management.Antibiotic and venous thromboembolism prophylaxis should be considered in every patient with severe Cushing's syndrome.
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60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH.
Gallo-Payet, Nicole
2016-05-01
The pituitary adrenocorticotropic hormone (ACTH) plays a pivotal role in homeostasis and stress response and is thus the major component of the hypothalamo-pituitary-adrenal axis. After a brief summary of ACTH production from proopiomelanocortin (POMC) and on ACTH receptor properties, the first part of the review covers the role of ACTH in steroidogenesis and steroid secretion. We highlight the mechanisms explaining the differential acute vs chronic effects of ACTH on aldosterone and glucocorticoid secretion. The second part summarizes the effects of ACTH on adrenal growth, addressing its role as either a mitogenic or a differentiating factor. We then review the mechanisms involved in steroid secretion, from the classical Cyclic adenosine monophosphate second messenger system to various signaling cascades. We also consider how the interaction between the extracellular matrix and the cytoskeleton may trigger activation of signaling platforms potentially stimulating or repressing the steroidogenic potency of ACTH. Finally, we consider the extra-adrenal actions of ACTH, in particular its role in differentiation in a variety of cell types, in addition to its known lipolytic effects on adipocytes. In each section, we endeavor to correlate basic mechanisms of ACTH function with the pathological consequences of ACTH signaling deficiency and of overproduction of ACTH. © 2016 Society for Endocrinology.
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Rousseau, Elise; Joubert, Michael; Trzepla, Géraldine; Parienti, Jean Jacques; Freret, Thomas; Vanthygem, Marie Christine; Desailloud, Rachel; Lefebvre, Hervé; Coquerel, Antoine; Reznik, Yves
2015-01-01
Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated. Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m2/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients' cortisol AUC in the control range. Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients' cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m2/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement. Patients receiving a 6mg/m2 hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol may be an adjunct for further hydrocortisone
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Trzepla, Géraldine; Parienti, Jean Jacques; Freret, Thomas; Vanthygem, Marie Christine; Desailloud, Rachel; Lefebvre, Hervé; Coquerel, Antoine; Reznik, Yves
2015-01-01
Background Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated. Methods Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m2/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients’ cortisol AUC in the control range. Results Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients’ cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m2/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement. Conclusions Patients receiving a 6mg/m2 hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol
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Aged PROP1 Deficient Dwarf Mice Maintain ACTH Production
Bavers, David L.; Beuschlein, Felix; Mortensen, Amanda H.; Keegan, Catherine E.; Hammer, Gary D.; Camper, Sally A.
2011-01-01
Humans with PROP1 mutations have multiple pituitary hormone deficiencies (MPHD) that typically advance from growth insufficiency diagnosed in infancy to include more severe growth hormone (GH) deficiency and progressive reduction in other anterior pituitary hormones, eventually including adrenocorticotropic hormone (ACTH) deficiency and hypocortisolism. Congenital deficiencies of GH, prolactin, and thyroid stimulating hormone have been reported in the Prop1null (Prop1-/-) and the Ames dwarf (Prop1df/df) mouse models, but corticotroph and pituitary adrenal axis function have not been thoroughly investigated. Here we report that the C57BL6 background sensitizes mutants to a wasting phenotype that causes approximately one third to die precipitously between weaning and adulthood, while remaining homozygotes live with no signs of illness. The wasting phenotype is associated with severe hypoglycemia. Circulating ACTH and corticosterone levels are elevated in juvenile and aged Prop1 mutants, indicating activation of the pituitary-adrenal axis. Despite this, young adult Prop1 deficient mice are capable of responding to restraint stress with further elevation of ACTH and corticosterone. Low blood glucose, an expected side effect of GH deficiency, is likely responsible for the elevated corticosterone level. These studies suggest that the mouse model differs from the human patients who display progressive hormone loss and hypocortisolism. PMID:22145038
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Zaretsky, Dmitry V.; Zaretskaia, Maria V.; DiMicco, Joseph A.; Durant, Pamela J.; Ross, Christian T.; Rusyniak, Daniel E.
2013-01-01
Acute and chronic complications from the substituted amphetamine 3,4-methylenedioxymethamphetamine (MDMA) are linked to activation of the hypothalamic-pituitary-adrenal (HPA) axis. How MDMA activates the HPA axis is not known. HPA responses to stress are known to be mediated through the paraventricular (PVH) hypothalamus and to involve serotonin-1a (5-HT1A) receptors. We sought to determine if the PVH and 5-HT1A receptors were also involved in mediating HPA responses to MDMA. Rats were pretreated with either saline or a 5-HT1A antagonist, WAY-100635 (WAY), followed by a systemic dose of MDMA (7.5 mg/kg i.v.). Animals pretreated with WAY had significantly lower plasma ACTH concentrations after MDMA. To determine if neurons in the PVH were involved, and if their involvement was mediated by 5-HT1A receptors, rats implanted with guide cannulas targeting the PVH were microinjected with the GABAA receptor agonist muscimol, aCSF, or WAY followed by MDMA. Compared to aCSF microinjections of muscimol significantly attenuated the MDMA-induced rise in plasma ACTH (126 vs. 588 pg/ml, P=<0.01). WAY had no effect. Our data demonstrates that neurons in the PVH, independent of 5-HT1A receptors, mediate ACTH responses to MDMA. PMID:23933156
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Bocheva, A; Dzambazova, E; Hadjiolova, R; Traikov, L; Mincheva, R; Bivolarski, I
2008-10-01
1. Studies, using a wide variety of stressors, have clearly indicated that the pattern of neuroendocrine response is dependent upon the stress stimulus applied. 2. The Tyr-MIF-1 family of peptides (Tyr-MIF-1s) includes MIF-1, Tyr-MIF-1, Tyr-W-MIF-1 and Tyr-K-MIF-1. These neuropeptides, neuromodulators are able to inhibit the expression of some forms of stress-induced analgesia. 3. The aim of this study was to compare changes in ACTH and corticosterone (CORT) concentration after various stressors (immobilization, cold and heat), as well as after injection of investigated Tyr-MIF-1s peptides. 4. According to our results, hypothalamic-pituitary-adrenal (HPA) system was activated by all the stressors applied. Heat and immobilization are stronger stressors, as the exposure of animals to a high ambient temperature and immobilization resulted in the highest rise of plasma ACTH and CORT concentration when compared with cold stress. Moreover, all the investigated peptides from Tyr-MIF-1 family, administered after application of stressors, inhibited the elevations in adrenocorticotropic hormone (ACTH) and corticosterone (CORT) plasma concentrations significantly. 5. In conclusion, the various stressors applied seem to induce a different response of the HPA system as judged by quantitative changes in ACTH and CORT release. We suggest that Tyr-MIF-1 peptides may possess anti-stressor effects, as they inhibited stress-induced rising in two hormones that were investigated.
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Ectopic ACTH syndrome caused by pulmonary carcinoid tumourlets.
Povedano, S T; Pastor, C V; Seoane, C P; Reina, L J; Moreno, M A; Ortega, R P; López-Rubio, F; López, P B
2001-06-01
The differential diagnosis of Cushing's syndrome is a major challenge to clinical endocrinologists, especially those infrequent cases referred to as occult ectopic ACTH syndromes. Although bronchial carcinoids are well known to be a cause of Cushing's syndrome due to ectopic ACTH secretion, very few cases of carcinoid tumourlets causing an ACTH ectopic syndrome have been reported, and their origin remains controversial. For some authors, tumourlets and typical carcinoids represent distinct pathological entities, whilst others hold that tumourlets are merely microscopic carcinoid tumours. We report a patient with an aggressive Cushing's syndrome that required bilateral adrenalectomy, diagnosed 22 years before a 3-cm lung nodule became apparent on routine chest X-ray. The biopsy after lung surgery revealed a typical peripheral bronchial carcinoid surrounded by tumourlets. Both tumourlets and carcinoid tumour showed strongly positive ACTH immunostaining. Recently, Arioglu et al. (1998) reported a case of Cushing's syndrome caused by pulmonary carcinoid tumourlets, concluding that this entity should be considered in the differential diagnosis of occult ectopic ACTH syndrome. Furthermore, we consider that the carcinoid tumourlets found in our patient, were the initial source of ACTH, leading to Cushing's syndrome with a rapid onset, and that a loss of cell proliferation control in one of such tumourlets many years later, could have resulted in the development of a typical carcinoid tumour, reinforcing the theory of a common origin of these lesions.
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Somatotype and stress hormone levels in young soccer players.
Handziska, E; Handziski, Z; Gjorgoski, I; Dalip, M
2015-11-01
The relationship between somatotype and cortisol and adrenocorticotropic (ACTH) hormone concentrations at rest or after exercise in adolescent soccer players at different time points throughout a soccer season is not understood. Therefore, the aim of this study was to examine the relationship between somatotype and cortisol and ACTH concentrations at rest and after exercise in adolescent soccer players at different time points during a soccer season. During the first 4 months of the soccer season, 47 soccer players (between 15-17 years of age) were tested at three different time points including at baseline, after 6 weeks, and at the end of 4 months. Testing included anaerobic threshold (AnT, km/h) and maximal speed of running (Max, km/h) were measured with Conconi protocol on treadmill. Before and after a maximal exercise Test, plasma levels of cortisol (ug/dL) and ACTH (pg/ml) were assessed by chemiluminometry enzyme amplificated method. Heath-Carter anthropometric somatotype model was used to determine 13 elements of somatotype. Descriptive statistics and multiple regression were used for statistical analysis (P<0.05). Body composition and AnT were not significantly different between each time point of testing. The mesomorph-ectomorph (N.=21), balanced mesomorph (N.=8) and balanced ectomorph (N.=7) were the most frequent somatotypes. There were significant decrements of cortisol plasma levels (at rest 33.4%; after test 27.46%), with insignificant changes of ACTH plasma levels, after 6 weeks of preparation phase and after finishing of half season, at rest and after maximal treadmill test. There were significant correlation between ACTH levels at rest (R=0.44; P<0.01) and some somatotypes (mesomorph endomorph, central and balanced endomorph) and ACTH levels after maximal exercise test (R=0.36; P<0.05) and balanced ectomorph and endomorph mesomorph. There were significant correlation between cortisol levels after maximal exercise test at the beginning of training
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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.
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Cushing's syndrome in infancy due to ectopic ACTH secretion by a sacro-coccygeal teratoma.
Rydzewska, Marta; Krawczuk-Rybak, Maryna; Zajkowska, Adrianna; Jurczuk, Natalia; Polnik, Dariusz; Szalecki, Mieczysław; Moszczyńska, Elżbieta; Savage, Martin O; Bossowski, Artur
2017-04-01
Adenocorticotropic hormone (ACTH)-dependent Cushing's syndrome in infancy is extremely rare. We describe the case of a sacro-coccygeal ectopic ACTH-secreting immature teratoma in an infant who also presented the triad of defects characteristic of Currarino syndrome. A girl was born with a large immature teratoma in the sacro-coccygeal region associated with anal atresia. At the age of 7 days, the concentration of α-fetoprotein (AFP) was above the age-specific normal range. Two non-radical surgical excisions of the tumour were performed. At the age of 7 months, she developed polyphagia, acne, hirsutism, hypertension and hypokalemia with elevated ACTH and absence of serum cortisol circadian rhythm. Immunostaining of tumour tissue showed ACTH-immunoreactive cells. Due to unsuccessful therapy with ketoconazole and resistance to antihypertensive medications [blood pressure (BP) 210/160 mmHg], metyrapone was administered, which controlled her ACTH and cortisol levels in the normal range. Following further removal of tumour bulk after three operations during the first year of life, there was a decrease of BP to normal values. A rare case of ectopic ACTH syndrome causing Cushing's syndrome in infancy in the context of Currarino syndrome is reported. Radical surgery has resulted in excision of the tumour and current control of Cushing's syndrome.
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A rare case of an ACTH/CRH co-secreting midgut neuroendocrine tumor mimicking Cushing's disease.
Streuli, Regina; Krull, Ina; Brändle, Michael; Kolb, Walter; Stalla, Günter; Theodoropoulou, Marily; Enzler-Tschudy, Annette; Bilz, Stefan
2017-01-01
Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing's syndrome and only a few cases have been reported in the literature. Differentiating between Cushing's disease and ectopic Cushing's syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing's disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS). We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing's syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing's disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT) of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing's disease. The discrimination between a Cushing's disease and ectopic Cushing's syndrome is challenging and has many caveats.Ectopic ACTH/CRH co-secreting tumors are very rare.Dynamic tests as well as BIPSS may be compatible with Cushing's disease in ectopic CRH-secretion.High levels of CRH may induce hyperplasia of the corticotroph cells in the pituitary. This could be the cause of a preserved pituitary response to dexamethasone and CRH.Clinical features of ACTH-dependent hypercortisolism with rapid development of Cushing's syndrome, hyperpigmentation, high circulating levels of cortisol with associated hypokalemia, peripheral edema and proximal myopathy should be a warning flag of ectopic Cushing's syndrome and lead to further investigations.
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A rare case of an ACTH/CRH co-secreting midgut neuroendocrine tumor mimicking Cushing's disease
Streuli, Regina; Krull, Ina; Brändle, Michael; Kolb, Walter; Stalla, Günter; Theodoropoulou, Marily; Enzler-Tschudy, Annette
2017-01-01
Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing’s syndrome and only a few cases have been reported in the literature. Differentiating between Cushing’s disease and ectopic Cushing’s syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing’s disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS). We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing’s syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing’s disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT) of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing’s disease. Learning points: The discrimination between a Cushing’s disease and ectopic Cushing’s syndrome is challenging and has many caveats. Ectopic ACTH/CRH co-secreting tumors are very rare. Dynamic tests as well as BIPSS may be compatible with Cushing’s disease in ectopic CRH-secretion. High levels of CRH may induce hyperplasia of the corticotroph cells in the pituitary. This could be the cause of a preserved pituitary response to dexamethasone and CRH. Clinical features of ACTH-dependent hypercortisolism with rapid development of Cushing’s syndrome, hyperpigmentation, high circulating levels of cortisol with associated hypokalemia, peripheral edema and proximal myopathy should be a warning flag of ectopic Cushing’s syndrome and lead to further investigations
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The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome.
de Keyzer, Y; Lenne, F; Auzan, C; Jégou, S; René, P; Vaudry, H; Kuhn, J M; Luton, J P; Clauser, E; Bertagna, X
1996-01-01
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
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The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome.
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
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Prostaglandin E2 releases ovine fetal ACTH from a site not perfused by the carotid vasculature.
Cudd, T A; Wood, C E
1992-07-01
Placental prostaglandin E2 (PGE2) is thought to influence the ovine fetal adrenocortical system to control the timing of parturition. We investigated whether physiological infusions of PGE2 increase fetal immunoreactive adrenocorticotropin (iACTH) at the fetal brain or pituitary or at a site not perfused by the carotid vasculature. PGE2 was infused into the carotid artery (ica) at 0 (n = 5), 10 (n = 5), or 100 ng/min (n = 4) or into the vena cava (ivc) at 10 (n = 5) or 100 ng/min (n = 5) for 30 min in fetuses between 119 and 130 days gestation. Blood gases, vasopressin, cortisol, and arterial and central venous pressure were unchanged. Heart rate increased only in the 100 ng/min ica group. iACTH increased only in the 100 ng/min ivc group from 59 +/- 26 to 180 +/- 73 pg/ml. We conclude that PGE2 infused to create physiological plasma concentrations similar to those at the end of gestation stimulates iACTH from a site other than the fetal brain or pituitary.
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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.
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Borba, Clarissa Groberio; Batista, Rafael Loch; Musolino, Nina Rosa de Castro; Machado, Vanielle Carvalho; Alcantara, Ana Elisa Evangelista; da Silva, Gilberto Ochman; Sperling Cescato, Valter Angelo; da Cunha Neto, Malebranche Berardo Carneiro
2015-01-01
Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH). It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing's disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15%) and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.
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Gunasekaran, N; Long, L E; Dawson, B L; Hansen, G H; Richardson, D P; Li, K M; Arnold, J C; McGregor, I S
2009-11-01
Delta(9)-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. 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. 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-Delta(9)-tetrahydrocannabinol (THC-COOH) in the blood of rats that had been pre-exposed to repeated THC injections. 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'.
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Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R
2000-03-01
Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.
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Detection of tetracosactide in plasma by enzyme-linked immunosorbent assay (ELISA).
Martin, Laurent; Chaabo, Ayman; Lasne, Françoise
2015-06-01
As a synthetic analogue of adrenocorticotropic hormone (ACTH), tetracosactide is prohibited in sport by the World Anti-Doping Agency (WADA). An enzyme-linked immunosorbent assay (ELISA) method is proposed for detection of this drug in plasma. Since its structure corresponds to the 24 N-terminal of the 39 amino acids of the natural endogenous peptide ACTH, tetracosactide can be detected with a commercial ELISA kit for ACTH that uses antibodies, the epitopes of which are located in the 1-24 part of ACTH. However, an essential condition for detection specificity is the preliminary total clearance of endogenous ACTH in the plasma samples. This is achieved by a preparative step based on cation-exchange chromatography before ELISA. The method is specific and sensitive (LOD: 30 pg/mL) and may be used as a screening analysis in anti-doping control. The pre-analytical conditions are shown to be of the upmost importance and recommendations for blood collection (EDTA tubes), sample transport (4 °C) and plasma sample storage (-20 °C) are presented. Copyright © 2014 John Wiley & Sons, Ltd.
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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
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Zou, Li-Ping; Wang, Xu; Dong, Chang-Hong; Chen, Chun-Hong; Zhao, Wei; Zhao, Ruo-Yan
2010-04-01
Infantile spasms (IS) is an age-specific and severe epileptic encephalopathy that occurs in infancy and early childhood and is usually refractory to conventional antiepileptic drugs. Adrenocorticotropic hormone (ACTH) has been the treatment of choice for IS, but ACTH use has been associated with infection and hypertension. Magnesium ion is an N-methyl-D-aspartic acid (NMDA)-noncompetitive antagonist that might inhibit NMDA activity and has antiepileptic and neuroprotective effects. This study compared the efficacy and tolerability of ACTH + magnesium sulfate (MgSO(4)) versus ACTH monotherapy for the treatment of IS. This 24-week, randomized, open-label follow-up study enrolled male and female infants with IS. Patients were randomly assigned to receive ACTH 25 U/d + MgSO(4) 0.25 g/kg/d, or ACTH 25 U/d only (control), intravenously for 3 weeks. Efficacy was assessed over a period of 24 weeks based on seizure frequency, EEG, and Gesell testing of psychomotor skills (subscales: language, motor, adaptive, and personal-social skills; measured using a developmental quotient [DQ] ). Tolerability was assessed by monitoring for adverse events using laboratory analysis and clinical evaluation. Thirty-eight infants were enrolled (23 male, 15 female; median age, 9.2 months; 19 patients per group). At 12 weeks, 14 patients (73.7%) who received ACTH + MgSO(4) and 9 patients (47.4%) in the control group were seizure free. At 24 weeks, seizure-free rates were 12 (63.2%) in the ACTH + MgSO(4) group and 10 (52.6%) in the control group. On EEG, 9 patients (47.4%) in the ACTH + MgSO(4) group achieved complete recovery (normalized EEG), 5 (26.3 %) attained partial improvement (multifocal spike wave), and 5 (26.3%) had no improvement (hypsarrhythmia or modified hypsarrhythmia). At 4 weeks, in the control group, 5 patients (26.3 %) achieved complete recovery, 6 (31.6%) achieved partial improvement, and 8 (42.1%) had no improvement. Of the 12 patients who were seizure free at 24 weeks in
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On the mode of action of ACTH on the isolated perfused adrenal gland
Jaanus, Siret D.; Rosenstein, M. J.; Rubin, R. P.
1970-01-01
1. Isolated cat adrenal glands were perfused with Locke solution, and the corticosteroid outputs in response to adrenocorticotrophin (ACTH) were studied. 2. Steroid outputs varied with the ACTH concentration, as well as with the duration of exposure to a given ACTH concentration. 3. Omission of calcium from the perfusion medium markedly depressed ACTH-evoked steroid release. The steroid output was directly related to the extracellular calcium concentration up to 0·5 mM. 4. During a constant exposure to ACTH, steroid output was maintained for at least 2-3 hr, provided that calcium was present in the perfusion medium. 5. Strontium, but not barium or magnesium, replaced calcium in maintaining the secretory response to ACTH. 6. Magnesium depressed ACTH-evoked secretion in the presence of calcium, and this depression of secretion was antagonized by increasing the calcium concentration. 7. Prolonged perfusion with sodium-free or potassium-free solutions did not markedly inhibit steroid output in response to ACTH. Excess potassium (56 mM) did not produce a consistent or marked increase in spontaneous steroid output and did not affect the response to ACTH. 8. The steroid content of adrenal glands perfused with Locke solution and exposed to ACTH was about 10% of the amount which was secreted. By contrast, adrenal glands perfused with calcium-free media and exposed to ACTH contained much higher amounts of steroid, despite the negligible amount secreted. 9. These data suggest that calcium plays a critical role in the mechanism of corticosteroid secretion from the adrenal cortex. PMID:4322584
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ACTH stimulation test in the captive cheetah (Acinonyx jubatus).
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).
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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.
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Secombe, C J; Tan, R H H; Perara, D I; Byrne, D P; Watts, S P; Wearn, J G
2017-09-01
Longitudinal evaluation of plasma endogenous ACTH concentration in clinically normal horses has not been investigated in the Southern Hemisphere. To longitudinally determine monthly upper reference limits for plasma ACTH in 2 disparate Australian geographic locations and to examine whether location affected the circannual rhythm of endogenous ACTH in the 2 groups of horses over a 12-month period. Clinically normal horses <20 years of age from 4 properties (institutional herd and client owned animals) in Perth (n = 40) and Townsville (n = 41) were included in the study. A prospective longitudinal descriptive study to determine the upper reference limit and confidence intervals for plasma ACTH in each geographic location using the ASVCP reference interval (RI) guidelines, for individual months and monthly groupings for 12 consecutive months. Plasma endogenous ACTH concentrations demonstrated a circannual rhythm. The increase in endogenous ACTH was not confined to the autumnal months but was associated with changes in photoperiod. During the quiescent period, plasma ACTH concentrations were lower, ≤43 pg/mL (upper limit of the 90% confidence interval (CI)) in horses from Perth and ≤67 pg/mL (upper limit of the 90% CI) in horses from Townsville, than at the acrophase, ≤94 pg/mL (upper limit of the 90% CI) in horses from Perth, ≤101 pg/mL (upper limit of the 90% CI) in horses from Townsville. Circannual rhythms of endogenous ACTH concentrations vary between geographic locations, this could be due to changes in photoperiod or other unknown factors, and upper reference limits should be determined for specific locations. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
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Bradley, A J; Stoddart, D M
1990-11-01
The effects of cortisol, ACTH, adrenalin and insulin on indices of carbohydrate, fat and protein metabolism were investigated in the conscious marsupial sugar glider Petaurus breviceps. Short-term i.v. infusion of cortisol at dose rates of 0.02, 0.2 and 1.0 mg/kg per h caused the plasma glucose concentration to rise sharply from the normal range of 3.3-4.4 to 8.1-8.7 mmol/l at the end of the infusion period without significant alteration in plasma free fatty acid (FFA), amino acid or urea concentrations. Infusions of ACTH at dose rates of 0.02, 0.06 and 0.45 IU/kg per h caused a similar rise in plasma glucose concentration; however, this was now accompanied by an elevation in plasma FFA concentration, but again without significant changes in either plasma amino acid or urea concentrations. Infusion of adrenalin at 10 micrograms/kg per h caused an increase in the plasma concentrations of both glucose and FFA. Intravenous injections of 0.15 IU insulin/kg caused a rapid and marked decrease in the plasma glucose concentration within 30 min and an increase in the plasma free cortisol concentration. Associated with this change was a marked rise in the plasma concentration of both FFA and free cortisol. The rise in free cortisol was, however, significantly reduced by infusion of glucose. Pretreatment with five daily i.m. injections of 1 mg cortisol acetate/kg, which produced an increase in plasma free cortisol concentration to near the maximum of the physiological range, caused a marked reduction in insulin sensitivity. Cortisol pretreatment caused an increase in the plasma FFA and amino acid concentrations. Petaurus breviceps is highly sensitive to the metabolic effects of glucocorticoids and is similar in this respect to the brush-tailed possum Trichosurus vulpecula. The interactive effects between insulin and glucocorticoids on carbohydrate, fat and protein metabolism in Petaurus breviceps are similar to those shown by Trichosurus vulpecula and some eutherian mammals
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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...
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Influence of E. coli endotoxin on ACTH induced adrenal cell steroidogenesis.
Garcia, R; Viloria, M D; Municio, A M
1985-03-01
The effect of endotoxin (lipopolysaccharide from E. coli) on isolated adrenocortical cells was examined. Lipopolysaccharide decreased the ACTH-induced steroidogenesis. This effect was shown by all corticotropin concentrations studied, and the longer the incubation time, the higher the effect produced. The rate of decrease of ACTH-induced steroidogenesis was dependent on the concentration of lipopolysaccharide in the medium. Binding of [125I]ACTH to adrenocortical cells was modified by lipopolysaccharide; this modification was related to a decrease of the ACTH-induced steroidogenesis. This effect supports the hypothesis of a direct interaction between lipopolysaccharide and the cell membrane with a concomitant distortion of the cell surface affecting the ACTH receptor sites of their environment. [14C]Lipopolysaccharide binds to isolated adrenocortical cells. Binding specificity was investigated by competitive experiments in the presence of various types of endotoxins, polypeptide hormones and proteins. Unlabelled lipopolysaccharide from the same bacterial strain and isolated under identical conditions than the labelled lipopolysaccharide exerted the strongest inhibitory activity. Unlabelled lipopolysaccharide of various strains different from that originating the labelled lipopolysaccharide exerted the less displacement. It would imply a certain kind of specificity but the decrease in the binding of lipopolysaccharide produced by ACTH and glucagon suggests the existence of non-specific interactions between lipopolysaccharide and cell membrane.
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Elevated plasma prolactin in abstinent methamphetamine-dependent subjects.
Zorick, Todd; Mandelkern, Mark A; Lee, Buyean; Wong, Ma-Li; Miotto, Karen; Shabazian, Jon; London, Edythe D
2011-01-01
Methamphetamine (MA) use disorders are pervasive global social problems that produce large medical and public health burdens. Abnormalities in pituitary hormonal regulation have been observed in preclinical models of substance abuse and in human substance abusers. They have, however, not been studied before in MA-dependent human subjects. To determine if MA-dependent research volunteers differ from healthy control subjects in plasma levels of adrenocorticotropic hormone (ACTH), cortisol, or prolactin, or in pituitary dopamine D(2) receptor availability during early abstinence from MA. MA-dependent subjects (N = 31), who were not seeking treatment, resided on an inpatient ward for up to 5 weeks. Abstinence was confirmed by daily urine drug screening. Venous blood was sampled for plasma hormone levels, and positron emission tomography with [(18)F]fallypride was performed to determine dopamine D(2) receptor availability during the first week of abstinence. Venous blood was sampled again for hormone levels during the fourth week of abstinence. Matched healthy volunteers (N = 23) participated as a comparison group. MA-dependent and healthy comparison subjects did not differ in plasma ACTH or cortisol levels, but had an elevated plasma prolactin at both the first week and fourth week of abstinence. There was no group difference in pituitary dopamine D(2) receptor availability. MA-dependent individuals have abnormalities in prolactin regulation, which is not likely due to alterations in pituitary dopamine D(2) receptor availability. MA dependence is associated with elevated prolactin levels, which may contribute to medical comorbidity in afflicted individuals.
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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.
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Corticotropin (ACTH) regulates alternative RNA splicing in Y1 mouse adrenocortical tumor cells.
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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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ACTH Modulates PTP-PEST Activity and Promotes Its Interaction With Paxillin.
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. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.
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Can ACTH therapy improve the long-term outcome of drug-resistant frontal lobe epilepsy?
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.
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Schneider, E; Jacobi, P; van Riezen, H; Voerman, J W; Fischer, P A
1981-09-01
The effects of ACTH4-10 (Org O163) and of the ACTH4-9 analog (Org 2766) were tested in 20 male patients suffering from a mild to moderate cerebroorganic impairment. Patients were aged between 51-72 years (mean 60.9). Org 2766 was given in dosages of 0.05 mg, 0.5 mg and 5 mg, Org O163 in a dosage of 30 mg. The investigation was based on a randomized incomplete crossover design. By means of psychological tests the effects of the synthetic neuropeptides on memory, state of well-being, attention, vigilance and psychomotor function were investigated. The statistical analysis of the results did not reveal any effects of both substances on the functions tested. These results are in agreement with those of other studies in man using similar methods and acute administration of ACTH4-10 and/or Org 2766. In such studies only effects of reactive inhibition of attention and motivation could be demonstrated consistently.
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Nilsson, P.B.; Hollmén, Tuula E.; Atkinson, S.; Mashburn, K.L.; Tuomi, P.A.; Esler, Daniel N.; 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.
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Matthews, E. K.; Saffran, M.
1973-01-01
1. The effects of changes of ionic environment upon corticosteroid production by rabbit adrenal glands have been investigated in vitro using a superfusion technique and on-line steroid analysis by an automated fluorescence method. In some experiments micro-electrode recordings of adrenocortical transmembrane potentials were made concomitantly with measurement of steroid output. 2. Adrenocorticotrophic hormone (ACTH), 10 m-u./ml., induced a sevenfold increase in corticosteroid production rate in normal Krebs solution. 3. The steroidogenic response to ACTH was not impaired after omission of [K]o for 1 hr but was inhibited following exposure to K+-free medium for 3 hr. Increase of [K]o tenfold to 47 mM increased the basal but not the ACTH-stimulated output of corticosteroid whereas raising [K]o twentyfold to 94 mM enhanced both the basal and ACTH-stimulated steroid production rate. In K+-free solution the adrenocortical cells hyperpolarized from - 67 to - 86 mV; subsequently on addition of ACTH they depolarized. Reintroduction of K+ restored the membrane potential. 4. Omission of Ca2+ partially depolarized the cells but only affected the steroidogenic response to ACTH in the presence of EDTA. A threefold increase of [Ca]o, to 7·68 mM, had no effect on either membrane potentials or steroid formation, but increasing [Ca]o tenfold to 25·6 mM partially blocked ACTH action. Increasing [Mg]o twentyfold to 22·6 mM had little effect on ACTH-stimulated corticosteroid output and Sr 2·56 mM, in substitution for Ca2+, supported ACTH action, but La, 0·25 mM, completely blocked the steroidogenic effect of ACTH. 5. Replacement of NaCl, 118 mM by choline chloride, 118 mM, was without effect on ACTH-induced steroidogenesis, whereas LiCl, 118 mM, reduced it by 50%. NaF, 1 and 10 mM, inhibited ACTH-induced steroidogenesis by approximately 60%. 6. Nupercaine, 10-4 M, inhibited the steroid response to ACTH with no effect upon membrane potentials: increasing the nupercaine
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Inhibition of the pituitary-adrenal response to stress during deprivation-induced feeding
NASA Technical Reports Server (NTRS)
Heybach, J. P.; Vernikos-Danellis, J.
1979-01-01
Plasma corticosterone and plasma and pituitary ACTH concentrations were determined during feeding and after application of an acute stress at various times after food and water presentation to male rats maintained on a restricted feeding and watering schedule. Both plasma corticosterone and ACTH concentrations fell after the presentation of food and water, and this fall was accompanied by increased levels of ACTH in the pituitary gland. In addition, a rise in plasma levels of ACTH was inhibited in response to an acute stress applied at 0-5 min after presentation of food and water, but ACTH synthesis was not. This inhibition of ACTH and corticosterone secretion in response to stress was transient and dissipated as a relatively linear function of the interval between food presentation and application of the stress. The results suggest that this feeding-induced, corticosteroid-independent inhibition of pituitary-adrenal activity involves active inhibitory mechanisms operating initially on ACTH secretory processes of the pituitary and later on the synthesis of ACTH or on the secretion of hypothalamic corticotropin-releasing factor.
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Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E; Nagy, Gyorgy M; Vecsernyés, Miklós
2009-01-01
Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and beta-lipotropin in corticotropes of the anterior lobe, and to alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D(2) type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence alpha-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E(2))-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in alpha-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by alpha-methyl-p-tyrosine (alphaMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma alpha-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E(2) animals. In lactating mothers, BRC was able to block ACTH responses induced by both alphaMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is
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Oláh, Márk; Fehér, Pálma; Ihm, Zsófia; Bácskay, Ildikó; Kiss, Timea; Freeman, Marc E.; Nagy, György M.; Vecsernyés, Miklós
2009-01-01
Pro-opiomelanocortin (POMC) is processed to adrenocorticotropic hormone (ACTH) and β-lipotropin in corticotropes of the anterior lobe, and to α-melanocyte-stimulating hormone (α-MSH) and β-endorphin in melanotropes of the intermediate lobe (IL) of the pituitary gland. While ACTH secretion is predominantly under the stimulatory influence of the hypothalamic factors, hormone secretion of the IL is tonically inhibited by neuroendocrine dopamine (NEDA) neurons. Lobe-specific POMC processing is not absolute. For example, D2 type DA receptor (D2R)-deficient mice have elevated plasma ACTH levels, although it is known that corticotropes do not express D2R(s). Moreover, observations that suckling does not influence α-MSH release, while it induces an increase in plasma ACTH is unexplained. The aim of the present study was to investigate the involvement of the NEDA system in the regulation of ACTH secretion and the participation of the IL in ACTH production in lactating rats. Untreated and estradiol (E2)-substituted ovariectomized (OVX) females were also studied. The concentration of ACTH in the IL was higher in lactating rats than in OVX rats, while the opposite change in α-MSH level of the IL was observed. DA levels in the IL and the neural lobe were lower in lactating rats than in OVX rats. Suckling-induced ACTH response was eliminated by pretreatment with the DA receptor agonist, bromocriptine (BRC). Inhibition of DA biosynthesis by α-methyl-p-tyrosine (αMpT) and blockade of D2R by domperidone (DOM) elevated plasma ACTH levels, but did not influence plasma α-MSH levels in lactating rats. The same drugs had opposite effects in OVX and OVX + E2 animals. In lactating mothers, BRC was able to block ACTH responses induced by both αMpT and DOM. Surgical denervation of the IL elevated basal plasma levels of ACTH. Taken together, these data indicate that melanotropes synthesize ACTH during lactation and its release from these cells is regulated by NEDA neurons. PMID
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Early-onset severe obesity with ACTH deficiency and red hair in a boy: the POMC deficiency.
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.
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White, R B; Thomas, P
1992-12-01
To investigate the possible involvement of pituitary hormones in the regulation of steroidogenesis during reptilian sexual differentiation, we tested the ability of gonadotropin (ovine FSH), adrenocorticotropin (porcine ACTH), and growth hormone (bovine GH) to stimulate in vitro steroidogenesis in embryonic adrenal-kidney-gonad complexes (AKGs) of a turtle, Trachemys scripta, during and after the temperature-sensitive period for sex determination (TSP). Radioimmunoassays were used to measure progesterone, testosterone, estradiol, and corticosterone in incubation media; additionally, immunoreactive ACTH was measured in plasma. Presumptive male and female AKGs were stimulated by both FSH and ACTH at each stage investigated. Secretion of progesterone and corticosterone was usually far greater than that of testosterone or estradiol in both basal and hormone-stimulated incubations. In general, AKGs from presumptive males secreted more progesterone and corticosterone than AKGs from presumptive females. Progesterone and estradiol secretions were stimulated by both FSH and ACTH, but testosterone secretion was stimulated only by ACTH. Corticosterone secretion was strongly stimulated by ACTH. GH failed to significantly stimulate steroid secretion. Plasma ACTH levels were significantly higher in males than in females, and both sexes had significantly higher plasma levels of ACTH after the TSP compared to during the TSP. Our data demonstrate that during the temperature-sensitive period AKGs are responsive to both gonadotropin and ACTH, and that there are significant sex differences in steroidogenesis, sensitivity to gonadotropin and ACTH, and plasma ACTH levels.
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Gisquet-Verrier, Pascale; Botreau, Fanny; Venero, Cesar; Sandi, Carmen
2004-05-01
Memory retrieval can be facilitated by pretest exposure to cues associated with the original training. The present series of experiments was aimed at investigating whether the effectiveness of the retrieval cues might be due to their emotional value and thus be associated to a particular pattern of activation of stress systems. Therefore, the effects of exposing rats to different cueing conditions were investigated both on retention performance and on the level of different stress hormones (ACTH, corticosterone and glucose; the latter as an indirect index of adrenergic/sympathetic nervous system activation). Rats trained in a brightness avoidance discrimination task exhibited an enhancement of the retention performance following exposure to the light discriminative stimulus when delivered 1-day after training and not after 21 days, while exposure to contextual cues led to opposite effects on the retention performance, confirming our previous results. Analyses of the level of stress hormones at the time of testing indicated that when the retrieval cues were effective at the behavioral level, cued rats exhibited higher ACTH plasmatic levels than controls, but did not differ in their glucose or corticosterone levels. Further experiments showed that one day after training, both ACTH and corticosterone levels were elevated in light-cued rats if hormone samples were taken 15 min after cueing. These results show that exposure to an effective retrieval cue is accompanied by the activation of the hypothalamus-pituitary-adrenal axis. The possible involvement of the Corticotropin Releasing Factor at the level of the hypothalamus and amygdala (particularly the central nucleus) on the facilitating effect on retention performance following exposure to aversive training-associated cues is discussed. The present results strengthen the notion that emotion can interact with retrieval processes.
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Exercise training alters effect of high-fat feeding on the ACTH stress response in pigs.
Jankord, Ryan; Ganjam, Venkataseshu K; Turk, James R; Hamilton, Marc T; Laughlin, M Harold
2008-06-01
Eating and physical activity behaviors influence neuroendocrine output. The purpose of this study was to test, in an animal model of diet-induced cardiovascular disease, the effects of high-fat feeding and exercise training on hypothalamo-pituitary-adrenocortical (HPA) axis activity. We hypothesized that a high-fat diet would increase circulating free fatty acids (FFAs) and decrease the adrenocorticotropic hormone (ACTH) and cortisol response to an acute stressor. We also hypothesized that exercise training would reverse the high-fat diet-induced changes in FFAs and thereby restore the ACTH and cortisol response. Pigs were placed in 1 of 4 groups (normal diet, sedentary; normal diet, exercise training; high-fat diet, sedentary; high-fat diet, exercise training; n = 8/group). Animals were placed on their respective dietary and activity treatments for 16-20 weeks. After completion of the treatments animals were anesthetized and underwent surgical intubation. Blood samples were collected after surgery and the ACTH and cortisol response to surgery was determined and the circulating concentrations of FFAs, glucose, cholesterol, insulin, and IGF-1 were measured. Consistent with our hypothesis, high-fat feeding increased FFAs by 200% and decreased the ACTH stress response by 40%. In exercise-trained animals, the high-fat diet also increased FFA; however, the increase in FFA in exercise-trained pigs was accompanied by a 60% increase in the ACTH response. The divergent effect of high-fat feeding on ACTH response was not expected, as exercise training alone had no effect on the ACTH response. Results demonstrate a significant interaction between diet and exercise and their effect on the ACTH response. The divergent effects of high-fat diet could not be explained by changes in weight gain, blood glucose, insulin, or IGF-1, as these were altered by high-fat feeding, but unaffected by exercise training. Thus, the increase in FFA with high-fat feeding may explain the blunted
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Exercise training alters effect of high-fat feeding on the ACTH stress response in pigs
Jankord, Ryan; Ganjam, Venkataseshu K.; Turk, James R.; Hamilton, Marc T.; Laughlin, M. Harold
2009-01-01
Eating and physical activity behaviors influence neuroendocrine output. The purpose of this study was to test, in an animal model of diet-induced cardiovascular disease, the effects of high-fat feeding and exercise training on hypothalamo–pituitary–adrenocortical (HPA) axis activity. We hypothesized that a high-fat diet would increase circulating free fatty acids (FFAs) and decrease the adrenocorticotropic hormone (ACTH) and cortisol response to an acute stressor. We also hypothesized that exercise training would reverse the high-fat diet-induced changes in FFAs and thereby restore the ACTH and cortisol response. Pigs were placed in 1 of 4 groups (normal diet, sedentary; normal diet, exercise training; high-fat diet, sedentary; high-fat diet, exercise training; n = 8/group). Animals were placed on their respective dietary and activity treatments for 16–20 weeks. After completion of the treatments animals were anesthetized and underwent surgical intubation. Blood samples were collected after surgery and the ACTH and cortisol response to surgery was determined and the circulating concentrations of FFAs, glucose, cholesterol, insulin, and IGF-1 were measured. Consistent with our hypothesis, high-fat feeding increased FFAs by 200% and decreased the ACTH stress response by 40%. In exercise-trained animals, the high-fat diet also increased FFA; however, the increase in FFA in exercise-trained pigs was accompanied by a 60% increase in the ACTH response. The divergent effect of high-fat feeding on ACTH response was not expected, as exercise training alone had no effect on the ACTH response. Results demonstrate a significant interaction between diet and exercise and their effect on the ACTH response. The divergent effects of high-fat diet could not be explained by changes in weight gain, blood glucose, insulin, or IGF-1, as these were altered by high-fat feeding, but unaffected by exercise training. Thus, the increase in FFA with high-fat feeding may explain the
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Sharma, S. T.; Raff, H.
2011-01-01
Context: Anomalous venous drainage can lead to false-negative inferior petrosal sinus sampling (IPSS) results. Baseline inferior petrosal sinus to peripheral (IPS/P) prolactin ratio higher than 1.8 ipsilateral to the highest ACTH ratio has been proposed to verify successful catheterization. Prolactin-normalized ACTH IPS/P ratios may differentiate Cushing's disease (CD) from ectopic ACTH syndrome (EAS). Objective: Our objective was to examine the utility of prolactin measurement during IPSS. Design, Setting, and Participants: We conducted a retrospective analysis of prolactin levels in basal and CRH-stimulated IPSS samples in ACTH-dependent Cushing's syndrome (2007–2010). Results: Twenty-five of 29 patients had a pathologically proven diagnosis (17 CD and eight EAS). IPSS results were partitioned into true positive for CD (n = 16), true negative (n = 7), false negative (n = 1), and false positive (n = 1). Prolactin IPS/P ratio suggested successful IPSS in eight of 11 with abnormal venograms. Baseline prolactin IPS/P ratio was helpful in two patients with abnormal venograms and false-negative (catheterization unsuccessful) or true-negative (catheterization successful) IPSS results; the normalized ratio correctly diagnosed their disease. Normalized ACTH IPS/P ratio was at least 1.3 in all with CD, but prolactin IPS/P ratios were misleadingly low in two. One patient with cyclic EAS had a false-positive IPSS when eucortisolemic (baseline prolactin IPS/P = 1.7; normalized ratio = 5.6). All other EAS patients had normalized ratios no higher than 0.7. Conclusion: Prolactin measurement and evaluation of the venogram can improve diagnostic accuracy when IPSS results suggest EAS but is not necessary with positive IPSS results. Confirmation of hypercortisolemia remains a prerequisite for IPSS. A normalized ratio of 0.7–1.3 was not diagnostic. PMID:22031511
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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.
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Rotllant, David; Ons, Sheila; Carrasco, Javier; Armario, Antonio
2002-08-01
Metyrapone, a 11-beta steroid hydroxylase inhibitor that blocks stress-induced glucocorticoid release, is extensively used to study the physiological and behavioural roles of glucocorticoids. However, there is circumstantial evidence suggesting that metyrapone could act as a pharmacological stressor. Thus, the effects of various doses of metyrapone on two well-characterized stress markers (ACTH and glucose) were studied in male rats. Metyrapone administration, while exerting a modest effect on plasma corticosterone levels, dose-dependently increased plasma ACTH and glucose levels. Using the highest doses previously tested (200 mg/kg) we further observed, as evaluated by fos-like immunoreactivity (FLI), a strong activation of a wide range of brain areas, including the parvocellular region of the hypothalamic paraventricular nucleus (PVNp), the origin of the main ACTH secretagogues. Metyrapone-induced FLI was observed in neocortical and allocortical areas, in several limbic, thalamic and hypothalamic nuclei and, to a lesser extent, in the brainstem. In a final experiment, a dose-response study of metyrapone-induced FLI was carried out focusing on selected brain areas. The study revealed that the paraventricular thalamic nucleus and central amygdala were the areas most sensitive to metyrapone as they responded even to the lowest dose of the drug. Most areas, among them the PVNp, only showed enhanced FLI with the two highest doses, i.e. when it was associated with ACTH and glucose responses. These data suggest that some of the effects of metyrapone could be due to its stressful properties rather than its ability to inhibit glucocorticoid synthesis. The exact mechanisms involved remain to be established.
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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.
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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
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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.
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Crofford, L J; Kalogeras, K T; Mastorakos, G; Magiakou, M A; Wells, J; Kanik, K S; Gold, P W; Chrousos, G P; Wilder, R L
1997-04-01
Systemic symptoms in rheumatoid arthritis (RA) are mediated, at least in part, by elevated levels of circulating interleukin (IL)-6, and this cytokine is also a potent stimulus of the hypothalamic-pituitary-adrenal axis. To evaluate the 24-h circadian secretory dynamics of ACTH, cortisol, and IL-6 and their interactions in patients with early untreated RA, we recruited and studied five newly diagnosed, untreated RA patients early in the course of their disease and five age-, gender-, and race-matched control subjects. We collected serial blood samples over 24 h and measured plasma ACTH and cortisol every 30 min and IL-6 every hour. The 24-h collection was followed by administration of ovine CRH (oCRH) and post-oCRH serial blood samples over 2 h. We analyzed the 24-h overall levels of these hormones and their circadian variations and performed time-lagged cross-correlation analyses among them. The untreated RA patients had 24 h time-integrated plasma ACTH, plasma cortisol levels, and urinary free cortisol excretion that were not significantly different from control subjects, in spite of their disease activity. However, an earlier morning surge of plasma ACTH and cortisol in the patients was suggested. Plasma ACTH and cortisol responses to oCRH were similar in RA patients and controls. IL-6 levels were significantly increased in the RA patients compared with control subjects during the early morning hours (P < 0.05). There was pronounced circadian variation of plasma Il-6 levels. In the RA patients, we detected a positive temporal correlation between plasma levels of IL-6 and ACTH/cortisol, with elevated levels of IL-6 before the elevations of ACTH and cortisol by 1 and 2 h, respectively. In the same patients, we detected a negative effect of cortisol upon IL-6 exerted with a delay of 5 h. The data presented here suggest that although endogenous IL-6 may stimulate secretion of ACTH and cortisol, overall activity of the hypothalamic-pituitary-adrenal axis remains
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Calis, M; Gökçe, C; Ates, F; Ulker, S; Izgi, H B; Demir, H; Kirnap, M; Sofuoglu, S; Durak, A C; Tutus, A; Kelestimur, F
2004-01-01
Primary fibromyalgia syndrome (PFS) is characterized by widespread chronic pain that affects the musculoskeletal system, fatigue, anxiety, sleep disturbance, headache and postural hypotension. The pathophysiology of PFS is unknown. The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in PFS. Both hyperactivity and hypoactivity of the HPA axis have been reported in patients with PFS. In this study we assessed the HPA axis by 1 microg ACTH stimulation test and metyrapone test in 22 patients with PFS and in 15 age-, sex-, and body mass index (BMI)- matched controls. Metyrapone (30 mg/kg) was administered orally at 23:00 h and blood was sampled at 08:30 h the following morning for 11-deoxycortisol. ACTH stimulation test was carried out by using 1 microg (iv) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. Peak cortisol level (659.4 +/- 207.2 nmol/l) was lower in the patients with PFS than peak cortisol level (838.7 +/- 129.6 nmol/l) in the control subjects (p < 0.05). Ten patients (45%) with PFS had peak cortisol responses to 1 microg ACTH test lower than the lowest peak cortisol detected in healthy controls. After metyrapone test 11-deoxycortisol level was 123.7 +/- 26 nmol/l in patients with PFS and 184.2 +/- 17.3 nmol/l in the controls (p < 0.05). Ninety five percent of the patients with PFS had lower 11-deoxycortisol level after metyrapone than the lowest 11-deoxycortisol level after metyrapone detected in healthy controls. We also compared the adrenal size of the patients with that of the healthy subjects and we found that the adrenal size between the groups was similar. This study clearly shows that HPA axis is underactivated in PFS, rather than overactivated.
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Oda, Naohiro; Miyahara, Nobuaki; Tabata, Masahiro; Minami, Daisuke; Ninomiya, Kiichiro; Kanehiro, Arihiko; Komatsubara, Motoshi; Inagaki, Kenichi; Tanimoto, Mitsune; Kiura, Katsuyuki
2017-01-01
We herein report the case of a 44-year-old man who was diagnosed with pneumocystis pneumonia (PCP) concomitant with ectopic adrenocorticotropic hormone (ACTH) syndrome, which had been caused by a large cell neuroendocrine carcinoma of the thymus. Chest computed tomography revealed ground-glass opacities in the lungs. PCP was diagnosed by a polymerase chain reaction with bronchoalveolar lavage. The levels of cortisol were slowly corrected with an adrenal enzyme inhibitor, and the exacerbation of PCP was successfully avoided. Our case indicates that in addition to prophylaxis, the early diagnosis of PCP and the slow correction of hypercortisolemia should be considered in order to prevent an exacerbation due to the reconstitution of the immune function in patients with ectopic ACTH syndrome.
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Gan, Earn H; MacArthur, Katie; Mitchell, Anna L; Hughes, Beverly A; Perros, Petros; Ball, Stephen G; James, R Andrew; Quinton, Richard; Chen, Shu; Furmaniak, Jadwiga; Arlt, Wiebke; Pearce, Simon H S
2014-01-01
Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease. Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. The intervention included a 20-week study of regular sc tetracosactide (ACTH1-24) therapy. Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement. This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.
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Castinetti, F; Morange, I; Dufour, H; Jaquet, P; Conte-Devolx, B; Girard, N; Brue, T
2007-09-01
Corticotropin-releasing hormone (CRH)-stimulated petrosal sinus sampling is currently the gold standard method for the differential diagnosis between pituitary and ectopic ACTH-dependent Cushing's syndrome. Our objective was to determine sensitivity and specificity of desmopressin test during petrosal sinus sampling. Forty-three patients had petrosal sinus sampling because of the lack of visible adenoma on magnetic resonance imaging (MRI) and/or because of discordant cortisol response to high-dose dexamethasone suppression test. ACTH sampling was performed in an antecubital vein, right and left petrosal sinuses, then at each location 5 and 10 min after injection of desmopressin. Diagnosis was based on the ACTH ratio between petrosal sinus and humeral vein ACTH after desmopressin test. Diagnosis was confirmed after surgery. A receiver operating characteristics curve was used to determine optimal sensitivity and specificity. Thirty-six patients had Cushing's disease (CD) and seven had ectopic ACTH secretion. A ratio > 2 after desmopressin was found in 35 of the 36 cases of CD (sensitivity: 95%). A ratio < or = 2 was found in the seven patients with ectopic ACTH secretion (specificity: 100%). Sinus sampling was ineffective in determining the left or right localization of the adenoma (sensitivity = 50%). No major adverse effects were observed during or after the procedure. Desmopressin test during petrosal sinus sampling is a safe and effective diagnostic procedure in ACTH-dependent Cushing's syndrome. It thus represents a valuable alternative to CRH.
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Botticelli, G; Bacchi Modena, A; Bresciani, D; Villa, P; Aguzzoli, L; Florio, P; Nappi, R E; Petraglia, F; Genazzani, A R
1992-12-01
The effect of an acute physical stress on hormone secretions before and after a 10-day naltrexone treatment in untrained healthy and amenorrheic women was investigated. Plasma levels of pituitary (LH, FSH, prolactin, GH, ACTH, beta-endorphin) and adrenal (cortisol, androstenedione, testosterone) hormones were measured at rest and in response to 60 min of physical exercise. The test was done both before and after a 10-day naltrexone (50 mg/day) treatment. Graded levels of treadmill exercise (50, 70 and 90% of maximal oxygen uptake (VO2) every 20 min) was used as physical stressor. While mean +/- SE plasma LH levels in control women were higher than in amenorrheic patients and increased following the naltrexone treatment (p < 0.01), no significant differences of basal plasma hormonal levels were observed between amenorrheic and eumenorrheic women, both before and after naltrexone treatment. Physical exercise at 90% VO2 induced a significant increase in plasma GH, ACTH, beta-endorphin, cortisol, androstenedione and testosterone levels in controls before naltrexone treatment (p < 0.01). The mean increase in plasma androstenedione and testosterone levels in control women was significantly higher after naltrexone treatment (p < 0.01). In amenorrheic patients before naltrexone, physical exercise induced an increase in plasma prolactin and GH levels, but not in plasma ACTH, beta-endorphin, cortisol, testosterone and androstenedione. After naltrexone treatment, the exercise induced a significant plasma ACTH, beta-endorphin and cortisol levels, while the increase of plasma prolactin levels was significantly higher than before treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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Allolio, B; Hoffmann, J; Linton, E A; Winkelmann, W; Kusche, M; Schulte, H M
1990-08-01
The circadian rhythm of salivary cortisol was studied in 10 healthy women every 4 weeks throughout pregnancy. In addition, in 12 women the diurnal patterns of salivary cortisol, serum cortisol, plasma ACTH, plasma CRH and serum progesterone were analysed in late third trimester pregnancy and again 3-5 days after delivery. Salivary cortisol profiles exhibited a clear circadian rhythm during pregnancy with an increase in mean salivary cortisol from the 25th to 28th week onwards reaching concentrations in late pregnancy more than twice as high as in non-pregnant controls, rapidly returning to normal concentrations after delivery. The coefficient of variation of salivary cortisol profiles decreased in third trimester pregnancy due to a parallel upward shift of cortisol concentrations (40.2 +/- 3.4% vs 77.6 +/- 6.6% after delivery, P less than 0.01). A diurnal pattern was also found for plasma ACTH and serum cortisol before and after delivery with lower concentrations post-partum (P less than 0.01). In late pregnancy, progesterone concentrations were significantly higher in the evening (930 +/- 85 nmol/l vs 813 +/- 74 nmol/l at 0900 h, P less than 0.01) but showed no diurnal variation post-partum. Plasma CRH was significantly elevated in late third trimester pregnancy (1.22 +/- 0.23 micrograms/l at 0900 h) but showed no diurnal change (1.30 +/- 0.28 micrograms/l at 1900 h). Moreover, no correlation between the free cortisol increase in late pregnancy and plasma CRH was noted despite a wide range of CRH levels (0.13-3.60 micrograms/l). In contrast, a significant correlation was observed between the serum progesterone increase and the salivary cortisol increase in late pregnancy (r = 0.70, P less than 0.05). These findings demonstrate that placental CRH is not the only regulator of maternal ACTH and cortisol release. Instead, our study suggests that placental CRH has little influence on baseline maternal adrenocortical function in pregnancy. The elevated salivary cortisol
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ACTH has beneficial effects on stuttering in ADHD and ASD patients with ESES: A retrospective study.
Altunel, Attila; Sever, Ali; Altunel, Emine Özlem
2017-02-01
Etiology of stuttering remains unknown and no pharmacologic intervention has been approved for treatment. We aimed to evaluate EEG parameters and the effect of adrenocorticotropic hormone (ACTH) therapy in stuttering. In this retrospective study, 25 patients with attention deficit and hyperactivity (ADHD) or autism spectrum disorder (ASD), and comorbid stuttering were followed and treated with ACTH for electrical status epilepticus in sleep (ESES). Sleep EEGs were recorded at referral and follow-up visits and short courses of ACTH were administered when spike-wave index (SWI) was ⩾15%. The assessment of treatment effectiveness was based on reduction in SWI, and the clinician-reported improvement in stuttering, and ADHD or ASD. Statistical analyses were conducted in order to investigate the relationship between the clinical and EEG parameters. Following treatment with ACTH, a reduction in SWI in all the patients was accompanied by a 72% improvement in ADHD or ASD, and 83.8% improvement in stuttering. Twelve of the 25 patients with stuttering showed complete treatment response. Linear regressions established that SWI at final visit significantly predicted improvement in ADHD or ASD, and in stuttering. If symptoms had recurred, improvement was once again achieved with repeated ACTH therapies. Stuttering always improved prior to, and recurred following ADHD or ASD. The underlying etiology leading to ESES may play a significant role in the pathophysiology of stuttering and connect stuttering to other developmental disorders. ACTH therapy has beneficial effects on stuttering and improves EEG parameters. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
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Tirosh, Amit; Lodish, Maya B; Lyssikatos, Charalampos; Belyavskaya, Elena; Papadakis, Georgios Z; Stratakis, Constantine A
2017-01-01
The utility of circadian cortisol variation in estimating the degree of hypercortisolemia in different forms of endogenous Cushing syndrome (CS) has not been evaluated in children yet. A retrospective cohort study, including children who underwent surgery due to CS (n = 115), was divided into children with a pituitary adenoma (Cushing disease) (n = 88), primary adrenal CS (n = 21), or ectopic adrenocorticotropin- or corticotropin-releasing hormone (ACTH-/CRH)-secreting tumors (n = 6). Circadian plasma cortisol measurements were obtained at 11: 30 p.m. and at midnight, and at 7: 30 and 8: 00 a.m. The ratios between the morning and late-night concentrations were calculated. Plasma cortisol early-morning and midnight (AM/PM) ratios negatively correlated with 24-h urinary free cortisol (UFC) collections among the full study population and in each of the individual etiologies. Plasma ACTH concentrations positively correlated with plasma cortisol AM/PM ratios among patients with ACTH-independent CS. Finally, patients with primary pigmented nodular adrenocortical disease showed no correlation between UFC collections and the plasma cortisol AM/PM ratio, in contrast with other etiologies for primary adrenal CS, which showed a strong negative correlation between them. Our study shows the association between the plasma cortisol AM/PM ratio and the degree of hypercortisolemia in children with CS. © 2017 S. Karger AG, Basel.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Sarma, Asha, E-mail: ashasarma@gmail.com; Shyn, Paul B., E-mail: pshyn@partners.org; Vivian, Mark A.
Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.
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Scheidegger, M D; Gerber, V; Bruckmaier, R M; van der Kolk, J H; Burger, D; Ramseyer, A
2017-10-01
This study tested the hypothesis that adrenocortical function would be altered in horses with equine gastric ulcer syndrome (EGUS). Twenty-six sport horses competing at national or international levels in eventing (n=15) or endurance (n=11) were subjected to a gastroscopic examination and an adrenocorticotropic hormone (ACTH) stimulation test. Salivary cortisol concentrations were measured before (baseline) and after (30, 60, 90, 120 and 150min) IV ACTH injection (1μg/kg bodyweight). Within EGUS, two distinct diseases, equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD), can be distinguished. ESGD was diagnosed in 8/11 (73%; 95% confidence intervals [95%CI], 43-92%) endurance horses and 5/15 (33%; 95% CI, 14-58%) eventing horses. EGGD was observed in 9/11 (82%; 95% CI, 53-96%) endurance horses and 9/15 (60%; 95% CI, 35-81%) eventing horses. The presence or severity of ESGD was unrelated to the presence or severity of EGGD. ACTH stimulation induced a larger increase in cortisol concentration in horses with moderate EGGD than in horses with mild EGGD. Cortisol concentration during the entire sampling period (total increase in cortisol concentration during the entire sampling period [dAUC], 31.1±6.4ng/mL) and the highest measured concentration at a single time point (maximal increase in cortisol concentration [dMAX], 10.3±2.3ng/mL) were increased (P=0.005 and P=0.038, respectively), indicating that horses with glandular gastric disease exhibited increased adrenocortical responses to ACTH stimulation. These results suggest that EGGD might be associated with an enhanced adrenocortical sensitivity. Further investigations are warranted to confirm the association between adrenocortical sensitivity and EGGD and to elucidate the pathophysiological mechanisms involved. Copyright © 2017 Elsevier Ltd. All rights reserved.
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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.
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Muscle transcriptome response to ACTH administration in a free-ranging marine mammal
Champagne, Cory D.; Preeyanon, Likit; Ortiz, Rudy M.; Crocker, Daniel E.
2015-01-01
While much of our understanding of stress physiology is derived from biomedical studies, little is known about the downstream molecular consequences of adaptive stress responses in free-living animals. We examined molecular effectors of the stress hormones cortisol and aldosterone in the northern elephant seal, a free-ranging study system in which extreme physiological challenges and cortisol fluctuations are a routine part of life history. We stimulated the neuroendocrine stress axis by administering exogenous adrenocorticotropic hormone (ACTH) and examined the resultant effects by measuring corticosteroid hormones, metabolites, and gene expression before, during, and following administration. ACTH induced an elevation in cortisol, aldosterone, glucose, and fatty acids within 2 h, with complete recovery observed within 24 h of administration. The global transcriptional response of elephant seal muscle tissue to ACTH was evaluated by transcriptomics and involved upregulation of a highly coordinated network of conserved glucocorticoid (GC) target genes predicted to promote metabolic substrate availability without causing deleterious effects seen in laboratory animals. Transcriptional recovery from ACTH was characterized by downregulation of GC target genes and restoration of cell proliferation, metabolism, and tissue maintenance pathways within 24 h. Differentially expressed genes included several adipokines not previously described in muscle, reflecting unique metabolic physiology in fasting-adapted animals. This study represents one of the first transcriptome analyses of cellular responses to hypothalamic-pituitary-adrenal axis stimulation in a free-living marine mammal and suggests that compensatory, tissue-sparing mechanisms may enable marine mammals to maintain cortisol and aldosterone sensitivity while avoiding deleterious long-term consequences of stress. PMID:26038394
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Kobayashi, Hiroki; Haketa, Akira; Takahiro, Ueno; Otsuka, Hiromasa; Tanaka, Sho; Hatanaka, Yoshinari; Ikeda, Yukihiro; Abe, Masanori; Fukuda, Noboru; Soma, Masayoshi
2017-03-01
Although plasma aldosterone concentration (PAC) varies depending on primary aldosteronism (PA) subtypes, patients with different subtypes may have similar blood pressure (BP). The authors hypothesized that hormones other than aldosterone might influence BP in PA patients. A total of 73 PA cases, including 30 cases of aldosterone-producing adenomas (APAs), 29 cases of bilateral hyperaldosteronism, and 24 control cases of essential hypertension were enrolled retrospectively. The authors examined the levels of aldosterone, cortisol, renin, and adrenocorticotropic hormone (ACTH) measured at 12 am, 6 am, 12 pm, and 6 pm and BP in the early morning (6 am to 7 am), late morning (9 am to 11 am), and early evening (5 pm to 7 pm). Results showed no statistically significant correlation between PAC and BP in the patients with PA; however, early and late morning systolic BP strongly correlated with ACTH at 6 am in patients with APA. These results suggest that hormones other than aldosterone, such as ACTH, may affect BP in patients with APA. ©2016 Wiley Periodicals, Inc.
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MacKenzie, Scott M; Freel, E Marie; Connell, John M; Fraser, Robert; Davies, Eleanor
2017-03-07
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.
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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 Chemistry...
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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 Chemistry...
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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 Chemistry...
