Plasma Adrenocorticotropic Hormone Concentrations Research Articles

Effects of endogenous glucocorticoid deprivation on immune response of allergic rhinitis in mice

Objective: To study the effect of dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis on the pathogenesis of allergic rhinitis (AR) by the mouse model of decreased endogenous glucocorticoid (GC) after adrenalectomy, and further explore the mechanism of neural-endocrine regulation. Methods: According to literatures, adrenalectomized (ADX) mice and AR model were established. Eighty mice were randomly divided into four groups (n=20 per group) including control group, AR group of normal mice (AR group), AR group of bilateral ADX (bilateral ADX/AR group) and AR group of unilateral ADX (unilateral ADX/AR group). In order to assess the model of ADX, adrenal gland tissue was assayed by HE staining and the plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). The behavioral observation, OVA-sIgE assessments and count of eosinophils/mast cells by the HE/Toluidine Blue staining of nasal septum mucosa tissue were performed to evaluate the AR model. The expression of peripheral blood CD4(+) IL4(+) T cells (Th2 cells) and CD4(+) IFN-γ(+) T cells (Th1 cells), splenocytes of CD4(+) CD25(+) Treg cells (Treg cells) were measured by flow cytometry to study the influence of endogenous GC on immunological indexes in different groups of mice. SPSS 16.0 software was used to analyze the data. Results: The concentrations of OVA-sIgE in control group, AR group, bilateral ADX/AR group and unilateral ADX/AR group mice were (28.86±3.62) ng/ml, (76.27±16.47) ng/ml, (48.37±8.89) ng/ml, (49.86±7.19) ng/ml, respectively. There was statistically significant difference between control group and AR group (t=7.09, P<0.05), AR group and bilateral ADX/AR group (t=4.81, P<0.05), AR group and unilateral ADX/AR group (t=5.21, P<0.05). The level of Th2 cells in different four groups were (0.71±0.24)%, (7.03±1.95)%, (2.44±2.06)%, (3.20±1.21)%, respectively. There was statistically significant difference between control group and AR group (t=-2.93, P<0.05), AR group and bilateral ADX/AR group (t=-4.67, P<0.05), AR group and unilateral ADX/AR group (t=-3.61, P<0.05). The expression of Th2 in bilateral ADX/AR group is lower than that in unilateral ADX/AR group without significant difference (t=4.39, P>0.05). Meanwhile, the level of Th1 cells in different four groups was (0.58±0.76)%, (0.57±0.59)%, (0.72±0.34)%, (1.03±0.32)%, respectively, with no significant difference among these groups. The proportion of Treg cells was (11.10±2.18)%, (4.10±1.07)%, (7.15±0.92)%, (4.58±1.05)%, respectively, with significant difference between control and other groups (t value was -7.171, -8.273, -8.360, respectively, all P<0.05). Compared with AR group, Treg cells increased significantly in bilateral ADX/AR group (t=-2.607, P<0.05). In addition, lower expression of eosinophil and mast cell were detected in the local nasal tissue of bilateral ADX/AR group, and mast cell degranulation wasn't be observed. Conclusion: Unilateral or bilateral ADX leads to HPA axis dysfunction and endogenous GC deprivation, possibly regulating the mechanism of AR through Th1/Th2 immune bias and Tregs cell' activity.

Changes in energy metabolism, and levels of stress-related hormones and electrolytes in horses after intravenous administration of romifidine and the peripheral \u03b1-2 adrenoceptor antagonist vatinoxan