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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 Chemistry...
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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 Chemistry...
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Lee, Ellen E.; Nieman, Lynnette K.; Martinez, Pedro E.; Harsh, Veronica L.; Rubinow, David R.
2012-01-01
Context: During conditions of ovarian suppression, women with premenstrual dysphoria (PMD) experience abnormal behavioral responses to physiological levels of ovarian steroids. Although hypothalamic-pituitary-adrenal (HPA) axis dysregulation frequently accompanies depression, and ovarian steroids regulate HPA axis responsivity, the role of HPA axis dysregulation in PMD is not known. We hypothesized that women with PMD would show abnormalities of HPA axis function analogous to those reported in depressive illness, and that ovarian steroids would differentially regulate HPA axis function in women with PMD compared with asymptomatic controls (AC). Objective: Our objective was to characterize the HPA axis response to physiological levels of estradiol and progesterone in women with PMD and AC. Design and Setting: We conducted an open-label trial of the GnRH agonist depot Lupron with ovarian steroid replacement administered in a double-blind crossover design in an outpatient clinic. Participants: Forty-three women (18 with prospectively confirmed PMD and 25 AC) participated. Interventions: Women received Lupron for 6 months. After 3 months of hypogonadism, women received 5 wk each of estradiol (100-μg patch daily) or progesterone (suppositories 200 mg twice daily). During each condition, combined dexamethasone-suppression/CRH-stimulation tests and 24-h urinary free cortisol levels were performed. Main Outcome Measures: Plasma cortisol and ACTH levels were evaluated. Results: HPA axis function was similar in PMD compared with AC. In all, progesterone significantly increased the secretion of cortisol compared with estradiol [area under the curve (t74 = 3.1; P < 0.01)] and urinary free cortisol (t74 = 3.2; P < 0.01) and ACTH compared with hypogonadism [area under the curve (t74 = 2.4; P < 0.05)]. Conclusions: HPA axis regulation is normal in PMD, suggesting that the pathophysiology of PMD differs from major depression. As observed previously, progesterone but not estradiol
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Ekman, Bertil; Bachrach-Lindström, Margareta; Lindström, Torbjörn; Wahlberg, Jeanette; Blomgren, Johan; Arnqvist, Hans J
2012-07-01
Current guidelines on how to divide the daily cortisol substitution dose in patients with primary adrenal insufficiency (PAI) are controversial and mainly based on empirical data. To assess how an equal dose of hydrocortisone (HC) given either four times daily or twice daily influence diurnal profiles of cortisol and ACTH, patient preferences and health-related quality of life (HRQoL). Double blind, crossover. Fifteen patients with PAI (six women) were included. Capsules of HC or placebo were given at 07:00, 12:00, 16:00 and 22:00 h in 4-week treatment periods: either one period with four doses (10 + 10 + 5 + 5 mg) or one period with two doses (20 + 0 + 10 + 0 mg). Diurnal profiles of cortisol and ACTH were collected, and area under the curve (AUC) was calculated. Questionnaires were used to evaluate patient preferences and HRQoL. The four-dose regimen gave a higher serum cortisol before tablet intake in the morning (P = 0·027) and a higher 24-h cortisol(AUC) (P < 0·0001) compared with the two-dose period. In contrast, a lower median plasma ACTH in the morning before tablet intake (P = 0·003) and a lower 24-h ln(ACTH(AUC) ) were found during the four-dose period. The patients preferred the four-dose regimen (P = 0·03), and the HRQoL scores tended to be higher (high score indicates better HRQoL) for the four-dose period. In summary, a four-dose regimen gives increased availability of cortisol and an enhanced effect with a less elevated ACTH in the morning in comparison with a two-dose regimen but the effect on HRQoL remains inconclusive. © 2012 Blackwell Publishing Ltd.
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[The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome].
Cui, Jia; Dou, Jingtao; Yang, Guoqing; Zang, Li; Jin, Nan; Chen, Kang; Du, Jin; Gu, Weijun; Wang, Xianling; Yang, Lijuan; Lyu, Zhaohui; Ba, Jianming; Mu, Yiming; Lu, Juming; Li, Jiangyuan; Pan, Changyu
2015-07-01
Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid. As a consequence, long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects. The present study was to analyze the changes of renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test. We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014. Among them, 128 patients were diagnosed as adreno-cortico-tropic-hormone (ACTH)-independent Cushing's syndrome, and 22 were ACTH-dependent Cushing's syndrome. All patients were undertaken the posture test. Plasma renin activity (PRA), angiotensin II, plasma aldosterone concertration (PAC) levels were measured before and after the test. Basal plasma PRA [0.5 (0.2,1.3)µg·L(-1)·h(-1), angiotensin II [(48.9±20.1) ng/L] and PAC [(285.0±128.1) pmol/L] levels were within the normal range in supine position. Compared with the subjects with ACTH-independent Cushing's syndrome, the basal PAC levels were higher in subjects with ACTH-dependent Cushing's syndrome [(348.0±130.4) pmol/L vs (274.2±125.0) pmol/L, P<0.05]. However, the PAC response in subjects with ACTH-dependent Cushing's syndrome [(49.7±26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2±69.3)%] upon upright posture stimulation (P<0.05). There were no statistical significances in PRA and angiotensin II levels between the two groups. The basal PAC and PRA levels were positively correlated with ACTH, whereas PAC response was negatively correlated with ACTH. The renin-angiotensin-aldosterone-system activity in subjects with Cushing's syndrome was similar to that in normal control. The basal PAC level and its response to upright posture are differently associated with ACTH level in Cushing's syndrome.
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Branconnier, R J; Cole, J O; Gardos, G
1979-03-22
Eighteen male and female volunteers over the age of sixty who exhibited mild senile organic brain syndrome were administered ACTH 4-10 (Org OI 63) (30 mg, s.c.) or saline in a 2 X 2 Latin square design. Subjects experienced a reduction in depression and confusion and an increase in vigor. This evidence of an increase in vigor was supported behaviorally by a delay in the onset of increased latency in reaction time. Data also indicated that retrieval from memory may be enhanced by this compound. The electroencephalogram evinced a shift to lower frequencies under ACTH 4-10, but this effect was primarily noted in the females who received drug followed by placebo. These effects of ACTH 4-10 are intriguing and suggest that further work in this area should be encouraged.
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Bosch, Oliver G; Eisenegger, Christoph; Gertsch, Jürg; von Rotz, Robin; Dornbierer, Dario; Gachet, M Salomé; Heinrichs, Markus; Wetter, Thomas C; Seifritz, Erich; Quednow, Boris B
2015-12-01
Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist. Reports from GHB abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We measured the effects of GHB on mood, prosocial behavior, social and non-social cognition and assessed potential underlying neuroendocrine mechanisms. GHB (20mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed by visual-analogue-scales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the Charity Donation Task, the Social Value Orientation test, and the Reciprocity Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood plasma levels of GHB, oxytocin, testosterone, progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropic-hormone (ACTH) were determined. GHB showed stimulating and sedating effects, and elicited euphoria, disinhibition, and enhanced vitality. In participants with low prosociality, the drug increased donations and prosocial money distributions. In contrast, social cognitive abilities such as emotion recognition, empathy, and theory-of-mind, and basal cognitive functions were not affected. GHB increased plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone, DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial effects without affecting social hormones such as oxytocin and testosterone. These data suggest a potential involvement of GHB-/GABAB-receptors and progesterone in mood and prosocial behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Wheatland, R
2005-01-01
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a commonly recognized feature of many pathological conditions. Abnormal adrenal responses to experimental manipulation have been well documented in patients suffering from chronic fatigue syndrome, anorexia nervosa and major depression. Yet no defect of any single organ, gland or brain region has been identified as a cause of these abnormalities. The disruption of the HPA axis that occurs in these conditions can be understood if an interfering factor is present in these patients. Evidence indicates that this interfering factor is adrenocorticotropin hormone (ACTH) autoantibodies. Chronic high levels of ACTH autoantibodies will significantly disrupt the HPA axis and force the body to compensate for an impaired cortisol response. The resulting effect of chronic ACTH autoantibody interference is the manifestation of adrenocortical insufficient symptoms and psychological disturbances. Some symptoms of chronic fatigue syndrome, anorexia nervosa and major depression, such as anxiety, are the adverse effects of mechanisms compensating for less effective ACTH due to autoantibodies. Furthermore, these patients engage in extraordinary behaviors, such as self-injury, to increase their cortisol levels. When this compensation is inadequate, symptoms of adrenocortical insufficiency appear. Corticosteroid supplements have been demonstrated to be an effective treatment for chronic fatigue syndrome, anorexia nervosa and major depression. It allows the patients to have the corticosteroids they require for daily functioning and daily stressors. This therapy will relieve the patients of their symptoms of adrenocortical insufficiency and permit their cortisol-stimulating mechanisms to operate at levels that will not cause pathological problems.
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Langlois, Daniel K; Fritz, Michele C; Schall, William D; Bari Olivier, N; Smedley, Rebecca C; Pearson, Paul G; Bailie, Marc B; Hunt, Stephen W
2018-05-02
Cushing's syndrome in humans shares many similarities with its counterpart in dogs in terms of etiology (pituitary versus adrenal causes), clinical signs, and pathophysiologic sequelae. In both species, treatment of pituitary- and adrenal-dependent disease is met with limitations. ATR-101, a selective inhibitor of ACAT1 (acyl coenzyme A:cholesterol acyltransferase 1), is a novel small molecule therapeutic currently in clinical development for the treatment of adrenocortical carcinoma, congenital adrenal hyperplasia, and Cushing's syndrome in humans. Previous studies in healthy dogs have shown that ATR-101 treatment led to rapid, dose-dependent decreases in adrenocorticotropic hormone (ACTH) stimulated cortisol levels. The purpose of this clinical study was to investigate the effects of ATR-101 in dogs with Cushing's syndrome. ATR-101 pharmacokinetics and activity were assessed in 10 dogs with naturally-occurring Cushing's syndrome, including 7 dogs with pituitary-dependent disease and 3 dogs with adrenal-dependent disease. ATR-101 was administered at 3 mg/kg PO once daily for one week, followed by 30 mg/kg PO once daily for one (n = 4) or three (n = 6) weeks. Clinical, biochemical, adrenal hormonal, and pharmacokinetic data were obtained weekly for study duration. ATR-101 exposure increased with increasing dose. ACTH-stimulated cortisol concentrations, the primary endpoint for the study, were significantly decreased with responders (9 of 10 dogs) experiencing a mean ± standard deviation reduction in cortisol levels of 50 ± 17% at study completion. Decreases in pre-ACTH-stimulated cortisol concentrations were observed in some dogs although overall changes in pre-ACTH cortisol concentrations were not significant. The compound was well-tolerated and no serious drug-related adverse effects were reported. This study highlights the potential utility of naturally occurring canine Cushing's syndrome as a model for human disease and provides proof of
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Kim, Y; McGee, S; Czeczor, J K; Walker, A J; Kale, R P; Kouzani, A Z; Walder, K; Berk, M; Tye, S J
2016-01-01
Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg−1) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 μA, 90 μS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST (P<0.05). NAc DBS effectively improved FST mobility in ACTH-treated animals (P<0.05). No improvement in mobility was observed for sham control animals (P>0.05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation. PMID:27327257
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Simforoosh, Nasser; Razzaghy Azar, Maryam; Soltani, Mohmmad Hossein; Nourbakhsh, Mona; Shemshaki, Hamidreza
2017-08-29
ACTH-independent Cushing's syndrome is an uncommon disorder in children. While laparoscopic adrenalectomy is well-established in adults, it is rarely used in infants and is associated with some concerns. A seven-month infant was referred to our hospital due to progressive signs and symptoms of Cushing's syndrome. Laboratory data confirmed ACTH-independent hypercortisolism. No history of exogenous corticosteroid contact was observed. The patient underwent left transperitoneal laparoscopic adrenalectomy when she was 7 months old, nevertheless,complete response was not seen. The patient underwent right laparoscopic adrenalectomy (contra-lateral adrenal gland) when she was 20 months old. The signs and symptoms of Cushing's syndrome began to resolve and serum and urine cortisol levels became normal 3 months after the second surgery. laparoscopic adrenalectomy is safe and feasible in infants, and in this case, relieved patient of the symptoms and saved her life.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Tsigos, C.; Arai, K.; Latronico, A.C.
1995-07-01
Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by primary adrenocortical insufficiency, usually without mineralocorticoid deficiency. Occasionally, the disorder is associated with alacrima and achalasia of the esophagus (triple A syndrome), suggesting potential heterogeneity in its etiology. Mutations in the ACTH receptor gene have been reported in several families with IGD. We have amplified and directly sequenced the entire intronless ACTH receptor gene in 1 other family with IGD and 2 famlies with triple A syndrome. The proband with IGD was a homozygote for an A {r_arrow}G substitution, changing tyrosine 254 to cysteine in the third extracellular loopmore » of the receptor protein, probably interfering with ligand binding. Both of her parents were heterozygotes for this mutation, which was not detected in 100 normal alleles. No mutations were identified in the entire coding area of the ACTH receptor in the 2 families with triple A syndrome, supporting the idea of a developmental or postreceptor defect in this syndrome. 19 refs., 1 fig.« less
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Alsaleem, Mahdi; Saadeh, Lina; Misra, Amrit; Madani, Shailender
2016-08-17
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. 2016 BMJ Publishing Group Ltd.
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Takahashi, L K; Kalin, N H
1991-08-30
Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.
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Corticotropin-releasing hormone testing in pituitary disease.
Loriaux, D L; Nieman, L
1991-06-01
The availability of CRH for clinical use and the data so far generated by clinical investigators interested in its application to the problem of Cushing's syndrome have resulted in a new approach to the differential diagnosis of Cushing's syndrome (Fig. 2). Once the diagnosis of Cushing's syndrome is made with certainty, an initial separation into ACTH-dependent versus ACTH-independent categories is made on the basis of the plasma ACTH response to CRH. Plasma ACTH levels in excess of 10 pg/mL imply an ACTH-dependent process. Patients with an ACTH-dependent process are then divided into eutopic versus ectopic sources on the basis of the central to peripheral gradient of ACTH measured in the inferior petrosal sinuses simultaneously 3 to 5 minutes after the administration of CRH, 1 microgram/kg. The average post-CRH gradient in patients with eutopic ACTH-dependent Cushing's syndrome is 50. The lower bound is 3.3. Ectopic sources have a gradient of less than 2. Patients with ACTH-independent Cushing's syndrome can be confidently evaluated with imaging techniques, such as CT or MRI, looking for adrenal neoplasm or the "normal to small" glands characteristic of micronodular adrenal dysplasia.
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Maniu, Adina; Aberdeen, Graham; Lynch, Terrie J.; Albrecht, Eugene D.
2016-01-01
We showed that the volume of the fetal zone of the fetal adrenal gland and serum dehydroepiandrosterone sulfate (DHAS) levels at term were increased in baboons in which estradiol levels were suppressed by treatment with aromatase inhibitor 4,4-[1,2,3-triazol-1yl-methylene] bis-benzonitrite (letrozole). The fetal zone remodels postnatally into the reticular zone and DHAS production, and serum levels decline with age. Therefore, we determined whether the trajectory of reticular zone DHAS secretion and response to ACTH were altered in offspring deprived of estrogen in utero. Female offspring were delivered to baboons untreated or treated daily throughout the second half of gestation with letrozole (estradiol reduced >95%) or letrozole plus estradiol and cortisol and DHAS determined in blood samples obtained bimonthly between 4 and 125 months and after iv bolus of ACTH. The slope/rate of decline in serum DHAS with advancing age was greater (P < .01) in letrozole-treated (−0.54 ± 0.005) than untreated (−0.32 ± 0.003) baboons and partially restored by letrozole-estradiol (−0.43 ± 0.004). Serum cortisol was similar and relatively constant in all offspring. Moreover, in letrozole-treated offspring, serum DHAS at 61–66, 67–95, and 96–125 months were lower (P < .05), and cortisol to DHAS ratio was greater (P < .05) than in untreated offspring. ACTH at high level increased cortisol and DHAS in untreated baboons and cortisol but not DHAS in letrozole-treated offspring. We propose that postnatal development of the primate adrenal cortex, including the decline in reticular zone DHAS production, response to ACTH and maintenance of cortisol to DHAS ratio with advancing age is modulated by exposure of the fetal adrenal to estradiol. PMID:26990066
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Parotid fluid cortisol and cortisone
Katz, Fred H.; Shannon, Ira L.
1969-01-01
Parotid fluid corticosteroids, substantially comprised of cortisol and cortisone, were previously demonstrated to rise to far greater levels 4 hr after administration of ACTH than they did in the third trimester of pregnancy, although the plasma total corticosteroid concentrations were similar in these two states. It was therefore suggested that only nonproteinbound corticosteroid gains access to parotid fluid. In the present study parotid fluid cortisol and cortisone and plasma dialyzable cortisol concentrations have been measured in normal men before and 2 hr after 40 U ACTH, and, in another group, before and after 10 days of diethystilbestrol (5 mg daily). Total plasma cortisol rose from a mean of 6.3 to 17.9 μg/100 ml after ACTH and from 14.6 to 39.4 mg/100 ml after the estrogen. However parotid fluid cortisol plus cortisone rose from 0.8 to 2.6 μg/100 ml after ACTH and to only 2.2 after estrogen. This rise resembled that of the plasma dialyzable cortisol (control 0.4, ACTH 1.8, estrogen 1.2 μg/100 ml) rather than the increase in total plasma cortisol which was over twice as high after estrogen as after ACTH. Thus parotid fluid corticosteroids seem to be a good measure of nonprotein-bound corticosteroid, the cortisol available to the cell. The total amount of cortisol plus cortisone excreted is approximately constant, independent of parotid fluid flow rate. Cortisone exceeds cortisol in parotid fluid in the basal state, but after ACTH the situation is reversed. PMID:4305375
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Rees, D A; Hepburn, P J; McNicol, A M; Francis, K; Jasani, B; Lewis, M D; Farrell, W E; Lewis, B M; Scanlon, M F; Ham, J
2002-03-28
The proopiomelanocortin (POMC) gene is highly expressed in the pituitary gland where the resulting mRNA of 1200 base pairs (bp) gives rise to a full-length protein sequence. In peripheral tissues however both shorter and longer POMC variants have been described, these include for example placental tissue which contain 800 (truncated at the 5' end) and 1500 as well as the 1200 bp transcripts. The importance of the 800 bp transcript is unclear as the lack of a signal sequence renders the molecule to be non-functional. This transcript has not been previously demonstrated in the pituitary gland. In this report we show evidence of a 5' truncated POMC gene in human pituitary corticotroph macroadenoma cells (JE) maintained in primary culture for >1 year. The original tumour tissue and the derived cells during early passage (up to passage 4-5) immunostained for ACTH and in situ hybridisation confirmed the presence of the POMC gene in the cultured cells. These cells also secreted 15-40 pg/10(5) cells/24 h ACTH. In addition, as expected RT-PCR demonstrated the presence of all three POMC gene exons and is thus indicative of a full-length POMC gene. In late culture passages (passages 8-15) JE cells ceased to express ACTH and cell growth became very slow due presumably to cells reaching their Hayflick limit. ACTH immunostaining in these cells was undetectable and ACTH secretion was also at the detection limits of the assay and no greater than 10 pg/10(5) cells/24 h. ACTH precursor molecules were also undetectable. RT-PCR for the POMC gene in these late passage cells showed that only exon 3 was detectable, in contrast to early passage cells where all three exons were present. In summary we isolated in culture, human pituitary cells that possessed initially all three exons of the POMC gene and immunostained for ACTH. On further passaging these cells showed a loss of exons 1 and 2 in the POMC gene and a loss of ACTH immunostaining and secretion. We would like to suggest that the
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Zhang, Weiwei; Yu, Yerong; Tan, Huiwen; Wang, Chun; Li, Jianwei; An, Zhenmei; Liu, Yuping
2016-03-22
To investigate the value of desmopressin (DDAVP) stimulation test and high dose dexamethasone suppression test (HDDST) in establishing the cause of ACTH dependent Cushing's syndrome. The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard. A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively. The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test. When the two tests had consistent results, the diagnostic accordance rate was 100%. DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.
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Takahashi, L K; Kim, H
1995-04-01
Recent investigations revealed that adrenalectomized (ADX) rat pups exhibit deficits in behavioral inhibition. Furthermore, administration of exogenous corticosterone (CORT) restores behavioral inhibition in ADX pups. Although these studies suggest that CORT has an important role in the development of behavioral inhibition, the relative behavioral effects of elevated pituitary hormone secretion induced by ADX are not known. Therefore, experiments were conducted to assess the potential behavioral effects of elevated adrenocorticotropin (ACTH) secretion induced by ADX and to further evaluate the contribution of endogenous CORT to the development of behavioral inhibition. In Experiment 1., we verified that 10-day-old ADX rats exhibit high levels of plasma ACTH throughout the preweaning period associated with the development of behavioral inhibition. In Experiment 2, 10-day-old pups were hypophysectomized (HYPOX) and ADX and were compared behaviorally to sham-operated controls on day 14. When tested in the presence of an anesthetized unfamiliar adult male rat, HYPOX + ADX pups exhibited low levels of freezing accompanied by ultrasonic vocalizations. These pups also had reduced concentrations of plasma ACTH and CORT. In Experiment 3, 10-day-old pups were HYPOX and tested for behavioral inhibition on day 14. In comparison to sham-operated controls, HYPOX rats exhibited significantly lower levels of freezing and had reduced plasma concentrations of ACTH and CORT. Results demonstrate clearly that deficits in freezing occur even in the presence of low plasma ACTH concentrations. Therefore, elevated secretion of pituitary hormones is not a major factor that contributes to the ADX-induced deficits in behavioral inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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Tönük, Şükrü Burak; Serin, Erdinc; Ayhan, Fikriye Figen; Yorgancioglu, Zeynep Rezan
2016-01-01
Abstract To investigate the effects of physical agents on the levels of stress hormones in patients with osteoarthritis (OA). Transcutaneous electrical nerve stimulation, hot packs, and therapeutic ultrasound were applied to the lumbar region and knees of patients with OA. Blood samples were taken for the measurement of the serum levels of glucose, insulin (INS), growth hormone (GH), prolactin (PRL), cortisol (COR), and plasma adrenocorticotropic hormone (ACTH) immediately before and after the 1st session, to investigate the acute effects of those physical agents on the endocrine system. The hormone levels were also measured every 5 sessions in a total of 10 sessions. The treatment response was also evaluated by using the visual analogue scale (VAS), Roland Morris Disability Questionnaire (RMDQ), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) throughout the therapy period. After the 1st session, there was a decrease in INS levels and a mild decrease in PRL levels (P = 0.001 and P < 0.05, respectively). Throughout the 10-session therapy period, the INS levels increased, whereas the ACTH and COR levels decreased (P < 0.05 for all). The VAS-spine, RMDQ, VAS-knee, and WOMAC scores decreased (P = 0.001 for VAS-spine and P < 0.001 for all others). A positive correlation was detected between the changes in serum COR and WOMAC-pain score (P < 0.05). Although the combination therapy caused changes in INS level accompanied with steady glucose levels, the application of physical agents did not adversely affect the hormone levels. The decrease in ACTH and COR levels may be attributed to the analgesic effect of agents and may be an indicator of patient comfort through a central action. PMID:27583888
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Lingis, Melissa; Richards, Elaine M.
2011-01-01
During pregnancy, plasma ACTH and cortisol are chronically increased; this appears to occur through a reset of hypothalamo-pituitary-adrenal (HPA) activity. We have hypothesized that differences in mineralocorticoid receptor activity in pregnancy may alter feedback inhibition of the HPA axis. We tested the effect of MR antagonism in pregnant and nonpregnant ewes infused for 4 h with saline or the MR antagonist canrenoate. Pregnancy significantly increased plasma ACTH, cortisol, angiotensin II, and aldosterone. Infusion of canrenoate increased plasma ACTH, cortisol, and aldosterone in both pregnant and nonpregnant ewes; however, the temporal pattern of these responses differed between these two reproductive states. In nonpregnant ewes, plasma ACTH and cortisol transiently increased at 1 h of infusion, whereas in pregnant ewes the levels gradually increased and were significantly elevated from 2 to 4 h of infusion. MR blockade increased plasma aldosterone from 2 to 4 h in the pregnant ewes but only at 4 h in the nonpregnant ewes. In both pregnant and nonpregnant ewes, the increase in plasma aldosterone was significantly related to the timing and magnitude of the increase in plasma potassium. The results indicate a differential effect of MR activity in pregnant and nonpregnant ewes and suggest that the slow changes in ACTH, cortisol, and aldosterone are likely to be related to blockade of MR effects in the kidney rather than to effects of MR blockade in hippocampus or hypothalamus. PMID:21205934
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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.
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Kussman, B D; Gruber, E M; Zurakowski, D; Hansen, D D; Sullivan, L J; Laussen, P C
2001-11-01
We evaluated the relationship of the bispectral index (BIS) to commonly used indices of depth of anaesthesia in 19 infants enrolled in a prospective study of the stress response to hypothermic cardiopulmonary bypass. Group 1 (n=8) received high-dose fentanyl by bolus technique; group 2 (n=6) received high-dose fentanyl by continuous infusion; and group 3 (n=5) received a fentanyl-midazolam infusion. Blood pressure (BP), heart rate (HR) and plasma epinephrine, norepinephrine, cortisol, ACTH, glucose, lactate and fentanyl were analysed 15 min postinduction, 15 min poststernotomy, 15 min on CPB during cooling and during skin closure. Mean BIS (SD) values for all 19 patients were 45.3 (12.3), 40.4 (14.5), 24.4 (12.4) and 47.9 (13.9), at the successive time points. No significant differences were observed in changes in BIS over time between the groups. A significant correlation was found 15 min postinduction between BIS and BP (systolic r=0.51, mean r=0.56) in all groups, but not between BIS and HR. BIS did not correlate with BP or HR at any other time point. There was no significant correlation between BIS and hormonal, biochemical or plasma fentanyl levels for any group at any time point. We were unable to demonstrate a relationship between the BIS and haemodynamic, metabolic or hormonal indices of anaesthetic depth. Further evaluation of the BIS algorithm is required in neonates and infants.
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Jankowski, M. D.; Wittwer, D. J.; Heisey, D. M.; Franson, J. C.; Hofmeister, E. 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. PMID:19199814
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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.
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De Kock, S; De Kloet, E R
1987-09-23
The Porsolt swimming test, which was originally designed as an experimental model to screen potential antidepressants demands that rats be forced to swim for 15 min in a narrow cylinder. Twenty four hours later they are retested for 5 min during which they stay immobile for approximately 70% of the time. The present study showed that hypophysectomized animals, 14 days after operation, were unable to retain the acquired immobility. Subcutaneous glucocorticoid administration did not restore the retention of acquired immobility in contrast to our earlier finding with adrenalectomized animals. The deficit in responsiveness to glucocorticoids was eliminated when the hypophysectomized rats received ACTH-(4-10)s.c. (20 micrograms/rat) every other day. Chronic treatment with only the peptide did not improve the impaired retention of hypophysectomized rats and a single ACTH-(4-10) injection 1 day or 1 h prior to initial testing was also ineffective. We conclude that the neurotrophic peptide ACTH-(4-10) permits the expression of the glucocorticoid effect on retention of acquired immobility in the swimming test.
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Ectopic ACTH and CRH co-secreting tumor localized by 68Ga-DOTA-TATE PET/CT
Papadakis, Georgios Z.; Bagci, Ulas; Sadowski, Samira M.; Patronas, Nicholas J.; Stratakis, Constantine A.
2015-01-01
Diagnosis of ectopic adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) co-secreting tumors causing Cushing syndrome (CS) is challenging, since these tumors are rare and their diagnosis is frequently confused with Cushing disease (CD), due to the effect of CRH on the pituitary. We report a case of a 21-year-old male who was referred to our institution with persistent hypercortisolemia and CS after undergoing unnecessary transsphenoidal surgery (TSS). 68Ga-DOTA-TATE PET/CT revealed increased tracer uptake in the thymus which was histologically proved to be neuroendocrine tumor (NET) staining positive for ACTH and CRH. Imaging with 18F-FDG PET/CT was not diagnostic. PMID:26018709
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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.
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Bloch, M; Schmidt, P J; Su, T P; Tobin, M B; Rubinow, D R
1998-06-15
Premenstrual syndrome (PMS) is a cyclic mood disorder, widely believed, yet not conclusively shown, to be of endocrine etiology. This study examines basal levels of several hormones reported, albeit inconsistently, to differ in women with PMS compared with controls. Subjects (10 PMS patients and 10 controls) had their blood drawn for one full menstrual cycle. Subjects' mood and behavioral symptoms were assessed by daily self-ratings and objective ratings. Plasma was assayed for total and free testosterone (T), beta-endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and cortisol. No differences were observed between the PMS and control groups for beta-EP, ACTH, or cortisol. PMS subjects had significantly lower total and free T plasma levels with a blunting of the normal periovulatory peak, a finding that may be epiphenomenal to age. This study does not confirm previous reports of abnormalities in plasma levels of either ACTH or beta-EP in women with PMS; it also fails to replicate a previous observation of high free T levels in women with PMS. These results are not supportive of a primary endocrine abnormality in PMS patients.
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Thomas, Alexa L; Maekawa, Fumihiko; Kawashima, Takaharu; Sakamoto, Hirotaka; Sakamoto, Tatsuya; Davis, Perry; Dores, Robert M
2018-01-15
In order to better understand the roles that melanocortin receptors (cMCRs) and melanocortin-2 receptor accessory proteins (cMRAP1 and cMRAP2) play in the HPA axis and hypothalamus, adrenal gland and hypothalamus mRNA from 1day-old white leghorn chicks (Gallus gallus), were analyzed by real-time PCR. mRNA was also made for kidney, ovary, and liver. Mrap1 mRNA could be detected in adrenal tissue, but not in any of the other tissues, and mrap2 mRNA was also detected in the adrenal gland. Finally, all five melanocortin receptors mRNAs could be detected in the adrenal gland; mc2r and mc5r mRNAs were the most abundant. To evaluate any potential interactions between MRAP1 and the MCRs that may occur in adrenal cells, individual chick mcr cDNA constructs were transiently expressed in CHO cells either in the presence or absence of a chick mrap1 cDNA, and the transfected cells were stimulated with hACTH(1-24) at concentrations ranging from 10 -13 M to 10 -6 M. As expected, MC2R required co-expression with MRAP1 for functional expression; whereas, co-expression of cMC3R with cMRAP1 had no statistically significant effect on sensitivity to hACTH(1-24). However, co-expression of MC4R and MC5R with MRAP1, increased sensitivity for ACTH(1-24) by approximately 35 fold and 365 fold, respectively. However, co-expressing of cMRAP2 with these melanocortin receptors had no effect on sensitivity to hACTH(1-24). Since the real-time PCR analysis detected mrap2 mRNA and mc4r mRNA in the hypothalamus, the interaction between cMC4R and cMRAP2 with respect to sensitivity to ACTH(1-13)NH 2 stimulation was also evaluated. However, no effect, either positive or negative, was observed. Finally, the highest levels of mc5r mRNA were detected in liver cells. This observation raises the possibility that in one-day old chicks, activation of the HPA axis may also involve a physiological response from liver cells. Copyright © 2017 Elsevier Inc. All rights reserved.
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Mendola, Marco; Dolci, Alessia; Piscopello, Lanfranco; Tomei, Giustino; Bauer, Dario; Corbetta, Sabrina; Ambrosi, Bruno
2014-01-01
We describe a patient affected by Cushing's disease due to the presence of double pituitary adenomas, one located within the anterior pituitary and the other in the infundibulum associated with a remnant of Rakthe's pouch. Cure was achieved only after the infundibulum lesion was surgically removed. A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia. Hormonal studies indicated Cushing's disease and MRI showed an enlarged pituitary gland with a marked and homogeneous enhancement after injection of gadolinium and an enlarged infundibulum with a maximum diameter of 8 mm. As a venous sampling of the inferior petrosal sinus after 10 μg iv desmopressin stimulation revealed a central to peripheral ACTH ratio consistent with a pituitary ACTH-secreting tumor, transphenoidal explorative surgery was performed and a 4-mm pituitary adenoma immunopositive for ACTH was disclosed and removed. Since postoperative hormonal evaluation showed persistent hypercortisolism, confirmed by dynamic tests, the patient again underwent surgery by transcranial access and the infundibulum mass was removed. Histology and immunochemistry were consistent with an ACTH-secreting adenoma. A few months after the second operation, cushingoid features were significantly reverted and symptoms improved. Although Cushing's patients bearing multiple adenomas have already been documented, the presence of two adenomas both immunohistochemically positive for ACTH is a very rare cause of Cushing's disease and this is the first report of a case of double ACTH-producing adenomas, one located in the pituitary gland and one attached to the stalk.
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Incompatibility between fasting and postprandial plasma glucose in patients with Cushing's syndrome.
Otsuki, Michio; Kitamura, Tetsuhiro; Tamada, Daisuke; Tabuchi, Yukiko; Mukai, Kosuke; Morita, Shinya; Kasayama, Soji; Shimomura, Iichiro; Koga, Masafumi
2016-11-30
It is shown that glucocorticoids have discordant effects on plasma glucose concentration through their effects on hepatic glycogen deposition, gluconeogenesis and peripheral insulin resistance. Cushing's syndrome caused by cortisol overproduction is frequently accompanied with diabetes mellitus, but fasting plasma glucose (FPG) and post-glucose load plasma glucose levels are not examined in patients with Cushing's syndrome. The aim of this study was to investigate FPG, HbA1c and oral glucose tolerance test (OGTT) 2-h PG and their relationship in patients with Cushing's syndrome, in comparison with control subjects. Sixteen patients with Cushing's syndrome (ACTH-dependent 31%, ACTH-independent 69% and diabetes mellitus 50%) and 64 controls (32 patients with type 2 diabetes mellitus and 32 non-diabetic subjects matched for age, sex and BMI) were enrolled in this study. HbA1c and FPG in the patients with Cushing's syndrome were not different from the controls, whereas the FPG/HbA1c ratio was significantly lower in the patients with Cushing's syndrome than the controls. OGTT 2-h PG was significantly higher in the non-diabetic patients with Cushing's syndrome than the non-diabetic controls, while HbA1c was not different between both groups and FPG was significantly lower in the patients with Cushing's syndrome than the controls. HOMA-β but not HOMA-R was significantly higher in the patients with Cushing's syndrome than the controls. In conclusion, FPG was rather lower in the patients with Cushing's syndrome than the controls. Postprandial PG or post-glucose loaded PG, but not FPG, is useful to evaluate the abnormality of glucose metabolism in patients with Cushing's syndrome.
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Low plasma progranulin levels in children with autism
2011-01-01
Background Autoimmunity to brain may play a pathogenic role in autism. In autoimmune disorders, the formation of antigen-antibody complexes triggers an inflammatory response by inducing the infiltration of neutrophils. Local administration of recombinant progranulin, which is an anti-inflammatory neurotrophic factor, potently inhibit neutrophilic inflammation in vivo, demonstrating that progranulin represents a crucial inflammation-suppressing mediator. We are the first to measure plasma progranulin levels in autism. Methods Plasma levels of progranulin were measured, by ELISA, in 40 autistic patients, aged between 3 and 12 years, and 40 healthy-matched children. Results Autistic children had significantly lower plasma progranulin levels, P = 0.001. Reduced plasma progranulin levels were found in 65% (26/40) of autistic children. On the other hand, there was a non significant difference between plasma progranulin levels of children with mild to moderate autism and patients with severe autism, P = 0.11. Conclusions Plasma progranulin levels were reduced in a subgroup of patients with autism. Progranulin insufficiency in some patients with autism may result in many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation that may have a role in autism. However, these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the decrease of plasma progranulin levels is a mere consequence of autism or has a pathogenic role in the disease. The role of progranulin therapy should also be studied in autism. PMID:21892962
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Low plasma progranulin levels in children with autism.
Al-Ayadhi, Laila Y; Mostafa, Gehan A
2011-09-05
Autoimmunity to brain may play a pathogenic role in autism. In autoimmune disorders, the formation of antigen-antibody complexes triggers an inflammatory response by inducing the infiltration of neutrophils. Local administration of recombinant progranulin, which is an anti-inflammatory neurotrophic factor, potently inhibit neutrophilic inflammation in vivo, demonstrating that progranulin represents a crucial inflammation-suppressing mediator. We are the first to measure plasma progranulin levels in autism. Plasma levels of progranulin were measured, by ELISA, in 40 autistic patients, aged between 3 and 12 years, and 40 healthy-matched children. Autistic children had significantly lower plasma progranulin levels, P = 0.001. Reduced plasma progranulin levels were found in 65% (26/40) of autistic children.On the other hand, there was a non significant difference between plasma progranulin levels of children with mild to moderate autism and patients with severe autism, P = 0.11. Plasma progranulin levels were reduced in a subgroup of patients with autism. Progranulin insufficiency in some patients with autism may result in many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation that may have a role in autism. However, these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the decrease of plasma progranulin levels is a mere consequence of autism or has a pathogenic role in the disease. The role of progranulin therapy should also be studied in autism.
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Bonfig, Walter; Krude, Heiko; Schmidt, Heinrich
2011-08-01
The LHX3 LIM-homeodomain transcription factor gene is required for normal pituitary and motoneuron development. LHX3 mutations are associated with growth hormone, prolactin, gonadotropin, and TSH deficiency; abnormal pituitary morphology; and may be accompanied with limited neck rotation and sensorineural hearing loss. We report on a boy, who presented with hypoglycemia in the newborn period. He is the second child of healthy unrelated parents. Short neck, growth hormone deficiency, and central hypothyroidism were diagnosed at a general pediatric hospital. Growth hormone and levothyroxine treatment were started, and blood sugar normalized with this treatment. On cerebral MRI, the anterior pituitary gland was hypoplastic. Sensorineural hearing loss was diagnosed by auditory testing. During follow-up, six repeatedly low morning cortisol levels (<1 μg/dl) and low ACTH levels (<10 pg/ml) were documented, so ACTH deficiency had developed over time and therefore hydrocortisone replacement was started at 1.5 years of age. Mutation analysis of the LHX3 gene revealed a homozygous stop mutation in exon 2: c.229C>T (CGA > TGA), Arg77stop (R77X). A complete loss of function is assumed with this homozygous stop mutation. We report a novel LHX3 mutation, which is associated with combined pituitary hormone deficiency including ACTH deficiency, short neck, and sensorineural hearing loss. All patients with LHX3 defects should undergo longitudinal screening for ACTH deficiency, since corticotrope function may decline over time. All patients should have auditory testing to allow for regular speech development.
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Michels, Meta; Japtok, Lukasz; Alisjahbana, Bachti; Wisaksana, Rudi; Sumardi, Uun; Puspita, Mita; Kleuser, Burkhard; de Mast, Quirijn; van der Ven, Andre J A M
2015-10-01
A transient endothelial hyperpermeability is a hallmark of severe dengue infections. Sphingosine-1-phosphate (S1P) maintains vascular integrity and protects against plasma leakage. We related plasma S1P levels to dengue-induced plasma leakage and studied mechanisms that may underlie the decrease in S1P levels in dengue. We determined circulating levels of S1P in 44 Indonesian adults with acute dengue and related levels to plasma leakage, as determined by daily ultrasonography, and to levels of its chaperone apolipoprotein M, other lipoproteins and platelets. Plasma S1P levels were decreased during dengue and patients with plasma leakage had lower median levels compared to those without (638 vs. 745 nM; p < 0.01). ApoM and other lipoprotein levels were also decreased during dengue, but did not correlate to S1P levels. Platelet counts correlated positively with S1P levels, but S1P levels were not higher in frozen-thawed platelet rich plasma, arguing against platelets as an important cellular source of S1P in dengue. Decreased plasma S1P levels during dengue are associated with plasma leakage. We speculate that decreased levels of ApoM underlies the lower S1P levels. Modulation of S1P levels and its receptors may be a novel therapeutic intervention to prevent plasma leakage in dengue. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
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Ye, Ping; Kenyon, Christopher J; MacKenzie, Scott M; Nichol, Katherine; Seckl, Jonathan R; Fraser, Robert; Connell, John M C; Davies, Eleanor
2008-01-01
Using a highly sensitive quantitative RT-PCR method for the measurement of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs, we previously demonstrated that CYP11B2 expression in the central nervous system (CNS) is subject to regulation by dietary sodium. We have now quantified the expression of these genes in the CNS of male Wistar Kyoto (WKY) rats in response to systemic ACTH infusion, dexamethasone infusion, and to adrenalectomy. CYP11B1 and CYP11B2 mRNA levels were measured in total RNA isolated from the adrenal gland and discrete brain regions using real-time quantitative RT-PCR. ACTH infusion (40 ng/day for 7 days, N=8) significantly increased CYP11B1 mRNA in the adrenal gland, hypothalamus, and cerebral cortex compared with animals infused with vehicle only. ACTH infusion decreased adrenal CYP11B2 expression but increased expression in all of the CNS regions except the cortex. Dexamethasone (10 μg/day for 7 days, N=8) reduced adrenal CYP11B1 mRNA compared with control animals but had no significant effect on either gene's expression in the CNS. Adrenalectomy (N=6 per group) significantly increased CYP11B1 expression in the hippocampus and hypothalamus and raised CYP11B2 expression in the cerebellum relative to sham-operated animals. This study confirms the transcription of CYP11B1 and CYP11B2 throughout the CNS and demonstrates that gene transcription is subject to differential regulation by ACTH and circulating corticosteroid levels. PMID:18252953
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Torres-Farfan, C; Abarzua-Catalan, L; Valenzuela, F J; Mendez, N; Richter, H G; Valenzuela, G J; Serón-Ferré, M
2009-06-01
Timely production of glucocorticoid hormones in response to ACTH is essential for survival by coordinating energy intake and expenditure and acting as homeostatic regulators against stress. Adrenal cortisol response to ACTH is clock time dependent, suggesting that an intrinsic circadian oscillator in the adrenal cortex contributes to modulate the response to ACTH. Circadian clock gene expression has been reported in the adrenal cortex of several species. However, there are no reports accounting for potential involvement of adrenal clock proteins on cortisol response to ACTH. Here we explored whether the clock protein cryptochrome 2 (CRY2) knockdown modifies the adrenal response to ACTH in a primate. Adrenal gland explants from adult capuchin monkey (n = 5) were preincubated for 6 h with transfection vehicle (control) or with two different Cry2 antisense and sense probes followed by 48 h incubation in medium alone (no ACTH) or with 100 nm ACTH. Under control and sense conditions, ACTH increased cortisol production, whereas CRY2 suppression inhibited ACTH-stimulated cortisol production. Expression of the steroidogenic enzymes steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase at 48 h of incubation was increased by ACTH in control explants and suppressed by Cry2 knockdown. Additionally, we found that Cry2 knockdown decreased the expression of the clock gene brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (Bmal1) at the mRNA and protein levels. Altogether these results strongly support that the clock protein CRY2 is involved in the mechanism by which ACTH increases the expression of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase. Thus, adequate expression levels of components of the adrenal circadian clock are required for an appropriate cortisol response to ACTH.
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Plasma Shh levels reduced in pancreatic cancer patients
El-Zaatari, Mohamad; Daignault, Stephanie; Tessier, Art; Kelsey, Gail; Travnikar, Lisa A.; Cantu, Esperanza F.; Lee, Jamie; Plonka, Caitlyn M.; Simeone, Diane M.; Anderson, Michelle A.; Merchant, Juanita L.
2012-01-01
Objectives Normally, sonic hedgehog (Shh) is expressed in the pancreas during fetal development and transiently after tissue injury. Although pancreatic cancers express Shh, it is not known if the protein is secreted into the blood and whether its plasma levels change with pancreatic transformation. The goal of this study was to develop an ELISA to detect human Shh in blood, and determine the levels in subjects with and without pancreatic cancer. Methods A human Shh ELISA assay was developed, and plasma Shh levels were measured in blood samples from normal volunteers and subjects with pancreatitis or pancreatic cancer. The biological activity of plasma Shh was tested using NIH-3T3 cells. Results The average levels of Shh in human blood were lower in pancreatitis and pancreatic cancer patients than in normal individuals. Hematopoietic cells did not express Shh suggesting that Shh is secreted into the bloodstream. Plasma fractions enriched for Shh did not induce Gli-1 mRNA suggesting that the protein was not biologically active. Conclusions Shh is secreted from tissues and organs into the circulation but its activity is blocked by plasma proteins. Reduced plasma levels were found in pancreatic cancer patients, but alone were not sufficient to predict pancreatic cancer. PMID:22513293
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Plasma Shh levels reduced in pancreatic cancer patients.
El-Zaatari, Mohamad; Daignault, Stephanie; Tessier, Art; Kelsey, Gail; Travnikar, Lisa A; Cantu, Esperanza F; Lee, Jamie; Plonka, Caitlyn M; Simeone, Diane M; Anderson, Michelle A; Merchant, Juanita L
2012-10-01
Normally, sonic hedgehog (Shh) is expressed in the pancreas during fetal development and transiently after tissue injury. Although pancreatic cancers express Shh, it is not known if the protein is secreted into the blood and whether its plasma levels change with pancreatic transformation. The goal of this study was to develop an enzyme-linked immunosorbent assay to detect human Shh in blood and determine its levels in subjects with and without pancreatic cancer. A human Shh enzyme-linked immunosorbent assay was developed, and plasma Shh levels were measured in blood samples from healthy subjects and patients with pancreatitis or pancreatic cancer. The biological activity of plasma Shh was tested using NIH-3T3 cells. The mean levels of Shh in human blood were lower in patients with pancreatitis and pancreatic cancer than in healthy subjects. Hematopoietic cells did not express Shh, suggesting that Shh is secreted into the bloodstream. Plasma fractions enriched with Shh did not induce Gli-1 messenger RNA, suggesting that the protein was not biologically active. Shh is secreted from tissues and organs into the circulation, but its activity is blocked by plasma proteins. Reduced plasma levels were found in pancreatic cancer patients, but alone were not sufficient to predict pancreatic cancer.
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Giovannini, C; Sellini, M; Manzo, G; Barletta, C; Scavo, D
1981-12-30
The Lysin-8-Vasopressin test has been experimented in ten healthy subjects during normocaloric balanced diet and after hyperproteic-normocaloric diet. The levels of ACTH, Cortisol and GH are significantly more elevated after hyperproteic-normocaloric diet than in basal conditions. The levels of Prolactin do not show any remarkable change. These results can indicate the increased reactivity of the diencephalon-hypophysis-adrenal axis and of the hormones connected with the mechanisms of homeostasis and stress, probably correlated to more disposable proteic material and to the metabolic effects which follow.
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Wong, M L; Kling, M A; Munson, P J; Listwak, S; Licinio, J; Prolo, P; Karp, B; McCutcheon, I E; Geracioti, T D; DeBellis, M D; Rice, K C; Goldstein, D S; Veldhuis, J D; Chrousos, G P; Oldfield, E H; McCann, S M; Gold, P W
2000-01-04
Both stress-system activation and melancholic depression are characterized by fear, constricted affect, stereotyped thinking, and similar changes in autonomic and neuroendocrine function. Because norepinephrine (NE) and corticotropin-releasing hormone (CRH) can produce these physiological and behavioral changes, we measured the cerebrospinal fluid (CSF) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression. Plasma adrenocorticotropic hormone (ACTH) and cortisol levels were obtained every 30 min. Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock. Diurnal variations in CSF NE and plasma cortisol levels were virtually superimposable and positively correlated with each other in both patients and controls. Despite their hypercortisolism, depressed patients had normal levels of plasma ACTH and CSF CRH. However, plasma ACTH and CSF CRH levels in depressed patients were inappropriately high, considering the degree of their hypercortisolism. In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls, patients with depression showed no statistical relationship between these parameters. These data indicate that persistent stress-system dysfunction in melancholic depression is independent of the conscious stress of the disorder. These data also suggest mutually reinforcing bidirectional links between a central hypernoradrenergic state and the hyperfunctioning of specific central CRH pathways that each are driven and sustained by hypercortisolism. We postulate that alpha-noradrenergic blockade, CRH antagonists, and treatment with antiglucocorticoids may act at different loci, alone or in combination, in the treatment of major depression with melancholic features.
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Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.
Genazzani, A D; Bersi, C; Luisi, S; Fruzzetti, F; Malavasi, B; Luisi, M; Petraglia, F; Genazzani, A R
2001-09-01
To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Controlled clinical study. Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.
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Gene- and environment-dependent neuroendocrine etiogenesis of homosexuality and transsexualism.
Dörner, G; Poppe, I; Stahl, F; Kölzsch, J; Uebelhack, R
1991-01-01
Sexual brain organization is dependent on sex hormone and neurotransmitter levels occurring during critical developmental periods. The higher the androgen levels during brain organization, caused by genetic and/or environmental factors, the higher is the biological predisposition to bi- and homosexuality or even transsexualism in females and the lower it is in males. Adrenal androgen excess, leading to heterotypical sexual orientation and/or gender role behavior in genetic females, can be caused by 21-hydroxylase deficiency, especially when associated with prenatal stress. The cortisol (F) precursor 21-deoxycortisol (21-DOF) was found to be significantly increased after ACTH stimulation in homosexual as compared to heterosexual females. 21-DOF was increased significantly before and even highly significantly after ACTH stimulation in female-to-male transsexuals. In view of these data, heterozygous and homozygous forms, respectively, of 21-hydroxylase deficiency represent a genetic predisposition to androgen-dependent development of homosexuality and transsexualism in females. Testicular androgen deficiency in prenatal life, giving rise to heterotypical sexual orientation and/or gender role behavior in genetic males, may be induced by prenatal stress and/or maternal or fetal genetic alterations. Most recently, in mothers of homosexual men--following ACTH stimulation--a significantly increased prevalence of high 21-DOF plasma values and 21-DOF/F ratios was found, which surpassed the mean + 1 SD level of heterosexual control women. In homosexual men as well--following ACTH stimulation--most of the 21-DOF plasma values and 21-DOF/F ratios also surpassed the mean + 1 SD level of heterosexual men. In only one out of 9 homosexual males, neither in his blood nor in that of his mother increased 21-DOF values and 21-DOF/F ratios were found after ACTH stimulation. In this homosexual man, however, the plasma dehydroepiandrosterone sulfate (DHEA-S) values and the DHEA-S/1000 x A
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Roper, J A; Craighead, M; O’Carroll, A-M; Lolait, S J
2010-01-01
Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors. PMID:20846299
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Roper, J A; Craighead, M; O'Carroll, A-M; Lolait, S J
2010-11-01
Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors. © 2010 The Authors. Journal of Neuroendocrinology © 2010 Blackwell Publishing Ltd.
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Effects of dietary sesame seeds on plasma tocopherol levels.
Cooney, R V; Custer, L J; Okinaka, L; Franke, A A
2001-01-01
The tocopherols, the major vitamers of vitamin E, are believed to play a role in the prevention of human aging-related diseases such as cancer and heart disease, yet little is known concerning determinants of their plasma concentrations. Evidence from animal studies suggests that the dietary source of gamma-tocopherol can significantly affect plasma levels of this tocopherol as well as its functional vitamin E activity. To determine whether plasma levels of tocopherols in humans are similarly altered, a study was undertaken in which subjects (n = 9) were fed muffins containing equivalent amounts of gamma-tocopherol from sesame seeds, walnuts, or soy oil. We observed that consumption of as little as 5 mg of gamma-tocopherol per day over a three-day period from sesame seeds, but not from walnuts or soy oil, significantly elevated serum gamma-tocopherol levels (19.1% increase, p = 0.03) and depressed plasma beta-tocopherol (34% decrease, p = 0.01). No significant changes in baseline or postintervention plasma levels of cholesterol, triglycerides, or carotenoids were seen for any of the intervention groups. All subjects consuming sesame seed-containing muffins had detectable levels of the sesame lignan sesamolin in their plasma. Consumption of moderate amounts of sesame seeds appears to significantly increase plasma gamma-tocopherol and alter plasma tocopherol ratios in humans and is consistent with the effects of dietary sesame seeds observed in rats leading to elevated plasma gamma-tocopherol and enhanced vitamin E bioactivity.
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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. Copyright © 2015 Elsevier Inc. All rights reserved.
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Plasma leptin concentrations are highly correlated to emotional states throughout the day
Licinio, J; Negrao, A B; Wong, M-L
2014-01-01
Previous work has shown that leptin appears to regulate the plasma levels of hormones such as adrenocorticotropic hormone (ACTH) and cortisol in humans and that it has antidepressant effects in animals. It is unknown whether fluctuations in circulating leptin levels are correlated to changes in human emotions. This study was conducted to determine whether minute-to-minute fluctuations in the plasma concentrations of human leptin were associated with psychological variables. Leptin was sampled every 7 min throughout the day in 10 healthy subjects (five men and five women) studied in a clinical research center, and visual analog scales were applied every hour. We found highly significant correlations between fluctuations in plasma leptin concentrations and three psychological variables: sadness, carbohydrate craving and social withdrawal. We showed that during the course of the day increases in leptin levels are associated with decreased search for starchy foods, decreased feelings of sadness and increased social withdrawal. Our findings support the hypothesis that during the course of the day as leptin levels increase individuals subjectively feel happier (less sad) and have less inclination to interact socially. Conversely, when leptin levels decrease, we show increases in sadness and social cooperation, which might facilitate the search for food. We suggest that increased human leptin levels may promote positive feelings and that decreased leptin levels might modulate inner states that motivate and facilitate the search for nutrients. PMID:25350298
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Lindahl, Magnus S; Olovsson, Matts; Nyberg, Sigrid; Thorsen, Kim; Olsson, Tommy; Sundström Poromaa, Inger
2007-01-01
To assess the hypothalamic-pituitary-adrenal (HPA) axis at all levels, to determine the origin of the previously reported hypercortisolism in patients with functional hypothalamic amenorrhea. A secondary aim was to evaluate factors outside the central nervous system which are known to affect the HPA axis, i.e., circulating levels of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and fat mass-adjusted leptin levels, in patients with functional hypothalamic amenorrhea and healthy controls. Cross-sectional study. Umeå University Hospital, Umeå, Sweden. Fifteen subjects with hypothalamic amenorrhea, and 14 age- and weight-matched controls. None. We collected blood samples four times during a 24-hour interval for analysis of cortisol, leptin, IL-1Ra, and IL-6 levels. We performed a low-dose oral dexamethasone test and a low-dose ACTH test. We measured body-fat percentage using a dual-energy X-ray absorptiometer. Patients with hypothalamic amenorrhea had increased diurnal cortisol levels (P<.001). The cortisol response to intravenous low-dose ACTH was increased in functional hypothalamic amenorrhea patients compared to control subjects (P<.01), but they had similar rates of dexamethasone suppression. Patients with hypothalamic amenorrhea also had decreased diurnal leptin (P<.05), and decreased diurnal IL-1Ra levels (P<.05), compared to controls. Body-fat percentage was the main predictor of leptin levels. The present study suggests novel links for the development of functional hypothalamic amenorrhea, including increased adrenal responsiveness and impairments in proinflammatory cytokine pathways.
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Weber, E; Voigt, K H; Martin, R
1978-05-01
Slices of unembedded rat anterior pituitaries, fixed with a periodate-lysine-paraformaldehyde (PLP) fixative, were incubated with guinea pig antiserum to ACTH and stained with a peroxidase-conjugated IgG fraction of anti-guinea pig gamma-globulin serum from rabbits. The fine structure of the stained cells was identical to that of the ACTH-secreting cell, as described by Siperstein and coworkers. Immunoreactive granules were mainly located at the periphery of the cell. Numerous granules of the inner cytoplasm and also the Golgi complex were nonreactive to the antiserum. The differential labeling for granules and Golgi apparatus peptide.
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Increased plasma agmatine levels in patients with schizophrenia.
Uzbay, Tayfun; Goktalay, Gokhan; Kayir, Hakan; Eker, Salih S; Sarandol, Asli; Oral, Sema; Buyukuysal, Levent; Ulusoy, Gokhan; Kirli, Selcuk
2013-08-01
Agmatine is an endogenous substance, synthesized from l-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. This study was organized to investigate plasma agmatine in patients with schizophrenia and in healthy controls. Eighteen patients with schizophrenia and 19 healthy individuals constituted the subjects. Agmatine levels in the plasma were measured using the HPLC method. The S100B protein level, which is a peripheral biomarker for brain damage, was also measured using the ELISA method. While plasma levels of agmatine in patients with schizophrenia were significantly increased (p < 0.0001) compared to those of healthy individuals (control), there were no significant changes in the levels of S100B protein (p = 0.660). An ROC (receiver operating characteristic) curve analysis revealed that measuring plasma agmatine levels as a clinical diagnostic test would significantly differentiate between patients with schizophrenia and those in the control group (predictive value: 0.969; p < 0.0001). The predictive value of S100B measurements was not statistically significant (p > 0.05). A multiple regression analysis revealed that the age of the patient and the severity of the illness, as indicated by the PANSS score, significantly contributed the plasma agmatine levels in patients with schizophrenia. These results support the hypothesis that an excess agmatine release is important in the development of schizophrenia. The findings also imply that the plasma agmatine level may be a potential biomarker of schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Plasma and semen ascorbic levels in spermatogenesis.
Ebesunun, M O; Solademi, B A; Shittu, O B; Anetor, J I; Onuegbu, J A; Olisekodiaka, J M; Agbedana, E O; Onyeaghala, A A
2004-01-01
Conflicting reports on the mechanism of action of ascorbic acid level in male reproductive system exist and very little is known about the ascorbic acid status in Nigerian males with weak fertility. Ascorbate that accumulates preferentially in the testis, the lipid and lipoprotein levels were determined in the plasma of Nigerian males. Twenty-seven (27) male with inadequate spermatogenesis (36+/-1.0) years, with mean value of 15.6+/-6.90 million/cm3 sperm count and fourteen (14) controls (34+/-0.6) years, with mean value of 108.0+/-25.42 million/cm3 sperm count were selected for this study. The anthropometric indices were also determined. There were highly significant decreases in sperm cell count, percentage motility and percentage vitality (p<0.001) in each case, while percentage morphologically abnormal sperm cells was significantly elevated (p<0.001) compared with the control values. There were significant decreases in the seminal and plasma ascorbic acid concentrations (p<0.001) in the males who had inadequate spermatogenesis compared with the control values. The plasma total cholesterol (TC) and body mass index (BMI) were not significantly different from the corresponding control values, but the plasma low density lipoprotein (LDLC) (p<0.001) and triglyceride (TG)(p<0.01) concentrations were significantly increased in all the patients. While the plasma high density lipoprotein cholesterol (HDLC)(p<0.001) was significantly decreased compared with the controls. The plasma lipid and lipoprotein levels did not demonstrate any definite pattern with the sperm characteristics. The decreased semen ascorbate level may play a significant role in the reduced sperm characteristics in these patients.
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[Aldosterone response to various stimuli in hyperthyroidism: in vivo and in vitro studies].
Kigoshi, T; Kaneko, M; Nakano, S; Azukizawa, S; Uchida, K; Morimoto, S
1993-06-20
Responses of plasma aldosterone (PA) to alpha-ACTH-(1-24) (250 micrograms, im) injection and graded angiotensin II (AII) infusions (2, 4 and 8ng/kg/min for 30 min at each dose) on a constant sodium intake (170mEq daily) were assessed in 17 patients with Basedow's disease and 13 age-matched normal subjects. Aldosterone production in response to ACTH, AII and potassium in adrenal zona glomerulosa cells from L-thyroxine-induced hyperthyroid rats (H-rats) were also examined. Basal levels of plasma renin activity (PRA) and urinary aldosterone excretion were significantly higher (p < 0.01 and p < 0.05, respectively) in the patients with Basedow's disease than in the normal subjects, whereas basal PA level was similar in the two groups. The ACTH injection induced similar increases in plasma cortisol, plasma 18-hydroxycorticosterone (18-OHB) and PA in the two groups. The graded AII infusions also produced increases in plasma 18-OHB and PA in the two groups. Responses of these two corticosteroids to AII were, however, significantly lower (p < 0.05) in the patients with Basedow's disease than in the normal subjects. In the experimental animal study, basal PRA levels and the adrenal glomerulosa cell count/adrenal were significantly higher (p < 0.05) in the H-rats than in the control rats, whereas basal PA levels were similar in the two groups. Aldosterone production in response to AII, ACTH, and potassium increased in a dose-dependent manner in the two groups. Responses of aldosterone production to AII were, however, significantly lower (p < 0.05) in the H-rats than in the control rats. These results suggest that the impaired responsiveness of adrenal zona glomerulosa cells to AII, as well as an increased metabolic clearance rate of aldosterone, may be involved in the abnormal aldosterone metabolism in hyperthyroidism.
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Influence of a prenatal stressor on ACTH-induced cortisol secretion in yearling Brahman heifers
USDA-ARS?s Scientific Manuscript database
The objective of this study was to test whether prenatal stress affects postnatal adrenocortical responsiveness to exogenous adrenocorticotropin-releasing hormone (ACTH) in calves of Brahman cows transported for 2-hour periods at 60, 80, 100, 120, and 140 days of gestation. Prenatally stressed yearl...
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Plasma kisspeptin levels in male cases with hypogonadism.
Kotani, Masato; Katagiri, Fumihiko; Hirai, Tsuyoshi; Kagawa, Jiro
2014-01-01
The hypothalamic hormone kisspeptin (metastin) regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is detected in peripheral blood, although GnRH is not. In this study, we measured plasma kisspeptin levels in four male cases with hypogonadism and seven normal male controls using enzyme immunoassay (EIA) to elucidate the clinical implications of kisspeptin levels in male hypogonadism. The results showed a variety of plasma kisspeptin levels: 6.0 fmol/mL in a male with isolated hypogonadotropic hypogonadism (IHH), 43.2 fmol/mL in a male with Kallmann's syndrome, 40.7 fmol/mL in a male with azoospermia, 323.2 fmol/mL in a male with hypergonadotropic hypogonadism, and 12.3 ± 2.5 fmol/mL (mean ± SD) in seven normal controls. Except for the case with IHH, the plasma kisspetin levels were elevated in the three cases with Kallmann's syndrome, azoospermia, and hypergonadotropic hypogonadism. The reason why the three cases had high values was their lesions were downstream of the kisspeptin neuron in the hypothalamic-pituitary-gonadal axis, suggesting that elevated kisspeptin levels were implicated in hypothalamic kisspeptin secretion under decreased negative feedback of gonadal steroids. The result that the plasma kisspeptin levels were decreased by gonadotropin therapy in the case with Kallmann's syndrome supported this hypothesis. In conclusion, to measure plasma kisspeptin levels could be useful for better understanding of male hypogonadism.
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[Plasma orexin-A level in patients with obstructive apnea-hypopnea syndrome].