BackgroundRomifidine, an α-2 adrenoceptor agonist, is a widely-used sedative in equine medicine. Besides the desired sedative and analgesic actions, α-2 adrenoceptor agonists have side effects like alterations of plasma concentrations of glucose and certain stress-related hormones and metabolites in various species. Vatinoxan (previously known as MK-467), in turn, is an antagonist of α-2 adrenoceptors. Because vatinoxan does not cross the blood brain barrier in significant amounts, it has only minor effect on sedation induced by α-2 adrenoceptor agonists. Previously, vatinoxan is shown to prevent the hyperglycaemia, increase of plasma lactate concentration and the decrease of insulin and non-esterified free fatty acids (FFAs) caused by α-2 adrenoceptor agonists in different species. The aim of our study was to investigate the effects of intravenous romifidine and vatinoxan, alone and combined, on plasma concentrations of glucose and some stress-related hormones and metabolites in horses.ResultsPlasma glucose concentration differed between all intravenous treatments: romifidine (80 μg/kg; ROM), vatinoxan (200 μg/kg; V) and the combination of these (ROM + V). Glucose concentration was the highest after ROM and the lowest after V. Serum FFA concentration was higher after V than after ROM or ROM + V. The baseline serum concentration of insulin varied widely between the individual horses. No differences were detected in serum insulin, cortisol or plasma adrenocorticotropic hormone (ACTH) concentrations between the treatments. Plasma lactate, serum triglyceride or blood sodium and chloride concentrations did not differ from baseline or between the treatments. Compared with baseline, plasma glucose concentration increased after ROM and ROM + V, serum cortisol, FFA and base excess increased after all treatments and plasma ACTH concentration increased after V. Serum insulin concentration decreased after V and blood potassium decreased after all treatments.ConclusionsRomifidine induced hyperglycaemia, which vatinoxan partially prevented despite of the variations in baseline levels of serum insulin. The effects of romifidine and vatinoxan on the insulin concentration in horses need further investigation.

Plasma adrenocorticotropic hormone (ACTH) concentrations in ponies measured by two different assays suggests seasonal cross-reactivity or interference.

Analysis of plasma adrenocorticotropic hormone concentration [ACTH] aids diagnosis of pituitary pars intermedia dysfunction (PPID). Comparisons of the validated chemiluminescent-immunoassay (CI) and immunofluorescent (IF) assays are limited. To compare the results of [ACTH] analysis by CI and IF methods of samples collected in autumn and spring and assess cross-reactivity. Method comparison. Plasma from nonlaminitic ponies was analysed concurrently using the IF and CI methods in autumn and the following spring. Diagnostic thresholds for the IF method were derived using ROC curves and Youden indices to correspond with CI thresholds. Assay specificity was assessed using commercially available ACTH fragments and degradation products of endogenous ACTH. CI and IF methods yielded different results (P<0.001); mean differences (CI-IF), (95% confidence intervals): Autumn (n=99) 38.6 (30.6-46.5)pg/ml, Spring (n=88) 5.1 (3.9-6.3)pg/ml. The association between CI and IF results differed in autumn and spring, consistent with seasonally dependent cross-reactivity or interference. Good (κ=0.66-0.74) agreement was obtained for binary interpretation in spring between IF and CI using thresholds of >24 and >29pg/ml respectively and in autumn between IF and CI using thresholds of >27 and >47pg/ml respectively or >33 and >77pg/ml respectively. Of 88 ponies with both spring and autumn samples, 56 (64%) exceeded a published autumn CI threshold (>47pg/ml), of which 39 (70%) were below the equivalent threshold (<29pg/ml) the following spring without treatment. The CI assay showed apparent increases in [ACTH] following addition of CLIP (ACTH 18-39). Degradation of ACTH during storage affected the assays differently. Limited numbers of PPID cases were included. Immunoreactivity of commercially available peptides may differ from their endogenous equivalents. The methods yielded different absolute values but the agreement for binary classification was good. An altered pituitary secretome in autumn that affects apparent [ACTH] values is likely. The Summary is available in Spanish - seeSupporting information.

Pituitary size alteration and adverse effects of radiation therapy performed in 9 dogs with pituitary-dependent hypercortisolism

The purpose of this study was to determine the therapeutic and/or adverse effects of radiation therapy (RT) against pituitary tumors in dogs with pituitary-dependent hypercortisolism, as monitored by frequent post-RT detailed MRI examinations, clinical signs, and changes in hormone concentrations. Nine dogs with an adrenocorticotropic hormone (ACTH)-secreting pituitary mass diagnosed by magnetic resonance imaging (MRI) underwent RT for 4weeks (total of 48Gy in 4-Gy fractions). Pituitary height/brain area (P/B) value, clinical signs, basal plasma ACTH concentrations, serum cortisol concentrations (pre- and post-ACTH stimulation test) and adverse effects of RT were evaluated before and post-RT.The P/B value was significantly lower in all nine dogs post-RT. One dog lacking any neurological signs demonstrated no change in clinical signs pre and post-RT. Out of 8 dogs which exhibited neurological signs pre-RT, half of them demonstrated complete resolution of their signs, whereas the other half showed transient resolution. In all animals with recurrence of neurological signs, pituitary tumor regrowth was not observed; however, MRI revealed moderate to severe pituitary hemorrhage. Late adverse effect (bilateral otitis media) was observed in three of nine dogs post-RT. RT did not induce any significant changes in the dogs' basal plasma ACTH concentration and pre- and post-ACTH serum cortisol concentrations.In conclusion, RT is effective to reduce pituitary size and the mass effect, but does not appear to affect blood hormone concentrations, necessitating additional medical treatment against hypercortisolism. Periodic MRI imaging post-RT enables early detection of adverse effects of RT.

Profiles of pro-opiomelanocortin and encoded peptides, and their processing enzymes in equine pituitary pars intermedia dysfunction.

Equine pituitary pars intermedia dysfunction (PPID) is characterized by hyperplasia of the pars intermedia (PI) melanotrophs of the pituitary gland (PG), and increased production of proopiomelanocortin (POMC). POMC is cleaved by prohormone convertase 1 (PC1) to produce adrenocorticotropic hormone (ACTH), and further processing of ACTH by PC2 to produce alpha-melanocyte stimulating hormone (α-MSH) and corticotropin-like intermediate peptide (CLIP). High plasma ACTH concentrations in horses with PPID might be related to reduced conversion of ACTH to α-MSH by PCs. The hypothesis of this study was that PC1 and PC2 expression in the pituitary gland are altered in PPID, resulting in an abnormal relative abundance of POMC derived proteins. The objectives of this study were to identify the partial sequences of equine POMC, PC1, and PC2 mRNAs; and to determine whether the expression of POMC, PC1, and PC2 mRNAs in whole pituitary extracts, and POMC-protein in the cavernous sinus blood of horses are altered in PPID. We confirmed (RT-PCR and sequencing) that the partial sequences obtained match the corresponding regions of predicted equine POMC, PC1 and PC2 sequences. The expression (quantification by RT-qPCR) of POMC, PC1 and PC2 mRNAs were found upregulated in the pituitary of horses with PPID. Plasma (measured using RIA/ELISA) ACTH and α-MSH were elevated in PPID horses. These results indicate distinct differences in gene and protein expression of POMC and its intermediates, and processing enzymes in PPID. It provides evidence to support the notion that local, pituitary-specific inadequacies in prohormone processing likely contribute to equine PPID.

TRH-induced secretion of adrenocorticotropin and cortisol in dogs with pituitary-dependent hypercortisolism