Yao, Xingqi; Yang, Hui; Zhang, Guifeng; Tang, Ying
2006-06-01
To investigate the effect of uvulopalatopharyngoplasty (UPPP) on changes of plasma orexin-A levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Fifty-four cases with OSAHS diagnosed by polysomnography were treated with uvulopalatopharyngoplasty and hyoid suspension. Plasma orexin-A levels in patients with OSAHS before and after surgical procedure 6 months, and in 20 healthy people with age,sex and BMI matched controls were measured by radioimmunoassay. The plasma was deproteinized by chromatography. Correlations between orexin-A levels and AHI, MAI and SaO2 min were analyzed. The plasma orexin-A levels in the OSAHS group was significantly higher than those in the control group (P < 0.01). Plasma orexin A levels in the patients with OSAHS correlated positively with the AHI (r < 0.658, P < 0.05) and MAI. (r = 0.464, P < 0.05) but correlated negatively with the SaO2 min. The plasma orexin-A levels of 54 responders after 6 months were significantly decreased (P < 0.01) than that of pre-operation, and there is no correlation between plasma orexin-A levels and BMI. The plasma orexin-A levels in the OSAHS patients are increased which may be caused by repeated nocturnal apnoea and hypoxia due to OSAHS. Surgical procedures may decreased the plasma orexin-A levels.
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NASA Astrophysics Data System (ADS)
Assenmacher, I.; Mekaouche, M.; Maurel, D.; Barbanel, G.; Givalois, L.; Boissin, J.; Malaval, F.; Ixart, G.
The tail-cast suspension rat model has been developed in ground laboratories interested in space physiology for extensive study of mechanisms causing the pathophysiological syndrome associated with space flights. We used individually-caged male rats to explore the effects of acute and chronic (7d) orthostatic restraint (OR) and head-down anti-orthostatic restraint (AOR) on a series of physiological variables. The acute restraint study showed that (1) the installation of the OR device induced an acute reaction for 2 days, with a substantial rise in ACTH (x2) and CORT (x6), and that (2) the head-down tilt from OR to AOR induced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-cerebro-ventricular pressure (Picv) monitored with an icv telemetric recording system, which receded to normal between 60 and 120 min; and (ii) within 30 min a short-lived 4-fold rise in plasma ACTH and CORT levels. Chronic OR induced (1) the suppression of the diurnal ACTH/CORT rhythm, with increased mean levels, especially for ACTH, (2) a degraded circadian locomotor activity rhythm manifested by a significant reduction in the spectral power of the 24h periodicity and a concomitant emergence of shorter (ultradian) periodicities, (3) an associated, but less pronounced alteration of the diurnal rhythm in body temperature; and (4) a marked increase in baseline plasma levels of IL-1β and an increased reactivity in cytokine release following an E. coli endotoxin (LPS) challenge. AOR induced (1) a similar obliteration of the circadian ACTH/CORT rhythm, (2) the loss of close correlation between ACTH and CORT, (3) a generalized increase in baseline plasma IL-1β levels and (4) more extensive degradation of the arcadian periodicity for both locomotor activity and, to a lesser extent, body temperature, replaced by dominant spectral powers for ultradian periodicities (3 to 10h). In conclusion, both experimental paradigms — but AOR more than OR — caused a blockade of the arcadian
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Increased Plasma Levels of Heme Oxygenase-1 in Human Brucellosis.
Chen, Zhe; Zhang, Yu-Xue; Fu, Dong-Wei; Gao, Qing-Feng; Ge, Feng-Xia; Liu, Wei-Hua
2016-08-01
Brucellosis is associated with inflammation and the oxidative stress response. Heme oxygenase-1 (HO-1) is a cytoprotective stress-responsive enzyme that has anti-inflammatory and anti-oxidant effects. Nevertheless, the role of HO-1 in human brucellosis has not yet been studied. The aim of this study was to examine the plasma levels of HO-1 in patients with brucellosis and to evaluate the ability of plasma HO-1 levels as an auxiliary diagnosis, a severity predictor, and a monitor for brucellosis treatments. A total of 75 patients with brucellosis were divided into the acute, subacute, chronic active, and chronic stable groups. An additional 20 volunteers were included as the healthy control group. The plasma HO-1 levels and other laboratory parameters were measured in all groups. Furthermore, the plasma levels of HO-1 in the acute group were compared before and after treatment. The plasma HO-1 levels were considerably increased in the acute (4.97 ± 3.55), subacute (4.98 ± 3.23), and chronic active groups (4.43 ± 3.00) with brucellosis compared to the healthy control group (1.03 ± 0.63) (p < 0.01). In the acute group, the plasma HO-1 levels in the post-treatment group (2.33 ± 2.39) were significantly reduced compared to the pre-treatment group (4.97 ± 3.55) (p < 0.01). On the other hand, the plasma HO-1 levels were higher in the chronic active group (4.43 ± 3.00) than the chronic stable group (2.74 ± 2.23) (p < 0.05). However, the plasma HO-1 levels in the chronic stable group (2.74 ± 2.23) remained higher than the levels in the healthy control group (1.03 ± 0.63) (p < 0.05). The HO-1 levels were positively correlated with the C-reactive protein (CRP) levels in patients with brucellosis (r = 0.707, p < 0.01). The plasma HO-1 levels can reflect patients' brucellosis status and may be used as a supplementary plasma marker for diagnosing brucellosis and monitoring its treatment.
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Plasma levels of acylated ghrelin in patients with functional dyspepsia
Kim, Yeon Soo; Lee, Joon Seong; Lee, Tae Hee; Cho, Joo Young; Kim, Jin Oh; Kim, Wan Jung; Kim, Hyun Gun; Jeon, Seong Ran; Jeong, Hoe Su
2012-01-01
AIM: To investigate the relationship between plasma acylated ghrelin levels and the pathophysiology of functional dyspepsia. METHODS: Twenty-two female patients with functional dyspepsia and twelve healthy volunteers were recruited for the study. The functional dyspepsia patients were each diagnosed based on the Rome III criteria. Eligible patients completed a questionnaire concerning the severity of 10 symptoms. Plasma acylated ghrelin levels before and after a meal were determined in the study participants using a commercial human acylated enzyme immunoassay kit; electrogastrograms were performed for 50 min before and after a standardized 10-min meal containing 265 kcal. RESULTS: There were no significant differences in plasma acylated ghrelin levels between healthy volunteers and patients with functional dyspepsia. However, in patients with functional dyspepsia, there was a negative correlation between fasting plasma acylated ghrelin levels and the sum score of epigastric pain (r = -0.427, P = 0.047) and a positive correlation between the postprandial/fasting plasma acylated ghrelin ratio and the sum score of early satiety (r = 0.428, P =0.047). Additionally, there was a negative correlation between fasting acylated ghrelin plasma levels and fasting normogastria (%) (r = -0.522, P = 0.013). Interestingly, two functional dyspepsia patients showed paradoxically elevated plasma acylated ghrelin levels after the meal. CONCLUSION: Abnormal plasma acylated ghrelin levels before or after a meal may be related to several of the dyspeptic symptoms seen in patients with functional dyspepsia. PMID:22611317
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Liu, Shunli; Wang, Liyuan; Cai, Xiao Tang; Zhou, Hui; Yu, Dan; Wang, Zhiling
2018-05-01
The case report aims to discuss the clinical symptoms and treatment of encephalopathy caused by a novel syntaxin- binding protein 1 (STXBP1) genetic mutation. The patient, a girl, was born at 38+4 weeks of gestation. She had frequent spasm attacks accompanied by obvious psychomotor development retardation since the neonatal period. Genetic screening identified a novel STXBP1 genetic mutation. Early-onset epileptic encephalopathy with STXBP1 mutation. We adjusted the antiepileptic strategy to oral levetiracetam and topiramate, and intravenous administration of adrenocorticotropic hormone(ACTH) for 2 weeks. Subsequently, prednisone was continued, and gradually reduced and withdrawn over 3 months. The treatment was effective with complete control of the epileptic seizures and improvements in the electroencephalogram readings. However, the effects on psychomotor ability were slow and limited. A literature review of STXBP1 mutation cases in which ACTH was administered showed that complete seizure control is observed in 60% of cases, 20% are partially affected, and the remaining 20% show no effect. ACTH and levetiracetam had good therapeutic effects in epilepsy control in this case of de novo STXBP1 mutation. ACTH is an effective drug for early-onset epileptic encephalopathy caused by STXBP1 mutation. However, controlling epilepsy using this therapy does not alter the psychomotor development retardation caused by the STXBP1 mutation.
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Betterle, Corrado; Garelli, Silvia; Presotto, Fabio; Furmaniak, Jadwiga
2016-01-01
Recent progress in the immunopathology field has greatly improved our understanding of the natural history of autoimmune diseases, particularly of Addison's disease. Addison's disease is known to be a chronic illness characterized by adrenocortical gland insufficiency that develops following a long and mainly asymptomatic period, characterized by the presence of circulating autoantibodies directed to adrenal cortex antigens. In this chapter we describe the groups of subjects at risk of developing Addison's disease, together with the diagnostic tests considered the most appropriate for evaluating adrenal function: determination of basal plasma adrenocorticotropic hormone (ACTH) levels, plasma renin activity, plasma aldosterone and cortisol levels, and cortisol levels after intravenous stimulation with ACTH (ACTH test). The employment of specific clinical, immunological and functional criteria in the subjects with autoantibodies to the adrenal cortex allows identifying those at risk of developing overt disease. The independent risk factors for the progression to adrenal failure have also been identified and they contribute to different risks of developing clinical Addison's disease. Based on the risk level, the subjects should be monitored over time to observe early signs of adrenal dysfunction, and start substitutive treatment as soon as possible. For patients presenting with high risk, prevention strategies and trials might be available. © 2016 S. Karger AG, Basel.
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Sellini, M; Giovannini, C; Manzo, G; Barletta, C; Borboni, P
1983-01-31
In 16 normal subjects the circadian rhythm of ACTH has been studied during normal calories diet and after a 15 days period of high protein content diet (2 g/Kg body weight). The statistical study, according Cosinor method, has shown a significant increase of the mesor and of the amplitude, but has not shown any change of the ACTH and Cortisol rhythm, after hyperproteic diet. Data advise the increase of the tonic and fasic secretion of both hormones and shown the mantained acrophase. The action of the protein on the ACTH and Cortisol secretion does not seem related to mechanism like stress, neither to the probable mediation of intestinal like-ACTH messengers. On the contrary it seems related to a direct stimulus on the diencephalo-pituitary axis; it is possible that some amino-acids (tryptophan, arginine) act as a mediator, even if data concern just the effect of the over mentioned amino-acid in large doses.
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[Unconsciousness due to hyponatremia in a patient with short stature with panhypopituitarism].
Notsu, K; Takagi, C; Umaki, I
1995-03-20
An unconscious woman of short stature (141 cm) was admitted to our hospital in March, 1994. She had hyponatremia (120 mEq/l) and had experienced massive bleeding during delivery. No increment of either plasma ACTH or cortisol levels was observed after insulin-induced hypoglycemia. However, urinary 17OHCS levels gradually increased after repeated intramuscular injections of ACTH. Plasma free T3 and free T4 levels were low. Neither plasma TSH nor prolactin (PRL) levels increased after an intravenous injection of TRH. Basal plasma LH, FSH and growth hormone (GH) levels were low and there were no observable responses to any of the stimulation tests. A magnetic resonance image (MRI) of her pituitary gland showed an empty sella. These results showed that she had a panhypopituitarism with primary empty sella. Replacement therapy with glucocorticoid was started and serum sodium levels normalized immediately. Levothyroxine was also administered. The possibility of pituitary dwarfism during her youth and a gradual postpartum reduction of other pituitary hormones may have caused an impairment of the hypothalamo-pituitary-adrenal axis.
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ICA Occlusion by an ACTH-secreting pituitary adenoma post-TSS and irradiation
El-Zammar, Diala; Akagami, Ryojo
2011-01-01
Occlusion of intracranial arteries by a pituitary adenoma with ensuing infarction is a rare occurrence. In this case study, we show the instance of a pituitary macroadenoma and apoplexy causing mechanical obstruction of the internal carotid artery with consequent infarction following transphenoidal surgery (TSS) and radiation therapy in a patient with Cushing's disease. We report a 44-year-old woman presented with amenorrhea and headaches. Necessary investigations, resection by TSS, and microscopic examination revealed an adenocorticotropin (ACTH)-secreting pituitary macroadenoma. The pituitary tumour recurred in subsequent years, resulting in the development of Cushing's disease and syndrome. Despite two more transphenoidal surgeries, radiotherapy, and medical suppressive therapy, the pituitary adenoma continued to enlarge, and the hypercortisolemia and Cushingoid symptoms persisted. A craniotomy was arranged as the next step in the treatment strategy. Only hours prior to the scheduled surgery, the patient developed left-sided hemiplegia, was diagnosed with acute occlusion of the right ICA and underwent an emergency bifrontal craniotomy with evacuation of the tumour and decompression. Pathological examination revealed evidence of apoplexy in the ACTH-secreting pituitary adenoma. This case demonstrates the vast scope of complications that can arise from pituitary adenomas despite combination therapy and forewarns clinicians to be prepared to manage these infrequent but conceivable occurrences. PMID:22399870
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Association of plasma manganese levels with chronic renal failure.
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. Copyright © 2015 Elsevier GmbH. All rights reserved.
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Plasma folate levels and risk of spontaneous abortion.
George, Lena; Mills, James L; Johansson, Anna L V; Nordmark, Anna; Olander, Bodil; Granath, Fredrik; Cnattingius, Sven
2002-10-16
Both folate deficiency and folic acid supplements have been reported to increase the risk of spontaneous abortion. The results are inconclusive, however, and measurements of folate have not been available in all studies. To study the association between plasma folate levels and the risk of spontaneous abortion. Population-based, matched, case-control study of case women with spontaneous abortion and control women from January 1996 through December 1998 in Uppsala County, Sweden. Plasma folate measurements were available for 468 cases and 921 controls at 6 to 12 gestational weeks. Risk of spontaneous abortion vs maternal plasma folate level. Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL (5.0 and 8.9 nmol/L), women with low (< or =2.19 ng/mL [< or =4.9 nmol/L]) folate levels were at increased risk of spontaneous abortion (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.14), whereas women with higher folate levels (3.96-6.16 ng/mL [9.0-13.9 nmol/L] and > or =6.17 ng/mL [> or =14.0 nmol/L]) showed no increased risk of spontaneous abortion (OR, 0.84; 95% CI, 0.59-1.20; and OR, 0.74; 95% CI, 0.47-1.16, respectively). Low folate levels were associated with a significantly increased risk when the fetal karyotype was abnormal (OR, 1.95; 95% CI, 1.09-3.48) but not when the fetal karyotype was normal (OR, 1.11; 95% CI, 0.55-2.24) or unknown (OR, 1.45; 95% CI, 0.90-2.33). Low plasma folate levels were associated with an increased risk of early spontaneous abortion.
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Hypothermic and antipyretic effects of ACTH (1-24) and alpha-melanotropin in guinea-pigs
NASA Technical Reports Server (NTRS)
Kandasamy, S. B.; Williams, B. A.
1984-01-01
Intracerebroventricular administration of adrenocorticotropin (ACTH 1-24) and alpha-melanotropin (alpha-MSH), peptides which occur naturally in brain induced dose-related hypothermia in guinea-pigs at room temperature (21 C) and also produced greater hypothermia at low (10 C) ambient temperature. However, when the experiments were repeated in a warm (30 C) environment, no effect on body temperature was observed. These results indicate that the peptides did not reduce the central set-point of temperature control. The hypothermia induced by ACTH and alpha-MSH was not mediated via histamine H1- or H2-receptors and serotonin since the H1-receptor antagonist, mepyramine, the H2-receptor antagonist, cimetidine, and the serotonin antagonist, methysergide, had no antagonistic effects. The peptides were antipyretic since they reduced pyrogen-induced-fever and hyperthermia due to prostaglandin E2, norepinephrine and dibutyryl cAMP, at a dose which did not affect normal body temperature. The powerful central effects of these peptides on normal body temperature, fever and hyperthermia, together with their presence of the brain regions important to temperature control, suggest that they participate in thermoregulation.
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Effects of plasma transfusions on antithrombin levels after paediatric liver transplantation.
Arni, D; Wildhaber, B E; McLin, V; Rimensberger, P C; Ansari, M; Fontana, P; Karam, O
2018-05-15
Thrombotic complications affect 3-10% of patients after liver transplantation (LT), leading to potentially life-threatening complications. In the days following LT, antithrombin (AT) is decreased longer than pro-coagulant factors, thus favouring a pro-thrombotic profile. Plasma transfusions are given empirically in some centres to correct AT levels following LT. We assessed the effect of plasma transfusion on AT levels after paediatric LT. Prospective single-centre observational study in 20 consecutive paediatric LT recipients over a 24-month period. Plasma was administered twice daily (10 ml/kg/dose) according to an existing protocol. AT levels were measured once daily, immediately prior to and one hour after the morning plasma transfusion. Sample size was calculated based on a non-inferiority hypothesis. The median age and weight were 11.6 years (IQR 2.8; 14.7) and 40 kg (IQR 12.75; 44.8), respectively. We collected 85-paired blood samples. The median AT level prior to plasma transfusion was 58%. The median difference in AT levels before and after plasma transfusion was 4.2% (P = 0.001). Changes in AT levels after plasma transfusion were not correlated with baseline AT levels (R = 0.19) or patient weight (R = 0.18). Plasma transfusions only marginally increase AT levels in children after LT. Therefore, prophylactic plasma transfusions probably do not seem to confer an advantage in the routine management of paediatric LT patients. Randomized controlled trials are needed to identify the optimal anticoagulation strategy in this specific population. © 2018 International Society of Blood Transfusion.
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Does the CRH binding protein shield the anterior pituitary from placental CRH?
Thomson, M
1998-12-01
Corticotropin releasing factor (CRH) is released from the hypothalamus and travels to the anterior pituitary where it stimulates the release of adrenocorticotropin (ACTH). In turn, ACTH travels through the blood and stimulates the release of cortisol from the adrenal. The placenta is also a source of CRH and is responsible for the dramatic rises in CRH plasma levels in the third trimester of pregnancy. A CRH binding protein may stop placental CRH from overstimulating the pituitary and may contribute to the reason that pregnant women show only mildly elevated levels of ACTH in the blood. There is evidence to suggest, however, that the CRH binding protein does not completely shield the corticotrope from placental CRH.
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Plasma BDNF levels following weight recovery in anorexia nervosa.
Phillips, Kathryn E; Jimerson, David C; Pillai, Anilkumar; Wolfe, Barbara E
2016-10-15
Preclinical studies have implicated brain-derived neurotrophic factor (BDNF) in the regulation of eating behavior and body weight. As reviewed in this report, prior studies of BDNF levels in anorexia nervosa have yielded variable results, perhaps reflecting effects of malnutrition and psychiatric comorbidity. The goal of the current report was to assess plasma BDNF as a biomarker in weight-recovered individuals with a history of anorexia nervosa (ANWR). Study groups included women meeting criteria for ANWR and healthy female controls. Participants were in a normal weight range, free of current major psychiatric disorder, and free of medication. Self-ratings included eating disorder symptoms, depression and anxiety. Plasma BDNF levels were measured by enzyme linked immunoassay. Plasma BDNF levels were not significantly different for ANWR and control groups. Plasma BDNF levels were inversely correlated with anxiety ratings in controls (p<0.02) but not in the ANWR group. This report provides new evidence that circulating BDNF concentrations do not differ in healthy controls and ANWR free of psychiatric comorbidity. Additionally, the data provide new information on the relationship between plasma BDNF and anxiety in these two study groups. Copyright © 2016 Elsevier Inc. All rights reserved.
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Chemotherapy and plasma adipokines level in patients with colorectal cancer.
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.
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Clinical Characteristics of Endogenous Cushing's Syndrome at a Medical Center in Southern Taiwan
Tung, Shih-Chen; Wang, Pei-Wen; Liu, Rue-Tsuan; Chen, Jung-Fu; Hsieh, Ching-Jung; Kuo, Ming-Chun; Yang, Joseph W.; Lee, Wei-Ching; Cheng, Min-Hsiung; Lee, Tao-Chen
2013-01-01
From January 1987 to December 2011, over a total of 25 years, 84 patients with Cushing's syndrome (CS) were identified at a medical center in southern Taiwan. We observed a higher incidence of ACTH-independent CS (75%) than ACTH-dependent CS (25%). A higher incidence of adrenocortical adenoma (58.3%) than Cushing's disease (CD, 21.4%) was also found. The sensitivity of the definitive diagnostic tests for CS, including loss of plasma cortisol circadian rhythm, a baseline 24 h urinary free cortisol (UFC) value >80 μg, and overnight and 2-day low-dose dexamethasone suppression test, was between 94.4% and 100%. For the 2-day high-dose dexamethasone suppression test for the differential diagnosis of CD, the sensitivity of 0800 h plasma cortisol and 24 h UFC was 44.4% and 85.7%, respectively. For the differential diagnosis of adrenal CS, the sensitivities of the 0800 h plasma cortisol and 24 h UFC were 95.5% and 88.9%, respectively. In patients with ACTH-independent CS and ACTH-dependent CS, the baseline plasma ACTH levels were all below 29 pg/mL and above 37 pg/mL, respectively. The postsurgical hospitalization stay following retroperitoneoscopic adrenalectomy was shorter than that observed for transabdominal adrenalectomy (4.3 ± 1.6 versus 8.8 ± 3.7 days, P < 0.001). It was easy to develop retroperitoneal and peritoneal seeding of adrenocortical carcinoma via laparoscopic adrenalectomy. PMID:24062770
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A role for 11C-methionine PET imaging in ACTH-dependent Cushing's syndrome.
Koulouri, Olympia; Steuwe, Andrea; Gillett, Daniel; Hoole, Andrew C; Powlson, Andrew S; Donnelly, Neil A; Burnet, Neil G; Antoun, Nagui M; Cheow, Heok; Mannion, Richard J; Pickard, John D; Gurnell, Mark
2015-10-01
We report our experience of functional imaging with (11)C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome. Twenty patients with i) de novo Cushing's disease (CD, n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy; n=8) or iii) ectopic Cushing's syndrome (n=2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI. All patients underwent (11)C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of (11)C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging. In seven of ten patients with de novo CD, asymmetric (11)C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal (11)C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, (11)C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region. (11)C-methionine PET-CT can aid the detection of
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Şimşek, Şeref; Gençoğlan, Salih; Yüksel, Tuğba; Kaplan, İbrahim; Alaca, Rümeysa
2016-07-01
In this study, we investigated serum brain-derived neurotrophic factor (BDNF), adrenocorticotropic hormone (ACTH), and cortisol levels between children with obsessive-compulsive disorder (OCD) prior to treatment and healthy controls. In addition, the study aimed to assess any correlations between OCD symptom severity and BDNF, ACTH, and cortisol levels. Twenty-nine children, aged from 7 to 17 years (male/female: 21/8) and diagnosed with OCD according to DSM-IV prior to treatment, were compared with 25 healthy control subjects (male/female: 16/9). The study was conducted between December 2012 and December 2013. The Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version (K-SADS-PL), Children's Yale-Brown Obsessive Compulsive Scale, and Children's Depression Inventory (CDI) were administered to the children. BDNF, ACTH, and cortisol levels were detected using a prepared kit with the enzyme-linked immunosorbent assay method. BDNF, ACTH, and cortisol levels in the OCD group were significantly higher when compared with the control group (P = .02, P = .03, and P = .046, respectively). No association was detected between the severity and duration of OCD symptoms and BDNF, ACTH, and cortisol levels. CDI scores in both groups were similar. The mean (SD) duration of OCD symptoms was 17.9 (18.5) months. Our findings suggest that BDNF levels adaptively increase as a result of the damaging effects of the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity on brain tissue in the early stages of OCD. HPA axis abnormalities and BDNF may play a role in the pathogenesis of the disease. © Copyright 2016 Physicians Postgraduate Press, Inc.
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Pavlovian autoshaping procedures increase plasma corticosterone levels in rats.
Tomie, Arthur; Silberman, Yuval; Williams, Kayon; Pohorecky, Larissa A
2002-06-01
Pavlovian autoshaping conditioned responses (CRs) are complex sequences of conditioned stimulus (CS)-directed skeletal-motor responses that are elicited by CS objects predictive of food unconditioned stimulus (US). Autoshaping CRs are observed under conditions known to be conducive to elevations in plasma corticosterone levels, as, for example, in response to the eating of food as well as in response to signals predictive of food. Two experiments investigated the relationships between Pavlovian autoshaping procedures, the performance of Pavlovian autoshaping CRs, and plasma corticosterone levels in male Long-Evans rats. In Experiment 1, rats in the CS-US paired group (n=30) were given 20 daily sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of the food US. Tail blood samples obtained after the 20th autoshaping session revealed higher plasma corticosterone levels in the CS-US paired group than in the CS-US random control group (n=10). In Experiment 2, rats (n=35) were assessed for basal plasma corticosterone levels 2 weeks prior to autoshaping training. Plasma samples obtained immediately following the first autoshaping session, and prior to the acquisition of lever-press autoshaping CR performance, revealed higher plasma corticosterone levels in the CS-US paired group (n=24) relative to basal levels. This effect was not observed in the CS-US random control group (n=11). Data suggest that corticosterone release is a physiological endocrine Pavlovian CR induced by lever CS-food US pairings during Pavlovian autoshaping procedures, rather than a by-product of autoshaping CR performance. Implications of the link between autoshaping procedures and corticosterone release are discussed.
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A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome.
Reincke, Martin; Ritzel, Katrin; Oßwald, Andrea; Berr, Christina; Stalla, Günter; Hallfeldt, Klaus; Reisch, Nicole; Schopohl, Jochen; Beuschlein, Felix
2015-10-01
Our aim was to review short- and long-term outcomes of patients treated with bilateral adrenalectomy (BADx) in ACTH-dependent Cushing's syndrome. We reviewed the literature and analysed our experience with 53 patients treated with BADx since 1990 in our institution. BADx is considered if ACTH-dependent Cushing's syndrome is refractory to other treatment modalities. In Cushing's disease (CD), BADx is mainly used as an ultima ratio after transsphenoidal surgery and medical therapies have failed. In these cases, the time span between the first diagnosis of CD and treatment with BADx is relatively long (median 44 months). In ectopic Cushing's syndrome, the time from diagnosis to BADx is shorter (median 2 months), and BADx is often performed as an emergency procedure because of life-threatening complications of severe hypercortisolism. In both situations, BADx is relatively safe (median surgical morbidity 15%; median surgical mortality 3%) and provides excellent control of hypercortisolism; Cushing's-associated signs and symptoms are rapidly corrected, and co-morbidities are stabilised. In CD, the quality of life following BADx is rapidly improving, and long-term mortality is low. Specific long-term complications include the development of adrenal crisis and Nelson's syndrome. In ectopic Cushing's syndrome, long-term mortality is high but is mostly dependent on the prognosis of the underlying malignant neuroendocrine tumour. BADx is a relatively safe and highly effective treatment, and it provides adequate control of long-term co-morbidities associated with hypercortisolism. © 2015 European Society of Endocrinology.
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Krysiak, Robert; Kowalska, Beata; Żmuda, Witold; Okopień, Bogusław
2015-04-01
Aggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70 mg/dL. The study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. Replacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. Our results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
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High plasma neopterin levels in Chinese children with autism spectrum disorders.
Zhao, Hong-xiang; Yin, Sha-sha; Fan, Jin-gang
2015-04-01
Neopterin, a pteridine mainly synthesized by activated macrophages, is a marker of inflammation, immune system activation and an active participant in Autism spectrum disorders (ASD). The aim of this study was to assess the clinical significance of plasma neopterin levels in ASD. Eighty patients diagnosed with ASD and 80 sex and age matched typically developing children were assessed for plasma levels of neopterin at admission. Plasma neopterin levels were measured using a human ELISA kit and severity of ASD were evaluated with the Childhood Autism Rating Scale (CARS) score. We found that the mean plasma neopterin level was significantly (P<0.0001) higher in children with ASD as compared to controls. Plasma neopterin increased with increasing severity of ASD as defined by the CARS score. Based on the ROC curve, the optimal cutoff value of plasma neopterin level as an indicator for auxiliary diagnosis of ASD was projected to be 8.5nmol/L, which yielded a sensitivity of 84.2% and a specificity of 80.1%, with the area under the curve at 0.876 (95% CI, 0.825-0.928). Elevated neopterin (≥8.5nmol/L) was an independent diagnosis indicator of ASD with an adjusted OR of 12.11 (95% CI: 5.48-28.11; P<0.0001). These results indicated that autistic children had higher plasma levels of neopterin, and elevated plasma neopterin levels may be associated with severity of ASD among Chinese children. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Concentrations in plasma clozapine levels in schizophrenic and schizoaffective patients.
Iglesias García, Celso; Iglesias Alonso, Ana; Bobes, Julio
There is great variability in plasma levels of clozapine. The objective of this study is to know the characteristics of patients treated with clozapine and the relationship between them and the variability of plasma levels. Descriptive, cross-sectional study of all patients currently treated with clozapine in a Psychiatric Service with a diagnosis of schizophrenic psychosis or schizoaffective disorder. The present study assessed physical situation, psychopathology and functionality of the patients and explored the associations and correlations between clinical variables and plasma levels. We studied 39 patients, predominantly men, with negative and depressive symptoms and cardiovascular risk factors (metabolic syndrome and smoking). Significant variability in dose and even greater in clozapine levels were observed. The levels of clozapine at equal doses/kg of body weight were higher in non-smokers, they had positive correlation with BMI and negative correlation with systolic BP, disruptive behaviors and number of cigarettes consumed. Plasma level monitoring clozapine is an important tool to avoid clozapine plasma levels monitoring and minimize undesirable clinical situations (metabolic syndrome, sedation, negative symptoms and functional impairment). It is also important to control the effects of a smoking habit for optimum drug bioavailability. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.
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Jouffe, Vincent; Rowe, Suzanne; Liaubet, Laurence; Buitenhuis, Bart; Hornshøj, Henrik; SanCristobal, Magali; Mormède, Pierre; de Koning, D J
2009-07-16
Microarray studies can supplement QTL studies by suggesting potential candidate genes in the QTL regions, which by themselves are too large to provide a limited selection of candidate genes. Here we provide a case study where we explore ways to integrate QTL data and microarray data for the pig, which has only a partial genome sequence. We outline various procedures to localize differentially expressed genes on the pig genome and link this with information on published QTL. The starting point is a set of 237 differentially expressed cDNA clones in adrenal tissue from two pig breeds, before and after treatment with adrenocorticotropic hormone (ACTH). Different approaches to localize the differentially expressed (DE) genes to the pig genome showed different levels of success and a clear lack of concordance for some genes between the various approaches. For a focused analysis on 12 genes, overlapping QTL from the public domain were presented. Also, differentially expressed genes underlying QTL for ACTH response were described. Using the latest version of the draft sequence, the differentially expressed genes were mapped to the pig genome. This enabled co-location of DE genes and previously studied QTL regions, but the draft genome sequence is still incomplete and will contain many errors. A further step to explore links between DE genes and QTL at the pathway level was largely unsuccessful due to the lack of annotation of the pig genome. This could be improved by further comparative mapping analyses but this would be time consuming. This paper provides a case study for the integration of QTL data and microarray data for a species with limited genome sequence information and annotation. The results illustrate the challenges that must be addressed but also provide a roadmap for future work that is applicable to other non-model species.
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[Uncommon neonatal case of hypoglycemia: ACTH resistance syndrome].
Delmas, O; Marrec, C; Caietta, E; Simonin, G; Morel, Y; Girard, N; Roucher, F; Sarles, J; Chabrol, B; Reynaud, R
2014-12-01
Monitoring of blood glucose is usually reported to reduce the risk of hypoglycemia in term newborns with high risk factors and for prematurity in neonatal intensive care unit patients. Differential diagnosis has rarely been discussed. In the eutrophic term newborn, hypoglycemia remains rare and an etiological diagnosis must be made. Intensive management of neonatal hypoglycemia is required to prevent neurodevelopmental defects. Without evident cause or if hypoglycemia persists, a systematic review of possible causes should be made. We report isolated glucocorticoid deficiency diagnosed in an infant at 10 months of age. This boy had neonatal hypoglycemia and mild jaundice that had not been investigated. During his first 9 months of life, he presented frequent infections. At 10 months of age, febrile seizures occurred associated with shock, hypoglycemia, hyponatremia, mild hyperpigmentation, and coma. He was diagnosed with hypocortisolemia and elevated ACTH levels. Brain injury was revealed by MRI after resuscitation, with hypoxic-ischemic and hypoglycemic encephalopathy. The molecular studies demonstrated the presence of p.Asp107Asn and previously unreported frameshift p.Pro281GlnfsX9 MC2R gene mutations. A substitutive hormone therapy was provided and during a follow-up of 12 months no adrenal crisis was noted. We report an unusual case of familial glucocorticoid deficiency with severe neurological injury. This case demonstrates the importance of an appropriate etiological diagnosis in neonatal hypoglycemia. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
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Plasma oxalic acid and calcium levels in oxalate poisoning
Zarembski, P. M.; Hodgkinson, A.
1967-01-01
Observations are reported on five cases of suicide or attempted suicide by poisoning with oxalic acid or ethylene glycol. Elevated oxalic acid levels were observed in the plasma, stomach contents, and a number of tissues. Raised oxalic acid levels in plasma were associated with reduced total and ultrafilterable calcium levels. It is suggested that the reduction in plasma total calcium level is due mainly to the deposition of calcium oxalate in the soft tissues, but inhibition of the parathyroid glands may be a contributory factor. Microscopic examination of various tissues indicated that oxalic acid is deposited in the tissues in two forms: (1) crystalline calcium oxalate dihydrate in the kidney and (2) a non-crystalline complex of calcium oxalate and lipid in liver and other tissues. PMID:5602563
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Nyberg, M; Mortensen, S P; Hellsten, Y
2013-03-01
Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study 2, young (23 ± 1 years, n = 8), older lifelong sedentary (66 ± 2 years, n = 8) and older lifelong endurance-trained (62 ± 2 years, n = 8) subjects were studied in a cross-sectional design. Skeletal muscle and plasma endothelin-1 levels were increased with age and plasma endothelin-1 levels were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension. This effect may explain some of the beneficial effects of training on the cardiovascular system in older and hypertensive subjects. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.
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Yamashita, A; Koike, Y; Takahashi, A; Hirayama, M; Murakami, N; Sobue, G
1997-08-01
We evaluated plasma noradrenaline (NA) levels at test and during head-up tilt test in 20 patients with sporadic amyotrophic lateral sclerosis (ALS). Their fasting plasma NA levels ranged from 195 to 4227 pg/ml. The average plasma NA level was 483 pg/ml in five ambulatory patients, 341 in two wheelchair-bound patients, 1264 in 11 bedridden patients, and 208 in two respirator-dependent patients whose disability grading was the worst among the four groups. Arterial carbon dioxide (PCO2) was evaluated as a measure of respiratory function. The coefficient of correlation between PCO2 and plasma NA was r = 0.654 (p < 0.01). Either respiratory failure or lower motor neuron dysfunction may relate to the elevation of plasma NA levels. In the two bedridden patients, plasma NA levels and heart rate at rest increased significantly as the disease progressed. Cardiovascular responses to head-up tilting were normal. These data suggest that the elevation of plasma NA levels may be related to progression of respiratory failure and lower motor neuron dysfunction. In conclusion, sympathetic hyperactivity in ALS is considered to be not primary, but secondary to somatic motor disabilities and respiratory failure.
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Study of plasma adrenomedullin level in normal pregnancy and preclampsia.
Senna, Azza Abo; Zedan, Magda; el-Salam, Gamal E Abd; el-Mashad, Ashraf I
2008-02-06
The aim of this study was to evaluate whether maternal circulating adrenomedullin (AM) values in patients with preeclampsia are different from those in normotensive pregnant women at different gestational ages. In a prospective clinical study, 90 women aged 17 to 40 years old, were divided into 4 main groups: group I (45 women): Normotensive pregnant women at first trimester (15 women), second trimester (15 women), and third trimester (15 women) of pregnancies. Group II (15 women): Pregnant women with preeclampsia at 25 to 38 weeks of gestation. Group III (15 women): Normotensive healthy nonpregnant women. Group IV (15 women): Hypertensive nonpregnant women. The plasma AM concentration was measured in all women by using enzyme immunoassay kits. Plasma AM levels in pregnant women with normal blood pressure at different gestational ages (first, second, and third trimesters) were statistically significantly higher than those detected in nonpregnant normotensive women and significantly increased with increasing gestational age (P < .001). Moreover, there was significant positive correlation between plasma AM levels and increasing gestational age (r = 0.915, P < .001). Preeclamptic patients had the highest mean plasma AM levels compared with all other groups, which is statistically significant (P < .001) and there was a significant positive correlation between plasma AM levels and systolic blood pressure, diastolic blood pressure, severity of preeclampsia, and proteinuria in pregnant patients with preeclampsia. Maternal plasma AM concentration increases throughout pregnancy and increases as gestational age progresses. AM production starts very early in gestation, suggesting that it may have an important role in human reproduction, from implantation to delivery. Maternal plasma AM level in preeclampsia appears to be higher than that in normal pregnancy.
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Plasma RANTES and eotaxin levels are correlated with the severity of chronic rhinosinusitis.
Chao, Pin-Zhir; Chou, Chi-Ming; Chen, Chen-Ho
2012-11-01
Eosinophilia occurs in up to 75-90% of nasal polyps in Caucasians. The chemokines eotaxin and RANTES increase eosinophil recruitment, activation, and survival, and these chemokines are significantly expressed in nasal polyps. We hypothesized that eotaxin and RANTES plasma levels might be correlated with disease severity. We compared the eotaxin and RANTES plasma levels in 20 Taiwanese patients with chronic rhinosinusitis and nasal polyps and 20 Taiwanese healthy controls. Eotaxin and RANTES plasma levels were measured by ELISA and disease severity was scored by CT scans. Compared to controls, patients with nasal polyps had significantly elevated plasma levels of eotaxin and RANTES and increased peripheral blood eosinophils (p < 0.001). Eotaxin plasma levels were significantly correlated with disease severity in patients with chronic rhinosinusitis to a greater extent than were RANTES levels. RANTES and eotaxin levels were also positively correlated with the percentages of peripheral blood eosinophils. Eotaxin plasma levels are significantly correlated with disease severity in Taiwanese patients with nasal polyposis to a greater degree than are RANTES levels. Additional studies are needed to assess whether eotaxin plasma levels can be used to monitor disease progression and attenuation.
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Leptin inhibits and ghrelin augments hypothalamic noradrenaline release after stress.
Kawakami, Akio; Okada, Nobukazu; Rokkaku, Kumiko; Honda, Kazufumi; Ishibashi, Shun; Onaka, Tatsushi
2008-09-01
Metabolic conditions affect hypothalamo-pituitary-adrenal responses to stressful stimuli. Here we examined effects of food deprivation, leptin and ghrelin upon noradrenaline release in the hypothalamic paraventricular nucleus (PVN) and plasma adrenocorticotropic hormone (ACTH) concentrations after stressful stimuli. Food deprivation augmented both noradrenaline release in the PVN and the increase in plasma ACTH concentration following electrical footshocks (FSs). An intracerebroventricular injection of leptin attenuated the increases in hypothalamic noradrenaline release and plasma ACTH concentrations after FSs, while ghrelin augmented these responses. These data suggest that leptin inhibits and ghrelin facilitates neuroendocrine stress responses via noradrenaline release and indicate that a decrease in leptin and an increase in ghrelin release after food deprivation might contribute to augmentation of stress-induced ACTH release in a fasting state.
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Effect of laparotomy on the pituitary-adrenal axis in dogs.
Skovira, Emily J; Behrend, Ellen N; Martin, Linda G; Palmer, Lee E; Kemppainen, Robert J; Lee, Hollie P
2017-08-01
OBJECTIVE To assess effects of major abdominal surgery on serum cortisol and aldosterone and plasma canine ACTH (cACTH) concentrations. ANIMALS 39 healthy dogs undergoing laparotomy during veterinary student surgical laboratories. PROCEDURES Blood samples were obtained before and at completion of surgery. Serum cortisol and aldosterone and plasma cACTH concentrations were measured by use of validated radioimmunoassays. Changes in concentrations (postoperative concentration minus preoperative concentration) were calculated. Data were analyzed by use of the Wilcoxon signed rank test, Pearson correlation analysis, and Mann-Whitney rank sum test. RESULTS Cortisol, aldosterone, and cACTH concentrations increased significantly from before to after surgery. Although cortisol and aldosterone concentrations increased in almost all dogs, cACTH concentrations decreased in 6 of 32 (19%) dogs. All dogs had preoperative cortisol concentrations within the reference range, but 24 of 39 (62%) dogs had postoperative concentrations above the reference range. A correlation between the change in cACTH concentration and the change in cortisol concentration was not detected. CONCLUSIONS AND CLINICAL RELEVANCE Laparotomy caused a significant increase in serum cortisol and aldosterone concentrations. In most dogs, but not all dogs, plasma cACTH concentrations increased. Lack of correlation between the change in cACTH concentration and the change in cortisol concentration suggested that increased postoperative cortisol concentrations may have been attributable to ACTH-independent mechanisms, an early ACTH increase that caused a sustained cortisol release, or decreased cortisol clearance. Further studies are indicated to evaluate the effects of various anesthetic protocols and minimally invasive surgical techniques on the stress response.
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Nikaido, Y; Nakashima, T
2009-05-16
Although various emotional behaviors and activation of the hypothalamic-pituitary-adrenal (HPA) axis of rats are induced by the exposure of 2,5-dihydro-2,4,5-trimethylthiazoline: TMT, a component of fox odor, these odor-induced responses are influenced by the external environment. Our previous study demonstrated that exposure to green odor, a mixture of cis-3-hexenol and trans-2-hexenal, attenuated stress-induced elevation of the plasma ACTH level in rats. The present study investigated the effect of TMT or green odor on emotional behavior and the HPA axis stress response with or without the influence of environmental novelty. We exposed rats to TMT or green odor in "familiar" or "unfamiliar" environments and compared the various responses, including fear-related behaviors, non-defensive behaviors and plasma ACTH concentrations. TMT induced enhanced freezing behavior, reduced exploration behavior and elevations in plasma ACTH concentrations in two environmental conditions. Comparing TMT-induced responses in an unfamiliar environment with the familiar environment showed that environmental novelty enhanced TMT-induced fear-related behaviors and elevations of plasma ACTH concentrations. These results revealed that TMT causes fear and stress responses in both familiar and unfamiliar environments, although the novelty of an unfamiliar environment enhances these TMT-induced responses. On the other hand, green odor did not induce any responses in either environment. These findings indicate that odor-induced responses are influenced by the surrounding environment.
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Clozapine-Related EEG Changes and Seizures: Dose and Plasma-Level Relationships
Varma, Seema; Bishara, Delia; Besag, Frank M. C.; Taylor, David
2011-01-01
Clozapine is a widely used atypical antipsychotic with a unique effectiveness in treatment-resistant schizophrenia. An important adverse effect is seizures, which have been observed at all stages of clozapine treatment. Valproate has traditionally been considered the drug of choice for the prophylaxis of clozapine seizures, however it may not be the most suitable choice for all patients. There is disagreement as to the best point to prescribe valproate or a suitable antiepileptic: as seizure prophylaxis at a certain clozapine dose or level, or only as remedial treatment. In this review, we examine the relevant literature with an aim to evaluate the following relationships: clozapine dose and electroencephalogram (EEG) abnormalities, plasma levels and EEG abnormalities, dose and occurrence of seizures and plasma levels and occurrence of seizures. Weighted linear regression models were fitted to investigate these relationships. There was a strong relationship between clozapine dose and plasma level and occurrence of clozapine-induced EEG abnormalities. However, a statistically significant relationship between dose and occurrence of seizures was not found. A relationship between clozapine plasma level and occurrence of seizures was not established because of the scarcity of useful data although our review found three case reports which suggested that there is a very substantial risk of seizures with clozapine plasma levels exceeding 1300 μg/l. Seizures are more common during the initiation phase of clozapine treatment, suggesting a slow titration to target plasma levels is desirable. An antiepileptic drug should be considered when the clozapine plasma level exceeds 500 μg/l, if the EEG shows clear epileptiform discharges, if seizures, myoclonic jerks or speech difficulties occur and when there is concurrent use of epileptogenic medication. The antiepileptics of choice for the treatment and prophylaxis of clozapine-induced seizures are valproate (particularly where
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Study of Plasma Adrenomedullin Level In Normal Pregnancy and Preclampsia
Senna, Azza Abo; Zedan, Magda; Abd El Salam, Gamal E.; El Mashad, Ashraf I.
2008-01-01
Aim The aim of this study was to evaluate whether maternal circulating adrenomedullin (AM) values in patients with preeclampsia are different from those in normotensive pregnant women at different gestational ages. Subjects and Methods In a prospective clinical study, 90 women aged 17 to 40 years old, were divided into 4 main groups: group I (45 women): Normotensive pregnant women at first trimester (15 women), second trimester (15 women), and third trimester (15 women) of pregnancies. Group II (15 women): Pregnant women with preeclampsia at 25 to 38 weeks of gestation. Group III (15 women): Normotensive healthy nonpregnant women. Group IV (15 women): Hypertensive nonpregnant women. The plasma AM concentration was measured in all women by using enzyme immunoassay kits. Results Plasma AM levels in pregnant women with normal blood pressure at different gestational ages (first, second, and third trimesters) were statistically significantly higher than those detected in nonpregnant normotensive women and significantly increased with increasing gestational age (P < .001). Moreover, there was significant positive correlation between plasma AM levels and increasing gestational age (r = 0.915, P < .001). Preeclamptic patients had the highest mean plasma AM levels compared with all other groups, which is statistically significant (P < .001) and there was a significant positive correlation between plasma AM levels and systolic blood pressure, diastolic blood pressure, severity of preeclampsia, and proteinuria in pregnant patients with preeclampsia. Conclusion Maternal plasma AM concentration increases throughout pregnancy and increases as gestational age progresses. AM production starts very early in gestation, suggesting that it may have an important role in human reproduction, from implantation to delivery. Maternal plasma AM level in preeclampsia appears to be higher than that in normal pregnancy. PMID:18382699
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Plasma Actin, Gelsolin and Orosomucoid Levels after Eccentric Exercise.
Tékus, Éva; Váczi, Márk; Horváth-Szalai, Zoltán; Ludány, Andrea; Kőszegi, Tamás; Wilhelm, Márta
2017-02-01
The present study investigated the acute effect of eccentric exercise on blood plasma actin, gelsolin (GSN) and orosomucoid (AGP) levels in untrained and moderately trained individuals, and their correlation with exercise induced muscle damage (EIMD) markers (CK, intensity of muscle soreness and maximal voluntary contraction torque deficit). Healthy physical education students (6 untrained, 12 moderately trained) participated in this research. Actin, GSN, AGP and CK levels were measured in blood plasma at baseline, immediately, 1 h, 6 h and 24 h post-exercise comprising 90 eccentric quadriceps contractions performed on a dynamometer. There was significant time main effect for GSN, AGP, CK and significant difference was found between baseline and the lowest value of post-exercise GSN (p < 0.05), as well as baseline and the highest value of post-exercise AGP (p < 0.05). Relationships were found between GSN levels and other indirect EIMD markers (between all GSN levels at post-exercise and CK activity at 6 h, p < 0.05; GSNMIN and muscle soreness at post-exercise, p < 0.04), GSN and AGP; however, actin did not correlate at any time points with GSN. Actin, GSN, AGP and CK responses after eccentric exercise do not seem sensitive to training status. The plasma actin level is used as an indicator of injury, however, our results suggest that it is not an accurate marker of EIMD, while plasma GSN concentrations show a better relationship with EIMD and the post-exercise inflammatory process. The elevated plasma AGP and the correlation between GSN and AGP seem to be promising for assessment of exercise-induced muscle injury.
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Plasma Actin, Gelsolin and Orosomucoid Levels after Eccentric Exercise
Váczi, Márk; Horváth-Szalai, Zoltán; Ludány, Andrea; Kőszegi, Tamás; Wilhelm, Márta
2017-01-01
Abstract The present study investigated the acute effect of eccentric exercise on blood plasma actin, gelsolin (GSN) and orosomucoid (AGP) levels in untrained and moderately trained individuals, and their correlation with exercise induced muscle damage (EIMD) markers (CK, intensity of muscle soreness and maximal voluntary contraction torque deficit). Healthy physical education students (6 untrained, 12 moderately trained) participated in this research. Actin, GSN, AGP and CK levels were measured in blood plasma at baseline, immediately, 1 h, 6 h and 24 h post-exercise comprising 90 eccentric quadriceps contractions performed on a dynamometer. There was significant time main effect for GSN, AGP, CK and significant difference was found between baseline and the lowest value of post-exercise GSN (p < 0.05), as well as baseline and the highest value of post-exercise AGP (p < 0.05). Relationships were found between GSN levels and other indirect EIMD markers (between all GSN levels at post-exercise and CK activity at 6 h, p < 0.05; GSNMIN and muscle soreness at post-exercise, p < 0.04), GSN and AGP; however, actin did not correlate at any time points with GSN. Actin, GSN, AGP and CK responses after eccentric exercise do not seem sensitive to training status. The plasma actin level is used as an indicator of injury, however, our results suggest that it is not an accurate marker of EIMD, while plasma GSN concentrations show a better relationship with EIMD and the post-exercise inflammatory process. The elevated plasma AGP and the correlation between GSN and AGP seem to be promising for assessment of exercise-induced muscle injury. PMID:28469748
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Plasma substance P levels in patients with persistent cough.
Otsuka, Kojiro; Niimi, Akio; Matsumoto, Hisako; Ito, Isao; Yamaguchi, Masafumi; Matsuoka, Hirofumi; Jinnai, Makiko; Oguma, Tsuyoshi; Takeda, Tomoshi; Nakaji, Hitoshi; Chin, Kazuo; Sasaki, Kazuhiko; Aoyama, Norihito; Mishima, Michiaki
2011-01-01
Substance P (SP) is involved in the pathogenesis of cough in animal models. However, few studies in humans have been reported and the roles of SP in clinical cough remain obscure. To clarify the relevance of plasma levels of SP in patients with persistent cough. We studied 82 patients with cough persisting for at least 3 weeks and 15 healthy controls. Patients were classified as having asthmatic cough (cough-variant asthma and cough-predominant asthma; n = 61) or nonasthmatic cough (n = 21; postinfectious cough, n = 6; gastroesophageal reflux disease, n = 5; idiopathic cough, n = 5, and others, n = 5). Correlations were evaluated between plasma SP levels as measured with ELISA and methacholine airway hyperresponsiveness (airway sensitivity and airway reactivity), capsaicin cough sensitivity, sputum eosinophil and neutrophil counts, and pulmonary function. Plasma SP levels were significantly elevated in patients with both asthmatic and nonasthmatic cough compared with controls [31.1 pg/ml (range 18.0-52.2) and 30.0 pg/ml (range 15.1-50.3) vs. 15.4 pg/ml (range 11.3-23.7); p = 0.003 and p = 0.038, respectively] but did not differ between the two patient groups (p = 0.90). Plasma SP levels correlated with airway sensitivity (threshold dose of methacholine) in the patients with asthmatic cough (r = -0.37, p = 0.005) but not with airway reactivity, cough sensitivity, FEV1 values, or sputum eosinophil and neutrophil counts in either group. Increased levels of SP in plasma are associated with persistent cough in humans and might be related to airway sensitivity in asthmatic cough. Copyright © 2011 S. Karger AG, Basel.
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Impact and Timing of Bilateral Adrenalectomy for Refractory ACTH-Dependent Cushing’s Syndrome
Morris, Lilah F.; Harris, Rachel S.; Milton, Denái R.; Waguespack, Steven G.; Habra, Mouhammed A.; Jimenez, Camilo; Vassilopoulou-Sellin, Rena; Lee, Jeffrey E.; Perrier, Nancy D.; Grubbs, Elizabeth G.
2014-01-01
Introduction In patients with refractory ACTH-dependent Cushing’s syndrome (CS), we evaluated steroidogenesis inhibition (SI) and bilateral adrenalectomy (BA) to predict which patients might benefit most from each treatment modality. Methods Clinical data from patients treated 1970-2012 were retrospectively reviewed by treatment group (SI or SI+BA). Validated severity scales were used to calculate metabolic (M) score (hypokalemia, hyperglycemia, hypertension, proximal muscle weakness) and adverse events (AE) score (thrombosis, fracture, infection). Results 65 patients (16 pituitary, 49 ectopic) were treated with SI+BA (n=21,32%) or SI alone (n=44,68%). Presenting M scores and source of ACTH excess (ectopic vs. pituitary) were similar. Both groups improved metabolically after treatment. 39% of AEs in the SI+BA group occurred within 12 months of presentation. 24(55%) SI patients died (median survival 24.0 months); steroid excess contributed to 71%. Six SI+BA patients died (29%), including all 3 patients with recurrent CS after BA. Minor perioperative complications occurred in 7 patients (33%). Conclusions Post-treatment M and AE scores improved for all patients and 70% of AEs occurred in SI+BA patients within 12 months of presentation, emphasizing the importance of early surgical intervention. These data argue for the safety and efficacy of early BA in selected patients with uncontrollable CS. PMID:24383115
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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.
2014-01-01
Abstract 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. PMID:25209674
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Márquez, Cristina; Belda, Xavier; Armario, Antonio
2002-02-01
Acute immobilization in male rats elicited the same ACTH, corticosterone and glucose response as foot shock when measured immediately after stress. However, post-stress recovery of plasma ACTH, corticosterone and glucose levels were delayed in immobilized versus shocked rats. Similarly, stress-induced anorexia was much greater in the former animals. All these data suggest that post-stress speed of recovery of some physiological variables is positively related to stressor intensity and could be used to evaluate it.
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Effects of whole-body vibration on plasma sclerostin level in healthy women.
Çidem, Muharrem; Karakoç, Yunus; Ekmekçi, Hakan; Küçük, Suat Hayri; Uludağ, Murat; Gün, Kerem; Karamehmetoğlu, Safak Sahir; Karacan, İlhan
2014-01-01
To determine whether plasma sclerostin levels are affected by applying whole-body vibration treatments. Following a pilot study, the pretsent prospective, randomized, controlled single-blind study was performed on 16 healthy volunteer women (ages 20 to 40 years). Subjects were randomly divided into 2 groups, and whole-body vibration was applied to the treatment group but not to the controls. The plasma sclerostin levels were measured before the treatment and at the 10th minute after whole-body vibration on the 1st, 2nd, and 5th days of application. The plasma sclerostin level measured at 10 min after the whole-body vibration treatment increased 91% (P = 0.024) on the 1st day and decreased 31.5% (P = 0.03) on the 5th day in the whole-body vibration group. In the control group, there was no change in the plasma sclerostin level at any time. A progressive increase in baseline plasma sclerostin levels during the 5 days of vibration sessions was also found. Our study demonstrated that whole-body vibration can change plasma sclerostin levels, and that this change is detectable 10 min after whole-body vibration treatments.
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Immunoglobulin G levels during collection of large volume plasma for fractionation.
Burkhardt, Thomas; Rothe, Remo; Moog, Rainer
2017-06-01
There is a need of comprehensive work dealing with the quality of plasma for fractionation with respect to the IgG content as today most plasma derivates are used to treat patients with immunodeficiencies and autoimmune disorders. Therefore, a prospective study was carried out to analyse IgG levels before plasmapheresis and every 200ml collected plasma. Fifty-four experienced plasmapheresis donors were recruited for subsequent 850ml plasmapheresis using the Aurora Plasmapheresis System. Donorś peripheral blood counts were analysed before and after plasmapheresis using an electronic counter. Total protein, IgG and citrate were measured turbidometrically before, during and after apheresis as well as in the plasma product. Furthermore, platelets, red and white blood cells were analysed as parameters of product quality. An average of 2751±247ml blood was processed in 47±6min. The collected plasma volume was 850±1mL and citrate consumption was 177±15mL. A continuous drop of donors' IgG level was observed during plasmapheresis. The drop was 13% of the IgG baseline value at 800mL collected plasma. Total protein, IgG and cell counts of the plasma product met current guidelines of plasma for fractionation. Donors' IgG levels during apheresis showed a steady decrease without compromising the quality of plasma product. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Lennon, Elizabeth M; Boyle, Tonya E; Hutchins, Rae Grace; Friedenthal, Arit; Correa, Maria T; Bissett, Sally A; Moses, Lorra S; Papich, Mark G; Birkenheuer, Adam J
2007-08-01
To determine whether basal serum or plasma cortisol concentration can be used as a screening test to rule out hypoadrenocorticism in dogs. Retrospective case-control study. 110 dogs with nonadrenal gland illnesses and 13 dogs with hypoadrenocorticism. Sensitivity and specificity of basal serum or plasma cortisol concentrations of either
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Plasma klotho levels decrease in both anorexia nervosa and obesity.
Amitani, Marie; Asakawa, Akihiro; Amitani, Haruka; Kaimoto, Kaori; Sameshima, Nanami; Koyama, Ken Ichiro; Haruta, Izumi; Tsai, Minglun; Nakahara, Toshihiro; Ushikai, Miharu; Cheng, Kai-Chun; Hamada, Satoshi; Inui, Akio
2013-09-01
The aim of this study was to examine the associations of klotho with body mass index (BMI) in patients with restricting-type anorexia nervosa (r-AN) and obesity. We examined plasma klotho as well as adiponectin and its isoform levels in comparison in 11 obese patients, 12 r-AN patients, and 11 control participants. Plasma klotho levels were markedly lower in the obesity and r-AN groups than in the control group. Moreover, plasma klotho levels increased significantly after the recovery of BMI in r-AN patients. Total and high-molecular-weight adiponectin levels were significantly decreased only in obesity. There was no relationship between klotho and total adiponectin levels or klotho and respective adiponectin isoform levels in the entire study population. These results suggest that klotho may reflect normal nutritional state, and that the decrease of klotho in r-AN and obesity may underlie the deteriorating processes of these disorders. Copyright © 2013 Elsevier Inc. All rights reserved.
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Effects of blood lead and cadmium levels on homocysteine level in plasma.
Cai, R; Zheng, Y-F; Bu, J-G; Zhang, Y-Y; Fu, S-L; Wang, X-G; Guo, L-L; Zhang, J-R
2017-01-01
We studied the effect of non-occupational exposure to lead and cadmium on homocysteine level in plasma. Homocysteine is a marker for plasma folate folic acid metabolism in urban populations. 159 individuals from Beijing, Guangzhou, Shenzhen and Shanghai with no history of close exposure to heavy metals and no history of metabolic diseases were enrolled to participate in this study. Blood lead and cadmium levels were detected using ICP-MS method and the level of homocysteine was also measured using enzyme method. Our results showed that blood lead and cadmium levels in males were significantly higher than those in females. Also, blood lead and cadmium levels in smokers were higher than those in non-smokers; homocysteine level was significantly higher in smokers as well. According to blood lead and cadmium levels, cases were divided into four groups. Our results showed that a surge in blood lead and cadmium levels could result in an increase in homocysteine level. We concluded that in the Chinese population, smoking and gender might be the risk factors for elevated levels of lead and cadmium. Meanwhile, blood lead and cadmium levels may influence the homocysteine levels in the body. It is possible to speculate that non-occupational exposure to lead and cadmium, by increasing the homocysteine levels, negatively affect the cardiovascular and nervous system.
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Mamillapalli, Ramanaiah; Wysolmerski, John
2013-01-01
The calcium-sensing receptor (CaR) is a G-protein-coupled receptor (GPCR) that binds and signals in response to extracellular calcium and other polycations. It is highly expressed on parathyroid and kidney cells, where it participates in the regulation of systemic calcium homeostasis. It is also expressed on many other cell types and is involved in a wide array of biological functions such as cell growth and differentiation, ion transport and hormone secretion. It has been described to couple to several different G-proteins including Gαi/0, Gαq/11 and Gα12/13. Recently, it has also been shown to stimulate cAMP production by coupling to Gαs in immortalized or malignant breast cells. The CaR is expressed on cells in the anterior pituitary and had previously been described to stimulate cAMP production in these cells. In this report, we examined signaling from the CaR in murine pituitary corticotroph-derived, AtT-20 cells. We found that CaR activation led to the stimulation of cAMP production, and PTHrP and ACTH secretion from these cells. Furthermore, manipulation of cAMP levels was able to modulate PTHrP and ACTH secretion independent of changes in extracellular calcium. Finally, we demonstrated that the CaR couples to Gαs in AtT-20 cells. Therefore, in pituitary corticotroph-like cells, as in breast cancer cells, the CaR utilizes Gαs and activates cAMP production to stimulate hormone secretion. PMID:20032198
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Decreased plasma agmatine levels in autistic subjects.
Esnafoglu, Erman; İrende, İlhan
2018-04-01
Agmatine is a polyamine endogenously synthesized from arginine and is considered to be a new neurotransmitter. Agmatine has been implicated in the pathophysiology of several diseases such as anxiety disorder, depression, and schizophrenia. Agmatine also possesses anticonvulsant, neuroprotective, antiapoptotic, antioxidant, anxiolytic, and antidepressant effects. Furthermore, agmatine inhibits the nitric oxide synthase enzyme and exerts antagonist effects on NMDA, alpha-2, and imidazoline receptors. Considering these characteristics, the present study investigated whether agmatine plays a role in the pathogenesis of autistic spectrum disorders (ASDs). Therefore, plasma agmatine levels were evaluated in 34 patients with ASD and 28 non-ASD controls. Plasma agmatine levels were measured using the HPLC method. The study found remarkably lower agmatine levels in patients with ASD compared with the non-ASD control group (p < 0.001). These findings support the notion that agmatine might contribute to the pathogenesis of ASD and may serve as a new target for treatment.
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Acromegaly and Cushing's syndrome associated with a foregut carcinoid tumor.
Leveston, S A; McKeel, D W; Buckley, P J; Deschryver, K; Greider, M H; Jaffe, B M; Daughaday, W H
1981-10-01
We report an 18-yr-old youth with a metastatic foregut carcinoid tumor, Cushing's syndrome, and hypersomatotropic gigantism. Administration of cyproheptadine caused a dramatic fall in urinary cortisol excretion and plasma ACTH levels associated with clinical remission of the Cushing's syndrome. GH secretion was not affected by cyproheptadine administration. Ectopic ACTH secretion was confirmed by RIA of tumor extracts and immunohistochemical demonstration of ACTH-containing cells in hepatic metastases. There were two sources of GH production demonstrated in this patient. Ectopic secretion of GH by the carcinoid hepatic metastases was documented by both RIA and immunohistochemical techniques. A somatotrophic pituitary tumor was also present. The histological characteristics of this tumor suggest adenomatous hyperplasia rather than de novo neoplastic change as the likely mechanism of its pathogenesis. GH releasing factor-like activity was demonstrated in extracts of plasma and in extracts of the carcinoid tumor. We conclude that cyproheptadine exerted an effect on the ectopic ACTH-producing cells but not on the ectopic GH-producing cells or on adenohypophyseal GH secretion. Production of a GH releasing factor-like activity by the carcinoid tumor may have caused the pituitary somatotrophic tumor.
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Grossrubatscher, E; Vignati, F; Dalino, P; Possa, M; Belloni, P A; Vanzulli, A; Bramerio, M; Marocchi, A; Rossetti, O; Zurleni, F; Loli, P
2005-01-01
Intraoperative [111In]-pentetreotide scintigraphy with a hand-held gamma detector probe has recently been proposed to increase the intraoperative detection rate of small neuroendocrine tumors and their metastases. We report a case of a 28-yr-old woman with ectopic Cushing's syndrome due to an ACTH-secreting bronchial carcinoid, in whom the use of radioguided surgery improved disease management. At presentation, radiolabeled pentetreotide scintigraphy was the only procedure able to detect the ectopic source of ACTH. After radiologic confirmation, the patient underwent removal of a bronchial carcinoid, with disease persistence. After surgery, pentetreotide scintigraphy showed pathologic uptake in the mediastinum not previously detected at surgery and only subsequently confirmed by radiologic studies. Despite a second thoracic exploration, hormonal, scintigraphic, and radiological evidence of residual disease persisted. Radioguided surgery was then performed using a hand-held gamma probe 48 h after iv administration of a tracer dose of radiolabeled [111In-DTPA-D-Phe1]-pentetreotide, which permitted detection and removal of multiple residual mediastinal lymph node metastases. Clinical and radiologic cure, with no evidence of tracer uptake at pentetreotide scintigraphy, was subsequently observed. The use of an intraoperative gamma counter appears a promising procedure in the management of metastatic ACTH-secreting bronchial carcinoids.
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The effect of hormone therapy on plasma homocysteine levels: a randomized clinical trial.
Tutuncu, Levent; Ergur, Ali Rustu; Mungen, Ercument; Gun, Ismet; Ertekin, Aktug; Yergok, Yusuf Ziya
2005-03-01
An elevated plasma homocysteine level is a risk factor for cardiovascular diseases. Hormone therapy (HT) may reduce fasting plasma homocysteine levels. We studied 80 postmenopausal women to determine the effect of medroxyprogesterone acetate (MPA) combined with conjugated equine estrogens (CEE) on fasting plasma homocysteine levels. In a randomized, double blind, prospective, placebo-controlled study, we randomly assigned 80 healthy postmenopausal women between CEE 0.625 mg/d combined with MPA 2.5 mg/d (n = 20), CEE 0.625 mg/d combined with MPA 5 mg/d (n = 20), unopposed CEE 0.625 mg/d (n = 20), and placebo (n = 20) all given for a duration of 6 months. Fasting plasma homocysteine levels were measured before and at the end of the treatment. Before treatment, plasma homocysteine concentrations were similar in all groups. After 6 months of unopposed CEE, the mean fasting plasma homocysteine levels decreased by 19.02% when compared with baseline levels (P < 0.05). The mean fasting plasma homocysteine concentrations decreased by 17.63% and 19.56% from baseline in both the CEE plus MPA 2.5 mg/d and CEE plus MPA 5 mg/d groups, respectively (P < 0.05 for each group). In contrast, plasma homocysteine levels increased by 11.66% in the placebo group. The homocysteine lowering effect did not differ significantly among the three groups of women receiving unopposed CEE alone and CEE plus MPA at two different doses. Six months of estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) significantly lower fasting plasma homocysteine levels in healthy postmenopausal women with equal efficacy.
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Merlo, Eduardo; Podratz, Priscila L; Sena, Gabriela C; de Araújo, Julia F P; Lima, Leandro C F; Alves, Izabela S S; Gama-de-Souza, Letícia N; Pelição, Renan; Rodrigues, Lívia C M; Brandão, Poliane A A; Carneiro, Maria T W D; Pires, Rita G W; Martins-Silva, Cristina; Alarcon, Tamara A; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B
2016-08-01
Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function.
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[Hormone content of the blood plasma of rats after a flight on the Kosmos-1129 biosatellite].
Tigranian, R A; Kalita, N F; Macho, L; Kvetnanský, R
1985-01-01
The concentration of ACTH, insulin, glucagon, glucose, epinephrine, norepinephrine, thyrotrophic hormone, thyroxine, and triiodothyronine was measured in plasma of the rats flown for 18.5 days on Cosmos-1129. As a result of the flight, the concentration of insulin, thyrotrophic hormone, and triiodothyronine increased and that of thyroxine decreased. It is suggested that the above changes have been induced by an acute stress associated with biosatellite reentry and touchdown.
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Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.
Pennacchio, Len A; Olivier, Michael; Hubacek, Jaroslav A; Krauss, Ronald M; Rubin, Edward M; Cohen, Jonathan C
2002-11-15
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 approximately 16% 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=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% of Caucasians, 14% of African-Americans and 28% 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% of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.
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Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.
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 triglyceridemore » 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.« less
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Liu, Yuguan; Weisberg, Lawrence S; Langman, Craig B; Logan, Amanda; Hunter, Krystal; Prasad, Deepali; Avila, Jose; Venkatchalam, Thaliga; Berns, Jeffrey S; Handelman, Garry J; Sirover, William D
2016-10-01
Ascorbic acid (AA) supplementation may increase hemoglobin levels and decrease erythropoiesis-stimulating agent dose requirement in patients with end stage renal disease (ESRD). While plasma AA levels >100μM may be supratherapeutic, levels of at least 30μM may be needed to improve wound healing and levels may need to reach 70μM to optimize erythropoiesis. Of concern, oxalate (Ox), an AA metabolite, can accumulate in ESRD. Historically, if plasma Ox levels remain ≥30μM, oxalosis was of concern. Contemporary hemodialysis (HD) efficiencies may decrease the risk of oxalosis by maintaining pre-HD Ox levels <30μM. This study focuses on the plasma Ox levels in HD patients. A prospective, observational study of 197 HD patients with pre-HD AA levels and pre-HD and post-HD Ox levels. Mean plasma Ox levels decreased 71% during the intradialytic period (22.3±11.1μM to 6.4±3.2μM, P<0.001). In regression analysis, pre-HD plasma AA levels ≤100μM were not associated with a pre-HD plasma Ox level≥30μM, even if ferritin levels were increased. Pre-HD plasma Ox levels ≥20 or ≥30μM were not associated with lower cumulative 4-year survival. Pre-HD plasma AA levels up to 100μM in HD patients do not appear to be associated with an increased risk of developing secondary oxalosis, as the corresponding pre-HD plasma Ox level appears to be maintained at tolerable levels. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
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Tirosh, A; Lodish, M B; Papadakis, G Z; Lyssikatos, C; Belyavskaya, E; Stratakis, C A
2016-09-01
Cortisol diurnal variation may be abnormal among patients with endogenous Cushing syndrome (CS). The study objective was to compare the plasma cortisol AM/PM ratios between different etiologies of CS. This is a retrospective cohort study, conducted at a clinical research center. Adult patients with CS that underwent adrenalectomy or trans-sphenoidal surgery (n=105) were divided to those with a pathologically confirmed diagnosis of Cushing disease (n=21) and those with primary adrenal CS, including unilateral adrenal adenoma (n=28), adrenocortical hyperplasia (n=45), and primary pigmented nodular adrenocortical disease (PPNAD, n=11). Diurnal plasma cortisol measurements were obtained at 11:30 PM and midnight and at 7:30 and 8:00 AM. The ratios between the mean morning levels and mean late-night levels were calculated. Mean plasma cortisol AM/PM ratio was lower among CD patients compared to those with primary adrenal CS (1.4±0.6 vs. 2.3±1.5, p<0.001, respectively). An AM/PM cortisol ratio≥2.0 among patients with unsuppressed ACTH (>15 pg/ml) excludes CD with a 85.0% specificity and a negative predictive value (NPV) of 90.9%. Among patients with primary adrenal CS, an AM/PM cortisol≥1.2 had specificity and NPV of 100% for ruling out a diagnosis of PPNAD. Plasma cortisol AM/PM ratios are lower among patients with CD compared with primary adrenal CS, and may aid in the differential diagnosis of endogenous hypercortisolemia. © Georg Thieme Verlag KG Stuttgart · New York.
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Factitious Cushing's syndrome masquerading as Cushing's disease.
Thynne, Tilenka; White, Graham H; Burt, Morton G
2014-03-01
Factitious Cushing's syndrome is extremely rare. The diagnosis is challenging as cross-reactivity of synthetic corticosteroids or their metabolites in immunoassay measurements of plasma or urinary cortisol can make distinguishing between true and factitious Cushing's syndrome difficult. Adrenocorticotropin (ACTH) is usually suppressed in factitious Cushing's syndrome. A 54-year-old woman presented with clinical and biochemical features of Cushing's syndrome and an unsuppressed ACTH concentration. She denied recent exogenous corticosteroid use. Initial investigations revealed a markedly elevated urinary free cortisol, mildly elevated midnight salivary cortisol and normal morning cortisol concentration. Plasma ACTH was not suppressed at 13 ng/l (RR 10-60 ng/l). A pituitary MRI was normal, but inferior petrosal sinus sampling (IPSS) revealed a post corticotrophin releasing hormone ACTH ratio >20:1 in the left petrosal sinus. Ketoconazole therapy amplified discordance between the urinary free and morning plasma cortisol concentrations. Further investigation of this discordance using high-pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) revealed a urinary free cortisol excretion of only 20 nmol/24 h, but prednisolone excretion of 16,200 nmol/24 h. Factitious Cushing's syndrome can mimic endogenous ACTH-dependent hypercortisolism during initial investigations and IPSS. This case highlights the importance of (i) recognizing the significance of discordant results; (ii) using an ACTH assay capable of reliably differentiating ACTH-dependent from ACTH-independent Cushing's syndrome; and (iii) appreciating that IPSS is only useful to localize the source of ACTH in confirmed ACTH-dependent Cushing's syndrome. In this case, measurement of corticosteroids by HPLC-MS/MS was essential in reaching the correct diagnosis. © 2013 John Wiley & Sons Ltd.
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Effect of social isolation on 24-h pattern of stress hormones and leptin in rats.
Perelló, Mario; Chacon, Fernando; Cardinali, Daniel P; Esquifino, Ana I; Spinedi, Eduardo
2006-03-13
This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6-8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.
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Dysregulated Plasma Glucagon Levels in Japanese Young-adult Type 1 Diabetes Patients.
Kawamori, Dan; Katakami, Naoto; Takahara, Mitsuyoshi; Miyashita, Kazuyuki; Sakamoto, Fumie; Yasuda, Tetsuyuki; Matsuoka, Taka-Aki; Shimomura, Iichiro
2018-05-16
Currently, the clinical dynamics of glucagon needs to be revised based on previous data obtained from conventional glucagon radioimmunoassays. In this study, we evaluated plasma glucagon levels in type 1 diabetes patients using a newly-developed sandwich enzyme-linked immunosorbent assay (ELISA), and its association with clinical parameters and markers of diabetes complications were statistically assessed. The plasma glucagon level in 77 Japanese type 1 diabetes patients was 28.1±17.7 pg/mL, and comparable to that reported previously for type 2 diabetes patients. However, the values were widely spread and did not correlate with plasma glucose values. Additionally, the average glucagon levels in patients in a hypoglycemic state (glucose level <80 mg/dL) did not increase (21.7±12.2 pg/mL). The average glucagon level of patients experiencing hypoglycemia unawareness was significantly lower. Plasma glucagon levels evaluated using the new ELISA were dysregulated in type 1 diabetes patients in respect of plasma glucose levels, suggesting dysregulation of secretion. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Carroll, Ty B; Fisco, Amy J H; Auchus, Richard J; Kennedy, Laurence; Findling, James W
2014-07-01
The use of ovine corticotropin releasing hormone (oCRH) maximizes the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in patients with adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome (CS). oCRH is marketed as ACTHrel and, understandably, may be confused with cosyntropin [ACTH (1-24)]. The inadvertent substitution of synthetic ACTH(1-24) for oCRH (ACTHrel) during IPSS may cause unexpected and misleading results. The aim of this report is to raise awareness of the potential confounding results created when synthetic ACTH(1-24) is mistakenly used during IPSS. We present 3 patients treated at 3 different centers with ACTH-dependent CS in whom ACTH(1-24) was mistakenly substituted for oCRH (ACTHrel) during IPSS. In all patients, there was an abrupt and unexpected decrease in plasma ACTH in the inferior petrosal sinus (IPS) samples after presumptive stimulation with oCRH. Re-evaluation of the patients' pharmacy records confirmed that synthetic ACTH(1-24) had been used rather than oCRH during each procedure. Because "sandwich" immunometric assays for ACTH measure the entire pool of endogenous ACTH, the administration of synthetic ACTH(1-24) artifactually decreases the endogenous plasma ACTH(1-39) measurement by binding only to the N-terminal antibody raised against ACTH(1-17) and not to the C-terminal antibody raised against ACTH(34-39). This results in a lack of a detectable sandwich complex and explains the apparent reduction in ACTH concentration. An abrupt decrease in ACTH during IPSS suggests that synthetic ACTH(1-24) rather than oCRH (ACTHrel) has been administered. The labeling of oCRH as ACTHrel poses a potential patient safety problem about which endocrinologists, interventional radiologists, and pharmacists should be aware.
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Wang, Ying; Yang, Meng; Lee, Sang-Gil; Davis, Catherine G; Kenny, Anne; Koo, Sung I; Chun, Ock K
2012-12-01
Increased plasma total antioxidant capacity (TAC) has been associated with a high consumption of fruits and vegetables. However, limited information is available on whether plasma TAC reflects the dietary intake of antioxidants and the levels of individual antioxidants in plasma. By using three different assays, the study aimed to determine if plasma TAC can effectively predict dietary intake of antioxidants and plasma antioxidant status. Forty overweight and apparently healthy postmenopausal women were recruited. Seven-day food records and 12-h fasting blood samples were collected for dietary and plasma antioxidant assessments. Plasma TAC was determined by vitamin C equivalent antioxidant capacity (VCEAC), ferric-reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) assays. TAC values determined by VCEAC were highly correlated with FRAP (r=0.79, P<.01) and moderately correlated with ORAC (r=0.34, P<.05). Pearson correlation analyses showed that plasma TAC values by VCEAC and ORAC had positive correlation with plasma uric acid (r=0.56 for VCEAC; r=0.49 for ORAC) and total phenolics (r=0.63 for VCEAC; r=0.36 for ORAC). However, TAC measured by FRAP was correlated only with uric acid (r=0.69). After multivariate adjustment, plasma TAC determined by VCEAC was positively associated with dietary intakes of γ-tocopherol (P<.001), β-carotene (P<.05), anthocyanidins (P<.05), flavones (P<.05), proanthocyanidins (P<.01) and TAC (P<.05), as well as with plasma total phenolics (P<.05), α-tocopherol (P<.001), β-cryptoxanthin (P<.05) and uric acid (P<.05). The findings indicate that plasma TAC measured by VCEAC reflects both dietary and plasma antioxidants and represents more closely the plasma antioxidant levels than ORAC and FRAP. Copyright © 2012 Elsevier Inc. All rights reserved.
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Normal fasting plasma glucose levels and type 2 diabetes in young men.
Tirosh, Amir; Shai, Iris; Tekes-Manova, Dorit; Israeli, Eran; Pereg, David; Shochat, Tzippora; Kochba, Ilan; Rudich, Assaf
2005-10-06
The normal fasting plasma glucose level was recently defined as less than 100 mg per deciliter (5.55 mmol per liter). Whether higher fasting plasma glucose levels within this range independently predict type 2 diabetes in young adults is unclear. We obtained blood measurements, data from physical examinations, and medical and lifestyle information from men in the Israel Defense Forces who were 26 to 45 years of age. A total of 208 incident cases of type 2 diabetes occurred during 74,309 person-years of follow-up (from 1992 through 2004) among 13,163 subjects who had baseline fasting plasma glucose levels of less than 100 mg per deciliter. A multivariate model, adjusted for age, family history of diabetes, body-mass index, physical-activity level, smoking status, and serum triglyceride levels, revealed a progressively increased risk of type 2 diabetes in men with fasting plasma glucose levels of 87 mg per deciliter (4.83 mmol per liter) or more, as compared with those whose levels were in the bottom quintile (less than 81 mg per deciliter [4.5 mmol per liter], P for trend <0.001). In multivariate models, men with serum triglyceride levels of 150 mg per deciliter (1.69 mmol per liter) or more, combined with fasting plasma glucose levels of 91 to 99 mg per deciliter (5.05 to 5.50 mmol per liter), had a hazard ratio of 8.23 (95 percent confidence interval, 3.6 to 19.0) for diabetes, as compared with men with a combined triglyceride level of less than 150 mg per deciliter and fasting glucose levels of less than 86 mg per deciliter (4.77 mmol per liter). The joint effect of a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more and a fasting plasma glucose level of 91 to 99 mg per deciliter resulted in a hazard ratio of 8.29 (95 percent confidence interval, 3.8 to 17.8), as compared with a body-mass index of less than 25 and a fasting plasma glucose level of less than 86 mg per deciliter. Higher fasting plasma glucose
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Acute social stress-induced immunomodulation in pigs high and low responders to ACTH.
Bacou, Elodie; Haurogné, Karine; Mignot, Grégoire; Allard, Marie; De Beaurepaire, Laurence; Marchand, Jordan; Terenina, Elena; Billon, Yvon; Jacques, Julien; Bach, Jean-Marie; Mormède, Pierre; Hervé, Julie; Lieubeau, Blandine
2017-02-01
Pig husbandry is known as an intensive breeding system, piglets being submitted to multiple stressful events such as early weaning, successive mixing, crowding and shipping. These stressors are thought to impair immune defences and might contribute, at least partly, to the prophylactic use of antibiotics. Robustness was recently defined as the ability of an individual to express a high-production potential in a wide variety of environmental conditions. Increasing robustness thus appears as a valuable option to improve resilience to stressors and could be obtained by selecting piglets upon their adrenocortical activity. In this study, we aimed at depicting the consequences of an acute social stress on the immune capacity of piglets genetically selected upon divergent hypothalamic-pituitary-adrenocortical (HPA) axis activity. For this purpose, we monitored neuroendocrine and immune parameters, in high- (HPA hi ) and low- (HPA lo ) responders to ACTH, just before and immediately after a one-hour mixing with unfamiliar conspecifics. As expected, stressed piglets displayed higher levels of circulating cortisol and norepinephrine. Blood cell count analysis combined to flow cytometry revealed a stress-induced leukocyte mobilization in the bloodstream with a specific recruitment of CD8α + lymphocytes. Besides, one-hour mixing decreased LPS-induced IL-8 and TNFα secretions in whole-blood assays (WBA) and reduced mononuclear cell phagocytosis. Altogether, our data demonstrate that acute social stress alters immune competence of piglets from both groups, and bring new insights in favour of good farming practices. While for most parameters high- and low-responders to ACTH behaved similarly, HPA hi piglets displayed higher number of CD4 + CD8α - T cells, as well as increased cytokine production in WBA (LPS-induced TNFα and PIL-induced IL-8), which could confer them increased resistance to pathogens. Finally, a principal component analysis including all parameters
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Plasma Amyloid-β Levels, Cerebral Small Vessel Disease, and Cognition: The Rotterdam Study.
Hilal, Saima; Akoudad, Saloua; van Duijn, Cornelia M; Niessen, Wiro J; Verbeek, Marcel M; Vanderstichele, Hugo; Stoops, Erik; Ikram, M Arfan; Vernooij, Meike W
2017-01-01
Plasma amyloid-β (Aβ) levels are increasingly studied as a potential, accessible marker of cognitive impairment and dementia. The most common plasma Aβ isoforms, i.e., Aβ1-40 and Aβ1-42 have been linked with risk of Alzheimer's disease. However, it remains under-explored whether plasma Aβ levels including novel Aβ1-38 relate to vascular brain disease and cognition in a preclinical-phase of dementiaObjective:To examine the association of plasma Aβ levels (i.e., Aβ1-38, Aβ1-40, and Aβ1-42) with markers of cerebral small vessel disease (SVD) and cognition in a large population-based setting. We analyzed plasma Aβ1 levels in 1201 subjects from two independent cohorts of the Rotterdam Study. Markers of SVD [lacunes, white matter hyperintensity (WMH) volume] were assessed on brain MRI (1.5T). Cognition was assessed by a detailed neuropsychological battery. In each cohort, the association of Aβ levels with SVD and cognition was performed using regression models. Estimates were then pooled across cohorts using inverse variance meta-analysis with fixed effects. Higher levels of plasma Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-40/ Aβ1-42 ratio were associated with increasing lacunar and microbleeds counts. Moreover, higher levels of Aβ1-40 and Aβ1-40/ Aβ1-42 were significantly associated with larger WMH volumes. With regard to cognition, a higher level of Aβ1-38 Aβ1-40 and Aβ1-40/ Aβ1-42 was related to worse performance on cognitive test specifically in memory domain. Higher plasma levels of Aβ levels are associated with subclinical markers of vascular disease and poorer memory. Plasma Aβ levels thus mark the presence of vascular brain pathology.
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Horns, W H; Rado, M; Goldstein, A
1975-06-01
Plasma methadone levels, symptom complaints, and urine tests for illicit opiate use were followed weekly in 17 patients on a methadone maintenance program. There were very large differences between patients in the plasma level established at a given dosage, implying large differences in the rate of methadone metabolism. Despite virtually constant daily dosage, the plasma methadone levels fluctuated greatly from week to week and from day to day in individual patients. With rate exceptions there was no relationship between plasma methadone level and symptom complaints or between weekly chamges in plasma methadone level and changes in symptom complaints. Except possible to identify the ocassional patient with unusually low plasam methadone levels, the determination of methadone levels is not likely to be or practical value in methadone programs.
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Simsek, Seref; Uysal, Cem; Kaplan, Ibrahim; Yuksel, Tugba; Aktas, Huseyin
2015-06-01
There are studies reporting that cortisol and brain-derived neurotropic factor (BDNF) play a role in the pathophysiology of post-traumatic stress disorder (PTSD). However, up-to-date no study evaluated the relationship between PTSD and the levels of cortisol and BDNF in children and adolescents who have sustained trauma. The aim of this study was to investigate whether BDNF, cortisol and adrenocorticotropine (ACTH) levels differ between individuals who developed PTSD or not following a sexual trauma. The study included 55 children aged between 6 and 17 years who sustained sexual assault (M/F: 13/42). The patients were divided into two groups, with or without PTSD based on the results of a structured psychiatric interview (K-SADS-PL and CAPS-CA). Of the participants, 49% (n=27) were diagnosed with PTSD. Cortisol, ACTH, and BDNF levels were evaluated using the ELISA method. There were no significant differences between patients with or without PTSD in terms of cortisol, ACTH, BDNF levels. There were no correlations between CAPS-CA scores and cortisol, ACTH, and BDNF levels in patients with or without PTSD. In patients with PTSD, decreased cortisol levels were found with increasing time after trauma, and no significant correlation was found with the cortisol levels in patients without PTSD. Although no significant association was found between biochemical parameters and the presence or severity of PTSD; decreasing cortisol levels with increasing time after trauma in patients with PTSD suggest that cortisol might have played a role in the pathophysiology of this disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Buckingham, J C; Safieh, B; Singh, S; Arduino, L A; Cover, P O; Kendall, M D
1992-06-01
Our recent observations in man suggested that the secretion of the thymic peptide, thymulin, is influenced by hormones of the pituitary-adrenal axis. In the present study, we have used the rat as a model in order to examine 1) the effects of corticotrophin (ACTH) and glucocorticoids on the release of thymulin in vivo and in vitro, and 2) the influence of an acute rise in plasma thymulin on the secretion of corticosterone and luteinizing hormone. Immunoreactive thymulin was readily detectable in plasma from male Sprague-Dawley rats(≃200 g). Chronic bilateral adrenalec-tomy, which effectively removed endogenous corticosterone, produced highly significant (P<0.01) increases in the plasma concentrations of both ACTH and thymulin. Treatment of the adrenalectomized rats with dexamethasone, in a dose sufficient to suppress the hypersecretion of ACTH, maintained the plasma thymulin at a low level which did not differ significantly (P > 0.2) from that in sham-operated controls. In vitro, two non-specific depolarizing agents, K(+) (56 mM) and veratridine (10 ≃M), caused significant (P<0.01) Ca(2+) -dependent increases in thymulin release from segments of rat thymic tissue. Their effects were mimicked by ACTH(1-39) . The secretory responses to ACTH (0.025 to 1 ng/ml) were concentration-dependent but a very high concentration (2 ng/ml) of the peptide was without effect. Dexamethasone (0.1 μM) reduced (P<0.05) the spontaneous release of thymulin in vitro but potentiated markedly (P<0.01) the secretory responses to ACTH (0.5 to 1.0 ng/ml). Administration of thymulin (0.1 and 10 μg/kg ip) produced, within 10 min, striking increases in the plasma thymulin concentration which were still evident at 30 min. The peptide concentration then declined rapidly and, within 24 h, was lower than that in the corresponding vehicle-treated controls. The serum concentrations of corticosterone and luteinizing hormone were unaffected by the thymulin treatment. The saline vehicle (2.0 ml/kg ip
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Ouyang, Yan; Chen, Bing; Pan, Xiaoxia; Wang, Zhaohui; Ren, Hong; Xu, Yaowen; Ni, Liyan; Yu, Xialian; Yang, Li; Chen, Nan
2018-04-01
Although plasma globotriaosylsphingosine (lyso-Gb3) is a promising biomarker of Fabry disease (FD), few studies have assessed the impact of lyso-Gb3 in patients with FD. A total of 38 patients diagnosed with FD at Ruijin Hospital between January 2012 and December 2014 were recruited in the current study. An additional 120 unrelated healthy individuals were selected as healthy controls. A simplified liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was performed to determine lyso-Gb3 levels in plasma. Protein precipitation and glycolipid extraction were conducted using acetone/methanol. Clinical performance, including diagnostic value and disease surveillance, were compared between plasma lyso-Gb3 levels and α-galactosidase A (α-gal A) enzyme activity. The overall coefficient of variation values between inter- and intra-days varied between 2.8 and 18.9% and linearity correlation coefficients were ≥0.99 for all assays. Therefore, the effectiveness of the LC-MS/MS method was validated. Furthermore, a cut-off value of 0.81 ng/ml plasma lyso-Gb3 was able to separate patients with FD from healthy individuals. The sensitivity of this cut-off was 94.7% and the specificity was 100%. Compared with α-gal A enzyme activity, the diagnostic rate of patients assessed using plasma lyso-Gb3 levels was similar; however, there was a tighter correlation between plasma lyso-Gb3 levels and the mainz severity score index score in male patients (r=0.711 vs. r=-0.687). The sensitivity of plasma lyso-Gb3 in diagnosing female patients with FD was higher than α-gal A enzyme activity (82.4 vs. 23.5%). To the best of our knowledge, the present study is the first to report the effectiveness of plasma lyso-Gb3 levels in diagnosing Chinese patients with FD. Using α-gal A activity as a reference, the results of current study indicated that plasma lyso-Gb3 levels are more useful at diagnosing female patients with FD. Furthermore, plasma lyso-Gb3 levels are more suitable at
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Tanaka, Nobuyuki; Kikuchi, Eiji; Matsumoto, Kazuhiro; Hayakawa, Nozomi; Ide, Hiroki; Miyajima, Akira; Nakamura, So; Oya, Mototsugu
2013-05-01
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Upper tract urothelial carcinoma (UTUC) is relatively uncommon, accounting for only ~5% of urothelial malignancies and 10% of all renal tumours. Radical nephroureterectomy (RNU) with bladder cuff excision is the surgical standard of care for treating localized UTUC, but the prognosis for patients who undergo RNU remains poor. Evidence suggests that an interactive relationship exists between haemostatic factors and tumour biology. A number of procoagulant and fibrinolytic factors have been found to be overexpressed in tumours. One of these factors is plasma fibrinogen. Recent studies have shown that elevated pre-therapeutic plasma fibrinogen levels are associated with worse outcome in various malignancies; however, the prognostic value of plasma fibrinogen levels for UTUC has not yet been reported. To the best of our knowledge, this is the first paper to evaluate the prognostic impact of preoperative plasma fibrinogen levels in patients with localized UTUC treated surgically. We believe that the present results may assist in decision-making with respect to the need for lymph node dissection and neoadjuvant chemotherapy. To investigate the prognostic value of plasma fibrinogen levels as a predictor of patient outcome in upper tract urothelial carcinoma (UTUC). A total of 218 patients who underwent radical nephroureterectomy (RNU) for localized UTUC (pTa-4N0M0) were identified between 1995 and 2009. The association between preoperative plasma fibrinogen levels and clinicopathological variables was analysed. Forty-five patients experienced tumour recurrence, and 36 died from disease during the mean follow-up of 51 months. The mean (sd) preoperative plasma fibrinogen level was 362 (103) mg/dL. Kaplan-Meier curves showed that subsequent tumour recurrence was strongly predicted in patients with preoperative plasma fibrinogen levels ≥450 mg/dL, and similar results were observed for cancer-specific survival. On
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The influence of bone and blood lead on plasma lead levels in environmentally exposed adults.
Hernández-Avila, M; Smith, D; Meneses, F; Sanin, L H; Hu, H
1998-01-01
There is concern that previously accumulated bone lead stores may constitute an internal source of exposure, particularly during periods of increased bone mineral loss (e.g., pregnancy, lactation, and menopause). Furthermore, the contribution of lead mobilized from bone to plasma may not be adequately reflected by whole-blood lead levels. This possibility is especially alarming because plasma is the main circulatory compartment of lead that is available to cross cell membranes and deposit in soft tissues. We studied 26 residents of Mexico City who had no history of occupational lead exposure. Two samples of venous blood were collected from each individual. One sample was analyzed by inductively coupled plasma-magnetic sector mass spectrometry for whole-blood lead levels. The other sample was centrifuged to separate plasma, which was then isolated and analyzed for lead content by the same analytical technique. Bone lead levels in the tibia and patella were determined with a spot-source 109Cd K-X-ray fluorescence instrument. Mean lead concentrations were 0.54 microg/l in plasma, 119 microg/l in whole blood, and 23.27 and 11.71 microg/g bone mineral in the patella and tibia, respectively. The plasma-to-whole-blood lead concentration ratios ranged from 0.27% to 0.70%. Whole-blood lead level was highly correlated with plasma lead level and accounted for 95% of the variability of plasma lead concentrations. Patella and tibia lead levels were also highly correlated with plasma lead levels. The bivariate regression coefficients of patella and tibia on plasma lead were 0.034 (p<0. 001) and 0.053 (p<0.001), respectively. In a multivariate regression model of plasma lead levels that included whole-blood lead, patella lead level remained an independent predictor of plasma lead level (ss = 0.007, p<0.001). Our data suggest that although whole-blood lead levels are highly correlated with plasma lead levels, lead levels in bone (particularly trabecular bone) exert an additional
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Scott, Richard A.; Henson, Donald E.; Lesak, Anne; Turner, Robert J.; Malikova, Stanislava; Hass, George M.
1973-01-01
Rabbits maintained for several weeks on a regimen of modest amounts of vitamin D and dietary cholesterol were placed in three groups in accordance with their response to repeated subcutaneous injections of nicotine in mineral oil. The group that had the greatest increase in plasma FFA following nicotine injections gradually developed, over a period of about 12 weeks, severe calcific atheroarteriosclerosis with peripheral thromboarteritis. Those that had a moderate increase in plasma FFA following nicotine injections developed calcific atheroarteriosclerosis but no thromboarteritis. Those that had the least increase in plasma FFA following nicotine injections developed no arterial lesions. Comparable or much greater increases in plasma FFA occurred in rabbits on the vitamin D-cholesterol regimen when adrenalin, ACTH or heparin was injected rather than nicotine. These animals did not develop calcific atheroarteriosclerotic thromboarteritis or any other lesions which could be correlated with the increased levels of plasma FFA. Inasmuch as nicotine, vitamin D or dietary cholesterol in the amounts used were innocuous when used alone, the interactions between the effects of at least these three factors need to be known in individual animals before the pathogenesis of the calcific atheroarteriosclerotic lesions with thrombosis can eventually be understood. ImagesFig 5Fig 6Fig 7Fig 8Fig 9Fig 1Fig 10Fig 2Fig 3Fig 4 PMID:4345831
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Clinical Implication of Plasma Hydrogen Sulfide Levels in Japanese Patients with Type 2 Diabetes.
Suzuki, Kunihiro; Sagara, Masaaki; Aoki, Chie; Tanaka, Seiichi; Aso, Yoshimasa
Objective The goal of the present study was to investigate the plasma hydrogen sulfide (H 2 S) levels in patients with type 2 diabetes, as the plasma H 2 S levels in Japanese patients with type 2 diabetes remain unclear. Methods The plasma H 2 S 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 H 2 S levels were measured using the methylene blue assay. The plasma H 2 S 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 H 2 S levels (45.115.5 M versus 54.026.4 M, p<0.05), which paralleled poor glycemic control. There was a significant correlation between a reduction in the plasma H 2 S levels and the HbA1c levels (=-0.505, p<0.01), Furthermore, a reduction in the plasma H 2 S levels was found to be related to a history of cardiovascular diseases in patients with type 2 diabetes (39.913.8 M versus 47.515.9 M, p<0.01). Conclusion Collectively, the plasma H 2 S 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).
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Joss, J M; Dores, R M; Crim, J W; Beshaw, M
1990-06-01
This immunocytochemical study of the pituitaries of the primitive actinopterygians, Acipenser transmontanus, Lepisosteus spatula, and Amia calva, showed a strict delineation between the hormonal fragments of proopiomelanocorticotropin (POMC) produced by corticotropes of the pars distalis and the melanotropes of the pars intermedia. Corticotropes were immunoreactive only for ACTH and not to either of the further degradation products, alpha-MSH or beta-endorphin. Melanotropes were shown to be immunoreactive to all three antisera but it is argued that immunoreactivity of melanotropes to ACTH antiserum is due to that antiserum's cross-reactivity with the cleavage product corticotropin-like intermediate peptide. The PAS positivity of both the corticotropes and the melanotropes of all three primitive fish argues for an ancient origin of a carbohydrate component of POMC and for its loss or reduction in teleosts where these cells are PAS negative.
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Plasma nesfatin-1 level is associated with severity of depression in Chinese depressive patients.
Xiao, Min-Min; Li, Jiang-Bo; Jiang, Lan-Lan; Shao, Hui; Wang, Bao-Long
2018-04-03
Nesfatin-1 plays a role in the regulation of emotional states like depression. The aim of this study was to investigate the plasma nesfatin-1levels in Chinese patients with depression and healthy subjects, and to determine the possible association between the plasma nesfatin-1 level and the severity of depression. A total of 103 depressive patients and 32 healthy subjects were assessed. According to HAMD-17scores, 51, 18, and 34 patients were enrolled in the mild depression, moderate depression, and severe depression groups, respectively. Plasma nesfatin-1 levels were determined by the ELISA method. Differences between groups were compared and associations between plasma nesfatin-1 and other variables were analyzed. The plasma nesfatin-1 was significantly positively correlated with HAMD-17 score (r = 0.651). Compared with healthy controls (8.11 ± 3.31 ng/mL), the plasma nesfatin-1 level significantly increased in patients with mild depression (11.17 ± 3.58 ng/mL), with moderate depression (16.33 ± 8.78 ng/mL), and with severe depression (27.65 ± 8.26 ng/mL) respectively. Plasma nesfatin-1 level (Odds ratio [OR] = 1.269) was an independent indicator for severe depression by multivariate logistic regression analysis. The plasma nesfatin-1 level is positively correlated with the severity of depression. Plasma nesfatin-1 level may be a potential indicator for depression severity.
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Physical activity affects plasma coenzyme Q10 levels differently in young and old humans.
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.
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Potential use of nutritional factors to optimize performance under stress
NASA Technical Reports Server (NTRS)
Munro, H. N.
1977-01-01
A study of the effects of amino acids on hypothalamo-pituitary capacity to secrete ACTH, and the response of the adrenal gland in terms of corticosterone level in the plasma was discussed in the first part of this report. Second, the report includes a study of the response of protein metabolism in various levels of corticosterone elevation in the plasma. This second part is regarded as having considerable significance for space travel, since this data indicate a threshold level of plasma corticosteroids above which there is increased catabolism of muscle protein.
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Systemic therapy of Cushing’s syndrome
2014-01-01
Cushing’s disease (CD) in a stricter sense derives from pathologic adrenocorticotropic hormone (ACTH) secretion usually triggered by micro- or macroadenoma of the pituitary gland. It is, thus, a form of secondary hypercortisolism. In contrast, Cushing’s syndrome (CS) describes the complexity of clinical consequences triggered by excessive cortisol blood levels over extended periods of time irrespective of their origin. CS is a rare disease according to the European orphan regulation affecting not more than 5/10,000 persons in Europe. CD most commonly affects adults aged 20–50 years with a marked female preponderance (1:5 ratio of male vs. female). Patient presentation and clinical symptoms substantially vary depending on duration and plasma levels of cortisol. In 80% of cases CS is ACTH-dependent and in 20% of cases it is ACTH-independent, respectively. Endogenous CS usually is a result of a pituitary tumor. Clinical manifestation of CS, apart from corticotropin-releasing hormone (CRH-), ACTH-, and cortisol-producing (malign and benign) tumors may also be by exogenous glucocorticoid intake. Diagnosis of hypercortisolism (irrespective of its origin) comprises the following: Complete blood count including serum electrolytes, blood sugar etc., urinary free cortisol (UFC) from 24 h-urine sampling and circadian profile of plasma cortisol, plasma ACTH, dehydroepiandrosterone, testosterone itself, and urine steroid profile, Low-Dose-Dexamethasone-Test, High-Dose-Dexamethasone-Test, after endocrine diagnostic tests: magnetic resonance imaging (MRI), ultra-sound, computer tomography (CT) and other localization diagnostics. First-line therapy is trans-sphenoidal surgery (TSS) of the pituitary adenoma (in case of ACTH-producing tumors). In patients not amenable for surgery radiotherapy remains an option. Pharmacological therapy applies when these two options are not amenable or refused. In cases when pharmacological therapy becomes necessary, Pasireotide should be used
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The hypothalamic-pituitary-adrenal axis: what can it tell us about stressors?
Armario, Antonio
2006-10-01
The hypothalamic-pituitary-adrenal (HPA) axis is an extremely sensitive physiological system whose activation, with the consequent release of ACTH and glucocorticoids, is triggered by a wide range of psychological experiences and physiological perturbations (stressors). The HPA axis is also activated by a high number of pharmacological agents that markedly differ in structure and function, although the precise mechanisms remain in most cases unknown. Activation of the HPA axis is the consequence of the convergence of stimulatory inputs from different brain regions into the paraventricular nucleus of the hypothalamus (PVN), where the most important ACTH secretagogues (corticotrophin releasing factor, CRF, and arginin-vasopressin, AVP) are formed. Plasma levels of ACTH and corticosterone (the latter under more restricted conditions), are considered as good markers of stress for three main reasons: (a) their plasma levels are proportional to the intensity of emotional and systemic stressors, (b) daily repeated exposure to a stressor usually resulted in reduced ACTH response to the same stressor, that is termed adaptation or habituation; and (c) chronic exposure to stressful situations results in tonic changes in the HPA axis that can be used as indices of the accumulative impact of these situations. These changes can be evaluated under resting conditions (i.e. adrenal weight, CRF and AVP gene expression in the PVN) or after some challenges (administration of CRF, ACTH or dexamethasone) that are classical endocrinological tests. There is also evidence that the activation of the HPA axis may also reflect subtle changes in the characteristics of the stressful situations (unpredictability, lack of control, omission of expected rewards, presence of conspecifics), although this is a topic that requires further studies.
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Progesterone and estradiol plasma levels in neonatally irradiated cycling rats
DOE Office of Scientific and Technical Information (OSTI.GOV)
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 preovulatorymore » 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.« less
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Alpha 2-adrenoceptor blockade, pituitary-adrenal hormones, and agonistic interactions in rats.
Haller, J; Barna, I; Kovács, J L
1994-08-01
The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. Alpha 2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an alpha 2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different alpha 2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the alpha 2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.
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Adrenocorticotropin-producing pituitary carcinoma with liver metastasis.
Lormeau, B; Miossec, P; Sibony, M; Valensi, P; Attali, J R
1997-04-01
We report here the extremely rare case of a twenty-eight year-old woman with a metastatic ACTH-secreting pituitary carcinoma. This is the thirteenth case to be described in the literature. Ten years ago Cushing's disease was diagnosed. After pituitary surgery, then bilateral adrenalectomy, a Nelson's syndrome appeared. The particularly extensive pituitary secondary development led to several pituitary surgical procedures, radiotherapy, and octreotide treatment. Eight years after Cushing's disease was diagnosed, liver tumors were discovered. Pathological examination and ACTH immunostaining demonstrated the secretory nature of these metastases. The lack of ectopic tumor, the LPH/ACTH equimolar ratio and a study of the plasma proopiomelanocortin derivatives by HPLC showed that the ACTH secretion originated in pituitary tissues (in situ and liver metastases). The processing of POMC seems thus to be normal in this kind of tumor and metastases. Intact POMC levels were very high, indicating an aggressive tumor, and ACTH/LPH production was paradoxically stimulated by octreotide. This case is also exceptional because of the slow development of the disease, which may be due to the complementary hepatic chemoembolization treatment.
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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.
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Johnson, Elizabeth O; Kamilaris, Themis C; Calogero, Aldo E; Gold, Philip W; Chrousos, George P
2005-07-01
Previous studies on the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones suggest a degree of adrenocortical hyperactivity in hyperthyroidism. We have previously shown that experimentally-induced hyperthyroidism is associated with significant alterations in pituitary-adrenal responsiveness to synthetic ovine corticotropin-releasing hormone (oCRH) that are contingent upon the duration of the altered thyroid function. The purpose of this study was to assess the time-dependent effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal cortex. The functional integrity of the HPA axis was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given 50 mug of thyroxine every day for 7 or 60 days. Responses to insulin-induced hypoglycemia and IL-1alpha stimulation were used to assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in response to low-dose adrenocorticotropic hormone (ACTH), following suppression of the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to basal plasma ACTH, corticosterone and thyroid indices were also determined. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were significantly increased. Basal plasma ACTH levels were similar to controls. Although plasma ACTH responses to hypoglycemic stress and IL-1alpha administration in both short- and long-term hyperthyroidism were normal, corticosterone responses to the ACTH release during the administration of these stimuli were significantly increased. The adrenal reserve was significantly elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was associated
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Plasma levels of coenzyme Q10 in children with hyperthyroidism.
Menke, Thomas; Niklowitz, Petra; Reinehr, Thomas; de Sousa, Gideon John; Andler, Werner
2004-01-01
In hyperthyroidism, increased oxygen consumption and free radical production in the stimulated respiratory chain leads to oxidative stress. Apart from its antioxidative function, coenzyme Q10 (CoQ10) is involved in electron transport in the respiratory chain. The aim of this study was to determine whether there is a correlation between an increased respiratory chain activity and the state of CoQ10 in children with hyperthyroidism. The CoQ10 plasma concentration was measured by high-performance liquid chromatography in 12 children with hyperthyroidism before and after treatment. In the hyperthyroid state, the plasma level of CoQ10 was significantly decreased in comparison with the level in the euthyroid state. The correction of the hyperthyroid state resulted in a normalization of the CoQ10 level. Plasma CoQ10 deficiency appears to be related to the stimulated respiratory chain activity in children with hyperthyroidism. Copyright 2004 S. Karger AG, Basel
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Assessments of plasma ghrelin levels in the early stages of parkinson's disease.
Song, Ning; Wang, Weiwei; Jia, Fengjv; Du, Xixun; Xie, Anmu; He, Qing; Shen, Xiaoli; Zhang, Jing; Rogers, Jack T; Xie, Junxia; Jiang, Hong
2017-10-01
Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD. Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels. We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD. Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.
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Sustained remission of Cushing's disease with mitotane and pituitary irradiation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schteingart, D.E.; Tsao, H.S.; Taylor, C.I.
1980-05-01
Low doses of mitotane were given orally to 36 patients with Cushing's disease, concurrently with or after pituitary cobalt irradiation. Clinical and biochemical remission occurred in 29. The response to treatment occurred early in 17 patients and late in 12. The different pattern of response to mitotane was not related to the dose given or to its serum level. Early biochemical indicators of adrenal suppression with mitotane were a sharp decrease in adrenal response to the infusion of ACTH and in plasma levels of dehydroepiandrosterone sulfate. Although mitotane was given together with pituitary irradiation, initial remission was due mainly tomore » the adrenal effect of mitotane. Plasma ACTH levels were still elevated when cortisol had returned to normal. In seventeen of the 29 patients who responded to treatment drug therapy has been discontinued, and they remain in remission of Cushing's syndrome. Side-effects have been dose dependent, with anorexia, nausea, decreased memory, and gynecomastia in men being the commonest.« less
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Hiramoto, K; Yamate, Y; Kobayashi, H; Ishii, M; Sato, E F; Inoue, M
2013-01-01
In previous studies, we made the unexpected finding that in mice, ultraviolet (UV)B irradiation of the eye increased the concentration of α-melanocyte-stimulating hormone (α-MSH) in plasma, and systemically stimulated epidermal melanocytes. To compare the extent of the pigmentation induced by social and restraint stress (which activate the hippocampus-pituitary system) with that induced by UVB irradiation. DBA/2 and sham-operated or hypophysectomized DBA/2 mice were subjected to local UVB exposure using a sunlamp directed at the eye, and two types of stress (social and restraint) were imposed. UVB irradiation of the eye or exposure to stress loading both increased the number of Dopa-positive melanocytes in the epidermis, and hypophysectomy strongly inhibited the UVB-induced and stress-induced stimulation of melanocytes. Irradiation of the eye caused a much greater increase in dopamine than did the stress load. Both UVB eye irradiation and stress increased the blood levels of α-MSH and adrenocorticotropic hormone (ACTH). In addition, the increase in plasma α-MSH was greater in animals subjected to UVB eye irradiation than in those subjected to stress loading, whereas the reverse occurred for plasma ACTH. UVB irradiation to the eye and stress loading increased the expression of prohormone convertase (PC)1/3 and PC2 in the pituitary gland. The increase in expression of pituitary PC2 was greater in animals subjected to UVB eye irradiation than to stress, whereas no difference was seen between the two groups for the increase in PC1/3. UVB eye irradiation exerts a stronger effect on pigmentation than stress loading, and is related to increased levels of α-MSH and PC2. © The Author(s). CED © 2012 British Association of Dermatologists.
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Plasma testosterone levels in Alzheimer and Parkinson diseases.
Okun, M S; DeLong, M R; Hanfelt, J; Gearing, M; Levey, A
2004-02-10
Testosterone deficiency, a treatable condition commonly seen in aging men, has been linked to Parkinson disease (PD) and Alzheimer disease (AD). In normal subjects, low testosterone levels are associated with cognitive and neuropsychiatric symptoms, yet the relationship between testosterone levels and cognitive function in PD and AD remains unclear. To examine the relationship of testosterone levels to age and cognitive function in PD and AD. Plasma testosterone levels were determined in men enrolled in a clinical registry of subjects with PD and AD, and neuropsychological testing was performed on subjects who consented. Testosterone levels in men with PD were compared with those in men with AD. In both groups, the relationship between testosterone levels and neuropsychological test scores was analyzed, adjusting for age and education. Linear regression analysis revealed that testosterone levels decreased with age in male PD patients (p < 0.03) and male AD patients (p < 0.07). The rate of decline was similar for the two groups. In PD patients, lower testosterone levels were associated with poorer performance on Trails B Seconds (p < 0.02). There is a similar age-related decline in plasma testosterone levels in men with either PD or AD. Previously described associations between low testosterone levels and frontal lobe dysfunction in normal aged men, together with these results, suggest that the hormonal deficiency may act as a "second hit" to impair cognitive function in neurodegenerative disease.
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Specific radioimmunoassay of human. beta. -endorphin in unextracted plasma
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wiedemann, E.; Saito, T.; Linfoot, J.A.
1979-09-01
With an antiserum against human ..beta..-endorphin (..beta..-EP) crossreacting <2% with human ..beta..-lipotropin (..beta..-LPH) by weight we have developed a radioimmunoassay that can detect 1 pg ..beta..-EP in diluted raw plasma. In a.m. fasting plasma of 14 normal subjects ..beta..-EP ranged from <5 to 45 pg/ml. ..beta..-EP was elevated in untreated, but normal in successfully treated Cushing's disease; undetectable in a patient with adrenal adenoma; extremely high in Nelson's syndrome; and elevated in a patient with bronchogenic carcinoma before, but undetectable after tumor resection. In subjects with intact hypothalamic-pituitary-adrenal axis, ..beta..-EP was undectectable after dexamethasone and increased after metyrapone administration andmore » insulin-induced hypoglycemia. ..beta..-EP concentration was considerably lower in serum than in simultaneously collected plasma, but increased in serum left unfrozen for several hours after clot removal. Thus, ..beta..-EP behaves like a hormone responding to the same stimuli as ACTH and ..beta..-LPH and blood appears to contain enzymes both generating and destroying immunoreactive ..beta..-EP.« less
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Addison's Disease and Pituitary Enlargement.
Winters, Stephen J; Vitaz, Todd; Nowacki, Michael R; Craddock, Durrett C; Silverman, Craig
2015-06-01
A 60-year-old man with Addison's disease, primary hypothyroidism and type 2 diabetes mellitus who was treated with stable doses of hydrocortisone and fludrocortisone developed increasing skin pigmentation and a bitemporal hemianopia. The plasma ACTH level was 14,464 pg/mL, and an invasive pituitary macroadenoma with suprasellar extension was found on magnetic resonance imaging leading to transnasal-transsphenoidal adenomectomy. The tumor demonstrated features of an eosinophilic adenoma and stained uniformly for ACTH. Residual tumor was treated with stereotactic radiotherapy. This case and the 13 cases published previously indicate that primary adrenal failure may predispose to corticotroph hyperplasia, and in some patients to the development of an invasive corticotroph adenoma. The ACTH level should be measured, and a pituitary magnetic resonance imaging is indicated when skin pigmentation increases in a patient with primary adrenal failure who is receiving customary treatment with glucocorticoids and mineralocorticoids.
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Uterine activty and plasma progesterone levels in pregnant goats.
Jones, D E; Kinfton, A
1977-01-01
Uterine activity was recorded during the last few weeks of pregnacy in goats, and related to changes in plasma progesterone concentration. In six of the 14 pregnancies, there was little activity until immediately pre-partum, but the remainder showed a progressive increase in uterine motility, particularly during the last seven days of pregnancy. There was a significant correlation between increased uterine activity and decline of peripheral plasma progesterone levels.
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Correlation between plasma component levels of cultured fish and resistance to bacterial infection
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.
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Smoking, COPD and 3-Nitrotyrosine Levels of Plasma Proteins
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jin, Hongjun; Webb-Robertson, Bobbie-Jo M.; Peterson, Elena S.
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 obstructivemore » 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.« less
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High levels of circulating triiodothyronine induce plasma cell differentiation.
Bloise, Flavia Fonseca; Oliveira, Felipe Leite de; Nobrega, Alberto Félix; Vasconcellos, Rita; Cordeiro, Aline; Paiva, Luciana Souza de; Taub, Dennis D; Borojevic, Radovan; Pazos-Moura, Carmen Cabanelas; Mello-Coelho, Valéria de
2014-03-01
The effects of hyperthyroidism on B-cell physiology are still poorly known. In this study, we evaluated the influence of high-circulating levels of 3,5,3'-triiodothyronine (T3) on bone marrow, blood, and spleen B-cell subsets, more specifically on B-cell differentiation into plasma cells, in C57BL/6 mice receiving daily injections of T3 for 14 days. As analyzed by flow cytometry, T3-treated mice exhibited increased frequencies of pre-B and immature B-cells and decreased percentages of mature B-cells in the bone marrow, accompanied by an increased frequency of blood B-cells, splenic newly formed B-cells, and total CD19(+)B-cells. T3 administration also promoted an increase in the size and cellularity of the spleen as well as in the white pulp areas of the organ, as evidenced by histological analyses. In addition, a decreased frequency of splenic B220(+) cells correlating with an increased percentage of CD138(+) plasma cells was observed in the spleen and bone marrow of T3-treated mice. Using enzyme-linked immunospot assay, an increased number of splenic immunoglobulin-secreting B-cells from T3-treated mice was detected ex vivo. Similar results were observed in mice immunized with hen egg lysozyme and aluminum adjuvant alone or together with treatment with T3. In conclusion, we provide evidence that high-circulating levels of T3 stimulate plasma cytogenesis favoring an increase in plasma cells in the bone marrow, a long-lived plasma cell survival niche. These findings indicate that a stimulatory effect on plasma cell differentiation could occur in untreated patients with Graves' disease.
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Kamata, Yayoi; Kimura, Utako; Matsuda, Hironori; Tengara, Suhandy; Kamo, Atsuko; Umehara, Yoshie; Iizumi, Kyoichi; Kawasaki, Hiroaki; Suga, Yasushi; Ogawa, Hideoki; Tominaga, Mitsutoshi; Takamori, Kenji
2016-12-01
Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H 1 -antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer cells that have been shown to modulate inflammation. However, the relationship between Gzms and pathology in AD remains unclear. This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients. Plasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays. Plasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD. Plasma GzmB levels may reflect the degree of pruritus and dermatitis in
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Occhi, Gianluca; Regazzo, Daniela; Albiger, Nora Maria; Ceccato, Filippo; Ferasin, Sergio; Scanarini, Massimo; Denaro, Luca; Cosma, Chiara; Plebani, Mario; Cassarino, Maria Francesca; Mantovani, Giovanna; Stalla, Günter K; Pecori Giraldi, Francesca; Paez-Pareda, Marcelo; Scaroni, Carla
2014-09-01
Cushing's disease (CD) is a rare condition in which hypercortisolemia is secondary to excessive ACTH release from a pituitary corticotroph adenoma. CD is associated with significant morbidity and mortality, and a safe therapy that effectively targets the pituitary tumor is still lacking. Retinoic acid (RA) and dopamine agonists (DAs) have recently been considered as monotherapy in CD patients, and satisfactory results have been reported, albeit in a limited number of patients. Given the permissive role of RA on the dopamine receptor type-2 (DRD2), the aim of the present study was to see whether a combination of 9-cis RA and the DA bromocriptine (Br) might represent a possible treatment for CD. Here we show that 9-cis RA induces a functional DRD2 in the pituitary corticotroph cell line AtT20, and increases cell sensitivity to Br via a mechanism only partially related to corticotroph-to-melanotroph transdifferentiation. In addition, 9-cis RA and Br act synergistically to modulate cell viability, with favorable implications for clinical use. In nearly 45% of corticotropinoma-derived primary cultures, the combined administration of 9-cis RA and Br lowered the steady-state level of the ACTH precursor proopiomelanocortin (POMC) more efficiently than either of the drugs alone. In conclusion, the effects of a combination of 9-cis RA and Br on ACTH synthesis/secretion and cell viability in AtT20, and on POMC transcriptional activity in human corticotropinomas might represent a suitable starting point for assessing the potential of this treatment regimen for ACTH-secreting pituitary adenomas. This study thus has potentially important implications for novel therapeutic approaches to CD.
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Arterial and venous plasma levels of bupivacaine following peripheral nerve blocks.
Moore, D C; Mather, L E; Bridenbaugh, L D; Balfour, R I; Lysons, D F; Horton, W G
1976-01-01
Mean arterial plasma (MAP) and peripheral mean venous plasma (MVP) levels of bupivacaine were ascertained in 3 groups of 10 patients each for: (1) intercostal nerve block, 400 mg; (2) block of the sciatic, femoral, and lateral femoral cutaneous nerves, with or without block of the obturator nerve, 400 mg; and (3) supraclavicular brachial plexus block, 300 mg. MAP levels were consistently higher than simultaneously sampled MVP levels, the highest levels occurring from bilateral intercostal nerve block. No evidence of systemic toxicity was observed. The results suggest that bupivacaine has a much wider margin of safety in humans than is now stated.
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[Is plasma selenium correlated to transthyretin levels in critically ill patients?
Freitas, Renata G B O N; Nogueira, Roberto Jose Negrão; Cozzolino, Silvia Maria Franciscato; Vasques, Ana Carolina Junqueira; Ferreira, Matthew Thomas; Hessel, Gabriel
2017-06-05
Selenium is an essential trace element, but critically ill patients using total parenteral nutrition (PN) do not receive selenium because this mineral is not commonly offered. Threfore, the eval uation of plasma selenium levels is very important for treating or preventing this deficiency. Recent studies have shown that transthyretin may reflect the selenium intake and could be considered a biomarker. However, this issue is still little explored in the literature. This study aims to investigate the correlation of transthyretin with the plasma selenium of critically ill patients receiving PN. This was a prospective cohort study with 44 patients using PN without selenium. Blood samples were carried out in 3 stages: initial, 7th and 14th day of PN. In order to evaluate the clinical condition and the inflammatory process, albumin, C-reactive protein (CRP), transthyretin, creatinine and HDL cholesterol levels were observed. To assess the selenium status, plasma selenium and glutathione peroxidase (GPx) in whole blood were measured. Descriptive analyses were performed and the ANOVA, Mann-Whitney and Spearman's coefficient tests were conducted; we assumed a significance level of 5%. A positive correlation of selenium with the GPx levels (r = 0.46; p = 0.03) was identified. During two weeks, there was a positive correlation of transthyretin with plasma selenium (r = 0.71; p = 0.05) regardless of the CRP values. Transthyretin may have reflected plasma selenium, mainly because the correlation was verified after the acute phase.
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Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease.
Ju, Chun-Rong; Chen, Miao; Zhang, Jian-Heng; Lin, Zhi-Ya; Chen, Rong-Chang
2016-01-01
To analyze plasma myostatin levels and investigate their relationship with right ventricular (RV) function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD). The study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE) less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP) levels were analyzed as a comparison of myostatin. The data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL) were significantly higher in patients with cor pulmonale (16.68 ± 2.95) than in those without (13.56 ± 3.09), and much higher than in controls (8.79±2.79), with each p<0.01. Significant differences were also found in plasma BNP levels among the three groups (p<0.05). Multivariate regression analysis suggested that myostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each p<0.05. Plasma myostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD.
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Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease
Ju, Chun-rong; Chen, Miao; Zhang, Jian-heng; Lin, Zhi-ya; Chen, Rong-chang
2016-01-01
Objective To analyze plasma myostatin levels and investigate their relationship with right ventricular (RV) function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD). Methods The study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE) less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP) levels were analyzed as a comparison of myostatin. Results The data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL) were significantly higher in patients with cor pulmonale (16.68 ± 2.95) than in those without (13.56 ± 3.09), and much higher than in controls (8.79±2.79), with each p<0.01. Significant differences were also found in plasma BNP levels among the three groups (p<0.05). Multivariate regression analysis suggested that myostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each p<0.05. Conclusions Plasma myostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD. PMID:26998756
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Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels.
Bershad, Anya K; Kirkpatrick, Matthew G; Seiden, Jacob A; de Wit, Harriet
2015-06-01
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), seems 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 2 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 levels. In study 1, 11 healthy adult volunteers attended 3 sessions during which they received methamphetamine (10 mg or 20 mg) or placebo under double-blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin levels were measured at regular intervals throughout the sessions. In study 2, 8 healthy adult volunteers attended a single session during which they received 1 beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin levels were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither of these drugs increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified.
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PLASMA OXYTOCIN LEVELS PREDICT SOCIAL CUE RECOGNITION IN INDIVIDUALS WITH SCHIZOPHRENIA
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
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Unraveling atomic-level self-organization at the plasma-material interface
NASA Astrophysics Data System (ADS)
Allain, J. P.; Shetty, A.
2017-07-01
The intrinsic dynamic interactions at the plasma-material interface and critical role of irradiation-driven mechanisms at the atomic scale during exposure to energetic particles require a priori the use of in situ surface characterization techniques. Characterization of ‘active’ surfaces during modification at atomic-scale levels is becoming more important as advances in processing modalities are limited by an understanding of the behavior of these surfaces under realistic environmental conditions. Self-organization from exposure to non-equilibrium and thermalized plasmas enable dramatic control of surface morphology, topography, composition, chemistry and structure yielding the ability to tune material properties with an unprecedented level of control. Deciphering self-organization mechanisms of nanoscale morphology (e.g. nanodots, ripples) and composition on a variety of materials including: compound semiconductors, semiconductors, ceramics, polymers and polycrystalline metals via low-energy ion-beam assisted plasma irradiation are critical to manipulate functionality in nanostructured systems. By operating at ultra-low energies near the damage threshold, irradiation-driven defect engineering can be optimized and surface-driven mechanisms controlled. Tunability of optical, electronic, magnetic and bioactive properties is realized by reaching metastable phases controlled by atomic-scale irradiation-driven mechanisms elucidated by novel in situ diagnosis coupled to atomistic-level computational tools. Emphasis will be made on tailored surface modification from plasma-enhanced environments on particle-surface interactions and their subsequent modification of hard and soft matter interfaces. In this review, we examine current trends towards in situ and in operando surface and sub-surface characterization to unravel atomic-scale mechanisms at the plasma-material interface. This work will emphasize on recent advances in the field of plasma and ion
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Association between plasma kisspeptin levels and adolescent gynecomastia.
Aluclu, Mustafa Arif; Sen, Selcuk; Cevik, Muazez
2016-01-01
Gynecomastia is defined as benign proliferation of male breast glandular tissue. To date, the pathophysiology of adolescent gynecomastia (AG) remains unclear. Kisspeptin is a polypeptide that plays an important role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis. In this study, we investigated whether there is a relationship between kisspeptin and AG. This study included 40 males between 9 and 18 years of age diagnosed with gynecomastia. The control group consisted of 30 young healthy males in the same age range. The participants were evaluated with respect to anthropometric measurements (age, height, body weight, body mass index, breast and pubic stages and testicular volume). The levels of kisspeptin, follicle-stimulating hormone, luteinizing hormone, estradiol (E2), testosterone (T), and ratio of E2 to T were measured in both groups. The mean age was 13.8 years. There were no differences between the groups in terms of anthropometric parameters, plasma gonadotropin levels, estrogen levels, and E2/T (P > 0.05). Plasma kisspeptin (0.77 and 0.54 ng/mL, P < 0.05) and T (253.9 ng/dL and 117.9 ng/dL) levels were significantly higher in the AG group than in the control group (P < 0.001). Kisspeptin levels are an important factor in AG.
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Elevated plasma midkine and pleiotrophin levels in patients with systemic lupus erythematosus.
Wu, Guo-Cui; Yuan, Hui; Pan, Hai-Feng; Ye, Dong-Qing
2017-06-20
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.
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Alsop, Derek; Ings, Jennifer S.; Vijayan, Mathilakath M.
2009-01-01
While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity. PMID:19649243
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Plasma Levels of Nitrite and Nitrate in Early and Recent Classes of Fish
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
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Childhood Chronic Physical Aggression Associates with Adult Cytokine Levels in Plasma
Provençal, Nadine; Suderman, Matthew J.; Vitaro, Frank; Szyf, Moshe; Tremblay, Richard E.