Background: In dogs, spontaneous Cushing’s syndrome is most often pituitary-dependent and caused by hypersecretion of adrenocorticotropic hormone (ACTH), resulting in increased adrenocortical glucocorticoid secretion similar to horses. In horses with Cushing’s syndrome (or pituitary pars intermedia dysfunction [PPID]) a thyrotropin-releasing hormone (TRH) stimulation test can be used for diagnosis, as TRH administration results in increased circulating ACTH and cortisol concentrations in affected horses.Objective: The aim of this study was to investigate the effect of TRH administration on the circulating ACTH and cortisol concentrations in dogs with pituitary-dependent hypercortisolism (PDH).Methods: Ten clinically normal control dogs and 10 dogs with PDH, all client owned, underwent a TRH stimulation test with measurement of plasma concentrations of ACTH and cortisol, before and after intravenous administration of 10 μg TRH/kg bodyweight.Results: Plasma ACTH concentration did not rise significantly after TRH stimulation, neither in PDH dogs nor in clinically normal dogs. In contrast, the plasma cortisol concentration did increase significantly after TRH stimulation in both groups (p = .003 in PDH and p < .001 in control). Immunohistochemistry of normal adrenal glands demonstrated the presence of TRH receptors in the whole adrenal cortex.Conclusions: The results of this study demonstrate that the TRH stimulation test should be rejected as a tool to diagnose PDH in dogs. The observed TRH-induced increase in plasma cortisol concentration without a significant rise in plasma ACTH concentration may be explained by a direct effect of TRH on adrenocortical cells mediated by adrenocortical TRH receptors.

Plasma ACTH concentration and pituitary gland histo-pathology in rats infected with Trypanosoma brucei brucei.

Human African trypanosomiasis is one of the neglected and re-emerging infectious diseases in Africa with over 60 million people being at risk of contracting the disease. To investigate the effects of Trypanosoma brucei brucei infection on secretion of adrenocorticotropic hormone (ACTH) and histology of the pituitary gland and paraventricular nucleus in rats. Rats were randomly divided into two groups, control and experimental. Experimental rats were injected intraperitonially with 0.2ml of blood containing 1.0 × 104 live T.b.brucei parasites. Tail blood samples were collected weekly for the determination of plasma concentration of ACTH. The pituitary gland and coronal section of brain were processed histologically and observed microscopically. There was a significant difference (p = 0.0190) in plasma ACTH concentration between the control and experimental rats. Histological alterations were observed in both the pituitary and paraventricular nucleus of experimental rats. T.b.brucei infection causes histological changes in both the paraventricular nucleus and pituitary gland in rats. These histological changes could account for the decrease in corticotropin releasing hormone (CRH) and ACTH production in the infected rats.

Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial

Cushing's disease is a rare debilitating endocrine disorder for which few prospective interventional studies have been done. We report results of the first phase 3 trial assessing long-acting intramuscular pasireotide in patients with Cushing's disease. In this phase 3 clinical trial we recruited patients aged 18 years or older with persistent, recurrent, or de-novo (non-surgical candidates) Cushing's disease who had a mean urinary free cortisol (mUFC) concentration (from three 24 h samples) of 1·5-5·0 times the upper limit of normal (ULN), a normal or greater than normal morning plasma adrenocorticotropic hormone concentration, and a pituitary source of Cushing's syndrome, from 57 sites across 19 countries. Exclusion criteria included previous pasireotide treatment, mitotane therapy within 6 months, and pituitary irradiation within 10 years. We randomly allocated patients 1:1 (block size of four) using an interactive-response-technology system to intramuscular pasireotide 10 mg or 30 mg every 4 weeks for 12 months (in the core phase). We stratified randomisation by screening mUFC concentration (1·5 to <2·0 × ULN and 2·0-5·0 × ULN). The dose could be uptitrated (from 10 mg to 30 mg or from 30 mg to 40 mg) at month 4 if the mUFC concentration was greater than 1·5 × ULN, and at month 7, month 9, or month 12 if the mUFC concentration was greater than 1·0 × ULN. Investigators, patients, site personnel, and those assessing outcomes were masked to dose group allocation. The primary endpoint was the proportion of patients in each group with an mUFC concentration of less than or equal to the ULN at month 7. Efficacy analyses were based on intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01374906. Between Dec 28, 2011, and Dec 9, 2014, we randomly allocated 150 patients to receive pasireotide 10 mg (74 [49%] patients) or 30 mg (76 [51%] patients). The primary efficacy endpoint was met by 31 (41·9% [95% CI 30·5-53·9]) of 74 patients in the 10 mg group and 31 (40·8% [29·7-52·7]) of 76 in the 30 mg group. The most common adverse events were hyperglycaemia (36 [49%] in the 10 mg group and 36 [47%] in the 30 mg group), diarrhoea (26 [35%] and 33 [43%]), cholelithiasis (15 [20%] and 34 [45%]), diabetes mellitus (14 [19%] and 18 [24%]), and nausea (15 [20%] and 16 [21%]). Serious adverse events suspected to be study drug related were reported in eight (11%) patients in the 10 mg group and four (5%) in the 30 mg group. Two (3%) patients in the 30 mg group died during the study (pulmonary artery thrombosis and cardiorespiratory failure); neither death was judged to be related to the study drug. Long-acting pasireotide normalised mUFC concentration in about 40% of patients with Cushing's disease at month 7 and had a similar safety profile to that of twice-daily subcutaneous pasireotide. Long-acting pasireotide is an efficacious treatment option for some patients with Cushing's disease who have persistent or recurrent disease after initial surgery or are not surgical candidates, and provides a convenient monthly administration schedule. Novartis Pharma AG.