2013-01-01
Background An increasing number of animal and human studies are indicating that inflammation is associated with behavioral disorders including aggression. This study investigates the association between chronic physical aggression during childhood and plasma cytokine levels in early adulthood. Methodology/Principal Findings Two longitudinal studies were used to select males on a chronic physical aggression trajectory from childhood to adolescence (n = 7) and a control group from the same background (n = 25). Physical aggression was assessed yearly by teachers from childhood to adolescence and plasma levels of 10 inflammatory cytokines were assessed at age 26 and 28 years. Compared to the control group, males on a chronic physical aggression trajectory from childhood to adolescence had consistently lower plasma levels of five cytokines: lower pro-inflammatory interleukins IL-1α (T(28.7) = 3.48, P = 0.002) and IL-6 (T(26.9) = 3.76, P = 0.001), lower anti-inflammatory interleukin IL-4 (T(27.1) = 4.91, P = 0.00004) and IL-10 (T(29.8) = 2.84, P = 0.008) and lower chemokine IL-8 (T(26) = 3.69, P = 0.001). The plasma levels of four cytokines accurately predicted aggressive and control group membership for all subjects. Conclusions/Significance Physical aggression of boys during childhood is a strong predictor of reduced plasma levels of cytokines in early adulthood. The causal and physiological relations underlying this association should be further investigated since animal data suggest that some cytokines such as IL-6 and IL-1β play a causal role in aggression. PMID:23922720
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Disuse atrophy, plasma corticosterone, and muscle glucocorticoid receptor levels
NASA Technical Reports Server (NTRS)
Steffen, J. M.; Musacchia, X. J.
1987-01-01
The effect of whole-body suspension on the time course and the extent of plasma corticosterone changes and the tissue sensitivity to glucocorticoids were investigated in rats subjected to seven days of whole-body suspension. Plasma corticosterone increased significantly on the first and the third days of suspension, but returned to control levels by day seven. Muscle glucocorticoid receptors exhibited a characteristic hormonal specificity (evaluated in competitive-displacement experiments). In controls, receptor site concentration in the slow-twitch soleus was comparable to that in the fast-twitch gastrocnemius and plantaris, but was significantly less than in the extensor; seven days of suspension resulted in significant differential effects on muscle receptor levels. The largest increase in receptor concentration was observed in the soleus in which it remained elevated after the receptor levels in other muscles returned to normal.
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Relevance of plasma malondialdehyde level and severity of portal hypertension in cirrhotic patients.
Wang, Sheng-Lan; Zhu, Xin-Yan; Zhang, Dong-Wei; Zhang, Zhao-Jie; Gao, Heng-Jun; Yang, Chang-Qing
2015-01-01
Portal hypertension is one of the death reasons for the liver cirrhosis patients. The oxidative stress is related to the occurrence and development of portal hypertension in cirrhosis. Malondialdehyde (MDA), one of the lipid peroxides, increases substantially in cirrhotic patients. To evaluate the relevance between the MDA level and portal hypertension in cirrhotic patients. 60 liver cirrhotic patients and 30 healthy controls were enrolled. The plasma MDA level and general blood tests including ALT, AST, ALB, total bilirubin, and platelet were measured. All people enrolled accepted endoscopic examination and B-Ultrasound check to evaluate the severity of portal hypertension. The MDA plasma level of cirrhotic patients was significantly higher than the controls (P<0.001) and increased significantly accompanied by the severity of liver fibrosis and portal hypertension (P<0.01). Further, the plasma MDA level of cirrhotic patients was significantly correlated with Child-Pugh classification of cirrhosis (r=0.820, P<0.001), the degree of esophageal varices (r=0.857, P<0.001) and the width of portal vein (r=0.652, P<0.001). The ROC curve analyses showed that the plasma MDA level is a strong predictor of liver cirrhosis and portal hypertension. Plasma MDA level may correlate with the severity of portal hypertension in cirrhotic patients.
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Association between lifestyle factors and plasma adiponectin levels in Japanese men.
Tsukinoki, Rumi; Morimoto, Kanehisa; Nakayama, Kunio
2005-11-02
Adiponectin is an adipocyte-specific protein that plays a role in obesity, insulin resistant, lipid metabolism, and anti-inflammation. Hypoadiponectinemia may be associated with a higher risk for type 2 diabetes and cardiovascular disease. Some studies suggest that adiponectin levels are modulated by lifestyle factors, but little is known about the associations between lifestyle factors and plasma adiponectin levels in Japanese people. We therefore investigated the associations between lifestyle factors and plasma adiponectin levels in general Japanese men. The subjects were 202 Japanese male workers who participated in an annual health check. They provided details about anthropometrical data, blood collection, their use of prescribed medication, and the clinical history of their families. They also completed a self-administered questionnaire about their lifestyles. Subjects with plasma adiponectin levels below 4.0 microg/ml had significantly lower levels of HDL cholesterol and higher levels of BMI, SBP, DBP, total cholesterol, FBG, and platelets than did subjects with higher adiponectin levels. In multiple logistic regression after multiple adjustment, a plasma adiponectin level below 4.0 microg/ml was significantly associated with smoking (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.01-4.30), a daily diet rich in deep-yellow vegetables (OR = 0.25, 95% CI= 0.07-0.91), frequent eating out (OR = 2.45, 95% CI = 1.19-5.08), and physical exercise two or more times a week (OR = 0.21, 95% CI = 0.06-0.74). Our findings show that adiponectin levels in general Japanese men are independently related to smoking, dietary factors, and physical exercise. We think that lifestyle habits might independently modulate adiponectin levels and that adiponectin might be the useful biomarker helping people to avoid developing type 2 diabetes and cardiovascular disease by modifying their lifestyles.
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Sid-Ahmed, Omer-Elfaroug; Sanhouri, Ahmed; Elwaseela, Badr-Eldin; Fadllalah, Imad; Mohammed, Galal-Eldin Elazhari; Möstl, Erich
2013-08-01
The aim of this study was to determine whether glucocorticoid production could be monitored non-invasively in dromedary camels by measuring faecal cortisol metabolites (FCMs). Five Sudanese dromedaries, two males and three females, were injected with a synthetic adrenocorticotropic hormone (ACTH) analogue. Blood samples were collected pre- and post-ACTH injection. Faeces were sampled after spontaneous defecation for five consecutive days (2 days before and 3 days after ACTH injection). Baseline plasma cortisol values ranged from 0.6 to 10.8 ng/ml in males and from 1.1 to 16.6 ng/ml in females, while peak values after ACTH injection were 10.9-41.9 in males and 10-42.2 ng/ml in females. Peak blood cortisol values were reached between 1.5 and 2.0 h after ACTH injection. The concentration of FCMs increased after ACTH injection in the faeces of both sexes, although steroid levels peaked earlier in males [24 h; (286.7-2,559.7 ng/g faeces)] than in females [36-48 h; (1,182.6-5,169.1 ng/g faeces)], reflecting increases of 3.1-8.3- and 4.3-8-fold above baseline levels. To detect chromatographic patterns of immunoreactive FCMs, faecal samples with high FCM concentrations from both sexes were pooled and subjected to reverse phase high performance liquid chromatography (RP-HPLC). RP-HPLC analysis revealed sex differences in the polarity of FCMs, with females showing more polar FCMs than males. We concluded that stimulation of adrenocortical activity by ACTH injection resulted in a measurable increase in blood cortisol that was reliably paralleled by increases in FCM levels. Thus, measurement of FCMs is a powerful tool for monitoring the adrenocortical responses of dromedaries to stressors in field conditions.
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Evaluation of plasma reactive oxygen metabolites levels in obese subjects with periodontal disease.
Suresh, Snophia; Mahendra, Jaideep; Sudhakar, Uma; Pradeep, A R; Singh, Gurdeep
2016-01-01
Obesity represents the systemic condition capable of influencing the onset and progression of periodontal disease. Obesity is associated with oxidative stress. Plasma level of reactive oxidative metabolites (ROMs) is measured as an indicator of oxidative stress in the body. The aim of this study is to assess and compare the plasma ROM levels in obese subjects with healthy and inflammatory periodontal status. Sixty subjects selected were grouped as 15 obese or overweight subjects with generalized chronic periodontitis, 15 obese or overweight subjects with generalized chronic gingivitis, 15 obese or overweight subjects with healthy periodontium, and 15 nonobese and healthy periodontium. The clinical periodontal parameters such as plaque index, gingival index, probing pocket depth, and clinical attachment level were measured. Blood samples were obtained to measure the plasma levels of ROM. In this study, obese subjects with chronic periodontitis (Group I) had mean plasma ROM levels (442.3 ± 15.65 Carratelli unit [CARR U]) showing 100% subjects with high oxidative stress. Obese subjects with chronic gingivitis (Group II) had mean plasma ROM levels (358.7 ± 20.61 CARR U) indicating 86.7% subjects with oxidative stress. Obese subjects with healthy periodontium (Group III) had 46.7% subjects with slight oxidative stress, and the mean ROM level was 320.2 ± 17.57. Nonobese subjects with healthy periodontium (Group IV) had 80% of subjects with normal oxidative stress and the mean plasma ROM level was 296.9 ± 20.35 CARR U. The intra- and inter-group comparison showed significant difference (P < 0.001). From our study, we report that obese subjects with periodontitis have more oxidative stress compared to obese subjects with healthy periodontium.
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Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy
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
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Cordoba-Chacón, José; Gahete, Manuel D; Pozo-Salas, Ana I; de Lecea, Luis; Castaño, Justo P; Luque, Raúl M
2016-07-01
Cortistatin (CORT) shares high structural and functional similarities with somatostatin (SST) but displays unique sex-dependent pituitary actions. Indeed, although female CORT-knockout (CORT-KO) mice exhibit enhanced GH expression/secretion, Proopiomelanocortin expression, and circulating ACTH/corticosterone/ghrelin levels, male CORT-KO mice only display increased plasma GH/corticosterone levels. Changes in peripheral ghrelin and SST (rather than hypothalamic levels) seem to regulate GH/ACTH axes in CORT-KOs under fed conditions. Because changes in GH/ACTH axes during fasting provide important adaptive mechanisms, we sought to determine whether CORT absence influences GH/ACTH axes during fasting. Accordingly, fed and fasted male/female CORT-KO were compared with littermate controls. Fasting increased circulating GH levels in male/female controls but not in CORT-KO, suggesting that CORT can be a relevant regulator of GH secretion during fasting. However, GH levels were already higher in CORT-KO than in controls in fed state, which might preclude a further elevation in GH levels. Interestingly, although fasting-induced pituitary GH expression was elevated in both male/female controls, GH expression only increased in fasted female CORT-KOs, likely owing to specific changes observed in key factors controlling somatotrope responsiveness (ie, circulating ghrelin and IGF-1, and pituitary GHRH and ghrelin receptor expression). Fasting increased corticosterone levels in control and, most prominently, in CORT-KO mice, which might be associated with a desensitization to SST signaling and to an augmentation in CRH and ghrelin-signaling regulating corticotrope function. Altogether, these results provide compelling evidence that CORT plays a key, sex-dependent role in the regulation of the GH/ACTH axes in response to fasting.
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Decreased Plasma BDNF Levels of Patients with Somatization Disorder
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
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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.
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Lipid and other plasma markers are associated with anxiety, depression, and fatigue.
Lieberman, Harris R; Kellogg, Mark D; Kramer, F Matthew; Bathalon, Gaston P; Lesher, Larry L
2012-03-01
Few peripheral metabolites have been shown to be associated with mood in healthy individuals or patients with central nervous system diseases. During military basic combat training (BCT), mood state, physical performance and body composition substantially improve, providing an opportunity to examine relationships between mood and nutritional and hormonal biomarkers. Thirty-five females enrolled in U.S. Marine BCT, an intense physically and mentally challenging 12-week course, were studied. Every 4 weeks, mood was assessed with the Profile of Mood States (POMS), as were nutritional, metabolic and hormonal plasma markers. Mood and fitness improved over BCT, and there were substantial changes in biochemical markers. Multiple regression demonstrated that, in combination, cholesterol (HDL, LDL), fructosamine, triglycerides, free fatty acids (FFA), dehydroepiandrosterone-sulfate (DHEA-S), ACTH, and substance P accounted for 44% of variation in anxiety, 40% confusion, 37% fatigue, 27% depression and 40% in total mood (p < .0001). Increased HDL, FFA, DHEA-S, and substance P were associated with degraded mood (p < .05). Increased LDL, triglycerides, fructosamine, and ACTH were associated with improved mood (p < .05). Other markers, including glucose, cortisol, and C-reactive protein were not associated with mood. Normal human mood state was associated with 8 plasma markers. Increased HDL and lower LDL, which are associated with improved cardiovascular status, were associated with negative affect. Fructosamine and substance P, not previously known to be related to mood, were associated with it. We are not aware of any biological parameters that in aggregate predict such a substantial proportion of variation in normal mood.
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Riddle, M A; Jatlow, P I; Anderson, G M; Cho, S C; Hardin, M T; Cohen, D J; Leckman, J F
1989-06-01
Plasma concentrations of unconjugated homovanillic acid (pHVA) reflect both central nervous system (CNS) and peripheral dopamine metabolism. Debrisoquin sulfate (DBQ) blocks peripheral, but not CNS, production of HVA from dopamine. Administration of DBQ has been used to decrease the proportion of peripherally produced HVA in pHVA measurements, making such measurements more reflective of CNS turnover of dopamine. We studied the relationships between DBQ dose, plasma DBQ (pDBQ) levels, and changes in pHVA in a group of 21 subjects (9 normal controls and 12 with Tourette's syndrome). DBQ dose was moderately correlated with pDBQ levels (r = 0.63, p = 0.002). Subjects (n = 8) with mean pDBQ levels above 60 ng/ml had a 48% to 66% decrease in mean pHVA levels; this may reflect nearly complete inhibition of peripheral HVA production. Subjects (n = 13) with mean pDBQ levels below 55 ng/ml had decreases in pHVA levels from 10% to 58%. No debrisoquin was detected in cerebrospinal fluid samples. These data suggest that pDBQ levels above 60 ng/ml are sufficient to assure substantial inhibition of peripheral HVA production and that monitoring pDBQ levels may be useful when employing this method for studying CNS metabolism.
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Li, R. C.; Krishnamoorthy, P.; DerOhannessian, S.; Doveikis, J.; Wilcox, M.; Thomas, P.; Rader, D. J.; Reilly, M. P.; Voorhees, A. Van; Gelfand, J. M.; Mehta, N. N.
2013-01-01
Summary Background Psoriasis is an inflammatory skin disease that may be associated with an adverse cardiometabolic profile including modulated plasma adiponectin and leptin levels. Whether these levels are independent of cardiometabolic risk factors, which are also prevalent in psoriasis, is not known. Methods A consecutive sample of 122 participants with varying degrees of psoriasis severity, and a random sample of 134 participants without psoriasis were recruited for this case–control study. Cardiometabolic risk factors including traditional cardiovascular risk factors, waist circumference, insulin resistance, and total plasma adiponectin and leptin were measured. Total plasma adiponectin and leptin levels were compared in unadjusted and adjusted analyses by psoriasis status. Results Participants with psoriasis had mostly mild disease and were mainly on topical therapies, but still had a more adverse cardiometabolic profile compared with those without psoriasis. Furthermore, plasma adiponectin levels were significantly lower in participants with psoriasis than those without {7.13 µg/mL [interquartile range (IQR) 4.9–11.3) vs. 14.5 µg/mL (IQR 8.4–24.1); P < 0.001]}. Plasma leptin (ng/mL) levels were higher in the psoriasis group but this did not reach statistical significance [11.3 (IQR 6.4–21.8) vs. 9.8 (IQR 4.9–20.5); P = 0.07]. In multivariable modelling, plasma adiponectin levels were still negatively associated with psoriasis status after adjusting for waist size (% difference = −41.2%, P < 0.001), insulin resistance (% difference = −39.5%, P < 0.001) and both waist size and insulin resistance (% difference = −38.5%, P < 0.001) Conclusion Plasma levels of adiponectin were lower in psoriasis, and this relationship persisted after adjusting for cardiometabolic risk factors known to decrease adiponectin levels. These findings suggest that inflammation present in psoriasis may be associated with adipose tissue dysfunction; however, direct
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Tsutamoto, T; Wada, A; Maeda, K; Mabuchi, N; Hayashi, M; Tsutsui, T; Ohnishi, M; Fujii, M; Matsumoto, T; Yamamoto, T; Takayama, T; Kinoshita, M
2001-12-01
Cardiac natriuretic peptides may induce apoptosis in myocytes; however, the relationship between plasma levels of cardiac natriuretic peptides and those of soluble Fas (sFas) and tumor necrosis factor (TNF)-alpha remains unknown in patients with congestive heart failure (CHF). We measured plasma levels of sFas and TNF-alpha and those of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, and endothelin 1 in 96 patients with CHF (ejection fraction < 45%). The patients were monitored for 3 years. Plasma levels of sFas and TNF-alpha increased with the severity of CHF. There was no significant correlation between sFas plasma levels and those of ANP and BNP. Cox proportional hazard analysis showed that high levels of sFas (P = .009) and BNP (P < .0001) and a low ejection fraction (P = .019) were independent significant prognostic predictors. There is no significant correlation between cardiac natriuretic peptide and sFas levels in plasma. Plasma sFas is a useful prognostic marker independent of neurohumoral factors, suggesting that immune activation and/or apoptosis play a significant role in the pathogenesis of CHF.
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Plasma levels of selenium-containing proteins in Inuit adults from Nunavik.
Achouba, Adel; Dumas, Pierre; Ouellet, Nathalie; Lemire, Mélanie; Ayotte, Pierre
2016-11-01
Selenium (Se) is highly abundant in marine foods traditionally consumed by Inuit of Nunavik (Northern Quebec, Canada) and accordingly, their Se intake is among the highest in the world. However, little is known regarding the biological implications of this high Se status in this Arctic indigenous population. We used a method combining affinity chromatography and inductively coupled plasma-mass spectrometry with quantification by post-column isotope dilution to determine total Se levels and concentrations of Se-containing proteins in archived plasma samples of Inuit adults who participated to the 2004 Nunavik Inuit Health Survey (N = 852). Amounts of mercury (Hg) associated with Se-containing proteins were also quantified. Results show that glutathione peroxidase 3 (GPx3), selenoprotein P (SelP) and selenoalbumin (SeAlb) represented respectively 25%, 52% and 23% of total plasma Se concentrations. In addition, small amounts of Hg co-eluted with each Se-containing protein and up to 50% of plasma Hg was associated to SelP. Total plasma Se concentrations (median = 139 μg L− 1; interquartile range (IQR) = 22.7 μg L− 1) were markedly lower and less variable than whole blood Se concentration (median = 261 μg L− 1, IQR = 166 μg L− 1). A non linear relation was observed between whole blood Se and plasma Se levels, with plasma Se concentrations leveling off at approximately 200 μg L− 1, whereas 16% and 3% of individuals exhibited whole blood concentrations higher than 500 μg L− 1 and 1000 μg L− 1, respectively. In contrast, a linear relationship was previously reported in communities consuming Brazil nuts which are rich Se, mainly present as selenomethionine. This suggests that a different selenocompound, possibly selenoneine, is present in the Arctic marine food chain and accumulates in the blood cellular fraction of Inuit.
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Gottsäter, A; Anwaar, I; Lind, P; Mattiasson, I; Lindgärde, F
1999-04-01
Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P < 0.01] was noted in levels of total cholesterol, and a decrease of 1.70 mmol/l [1.52-2.30 (28%); P < 0.01] in levels of low-density lipoprotein cholesterol. Plasma levels of fibrinogen had increased [from 4.81 g/l (4.26-5.27) to 5.17 g/l (4.81-5.67); P < 0.05], whereas no significant changes had occurred in intraplatelet levels of cGMP [decrease by 0.05 pmol/10(9) platelets (-0.17 to 0.24); NS], cAMP [decrease by 0.13 pmol/10(9) platelets (-0.37 to 0.86); NS], plasma endothelin-1 [decrease by 0.05 pg/ml (-0.60 to 0.70); NS], plasma factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.
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Plasma levels of serotonin, gastrointestinal symptoms,and sleep problems in children with autism.
Kheirouri, Sorayya; Kalejahi, Parinaz; Noorazar, Seyyed Gholamreza
2016-12-20
Autism is a neurodevelopmental disorder identified with higher frequency of serotonin abnormalities and gastrointestinal (GI) and sleep problems. This study aimed to evaluate the plasma levels of serotonin, GI symptoms, and sleep problems, and their relationship with autism severity in children with autism. Thirty-five children with autism and 31 healthy subjects were studied. GI problems, sleep disorders, and severity of disorder were assessed. Plasma serotonin was determined using ELISA. There was no significant association between GI problems and autism severity, but a significant positive correlation was seen between different indicators of sleep disorder and severity of autism. Plasma levels of serotonin were significantly higher in autistic children and a significant negative correlation was observed between plasma levels of serotonin and autism severity (r = -0.39, P = 0.02). Elevated plasma serotonin in autistic children and its negative correlation with disease severity may indicate involvement of the neurotransmitter in the neurophysiologic mechanism of autism.
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Highly resolved fluid flows: "liquid plasmas" at the kinetic level.
Morfill, Gregor E; Rubin-Zuzic, Milenko; Rothermel, Hermann; Ivlev, Alexei V; Klumov, Boris A; Thomas, Hubertus M; Konopka, Uwe; Steinberg, Victor
2004-04-30
Fluid flow around an obstacle was observed at the kinetic (individual particle) level using "complex (dusty) plasmas" in their liquid state. These "liquid plasmas" have bulk properties similar to water (e.g., viscosity), and a comparison in terms of similarity parameters suggests that they can provide a unique tool to model classical fluids. This allows us to study "nanofluidics" at the most elementary-the particle-level, including the transition from fluid behavior to purely kinetic transport. In this (first) experimental investigation we describe the kinetic flow topology, discuss our observations in terms of fluid theories, and follow this up with numerical simulations.
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Differential effect of protein and fat on plasma ghrelin levels in man.
Erdmann, Johannes; Lippl, Florian; Schusdziarra, Volker
2003-11-15
Ghrelin, a gastric hormone that stimulates food intake is decreased after ingestion of carbohydrate-rich meals. The acute effect of fat- and protein-rich meals on plasma ghrelin levels is still unknown. Accordingly, plasma ghrelin levels were determined in 10 healthy volunteers after ingestion of the three macronutrients and during vagal stimulation by modified sham feeding and following gastric distension with a highly viscous guar solution. After a solid carbohydrate-rich test meal ghrelin levels fell from 559+/-59.3 pg/ml to a nadir of 449+/-47.4 pg/ml within 60 min (p<0.05). Following an oral glucose load (75 g in 300 ml water), a similar decrease was observed (p<0.05). A fat-rich meal also decreased plasma ghrelin levels (p<0.05) leading to a nadir towards the end of the study period at 180 min. Protein intake, however, stimulated plasma ghrelin levels from 449+/-68.1 to a plateau of 520 pg/ml (p<0.05). There was no significant change of ghrelin levels after modified sham feeding or gastric distension. In conclusion, the decrease of ghrelin levels after fat ingestion shows a different time pattern compared to carbohydrate, while protein ingestion stimulated ghrelin levels. This suggests that different and as yet unknown mechanisms contribute to the regulation of postprandial ghrelin release in man depending on the ingested macronutrients. Cephalic-vagal and intragastric neural mechanisms most likely do not contribute to the postprandial regulation of ghrelin secretion.
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Ten-year change in plasma amyloid beta levels and late-life cognitive decline.
Okereke, Olivia I; Xia, Weiming; Selkoe, Dennis J; Grodstein, Francine
2009-10-01
Plasma levels of amyloid beta peptide (Abeta) are potential biomarkers of early cognitive impairment and decline and of Alzheimer disease risk. To relate midlife plasma Abeta measures and 10-year change in plasma Abeta measures since midlife to late-life cognitive decline. Prospective study of a population-based sample. Academic research. Plasma Abeta40 and Abeta42 levels were measured in 481 Nurses' Health Study participants in late midlife (mean age, 63.6 years) and again 10 years later (mean age, 74.6 years). Cognitive testing also began 10 years after the initial blood draw. Participants completed 3 repeated telephone-based assessments (mean span, 4.1 years). Multivariable linear mixed-effects models were used to estimate relations of midlife plasma Abeta40 to Abeta42 ratios and Abeta42 levels to late-life cognitive decline, as well as relations of 10-year change in Abeta40 to Abeta42 ratios and Abeta42 levels to cognitive decline. The 3 primary outcomes were the Telephone Interview for Cognitive Status (TICS) findings, a global score averaging the results of all tests (TICS, immediate and delayed verbal recall, category fluency, and attention), and a verbal memory score averaging the results of 4 tests of verbal recall. Higher midlife plasma Abeta40 to Abeta42 ratios were associated with worse late-life decline on the global score (P = .04 for trend). Furthermore, increase in Abeta40 to Abeta42 ratios since midlife predicted greater decline in the global score (P = .03 for trend) and in the TICS (P = .02 for trend). There was no association of cognitive decline with midlife plasma Abeta42 levels alone or with change in Abeta42 levels since midlife. In this large community-dwelling sample, higher plasma Abeta40 to Abeta42 ratios in late midlife and increases in Abeta40 to Abeta42 ratios 10 years later were significantly associated with greater decline in global cognition at late life.
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Cognitive style, alprazolam plasma levels, and treatment response in panic disorder.
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. Published 2007 Wiley-Liss, Inc.
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Samson, W K; Baker, J R; Samson, C K; Samson, H W; Taylor, M M
2004-10-01
Neuropeptide B (NPB) was identified to be an endogenous, peptide ligand for the orphan receptors GPR7 and GPR8. Because GPR7 is expressed in rat brain and, in particular, in the hypothalamus, we hypothesized that NPB might interact with neuroendocrine systems that control hormone release from the anterior pituitary gland. No significant effects of NPB were observed on the in vitro releases of prolactin, adrenocorticotropic hormone (ACTH) or growth hormone (GH) when log molar concentrations ranging from 1 pM to 100 nM NPB were incubated with dispersed anterior pituitary cells harvested from male rats. In addition NPB (100 nM) did not alter the concentration response stimulation of prolactin secretion by thyrotropin-releasing hormone, ACTH secretion by corticotropin-releasing factor (CRF) and GH secretion by GH-releasing hormone. However, NPB, when injected into the lateral cerebroventricle (i.c.v.) of conscious, unrestrained male rats, elevated prolactin and corticosterone, and lowered GH levels in circulation. The threshold dose for the effect on corticosterone and prolactin levels was 1.0 nmol, while that for the effect on GH release was 3.0 nmol NPB. Pretreatment with a polyclonal anti-CRF antiserum completely blocked the ability of NPB to stimulate ACTH release and significantly inhibited the effect of NPB on plasma corticosterone levels. NPB administration i.c.v. did not significantly alter plasma vasopressin and oxytocin levels in conscious rats. It did stimulate feeding (minimum effective dose 1.0 nmol) in sated animals in a manner similar to that of the other endogenous ligand for GPR7, neuropeptide W. We conclude that NPB can act in the brain to modulate neuroendocrine signals accessing the anterior pituitary gland, but does not itself act as a releasing or inhibiting factor in the gland, at least with regard to prolactin, ACTH and GH secretion.
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Carrico, Adam W; Rodriguez, Violeta J; Jones, Deborah L; Kumar, Mahendra
2018-01-01
This study examined if methamphetamine use alone (METH + HIV-) and methamphetamine use in combination with HIV (METH + HIV+) were associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation as well as insulin resistance relative to a nonmethamphetamine-using, HIV-negative comparison group (METH-HIV-). Using an intact groups design, serum levels of HPA axis hormones in 46 METH + HIV- and 127 METH + HIV+ men who have sex with men (MSM) were compared to 136 METH-HIV- men. There were no group differences in prevailing adrenocorticotropic hormone (ACTH) or cortisol levels, but the association between ACTH and cortisol was moderated by METH + HIV+ group (β = -0.19, p < .05). Compared to METH-HIV- men, METH + HIV+ MSM displayed 10% higher log 10 cortisol levels per standard deviation lower ACTH. Both groups of methamphetamine-using MSM had lower insulin resistance and greater syndemic burden (i.e., sleep disturbance, severe depression, childhood trauma, and polysubstance use disorder) compared to METH-HIV- men. However, the disaggregated functional relationship between ACTH and cortisol in METH + HIV+ MSM was independent of these factors. Further research is needed to characterize the bio-behavioral pathways that explain dysregulated HPA axis functioning in HIV-positive, methamphetamine-using MSM. Copyright © 2017 John Wiley & Sons, Ltd.
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Cannabis use is associated with increased CCL11 plasma levels in young healthy volunteers.
Fernandez-Egea, Emilio; Scoriels, Linda; Theegala, Swathi; Giro, Maria; Ozanne, Susan E; Burling, Keith; Jones, Peter B
2013-10-01
Cannabis is a widely used recreational drug. Its effect on human health and psychosis remains controversial. In this study, we aimed to explore the possibility that cannabis use influenced CCL11 plasma levels. Increased CCL11 chemokine has been reported in schizophrenia and cannabis is a known trigger of schizophrenia. Additionally, plasma levels of the chemokine CCL11 have recently been shown to increase with age and with cognitive deficits and hippocampal neurogenesis. For this study, a total of 87 healthy volunteers (68% men, age range 18-35 years) completed the Cannabis Experience Questionnaire that included information on sociodemographic and morphometric data and provided a blood sample for CCL11 measurement. 'Current users' of cannabis (n=18) had significantly higher CCL11 plasma levels compared to 'past users' (n=33) and 'never users' (n=36) [F(3,84)=3.649; p=0.030]. The latter two groups had similar CCL11 levels. Higher CCL11 plasma levels could not be attributed to gender, age, body mass index, physical activity or use of other legal/illegal drugs. These results suggest that cannabis use increases CCL11 plasma levels and the effects are reversible when cannabis use ceases. © 2013.
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Russell, James A; Fjell, Chris; Hsu, Joseph L; Lee, Terry; Boyd, John; Thair, Simone; Singer, Joel; Patterson, Andrew J; Walley, Keith R
2013-08-01
Changes in plasma cytokine levels may predict mortality, and therapies (vasopressin versus norepinephrine) could change plasma cytokine levels in early septic shock. Our hypotheses were that changes in plasma cytokine levels over 24 hours differ between survivors and nonsurvivors, and that there are different effects of vasopressin and norepinephrine on plasma cytokine levels in septic shock. We studied 394 patients in a randomized, controlled trial of vasopressin versus norepinephrine in septic shock. We used hierarchical clustering and principal components analysis of the baseline cytokine concentrations to subgroup cytokines; we then compared survivors to nonsurvivors (28 d) and compared vasopressin- versus norepinephrine-induced changes in cytokine levels over 24 hours. A total of 39 plasma cytokines were measured at baseline and at 24 hours. Hierarchical clustering and principal components analysis grouped cytokines similarly. Survivors (versus nonsurvivors) had greater decreases of overall cytokine levels (P < 0.001). Vasopressin decreased overall 24-hour cytokine concentration compared with norepinephrine (P = 0.037). In less severe septic shock, the difference in plasma cytokine reduction over 24 hours between survivors and nonsurvivors was less pronounced than that seen in more severe septic shock. Furthermore, vasopressin decreased interferon-inducible protein 10 and granulocyte colony-stimulating factor more than did norepinephrine in less severe septic shock, whereas vasopressin decreased granulocyte-macrophage colony-stimulating factor in patients who had more severe shock. Survivors of septic shock had greater decreases of cytokines, chemokines and growth factors in early septic shock. Vasopressin decreased 24-hour plasma cytokine levels more than did norepinephrine. The vasopressin-associated decrease of cytokines differed according to severity of shock. Clinical trial registered with www.controlled-trials.com (ISRCTN94845869).
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Riquelme, Raquel A; Sánchez, Gina; Liberona, Leonel; Sanhueza, Emilia M; Giussani, Dino A; Blanco, Carlos E; Hanson, Mark A; Llanos, Aníbal J
2002-01-01
The hypothesis that nitric oxide plays a key role in the regulation of adrenal blood flow and plasma concentrations of cortisol and catecholamines under basal and hypoxaemic conditions in the llama fetus was tested. At 0.6-0.8 of gestation, 11 llama fetuses were surgically prepared for long-term recording under anaesthesia with vascular and amniotic catheters. Following recovery all fetuses underwent an experimental protocol based on 1 h of normoxaemia, 1 h of hypoxaemia and 1 h of recovery. In nine fetuses, the protocol occurred during fetal i.v. infusion with saline and in five fetuses during fetal i.v. treatment with the nitric oxide synthase inhibitor l-NAME. Adrenal blood flow was determined by the radiolabelled microsphere method during each of the experimental periods during saline infusion and treatment with l-NAME. Treatment with l-NAME during normoxaemia led to a marked fall in adrenal blood flow and a pronounced increase in plasma catecholamine concentrations, but it did not affect plasma ACTH or cortisol levels. In saline-infused fetuses, acute hypoxaemia elicited an increase in adrenal blood flow and in plasma ACTH, cortisol, adrenaline and noradrenaline concentrations. Treatment with l-NAME did not affect the increase in fetal plasma ACTH, but prevented the increments in adrenal blood flow and in plasma cortisol and adrenaline concentrations during hypoxaemia in the llama fetus. In contrast, l-NAME further enhanced the increase in fetal plasma noradrenaline. These data support the hypothesis that nitric oxide has important roles in the regulation of adrenal blood flow and adrenal corticomedullary functions during normoxaemia and hypoxaemia functions in the late gestation llama fetus. PMID:12356897
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Fructose levels are markedly elevated in cerebrospinal fluid compared to plasma in pregnant women.
Hwang, Janice J; Johnson, Andrea; Cline, Gary; Belfort-DeAguiar, Renata; Snegovskikh, Denis; Khokhar, Babar; Han, Christina S; Sherwin, Robert S
2015-01-01
Fructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000 th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS) fructose production from glucose via the polyol pathway (glucose → sorbitol → fructose) contributes to brain exposure to fructose. In this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF), maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM) undergoing spinal anesthesia and elective cesarean section. As expected, CSF glucose was ~ 60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001), and CSF sorbitol was ~ 9-times higher than plasma levels (p < 0.001). Moreover, CSF fructose correlated positively with CSF glucose (ρ 0.45, p = 0.02) and sorbitol levels (ρ 0.75, p < 0.001). Cord blood sorbitol was also ~ 7-fold higher than maternal plasma sorbitol levels (p = 0.001). There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups. These data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption.
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Catena, Cristiana; Colussi, GianLuca; Martinis, Flavia; Novello, Marileda; Sechi, Leonardo A
2017-12-01
Identification of factors that contribute to urinary albumin losses in hypertensive nephropathy is crucial for prevention of renal deterioration. The aim of this study was to investigate the relationship of low-grade albuminuria with plasma aldosterone levels in treatment-naïve hypertensive patients free of additional comorbidities that might affect renal function. In 242 newly diagnosed patients with uncomplicated primary hypertension, we obtained duplicate 24-h urine collections for measurement of urinary albumin/creatinine ratio (UACR) and measured plasma aldosterone levels. Patients with diabetes, overt proteinuria (>300 mg/day), glomerular filtration rate less than 30 ml/min per 1.73 m, and previous renal diseases were excluded. Increasing UACR was associated with significantly and progressively higher blood pressure (BP), HDL-cholesterol, and plasma aldosterone levels, and with lower glomerular filtration. Microalbuminuria (30-300 mg/day) was detected in 41 (17%) of 242 hypertensive patients, and these patients had significantly higher BP and plasma aldosterone levels (178 ± 113 vs. 128 ± 84 pg/ml; P = 0.001), and lower glomerular filtration than patients without microalbuminuria. UACR was directly and independently correlated with BP and plasma aldosterone levels. In a logistic regression model, presence of microalbuminuria was associated with plasma aldosterone levels independently of glomerular filtration and demographic, anthropometric, and metabolic variables. In nondiabetic, treatment-naïve patients with hypertension, low-grade albuminuria is independently associated with elevated plasma aldosterone. These findings suggest a contribution of aldosterone to the early glomerular changes occurring in hypertensive nephropathy.
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Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women
Hwang, Janice J.; Johnson, Andrea; Cline, Gary; Belfort-DeAguiar, Renata; Snegovskikh, Denis; Khokhar, Babar; Han, Christina S.; Sherwin, Robert S.
2015-01-01
Background Fructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS) fructose production from glucose via the polyol pathway (glucose→sorbitol→fructose) contributes to brain exposure to fructose. Methods In this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF), maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM) undergoing spinal anesthesia and elective cesarean section. Results As expected, CSF glucose was ~60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001), and CSF sorbitol was ~9-times higher than plasma levels (p < 0.001). Moreover, CSF fructose correlated positively with CSF glucose (ρ 0.45, p = 0.02) and sorbitol levels (ρ 0.75, p < 0.001). Cord blood sorbitol was also ~7-fold higher than maternal plasma sorbitol levels (p = 0.001). There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups. Conclusions These data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption. PMID:26035307
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Aoki, Kazutaka; Kamiyama, Hiroshi; Masuda, Kiyomi; Kamiko, Kazunari; Noguchi, Yoshihiko; Tajima, Kazuki; Terauchi, Yasuo
2014-01-01
We previously reported that combination therapy with an α-glucosidase inhibitor (αGI) and a dipeptidyl peptidase-4 (DPP-4) inhibitor increased active glucagon-like peptide-1 (GLP-1) levels and decreased total glucose-dependent insulinotropic polypeptide (GIP) levels, compared with monotherapy, in non-diabetic men. However, the peptide YY (PYY), cholecystokinin (CCK), ghrelin, and obestatin levels in patients receiving a combination of αGIs and DPP-4 inhibitors have not been previously reported. We evaluated the effect of miglitol, vildagliptin, or their combination on these parameters. Miglitol and/or vildagliptin were administered according to four different intake schedules in eleven non-diabetic men (C: no drug, M: miglitol; V: vildagliptin, M+V: miglitol+vildagliptin). Blood samples were collected at 0, 30, 60, and 120 min after the start of breakfast. The plasma glucose, serum insulin, serum total PYY (PYY1-36 and PYY3-36), plasma CCK, plasma active ghrelin, and plasma obestatin levels were measured. The area under the curve (AUC) of the serum total PYY level in the M group was significantly greater than that in the C group, and the AUC of the serum total PYY level in the M+V group was significantly lower than that in the M group. The combination therapy did not change the AUC of the plasma CCK, plasma active ghrelin, plasma obestatin, and ghrelin/obestatin levels, compared with the control. The results of our study suggested that combination therapy with miglitol and vildagliptin had no effect on appetite regulation hormones, such as total PYY, CCK, active ghrelin, and obestatin, compared with the levels in the control group.
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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.
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Plasma catecholamine levels before and after paroxetine treatment in patients with panic disorder.
Oh, Jae-Young; Yu, Bum-Hee; Heo, Jung-Yoon; Yoo, Ikki; Song, Hyemin; Jeon, Hong Jin
2015-02-28
Catecholamines such as norepinephrine, epinephrine, and dopamine are closely related to the autonomic nervous system, suggesting that panic disorder may involve elevated catecholamine levels. This study investigated basal and posttreatment catecholamine levels in patients with panic disorder. A total of 29 patients with panic disorder and 23 healthy controls participated in the study. Panic disorder patients received paroxetine treatment for 12 weeks after clinical tests and examination had been conducted. We investigated the difference in basal levels of catecholamine and measured the changes in catecholamine levels before and after drug treatment in panic disorder patients. The basal plasma epinephrine (48.87±6.18 pg/ml) and dopamine (34.87±3.57 pg/ml) levels of panic disorder patients were significantly higher than those (34.79±4.72 pg/ml and 20.40±3.53 pg/ml) of the control group. However, basal plasma norepinephrine levels did not show statistically significant differences between patients and controls. After drug therapy, plasma catecholamine levels were nonsignificantly decreased and norepinephrine levels showed a tendency toward a decrease that did not reach significance. In conclusion, this study suggests the possibility of a baseline increase of plasma catecholamine levels and activation of sympathetic nervous systems in patients with panic disorder which may normalize after treatment with paroxetine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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Gen, Ramazan; Akbay, Esen; Muslu, Necati; Sezer, Kerem; Cayan, Filiz
2009-04-01
The present study was undertaken to investigate the association between plasma visfatin concentrations and inflammatory markers such as interleukin-6 (IL-6) and high-sensitive C-reactive protein (hsCRP) in company with several metabolic parameters in lean women with polycystic ovary syndrome (PCOS). The study group consisted of 21 lean women with PCOS (BMI 20.74 +/- 1.74 kg/m(2)) and 15 healthy, normally menstruating women (BMI 20.85 +/- 2.08 kg/m(2) control group). PCOS was defined according to the Rotterdam criteria. Visfatin, IL-6, hsCRP, hyperandrogenism markers and metabolic markers were examined in all PCOS and control women. Plasma visfatin level in the PCOS group was higher than that in the control group. Plasma hsCRP and IL-6 levels in PCOS group were similar with the control group. Plasma visfatin levels were positively associated with total cholesterol, high density lipoprotein, hirsutism score, total testosterone and FAI. Plasma visfatin level was negatively associated with SHBG. However, there were no correlation between plasma visfatin level and IL-6 and hsCRP. In multivariate regression analyses, only FAI and high density lipoprotein-cholesterol (HDL-C) showed a significant association with serum visfatin. Our data indicates that plasma visfatin levels are associated with HDL-C and markers of hyperandrogenism, but it is not associated with proinflammatory markers and insulin resistance in lean women with PCOS.
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Stefanutti, Claudia; Mazza, Fabio; Steiner, Michael; Watts, Gerald F.; De Nève, Joel; Pasqualetti, Daniela; Paal, Juergen
2016-01-01
The effect of lipoprotein apheresis (Direct Adsorption of Lipids, DALI) (LA) on plasma levels of pentraxin 3 (PTX3), an inflammatory marker that reflects coronary plaque vulnerability, and expression of PTX3 mRNA was evaluated in patients with hyperLp(a)lipoproteinemia and angiographically defined atherosclerosis/coronary artery disease. Eleven patients, aged 55 ± 9.3 years (mean ± SD), were enrolled in the study. PTX3 soluble protein levels in plasma were unchanged by 2 sessions of LA; however, a downregulation of mRNA expression for PTX3 was observed, starting with the first session of LA (p < 0.001). The observed reduction was progressively increased in the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session. A statistically significantly greater treatment-effect correlation was observed in patients undergoing weekly treatments, compared with those undergoing treatment every 15 days. A progressive reduction in plasma levels of C-reactive protein was also seen from the first session of LA, with a statistically significant linear correlation for treatment-effect in the change in plasma levels of this established inflammatory marker (R 2 = 0.99; p < 0.001). Our findings suggest that LA has anti-inflammatory and endothelium protective effects beyond its well-established efficacy in lowering apoB100-containing lipoproteins. PMID:26903710
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Xu, Ming; Liu, Xiaoxia; Mei, Guanghai; Zhang, Junjie; Wang, Weixing; Xu, Hongzhi
2018-05-09
Aberrant expression of angiogenic factors has been anecdotally documented in brain arteriovenous malformation (AVM) nidus vessels; however, no data is available on the effect of radiosurgery on the levels of angiogenic factors in AVM patients. We sought to determine the plasma contents of VEGF, TGF-β, Ang-2 and bFGF in 28 brain AVM patients at baseline and post radiosurgery and further analyzed the relationship between plasma contents of these angiogenic factors with clinicopathologic variables of these patients. We enrolled brain AVM patients who underwent Cyberknife radiosurgery at our hospital between January 2014 and December 2015. Brain AVM was confirmed by cerebral angiography and radiosurgery was performed with Cyberknife irradiation. Plasma contents of VEGF, TGF-β, Ang-2 and bFGF were analyzed using commercially available enzyme-linked immunoassay (ELISA) kits. The baseline plasma VEGF content was 222.63 pg/mL (range 43.25-431.25 pg/mL). At three months post surgery, there was a significant -34.29% decline in plasma VEGF content versus baseline (P = 0.000). Furthermore, the median baseline plasma VEGF levels were higher in brain AVM with a nidus volume ≥ 10 cm 3 ) than those with a nidus volume < 10 cm 3 [median(IQR) 293.5 (186.5,359.25) vs. 202 (59.75, 270.75) pg/mL, P = 0.057]. The baseline plasma TGF-β content was 556.17 pg/mL (range 44.44-1486.11 pg/mL) and there was a significant -27.47% decline in plasma TGF-β content at 3 months post radiosurgery versus baseline (P = 0.015). Moreover, the baseline plasma ANG-2 content was 214.27 pg/mL (range 77.14-453.76 pg/mL). There was an immediate and significant -12.47% decline in plasma ANG-2 content post surgery versus baseline (P = 0.002). At three months post surgery, the plasma ANG-2 content still remained significantly depressed versus baseline (P = 0.002). In addition, the baseline plasma bFGF content was 9.17 pg/mL (range 3.67-36.78 pg/mL). No
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Kho, H G; Kloppenborg, P W; van Egmond, J
1993-05-01
The effects of acupuncture and transcutaneous electrical stimulation (TES) on plasma adrenaline (A) and noradrenaline (NA), adrenocorticotropic hormone (ACTH), beta-endorphin (beta E), anti-diuretic hormone (ADH) and hydrocortisone (cortisol) were evaluated during and, for four days after surgery in 42 male patients submitted to a standardized major abdominal operation in a comparative study of three different anaesthetic techniques. Group 1 received acupuncture and transcutaneous stimulation as the main non-pharmacological analgesic during surgery. Group 2 received moderate-dose fentanyl (initial bolus of 10 micrograms kg-1 followed by continuous infusion of 5 micrograms kg-1 h-1 for the first hour, and then 4 micrograms kg-1 h-1. Group 3 received a combination of both methods. In all three groups analgesia was supplemented, if necessary, by small bolus injections of 50 micrograms fentanyl. Anaesthesia was induced in all groups with thiopentone 5 mg kg-1 and vecuronium 0.1 mg kg-1 and patients were ventilated (N2O:O2 = 2:1) to achieve normocapnia without the use of a halogenated agent. Pre-operatively acupuncture plus TES in Groups 1 and 3 led to a rise in beta E (P < 0.05) without changes of haemodynamics. After intubation beta E did not increase further. Intubation in Group 2 led to an increase of beta E (P < 0.05) also, and to a rise in pulse rate and blood pressure (P < 0.05) in all three groups. Per-operatively acupuncture plus TES in Group 1 showed a response of circulating NA and cortisol similar to that in Groups 2 and 3, whereas the responses of the circulating A, ACTH, beta E and ADH in Group 1 were more pronounced (P < 0.01). Post-operatively no differences in the hormonal profiles could be discerned between the groups with or without acupuncture plus TES (Group 2 vs. Group 3) nor between those with or without moderate-dose fentanyl anaesthesia (Group 1 vs. Group 3). It is concluded that acupuncture and TES have no effect on the cardiovascular response
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Plasma catalase activity and malondialdehyde level in patients with cataract.
Ateş, N A; Yildirim, O; Tamer, L; Unlü, A; Ercan, B; Muşlu, N; Kanik, A; Hatungil, R; Atik, U
2004-08-01
Oxidative mechanisms play a major role in the aetiology and pathogenesis of cataract, especially in age-related cataract. Our study aims to investigate systemic oxidant and antioxidant markers in cataract patients. The activity of erythrocyte catalase and the level of malondialdehyde in plasma were measured in 40 patients with cataract and 60 healthy control subjects. The malondialdehyde level, as an index of lipid peroxidation, was determined by thiobarbitüric acid reaction according to Yagi. The determination of catalase activity was measured by a method that was defined by Beutler. Catalase enzyme activity and malondialdehyde level were evaluated to find out whether there was a significant difference in these variables. Analysis of variance was used by forming a general linear model that takes age and gender as the covariate. CAT activity was found to be 13 920.2 +/- 847.9 U/l in cataract patients and 16 061.3 +/- 1126.6 U/l in control subjects. CAT activity in cataract patients was significantly lower than the control subjects (P = 0.008). Plasma MDA level is significantly higher in patients with cataract 4.47 +/- 0.35 nmol/ml compared to the control subjects 2.94 +/- 0.26 nmol/ml (P = 0.0001). There was no significant difference between different cataract subgroups when erythrocyte CAT activities and plasma MDA levels were compared (P = 0.322, 0.062). This study shows that oxidant/antioxidant balances alter in the presence of cataract.
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Ferreira, G A; Teixeira, A L; Sato, E I
2010-07-01
A recent study showed transcriptional levels of interferon-inducible chemokines in peripheral blood cells were associated with disease activity and organ damage in systemic lupus erythematosus, and may be useful in monitoring disease activity and prognosis. Our objective was to evaluate the capacity of atorvastatin to reduce plasma levels of interferon-regulated chemokines (CCL2, CCL3 and CXCL9) and to study the correlation between these chemokines and disease activity in patients with systemic lupus erythematosus. Eighty-eight female patients with systemic lupus erythematosus were divided into two groups: 64 receiving 20 mg/day of atorvastatin (intervention group) and 24 without atorvastatin (control group). All patients were followed for 8 weeks. At baseline and after 8 weeks laboratory tests were performed for all patients. Plasma levels of chemokines were measured by ELISA using commercial kits (DuoSet, R&D Systems, Minneapolis, USA). In a univariate analysis we found correlation between CCL2, CCL3 and CXCL9 plasma levels and SLEDAI score. In the intervention group we observed a significant decrease in CXCL9 plasma levels comparing baseline and levels at the end of the study (p = 0.04); however, no differences were observed regarding CCL2 or CCL3 plasma levels in this study. No significant difference was observed in the plasma levels of these chemokines in the control group. We conclude that treatment with atorvastatin was associated with a significant decrease in the plasma levels of CXCL9 in patients with systemic lupus erythematosus. As the plasma levels of CXCL9 correlated with the SLEDAI score, we ask whether reducing levels of this chemokine could help to control systemic lupus erythematosus activity.
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Plasma arginine vasopressin level in hypothyroid women in relation to dietary sodium supply.
Marcisz, Czesław; Marcisz-Orzeł, Magdalena; Straszecka, Joanna; Derejczyk, Małgorzata
2012-01-01
A disturbed regulation mechanism of arginine vasopressin secretion in response to plasma osmolality and volaemia changes occurs in hypothyroidism. The aim of this study was to determine plasma arginine vasopressin concentration in hypothyroid women under conditions of a low sodium diet and in an upright position. Twenty-six women with primary hypothyroidism and 24 healthy women (control group) were investigated. In all the patients, the plasma arginine vasopressin and serum sodium and potassium levels, as well as plasma osmolality, were measured first under basal conditions, i.e. after three days of a normal sodium diet (120 mmol sodium per day) in a horizontal position, and next after three days of a low sodium diet (10 mmol Na per day) in an upright position. In hypothyroid patients, the investigations were repeated after a euthyroid state as a result of L-thyroxine treatment had been attained. An increase of vasopressinaemia, measured under basal conditions as well as after three days of the low sodium diet, was shown in untreated hypothyroid patients compared to the control group. The arginine vasopressin plasma level normalised after a euthyroid state had been attained. As a result of the low sodium diet and the upright position, a significant increase of arginine vasopressin secretion was observed in the control group and hypothyroid women in the euthyroid state. No significant increase of this neuropeptide level in untreated patients was shown while applying the low sodium diet and upright position. Plasma osmolality and natraemia were decreased in the untreated hypothyroid patients. No correlation between vasopressinaemia and plasma osmolality was shown. The plasma arginine vasopressin level is increased in hypothyroid women, and does not change in the upright position under the influence of a low sodium diet.
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Ishikawa, Tsuyoshi; Aibe, Yuki; Matsuda, Takashi; Iwamoto, Takuya; Takami, Taro; Sakaida, Isao
2017-09-01
The purpose of this study was to evaluate predictors of reduction in ammonia levels by occlusion of portosystemic shunts (PSS) in patients with cirrhosis. Forty-eight patients with cirrhosis (21 women, 27 men; mean age, 67.8 years) with PSS underwent balloon-occluded retrograde transvenous obliteration (BRTO) at one institution between February 2008 and June 2014. The causes of cirrhosis were hepatitis B in one case, hepatitis C in 20 cases, alcohol in 15 cases, nonalcoholic steatohepatitis in eight cases, and other conditions in four cases. The Child-Pugh classes were A in 24 cases, B in 23 cases, and C in one case. The indication for BRTO was gastric varices in 40 cases and hepatic encephalopathy in eight cases. Testing was conducted before and 1 month after the procedure. Statistical analyses were performed to identify predictors of a clinically significant decline in ammonia levels after BRTO. Occlusion of PSS resulted in a clinically significant decrease in ammonia levels accompanied by increased portal venous flow and improved Child-Pugh score. Univariate analyses showed that a reduction in ammonia levels due to BRTO was significantly related to lower plasma glucose levels, higher RBC counts, and higher hemoglobin concentration before the treatment. Furthermore, multivariate logistic regression identified preoperative plasma glucose level as the strongest independent predictor of a significant ammonia reduction in response to BRTO. In addition, although BRTO resulted in significantly declined ammonia levels in patients with normal glucose tolerance before the procedure, ammonia levels were not significantly decreased after shunt occlusion in patients with diabetes mellitus or impaired glucose tolerance before BRTO, according to 75-g oral glucose tolerance test results. Preoperative plasma glucose level is a useful predictor of clinically significant ammonia reduction resulting from occlusion of PSS in patients with cirrhosis. Even if PSS are present, control
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Ohara, Makoto; Watanabe, Kentaro; Suzuki, Tatsuya; Sekimizu, Ken-ichi; Motoyama, Masayuki; Ishii, Kazuhito; Sawai, Keisuke; Nakano, Hiroshi; Oba, Kenzo; Mizuno, Kyoichi
2013-01-01
This study aimed to evaluate the relationship between improvement of glucose metabolism and plasma levels of diacron-reactive oxygen metabolites (d-ROMs) in patients with type 2 diabetes. As the first daily profile, the plasma levels of glucose and d-ROMs were determined on admission. Then, after treatment to lower plasma glucose levels, the second daily profile of these levels was evaluated. Fasting plasma glucose (FPG), the total area under the curve (AUC) of the daily plasma glucose profile (AUCDP), the AUC of the postprandial plasma glucose levels (AUCPP), the AUC of the daily plasma d-ROMs profile (AUCd-ROMs), the coefficient of variation (CV) of plasma glucose (CVPG), and the mean amplitude of glycemic excursions (MAGE) were calculated. The relationship between the improvement of glucose metabolism and that of oxidative stress in patients with type 2 diabetes was evaluated. The second determinations of FPG, AUCDP, AUCPP, MAGE, and AUCd-ROMs were significantly lower than those of the first determinations, but no significant difference was observed in CVPG. Linear regression analysis demonstrated significant associations between the changes in AUCd-ROMs and the changes in both FPG and AUCDP, whereas no significant association was observed between the change in AUCd-ROMs and the change in AUCPP, CVPG, or MAGE. This study has demonstrated that improvement of the FPG level, but not of the postprandial glucose level, is associated with a reduction of the plasma level of d-ROMs in patients with type 2 diabetes.
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Barouei, Javad; Moussavi, Mahta; Hodgson, Deborah M.
2012-01-01
Objective To examine whether maternal probiotic intervention influences the alterations in the brain-immune-gut axis induced by neonatal maternal separation (MS) and/or restraint stress in adulthood (AS) in Wistar rats. Design Dams had free access to drinking water supplemented with Bifidobacterium animalis subsp lactis BB-12® (3×109 CFU/mL) and Propionibacterium jensenii 702 (8.0×108 CFU/mL) from 10 days before conception until postnatal day (PND) 22 (weaning day), or to control ad lib water. Offspring were subjected to MS from PND 2 to 14 or left undisturbed. From PND 83 to 85, animals underwent 30 min/day AS, or were left undisturbed as controls. On PND 24 and 86, blood samples were collected for corticosterone, ACTH and IgA measurement. Colonic contents were analysed for the composition of microflora and luminal IgA levels. Results Exposure to MS significantly increased ACTH levels and neonatal fecal counts of aerobic and anaerobic bacteria, E. coli, enterococci and clostridia, but reduced plasma IgA levels compared with non-MS animals. Animals exposed to AS exhibited significantly increased ACTH and corticosterone levels, decreased aerobic bacteria and bifidobacteria, and increased Bacteroides and E. coli counts compared to non-AS animals. MS coupled with AS induced significantly decreased anaerobes and clostridia compared with the non-stress adult controls. Maternal probiotic intervention significantly increased neonatal corticosterone levels which persisted until at least week 12 in females only, and also resulted in elevated adult ACTH levels and altered neonatal microflora comparable to that of MS. However, it improved plasma IgA responses, increased enterococci and clostridia in MS adults, increased luminal IgA levels, and restored anaerobes, bifidobacteria and E. coli to normal in adults. Conclusion Maternal probiotic intervention induced activation of neonatal stress pathways and an imbalance in gut microflora. Importantly however, it improved the
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Therapeutic Plasma Exchange Decreases Levels of Routinely Used Cardiac and Inflammatory Biomarkers
Beutel, Gernot; Bauersachs, Johann; David, Sascha; Schmidt, Bernhard M. W.; Lichtinghagen, Ralf; Kielstein, Jan T.
2012-01-01
Background Therapeutic plasma exchange (TPE) plays a key role in the management of various diseases, from thrombotic thrombocytopenic purpura and Goodpasture's syndrome to cardiac allograft rejection. In many of these disease states cardiac and inflammatory involvement is common and biomarkers are routinely used for diagnosis or assessment of therapeutic success. The effect of TPE on biomarkers used in the clinical routine has not been investigated. Methods TPE was initiated for established clinical conditions in 21 patients. Troponin T, NT-proBNP, C-reactive protein, procalcitonin and routine chemistry were drawn before and after TPE, as well as before and after the 2nd TPE. The total amount of these markers in the waste bag was also analyzed. Results In 21 patients 42 TPEs were performed. The procedure reduced plasma levels of the examined biomarkers: 23% for NT-proBNP (pre vs. post: 4637±10234 ng/l to 3565±8295 ng/l, p<0.001), 64% for CRP (21.9±47.0 mg/l vs. 7.8±15.8 mg/l, p<0.001) and 31% for procalcitonin (0.39±1.1 µg/l vs. 0.27±0.72 µg/l, p=0.004). TPE also tended to reduce plasma levels of troponin T by about 14% (60.7±175.5 ng/l vs. 52.2±141.3 ng/l), however this difference was not statistical significant (p=0.95). There was a significant correlation between the difference of pre TPE levels to post TPE levels of all examined biomarkers and the total amount of the removed biomarker in the collected removed plasma. Conclusions TPE significantly reduces plasma levels of inflammatory and cardiac biomarkers. Therefore, post TPE levels of cardiac and inflammatory biomarkers should be viewed with caution. PMID:22685586
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Plasma apolipoprotein O level increased in the patients with acute coronary syndrome
Yu, Bi-lian; Wu, Chen-lu; Zhao, Shui-ping
2012-01-01
Apolipoprotein (apo) O is a novel apolipoprotein that is present predominantly in high density lipoprotein (HDL). However, overexpression of apoO does not impact on plasma HDL levels or functionality in human apoA-I transgenic mice. Thus, the physiological function of apoO is not yet known. In the present study, we investigated relationships between plasma apoO levels and high-sensitive C-reactive protein (hs-CRP) levels, as well as other lipid parameters in healthy subjects (n = 111) and patients with established acute coronary syndrome (ACS) (n = 50). ApoO was measured by the sandwich dot-blot technique with recombinant apoO as a protein standard. Mean apoO level in healthy subjects was 2.21 ± 0.83 µg/ml whereas it was 4.94 ± 1.59 µg/ml in ACS patients. There were significant differences in plasma level of apoO between two groups (P < 0.001). In univariate analysis, apoO correlated significantly with lg(hsCRP) (r = 0.48, P < 0.001) in ACS patients. Notably, no significant correlation between apoO and other lipid parameters was observed. Logistic regression analysis showed that plasma apoO level was an independent predictor of ACS (OR = 5.61, 95% CI 2.16–14.60, P < 0.001). In conclusion, apoO increased in ACS patients, and may be regarded as an independent inflammatory predictor of ACS patients. PMID:22693255
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Xia, Yan; Wang, Dawei; Zhang, Nan; Wang, Zhihao; Pang, Li
2018-02-01
To investigate the prognostic value of plasma serotonin levels in colorectal cancer (CRC). Preoperative plasma serotonin levels of 150 healthy control (HC) cases, 150 benign colorectal polyp (BCP) cases, and 176 CRC cases were determined using radioimmunoassay assay. Serotonin levels were compared between HC, BCP, and CRC cases, and those in CRC patients were related to 5-year outcome. Plasma serotonin levels were markedly higher in CRC patients than in either HCs or BCP cases. An elevated serotonin level was significantly associated with advanced tumor node metastasis. Receiver operating characteristic curve analysis showed that the level of serotonin had a high predictive value for disease recurrence and mortality. Multivariate analysis revealed that high serotonin level was significantly associated with poor recurrence-free survival and overall survival. Our results suggest that a high peri-operative plasma serotonin level is useful as a prognostic biomarker for CRC recurrence and poor survival. © 2017 Wiley Periodicals, Inc.
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Xu, Xin-Jie; Shou, Xiao-Jing; Li, Jin; Jia, Mei-Xiang; Zhang, Ji-Shui; Guo, Yan; Wei, Qing-Yun; Zhang, Xiu-Ting; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng
2013-01-01
Background Autism is a pervasive neurodevelopmental disorder,thought to be caused by a combination of genetic heritability and environmental risk factors. Some autistic-like traits have been reported in mothers of autistic children. We hypothesized that dysregulation of oxytocin (OXT), Arg-vasopressin (AVP) and sex hormones, found in autistic children, may also exist in their mothers. Methods We determined plasma levels of OXT (40 in autism vs. 26 in control group), AVP (40 vs. 17) and sex hormones (61 vs. 47) in mothers of autistic and normal children by enzyme immunoassay and radioimmunoassay, respectively and investigated their relationships with the children’s autistic behavior scores (Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC)). Results Significantly lower plasma concentrations of OXT (p<0.001) and AVP (p<0.001), as well as a higher level of plasma testosterone (p<0.05), were found in mothers of autistic children vs. those of control. The children’s autistic behavior scores were negatively associated with maternal plasma levels of OXT and AVP. Conclusions These results suggest that dysregulation of OXT, AVP and/or testosterone systems exist in mothers of autistic children, which may impact children’s susceptibility to autism. PMID:24086383
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Xu, Xin-Jie; Shou, Xiao-Jing; Li, Jin; Jia, Mei-Xiang; Zhang, Ji-Shui; Guo, Yan; Wei, Qing-Yun; Zhang, Xiu-Ting; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng
2013-01-01
Autism is a pervasive neurodevelopmental disorder,thought to be caused by a combination of genetic heritability and environmental risk factors. Some autistic-like traits have been reported in mothers of autistic children. We hypothesized that dysregulation of oxytocin (OXT), Arg-vasopressin (AVP) and sex hormones, found in autistic children, may also exist in their mothers. We determined plasma levels of OXT (40 in autism vs. 26 in control group), AVP (40 vs. 17) and sex hormones (61 vs. 47) in mothers of autistic and normal children by enzyme immunoassay and radioimmunoassay, respectively and investigated their relationships with the children's autistic behavior scores (Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC)). Significantly lower plasma concentrations of OXT (p<0.001) and AVP (p<0.001), as well as a higher level of plasma testosterone (p<0.05), were found in mothers of autistic children vs. those of control. The children's autistic behavior scores were negatively associated with maternal plasma levels of OXT and AVP. These results suggest that dysregulation of OXT, AVP and/or testosterone systems exist in mothers of autistic children, which may impact children's susceptibility to autism.
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Jakobsdóttir, S; Twisk, J W R; Drent, M L
2009-12-01
In studies investigating the influence of glucose levels on the pituitary function the methods used have been variable and mainly focused on the change in function as a reaction to unphysiological low or high blood glucose levels. In the present study the impact of physiological and elevated blood glucose levels on adrenocorticotropin hormone (ACTH) and growth hormone release are investigated. The euglycaemic and hyperglycaemic clamp techniques were used to reach stable levels of 4, 8 and 12 mmol/l blood glucose levels. After a stabilization phase of 2 h, a corticotropin releasing hormone (CRH) or a growth hormone releasing hormone (GHRH) stimulation test was performed. Seven and eight healthy male volunteers, belonging to two groups, participated in this study. The area under the curve (AUC), peak values and time to peak of ACTH, cortisol and growth hormone were calculated to evaluate the response to the CRH and GHRH stimulation test. The peak values of ACTH, cortisol and growth hormone seemed to be the highest during the 4 mmol/l clamp sessions, compared with the 8 and 12 mmol/l clamps, although the differences were not statistically significant when analysed for every subject individually. The AUC and time to peak measurements were comparable during the three clamp procedures. The pituitary reaction on CRH and GHRH was not significantly changed by various blood glucose levels. © 2009 Blackwell Publishing Ltd.
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Naciute, Milda; Mieliauskaite, Diana; Rugiene, Rita; Maciunaite, Gabriele; Mauricas, Mykolas; Murovska, Modra; Girkontaite, Irute
2017-08-01
Parvovirus B19 (B19V) infection is associated with various autoimmune diseases. We investigated the levels of pro-inflammatory (IFNᵧ, TNFα, IL-2, IL-12) and anti-inflammatory (IL-4, IL-10) cytokines in the plasma of B19V DNA positive (B19 + ) and negative (B19 - ) rheumatoid arthritis (RA) patients in comparison with the control group (healthy persons). Blood samples were collected from 118 patients with RA and 49 healthy voluntaries. B19V sequence was determined in whole blood and cell-free plasma DNA by nested PCR. The levels of cytokines in the plasma and cell culture medium from Concanavalin A (ConA) or B19V VP1 protein stimulated PBMC were determined by ELISA. The levels of IL-4, IL-10, IL-12, IL-2 and TNFα were higher in plasma of RA patients in comparison with control persons. B19 + controls and RA patients had lower levels of IFNᵧ in comparison with B19 - controls and RA patients. Within RA patients the plasma levels of IFNᵧ were lower in patients with low RA disease activity or remission. Plasma level of IL-4 was increased and IL-10 level was decreased in B19 + RA patients in comparison with B19 - RA patients and did not differ between B19 + and B19 - controls. B19V infection did not affect plasma levels of IL-12, IL-2, and TNFα. ConA and B19 VP1 protein stimulated PBMC from RA patients produced less IFNᵧ than stimulated PBMC from the healthy controls. B19V infection could differently modulate the amount of cytokines in the plasma of healthy persons and RA patients. Decreased production of IFNᵧ and raised level of plasma IL-4 in RA patients could lower antiviral clearance. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Plasma endothelin-1 and big endothelin-1 levels in women with pre-eclampsia.
Sudo, N; Kamoi, K; Ishibashi, M; Yamaji, T
1993-08-01
To examine a possible role for endothelin-1 (ET-1) and conversion of big ET-1 to ET-1 in the pathophysiology of pre-eclampsia, we measured plasma levels of ET-1 and big ET-1 in 16 women with pre-eclampsia in the third trimester and compared them with those in 11 age-matched normotensive pregnant women and in 10 age-matched pregnant women with chronic hypertension in the third trimester. The plasma concentrations of ET-1 and big ET-1 in the normotensive pregnant women were significantly lower than those in 16 non-pregnant women with a higher molar ratio of big ET-1 to ET-1 in the former group. The plasma concentrations of ET-1 and big ET-1 in the women with pre-eclampsia, on the other hand, were significantly higher than those in the normotensive pregnant women and the molar ratio of big ET-1 to ET-1 in the former group was less than that in the latter group. In sharp contrast, plasma ET-1 and big ET-1 levels in the pregnant women with chronic hypertension were not significantly different from those in the normotensive pregnant women. When examined after delivery, elevated plasma ET-1 and big ET-1 in the women with pre-eclampsia declined, with restoration of normal blood pressure, to the levels in the normotensive women after parturition. There were no significant differences of the levels of ET-1 and big ET-1 in umbilical venous plasma and simultaneously drawn maternal plasma at cesarean section between normotensive pregnant women and women with pre-eclampsia, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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Vidakovic, Aleksandra Jelena; Jaddoe, Vincent WV; Voortman, Trudy; Demmelmair, Hans; Koletzko, Berthold; Gaillard, Romy
2017-01-01
Background and Aims Maternal polyunsaturated fatty acid (PUFA) levels are associated with cord blood lipid and insulin levels. Not much is known about the influence of maternal PUFAs during pregnancy on long-term offspring lipid and insulin metabolism. We examined the associations of maternal plasma n-3 and n-6 PUFA levels during pregnancy with childhood lipids and insulin levels. Methods and Results In a population-based prospective cohort study among 3,230 mothers and their children, we measured maternal second trimester n-3 and n-6 PUFA plasma levels. At the median age of 6.0 years (95% range, 5.6-7.9), we measured childhood total-cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, insulin and c-peptide levels. Higher maternal total n-3 PUFA levels, and specifically DHA levels, were associated with higher childhood total-cholesterol, HDL-cholesterol and insulin levels (p-values <0.05), but not with LDL-cholesterol and triglycerides. Maternal total n-6 PUFA levels were not associated with childhood outcomes, but higher levels of the individual n-6 PUFAs, EDA and DGLA were associated with a lower childhood HDL-cholesterol, and higher AA levels with higher childhood total-cholesterol and HDL-cholesterol levels (all p-values <0.05). A higher maternal n-6/n-3 PUFA ratio was only associated with lower childhood HDL-cholesterol and insulin levels (p-values <0.05). These associations were not explained by childhood body mass index. Conclusions Higher maternal total n-3 PUFAs and specifically DHA levels during pregnancy are associated with higher childhood total-cholesterol, HDL-cholesterol and insulin levels. Only individual maternal n-6 PUFAs, not total maternal n-6 PUFA levels, tended to be associated with childhood lipids and insulin levels. PMID:27919543
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Homan, Philipp; Grob, Simona; Milos, Gabriella; Schnyder, Ulrich; Hasler, Gregor
2013-09-01
There is increasing preclinical and clinical evidence of the important role played by the gastric peptide hormone ghrelin in the pathogenesis of symptoms of depression and eating disorders. To investigate the role of ghrelin and its considered counterpart, peptide tyrosine tyrosine (PYY), in the development of bulimic and depressive symptoms induced by catecholamine depletion, we administered the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine (AMPT) in a randomized, double-blind, placebo-controlled crossover, single-site experimental trial to 29 healthy controls and 20 subjects with fully recovered bulimia nervosa (rBN). We found a decrease between preprandial and postprandial plasma ghrelin levels (p<0.0001) and a postprandial rise in plasma PYY levels (p<0.0001) in both conditions in the entire study population. Plasma ghrelin levels decreased in the entire study population after treatment with AMPT compared to placebo (p<0.006). AMPT-induced changes in plasma ghrelin levels were negatively correlated with AMPT-induced depressive symptoms (p<0.004). Plasma ghrelin and plasma PYY levels were also negatively correlated (p<0.05). We did not observe a difference in ghrelin or PYY response to catecholamine depletion between rBN subjects and healthy controls, and there was no correlation between plasma ghrelin and PYY levels and bulimic symptoms induced by catecholamine depletion. These findings suggest a relationship between catecholamines and ghrelin with depressive symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Miranda, L A; Affanni, J M; Paz, D A
2000-04-01
The actions of several neuropeptides as hypothalamic mediators in the regulation of Bufo arenarum metamorphosis were investigated. Prometamorphic larvae were injected with 1.5 microg thyrotropin-releasing hormone (TRH), 2 microg ovine corticotropin-releasing factor (oCRF), 2 microg mammalian gonadotropin-releasing hormone (mGnRH), 2 microg human growth hormone-releasing hormone (hGHRH), or Holtfreter solution (control group). Larvae received two injections with the same dose: one at the beginning of the experiment and the other 7 days later. Several morphologic parameters (total length, tail length, wet weight, hind limb length, and metamorphic stages) were measured as indicators of growth and metamorphic development. These measurements were taken in 20 larvae per treatment or control group at the beginning of the experiment, at day 7 and at day 14 when the experiment ended. We observed that only the administration of exogenous CRF stimulated resorption of the tail and accelerated the rate of metamorphosis. In the pituitary of CRF-treated larvae we observed that thyrotropin (TSH) and adrenocorticotropic hormone (ACTH) producing cells showed a weaker immunoreactivity, a decrease in cell number and a reduction of volume density when compared with normal larvae. In conclusion, the results obtained indicate a possible role for CRF in Bufo arenarum metamorphosis. CRF may regulate interrenal and thyroid activity by acting directly upon TSH and ACTH cells. On the other hand, TRH, GnRH and GHRH were inactive in stimulating growth or metamorphosis of Bufo arenarum. J. Exp. Zool. 286:473-480, 2000. Copyright 2000 Wiley-Liss, Inc.
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Plasma hepcidin levels and anemia in old age. The Leiden 85-Plus Study
den Elzen, Wendy P.J.; de Craen, Anton J.M.; Wiegerinck, Erwin T.; Westendorp, Rudi G.J.; Swinkels, Dorine W.; Gussekloo, Jacobijn
2013-01-01
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. PMID:23065507
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The neurochemistry and social flow of singing: bonding and oxytocin
Keeler, Jason R.; Roth, Edward A.; Neuser, Brittany L.; Spitsbergen, John M.; Waters, Daniel J. M.; Vianney, John-Mary
2015-01-01
Music is used in healthcare to promote physical and psychological well-being. As clinical applications of music continue to expand, there is a growing need to understand the biological mechanisms by which music influences health. Here we explore the neurochemistry and social flow of group singing. Four participants from a vocal jazz ensemble were conveniently sampled to sing together in two separate performances: pre-composed and improvised. Concentrations of plasma oxytocin and adrenocorticotropic hormone (ACTH) were measured before and after each singing condition to assess levels of social affiliation, engagement and arousal. A validated assessment of flow state was administered after each singing condition to assess participants' absorption in the task. The feasibility of the research methods were assessed and initial neurochemical data was generated on group singing. Mean scores of the flow state scale indicated that participants experienced flow in both the pre-composed (M = 37.06) and improvised singing conditions (M = 34.25), with no significant difference between conditions. ACTH concentrations decreased in both conditions, significantly so in the pre-composed singing condition, which may have contributed to the social flow experience. Mean plasma oxytocin levels increased only in response to improvised singing, with no significant difference between improvised and pre-composed singing conditions observed. The results indicate that group singing reduces stress and arousal, as measured by ACTH, and induces social flow in participants. The effects of pre-composed and improvised group singing on oxytocin are less clear. Higher levels of plasma oxytocin in the improvised condition may perhaps be attributed to the social effects of improvising musically with others. Further research with a larger sample size is warranted. PMID:26441614
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Nagata, Tomoyuki; Kobayashi, Nobuyuki; Shinagawa, Shunichiro; Yamada, Hisashi; Kondo, Kazuhiro; Nakayama, Kazuhiko
2014-04-01
In the present study, we examined whether neuropsychiatric symptoms were correlated with plasma brain-derived neurotrophic factor (BDNF) levels as a state marker or were associated with the BDNF polymorphism Val66Met in patients with amnestic mild cognitive impairment (A-MCI) or Alzheimer disease (AD). One hundred and seventy-six outpatients with AD (n = 129) or A-MCI (n = 47) were selected and their plasma BDNF concentrations measured. Next, we investigated the correlation between the plasma BDNF level and the Behavioral Pathology in Alzheimer Disease (Behave-AD) subscale scores, which reflect neuropsychiatric symptoms. We also compared the plasma BDNF level and the Behave-AD subscale scores among the BDNF Val66Met genotypic groups. Among the seven Behave-AD subscale scores, aggressiveness was positively correlated with the plasma BDNF level (ρ = 0.237, P < 0.005), but did not differ significantly among the three BDNF Val66Met genotypic groups. The Behave-AD total and other subscale scores did not differ significantly among the BDNF Val66Met genotypic groups and were not associated with the plasma BDNF level. Moreover, the plasma BDNF level did not differ significantly among the three BDNF Val66Met genotypic groups or between patients with A-MCI and those with AD. The plasma BDNF level was robustly correlated with aggressiveness, implying that the plasma BDNF level might be useful as a behavioral state marker in patients with AD or A-MCI.
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Low plasma vitamin D levels and muscle-related adverse effects in statin users.
Eisen, Alon; Lev, Eli; Iakobishvilli, Zaza; Porter, Avital; Brosh, David; Hasdai, David; Mager, Aviv
2014-01-01
Treatment with HMG-CoA reductase inhibitors (statins) is often complicated by muscle-related adverse effects (MAEs). Studies of the association between low plasma vitamin D levels and MAEs have yielded conflicting results. To determine if low plasma vitamin D level is a risk factorfor MAEs in statin users. Plasma levels of 25(OH) vitamin D were measured as part of the routine evaluation of unselected statin-treated patients attending the coronary and lipid clinics at our hospital during the period 2007-2010. Medical data on muscle complaints and statin use were retrieved from the medical files. Creatine kinase (CK) levels were derived from the hospital laboratory database. The sample included 272 patients (141 men) aged 33-89 years. Mean vitamin D level was 48.04 nmol/L. Levels were higher in men (51.0 +/- 20.5 versus 44.7 +/- 18.9 nmol/L, P = 0.001) and were unaffected by age. MAEs were observed in 106 patients (39%): myalgia in 95 (35%) and CK elevation in 20 (7%); 9 patients (3%) had both. There was no difference in plasma vitamin D levels between patients with and without myalgia (46.3 +/- 17.7 versus 48.9 +/- 21.0 nmol/L, P = 0.31), with and without CK elevation (50.2 +/- 14.6 versus 47.8 +/- 20.3 nmol/L, P = 0.60), or with or without any MAE (50.4 +/- 15.0 versus 47.8 +/- 10.2 nmol/L, P = 0.27). These findings were consistent when analyzed by patient gender and presence/absence of coronary artery disease, and when using a lower vitamin D cutoff (< 25 nmol/L). There is apparently no relationship between plasma vitamin D level and risk of MAEs in statin users.
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Plasma levels of soluble interleukin 1 receptor accessory protein are reduced in obesity.
Bozaoglu, Kiymet; 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
2014-09-01
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. 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. 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). 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. 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. 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.
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Plasma Levels of Soluble Interleukin 1 Receptor Accessory Protein Are Reduced in Obesity
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
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Ipamorelin, the first selective growth hormone secretagogue.
Raun, K; Hansen, B S; Johansen, N L; Thøgersen, H; Madsen, K; Ankersen, M; Andersen, P H
1998-11-01
The development and pharmacology of a new potent growth hormone (GH) secretagogue, ipamorelin, is described. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), which displays high GH releasing potency and efficacy in vitro and in vivo. As an outcome of a major chemistry programme, ipamorelin was identified within a series of compounds lacking the central dipeptide Ala-Trp of growth hormone-releasing peptide (GHRP)-1. In vitro, ipamorelin released GH from primary rat pituitary cells with a potency and efficacy similar to GHRP-6 (ECs) = 1.3+/-0.4nmol/l and Emax = 85+/-5% vs 2.2+/-0.3nmol/l and 100%). A pharmacological profiling using GHRP and growth hormone-releasing hormone (GHRH) antagonists clearly demonstrated that ipamorelin, like GHRP-6, stimulates GH release via a GHRP-like receptor. In pentobarbital anaesthetised rats, ipamorelin released GH with a potency and efficacy comparable to GHRP-6 (ED50 = 80+/-42nmol/kg and Emax = 1545+/-250ng GH/ml vs 115+/-36nmol/kg and 1167+/-120ng GH/ml). In conscious swine, ipamorelin released GH with an ED50 = 2.3+/-0.03 nmol/kg and an Emax = 65+/-0.2 ng GH/ml plasma. Again, this was very similar to GHRP-6 (ED50 = 3.9+/-1.4 nmol/kg and Emax = 74+/-7ng GH/ml plasma). GHRP-2 displayed higher potency but lower efficacy (ED50 = 0.6 nmol/kg and Emax = 56+/-6 ng GH/ml plasma). The specificity for GH release was studied in swine. None of the GH secretagogues tested affected FSH, LH, PRL or TSH plasma levels. Administration of both GHRP-6 and GHRP-2 resulted in increased plasma levels of ACTH and cortisol. Very surprisingly, ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation. This lack of effect on ACTH and cortisol plasma levels was evident even at doses more than 200-fold higher than the ED50 for GH release. In conclusion, ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. The
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Plasma level of cardiotrophin-1 as a prognostic predictor in patients with chronic heart failure.
Tsutamoto, Takayoshi; Asai, Shigeru; Tanaka, Toshinari; Sakai, Hiroshi; Nishiyama, Keizo; Fujii, Masanori; Yamamoto, Takashi; Ohnishi, Masato; Wada, Atsuyuki; Saito, Yoshihiko; Horie, Minoru
2007-10-01
Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines and is increased in patients with chronic heart failure (CHF). To evaluate the prognostic role of CT-1 in patients with CHF. We measured the plasma levels of CT-1, brain natriuretic peptide (BNP), and IL-6 in 125 patients with CHF. Patients were monitored for a mean follow-up period of 2.9 years. Plasma levels of CT-1 increased with severity of CHF. There was a significant negative correlation between plasma CT-1 and left ventricular ejection fraction. There was a significant correlation between plasma CT-1 and log IL-6. During the follow-up period, 37 patients died. High plasma levels of CT-1, BNP, and IL-6 were independent predictors of mortality on stepwise multivariate analysis. The hazard ratio for mortality in patients with plasma BNP>170 pg/mL and CT-1>658 fmol/mL was 2.48 (95% confidence interval, 1.217-5.060) compared to those with plasma BNP>170 pg/mL and CT-1<658 fmol/mL (p=0.0124). These findings indicate that plasma CT-1 measurement provides additional prognostic information and that combined levels of CT-1 and BNP are more accurate at predicting mortality in patients with CHF than either marker alone.
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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
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Nikolaou, Kakia; Kapoukranidou, Dorothea; Ndungu, Samuel; Floros, Georgios; Kovatsi, Leda
2017-01-01
Pre-clinical studies show that, following chronic opioid exposure, oxytocin neurons exhibit over-excitation upon withdrawal, causing an increase in oxytocin brain and plasma levels. Relevant clinical data on humans are scarce. This study investigates the opioid withdrawal stress effect on oxytocin plasma levels in humans. We evaluated 57 male chronic heroin users in a residential detoxification program. We determined plasma oxytocin levels by ELISA and measured the stress effects of withdrawal using the COWS scale for opioid withdrawal, the VAS scale for craving, and the Hamilton scales for anxiety and depression on the second day of admission. Out of the 57 patients enrolled in the study, 27 completed the 21-day program, while the remaining 30 dropped out prior to completion. Plasma oxytocin levels were significantly higher in those individuals who dropped out than in those who completed the program. Participants who dropped out at some stage scored higher in the COWS, VAS-Craving, and Hamilton-anxiety scales, indicating a higher stress and explaining the higher oxytocin levels. In addition, plasma oxytocin levels correlated positively with the scores achieved in the COWS and Hamilton-anxiety scales. Higher withdrawal stress levels are associated with higher plasma oxytocin levels and early treatment discharge.
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Hiramoto, Keiichi; Yamate, Yurika; Yokoyama, Satoshi
2018-05-01
Ultraviolet (UV) B irradiation has been shown to improve atopic dermatitis (AD). However, the relationship between UVB eye irradiation and AD is not known. This issue was addressed using a mouse model of AD. The eyes of NC/Nga mice were irradiated with UVB at a dose of 1.0 kJ/m 2 using a 20SE sunlamp for the duration of the experimental period. AD symptoms deteriorated upon UVB eye irradiation. The levels of adrenocorticotropic hormone (ACTH) in the plasma and nucleotide-binding domain and leucine-rich-containing family, pyrin domain-containing (NLRP)3 and neutrophil markers in the skin were increased in UVB-irradiated mice. Treatment with inhibitors of ACTH, caspase-1, interleukin-18, and thymic stromal lymphopoietin (TSLP) partly reversed the effects of irradiation, with the greatest improvement observed upon ACTH inhibition. The NLRP3 inflammasome was implicated in the effects of UVB irradiation. UVB eye irradiation causes AD symptom deterioration, which is likely mediated by ACTH and the activity of the inflammasome. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Ghrelin plasma levels in patients with idiopathic short stature.
Iñiguez, Germán; Román, Rossana; Youlton, Ronald; Cassorla, Fernando; Mericq, Verónica
2011-02-01
Novel molecular insights have suggested that ghrelin may be involved in the pathogenesis of some forms of short stature. Recently, growth hormone secretagogue receptor (GHSR) mutations that segregate with short stature have been reported. To study plasma ghrelin levels in prepubertal patients with idiopathic short stature (ISS). Fasting total plasma ghrelin levels (radioimmunoassay) in 41 prepubertal patients with ISS (18 females, age 7.9 ± 0.5 years) compared with 42 age- and sex-matched controls (27 females, age 8.0 ± 0.3 years) with normal height. In a subset of 28 patients, the ghrelin receptor was sequenced. ISS patients exhibited a higher level of ghrelin (1,458 ± 137 vs. 935 ± 55 pg/ml, p < 0.01) and similar IGF-I levels (-0.66 ± 1.29 vs. -0.32 ± 0.78 SDS) compared to controls. Ten patients with ISS had ghrelin levels greater than +2 SDS compared to controls. These patients did not differ in height, BMI or IGF-I SDS compared to ISS patients with ghrelin levels within the normal range. Molecular analysis of GHSR did not show any mutations, but showed some polymorphisms. These results suggest that in ISS patients, short stature does not appear to be frequently caused by abnormalities in ghrelin signaling. Copyright © 2010 S. Karger AG, Basel.
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Levels of plasma selenium and urinary total arsenic interact to affect the risk for prostate cancer.
Hsueh, Yu-Mei; Su, Chien-Tien; Shiue, Horng-Sheng; Chen, Wei-Jen; Pu, Yeong-Shiau; Lin, Ying-Chin; Tsai, Cheng-Shiuan; Huang, Chao-Yuan
2017-09-01
This study investigated whether plasma selenium levels modified the risk for prostate cancer (PC) related to arsenic exposure. We conducted a case-control study that included 318 PC patients and 318 age-matched, healthy control subjects. Urinary arsenic profiles were examined using HPLC-HG-AAS and plasma selenium levels were measured by ICP-MS. We found that plasma selenium levels displayed a significant dose-dependent inverse association with PC. The odds ratio (OR) and 95% confidence interval (CI) for PC was 0.07 (0.04-0.13) among participants with a plasma selenium level >28.06 μg/dL vs. ≤19.13 μg/dL. A multivariate analysis showed that participants with a urinary total arsenic concentration >29.28 μg/L had a significantly higher OR (1.75, 1.06-2.89) for PC than participants with ≤29.89 μg/L. The combined presence of a low plasma selenium level and a high urinary total arsenic concentration exponentially increased the OR for PC, and additively interacted with PSA at levels ≥20 ng/mL. This is the first epidemiological study to examine the combined effects of plasma selenium and urinary total arsenic levels on the OR for PC. Our data suggest a low plasma selenium level coupled with a high urinary total arsenic concentration creates a significant risk for aggressive PC. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Plasma IL-17A levels in patients with late-life depression.
Saraykar, Smita; Cao, Bo; Barroso, Lucelia S; Pereira, Kelly S; Bertola, Laiss; Nicolau, Mariana; Ferreira, Jessica D; Dias, Natalia S; Vieira, Erica L; Teixeira, Antonio L; Silva, Ana Paula M; Diniz, Breno S
2018-01-01
A consistent body of research has confirmed that patients with major depressive disorder (MDD) have increased concentrations of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, the soluble IL-2 receptor, and C-reactive protein, compared to controls; however, there is limited information on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e., patients with late-life depression (LLD), is conspicuously missing from the literature. The purpose of this study was to investigate the role of IL-17A in LLD. A convenience sample of 129 individuals, 74 with LLD and 55 non-depressed controls, were enrolled in this study. The Mann-Whitney U test was used to compare plasma IL-17A levels between LLD and controls subjects, and Spearman's rank order correlation was used to investigate correlation of these levels with clinical, neuropsychological, and cognitive assessments. Plasma IL-17A levels were not statistically different between LLD patients and controls (p = 0.94). Among all subjects (LLD + control), plasma IL-17A did not correlate significantly with depressive symptoms (rho = -0.009, p = 0.92) but a significant correlation was observed with cognitive assessments (rho = 0.22, p = 0.01). Our findings do not support an association between plasma IL-17A levels and LLD. Nevertheless, IL-17A may be associated with cognitive impairment in LLD patients. If this finding is confirmed in future longitudinal studies, modulation of the T-helper 17 cell (Th17) immune response may be a treatment target for cognitive impairment in this population.
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Decreased plasma neurotrophin-4/5 levels in bipolar disorder patients in mania.
Barbosa, Izabela G; Morato, Isabela B; Huguet, Rodrigo B; Rocha, Fabio L; Machado-Vieira, Rodrigo; Teixeira, Antônio L
2014-01-01
To evaluate two poorly explored neurotrophins (NT), NT-3 and NT-4/5, in bipolar disorder (BD). Forty patients with type I BD (18 in remission and 22 in mania) and 25 healthy controls matched for age, gender, and educational attainment were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview; the Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to evaluate severity of symptoms in BD patients. Plasma levels of NT-3 and NT-4/5 were measured by enzyme-linked immunosorbent assay (ELISA). BD patients in mania presented decreased NT-4/5 plasma levels in comparison with controls (p < 0.05). There were no significant differences in NT-3 plasma levels between BD patients and controls. These findings corroborate the view that neurotrophin dysfunction is associated with mood states in patients with BD.
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Chang, Jin-Biou; Chu, Nain-Feng; Lin, Fu-Huang; Hsu, Jhu-Ting; Chen, Pi-Yun
Adropin is a 76 amino acid peptide hormone with a molecular weight of 4999.9Da that may be associated with energy homeostasis, insulin resistance and lipid metabolism in mice and human. There is only a few studies that examine plasma adropin levels and body composition in children. This study is to evaluate the relationship between plasma adropin levels, body composition and lipid variables amongst young adolescents in Taiwan. We examined 492 adolescents (269 females and 223 males) ranging from 12 to 15 years old, with a mean age of 13.6 years. Body composition was measured using impedance method by Tanita-BC418. Plasma lipid variables were measured using standard methods and plasma adropin levels were measured using the ELISA method. There was no significant difference in plasma adropin levels between males and females (3.52 vs. 3.58ng/ml). Plasma adropin levels were negatively correlated with fat free mass (r=-0.12, p<0.01). More interestingly, children with higher plasma adropin levels had lower waist-to-hip ratios (WHR) and lower body fat percentage by mass. Furthermore, there is no difference in lipid profiles in high vs. low adropin subjects. Plasma adropin levels are not consistency associated with body composition and no association with lipid variables amongst Taiwanese adolescents. The role of adropin in the development of obesity is still not clear, and further studies are need especially for children. Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
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Plasma diamine oxidase levels in pregnancy complicated by threatened abortion.
Legge, M; Duff, G B
1981-01-01
Plasma diamine oxidase levels were assayed in 66 patients who presented with pregnancy complicated by threatened abortion. Levels within the normal range were associated with continuing pregnancies, whereas levels below the normal range were associated with subsequent abortion. Among those patients in whom gestation was greater than eight weeks, 66.6% of diamine oxidase levels correctly predicted the pregnancy outcome. Assay of the diamine oxidase levels at eight weeks of gestation or less gave little useful information. PMID:6785320
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Plasma diamine oxidase levels in pregnancy complicated by threatened abortion.
Legge, M; Duff, G B
1981-02-01
Plasma diamine oxidase levels were assayed in 66 patients who presented with pregnancy complicated by threatened abortion. Levels within the normal range were associated with continuing pregnancies, whereas levels below the normal range were associated with subsequent abortion. Among those patients in whom gestation was greater than eight weeks, 66.6% of diamine oxidase levels correctly predicted the pregnancy outcome. Assay of the diamine oxidase levels at eight weeks of gestation or less gave little useful information.
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The relation between plasma α-synuclein level and clinical symptoms or signs of Parkinson's disease.
Malec-Litwinowicz, Michalina; Plewka, Andrzej; Plewka, Danuta; Bogunia, Edyta; Morek, Michał; Szczudlik, Andrzej; Szubiga, Michał; Rudzińska-Bar, Monika
2018-03-01
Parkinson disease (PD) is the common neurodegenerative disease. α-Synuclein (ASN), main aggregating protein in neural cells of CNS in PD, was found in peripheral fluids. Testing ASN in plasma is potential test for diagnose PD, but previous studies are controversial. The aim of this study was to investigate if plasma ASN level may be a valuable biomarker, is the level of plasma ASN concentration different in various motor subtypes of diseases, is there a relation between the level of plasma ASN and the severity of motor symptoms. Patients with PD hospitalized in Neurology Department, Medical College were performed sequencing the 8th and 9th exon of GBA gene. Next plasma ASN level was tested in 58 patients with sequenced GBA gene and in 38 healthy volunteers (HV), matched by the age (respectively 68.43 vs. 64.57 years of age) and sex (female %, respectively: 43.10 vs.44.74). Patients were assessed with the scales: UPDRS (II, III, IV), Hoehn-Yahr (HY) and qualified to PIGD or TD subtype. For homogeneity of the group patients with GBA mutation were excluded from the analysis. The ASN level did not differ between patients and HV (respectively: 4.53 vs. 3.73ng/ml) and between patients with different subtypes. There was inverse correlation between ASN and HY in PIGD subtype. Plasma ASN level is not valuable marker of the disease. It does not differ in subtypes of the disease. There is relation between plasma ASN level and the severity of the disease in PIGD subtype. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.
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The differential effect of genetic variation on soluble CD14 levels in human plasma and milk.
Guerra, Stefano; Carla Lohman, I; LeVan, Tricia D; Wright, Anne L; Martinez, Fernando D; Halonen, Marilyn
2004-09-01
The protein CD14 is a pattern recognition receptor for bacterial lipopolysaccharide (LPS). Whether genetic variation has the same influence on soluble CD14 (sCD14) levels in human plasma and milk remains to be determined. We measured sCD14 levels in plasma during pregnancy (n = 196) and in milk in the postpartum (n = 152) for women genotyped for the single nucleotide polymorphisms (SNPs) at positions -1619, -550, and -159 from the transcription start site of the CD14 gene. Plasma- and milk-sCD14 levels differed significantly both by CD14/-1619 and CD14/-550 genotypes and by haplotypes. Most interestingly, sCD14 levels were regulated differentially by the same genetic variants in plasma and milk, with the CD14/-550T allele and the corresponding are ATC haplotype associated with high sCD14 in milk but low sCD14 in plasma. A correlation between sCD14 levels in plasma and milk was absent (r = 0.091, P = NS). Our findings suggest the existence of cell-specific regulation mechanisms of CD14 gene expression.
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Yao, Qi; Fan, Kai; Wang, Guo-Hong; Feng, Rui-Xiang; Liang, Yuan-Jiao; Chen, Li; Ge, Yi-Feng; Yao, Bing
2016-01-01
Objective This prospective study was designed to investigate the relationship between lipids levels in both serum and seminal plasma and semen parameters. Methods 631 subfertile men were enrolled. Their obesity-associated markers were measured, and semen parameters were analyzed. Also, seminal plasma and serum TC, TG, HDL and LDL and serum FFA, FSH, LH, total testosterone (TT), estradiol (E2) and SHBG levels were detected. Results Seminal plasma and serum TG, TC and LDL levels were positively related to age. Serum TC, TG and LDL were positively related to obesity-associated markers (P < 0.001), while only seminal plasma TG was positively related to them (P < 0.05). For lipids levels in serum and seminal plasma, only TG level had slightly positive correlation between them (r = 0.081, P = 0.042). There was no significant correlation between serum lipids levels and semen parameters. However, seminal plasma TG, TC, LDL and HDL levels were negatively related to one or several semen parameters, including semen volume (SV), sperm concentration (SC), total sperm count (TSC), sperm motility, progressive motility (PR) and total normal-progressively motile sperm counts (TNPMS). Moreover, seminal plasma TG, TC, LDL and HDL levels in patients with oligospermatism, asthenospermia and teratozoospermia were higher than those with normal sperm concentration, motility or morphology. After adjusting age and serum LH, FSH, TT, E2 and SHBG levels, linear regression analysis showed that SV was still significantly correlated with seminal plasma LDL (P = 0.012), both of SC and TSC with seminal plasma HDL (P = 0.028 and 0.002), and both of PR and sperm motility with seminal plasma TC (P = 0.012 and 0.051). Conclusion The abnormal metabolism of lipids in male reproductive system may contribute to male factor infertility. PMID:26726884
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Yorbik, Ozgur; Mutlu, Caner; Ozilhan, Selma; Eryilmaz, Gul; Isiten, Nuket; Alparslan, Serdar; Saglam, Esra
2015-06-01
There are limited studies investigating the relationship between oral release osmotic system-methylphenidate (OROS-MPH) doses and plasma methylphenidate (MPH) concentrations in children and adolescents. The aim of this study was to investigate the relationship between the doses of OROS-MPH and the plasma levels of the drug. We also examined the effects of the other drugs including aripiprazole, risperidone, fluoxetine, and sertraline on the levels of the MPH in the plasma. The files of 100 attention deficit hyperactivity disorder (ADHD) subjects (76 male, 24 female) who were diagnosed as ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria, were screened. The ages of subjects were between 6 and 18 years (mean = 11.5 ± 3.8 years). Plasma MPH levels were determined by high-performance liquid chromatography-tandem mass spectrometry assay. Daily mean OROS-MPH dose used in ADHD children was 0.7 ± 0.2 mg/kg (range: 0.3-1.3 mg/kg). The mean plasma OROS-MPH was 11.6 ± 7.3 ng/mL (range: 0.5-43.4 ng/mL). There was no group difference in the mean plasma MPH and dose-related MPH levels between the groups that used any additional drug including aripiprazole (n = 25), risperidone (n = 10), fluoxetine (n = 16), sertraline (n = 10), and did not use these drugs (P > 0.05). There was a positive correlation between the OROS-MPH doses (mg/kg) and the blood MPH levels (Pearson correlation = 0.40; P < 0.001). The plasma levels of MPH were found to be less than 13 ng/mL in 65% of the subjects. Our findings point to the fact that plasma levels of MPH show a wide range of changes at similar doses, correlate positively with the doses and, as expected, are not affected by using risperidone, sertraline, fluoxetine, and aripiprazole. Therapeutic drug monitoring may help to optimize MPH dose in patients not responding to treatment or in those experiencing serious side effects, but not in routine clinical practice. The presence of intermediate
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Plasma NOV/CCN3 Levels Are Closely Associated with Obesity in Patients with Metabolic Disorders
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
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Plasma beta-endorphin levels in obese and non-obese patients with polycystic ovary disease.
Martínez-Guisasola, J; Guerrero, M; Alonso, F; Díaz, F; Cordero, J; Ferrer, J
2001-02-01
The aim of this study was to determine the influence of body weight on circulating plasma levels of beta-endorphin and insulin in women with polycystic ovary disease (PCOD), as well as the correlation between the plasma levels of beta-endorphin and insulin. One-hundred and sixty-seven consecutive subjects with PCOD were recruited, 117 of whom had normal weight (body mass index (BMI) < 25) while 50 were obese (BMI > 25). A venous blood sample was taken and plasma concentrations of beta-endorphin, insulin, gonadotropins, prolactin, progesterone, 17 beta-estradiol, estrone, androgens, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) were measured. Mean beta-endorphin and insulin plasma levels were significantly higher (p < 0.05) in obese PCOD women than in non-obese ones. Correlation analysis showed a positive association between insulin and beta-endorphin, beta-endorphin and BMI (and weight), insulin and BMI (and weight), and a negative correlation was found between insulin and SHBG. A weak association was found between beta-endorphin and luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression analysis showed that plasma beta-endorphin concentrations correlate more with BMI than with insulinemia.
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[The clinical value of measuring plasma level of very long chain fatty acids in Addison disease].
Chen, Jun; Zhang, Jian; Wang, De-Xin
2007-09-01
To determine the level of very long chain fatty acids (VLCFA) in plasma to find out X-linked adrenoleukodystrophy (X-ALD) in patients with Addison disease. By using gas chromatography measurement of plasma levels of C(26:0), ratios of C(26:0)/C(22:0) and C(24:0)/C(22:0) was carried out in 36 patients with Addison disease. Among the 36 cases, 6 had elevated plasma VLCFA levels; thus the presence of X-ALD was confirmed. Misdiagnosis of X-ALD can be reduced by measuring plasma level of VLCFA early in male patients with Addison disease, especially in young ones.
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McLachlan, Stela; Page, Kathryn E; Lee, Seung-Min; Loguinov, Alex; Valore, Erika; Hui, Simon T; Jung, Grace; Zhou, Jie; Lusis, Aldons J; Fuqua, Brie; Ganz, Tomas; Nemeth, Elizabeta; Vulpe, Chris D
2017-11-01
Iron homeostasis is tightly regulated, and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex- and strain-dependent differences in mRNA and serum levels of hepcidin and reported conflicting data on the relationship between hepcidin ( Hamp1 ) mRNA levels and iron status. Our aim was to clarify the relationships between strain, sex, and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains. Two studies were done: first, Hamp1 mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, Hamp1 mRNA and plasma hepcidin levels in both sexes and iron levels in the heart, kidneys, liver, pancreas, and spleen in males were measured in nine inbred/recombinant inbred strains raised on an iron-sufficient or high-iron diet. Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). However, liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice fed iron-sufficient or high-iron diets, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males. We also measured plasma erythroferrone, performed RNA-sequencing analysis of liver samples from six inbred strains fed the iron-sufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels. NEW & NOTEWORTHY Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). Liver iron and diferric transferrin levels are not predictors of Hamp1 mRNA levels in mice, nor are the Hamp1 mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least
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Zhu, Pengli; Huang, Feng; Lin, Fan; Yuan, Yin; Chen, Falin; Li, Qiaowei
2013-11-01
To describe the relationship of plasma apelin levels with blood pressure in a coastal Chinese population. This cross-sectional study included a total of 1031 subjects from the coastal areas of China. One-way analysis of variance (ANOVA) and linear trend test, Pearson's correlation analysis, as well as multivariate linear regression analysis were used to evaluate the association between plasma apelin levels and blood pressure. Plasma apelin levels dropped with increasing quartiles of systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MABP) (all P<0.001). SBP, DBP, and MABP values decreased as the apelin levels increased within the quartiles. After adjusting for age and gender, the significant differences in SBP, DBP, and MABP between the groups within the apelin quartiles remained (all P<0.05). A significant negative correlation between SBP, DBP, as well as MABP and apelin levels was observed (all P<0.01); even after adjusting for cardiovascular confounding factors, this negative correlation remained (all P<0.001). A negative correlation between plasma apelin levels and blood pressure was found in this 1000-population-based epidemiological study. Apelin may become a potential therapeutic target of anti-hypertensive treatment.
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Reduced fasting plasma levels of diazepam-binding inhibitor in adolescents with anorexia nervosa.
Conti, Elisa; Tremolizzo, Lucio; Bomba, Monica; Uccellini, Orlando; Rossi, Maria Sara; Raggi, Maria Elisabetta; Neri, Francesca; Ferrarese, Carlo; Nacinovich, Renata
2013-09-01
Altered expression and/or function, both peripherally and centrally, of various neuropeptides is involved in the neurophysiology of anorexia nervosa (AN). Diazepam-binding inhibitor (DBI) is an interesting peptide for understanding this crosstalk. The aim of this work was to assess fasting plasma levels of DBI and leptin in patients with AN. Twenty-four AN adolescents were recruited together with 10 age-comparable healthy controls. Neuropeptide determinations were performed on plasma samples by enzyme-linked immunosorbent assays. Patients with AN were further characterized for the presence of a depressive state or anxiety by using, respectively, the Children's Depression Inventory or the State-Trait Anxiety Inventory form Y. Levels of both plasma DBI and leptin were reduced in patients with AN (∼40 and ∼70%, respectively). DBI levels displayed a tendency to increase in the presence of a depressive state, although not with anxiety, whereas leptin levels correlated exclusively with body mass index. These data further extend our knowledge of neuropeptide dysfunction in AN, and plasma DBI may represent a marker for this disease, in particular considering its correlation with comorbid mood disorders. Copyright © 2013 Wiley Periodicals, Inc.
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Tenenbaum, Ariel; Phillip, Moshe; de Vries, Liat
2014-01-01
Few studies have addressed the role of the glucagon stimulation test (GST) in evaluating the hypothalamic-pituitary-adrenal axis in children. We investigated the diagnostic value of the GST in evaluating the adrenocortical response in short healthy children. The GST was performed in 190 children investigated for short stature. A peak cortisol >500 nmol/l was considered a normal response. In the 45 (23.7%) with subnormal response, a 250-μg ACTH test was done. The rate of subnormal adrenal response to GST was higher among boys (33.9 vs. 8.9%, p < 0.001) and among children ≥6 years than among younger children (32.7 vs. 18.4%, p < 0.02). Both mean basal and peak cortisol levels were higher in girls than in boys: 381 ± 165 vs. 319 ± 151 nmol/l (p = 0.003) and 741 ± 102 vs. 595 ± 208 nmol/l (p < 0.001), respectively. Peak cortisol on GST was associated with basal cortisol (r = 0.45, p < 0.001) but not with glucose nadir (r = -0.31, p = 0.67), peak GH (r = 0.069, p = 0.33) or BMI-SDS (r = -0.08, p = 0.28). Peak cortisol was >500 nmol/l in all the patients undergoing an ACTH stimulation test. Since adrenal response to GST is age- and gender-related and the false-positive rate is high, its routine performance in healthy children warrants reconsideration. © 2014 S. Karger AG, Basel.
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Geisel, Olga; Panneck, Patricia; Hellweg, Rainer; Wiedemann, Klaus; Müller, Christian A
2015-03-30
Alterations in secretion of stress hormones within the hypothalamic-pituitary-adrenal (HPA) axis have repeatedly been found in substance-related addictive disorders. It has been suggested that glucocorticoids might contribute to the development and maintenance of substance use disorders by facilitatory effects on behavioral responses to substances of abuse. The objective of this pilot study was to investigate HPA axis activity in patients with non-substance-related addictive disorders, i.e. pathological gambling and internet use disorder. We measured plasma levels of copeptin, a vasopressin surrogate marker, adrenocorticotropic hormone (ACTH) and cortisol in male patients with pathological gambling (n=14), internet use disorder (n=11) and matched healthy controls for pathological gambling (n=13) and internet use disorder (n=10). Plasma levels of copeptin, ACTH and cortisol in patients with pathological gambling or internet use disorder did not differ among groups. However, cortisol plasma levels correlated negatively with the severity of pathological gambling as measured by the PG-YBOCS. Together with our findings of increased serum levels of brain-derived neurotrophic factor (BDNF) in pathological gambling but not internet use disorder, these results suggest that the pathophysiology of pathological gambling shares some characteristics with substance-related addictive disorders on a neuroendocrinological level, whereas those similarities could not be observed in internet use disorder. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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PAROTID FLUID CORTISOL AND CORTISONE.
Concentrations of parotid fluid cortisol and cortisone, and of plasma dialyzable cortisol, were measured in normal men before and 2 hours after...of 8.5 to 17.7 micrograms/100 ml. after ACTH treatment, and to 39.4 micrograms/100 ml. after administration of the estrogen. However, parotid fluid...the increase in total plasma cortisol (which was over twice as high after administration of estrogen as of ACTH). Thus parotid fluid corticosteroids
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Sanaka, Tsutomu; Funaki, Takenori; Tanaka, Toshihisa; Hoshi, Sayako; Niwayama, Jyun; Taitoh, Takashi; Nishimura, Hideki; Higuchi, Chieko
2002-05-01
The plasma pentosidine levels in patients with renal disease were measured by a simple method which was established for plasma and urinary pentosidine determinations. The method, which can be completed within a few hours, involves pretreating plasma with proteolytic enzyme (pronase) and measuring the concentration of pentosidine in the sample by ELISA using antipentosidine antibodies. The prepared antibodies showed no cross-reaction with the raw materials for pentosidine synthesis or with compounds having similar structures. SDS-PAGE indicated that the antibodies had a high purity. The reaction of the antibodies and keyhole limpet hemocyanin-pentosidine in the competitive ELISA system was inhibited by free pentosidine. Excellent standard curves for pentosidine determination were obtained. In actual measurements of clinical samples from patients, a good correlation (r = 0.9356) was obtained between the values measured by ELISA and HPLC. The plasma pentosidine level in patients with renal disease correlated significantly with plasma creatinine, urea nitrogen, beta2-microglobulin, and creatinine clearance, indicating its usefulness in evaluating the severity of renal disease. A significant elevation in plasma pentosidine levels was observed in mild renal dysfunction, whereas no significant increases in creatinine and urea nitrogen levels were detected, suggesting that the plasma pentosidine level is useful in the early diagnosis of beginning renal failure. In patients with chronic renal failure, no difference in plasma pentosidine levels was observed between diabetic nephropathy and chronic glomerulonephritis, while a significant correlation was observed with phosphatidylcholine hydroperoxide, suggesting the possibility that the plasma pentosidine level reflects injury due to oxidation. From these results, the quantitative measurement method developed by us is judged to be a superior innovation for measuring pentosidine in body fluids. The plasma pentosidine level may
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Fadel, Fatina I; Elshamaa, Manal F; Essam, Rascha G; Elghoroury, Eman A; El-Saeed, Gamila S M; El-Toukhy, Safinaz E; Ibrahim, Mona Hamed
2014-03-01
The high prevalence of protein-energy malnutrition is a critical issue for patients with chronic kidney disease (CKD). Serum albumin is the most commonly used nutritional marker. Another index is plasma amino acid (AA) profile. Of these, the plasma levels of glutamine, glutamate and homocysteine, correlate well with nutritional status. We measured some plasma AAs in children with different stages CKD to provide information in monitoring the therapeutic strategy, particularly in AA supplementary therapy or protein restriction. Three amino acids were evaluated along with albumin and high sensitivity C-reactive protein (hs-CRP) in 30 patients with advanced CKD stages 4 and 5. They were divided into two groups undergoing conservative treatment (CT) (n=15) or hemodialysis (HD) (n=15). An additional group of patients with nephrotic syndrome [CKD stage 2] was also studied to assess the alterations of plasma free amino acids with the early stage of CKD. Another 30 age- and sex-matched healthy children served as controls. A significant increase in plasma concentration of amino acid glutamine was observed in children with advanced CKD stages 4 and 5 when compared with controls (P=0.02).Plasma glutamine level was significantly higher in ESRD children on HD than in children with nephrotic syndrome (P=0.02). We did not find a significant difference between HD children and CT children as regard to glutamine level. Notable differences were in the plasma homocysteine level detected in the CKD groups patients, which was greater than that in controls (P=0.0001). Plasma homocysteine level was significantly higher in children on HD than in children with nephrotic syndrome (P=0.01). A significant differences was observed in hs-CRP levels between the CKD groups and the controls (P=0.04). Albumin levels were lower in CKD groups than in controls (p=0.01). Glutamine showed significant positive correlations with blood urea level (r=0.84, P=0.002) and blood ammonia level (r=0.72, P=0
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The Apo(a) gene is the major determinant of variation in plasma Lp(a) levels in African Americans.
Mooser, V; Scheer, D; Marcovina, S M; Wang, J; Guerra, R; Cohen, J; Hobbs, H H
1997-01-01
The distributions of plasma lipoprotein(a), or Lp(a), levels differ significantly among ethnic groups. Individuals of African descent have a two- to threefold higher mean plasma level of Lp(a) than either Caucasians or Orientals. In Caucasians, variation in the plasma Lp(a) levels has been shown to be largely determined by sequence differences at the apo(a) locus, but little is known about either the genetic architecture of plasma Lp(a) levels in Africans or why they have higher levels of plasma Lp(a). In this paper we analyze the plasma Lp(a) levels of 257 sibling pairs from 49 independent African American families. The plasma Lp(a) levels were much more similar in the sibling pairs who inherited both apo(a) alleles identical by descent (IBD) (r = .85) than in those that shared one (r = .48) or no (r = .22) parental apo(a) alleles in common. On the basis of these findings, it was estimated that 78% of the variation in plasma Lp(a) levels in African Americans is attributable to polymorphism at either the apo(a) locus or sequences closely linked to it. Thus, the apo(a) locus is the major determinant of variation in plasma Lp(a) levels in African Americans, as well as in Caucasians. No molecular evidence was found for a common "high-expressing" apo(a) allele in the African Americans. We propose that the higher plasma levels of Lp(a) in Africans are likely due to a yet-to-be-identified trans-acting factor(s) that causes an increase in the rate of secretion of apo(a) or a decrease in its catabolism. PMID:9311746
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Higher plasma level of STIM1, OPG are correlated with stent restenosis after PCI.
Li, Haibin; Jiang, Zhian; Liu, Xiangdong; Yang, Zhihui
2015-01-01
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. 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. 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. 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.
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Fy phenotype and gender determine plasma levels of monocyte chemotactic protein.
Jilma-Stohlawetz, P; Homoncik, M; Drucker, C; Marsik, C; Rot, A; Mayr, W R; Seibold, B; Jilma, B
2001-03-01
In vitro studies indicate that the Fy blood group system antigens serve as receptors for chemokines such as monocyte chemotactic protein-1 (MCP-1) and RANTES. However, it is unclear whether subjects with the Fy(a-b-) phenotype exhibit altered clearance and hence altered plasma levels of chemo-kines, because they still express Fy on endothelial cells. To clarify a possible in vivo role of Fy on RBCs in the regulation of chemo-kine levels, healthy young volunteers of common Fy phenotypes were compared in a cross-sectional study. More than 90 percent of the 34 subjects of African origin were Fy(a-b-), one black volunteer was Fy(a+b-), and two were Fy(a-b+). As expected, all 65 white volunteers were positive for either Fy(a) and/or Fy(b). Unexpectedly, persons expressing either Fy(a) and/or Fy(b) had significantly higher plasma levels of MCP-1 than Fy(a-b-) volunteers (women: 154 vs. 110 ng/L, p<0.01; men: 179 vs. 169 ng/L, p = 0.03). Surprisingly, plasma levels of MCP-1 were found to be sex-dependent: median MCP-1 levels averaged 180 ng per L in men but only 139 ng per L in women (p<0.001). Further, MCP-1 levels decreased significantly throughout the menstrual cycle of 18 women studied longitudinally. MCP-1 levels are about 30 percent higher in men than in premenopausal women, and MCP-1 levels are also higher in persons with RBCs expressing Fy antigens than in Fy(a-b-) persons. These findings have direct implications for the concept and interpretation of clinical studies measuring MCP-1 levels; the role of the observed differences in MCP-1 levels for the pathogenesis of MCP-1-dependent diseases, such as atherosclerosis, merits further investigation.
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Lower plasma choline levels are associated with sleepiness symptoms.
Pak, Victoria M; Dai, Feng; Keenan, Brendan T; Gooneratne, Nalaka S; Pack, Allan I
2018-04-01
Sleepiness and cardiovascular disease share common molecular pathways; thus, metabolic risk factors for sleepiness may also predict cardiovascular disease risk. Daytime sleepiness predicts mortality and cardiovascular disease, although the mechanism is unidentified. This study explored the associations between subjective sleepiness and metabolite concentrations in human blood plasma within the oxidative and inflammatory pathways, in order to identify mechanisms that may contribute to sleepiness and cardiovascular disease risk. An exploratory case-control sample of 36 subjects, categorized based on the Epworth Sleepiness Scale (ESS) questionnaire as sleepy (ESS ≥ 10) or non-sleepy (ESS < 10), was recruited among subjects undergoing an overnight sleep study for suspected sleep apnea at the University of Pennsylvania Sleep Center. The average age was 42.4 ± 10.5 years, the mean body mass index (BMI) was 40.0 ± 9.36 kg/m 2 , median Apnea Hypopnea Index (AHI) was 8.2 (IQR: 2.5-26.5), and 52% were male. Fasting morning blood plasma samples were collected after an overnight sleep study. Biomarkers were explored in subjects with sleepiness versus those without using the multiple linear regression adjusting for age, BMI, smoking, Apnea Hypopnea Index (sleep apnea severity), study cohort, and hypertension. The level of choline is significantly lower (P = 0.003) in sleepy subjects (N = 18; mean plasma choline concentration of 8.19 ± 2.62 μmol/L) compared with non-sleepy subjects (N = 18; mean plasma choline concentration of 9.14 ± 2.25 μmol/L). Other markers with suggestive differences (P < 0.1) include isovalerylcarnitine, Alpha-Amino apidipic acid, Spingosine 1 Phosphate, Aspartic Acid, Propionylcarnitine, and Ceramides (fatty acids; C14-C16 and C-18). This pilot study is the first to show that lower levels of plasma choline metabolites are associated with sleepiness. Further exploration of choline and other noted metabolites and their
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Malendowicz, L K; Nussdorfer, G G
1996-01-01
The bolus intraperitoneal administration of 5-bromo-2'-deoxyuridine (BrdU), at a dose in the range of those currently used for in vivo cell-kinetic studies, was found to provoke a marked rise in the plasma concentrations of adrenocorticotrophic hormone (ACTH), corticosterone and aldosterone in rats. This secretagogue effect of BrdU was annulled by the chronic pretreatment of animals with dexamethasone. The prolonged administration of endothelin-1 (ET-1) raised the blood level of aldosterone (but not of ACTH or corticosterone), and did not alter the response to BrdU. The pretreatment of rats with BQ-123 or BQ-788, two specific antagonists of ET-1 receptor subtypes A and B, did not affect the plasma concentrations of ACTH, corticosterone and aldosterone, but did partially reverse the effects of BrdU. In view of these findings we concluded that BrdU activates the pituitary-adrenal axis in rats, with its main mode of action being pituitary ACTH release; and the suppressive actions of BQ-123 and BQ-788 are independent of their antagonism on ET-1 receptors, and may be due to their interference with the intra-cellular mechanism(s) mediating the secretagogue action of BrdU. This effect of BrdU may have particular relevance to in vivo studies using BrdU labelling to assess cell kinetics of tissues (e.g. lymphatic tissue) affected profoundly by adrenal steroid hormones.
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Wang, Dean-Chuan; Chen, Tsan-Ju; Lin, Ming-Lu; Jhong, Yue-Cih; Chen, Shih-Chieh
2014-09-01
Both the detrimental effects of early life adversity and the beneficial effects of exercise on the hypothalamic-pituitary-adrenal (HPA) axis have been reported. Early life exposure to di-(2-ethylhexyl)-phthalate (DEHP) may impair the development of endocrine system. In this study, we investigated the effects of lactational DEHP exposure on stress responses in late adolescent female rats and examined the protective role of treadmill running. Sprague-Dawley dams were fed with DEHP (10mg/kg per day) or vehicle during lactation. After weaning, the female offspring rats were trained to exercise on a treadmill for 5 weeks and then stressed by exploring on an elevated plus maze. The activities of HPA axis were evaluated by measuring the plasma levels of ACTH and corticosterone, the expressions of adrenal enzymes cholesterol side-chain cleavage enzyme (CYP11A1) and cytochrome P-450 11β-hydroxylase (CYP11B1), and the expression of hypothalamic glucocorticoid receptors (GR). The results demonstrate that DEHP-exposed rats exhibited enhanced anxiety-like behaviors. Increased hypothalamic GR and plasma ACTH levels, but decreased adrenal CYP11A1 and corticosterone levels, were observed in DEHP-exposed animals under stressed condition. Importantly, in DEHP-exposed animals, exercise during childhood-adolescence reduced anxiety-like behaviors by normalizing stress-induced alterations in ACTH level and adrenal CYP11A1 expression. The findings of this study suggest that treadmill running may provide beneficial effects on ameliorating the dysregulation of HPA axis in lactational DEHP-exposed adolescent female rats. Copyright © 2014 Elsevier Inc. All rights reserved.
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Neuroactive steroid levels in plasma and cerebrospinal fluid of male multiple sclerosis patients.
Caruso, Donatella; Melis, Marta; Fenu, Giuseppe; Giatti, Silvia; Romano, Simone; Grimoldi, Maria; Crippa, Donatella; Marrosu, Maria Giovanna; Cavaletti, Guido; Melcangi, Roberto Cosimo
2014-08-01
Neuroactive steroid family includes molecules synthesized in peripheral glands (i.e., hormonal steroids) and directly in the nervous system (i.e., neurosteroids) which are key regulators of the nervous function. As already reported in clinical and experimental studies, neurodegenerative diseases affect the levels of neuroactive steroids. However, a careful analysis comparing the levels of these molecules in cerebrospinal fluid (CSF) and in plasma of multiple sclerosis (MS) patients is still missing. To this aim, the levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in CSF and plasma of male adults affected by Relapsing-Remitting MS and compared with those collected in control patients. An increase in pregnenolone and isopregnanolone levels associated with a decrease in progesterone metabolites, dihydroprogesterone, and tetrahydroprogesterone was observed in CSF of MS patients. Moreover, an increase of 5α-androstane-3α,17β-diol and of 17β-estradiol levels associated with a decrease of dihydrotestosterone also occurred. In plasma, an increase in pregnenolone, progesterone, and dihydrotestosterone and a decrease in dihydroprogesterone and tetrahydroprogesterone levels were reported. This study shows for the first time that the levels of several neuroactive steroids, and particularly those of progesterone and testosterone metabolites, are deeply affected in CSF of relapsing-remitting MS male patients. We here demonstrated that, the cerebrospinal fluid and plasma levels of several neuroactive steroids are modified in relapsing remitting multiple sclerosis male patients. Interestingly, we reported for the first time that, the levels of progesterone and testosterone metabolites are deeply affected in cerebrospinal fluid. These findings may have an important relevance in therapeutic and/or diagnostic field of multiple sclerosis. © 2014 International Society for Neurochemistry.
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PCK1 expression is correlated with the plasma glucose level in the duck.
Chen, L; Zeng, T; Li, G Q; Liu, R; Tian, Y; Li, Q H; Lu, L Z
2017-06-01
Phosphoenolpyruvate carboxykinase 1 (soluble) (PCK1) is a key gene in gluconeogenesis and glyceroneogenesis. Although its functions have been extensively studied in mice, bats and humans, little is known in ducks. Here, PCK1 functions were studied using a duck domestication model and a 48-h fasting experiment. We found PCK1 expression significantly decreased in two breeds of domestic ducks (Jinyun Pockmark ducks and Cherry Valley ducks) as compared with wild ducks (Anas platyrhynchos). Simultaneously, plasma levels of glucose, triglycerides and free fatty acid in domestic ducks were lower than in wild ducks. When compared with fed ducks, the plasma triglyceride level was observed to be significantly decreased, while the glucose and free fatty acid levels remained constant in 48-h fasting ducks. The expression analysis of gluconeogenic genes revealed that fructose-1,6-bisphosphatase genes (FBP1 and FBP2) and the glucose-6-phosphatase gene (G6PC2) were not changed, whereas PCK1 was significantly upregulated. In addition, the reported regulators of PCK1, including forkhead box A2 (FOXA2) gene and orphan nuclear receptor NR4A family genes (NR4A1, NR4A2 and NR4A3), exhibited similar expression levels between 48-h fasting ducks and fed ducks, suggesting that PCK1 is not regulated by these genes in the duck under fasting conditions. In conclusion, PCK1 expression may affect plasma levels of glucose, triglycerides and free fatty acid during the duck domestication process. This work demonstrates for the first time in duck that PCK1 is a key gene in maintaining plasma glucose homeostasis during fasting and that the upregulated expression of PCK1 may be responsible for constant plasma free fatty acid level by the glyceroneogenesis process. © 2017 Stichting International Foundation for Animal Genetics.
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Alteration of plasma prednisolone levels by indomethacin and naproxen.
Rae, S A; Williams, I A; English, J; Baylis, E M
1982-01-01
Eleven patients with stable rheumatoid disease (RD) who were receiving regular corticosteroid therapy (CS) were investigated to discover the effect on plasma prednisolone levels of additional therapy with the non-steroidal anti-inflammatory (NSAI) drugs, indomethacin and naproxen. There was a highly significant (P less than 0.001) increase in free prednisolone levels after concurrent therapy with either indomethacin or naproxen for 2 weeks. Total prednisolone levels were unchanged. These results could provide an explanation for clinical reports that these two NSAI drugs possess a steroid-sparing effect. PMID:7126420
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Germain, Natacha; Viltart, Odile; Loyens, Anne; Bruchet, Céline; Nadin, Katia; Wolowczuk, Isabelle; Estour, Bruno; Galusca, Bogdan
2016-01-01
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. 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. 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. 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.
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Kondoh, Y; Uemura, T; Murase, M; Yokoi, N; Ishikawa, M; Hirahara, F
2001-10-01
To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea. Retrospective cohort study. Yokohama City University, Yokohama, Japan. Twenty-four women with progestin-negative hypothalamic amenorrhea. Administration of human corticotropin-releasing hormone (hCRH) and treatment with a combination of estrogen and progesterone. Plasma cortisol and ACTH concentrations and period required for recovery from amenorrhea. Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the percent maximum increment (%Cmax) of ACTH were significantly lower in the amenorrheic patients compared with the control group patients. The basal cortisol was significantly higher, and the %Cmax of cortisol was significantly lower. In the 16 patients who recovered from amenorrhea, there was a significant positive correlation (Y = 1.93X-10.8, r = 0.629) between the basal cortisol concentrations (X) and the period for recovery (Y). The serum E2 gradually increased before recovery, and this E2 increase was preceded by changes in the plasma cortisol concentration and the %Cmax values of cortisol and ACTH. The CRH test might be useful for evaluating the roles of stress and for estimating the period required for recovery in hypothalamic amenorrhea.
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Tocopherols and tocotrienols plasma levels are associated with cognitive impairment.
Mangialasche, Francesca; Xu, Weili; Kivipelto, Miia; Costanzi, Emanuela; Ercolani, Sara; Pigliautile, Martina; Cecchetti, Roberta; Baglioni, Mauro; Simmons, Andrew; Soininen, Hilkka; Tsolaki, Magda; Kloszewska, Iwona; Vellas, Bruno; Lovestone, Simon; Mecocci, Patrizia
2012-10-01
Vitamin E includes 8 natural compounds (4 tocopherols, 4 tocotrienols) with potential neuroprotective activity. α-Tocopherol has mainly been investigated in relation to cognitive impairment. We examined the relation of all plasma vitamin E forms and markers of vitamin E damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Within the AddNeuroMed-Project, plasma tocopherols, tocotrienols, α-tocopherylquinone, and 5-nitro-γ-tocopherol were assessed in 168 AD cases, 166 MCI, and 187 cognitively normal (CN) people. Compared with cognitively normal subjects, AD and MCI had lower levels of total tocopherols, total tocotrienols, and total vitamin E. In multivariable-polytomous-logistic regression analysis, both MCI and AD cases had 85% lower odds to be in the highest tertile of total tocopherols and total vitamin E, and they were, respectively, 92% and 94% less likely to be in the highest tertile of total tocotrienols than the lowest tertile. Further, both disorders were associated with increased vitamin E damage. Low plasma tocopherols and tocotrienols levels are associated with increased odds of MCI and AD. Copyright © 2012 Elsevier Inc. All rights reserved.