Effects of dexmedetomidine on plasma glucose, cortisol and adrenocorticotropic hormone concentrations of canine undergoing ovariohysterectomy

Effects of dexmedetomidine on plasma glucose, cortisol and adrenocorticotropic hormone concentrations of canine undergoing ovariohysterectomy

Seasonal changes in plasma testosterone and cortisol suggest an androgen mediated regulation of the pituitary adrenal axis in the Tarabul’s gerbil Gerbillus tarabuli (Thomas, 1902)

In the desert gerbil Gerbillus tarabuli (Thomas, 1902), cortisol is the main glucocorticosteroid produced by the adrenal glands. Plasma cortisol concentrations show highest values when testosterone is reduced and lowest values during the breeding season which occurs from early winter to late spring. In order to specify the implication of testicular androgens in these corticosteroid seasonal variations we investigated the effects induced by gonadectomy performed during the breeding season on the pituitary adrenal axis. The animals collected in winter were assessed into three groups: sham-operated (Controls; n=13), gonadectomised (GDX; n=13) and testosterone replaced gonadectomised (GDX+T; n=13). Physiological replacement of testosterone enanthate (75µg/100gb.w./twice daily) was applied during one week, while GDX group received the vehicle (40µL sesame oil) alone. The right adrenal glands removed from euthanized animals were fixed for histomorphometry and androgen receptors (ARs) immunohistochemistry and the left ones were frozen with plasma samples until hormonal assays. Gonadectomy induces the enlargement of the adrenal cortex essentially due to that of zonae fasciculata (ZF) and reticularis (ZR) and perimedullary connective tissue which is abundant in the gerbil adrenals. The ARs immunostaining present at both cytoplasmic and nucleus level, is enhanced intensely in the ZR and moderately in the ZF and zona glomerulosa (ZG) cells. GDX group shows reduced plasma ACTH concentration (p=0.0126) by 61% despite the increase in cortisol concentration occurring both in plasma (+216%; p=0.0436) and adrenal tissue (+117%; p=0.0348). Plasma aldosterone is also enhanced significantly (p=0.0147) by 189% but androstenedione synthesis increased in adrenal tissue (p=0.0459) by 65% instead a decrease at circulatory level (p=0.0355) by 58% due to lack of testicular origin. So, testosterone deprivation activates corticosteroidogenesis also evidenced by the adrenal structure changes and the gonadectomy-induced increase in the plasma cholesterol. All of the gonadectomy-induced responses are reversible after physiological testosterone replacement. We conclude that the assessment of circulating adrenocorticotropic hormone (ACTH) concentrations together with cortisol levels essentially, reflecting the hypothalamic–pituitary adrenal (HPA) axis feedback loop control during the annual endogenous changes of testosterone secretion, represents a well-adapted response of this desert species living in an extreme environment.