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Plasma levels of nitrate and risk of prostate cancer: a prospective study.
Wu, Tianying; Wang, Yushan; Ho, Shuk-Mei; Giovannucci, Edward
2013-07-01
Nitrate and nitrite supplements have recently been shown to improve cardiovascular health, but there is concern that these supplements could contribute to the development of cancer. Previous small, cross-sectional studies reported positive associations between circulating nitrate/nitrite levels and cancer. Prospective studies examining the association between plasma nitrate and cancer, especially prostate cancer, are lacking. We conducted a nested case-control study within the Health Professionals Follow-up Study. Baseline blood samples were collected in 1994, and incident cases of prostate cancer were identified from 1997 to 2005. Baseline plasma levels of nitrate were measured in the 630 cases and 630 matched controls. We have found that baseline levels of plasma nitrate were not associated with risk of prostate cancer. Compared to quintile 1, the relative risk from quintiles 2 to 5 were 1.13 [95% confidence interval (CI), 0.78-1.63], 0.93 (95% CI, 0.63-1.38), 0.95 (95% CI, 0.65-1.39), and 0.99 (95% CI, 0.68-1.48); Ptrend was 0.9 after adjustment of multivariate risk factors. When analyses were restricted to men fasting more than 6 hours, the trend was similar. Furthermore, plasma nitrate seemed to be inversely associated with advanced-stage prostate cancer. The relative risk across extreme quartiles was 0.44 (95% CI, 0.17-1.12; Ptrend = 0.07) for the whole dataset and 0.30 (95% CI, 0.09-0.99; Ptrend = 0.05) for the fasting dataset. In summary, we did not find an increased risk of prostate cancer associated with higher plasma nitrate levels. A potential protective association between nitrate and aggressive forms of prostate cancer requires confirmation. Nitrate-nitrite-nitric oxide pathway has emerged as a new therapeutic pathway for chronic diseases. The results of this study certainly merit replications in other prospective studies.
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Genome-wide association study identifies two loci influencing plasma neurofilament light levels.
Li, Jie-Qiong; Yuan, Xiang-Zhen; Li, Hai-Yan; Cao, Xi-Peng; Yu, Jin-Tai; Tan, Lan; Chen, Wei-An
2018-05-10
Plasma neurofilament light (NFL) is a promising biomarker for Alzheimer disease (AD), which increases in the early stage of AD and is associated with the progression of AD. We performed a genome-wide association study (GWAS) of plasma NFL in Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) cohort to identify novel variants associated with AD. This study included 179 cognitively healthy controls (HC), 176 patients with mild cognitive impairment (MCI), and 172 patients with AD. All subjects were restricted to non-Hispanic Caucasian derived from the ADNI cohort and met all quality control (QC) criteria. Association of plasma NFL with the genetic variants was assessed using PLINK with an additive genetic model, i.e.dose-dependent effect of the minor alleles. The influence of a genetic variant associated with plasma NFL (rs7943454) on brain structure was further assessed using PLINK with a linear regression model. The minor allele (T) of rs7943454 in leucine zipper protein 2 gene (LUZP2) was associated with higher plasma NFL at suggestive levels (P = 1.39 × 10 - 6 ) in a dose-dependent fashion. In contrast, the minor allele (G) of rs640476 near GABRB2 was associated with lower plasma NFL at suggestive levels (P = 6.71 × 10 - 6 ) in a dose-dependent effect in all diagnostic groups except the MCI group. Furthermore, the minor allele (T) of rs7943454 within LUZP2 increased the onset risk of AD (odds ratio = 1.547, confidence interval 95% = 1.018-2.351) and was associated with atrophy of right middle temporal gyrus in the whole cohort in the longitudinal study (P = 0.0234). GWAS found the associations of two single nucleotide polymorphisms (rs7943454 and rs640476) with plasma NFL at suggestive levels. Rs7943454 in LUZP2 was associated with the onset risk of AD and atrophy of right middle temporal gyrusin the whole cohort. Using an endophenotype-based approach, we identified rs7943454 as a new AD risk locus.
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Khalangot, Mykola; Krasnienkov, Dmytro; Vaiserman, Alexander; Avilov, Ivan; Kovtun, Volodymir; Okhrimenko, Nadia; Koliada, Alexander; Kravchenko, Victor
2017-04-01
Type 2 diabetes mellitus is characterized by shorter leukocyte telomere length, but the relationship between leukocyte telomere length and type 2 diabetes mellitus development is rather questioned. Fasting and post-load glycaemia associated with different types of insulin resistance and their relation with leukocyte telomere length remains unknown. We compared leukocyte telomere length and fasting or post-load glucose levels in persons who do not receive glucose lowering treatment. For 82 randomly selected rural residents of Ukraine, aged 45+, not previously diagnosed with type 2 diabetes mellitus, the WHO oral glucose tolerance test and anthropometric measurements were performed. Leukocyte telomere length was measured by standardized method of quantitative monochrome multiplex polymerase chain reaction in real time. Spearman's or Pearson's rank correlation was used for correlation analysis between fasting plasma glucose or 2-h post-load plasma glucose levels and leukocyte telomere length. Logistical regression models were used to evaluate risks of finding short or long telomeres associated with fasting plasma glucose or 2-h post-load plasma glucose levels. No association of fasting plasma glucose and leukocyte telomere length was revealed, whereas 2-h post-load plasma glucose levels demonstrated a negative correlation ( P < 0.01) with leukocyte telomere length. Waist circumference and systolic blood pressure were negatively related ( P = 0.03) with leukocyte telomere length in men. Oral glucose tolerance test result-based glycemic categories did not show differences between mean leukocyte telomere length in categories of normal fasting plasma glucose and 2-h post-load plasma glucose (NGT, n = 33); diabetes mellitus (DM), n = 18 and impaired fasting glucose/tolerance (IFG/IGT, n = 31) levels. A correlation relationship between leukocyte telomere length and 2-h post-load plasma glucose level in NGT; IFG/IGT and DM groups ( P = 0.027; 0
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Beta2-microglobuline plasma level and painful shoulder in haemodialysed patients.
Barisić, Igor; Ljutić, Dragan; Vlak, Tonko; Bekavac, Josip; Perić, Irena; Mise, Kornelija; Klancnik, Marisa; Janković, Stipan
2010-03-01
Painful shoulder in patients on chronic haemodialyis is most often associated with dialysis arthropathy or accumulation of deposits containing modified fibrils of beta2- microglobuline especially in bones and joints due to insufficient elimination during the therapy. The aim of this study is to investigate whether there is connection between painful shoulder and plasma level of beta2-microglobuline and to corroborate that with morphologic parameters found in proved amyloidosis. It has to be emphasized that even other causes may contribute the development of painful shoulder. Real time sonography and conventional plain radiographs of the 108 shoulders were performed in 54 patients receiving chronic haemodialysis as a treatment of terminal renal failure (without previous history of rheumatoid arthritis), 27 symptomatic with persistent pain and stiffness in both shoulders and lasting for more than 6 weeks and restriction of movements in various degree and 27 asymptomatic. Plasma level of beta2-microglobuline, CRP and uric acid were taken periodically as routine procedure during a one year prospective trial, as well as plasma level of calcium, phosphor and alkaline phosphatase. Plasmatic level of beta2-microglobuline is strongly connected with painful shoulder in dialyzed patients, as well as CRP as sign of acute inflammation. That is proved by morphologic parameters associated with histological proved amyloidosis in patients on long term dialysis, more then 10 years.
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Effects of prolonged physical exercise and fasting upon plasma testosterone level in rats.
Guezennec, C Y; Ferre, P; Serrurier, B; Merino, D; Pesquies, P C
1982-01-01
Prolonged physical exercise and fasting in male rats were studied to determine the effect of these two treatments on plasma testosterone level. Blood and tissue samples were drawn after 1 h, 3 h, 5 h, and 7 h treadmill running, and after 24 h, 48 h, and 72 h of fasting. Both treatments resulted in a significant fall in plasma testosterone, plasma luteinizing hormone (LH), plasma Insulin (IRI) and in liver and muscle glycogen stores. In the course of these two treatments the injection of a supra maximal dose of Human Chorionic Gonadotropin (HCG) produced a rise in plasma testosterone similar to that in control rats. This indicates that the decrease of plasma LH may be responsible for the decrease in plasma testosterone, which is time-related with the decrease in glycogen stores. The possible metabolic role of the decrease in plasma testosterone is discussed.
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Plasma Soluble CD163 Level Independently Predicts All-Cause Mortality in HIV-1-Infected Individuals.
Knudsen, Troels Bygum; Ertner, Gideon; Petersen, Janne; Møller, Holger Jon; Moestrup, Søren K; Eugen-Olsen, Jesper; Kronborg, Gitte; Benfield, Thomas
2016-10-15
CD163, a monocyte- and macrophage-specific scavenger receptor, is shed as soluble CD163 (sCD163) during the proinflammatory response. Here, we assessed the association between plasma sCD163 levels and progression to AIDS and all-cause mortality among individuals infected with human immunodeficiency virus type 1 (HIV). Plasma sCD163 levels were measured in 933 HIV-infected individuals. Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with mortality were computed by Cox proportional hazards regression. At baseline, 86% were receiving antiretroviral treatment, 73% had plasma a HIV RNA level of <50 copies/mL, and the median CD4(+) T-cell count was 503 cells/µL. During 10.5 years of follow-up, 167 (17.9%) died. Plasma sCD163 levels were higher in nonsurvivors than in survivors (4.92 mg/L [interquartile range {IQR}, 3.29-8.65 mg/L] vs 3.16 mg/L [IQR, 2.16-4.64 mg/L]; P = .0001). The cumulative incidence of death increased with increasing plasma sCD163 levels, corresponding to a 6% or 35% increased risk of death for each milligram per liter or quartile increase, respectively, in baseline plasma sCD163 level (adjusted HR, 1.06 [95% CI, 1.03-1.09] and 1.35 [95% CI, 1.13-1.63], respectively). Plasma sCD163 was an independent marker of all-cause mortality in a cohort of HIV-infected individuals, suggesting that monocyte/macrophage activation may play a role in HIV pathogenesis and be a target of intervention. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
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Sirich, Tammy L; Plummer, Natalie S; Gardner, Christopher D; Hostetter, Thomas H; Meyer, Timothy W
2014-09-05
Numerous uremic solutes are derived from the action of colon microbes. Two such solutes, indoxyl sulfate and p-cresol sulfate, have been associated with adverse outcomes in renal failure. This study tested whether increasing dietary fiber in the form of resistant starch would lower the plasma levels of these solutes in patients on hemodialysis. Fifty-six patients on maintenance hemodialysis were randomly assigned to receive supplements containing resistant starch (n=28) or control starch (n=28) daily for 6 weeks in a study conducted between October 2010 and May 2013. Of these, 40 patients (20 in each group) completed the study and were included in the final analysis. Plasma indoxyl sulfate and p-cresol sulfate levels were measured at baseline and week 6. Increasing dietary fiber for 6 weeks significantly reduced the unbound, free plasma level of indoxyl sulfate (median -29% [25th percentile, 75th percentile, -56, -12] for fiber versus -0.4% [-20, 34] for control, P=0.02). The reduction in free plasma levels of indoxyl sulfate was accompanied by a reduction in free plasma levels of p-cresol sulfate (r=0.81, P<0.001). However, the reduction of p-cresol sulfate levels was of lesser magnitude and did not achieve significance (median -28% [-46, 5] for fiber versus 4% [-28, 36] for control, P=0.05). Increasing dietary fiber in hemodialysis patients may reduce the plasma levels of the colon-derived solutes indoxyl sulfate and possibly p-cresol sulfate without the need to intensify dialysis treatments. Further studies are required to determine whether such reduction provides clinical benefits. Copyright © 2014 by the American Society of Nephrology.
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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.
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Montero, Daniel; Terova, Genciana; Rimoldi, Simona; Tort, Lluis; Negrin, Davinia; Zamorano, María Jesús; Izquierdo, Marisol
2015-01-01
Dietary fatty acids have been shown to exert a clear effect on the stress response, modulating the release of cortisol. The role of fatty acids on the expression of steroidogenic genes has been described in mammals, but little is known in fish. The effect of different fatty acids on the release of cortisol and expression of stress-related genes of European sea bass (Dicentrarchus labrax) head kidney, induced by a pulse of adenocorticotrophin hormone (ACTH), was studied. Tissue was maintained in superfusion with 60 min of incubation with EPA, DHA, arachidonic acid (ARA), linoleic acid or α-linolenic acid (ALA) during 490 min. Cortisol was measured by RIA. The quantification of stress-related genes transcripts was conducted by One-Step TaqMan real-time RT-PCR. There was an effect of the type of fatty acid on the ACTH-induced release of cortisol, values from ALA treatment being elevated within all of the experimental period. The expression of some steroidogenic genes, such as the steroidogenic acute regulatory protein (StAR) and c-fos, were affected by fatty acids, ALA increasing the expression of StAR after 1 h of ACTH stimulation whereas DHA, ARA and ALA increased the expression of c-fos after 20 min. ARA increased expression of the 11β-hydroxylase gene. Expression of heat shock protein 70 (HSP70) was increased in all the experimental treatments except for ARA. Results corroborate previous studies of the effect of different fatty acids on the release of cortisol in marine fish and demonstrate that those effects are mediated by alteration of the expression of steroidogenic genes.
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Micke, P; Beeh, K M; Schlaak, J F; Buhl, R
2001-02-01
HIV infection is characterized by an enhanced oxidant burden and a systemic deficiency of the tripeptide glutathione (GSH), a major antioxidant. The semi-essential amino acid cysteine is the main source of the free sulfhydryl group of GSH and limits its synthesis. Therefore, different strategies to supplement cysteine supply have been suggested to increase glutathione levels in HIV-infected individuals. The aim of this study was to evaluate the effect of oral supplementation with two different cysteine-rich whey protein formulas on plasma GSH levels and parameters of oxidative stress and immune status in HIV-infected patients. In a prospective double blind clinical trial, 30 patients (25 male, 5 female; mean age (+/- SD) 42 +/- 9.8 years) with stable HIV infection (221 +/- 102 CD4 + lymphocytes L-1) were randomized to a supplemental diet with a daily dose of 45 g whey proteins of either Protectamin (Fresenius Kabi, Bad Hamburg, Germany) or Immunocal (Immunotec, Vandreuil, Canada) for two weeks. Plasma concentrations of total, reduced and oxidized GSH, superoxide anion (O2-) release by blood mononuclear cells, plasma levels of TNF-alpha and interleukins 2 and 12 were quantified with standard methods at baseline and after therapy. Pre-therapy, plasma GSH levels (Protectamin: 1.92 +/- 0.6 microM; Immunocal: 1.98 +/- 0.9 microM) were less than normal (2.64 +/- 0.7 microM, P = 0.03). Following two weeks of oral supplementation with whey proteins, plasma GSH levels increased in the Protectamin group by 44 +/- 56% (2.79 +/- 1.2 microM, P = 0.004) while the difference in the Immunocal group did not reach significance (+ 24.5 +/- 59%, 2.51 +/- 1.48 microM, P = 0.43). Spontaneous O2- release by blood mononuclear cells was stable (20.1 +/- 14.2 vs. 22.6 +/- 16.1 nmol h-1 10-6 cells, P = 0.52) whereas PMA-induced O2- release decreased in the Protectamin group (53.7 +/- 19 vs. 39.8 +/- 18 nmol h-1 10-6 cells, P = 0.04). Plasma concentrations of TNF-alpha and interleukins 2 and
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DeFilippis, Andrew P; Harper, Charles R; Cotsonis, George A; Jacobson, Terry A
2009-01-01
We previously reported a >50% increase in mean plasma eicosapentaenoic acid levels in a general medicine clinic population after supplementation with alpha-linolenic acid. In the current analysis, we evaluate the variability of changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid and evaluated the impact of baseline plasma fatty acids levels on changes in eicosapentaenoic acid levels in these individuals. Changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid ranged from a 55% decrease to a 967% increase. Baseline plasma fatty acids had no statistically significant effect on changes in eicosapentaenoic levels acid after alpha-linolenic acid supplementation. Changes in eicosapentaenoic acid levels varied considerably in a general internal medicine clinic population supplemented with alpha-linolenic acid. Factors that may impact changes in plasma eicosapentaenoic acid levels after alpha-linolenic acid supplementation warrant further study.
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Becerik, Sema; Öztürk, Veli Özgen; Celec, Peter; Kamodyova, Natalia; Atilla, Gül; Emingil, Gülnur
2017-11-01
This study was aimed to evaluate the gingival crevicular fluid (GCF) and plasma transglutaminase-2 (TGM-2), total antioxidant capacity (TAC), total oxidant status (TOS), ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) in patients with chronic periodontal disease. Twenty patients with chronic periodontitis (CP), 20 patients with gingivitis and 20 healthy subjects were enrolled in the study. Clinical periodontal parameters including probing depth, clinical attachment level, plaque index and papillary bleeding index were recorded. GCF and plasma levels of TGM-2, TAC, TOS, TBARS and FRAP were analyzed. GCF TGM-2 was significantly lower in CP group than in gingivitis patients (P=0.006). GCF FRAP in CP and gingivitis groups was significantly lower than in healthy subjects (P<0.001). Plasma FRAP level was lower in gingivitis group when compared to healthy subjects (P=0.003). There was no significant difference in GCF and plasma TAC, TOS, TBARS and plasma TGM-2 levels among the study groups (P>0.05). GCF TGM-2 level was positively correlated with GCF TAC and negatively correlated with CAL. Decreased FRAP in GCF and plasma indicating lower antioxidant status of CP patients might suggest the role of oxidative stress in periodontitis. GCF TGM-2 data might suggest that TGM2 is associated with stabilization of the extracellular matrix and wound healing in periodontium rather than gingival inflammation. Copyright © 2017. Published by Elsevier Ltd.
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Taste acuity, plasma zinc levels, and weight loss during radiotherapy: a study of relationships
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bolze, M.S.; Fosmire, G.J.; Stryker, J.A.
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 lossmore » 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.« less
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Taste acuity, plasma zinc levels, and weight loss during radiotherapy: a study of relationships
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bolze, M.S.; Fosmire, G.J.; Stryker, J.A.
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 lossmore » 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.« less
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The STRONG STAR Multidisciplinary PTSD Research Consortium
2014-11-01
hippocampus. Figure 2.7 shows the effects of adult and prenatal stress on plasma corticosterone levels (Task 1 Step 12; Task 2, Step 11). Prenatal...measure both basal and acute stress-induced levels of corticosterone and ACTH. Figure 2.7: Effect of prenatal...we administered the natural glucocorticoid agonist corticosterone . We also began another model in which we hoped to measure the effect of the
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Pei, Yuxin; Xu, Yuanyuan; Ruan, Jingwei; Rong, Liping; Jiang, Mengjie; Mo, Ying; Jiang, Xiaoyun
2016-01-01
The purpose of this study was to investigate the change of the plasma oxidative stress level in children with IgA nephropathy (IgAN) and analyze its relativity to the clinical and pathological classification. To discuss the early effects of angiotensin-converting enzyme inhibitors (ACEIs) on the plasma oxidative stress level in children with IgA nephropathy. Thirty-eight children with IgAN were divided into groups according to their clinical features, pathologic grades, and treatments. Twenty healthy children were included in the control group. The plasma level of advanced oxidation protein products (AOPPs), malonaldehyde (MDA), and superoxide dismutase (SOD) were detected. The plasma level of oxidative stress was significantly increased in the IgAN group, including a higher plasma level of AOPP and MDA and a lower plasma level of SOD. After treatment, the plasma level of oxidative stress was significantly decreased in the ACEI group. The children with IgAN had an increase in the plasma level of oxidative stress, expressed as an increased plasma level of AOPP and MDA and a decreased plasma level of SOD. Oxidative stress was associated with the progression of IgAN in children. Early treatment with ACEI therapy can significantly reduce the plasma level of oxidative stress in children with IgAN. © The Author(s) 2016.
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Glucose Intolerance, Plasma Insulin Levels, and Colon Adenomas in Japanese Men
Kono, Suminori; Abe, Hiroshi; Eguchi, Hiroyuki; Shimazaki, Kae; Hatano, Ben; Hamada, Hiroaki
2001-01-01
Hyperinsulinemia may be related to colon carcinogenesis. Several studies have suggested that diabetes mellitus is related to increased risk of colon cancer. We examined cross‐sectionally the relation of fasting plasma insulin levels and glucose tolerance status to colon adenomas. In a consecutive series of 951 men undergoing total colonoscopy for a health examination at the Japan Self Defense Forces Fukuoka Hospital from April 1998 to August 1999, we identified 233 cases of colon adenomas and 497 controls with normal colonoscopy. Glucose tolerance status was determined by a 75‐g oral glucose tolerance test, and subjects were classified as normal, unpaired glucose tolerance (IGT) or non‐insulin dependent diabetes mellitus (NIDDM). Plasma insulin levels were measured after subjects had fasted overnight. Logistic regression analysis and analysis of covariance was used to control for age and obesity. While plasma insulin levels were unrelated to colon adenomas, NIDDM was associated with a significantly increased risk of colon adenomas. There was no association between IGT and colon adenomas. NIDDM was more strongly associated with proximal colon adenomas. The findings suggest that long‐term hyperinsulinemic status associated with NIDDM may increase the risk of colon adenomas, and subsequently of colon cancer. PMID:11509114
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Increased plasma chemokine levels in children with Prader-Willi syndrome.
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. © 2015 Wiley Periodicals, Inc.
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Plasma Omentin-1 Level as a Predictor of Good Coronary Collateral Circulation.
Zhou, Ji-Peng; Tong, Xiao-Yu; Zhu, Ling-Ping; Luo, Jing-Min; Luo, Ying; Bai, Yong-Ping; Li, Chuan-Chang; Zhang, Guo-Gang
2017-09-01
Coronary collateral circulation (CCC) is crucial during an acute ischemic attack. Evidences showed that omentin-1 exhibited remarkable antiatherogenic effects and ischemia-induced revascularization. The aim of this study was to investigate the relationship between plasma omentin-1 levels and CCC in patients with ≥90% angiography-proven coronary occlusion. 142 patients with ≥90% luminal diameter stenosis in at least one major epicardial coronary artery were recruited. Among them, 79 patients with Rentrop 0-1 grade were classified into the poor CCC group and 63 patients with Rentrop 2-3 grade were included into the good CCC group. The association between plasma omentin-1 levels and CCC status was assessed. Plasma omentin-1 level was significantly higher in patients with good CCC than those with poor CCC (566.57±26.90 vs. 492.38±19.70 ng/mL, p=0.024). Besides, omentin-1 was positively correlated with total cholesterol (TC), high-density lipoprotein, and gensini score but inversely with hyperlipidemia and body mass index (all p values＜0.05). Multivariate regression analysis indicated that omentin-1 [odds ratio (OR)=1.002, 95% confidence interval (CI): 1.000-1.004, p=0.041)], TC, the number of the diseased vessels, a higher frequency of left circumflex artery and right coronary artery, chronic total occlusion, and gensini score remained as the independent predictors of good CCC. Higher plasma omentin-1 level was associated with better CCC development. Our findings suggest that omentin-1 may be an alternative marker for adequate CCC in patients with ≥90% coronary occlusion.
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Modulation of Human Plasma Fibronectin Levels Following Exercise,
1988-01-01
forms of this large molecular weight (440 kilodaltons) glycoprotein,(17. While the tissue type is cell-associated and important to cell adhesion and...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
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Villela-Torres, Maria De La Luz; Higareda-Mendoza, Ana Edith; Gómez-García, Anel; Alvarez-Paredes, Alfonso Rafael; García-López, Elvia; Stenvikel, Peter; Gu, Harvest F; Rashid-Qureshi, Abbul; Lindholm, Bengt; Alvarez-Aguilar, Cleto
2018-04-14
Chronic kidney disease (CKD) is a leading complication of type 2 diabetes mellitus (T2DM) and is considered as a public health problem. Copeptin is a surrogate marker of arginine vasopressin (AVP) system and is proposed as a biomarker of decline renal function. Evaluate whether plasma copeptin levels may be used as a biomarker of decline renal function in patients with T2DM. A total of 480 patients with T2DM and different stages of CKD were included. Plasma levels of copeptin, cystatin-C, and other biochemical parameters were measured. The correlation between copeptin and glomerular filtration rate (GFR), estimated based on plasma cystatin-C levels, was investigated. Plasma copeptin levels were gradually increased from the stage 1-5 of CKD in the patients with T2DM. In univariate linear regression analysis, high plasma levels of copeptin were associated with lower GFR (Standardized β = -0.535, R 2 = 0.287, p <0.0001). This association remained significant even after being adjusted for glucose levels and years of T2DM diagnosis, mean blood pressure, pharmacological treatment, gender, and age. The results show that high plasma copeptin levels are associated with the decline of renal function in patients with T2DM and, therefore, copeptin may be considered as a biomarker of renal function. Further evaluation of plasma copeptin levels to predict morbidity and mortality of T2DM patients, with or without CKD, has been taken into our consideration. Copyright © 2018. Published by Elsevier Inc.
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Relationship between microRNA-146a expression and plasma renalase levels in hemodialyzed patients
Koch, Wojciech; Kukula-Koch, Wirginia; Gaweł, Kinga; Bednarek-Skublewska, Anna; Małecka-Massalska, Teresa; Milanowski, Janusz; Petkowicz, Beata; Solski, Janusz
2017-01-01
Background microRNA (miRNA) belongs to the non-coding RNAs family responsible for the regulation of gene expression. Renalase is a protein composed of 342 amino acids, secreted by the kidneys and possibly plays an important role in the regulation of sympathetic tone and blood pressure. The aim of the present study was to investigate plasma renalase concentration, and explore the relationship between miRNA-146a-5p expression and plasma renalase levels in hemodialyzed patients. Methods The study population comprised 55 subjects who succumbed to various cardiac events, 27 women and 28 men, aged 65–70 years. The total RNA including miRNA fraction was isolated using QiagenmiRNEasy Serum/Plasma kit according to the manufacturer’s protocol. The isolated miRNAs were analyzed using a quantitative polymerase chain reaction (qRT-PCR) technique. The plasma renalase levels were measured using a commercial ELISA kit. Results In the group of patients with high levels of renalase, higher miRNA-146a expression was found, compared with those with low concentration of renalase. Patients with simultaneous low miRNA-146a expression and high level of renalase were confirmed to deliver a significantly longer survival time compared with other patients. Conclusions miRNA-146a and plasma renalase levels were estimated as independent prognostic factors of hemodialyzed patients’ survival time. Patients with low miRNA-146a expression demonstrated a significantly longer survival time in contrast to the patients with a high expression level of miRNA-146a. Moreover, a significantly longer survival time was found in patients with high renalase activity compared with patients with low activity of the enzyme. PMID:28614373
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Yuan, Lin; Liu, An; Qiao, Luxin; Sheng, Bo; Xu, Meng; Li, Wei; Chen, Dexi
2015-01-01
Although HAD is now rare due to HAART, the milder forms of HAND persist in HIV-infected patients. HIV-induced systemic and localized inflammation is considered to be one of the mechanisms of HAND. The levels of cytokines in CSF were associated with neurocognitive impairment in HIV infection. However, the changes of cytokines involved in cognition impairment in plasma have not been shown, and their relationships between CSF and plasma require to be addressed. We compared cytokine levels in paired CSF and plasma samples from HIV-infected individuals with or without neurocognitive impairment. Cytokine concentrations were measured by Luminex xMAP. In comparing the expression levels of cytokines in plasma and CSF, IFN-α2, IL-8, IP-10, and MCP-1 were significantly higher in CSF. Eotaxin was significantly higher in plasma, whereas G-CSF showed no difference between plasma and CSF. G-CSF (P = 0.0079), IL-8 (P = 0.0223), IP-10 (P = 0.0109), and MCP-1 (P = 0.0497) in CSF showed significant difference between HIV-CI and HIV-NC group, which may indicate their relationship to HIV associated neurocognitive impairment. In addition, G-CSF (P = 0.0191) and IP-10 (P = 0.0377) in plasma were significantly higher in HIV-CI than HIV-NC. The consistent changes of G-CSF and IP-10 in paired plasma and CSF samples might enhance their potential for predicting HAND. PMID:25821806
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FABP4 plasma levels are increased in familial combined hyperlipidemia.
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
2010-05-01
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) microg/l and 19.2 (9.2) microg/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.
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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…
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Development of a label-free immunosensor system for detecting plasma cortisol levels in fish.
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.
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Retinoic acid as a novel medical therapy for Cushing's disease in dogs.
Castillo, Victor; Giacomini, Damiana; Páez-Pereda, Marcelo; Stalla, Johanna; Labeur, Marta; Theodoropoulou, Marily; Holsboer, Florian; Grossman, Ashley B; Stalla, Günter K; Arzt, Eduardo
2006-09-01
Cushing's disease is almost always caused by an ACTH-secreting pituitary tumor, but effective medical therapy is currently limited. Because retinoic acid has been shown to be potentially useful in decreasing corticotroph secretion and proliferation in rodent models, we have studied its action in dogs with Cushing's disease. A randomized treatment with retinoic acid (n = 22) vs. ketoconazole (n = 20) in dogs with Cushing's disease was assigned for a period of 180 d. Clinical signs, plasma ACTH and alpha-MSH, the cortisol/creatinine urine ratio, and pituitary magnetic resonance imaging were assessed and compared at different time points. We recorded a significant reduction in plasma ACTH and alpha-MSH, and also in the cortisol/creatinine urine ratio, of the dogs treated with retinoic acid. Pituitary adenoma size was also significantly reduced at the end of retinoic acid treatment. Survival time and all the clinical signs evaluated showed an improvement in the retinoic-acid-treated dogs. No adverse events or signs of hepatotoxicity were observed, suggesting that the drug is not only effective but also safe. Retinoic acid treatment controls ACTH and cortisol hyperactivity and tumor size in dogs with ACTH-secreting tumors, leading to resolution of the clinical phenotype. This study highlights the possibility of using retinoic acid as a novel therapy in the treatment of ACTH-secreting tumors in humans with Cushing's disease.
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Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in Turks.
Hodoglugil, Ugur; Tanyolaç, Sinan; Williamson, David W; Huang, Yadong; Mahley, Robert W
2006-01-01
The apolipoprotein A-V gene (APOA5) plays an important role in determining plasma triglyceride levels. We studied the effects of APOA5 polymorphisms on plasma triglyceride levels in Turks, a population with low levels of HDL cholesterol and a high prevalence of coronary artery disease. We found 15 polymorphisms, three of which were novel. Seven haplotype-tagging single nucleotide polymorphisms (SNPs) were chosen and genotyped in approximately 3,000 subjects. The rare alleles of the -1464T>C, -1131T>C, S19W, and 1259T>C SNPs were significantly associated with increased triglyceride levels (19-86 mg/dl; P < 0.05) and had clear gene-dose effects. Haplotype analysis of the nine common APOA5 haplotypes revealed significant effects on triglyceride levels (P < 0.001). Detailed analysis of haplotypes clearly showed that the -1464T>C polymorphism had no effect by itself but was a marker for the -1131T>C, S19W, and 1259T>C polymorphisms. The -1131T>C and 1259T>C polymorphisms were in a strong but incomplete linkage disequilibrium and appeared to have independent effects. Thus, the APOA5 -1131T>C, S19W, and 1259T>C rare alleles were associated with significant increases in plasma triglyceride levels. At least one of these alleles was present in approximately 40% of the Turks. Similar associations were observed for -1131T>C and S19W in white Americans living in San Francisco, California.
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Increased plasma/serum levels of prolactin in multiple sclerosis: a meta-analysis.
Wei, Wei; Liu, Lei; Cheng, Zhong-Le; Hu, Bo
2017-08-01
Prolactin (PRL) is a polypeptide hormone that is known to stimulate humoral and cell mediated immune responses. PRL levels have been investigated in several autoimmune diseases including multiple sclerosis (MS); however, these have yielded different and inconsistent results. This study aims to perform a more precise evaluation on the plasma/serum PRL levels in MS patients, and to explore the available influential factors. Research related to plasma/serum PRL levels in MS patients and healthy controls were gathered using PubMed, EMBASE and The Cochrane Library database (until Mar 31 2016). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I 2 , and publication bias was evaluated using a funnel plot and Egger's linear regression test. 516 articles were obtained after searching databases, and 8 studies with 426 MS patients and 296 controls were finally included. Meta-analysis revealed that, compared with the control group, the MS group had significantly higher plasma/serum PRL levels, with the SMD of 0.55 and 95%CI (0.39, 0.72). Subgroup analyses showed that region, age and disease duration were associated with PRL level in MS patients. In summary, our meta-analysis revealed a significantly higher PRL level in MS patients than healthy controls, and it is influenced by region, age and disease duration.
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Al Qarni, Ali Ahmed; Joatar, Faris Elbahi; Das, Nagalla; Awad, Mohamed; Eltayeb, Mona; Al-Zubair, Ahmed Gasim; Ali, Muhalab E.; Al Masaud, Abdulaziz; Shire, Abdirashid M.; Gumaa, Khalid
2017-01-01
Background Although the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM. Methods Patients with T2DM (n=107, cases) and non-diabetic apparently healthy subjects (n=101, controls) from Saudi Arabia were included in this study. The biochemical profiles and plasma insulin levels of all subjects were analyzed, and IR was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Active ghrelin levels in plasma were measured using the radioimmunoassay technique. Results Only 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3 ≤HOMA-IR <5). HOMA-IR values were not associated with age, disease duration, or gender. Importantly, T2DM itself and the co-occurrence of IR with T2DM were significantly associated with low plasma ghrelin levels. However, ghrelin levels were inversely correlated with the HOMA-IR index, body weight, and fasting plasma insulin levels, mainly in the control subjects, which was indicative of the breakdown of metabolic homeostasis in T2DM. Conclusion The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM. PMID:28555463
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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.
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Jones, Peter J. H.; Lin, Lin; Gillingham, Leah G.; Yang, Haifeng; Omar, Jaclyn M.
2014-01-01
N-acylethanolamines (NAEs) are endogenous lipid-signaling molecules involved in satiety and energetics; however, how diet impacts circulating NAE concentrations and their downstream metabolic actions in humans remains unknown. Objectives were to examine effects of diets enriched with high-oleic canola oil (HOCO) or HOCO blended with flaxseed oil (FXCO), compared with a Western diet (WD), on plasma NAE levels and the association with energy expenditure and substrate oxidation. Using a randomized controlled crossover design, 36 hypercholesterolemic participants consumed three isoenergetic diets for 28 days, each containing 36% energy from fat, of which 70% was HOCO, FXCO, or WD. Ultra-performance liquid chromatography-MS/MS was used to measure plasma NAE levels and indirect calorimetry to assess energy expenditure and substrate oxidation. After 28 days, compared with WD, plasma oleoylethanolamide (OEA) and alpha-linolenoyl ethanolamide (ALEA) levels were significantly increased in response to HOCO and FXCO (P = 0.002, P < 0.001), respectively. Correlation analysis demonstrated an inverse association between plasma OEA levels and percent body fat (r = −0.21, P = 0.04), and a positive association was observed between the plasma arachidonoyl ethanolamide (AEA)/OEA ratio and android:gynoid fat (r = 0.23, P = 0.02), respectively. Results suggest that plasma NAE levels are upregulated via their dietary lipid substrates and may modulate regional and total fat mass through lipid-signaling mechanisms. PMID:25262934
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Chronic ethanol feeding inhibits plasma levels of insulin-like growth factor-1
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sonntag, W.E.; Boyd, R.L.
1988-01-01
The purpose of this study was to determine whether the generalized catabolic effects of chronic ethanol may be associated with a decline in plasma of insulin-like growth factor-1 (IGF-1). Male Sprague-Dawley rats were fed a liquid diet containing 5% ethanol or pair-fed a diet made isocaloric with maltose-dextrin. Animals were maintained on this diet for either 12 days or 4.5 months. Another groups of animals were fed control diet ad libitum for 2 weeks. After 12 days of feeding, plasma concentrations of IGF-1 in ad libitum fed rats were 771 +/- 41 ng/ml which was greater than concentrations in eithermore » pair-fed or ethanol-fed rats. After 4.5 months of feeding, plasma levels of IGF-1 in ad libitum and pair-fed rats were similar to the 12 day study. However, a significant decrease in plasma levels of IGF-1 was observed in ethanol-fed animals over the 4.5 month period. Results of a similar study in rats fed a high-fat diet for 4.5 months were similar to those found with the low-fat diet.« less
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Current-level triggered plasma-opening switch
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.
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Dietary sodium and plasma volume levels with exercise.
Luetkemeier, M J; Coles, M G; Askew, E W
1997-05-01
Sodium is the major cation of the extracellular fluid and has a potent influence on fluid movement. Sodium has been likened to a sponge that draws fluids into the extracellular space, including the plasma volume, to equalize gradients in concentration. Conventional wisdom suggests limiting dietary intake of Na+ to decrease risk of hypertension. However, there are some extreme occupational or exercise-related conditions where sweat losses are great and Na+ losses may exceed normal dietary intake. This can occur acutely such as in an ultra-endurance event or chronically as in hard manual work in the hear. In such cases, additional Na+ in the form of a higher Na+ diet or adding Na+ to beverages used for fluid replacement may be warranted. A higher Na+ diet also appears to accelerate the cardiovascular and thermoregulatory adaptations that accompany heat acclimation or short term exercise training. Saline ingestion before exercise causes an expansion of plasma volume at rest and throughout the subsequent exercise bout. This expansion of plasma volume alters cardiovascular and thermoregulatory responses to exercise in ways that may lead to beneficial changes in endurance exercise performance. Plasma volume expansion also occurs with saline infusion during exercise, but exercise performance advantages have yet to be reported. The purpose of this article is to review the literature concerning dietary sodium and its influence on fluid balance, plasma volume and thermoregulation during exercise. It contains 2 major sections. First, we will discuss manipulations in daily Na+ intake initiated before or throughout an exercise regime. Second, we will examine studies where an acute Na+ load was administered immediately before or during an exercise trial. The dependent variables that we will discuss pertain to: (i) body water compartments, i.e. plasma volume; (ii) thermoregulatory variables, i.e. core temperature and sweat rate; (iii) cardiovascular variables, i.e. heart rate and
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Lichtstein, D; Gati, I; Haver, E; Katz, U
1992-01-01
Digitalis-like compounds (DLC), constituents of animal tissues, are possible regulators of the Na+, K(+)-ATPase implicated in water and salt homeostasis. The distribution of DLC in the toad (Bufo viridis) was determined following methanol extraction and partial purification. DLC highest levels were found in the skin but it was also detected in the plasma and many internal organs. Short term (hours) exposure of the toad to hypertonic shock (1.5% NaCl) induced an increase in plasma osmolarity due to an increase in Na+ and Cl- levels. This treatment induced a transient, three fold, increase of DLC levels in the brain and transient reduction of its levels in the ventral skin. Acclimation of the toads to burrowing conditions for six weeks resulted in an increase in plasma osmolarity due to a large increase in plasma urea with a small increase in ion concentrations. Under these conditions DLC levels in the dorsal skin increased by 100% without alteration of its levels in the plasma, brain and ventral skin. DLC levels in the toad brain of control animals, showed a significant dependence on season, being highest in the summer and lowest in the winter. DLC levels in the skin peaked in May while the levels in the plasma were season independent. The changes in DLC levels induced by the short- as well as long-term perturbations in the animal environmental salinity together with the seasonal differences suggest that DLC in the toad is involved in water and salt homeostasis of these animals, but may also participate in other unknown functions.
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Tang, Lanhua; Xia, Zhuying; Luo, Zhongwei; Long, Haitao; Zhu, Yong; Zhao, Shushan
2017-08-01
Objective This study aimed to investigate the association between low plasma Platelet-derived growth factor-BB (PDGF-BB) levels and oestradiol in Postmenopausal osteoporosis (PMOP). Methods This prospective study measured plasma PDGF-BB and oestradiol levels in outpatients who were admitted to our hospital. Participants were screened and then allocated to three groups: normal young women, postmenopausal control, and PMOP. Additionally, Sprague-Dawley rats underwent either sham surgery or bilateral ovariectomy (OVX), and were divided into the following groups: sham, OVX, OVX + oestradiol, and OVX + PDGF-BB. Plasma oestradiol and PDGF-BB levels were measured using commercially available ELISA kits. Results A total of 121 participants, including 69 normal young women, 28 patients with primary PMOP, and 24 age-matched postmenopausal women were enrolled. Plasma oestradiol and PDGF-BB levels were lower in postmenopausal women, especially in PMOP ( P < 0.01). Pearson correlations analysis showed that PDGF-BB levels were positively correlated with oestradiol levels and inversely correlated with age ( P < 0.01). The OVX rat model showed that oestradiol replacement increased plasma PDGF-BB levels, while PDGF-BB systematic treatment had no effect on plasma oestradiol levels. Conclusions Plasma PDGF-BB levels are maintained by oestrogen in normal young women and play a major role in PMOP.
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Current-level triggered plasma-opening switch
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.
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Effects of matrix on plasma levels of EPA and DHA in dogs.
Goffin, Kay; van Maris, Marc; Corbee, Ronald J
2017-01-01
EPA and DHA are often used in veterinary medicine due to their beneficial effects for several medical conditions such as osteoarthritis. EPA and DHA are administered to dogs through different matrices. The aim of the present study was to determine the effects on the plasma levels in dogs caused by various matrices for EPA and DHA administration. In this study, three different n -3 PUFA formulations were used: soft chew tablet (CCx); liquid fish oil (LFO); and enriched kibbles (EK). The formulations were administered single-dose and compared in a randomised, cross-over designed study with a 1-week wash-out period. Several variables were observed after the administration of these formulations in thirteen dogs: the NEFA plasma concentration, the AUC for 1 d (AUC0-24 h), and maximum plasma concentration for both EPA and DHA. All plasma fatty acid levels reached baseline levels within 72 h. CCx (median = 2·987) had a significantly lower AUC0-24 h for EPA compared with LFO (median = 5·647, P = 0·043) and EK (median = 5·119, P = 0·032) ( F 2,22 = 4·637, P = 0·021). CCx (median = 2·471) AUC0-24 h for DHA was significantly lower compared with LFO (median = 4·837, Z = -2·56, P = 0·011) and EK (median = 4·413, Z = -2·59, P = 0·01). EPA and DHA plasma levels were affected by matrix, as with the CCx, the AUC0-24 h of EPA and DHA were both lower compared with LFO and EK. The effect of matrix on bioavailability is important for product development as well as for clinical trials studying effects of EPA and DHA.
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Plasma levels of nitrate and risk of prostate cancer: a prospective study
Wu, Tianying; Wang, Yushan; Ho, Shuk-Mei; Giovannucci, Edward
2013-01-01
Background Nitrate and nitrite supplements have recently been shown to improve cardiovascular health, but there is concern that these supplements could contribute to the development of cancer.Previous small, cross-sectional studies reported positive associations between circulating nitrate/nitrite levels and cancer. Prospective studies examining the association between plasma nitrate and cancer, especially prostate cancer (PCa), are lacking. Methods We conducted a nested case-control study within the Health Professionals Follow-up Study. Baseline blood samples were collected in 1994, and incident cases of PCa were identified from 1997–2005. Baseline plasma levels of nitrate were measured in the 630 cases and 630 matched controls. Results We have found that baseline levels of plasma nitrate were not associated with risk of PCa. Compared to quintile 1, the relative risk from quintiles 2–5 were 1.13 (95% CI, 0.78–1.63), 0.93 (95% CI, 0.63–1.38), 0.95 (95% CI, 0.65–1.39), and 0.99 (95% CI, 0.68–1.48); p for trend was 0.9 after adjustment of multivariate risk factors. When analyses were restricted to men fasting more than 6 hrs, the trend was similar. Further, plasma nitrate appeared to be inversely associated with advanced-stage PCa. The relative risk across extreme quartiles was 0.44 (95% CI, 0.17–1.12; p for trend = 0.07) for the whole data set and 0.30 (95% CI, 0.09–0.99; p for trend = 0.05) for the fasting data set. Conclusions In summary, we did not find an increased risk of PCa associated with higher plasma nitrate levels. A potential protective association between nitrate and aggressive forms of PCa requires confirmation. Impact Nitrate-nitrite-nitric oxide pathway has emerged as a new therapeutic pathway for chronic diseases. The results of this study certainly merit replications in other prospective studies. PMID:23677578
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Martini, Maurizio; de Pascalis, Ivana; D'Alessandris, Quintino Giorgio; Fiorentino, Vincenzo; Pierconti, Francesco; Marei, Hany El-Sayed; Ricci-Vitiani, Lucia; Pallini, Roberto; Larocca, Luigi Maria
2018-05-10
Vascular endothelial growth factor (VEGF) isoforms, particularly the diffusible VEGF-121, could play a major role in the response of recurrent glioblastoma (GB) to anti-angiogenetic treatment with bevacizumab. We hypothesized that circulating VEGF-121 may reduce the amount of bevacizumab available to target the heavier isoforms of VEGF, which are the most clinically relevant. We assessed the plasma level of VEGF-121 in a brain xenograft model, in human healthy controls, and in patients suffering from recurrent GB before and after bevacizumab treatment. Data were matched with patients' clinical outcome. In athymic rats with U87MG brain xenografts, the level of plasma VEGF-121 relates with tumor volume and it significantly decreases after iv infusion of bevacizumab. Patients with recurrent GB show higher plasma VEGF-121 than healthy controls (p = 0.0002) and treatment with bevacizumab remarkably reduced the expression of VEGF-121 in plasma of these patients (p = 0.0002). Higher plasma level of VEGF-121 was significantly associated to worse PFS and OS (p = 0.0295 and p = 0.0246, respectively). Quantitative analysis of VEGF-121 isoform in the plasma of patients with recurrent GB could be a promising predictor of response to anti-angiogenetic treatment.
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Beta blocker effects on plasma homocysteine levels in patients with hypertension.
Atar, Ilyas; Korkmaz, Mehmet Emin; Demircan, Senol; Atar, Inci Asli; Bozbaş, Hüseyin; Aydinalp, Alp; Ozin, Bülent; Yildirir, Aylin; Müderrisoğlu, Haldun
2005-08-01
Recent studies have shown that hyperhomocysteinemia might play a role in the pathogenesis of hypertension. The effects of antihypertensive agents on plasma homocysteine levels have not been tested extensively. We investigated the effects of beta-blocker therapy on homocysteine levels in patients with hypertension. In the study, 120 patients with newly diagnosed hypertension were enrolled. All patients received metoprolol succinate 100 mg/day initially. If blood pressure was above normal on the 15th day of follow-up, the metoprolol dosage was doubled. Before initiation of the antihypertensive medication and after the fourth month of treatment, homocysteine levels were measured. Of the 120 patients enrolled, 39 could not complete the study. Homocysteine levels decreased significantly by the end of the fourth month when compared with basal values (13.5+/-4.5 micromol/l versus 12.4+/-4.9 micromol/l; P = 0.001). There was no relation between homocysteine level and blood pressure control. There was a significant decrease in homocysteine levels in the women treated in this study (P = 0.001); however, this effect was absent in men (P = 0.185). We demonstrate that metoprolol succinate treatment significantly decreases plasma homocysteine levels in patients with hypertension, especially in women.
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van den Heuvel, Leigh; Suliman, Sharain; Malan-Müller, Stefanie; Hemmings, Sian; Seedat, Soraya
2016-11-01
Alterations in brain-derived neurotrophic factor (BDNF) expression and release may play a role in the pathogenesis of post-traumatic stress disorder (PTSD). This study evaluated road traffic accident (RTA) survivors to determine whether PTSD and trauma-related factors were associated with plasma BDNF levels and BDNF Val66Met carrier status following RTA exposure. One hundred and twenty-three RTA survivors (mean age 33.2 years, SD = 10.6 years; 56.9% male) were assessed 10 (SD = 4.9) days after RTA exposure. Acute stress disorder (ASD), as assessed with the Acute Stress Disorder Scale, was present in 50 (42.0%) of the participants. Plasma BDNF levels were measured with enzyme-linked immunosorbent assay and BDNF Val66Met genotyping was performed. PTSD, as assessed with the Clinician-Administered PTSD Scale, was present in 10 (10.8%) participants at 6 months follow-up. Neither BDNF Val66Met genotype nor plasma BDNF was significantly associated with the presence or severity of ASD or PTSD. Plasma BDNF levels were, however, significantly correlated with the lifetime number of trauma exposures. In RTA survivors, plasma BDNF levels increased with increasing number of prior trauma exposures. Plasma BDNF may, therefore, be a marker of trauma load.
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Plasma Omentin-1 Level as a Predictor of Good Coronary Collateral Circulation
Zhou, Ji-Peng; Tong, Xiao-Yu; Zhu, Ling-Ping; Luo, Jing-Min; Luo, Ying; Bai, Yong-Ping
2017-01-01
Aims: Coronary collateral circulation (CCC) is crucial during an acute ischemic attack. Evidences showed that omentin-1 exhibited remarkable antiatherogenic effects and ischemia-induced revascularization. The aim of this study was to investigate the relationship between plasma omentin-1 levels and CCC in patients with ≥ 90% angiography-proven coronary occlusion. Methods: 142 patients with ≥ 90% luminal diameter stenosis in at least one major epicardial coronary artery were recruited. Among them, 79 patients with Rentrop 0–1 grade were classified into the poor CCC group and 63 patients with Rentrop 2–3 grade were included into the good CCC group. The association between plasma omentin-1 levels and CCC status was assessed. Results: Plasma omentin-1 level was significantly higher in patients with good CCC than those with poor CCC (566.57 ± 26.90 vs. 492.38 ± 19.70 ng/mL, p = 0.024). Besides, omentin-1 was positively correlated with total cholesterol (TC), high-density lipoprotein, and gensini score but inversely with hyperlipidemia and body mass index (all p values < 0.05). Multivariate regression analysis indicated that omentin-1 [odds ratio (OR) = 1.002, 95% confidence interval (CI): 1.000 – 1.004, p = 0.041)], TC, the number of the diseased vessels, a higher frequency of left circumflex artery and right coronary artery, chronic total occlusion, and gensini score remained as the independent predictors of good CCC. Conclusion: Higher plasma omentin-1 level was associated with better CCC development. Our findings suggest that omentin-1 may be an alternative marker for adequate CCC in patients with ≥ 90% coronary occlusion. PMID:28123148
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Plasma ghrelin levels and polymorphisms of ghrelin gene in Chinese obese children and adolescents.
Zhu, J F; Liang, L; Zou, C C; Fu, J F
2010-09-01
To evaluate the role of fasting plasma ghrelin levels [ln(ghrelin)] and polymorphisms of ghrelin gene in Chinese obese children. Genotyping for ghrelin polymorphism was performed in 230 obese and 100 normal weight children. Among them, plasma ghrelin levels were measured in 91 obese and 23 health subjects. (1) Bivariate correlation analysis showed the ln(ghrelin) was inversely correlated with abnormality of glucose metabolism (r = -0.240, P = 0.023). Stepwise multiple regression analysis showed that abnormality of glucose metabolism was an independent determinant of plasma ghrelin levels (P = 0.023). (2) There was no difference in frequency of Leu72Met polymorphisms between obese and control groups (36.09 vs. 41.00%). Ghrelin is associated with obesity in childhood, especially associated with the glucose homeostasis. Lower ghrelin levels might be a result of obesity, but not a cause of obesity. The Leu72Met polymorphism of ghrelin gene is not associated with obesity and metabolic syndrome in Chinese children.
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Simşek, M; Naziroğlu, M; Simşek, H; Cay, M; Aksakal, M; Kumru, S
1998-12-01
The plasma levels of lipoperoxides, glutathione peroxidase (GSH-Px), reduced glutathione (GSH), beta carotene, vitamin A, E, some plasma biochemical and blood haematological parameters were investigated in 40 women with habitual abortion (HA) and controls. The levels of GSH, vitamin A, E and beta carotene were significantly lower in women with HA than in controls. However, the plasma levels of lipid peroxidation, alkaline phosphatase (ALP), glucose and blood haemoglobin were significantly higher in HA than in controls. In addition, plasma levels of GSH-Px, AST, ALT, total bilirubin, total protein, albumin, sodium, potassium, calcium and number of white blood cells, red blood cells, platelet and values of packet cell volume showed no significant differences between HA and controls. According to the results of this study, we observed that the levels of lipid peroxidation were increased and plasma levels of vitamin A, E and beta carotene were decreased in HA. The decrease of those antioxidants may play a significant role in women with habitual abortion.
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Mayado, A; Teodosio, C; Garcia-Montero, A C; Matito, A; Rodriguez-Caballero, A; Morgado, J M; Muñiz, C; Jara-Acevedo, M; Álvarez-Twose, I; Sanchez-Muñoz, L; Matarraz, S; Caldas, C; Muñoz-González, J I; Escribano, L; Orfao, A
2016-01-01
Systemic mastocytosis (SM) is a heterogeneous disease with altered interleukin (IL)-6 and IL13 plasma levels. However, no study has simultaneously investigated the plasma levels of IL1β, IL6, IL13, CCL23 and clusterin in SM at diagnosis and correlated them with disease outcome. Here we investigated IL1β, IL6, IL13, CCL23 and clusterin plasma levels in 75 SM patients--66 indolent SM (ISM) and 9 aggressive SM--and analyzed their prognostic impact among ISM cases grouped according to the extent of hematopoietic involvement of the bone marrow cells by the KIT D816V mutation. Although increased IL1β, IL6 and CCL23 levels were detected in SM patients versus healthy controls, only IL6 and CCL23 levels gradually increased with disease severity. Moreover, increased IL6 plasma levels were associated with ISM progression to more aggressive disease, in particular among ISM patients with multilineal KIT mutation (ISM-ML), these patients also showing a higher frequency of organomegalies, versus other ISM-ML patients. Of note, all ISM patients who progressed had increased IL6 plasma levels already at diagnosis. Our results indicate that SM patients display an altered plasma cytokine profile already at diagnosis, increased IL6 plasma levels emerging as an early marker for disease progression among ISM cases, in particular among high-risk ISM patients who carry multilineage KIT mutation.
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Plasma Levels of Glucose and Insulin in Patients with Brain Tumors
ALEXANDRU, OANA; ENE, L.; PURCARU, OANA STEFANA; TACHE, DANIELA ELISE; POPESCU, ALISA; NEAMTU, OANA MARIA; TATARANU, LIGIA GABRIELA; GEORGESCU, ADA MARIA; TUDORICA, VALERICA; ZAHARIA, CORNELIA; DRICU, ANICA
2014-01-01
In the last years there were many authors that suggest the existence of an association between different components of metabolic syndrome and various cancers. Two important components of metabolic syndrome are hyperglycemia and hyperinsulinemia. Both of them had already been linked with the increased risk of pancreatic, breast, endometrial or prostate cancer. However the correlation of the level of the glucose and insulin with various types and grades of brain tumors remains unclear. In this article we have analysed the values of plasma glucose and insulin in 267 patients, consecutively diagnosed with various types of brain tumors. Our results showed no correlation between the glycemia and brain tumor types or grades. High plasma levels of insulin were found in brain metastasis and astrocytomas while the other types of brain tumors (meningiomas and glioblastomas) had lower levels of the peptide. The levels of insulin were also higher in brain metastasis and grade 3 brain tumors when compared with grade 1, grade 2 and grade 4 brain tumors. PMID:24791202
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Williams, Tony D.; Ames, Caroline E.; Kiparissis, Yiannis; Wynne-Edwards, Katherine E.
2005-01-01
We investigated the relationship between plasma and yolk oestrogens in laying female zebra finches (Taeniopygia guttata) by manipulating plasma oestradiol (E2) levels, via injection of oestradiol-17β, in a sequence-specific manner to maintain chronically high plasma levels for later-developing eggs (contrasting with the endogenous pattern of decreasing plasma E2 concentrations during laying). We report systematic variation in yolk oestrogen concentrations, in relation to laying sequence, similar to that widely reported for androgenic steroids. In sham-manipulated females, yolk E2 concentrations decreased with laying sequence. However, in E2-treated females plasma E2 levels were higher during the period of rapid yolk development of later-laid eggs, compared with control females. As a consequence, we reversed the laying-sequence-specific pattern of yolk E2: in E2-treated females, yolk E2 concentrations increased with laying-sequence. In general therefore, yolk E2 levels were a direct reflection of plasma E2 levels. However, in control females there was some inter-individual variability in the endogenous pattern of plasma E2 levels through the laying cycle which could generate variation in sequence-specific patterns of yolk hormone levels even if these primarily reflect circulating steroid levels. PMID:15695208
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Wieczorek, Marek; Dunn, Adrian J.
2007-01-01
Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo–pituitary–adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1β (1 μg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2–4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1β injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1β also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1β-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1β-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only
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Wieczorek, Marek; Dunn, Adrian J
2006-09-01
Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo-pituitary-adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1beta (1 microg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2-4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1beta injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1beta also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1beta-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1beta-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only
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Daviu, Núria; Rabasa, Cristina; Nadal, Roser; Armario, Antonio
2014-03-01
Acute exposure to severe stressors causes marked activation of the hypothalamic-pituitary-adrenal (HPA) axis that is reflected on the day after higher resting levels of HPA hormones and sensitization of the HPA response to novel (heterotypic) stressors. However, whether a single exposure to a severe stressor or daily repeated exposure to the same (homotypic) stressor modifies these responses to the same extent has not been studied. In this experiment, we studied this issue in adult male Sprague-Dawley rats daily exposed for seven days to a severe stressor such as immobilization on boards (IMO). A first exposure to 1 h IMO resulted in a marked activation of the HPA axis as reflected in plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, and such activation was significantly reduced after the seventh IMO. On the day after the first IMO, higher resting levels of ACTH and corticosterone and sensitization of their responses to a short exposure to an open-field (OF) were observed, together with a marked hypoactivity in this environment. Repeated exposure to IMO partially reduced hypoactivity, the increase in resting levels of HPA hormones and the ACTH responsiveness to the OF on the day after the last exposure to IMO. In contrast, corticosterone response was gradually increased, suggesting partial dissociation from ACTH. These results indicate that daily repeated exposure to the same stressor partially reduced the HPA response to the homotypic stressor as well as the sensitization of HPA axis activity observed the day after chronic stress cessation.
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Discordant CSF/plasma HIV-1 RNA in patients with unexplained low-level viraemia.
Nightingale, Sam; Geretti, Anna Maria; Beloukas, Apostolos; Fisher, Martin; Winston, Alan; Else, Laura; Nelson, Mark; Taylor, Stephen; Ustianowski, Andrew; Ainsworth, Jonathan; Gilson, Richard; Haddow, Lewis; Ong, Edmund; Watson, Victoria; Leen, Clifford; Minton, Jane; Post, Frank; Pirmohamed, Munir; Solomon, Tom; Khoo, Saye
2016-12-01
The central nervous system has been proposed as a sanctuary site where HIV can escape antiretroviral control and develop drug resistance. HIV-1 RNA can be at higher levels in CSF than plasma, termed CSF/plasma discordance. We aimed to examine whether discordance in CSF is associated with low level viraemia (LLV) in blood. In this MRC-funded multicentre study, we prospectively recruited patients with LLV, defined as one or more episode of unexplained plasma HIV-1 RNA within 12 months, and undertook CSF examination. Separately, we prospectively collected CSF from patients undergoing lumbar puncture for a clinical indication. Patients with durable suppression of viraemia and no evidence of CNS infection were identified as controls from this group. Factors associated with CSF/plasma HIV-1 discordance overall were examined. One hundred fifty-three patients were recruited across 13 sites; 40 with LLV and 113 undergoing clinical lumbar puncture. Seven of the 40 (18 %) patients with LLV had CSF/plasma discordance, which was significantly more than 0/43 (0 %) with durable suppression in blood from the clinical group (p = 0.005). Resistance associated mutations were shown in six CSF samples from discordant patients with LLV (one had insufficient sample for testing), which affected antiretroviral therapy at sampling in five. Overall discordance was present in 20/153 (13 %) and was associated with nadir CD4 but not antiretroviral concentrations in plasma or CSF. CSF/plasma discordance is observed in patients with LLV and is associated with antiretroviral resistance associated mutations in CSF. The implications for clinical practice require further investigation.
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Direct spectrophotometric measurement of supra-physiological levels of ascorbate in plasma.
Witmer, Jordan R; Wetherell, Bailey J; Wagner, Brett A; Du, Juan; Cullen, Joseph J; Buettner, Garry R
2016-08-01
Supra-physiological concentrations of ascorbate, vitamin C, in blood, greater than 1mM, achieved through intravenous administration (IV), are being tested in clinical trials to treat human disease, e.g. cancer. These trials need information on the high levels of ascorbate achieved in blood upon IV administration of pharmacological ascorbate so appropriate clinical decisions can be made. Here we demonstrate that in the complex matrix of human blood plasma supra-physiological levels of ascorbate can be quantified by direct UV spectroscopy with use of a microvolume UV-vis spectrophotometer. Direct quantitation of ascorbate in plasma in the range of 2.9mM, lower limit of detection, up to at least 35mM can be achieved without any sample processing, other than centrifugation. This approach is rapid, economical, and can be used to quantify supraphysiological blood levels of ascorbate associated with the use of IV administration of pharmacological ascorbate to treat disease. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
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A Spectrum of PCSK9 Alleles Contributes to Plasma Levels of Low-Density Lipoprotein Cholesterol
Kotowski, Ingrid K.; Pertsemlidis, Alexander; Luke, Amy; Cooper, Richard S.; Vega, Gloria L.; Cohen, Jonathan C.; Hobbs, Helen H.