Effects of chronic stress depression on the circadian rhythm of peripheral neuroendocrine hormone of rats

To investigate the circadian rhythmic alterations of plasma hormone and peptide induced by chronic unpredictable mild stress(CUMS). Sixty male SD rats were randomly divided into two groups, model group and control group(n=30). Rats in model group received CUMS procedure (restraint, rotation, cage tilt, wet sawdust, cold, crowding, food or water deprivation, clamp tail and reverse light/dark cycle). Rats were randomly exposed to two stressors every day for 3 weeks. Exploratory locomotor activity was assessed by open field test and anxiety-like behavior was measured by elevated plus-maze test, and lack of pleasure by sucrose preference test. Blood samples were collected at each of six time points zeitgeber time (ZT1, 5, 9, 13, 17 and 21), 5 rats were executed at each time point. Plasma concentrations of corticosterone(CORT), melatonin (MT) and vasoactive intestinal peptide (VIP) were detected by ELISA kits, and plasma concentration of adrenocorticotropic hormone (ACTH) was determined by radioimmunoassay. The circadian rhythm changes of serum CORT, MT, VIP and ACTH in each group were compared by using cosinor. Compared with control group, locomotor activity, rearing, weight gain and sucrose consumption in model group were decreased significantly. The values of the percentage of open-arm time (OT) and open arm entries (OE) were obviously lower in the model group than those in the control group. The circadian rhythm of plasma ACTH and CORT showed an obvious disorder, including phase advance and decrease in amplitude, and markedly blunted circadian rhythm. There also showed a markedly blunted circadian rhythm and decreased levels of plasma MT. VIP still had 24-hour rhythm, but the amplitude was significantly lower, peak phase also delayed for six hours, and expression was significantly higher. CUMS induces these peptides and hormones desynchronized from suprachiasmatic nucleus(SCN), manifested as the disturbed circadian rhythms and the abnormal hormone secretion of these synchronizers.

Left-Sided Living Kidney Donation Leads to Transiently Reduced Adrenocortical Responsiveness.

Living kidney donation is safe and established, but can lead to long-term complications such as chronic fatigue. Since the adrenal vein is usually transected during left-sided donor nephrectomy-which is not necessary on the right-we hypothesized that venous congestion might lead to an impairment of adrenal function, offering a possible explanation. In this prospective open label, monocentric cohort study, adrenal function was compared in left- and right-sided living kidney donors. The primary endpoint was plasma cortisol response to low-dose adrenocorticotropic hormone (ACTH) stimulation. Secondary endpoints included plasma renin and ACTH concentration as well as adrenal volume in response to donor nephrectomy. A total of 30 healthy donors-20 left- and 10 right-sided donations-were included. On postoperative day 1, response to low-dose ACTH stimulation was intact, but significantly lower after left-sided donor nephrectomy. After 28 days, adrenal responsiveness to ACTH stimulation did not differ any longer. Magnetic resonance imaging volumetry showed no significant adrenal volume change over 4 weeks, neither after left- nor after right-sided nephrectomy. In conclusion, left-sided living kidney donation entails a transiently reduced adrenocortical responsiveness, which returns to baseline after 28 days.

Evaluation of Early Corticosteroid Therapy in Management of Pediatric Septic Shock in Pediatric Intensive Care Patients: A Randomized Clinical Study.