2006-01-01
Selected missense mutations in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) cause autosomal dominant hypercholesterolemia, whereas nonsense mutations in the same gene are associated with low plasma levels of low-density lipoprotein cholesterol (LDL-C). Here, DNA sequencing and chip-based oligonucleotide hybridization were used to determine whether other sequence variations in PCSK9 contribute to differences in LDL-C levels. The coding regions of PCSK9 were sequenced in the blacks and whites from the Dallas Heart Study (n=3,543) who had the lowest (<5th percentile) and highest (>95th percentile) plasma levels of LDL-C. Of the 17 missense variants identified, 3 (R46L, L253F, and A443T) were significantly and reproducibly associated with lower plasma levels of LDL-C (reductions ranging from 3.5% to 30%). None of the low–LDL-C variants were associated with increased hepatic triglyceride content, as measured by proton magnetic resonance spectroscopy. This finding is most consistent with the reduction in LDL-C being caused primarily by accelerating LDL clearance, rather than by reduced lipoprotein production. Association studies with 93 noncoding single-nucleotide polymorphisms (SNPs) at the PCSK9 locus identified 3 SNPs associated with modest differences in plasma LDL-C levels. Thus, a spectrum of sequence variations ranging in frequency (from 0.2% to 34%) and magnitude of effect (from a 3% increase to a 49% decrease) contribute to interindividual differences in LDL-C levels. These findings reveal that PCSK9 activity is a major determinant of plasma levels of LDL-C in humans and make it an attractive therapeutic target for LDL-C lowering. PMID:16465619
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Jones, Peter J H; Lin, Lin; Gillingham, Leah G; Yang, Haifeng; Omar, Jaclyn M
2014-12-01
N-Acylethanolamines (NAEs) are endogenous lipid-signaling molecules involved in satiety and energetics; however, how diet impacts circulating NAE concentrations and their downstream metabolic actions in humans remains unknown. Objectives were to examine effects of diets enriched with high-oleic canola oil (HOCO) or HOCO blended with flaxseed oil (FXCO), compared with a Western diet (WD), on plasma NAE levels and the association with energy expenditure and substrate oxidation. Using a randomized controlled crossover design, 36 hypercholesterolemic participants consumed three isoenergetic diets for 28 days, each containing 36% energy from fat, of which 70% was HOCO, FXCO, or WD. Ultra-performance liquid chromatography-MS/MS was used to measure plasma NAE levels and indirect calorimetry to assess energy expenditure and substrate oxidation. After 28 days, compared with WD, plasma oleoylethanolamide (OEA) and alpha-linolenoyl ethanolamide (ALEA) levels were significantly increased in response to HOCO and FXCO (P = 0.002, P < 0.001), respectively. Correlation analysis demonstrated an inverse association between plasma OEA levels and percent body fat (r = -0.21, P = 0.04), and a positive association was observed between the plasma arachidonoyl ethanolamide (AEA)/OEA ratio and android:gynoid fat (r = 0.23, P = 0.02), respectively. Results suggest that plasma NAE levels are upregulated via their dietary lipid substrates and may modulate regional and total fat mass through lipid-signaling mechanisms. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.
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FABP4 plasma levels are increased in familial combined hyperlipidemia
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
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PAI-1 4G/5G polymorphism and plasma levels association in patients with coronary artery disease.
Lima, Luciana Moreira; Carvalho, Maria das Graças; Fonseca Neto, Cirilo Pereira; Garcia, José Carlos Faria; Sousa, Marinez Oliveira
2011-12-01
Type-1 plasminogen activator inhibitor (PAI-1) 4G/5G polymorphism may influence the PAI-1 expression. High plasma levels of PAI-1 are associated with coronary artery disease (CAD). This study investigated the influence of PAI-1 4G/5G polymorphism on plasma PAI-1 levels and its association with CAD assessed by coronary angiography. Blood sample of 35 individuals with angiographically normal coronary arteries, 31 individuals presenting mild/moderate atheromatosis, 57 individuals presenting severe atheromatosis and 38 healthy individuals (controls) were evaluated. In patients and controls, the PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. Plasma PAI-1 levels were quantified by ELISA assay (American Diagnostica). No difference was found between groups regarding age, gender and body mass index. Plasma PAI-1 levels and 4G/4G genotype frequency were significantly higher in the severe atheromatosis group compared to the other groups (p<0.001). Furthermore, patients with 4G/4G genotype (r=0.28, p<0.001) had significantly higher plasma PAI-1 levels than those with 5G/5G genotype (r=0.02, p=0.4511). In addition, in a multiple logistic regression model, adjusted for all the other variables, PAI-1 was observed to be independently associated with CAD > 70% (p<0.001). The most important finding of this study was the association between 4G/4G genotype, high plasma PAI-1 levels and coronary stenosis higher than 70% in Brazilian individuals. Whether high plasma PAI-1 levels are a decisive factor for atherosclerosis worsening or it is a consequence remains to be established.
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Do Resting Plasma β-Endorphin Levels Predict Responses to Opioid Analgesics?
Bruehl, Stephen; Burns, John W; Gupta, Rajnish; Buvanendran, Asokumar; Chont, Melissa; Orlowska, Daria; Schuster, Erik; France, Christopher R
2017-01-01
Clinically feasible predictors of opioid analgesic responses for use in precision pain medicine protocols are needed. This study evaluated whether resting plasma β-endorphin (BE) levels predicted responses to an opioid analgesic, and whether chronic pain status or sex moderated these effects. Participants included 73 individuals with chronic low back pain (CLBP) and 88 pain-free controls, all using no daily opioid analgesics. Participants attended 2 identical laboratory sessions during which they received either intravenous morphine (0.08 mg/kg) or saline placebo, with blood samples obtained before drug administration to assay resting plasma BE levels. Once peak drug activity was achieved in each session, participants engaged in an ischemic forearm pain task (ISC) and a heat pain task. Morphine analgesic effects were derived reflecting the difference in pain outcomes between placebo and morphine conditions. In hierarchical regressions, significant Type (CLBP vs. control)×BE interactions (Ps<0.05) were noted for morphine effects on ISC tolerance, ISC intratask pain ratings, and thermal VAS unpleasantness ratings. These interactions derived primarily from associations between higher BE levels and smaller morphine effects restricted to the CLBP subgroup. All other BE-related effects, including sex interactions, for predicting morphine analgesia failed to reach statistical significance. BE was a predictor of morphine analgesia for only 3 out of 9 outcomes examined, with these effects moderated by chronic pain status but not sex. On the whole, results do not suggest that resting plasma BE levels are likely to be a clinically useful predictor of opioid analgesic responses.
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Reduced plasma levels of coagulation factors in relation to prostate cancer.
Beecken, Wolf-Dietrich; Bentas, Wassilios; Engels, Knut; Glienke, Wolfgang; Urbschat, Anja; Jonas, Dietger; Binder, Jochen; Scharrer, Inge
2002-10-01
Prostate cancer has historically been associated with coagulation abnormalities. This study was undertaken to investigate the prevalence of abnormalities of coagulation factors in patients with prostate cancer before and after radical prostatectomy (RP). Because coagulation factors have been shown to be involved in tumor angiogenesis, the vascular density of the prostate tumors was assessed. Plasma of 40 consecutive patients with histologically proven prostate cancer was investigated pre-RP and post-RP. The antigen level for antithrombin, plasminogen activator inhibitor-1, and heparin cofactor-II, and the plasma activity of antithrombin and plasminogen were determined by using immunologic and chromogenic assays. The values of these assays were compared with a group of 28 male, age-matched patients without any evidence of cancer and 18 patients with orthopedic interventions preoperatively and postoperatively. The vascular density of the prostate tumors was assessed by staining paraffin sections with an antibody to CD34. The median plasma antigen levels and/or activities of the investigated factors were below normal in the prostate cancer patients before RP. Furthermore, coagulation factors were significantly lower than in the age-matched control group and patients before and after orthopedic surgery. In prostate cancer patients, the median values of all investigated factors went up to normal levels within 2 weeks after RP, whereas postsurgical levels in orthopedic patients remained stable. No correlations to tumor parameters have been observed. We assume that the reduction of these coagulation factors is a principle concept in prostate cancer that needs further investigation. Copyright 2002 Wiley-Liss, Inc.
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Fetal Hypothalamus-Pituitary-Adrenal Responses to Estradiol Sulfate
2011-01-01
Estradiol (E2) is an important modifier of the activity of the fetal hypothalamus-pituitary-adrenal axis. We have reported that estradiol-3-sulfate (E2SO4) circulates in fetal blood in far higher concentrations than E2 and that the fetal brain expresses steroid sulfatase, required for local deconjugation of E2SO4. We performed the present study to test the hypothesis that chronic infusion of E2SO4 chronically increases ACTH and cortisol secretion and that it shortens gestation. Chronically catheterized fetal sheep were treated with E2SO4 intracerebroventricular (n = 5), E2SO4 iv (n = 4), or no steroid infusion (control group, n = 5). Fetuses were subjected to arterial blood sampling every other day until spontaneous birth for plasma hormone analysis. Treatment with E2SO4 attenuated preparturient increases in ACTH secretion near term without affecting the ontogenetic rise in plasma cortisol. Infusion of E2SO4 intracerebroventricularly significantly increased plasma E2, plasma E2SO4, and plasma progesterone and shortened gestation compared with all other groups. These results are consistent with the conclusion that E2SO4: 1) interacts with the hypothalamus-pituitary-adrenal axis primarily by stimulating cortisol secretion and inhibiting ACTH and pro-ACTH secretion by negative feedback; and 2) stimulates the secretion of E2 and E2SO4. We conclude that the endocrine response to E2SO4 in the fetus is not identical with the response to E2. PMID:21952234
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Bjørndal, Bodil; Alterås, Eva Katrine; Lindquist, Carine; Svardal, Asbjørn; Skorve, Jon; Berge, Rolf K
2018-01-01
The 4-thia fatty acid tetradecylthiopropionic acid (TTP) is known to inhibit mitochondrial β-oxidation, and can be used as chemically induced hepatic steatosis-model in rodents, while 3-thia fatty acid tetradecylthioacetic acid (TTA) stimulates fatty acid oxidation through activation of peroxisome proliferator activated receptor alpha (PPARα). We wished to determine how these two compounds affected in vivo respiration and mitochondrial efficiency, with an additional goal to elucidate whether mitochondrial function is reflected in plasma acylcarnitine levels. C57BL/6 mice were divided in 4 groups of 10 mice and fed a control low-fat diet, low-fat diets with 0.4% ( w /w) TTP, 0.4% TTA or a combination of these two fatty acids for three weeks ( n = 10). At sacrifice, β-oxidation and oxidative phosphorylation (OXPHOS) capacity was analysed in fresh liver samples. Hepatic mitochondria were studied using transmission electron microscopy. Lipid classes were measured in plasma, heart and liver, acylcarnitines were measured in plasma, and gene expression was measured in liver. The TTP diet resulted in hepatic lipid accumulation, plasma L-carnitine and acetylcarnitine depletion and elevated palmitoylcarnitine and non-esterified fatty acid levels. No significant lipid accumulation was observed in heart. The TTA supplement resulted in enhanced hepatic β-oxidation, accompanied by an increased level of acetylcarnitine and palmitoylcarnitine in plasma. Analysis of mitochondrial respiration showed that TTP reduced oxidative phosphorylation, while TTA increased the maximum respiratory capacity of the electron transport system. Combined treatment with TTP and TTA resulted in a profound stimulation of genes involved in the PPAR-response and L-carnitine metabolism, and partly prevented triacylglycerol accumulation in the liver concomitant with increased peroxisomal β-oxidation and depletion of plasma acetylcarnitines. Despite an increased number of mitochondria in the liver
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Simiti, Luminita Animarie Vida; Todor, Irina; Stoia, Mirela Anca; Goidescu, Cerasela Mihaela; Anton, Florin Petru; Farcas, Anca Daniela
2016-01-01
The involvement of leptin in atherosclerosis is very complex, including inflammation, the oxidative stress and thrombosis. Leptin has atherogenic and also antiatherogenic actions. In obesity elevated leptin levels are not sufficient to prevent disturbances of energy balance, suggesting that obese people are leptin resistant. The aim of the study was to investigate the relationship between baseline plasma levels of leptin and the incidence of new ischemic events in patients with CHD. Plasma levels of leptin in fifty nine consecutive patients (29 men and 30 women) with CHD hospitalized in the County Emergency Clinical Hospital of Cluj-Napoca were measured using commercially available ELISA at admission. Patients with active infectious disease, neoplasia, acute coronary syndrome, stroke, hepatic or renal failure and severe heart failure were excluded The relationship between leptin levels and incident cardiovascular events (angina, nonfatal myocardial infarction or heart failure) over two years follow-up was studied using MEDCALC version 9.6. 73.6% patients with CHD were overweight or suffered of obesity. There were no significant differences between women and men regarding the plasma levels of leptin, the body mass index (BMI), the number of rehospitalizations, rehospitalizations/patient, diabetes mellitus, hypertension or dyslipidemia. Only in women plasma levels of leptin are correlated with BMI. As compared with men with overweight and obesity (BMI≥25kg/m(2)), plasma levels of leptin were significantly higher in women with overweight and obesity (3905.97±463.91 pg/ml vs 1835.17±533.9 pg/ml) (p<0.002). Patient gender could not be demonstrated to influence prognosis. During the two years we recorded one or more readmissions in 26 patients (44%). The analysis of time till readmission using Kaplan-Meier curves, showed that leptin level (cut-off 2000 pg/ml, HR 0.38, 95% CI 0.17-0.83; p=0.01) and BMI (cut-off 28 kg/m(2), HR 0.3164, 95% CI 0.145-0.0689; p<0.01) were
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Wang, H; Weng, C; Chen, H
2017-07-01
Variants in G protein-coupled inward rectifier K + channels 4 (GIRK4 also known as KCNJ5) gene are associated with primary aldosteronism, which is the most common cause of secondary hypertension. The KCNJ5 rs2604204 variant was shown to be common (minor allele frequency=32.5%) in Chinese patients with essential hypertension (EH). The relationship between KCNJ5 variant and plasma aldosterone (ALD) levels in EH patients has not been reported. We collected 229 patients with newly diagnosed EH without any antihypertensive agents. According to the median standing plasma ALD, high-ALD and control groups were divided. Clinical data and blood samples were collected. KCNJ5 rs2604204 genotype was determined by PCR. The results showed that the levels of triglyceride, uric acid, insulin, insulin resistance (IR) index, renin, angiotensin I (Ang I), angiotensin II (Ang II), cortisol, 24 h mean systolic blood pressure (SBP) and daytime mean SBP were significantly increased in the high-ALD group than those in the control group, as well as 24 h s.d. of SBP and diastolic BP (DBP), and 24 h coefficient of variance of SBP and DBP. Notably, the distribution frequency of AC and CC genotypes, and the C allele of KCNJ5 were also significantly higher in the high-ALD group. Logistic regression analysis showed that the C allele of KCNJ5 rs2604204 was one risk factor for increased plasma ALD in Chinese EH patients (P=0.008, odds ratio=2.2 (95% confidence interval 1.2-4.1)). Our findings indicated that the variation of plasma ALD might be associated with increased IR and BP variability. Moreover, KCNJ5 rs2604204 polymorphism was related to increased plasma ALD level, but also plasma renin, Ang I and II levels in newly diagnosed, never-treated EH patients.
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Impact of bone lead and bone resorption on plasma and whole blood lead levels during pregnancy.
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.
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Determination of porcine plasma follitropin levels during superovulation treatment in cows.
Demoustier, M M; Beckers, J F; Van Der Zwalmen, P; Closset, J; Gillard, J L; Ectors, F
1988-08-01
Porcine follicle stimulating hormone (pFSH) and porcine luteinizing hormone (pLH), are widely used to induce superovulation in cows. An advantage of this treatment is that the LH:FSH ratio can be varied to optimize the growth of the ovarian follicles. However, due to the relatively short half-life of FSH, the superovulatory treatment requires numerous injections. A performant radioimmunoassay system (sensitivity=0.2 ng/ml plasma) was used to determine plasma pFSH levels in cows that were superovulated with 2 daily injections of 4 Armour Units (A.U.) of pFSH for 4 d. From plasma profiles, the half-life and the disappearance of pFSH were estimated at 5 h and at 10 to 12 h, respectively, confirming the necessity of using two daily injections.
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Plasma big endothelin-1 level and the severity of new-onset stable coronary artery disease.
Chen, Juan; Chen, Man-Hua; Guo, Yuan-Lin; Zhu, Cheng-Gang; Xu, Rui-Xia; Dong, Qian; Li, Jian-Jun
2015-01-01
To investigate the usefulness of the plasma big endothelin-1 (big ET-1) level in predicting the severity of new-onset stable angiography-proven coronary artery disease (CAD). A total of 963 consecutive stable CAD patients with more than 50% stenosis in at least one main vessel were enrolled. The patients were classified into the three groups according to the tertile of the Gensini score (GS, low GS ＜20, n=300; intermediate GS 20-40, n=356 and high GS ＞40, n=307), and the relationship between the big ET-1 level and GS was evaluated. The plasma levels of big ET-1 increased significantly in association with increases in the GS tertile (p=0.007). A multivariate analysis suggested that the plasma big ET-1 level was an independent predictor for a high GS (OR=2.26, 95%CI: 1.23-4.15, p=0.009), and there was a positive correlation between the big ET-1 level and the GS (r=0.20, p=0.000). The area under the receiver operating characteristic curve (AUC) for the big ET-1 level in predicting a high GS was 0.64 (95% CI 0.60-0.68, p=0.000), and the optimal cutoff value for the plasma big ET-1 level for predicting a high GS was 0.34 fmol/mL, with a sensitivity of 62.6% and specificity of 60.3%. In the high-big ET-1 level group (≥0.34 fmol/mL), there were significantly increased rates of three-vessel disease (43.6% vs. 35.4%, p=0.017) and a high GS [31 (17-54) vs. 24 (16-44), p=0.001] compared with that observed in the low-big ET-1 level group. The present findings indicate that the plasma big ET-1 level is a useful predictor of the severity of new-onset stable CAD associated with significant stenosis.
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The response of C19- and some C21-steroids during Synacthen and insulin tolerance test.
Šimůnková, Kateřina; Dušková, Michaela; Kolatorova, Lucie; Kosák, Mikuláš; Hill, Martin; Jandíková, Hana; Pospíšilová, Hana; Šrámková, Monika; Springer, Drahomíra; Stárka, Luboslav
2018-01-30
Testing of the adrenal function with ACTH 1-24 (Synacthen test) or insulin (insulin tolerance test-ITT) is commonly used. The question of ongoing debate is the dose of Synacthen. Moreover, it may be important from the physiological point of view besides measurement of cortisol levels and 17α-hydroxy-progesterone to know also the response of other steroids to these test. The plasma levels of 24 free steroids and their polar conjugates were followed after stimulation of 1 μg, 10 μg and 250 μg of ACTH 1-24 and after insulin administration in thirteen healthy subjects. The study aimed to describe a response of steroid metabolome to various doses of ACTH 1-24 and to find the equivalency of these tests. The additional ambition was to contribute to understanding of physiology of these stimulation tests and suggest an additional marker for HPA axis evaluation. No increase of most conjugated steroids and even decrease of some of them during all of the Synacthen tests and ITT at 60th min were observed. The levels of steroid conjugates decreased in ITT but did not during all of the Synacthen tests by 20 min of each test. Testosterone and estradiol did not increase during the Synacthen tests or ITT as expected. The results suggest that the conjugated steroids in the circulation can serve as reserve stock for rapid conversion into free steroids in the first minutes of the stress situation. Various doses of ACTH 1-24 used in the Synacthen tests implicate earlier or later occurrence of maximal response of stimulated steroids. The equivalent dose to ITT and standard 250 μg of ACTH 1-24 seemed to be dose of 10 μg ACTH 1-24 producing the similar response in all of the steroids in the 60th min of the test. Copyright © 2018 Elsevier Inc. All rights reserved.
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Cushing, Melissa M; Asmis, Lars; Calabia, Carmencita; Rand, Jacob H; Haas, Thorsten
2016-08-01
Factor V (FV) plays an important role in coagulation. As no purified concentrate is available to restore critical FV levels, the main blood product used to replace FV is plasma. The aim of the present in vitro study was to compare the efficacy of the different available plasma products on the reversal of moderate and severe FV deficiency as assessed by ROTEM® and FV levels. Five different plasma products (6 batches of each) were compared to determine their effectiveness in replacing FV in plasma moderately or severely deficient in FV. Effectiveness was measured using the ROTEM® EXTEM clotting time (CT) and a factor V assay. FFP, plasma frozen within 24 hours (FP24), Octaplas (solvent/detergent treated pooled plasma), as well as Octaplas and FP24 thawed and stored for 5 days (Octaplas TP and TP), were all used for in vitro replacement of FV. TP was significantly less effective at reversing a prolonged EXTEM CT and FV levels in FV deficient plasma than other tested products. There were no significant differences in EXTEM CT between Octaplas and Octaplas TP, while factor V activity was significantly lower in the Octaplas TP. There was no significant difference between Octaplas and FFP for EXTEM CT or FV activity. Octaplas and Octaplas TP appear to have an equivalent ability to improve the EXTEM CT and could be considered as a treatment alternative to FFP in patients with FV deficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.
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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.
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Interrenal dysfunction in fish from contaminated sites: In vivo and in vitro assessment
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hontela, A.
1998-01-01
Cortisol, synthesized in the interrenal cells of teleost head kidney, has a major role in the physiologic response to physical and chemical stressors. Plasma levels of cortisol increase in physiologically competent fish acutely exposed to stressors such as cadmium or mercury. The effects of chronic low level exposures are less well understood. The author has diagnosed an endocrine impairment characterized by a reduced capacity to elevate plasma cortisol levels in response to an acute standardized capture stress in yellow perch (Perca flavescens) and in northern pike (Esox lucius) sampled at sites contaminated by mixtures of pollutants (heavy metals, polycyclic aromaticmore » hydrocarbons, and polychlorinated biphenyls), by heavy metals, or by bleached kraft mill effluent. The studies with fish, as well as with amphibians at contaminated sites, demonstrated that low level chronic exposures impair secretion of corticosteroids. The author has developed new tests for assessment of the functional integrity of teleost and amphibian interrenal tissue using an adrenocorticotropic hormone (ACTH) challenge, in vivo and in vitro. The reduced ability to respond to ACTH indicates that the normal neuroendocrine response to stressors may be disrupted and that the ability to cope with biotic and abiotic stressors in the environment may be significantly reduced in the impaired animals.« less
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Serotonin (5-HT) receptor 5A sequence variants affect human plasma triglyceride levels
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
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Crossing the other side of the algorithm: a challenging case of adrenal Cushing's syndrome.
Antonio, Imelda Digna Soberano; Sandoval, Mark Anthony Santiago; Lantion-Ang, Frances Lina
2011-12-01
The diagnosis of endogenous Cushing's syndrome and its aetiology involved documenting the hypercotisolism and then determining whether that hypercortisolism is adrenocorticotropic hormone-dependent (ACTH-dependent) or not. Hence, following the algorithm, an undetected ACTH level points to an adrenal Cushing's while a detectable or elevated ACTH level points to either a pituitary or ectopic Cushing's syndrome. The authors present a case of florid adrenal Cushing's syndrome initially presenting with a normal ACTH level, which led to the investigation for an ACTH-secreting tumour. Adding to the confusion, a MRI done showed an intrasellar focus. Knowledge of how ACTH-dependent (versus ACTH-independent) Cushing's syndrome manifests clinically, supported by results of repeat laboratory tests, led to the true diagnosis. This case illustrates that a detectable ACTH does not rule out an adrenal Cushing's syndrome nor does a positive pituitary imaging confirm Cushing's disease.
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Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans
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
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Al-Biltagi, Mohammed A; Abo-Elezz, Ahmed Ahmed Abd ElBasset; Abu-Ela, Khaled Talaat; Suliman, Ghada Abudelmomen; Sultan, Tamer Gomaa Hassan
2017-06-01
The objective of this study was to evaluate the prognostic significance of soluble intercellular adhesion molecule 1 (sICAM-1) measurement in plasma for the prediction of outcome of acute lung injury (ALI) in children that may allow early recognition of critical cases. The study was performed as a prospective, controlled cohort study involving 40 children with ALI and 30 healthy children. The plasma level of sICAM-1 was measured at days 1 and 3 of development of ALI for the patient group and measured only once for the control group. C-Reactive protein was measured in both groups on day 1 only. There was significant increase in sICAM-1 in the patient group than in the control group ( P = .001*). The mortality rate reached 55% in children with ALI. The ceased group had significantly higher plasma sICAM-1 levels both at days 1 and 3 than the survived group ( P < .001*), and there was positive correlation between plasma sICAM-1 level and both duration of mechanical ventilation and the death rate, but more significant correlation was observed with plasma sICAM-1 levels at day 3 than day 1. Plasma sICAM-1 level served as a good predictor biomarker for both mechanical ventilation duration and the mortality risk in children with ALI.
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Borges, Natália A; Stenvinkel, P; Bergman, P; Qureshi, A R; Lindholm, B; Moraes, C; Stockler-Pinto, M B; Mafra, D
2018-04-12
Components present in the diet, L-carnitine, choline, and betaine are metabolized by gut microbiota to produce metabolites such as trimethylamine-N-oxide (TMAO) that appear to promote cardiovascular disease in chronic kidney disease (CKD) patients. The objective of this pilot study was to evaluate the effects of probiotic supplementation for 3 months on plasma TMAO levels in CKD patients on hemodialysis (HD). A randomized, double-blind trial was performed in 21 patients [54.8 ± 10.4 years, nine men, BMI 26.1 ± 4.8 kg/m 2 , dialysis vintage 68.5 (34.2-120.7) months]. Ten patients were randomly allocated to the placebo group and 11 to the probiotic group [three capsules, totaling 9 × 10 13 colony-forming units per day of Streptococcus thermophilus (KB19), Lactobacillus acidophilus (KB27), and Bifidobacteria longum (KB31). Plasma TMAO, choline, and betaine levels were measured by LC-MS/MS at baseline and after 3 months. While TMAO did not change after probiotic supplementation, there was a significant increase in betaine plasma levels. In contrast, the placebo group showed a significant decrease in plasma choline levels. Short-term probiotic supplementation does not appear to influence plasma TMAO levels in HD patients. Long-term studies are needed to determine whether probiotics may affect TMAO production in CKD patients.
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Tsuchiya, T; Horii, I
1995-01-01
Time-course variations in plasma testosterone levels after various periods of immobilization stress (10 min, 30 min, 2 h, 6 h) were examined in male Syrian hamsters. The immobilization stress consisted of placing the animals in a prone position and wrapping them with flexible steel wire gauze. This was done at room temperature. Testosterone levels were determined in blood samples taken after the hamsters were decapitated. Chronic (2 h, 6 h) immobilization stress produced a drastic and enduring fall in plasma testosterone levels. Reduction of plasma testosterone following the 6-h immobilization stress was observed even 18 h after the stress had been relieved. However, acute (10 min, 30 min) immobilization stress did not influence plasma testosterone. These findings indicated that the effect of immobilization stress on plasma testosterone in hamsters was not biphasic, which it is in rats. Further, these results suggest that immobilization stress in hamsters would be a valuable technique with which to investigate the effects of physiological ranges of testosterone on physiological and psychological functions.
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2013-01-01
Background Adrenal Cushing’s syndrome caused by ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) can be accompanied by aberrant responses to hormonal stimuli. We investigated the prevalence of adrenocortical reactions to these stimuli in a large cohort of AIMAH patients, both in vivo and in vitro. Methods In vivo cortisol responses to hormonal stimuli were studied in 35 patients with ACTH-independent bilateral adrenal enlargement and (sub-)clinical hypercortisolism. In vitro, the effects of these stimuli on cortisol secretion and steroidogenic enzyme mRNA expression were evaluated in cultured AIMAH and other adrenocortical cells. Arginine-vasopressin (AVP) receptor mRNA levels were determined in the adrenal tissues. Results Positive serum cortisol responses to stimuli were detected in 27/35 AIMAH patients tested, with multiple responses within individual patients occurring for up to four stimuli. AVP and metoclopramide were the most prevalent hormonal stimuli triggering positive responses in vivo. Catecholamines induced short-term cortisol production more often in AIMAH cultures compared to other adrenal cells. Short- and long-term incubation with AVP increased cortisol secretion in cultures of AIMAH cells. AVP also increased steroidogenic enzyme mRNA expression, among which an aberrant induction of CYP11B1. AVP type 1a receptor was the only AVPR expressed and levels were high in the AIMAH tissues. AVPR1A expression was related to the AVP-induced stimulation of CYP11B1. Conclusions Multiple hormonal signals can simultaneously induce hypercortisolism in AIMAH. AVP is the most prevalent eutopic signal and expression of its type 1a receptor was aberrantly linked to CYP11B1 expression. PMID:24034279
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Mercer, Aaron J; Stuart, Ronald C; Attard, Courtney A; Otero-Corchon, Veronica; Nillni, Eduardo A; Low, Malcolm J
2014-04-15
Hypothalamic proopiomelanocortin (POMC) neurons constitute a critical anorexigenic node in the central nervous system (CNS) for maintaining energy balance. These neurons directly affect energy expenditure and feeding behavior by releasing bioactive neuropeptides but are also subject to signals directly related to nutritional state such as the adipokine leptin. To further investigate the interaction of diet and leptin on hypothalamic POMC peptide levels, we exposed 8- to 10-wk-old male POMC-Discosoma red fluorescent protein (DsRed) transgenic reporter mice to either 24-48 h (acute) or 2 wk (chronic) food restriction, high-fat diet (HFD), or leptin treatment. Using semiquantitative immunofluorescence and radioimmunoassays, we discovered that acute fasting and chronic food restriction decreased the levels of adrenocorticotropic hormone (ACTH), α-melanocyte-stimulating hormone (α-MSH), and β-endorphin in the hypothalamus, together with decreased DsRed fluorescence, compared with control ad libitum-fed mice. Furthermore, acute but not chronic HFD or leptin administration selectively increased α-MSH levels in POMC fibers and increased DsRed fluorescence in POMC cell bodies. HFD and leptin treatments comparably increased circulating leptin levels at both time points, suggesting that transcription of Pomc and synthesis of POMC peptide products are not modified in direct relation to the concentration of plasma leptin. Our findings indicate that negative energy balance persistently downregulated POMC peptide levels, and this phenomenon may be partially explained by decreased leptin levels, since these changes were blocked in fasted mice treated with leptin. In contrast, sustained elevation of plasma leptin by HFD or hormone supplementation did not significantly alter POMC peptide levels, indicating that enhanced leptin signaling does not chronically increase Pomc transcription and peptide synthesis.
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Chen, Shiou-Lan; Lee, Sheng-Yu; Chang, Yun-Hsuan; Wang, Tzu-Yun; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band
2015-02-02
BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of long-term heroin use. Thus, we investigated the relationships between brain-derived neurotrophic factor (BDNF) plasma concentrations and the BDNF Val66Met nucleotide polymorphism (SNP) in heroin-dependent patients. The pretreatment expression levels of plasma BDNF and the BDNF Val66Met SNP in 172 heroin-dependent patients and 102 healthy controls were checked. BDNF levels were significantly lower in patients (F = 52.28, p < 0.0001), but the distribution of the SNP was not significantly different. Nor were plasma BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not affect plasma BDNF levels in our participants. In heroin-dependent patients, plasma BDNF levels were negatively correlated with the length of heroin dependency. Long-term (>15 years) users had significantly lower plasma BDNF levels than did short-term (<5 years) users. We conclude that plasma BDNF concentration in habitual heroin users are not affected by BDNF Val66Met gene variants, but by the length of the heroin dependency.
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Chen, Shiou-Lan; Lee, Sheng-Yu; Chang, Yun-Hsuan; Wang, Tzu-Yun; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band
2015-01-01
BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of long-term heroin use. Thus, we investigated the relationships between brain-derived neurotrophic factor (BDNF) plasma concentrations and the BDNF Val66Met nucleotide polymorphism (SNP) in heroin-dependent patients. The pretreatment expression levels of plasma BDNF and the BDNF Val66Met SNP in 172 heroin-dependent patients and 102 healthy controls were checked. BDNF levels were significantly lower in patients (F = 52.28, p < 0.0001), but the distribution of the SNP was not significantly different. Nor were plasma BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not affect plasma BDNF levels in our participants. In heroin-dependent patients, plasma BDNF levels were negatively correlated with the length of heroin dependency. Long-term (>15 years) users had significantly lower plasma BDNF levels than did short-term (<5 years) users. We conclude that plasma BDNF concentration in habitual heroin users are not affected by BDNF Val66Met gene variants, but by the length of the heroin dependency. PMID:25640280
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Bayraktar, F; Kebapcilar, L; Kocdor, M A; Asa, S L; Yesil, S; Canda, S; Demir, T; Saklamaz, A; Seçil, M; Akinci, B; Yener, S; Comlekci, A
2006-09-01
Ectopic production of corticotropin-releasing hormone (CRH) by a pheochromocytoma is an infrequent cause of Cushing's syndrome. We report the case of a 43-year-old man with Cushing's syndrome due to a CRH-producing adrenal pheochromocytoma. The patient had clinical and biochemical evidence of hypercortisolism in conjunction with high ACTH levels and non-suppressible serum cortisol levels on low-dose and high-dose dexamethasone suppression testing. In addition to these clinical features of one month's duration, the patient developed symptoms of pheochromocytoma including headache, hypertension that was resistant to conventional therapy and excessive sweating. Biochemical testing confirmed elevated 24-hour urinary catecholamines and metabolites. Abdominal CT revealed a 4.5 x 4 x 3.5 cm mass in the left adrenal gland. He underwent elective left adrenalectomy. Light microscopic and immunochemical studies revealed a pheochromocytoma that contained immunoreactive CRH and was negative for ACTH. Plasma ACTH and dexamethasone supression tests normalized after surgery. This is an unusual case of a CRH-secreting pheochromocytoma. This was complicated by renal infarction, illustrating further the complexity of Cushing's syndrome in a patient with pheochromocytoma caused by CRH hypersecretion.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hossain, Ekhtear; Islam, Khairul; Yeasmin, Fouzia
Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nailsmore » were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose–response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions. -- Highlights: ► Plasma Big ET-1 is an indicator of endothelial damage. ► Plasma Big ET-1 level increases dose-dependently in arsenic exposed individuals. ► Study subjects in arsenic-endemic areas with hypertension have elevated Big ET-1 levels. ► Study subjects with
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Hildebrandt, Tom; Shope, Sydney; Varangis, Eleanna; Klein, Diane; Pfaff, Donald W; Yehuda, Rachel
2014-06-01
Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer. Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity×frequency of exercise, age, and education abstained from exercise for 24 h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image. Between group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence. The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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Plasma amyloid levels within the Alzheimer's process and correlations with central biomarkers.
Hanon, Olivier; Vidal, Jean-Sébastien; Lehmann, Sylvain; Bombois, Stéphanie; Allinquant, Bernadette; Tréluyer, Jean-Marc; Gelé, Patrick; Delmaire, Christine; Blanc, Fredéric; Mangin, Jean-François; Buée, Luc; Touchon, Jacques; Hugon, Jacques; Vellas, Bruno; Galbrun, Evelyne; Benetos, Athanase; Berrut, Gilles; Paillaud, Elèna; Wallon, David; Castelnovo, Giovanni; Volpe-Gillot, Lisette; Paccalin, Marc; Robert, Philippe-Henri; Godefroy, Olivier; Dantoine, Thierry; Camus, Vincent; Belmin, Joël; Vandel, Pierre; Novella, Jean-Luc; Duron, Emmanuelle; Rigaud, Anne-Sophie; Schraen-Maschke, Suzanna; Gabelle, Audrey
2018-02-17
Diagnostic relevance of plasma amyloid β (Aβ) for Alzheimer's disease (AD) process yields conflicting results. The objective of the study was to assess plasma levels of Aβ 42 and Aβ 40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers. One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included. Plasma Aβ 1-42 and Aβ 1-40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively (P = .01 for overall difference between groups for Aβ 1-42 and P = .04 for Aβ 1-40 ). Globally, plasma Aβ 1-42 correlated with age, Mini-Mental State Examination, and APOE ε4 allele. Plasma Aβ 1-42 correlated with all CSF biomarkers in MCI but only with CSF Aβ 42 in AD. Plasma Aβ was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Kumar, Dayanidhi; Salian, Sujith Raj; Kalthur, Guruprasad
There is a paucity of data regarding the association between occupational radiation exposure and risk to human fertility. Recently, we provided the first evidence on altered sperm functional characteristics, DNA damage and hypermethylation in radiation health workers. However, there is no report elucidating the association between seminal plasma antioxidants and sperm chromatin integrity in occupationally exposed subjects. Here, we assessed the seminal plasma antioxidants and lipid peroxidation level in 83 men who were occupationally exposed to ionizing radiation and then correlated with the sperm chromatin integrity. Flow cytometry based sperm chromatin integrity assay revealed a significant decline in αt valuemore » in the exposed group in comparison to the non-exposed group (P<0.0001). Similarly, both total and reduced glutathione levels and total antioxidant capacity in the seminal plasma were significantly higher in exposed group than the non-exposed group (P<0.01, 0.001 and 0.0001, respectively). However, superoxide dismutase level and malondialdehyde level, which is an indicator of lipid peroxidation in the seminal plasma, did not differ significantly between two groups. The total antioxidant capacity (TAC) and GSH level exhibited a positive correlation with sperm DNA integrity in exposed subjects. To conclude, this study distinctly shows that altered sperm chromatin integrity in radiation health workers is associated with increase in seminal plasma antioxidant level. Further, the increased seminal plasma GSH and TAC could be an adaptive measure to tackle the oxidative stress to protect genetic and functional sperm deformities in radiation health workers. - Highlights: • Seminal plasma antioxidants were measured in men occupationally exposed to radiation. • Sperm chromatin integrity was significantly affected in the exposed group. • Glutathione and total antioxidant capacity was significantly higher in exposed group. • Sperm DNA damage in exposed
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Tanajak, Pongpan; Pongkan, Wanpitak; Chattipakorn, Siriporn C; Chattipakorn, Nipon
2018-05-01
Propose: To investigate the temporal relationship between plasma fibroblast growth factor 21 levels, insulin resistance, metabolic dysfunction and cardiac fibroblast growth factor 21 resistance in long-term high-fat diet-induced obese rats. In total, 36 male Wistar rats were fed with either a normal diet or high-fat diet for 12 weeks. Blood was collected from the tail tip, and plasma was used to determine metabolic profiles and fibroblast growth factor 21 levels. Rats were sacrificed at weeks 4, 8 and 12, and the hearts were rapidly removed for the determination of cardiac fibroblast growth factor 21 signalling pathways. Body weight and plasma fibroblast growth factor 21 levels were increased after 4 weeks of consumption of a high-fat diet. At weeks 8 and 12, high-fat diet rats had significantly increased body weight and plasma fibroblast growth factor 21 levels, together with increased plasma insulin, HOMA index, area under the curve of glucose, plasma total cholesterol, plasma low-density lipoprotein cholesterol, serum malondialdehyde and cardiac malondialdehyde levels. However, plasma high-density lipoprotein cholesterol levels and cardiac fibroblast growth factor 21 signalling proteins (p-FGFR1 Tyr 154 , p-ERK1/2 Thr 202 /Tyr 204 and p-Akt Ser 473 ) were decreased, compared with normal diet rats. These findings suggest that plasma fibroblast growth factor 21 levels could be an early predictive biomarker prior to the development of insulin resistance, metabolic disturbance and cardiac fibroblast growth factor 21 resistance.
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Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection.
Ahlgren, Erika; Hagberg, Lars; Fuchs, Dietmar; Andersson, Lars-Magnus; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus
2016-01-01
To investigate the role of homocysteine in neuronal injury in HIV infection. Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.
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Variation in dose and plasma level of lamotrigine in patients discharged from a mental health trust.
Douglas-Hall, Petrina; Dzahini, Olubanke; Gaughran, Fiona; Bile, Ahmed; Taylor, David
2017-01-01
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. 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. 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). 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.
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Zheng, Yi; Liu, Song-Qiao; Sun, Qin; Xie, Jian-Feng; Xu, Jing-Yuan; Li, Qing; Pan, Chun; Liu, Ling; Huang, Ying-Zi
2018-02-13
Mesenchymal stem cells (MSC) obviously alleviate the damage of the structure and function of pulmonary vascular endothelial cells (VEC). The therapeutic effects of MSC are significantly different between pulmonary ARDS (ARDSp) and extrapulmonary ARDS (ARDSexp). MicroRNAs (miRNAs), as important media of MSC regulating VEC, are not studied between ARDSp and ARDSexp. We aimed to explore the plasma levels difference of miRNAs that regulate VEC function and are associated with MSC (MSC-VEC-miRNAs) between ARDSp and ARDSexp patients. MSC-VEC-miRNAs were obtained through reviewing relevant literatures screened in PubMed database. We enrolled 57 ARDS patients within 24 h of admission to the ICU and then collected blood samples, extracted plasma supernatant. Patients' clinical data were collected. Then, plasma expression of MSC-VEC-miRNAs was measured by real-time fluorescence quantitative PCR. Simultaneously, plasma endothelial injury markers VCAM-1, vWF and inflammatory factors TNF-α, IL-10 were detected by ELISA method. Fourteen miRNAs were picked out after screening. A total of 57 ARDS patients were included in this study, among which 43 cases pertained to ARDSp group and 14 cases pertained to ARDSexp group. Plasma miR-221 and miR-27b levels in ARDSexp group exhibited significantly lower than that in ARDSp group (miR-221, 0.22 [0.12-0.49] vs. 0.57 [0.22-1.57], P = 0.008, miR-27b, 0.34 [0.10-0.46] vs. 0.60 [0.20-1.46], P = 0.025). Plasma vWF concentration in ARDSexp group exhibited significantly lower than that in ARDSp group (0.77 [0.29-1.54] vs. 1.80 [0.95-3.51], P = 0.048). Significant positive correlation was found between miR-221 and vWF in plasma levels (r = 0.688, P = 0.022). Plasma miR-26a and miR-27a levels in non-survival group exhibited significantly lower than that in survival group (miR-26a, 0.17 [0.08-0.20] vs. 0.69 [0.24-2.33] P = 0.018, miR-27a, 0.23 [0.16-0.58] vs. 1.45 [0.38-3.63], P = 0.021) in ARDSp patients. Plasma miR-221, miR-27b
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Goodale, Lindsay; Frank, Nicholas; Hermida, Pilar; D'Oench, Sarah
2015-05-01
To determine whether plasma ACTH concentrations vary following administration of a thyrotropin-releasing hormone (TRH) solution prepared for research purposes and stored at -20°C (rTRH) or prepared by a compounding pharmacy and stored at room temperature (approx 22°C; cTRH). 34 adult horses. The study consisted of 2 experiments. In experiment 1, each horse underwent 2 TRH stimulation tests separated by 24 hours; 10 horses were administered cTRH for the first test and rTRH for the second test (group 1), 10 horses were administered rTRH for the first test and cTRH for the second test (group 2), and 10 horses were administered rTRH for both tests (group 3). Plasma ACTH concentrations were measured at 0 (baseline) and 30 minutes after TRH administration and the delta ACTH responses (change in ACTH concentration after TRH administration) were calculated. In experiment 2, the design was the same as that for experiment 1 except there were 14 days between tests, ACTH was measured at 0 and 10 minutes after TRH administration, and 11, 9, and 10 horses were assigned to groups 1, 2, and 3, respectively. Adverse effects associated with TRH administration included transient coughing and yawning. In experiment 1, the median delta ACTH response for the second test was significantly lower than that for the first test for all groups. In experiment 2, the median delta ACTH response did not differ significantly between the first and second tests for any group, ACTH concentrations after rTRH administration were positively correlated (rs = 0.95) with those after cTRH administration, and the mean ± SD bias in post-TRH ACTH concentration between rTRH and cTRH was 2.9 ± 12.4 pg/mL. Results indicated that the TRH stimulation test should not be repeated within 24 hours, and cTRH solution stored at room temperature could be used to effectively perform TRH stimulation testing in horses.
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NASA Astrophysics Data System (ADS)
Hou, Ya-Yi; Han, Xiao-Dong; Suzuki, Yuzuru
2001-09-01
The profiles of cortisol, testosterone, 11-ketotestosterone and 17α, 20β-dihydroxy-4-pregnene-3-one in male rainbow trout reared under constant water temperature and natural photoperiod were determined by radioimmunoassay. Gonads of male rainbow trout reached maturity when the fish were two years old. Changes in the plasma levels of both sex steroid hormones and cortisol were closely related to the GSI. Plasma levels of testosterone, 11-ketotestosterone and 17α; 20β-dihydroxy 4-pregnene-3-one showed a clear peak in the annual breeding season, when the GSI reached their maxima. Plasma cortisol levels also showed clearly seasonal changes in both two- and three-year-old fish. The results suggest that the elevated plasma levels of cortisol may not just be due to stresses during the breeding season but have certain physiological functions in the reproduction of rainbow trout.
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Pesonen, Anu-Katriina; Räikkönen, Katri; Feldt, Kimmo; Heinonen, Kati; Osmond, Clive; Phillips, David I W; Barker, David J P; Eriksson, Johan G; Kajantie, Eero
2010-06-01
Animal models have linked early maternal separation with lifelong changes in hypothalamic-pituitary-adrenocortical (HPA) axis activity. Although this is paralleled in human studies, this is often in the context of other life adversities, for example, divorce or adoption, and it is not known whether early separation in the absence of these factors has long term effects on the HPA axis. The Finnish experience in World War II created a natural experiment to test whether separation from a father serving in the armed forces or from both parents due to war evacuation are associated with alterations in HPA axis response to psychosocial stress in late adulthood. 282 subjects (M=63.5 years, SD=2.5), of whom 85 were non-separated, 129 were separated from their father, and 68 were separated from both their caregivers during WWII, were enlisted to participate in a Trier Social Stress Test (TSST), during which we measured salivary cortisol and, for 215 individuals, plasma cortisol and ACTH concentrations. We used mixed models to study whether parental separation is associated with salivary and plasma cortisol or plasma ACTH reactivity, and linear regressions to analyse differences in the baseline, or incremental area under the cortisol or ACTH curves. Participants separated from their father did not differ significantly from non-separated participants. However, those separated from both parents had higher average salivary cortisol and plasma ACTH concentrations across all time points compared to the non-separated group. They also had higher salivary cortisol reactivity to the TSST. Separated women had higher baselines in plasma cortisol and ACTH, whereas men had higher reactivity in response to stress during the TSST. Participants who had experienced the separation in early childhood were more affected than children separated during infancy or school age. Separation from parents during childhood may alter an individual's stress physiology much later in adult life. Copyright
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NASA Technical Reports Server (NTRS)
Vernikos-Danellis, J.; Winget, C. M.; Hetherington, N. W.
1970-01-01
The existence of a biological rhythm in the response of animals to noxious stimuli and drugs is well known. However, the mechanism of this response is not well understood. This study was undertaken to describe the existence of a diurnal rhythm in the hypothalamic-pituitary-adrenocortical system before and after stress in female rats kept in controlled environmental conditions in 12L:12D, 24L:OD, or OL:24D. Plasma ACTH and plasma corticosterone concentrations were compared in unstressed animals. The time pattern in the response to stress was determined at four hourly intervals during a 24 hr period in which plasma ACTH and plasma corticosterone were measured at different time intervals. The stress response varied considerably with time of day in both magnitude and duration. The adrenals of rats exposed to constant light for 45 days atrophied, whereas the adrenals of animals kept in constant dark for the same period did not differ significantly from those of controls kept in 12L:12D. The increase in plasma ACTH in response to stress was greater both in the animals maintained in constant light and in constant dark than in the 12L:12D controls. Homeostatic mechanisms involved in these changes are discussed.
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Galan-Chilet, Inmaculada; Tellez-Plaza, Maria; Guallar, Eliseo; De Marco, Griselda; Lopez-Izquierdo, Raul; Gonzalez-Manzano, Isabel; Carmen Tormos, M; Martin-Nuñez, Gracia M; Rojo-Martinez, Gemma; Saez, Guillermo T; Martín-Escudero, Juan C; Redon, Josep; Javier Chaves, F
2014-09-01
The role of selenium exposure in preventing chronic disease is controversial, especially in selenium-repleted populations. At high concentrations, selenium exposure may increase oxidative stress. Studies evaluating the interaction of genetic variation in genes involved in oxidative stress pathways and selenium are scarce. We evaluated the cross-sectional association of plasma selenium concentrations with oxidative stress levels, measured as oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8-oxo-7,8-dihydroguanine (8-oxo-dG) in urine, and the interacting role of genetic variation in oxidative stress candidate genes, in a representative sample of 1445 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.76 µg/L. In fully adjusted models the geometric mean ratios for oxidative stress biomarker levels comparing the highest to the lowest quintiles of plasma selenium levels were 0.61 (0.50-0.76) for GSSG/GSH, 0.89 (0.79-1.00) for MDA, and 1.06 (0.96-1.18) for 8-oxo-dG. We observed nonlinear dose-responses of selenium exposure and oxidative stress biomarkers, with plasma selenium concentrations above ~110 μg/L being positively associated with 8-oxo-dG, but inversely associated with GSSG/GSH and MDA. In addition, we identified potential risk genotypes associated with increased levels of oxidative stress markers with high selenium levels. Our findings support that high selenium levels increase oxidative stress in some biological processes. More studies are needed to disentangle the complexity of selenium biology and the relevance of potential gene-selenium interactions in relation to health outcomes in human populations. Copyright © 2014 Elsevier Inc. All rights reserved.
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Li, Gang; Song, Xueqing; Xia, Jiyi; Li, Jing; Jia, Peng; Chen, Pengyuan; Zhao, Jian; Liu, Bin
2017-01-01
The aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure. Methods and results Plasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices. Plasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.
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He, Yingdong; Chen, Shi; Huang, He; Chen, Qian
2016-04-01
The aim of this study was to investigate the levels of different isoforms of soluble human leukocyte antigen-G (sHLA-G) in maternal plasma during early and late pregnancy, and to investigate the expression of sHLA-G isoforms in women with early or late-onset severe preeclampsia. This prospective, nested, case-control study was performed in 24 early-onset severe preeclamptic, 34 late-onset severe preeclamptic, and 74 uncomplicated pregnant women. Plasma levels of sHLA-G1/5 were measured using ELISA. Plasma sHLA-G1 levels in women with late-onset severe preeclampsia were markedly lower compared with normal controls (median: 0 vs. 1.22 ng/mL) at the first trimester, and plasma sHLA-G1 levels in women with early-onset severe preeclampsia were markedly lower compared with normal controls at the second (median: 0 vs. 1.24 ng/mL) and third (median: 0 vs. 1.34 ng/mL) trimesters. There was no difference between the late-onset and early-onset groups at three trimesters. As for sHLA-G5, there was no difference in concentrations among the three groups at any time point. However, compared with controls, more women with early- or late-onset severe preeclampsia had undetectable sHLA-G5 levels in the first (71.4% and 76.2% vs. 14.1%), second (75.0% and 73.3% vs. 19.0%), and third (100.0% and 70.4% vs. 14.8%, respectively) trimester (all P<0.05). sHLA-G1 levels in the first (odds ratio [OR]=0.254, 95% confidence interval [CI]=0.109-0.591, P=0.010), second (OR=0.315, 95% CI=0.158-0.627, P=0.001), and third (OR=0.170, 95% CI=0.054-0.533, P=0.002) trimester was a risk factor for severe preeclampsia. Severe preeclampsia was associated with low/undetectable maternal plasma levels of sHLA-G. Low sHLA-G1 levels might be a risk marker for severe preeclampsia.
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Hellum, Marit; Øvstebø, Reidun; Brusletto, Berit S; Berg, Jens P; Brandtzaeg, Petter; Henriksson, Carola E
2014-03-01
The plasma level of bacterial lipopolysaccharides (LPS) is associated with activation of the coagulation system, inhibition of fibrinolysis and the nature of the clinical presentation and outcome in patients with meningococcal disease. Tissue factor (TF)-bearing microparticles (MPs) appear to contribute to the pathogenesis of disseminated intravascular coagulation (DIC). The aim of this study was to investigate the relationship between MP-associated TF activity and the level of bacterial LPS in plasma from patients with meningococcal septic shock and meningitis. MPs isolated from citrated plasmas were assessed for TF-dependent activity with both a plasma-based thrombin generation assay (CAT) and whole blood-based thromboelastometry (ROTEM). The LPS level was measured using a chromogenic Limulus amebocyte lysate assay. MPs obtained from patients with meningococcal septic shock initiated significantly more efficient and TF-dependent thrombin generation in the CAT assay compared to MPs from patients with meningococcal meningitis. Differences in MP-associated TF activity between the septic shock patients and the meningitis patients were also evident when MPs were added to whole blood using ROTEM. The level of plasma LPS in patients with septic shock (range 2-2,100 EU/mL) was correlated with thrombogram parameters in the CAT assay; lagtime (r(s)=-0.84), time to peak (rs=-0.83), peak (r(s)=0.85) and ETP (r(s)=0.83). MPs obtained from patients with meningococcal septic shock displayed more efficient TF-dependent thrombin generation and clot formation compared to MPs from meningitis patients. MP-associated TF activity was closely associated with plasma LPS levels in the septic shock group. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Franke, AA; Lai, J.F.; Morrison, C.M.; Pagano, I.; Li, X; Halm, B.M.; Soon, R.; Custer, L.J.
2015-01-01
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. PMID:23829202
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Xia, Qing-Rong; Liang, Jun; Cao, Yin; Shan, Feng; Liu, Yang; Xu, Ya-Yun
2018-05-01
The aim of the present study was to evaluate the plasma nesfatin-1, corticosterone, and inflammatory cytokine (IL-6, CRP, and TNF-α) concentrations cross-sectionally in patients with major depressive disorder. Subjects in the patient group were randomly selected from the Anhui Mental Health Center, and subjects in the control group were selected from healthy volunteers. Healthy control subjects were matched in terms of weight and body mass index. The Hamilton Depression Rating Scale (HAM-D) was used to evaluate both groups. ELISAs were used for the measurement of plasma nesfatin-1, corticosterone, IL-6, CRP, and TNF-α levels. The HAM-D scores and average nesfatin-1, corticosterone, IL-6, and CRP levels were significantly higher in patients with major depressive disorder than those in the control group. Positive correlation was found between nesfatin-1 and corticosterone (r = 0.305, P = 0.007), IL-6 (r = 0.333, P = 0.003), and CRP (r = 0.244, P = 0.034) concentrations. Increased plasma nesfatin-1 levels may be associated with corticosterone, IL-6, and CRP levels in patients with major depressive disorder. Copyright © 2018 Elsevier B.V. All rights reserved.
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Kasai, Chika; Sugimoto, Kazushi; Moritani, Isao; Tanaka, Junichiro; Oya, Yumi; Inoue, Hidekazu; Tameda, Masahiko; Shiraki, Katsuya; Ito, Masaaki; Takei, Yoshiyuki; Takase, Kojiro
2016-10-04
Helicobacter pylori (H. pylori) infection and eradication therapy have been known to influence gastric ghrelin and leptin secretion, which may lead to weight gain. However, the exact relationship between plasma ghrelin/leptin levels and H. pylori infection has remained controversial. The aim of this study was to investigate plasma ghrelin and leptin levels in H. pylori-positive and -negative patients, to compare the two levels of the hormones before and after H. pylori eradication, and to examine the correlation between body mass index (BMI) and active ghrelin or leptin levels, as well as that between atrophic pattern and active ghrelin or leptin levels. Seventy-two H. pylori-positive patients who underwent upper gastrointestinal endoscopy, 46 diagnosed as having peptic ulcer and 26 as atrophic gastritis, were enrolled. Control samples were obtained from 15 healthy H. pylori-negative volunteers. The extent of atrophic change of the gastric mucosa was assessed endoscopically. Body weight was measured and blood was collected before and 12 weeks after H. pylori eradication therapy. Blood samples were taken between 8 and 10 AM after an overnight fast. Plasma ghrelin levels were significantly lower in H. pylori-positive patients than in H. pylori-negative patients. In particular, plasma active ghrelin levels were significantly lower in patients with gastritis compared with patients with peptic ulcer. Plasma ghrelin levels decreased after H. pylori eradication in both peptic ulcer and gastritis patients, while plasma leptin levels increased only in peptic ulcer patients. Plasma leptin levels and BMI were positively correlated, and active ghrelin levels and atrophic pattern were weakly negatively correlated in peptic ulcer patients. H. pylori infection and eradication therapy may affect circulating ghrelin/leptin levels. This finding suggests a relationship between gastric mucosal injury induced by H. pylori infection and changes in plasma ghrelin and leptin levels.
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Plasma Levels of Aβ42 and Tau Identified Probable Alzheimer's Dementia: Findings in Two Cohorts.
Lue, Lih-Fen; Sabbagh, Marwan N; Chiu, Ming-Jang; Jing, Naomi; Snyder, Noelle L; Schmitz, Christopher; Guerra, Andre; Belden, Christine M; Chen, Ta-Fu; Yang, Che-Chuan; Yang, Shieh-Yueh; Walker, Douglas G; Chen, Kewei; Reiman, Eric M
2017-01-01
The utility of plasma amyloid beta (Aβ) and tau levels for the clinical diagnosis of Alzheimer's disease (AD) dementia has been controversial. The main objective of this study was to compare Aβ42 and tau levels measured by the ultra-sensitive immunomagnetic reduction (IMR) assays in plasma samples collected at the Banner Sun Health Institute (BSHRI) (United States) with those from the National Taiwan University Hospital (NTUH) (Taiwan). Significant increase in tau levels were detected in AD subjects from both cohorts, while Aβ42 levels were increased only in the NTUH cohort. A regression model incorporating age showed that tau levels identified probable ADs with 81 and 96% accuracy in the BSHRI and NTUH cohorts, respectively, while computed products of Aβ42 and tau increased the accuracy to 84% in the BSHRI cohorts. Using 382.68 (pg/ml) 2 as the cut-off value, the product achieved 92% accuracy in identifying AD in the combined cohorts. Overall findings support that plasma Aβ42 and tau assayed by IMR technology can be used to assist in the clinical diagnosis of AD.
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Ramachandran, Surya; Venugopal, Anila; Kutty, V Raman; A, Vinitha; G, Divya; Chitrasree, V; Mullassari, Ajit; Pratapchandran, N S; Santosh, K R; Pillai, M Radhakrishna; Kartha, C C
2014-02-07
Cyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD). Study subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored. Plasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P < 0.001). Age, fasting blood sugar levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p < 0.001).Serum levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease. Our study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular
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Catena, Cristiana; Verheyen, Nicolas D; Url-Michitsch, Marion; Kraigher-Krainer, Elisabeth; Colussi, GianLuca; Pilz, Stefan; Tomaschitz, Andreas; Pieske, Burkert; Sechi, Leonardo A
2016-03-01
Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity in hypertension. Current evidence suggests a contribution to LVH of plasma aldosterone levels that are inappropriately elevated for the salt status. The aim of this study was to investigate whether inappropriate modulation of aldosterone production by a saline load is associated with left ventricular (LV) mass in hypertensive patients. In 90 hypertensive patients free of clinically relevant cardiovascular complications in whom secondary forms of hypertension were ruled out, we performed a standard intravenous saline load (0.9% NaCl, 2 l in 4 hours) with measurement of plasma aldosterone and active renin at baseline and end of infusion. Bi-dimensional echocardiography was performed for the assessment of cardiac morphology and function. LVH was present in 19% of patients who had significantly worse renal function and higher body mass, blood pressure, and plasma aldosterone levels measured both at baseline and after the saline load than patients without LVH. LV mass was directly related to age, body mass, systolic blood pressure, duration of hypertension, baseline, and post-saline load plasma aldosterone levels and inversely to glomerular filtration. Multivariate regression analysis showed independent correlation of LV mass with body mass, systolic blood pressure, and plasma aldosterone levels measured after intravenous saline load, but not at baseline. In patients with hypertension, aldosterone levels measured after intravenous saline load are related to LV mass independent of age, body mass, and blood pressure, suggesting that limited ability of salt to modulate aldosterone production could contribute to LVH. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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High Levels of Exosomes Expressing CD63 and Caveolin-1 in Plasma of Melanoma Patients
Logozzi, Mariantonia; De Milito, Angelo; Lugini, Luana; Borghi, Martina; Calabrò, Luana; Spada, Massimo; Perdicchio, Maurizio; Marino, Maria Lucia; Federici, Cristina; Iessi, Elisabetta; Brambilla, Daria; Venturi, Giulietta; Lozupone, Francesco; Santinami, Mario; Huber, Veronica; Maio, Michele; Rivoltini, Licia; Fais, Stefano
2009-01-01
Background Metastatic melanoma is an untreatable cancer lacking reliable and non-invasive markers of disease progression. Exosomes are small vesicles secreted by normal as well as tumor cells. Human tumor-derived exosomes are involved in malignant progression and we evaluated the presence of exosomes in plasma of melanoma patients as a potential tool for cancer screening and follow-up. Methodology/Principal Findings We designed an in-house sandwich ELISA (Exotest) to capture and quantify exosomes in plasma based on expression of housekeeping proteins (CD63 and Rab-5b) and a tumor-associated marker (caveolin-1). Western blot and flow cytometry analysis of exosomes were used to confirm the Exotest-based findings. The Exotest allowed sensitive detection and quantification of exosomes purified from human tumor cell culture supernatants and plasma from SCID mice engrafted with human melanoma. Plasma levels of exosomes in melanoma-engrafted SCID mice correlated to tumor size. We evaluated the levels of plasma exosomes expressing CD63 and caveolin-1 in melanoma patients (n = 90) and healthy donors (n = 58). Consistently, plasma exosomes expressing CD63 (504±315) or caveolin-1 (619±310) were significantly increased in melanoma patients as compared to healthy donors (223±125 and 228±102, respectively). While the Exotest for CD63+ plasma exosomes had limited sensitivity (43%) the Exotest for detection of caveolin-1+ plasma exosomes showed a higher sensitivity (68%). Moreover, caveolin-1+ plasma exosomes were significantly increased with respect to CD63+ exosomes in the patients group. Conclusions/Significance We describe a new non-invasive assay allowing detection and quantification of human exosomes in plasma of melanoma patients. Our results suggest that the Exotest for detection of plasma exosomes carrying tumor-associated antigens may represent a novel tool for clinical management of cancer patients. PMID:19381331
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High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients.
Logozzi, Mariantonia; De Milito, Angelo; Lugini, Luana; Borghi, Martina; Calabrò, Luana; Spada, Massimo; Perdicchio, Maurizio; Marino, Maria Lucia; Federici, Cristina; Iessi, Elisabetta; Brambilla, Daria; Venturi, Giulietta; Lozupone, Francesco; Santinami, Mario; Huber, Veronica; Maio, Michele; Rivoltini, Licia; Fais, Stefano
2009-01-01
Metastatic melanoma is an untreatable cancer lacking reliable and non-invasive markers of disease progression. Exosomes are small vesicles secreted by normal as well as tumor cells. Human tumor-derived exosomes are involved in malignant progression and we evaluated the presence of exosomes in plasma of melanoma patients as a potential tool for cancer screening and follow-up. We designed an in-house sandwich ELISA (Exotest) to capture and quantify exosomes in plasma based on expression of housekeeping proteins (CD63 and Rab-5b) and a tumor-associated marker (caveolin-1). Western blot and flow cytometry analysis of exosomes were used to confirm the Exotest-based findings. The Exotest allowed sensitive detection and quantification of exosomes purified from human tumor cell culture supernatants and plasma from SCID mice engrafted with human melanoma. Plasma levels of exosomes in melanoma-engrafted SCID mice correlated to tumor size. We evaluated the levels of plasma exosomes expressing CD63 and caveolin-1 in melanoma patients (n = 90) and healthy donors (n = 58). Consistently, plasma exosomes expressing CD63 (504+/-315) or caveolin-1 (619+/-310) were significantly increased in melanoma patients as compared to healthy donors (223+/-125 and 228+/-102, respectively). While the Exotest for CD63+ plasma exosomes had limited sensitivity (43%) the Exotest for detection of caveolin-1+ plasma exosomes showed a higher sensitivity (68%). Moreover, caveolin-1+ plasma exosomes were significantly increased with respect to CD63+ exosomes in the patients group. We describe a new non-invasive assay allowing detection and quantification of human exosomes in plasma of melanoma patients. Our results suggest that the Exotest for detection of plasma exosomes carrying tumor-associated antigens may represent a novel tool for clinical management of cancer patients.
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Hyperglycemia may determine fibrinopeptide A plasma level increase in humans.
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.