Septic shock is a major healthcare problem. Adrenal insufficiency (AI) in children with septic shock is a recognized complication, yet is controversial regarding its management and effect on mortality. According to the current guidelines, children with risk factors for AI should receive a stress dose of steroids in step 3 of treatment. This study aimed to evaluate and compare early corticosteroid therapy with the traditional use of steroids among pediatric septic shock patients. This prospective randomized interventional clinical study included 3 groups of patients (32 each) and was conducted in Alexandria University pediatric intensive care unit. By protocol, the first group received steroids in step 3 of the treatment according to the current international guidelines (group A), and the second group was managed as group A and was tested for AI by adrenal stimulation test using intramuscular adrenocorticotropic hormone (cosyntropin) (group B). The third group received steroids at the start of fluid therapy (group C). A fourth group (group D) was created by adding patients from groups A and B who needed corticosteroids in the third stage of therapy according to the international protocol in 1 group. All patients were evaluated for basal serum cortisol and plasma adrenocorticotropic hormone concentrations. The data showed a statistically significant shorter shock reversal time among patients receiving corticosteroids at the start of treatment compared with those who received it at the third step of treatment (P = 0.046); however, mortality was not statistically different among the groups. In addition, there was no superinfection in cases receiving early steroid therapy. Early use of corticosteroid in patients with septic shock might shorten the shock reversal time without increase in mortality or superinfection.

The Role of Cytokines in the Peripheral Blood of Major Depressive Patients

Recent technological advances offer an opportunity to further elucidate the complex cytokine network in Major Depressive Disorder (MDD). The objective of this study was to investigate the role of pro-inflammatory and anti-inflammatory cytokines in the mechanism of depressive disorders. Given the activating role of cytokines on the hypothalamic-pituitary-adrenal (HPA) axis, and the relevance of its regulation in MDD, we also analyzed the relationships between several cytokines and cortisol levels. Twenty-five unipolar depressive patients and 20 healthy controls were recruited in this study. Flow cytometric bead array system (FCM-CBA) was used to examine the concentration of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, INF-α) in peripheral blood. Plasma Adrenocorticotropic Hormone (ACTH) and serum cortisol concentrations were detected. Compared with the controls, depressive patients had a significant increase in concentration of IL-2, TNF, serum cortisol, and TNF/IL-4 (p < 0.05). There was a significant positive correlation between serum cortisol and IL-2, as well as ACTH and IL-2 (p < 0.05) in depressive patients. There was a significant positive correlation between IL-2 and the Hamilton depression rating scale (HAMD) total scores in depressive patients, and also with TNF (p < 0.05). There was no significant difference in concentration of IL-4, IL-6, IL-10, and INF-α between two groups (p > 0.05). The present results suggest that depressive patients had an increase in concentration of some pro-inflammatory cytokines. Both IL-2 and TNF play important roles in the development of depressive disorders, and their concentration in peripheral blood may be used to evaluate the severity of depressive disorders.

Effects of dietary supplementation of Chinese herb medicine mixture on rumen fermentation, nutrient digestion and blood profile in goats

Twenty adult goats, fitted with ruminal cannulae, were used to investigate the effects of dietary supplementation of Chinese herbal medicine (CHM) mixtures on rumen fermentation, nutrient digestion and blood profiles. The wethers were assigned equally to one of the two dietary treatments according to a randomized controlled trial design. One dietary treatment was the basal diet, while the other was the CHM mixture diet consisting of the basal diet and the CHM mixture. Chinese Mosla, Atractylodes rhizome, Officinal Magnolia bark, white hyacinth bean and Liriope root tuber were mixed with a weight ratio of 8:4:4:4:5 to make up the CHM mixture. This mixture was added to the basal diet at 15 g/kg feed. The dietary supplementation of the mixture increased ruminal fluid concentrations of acetate, butyrate and total volatile fatty acids, and the ruminal activities of avicelase, carboxymethyl cellulase, cellobiase and xylanase. It also improved the ruminal effective degradability of dry matter, organic matter and amylase-treated ash-free neutral detergent fibre from the forage, apparent total tract digestibility of gross energy, dry matter, organic matter, crude protein, amylase-treated ash-free neutral detergent fibre, ash-free acid detergent fibre and calcium. Whole blood pH and concentrations of actual bicarbonate, buffer excess and magnesium ion, plasma concentrations of leptin, total protein, albumin, globulin, C-reactive protein, immunoglobulin A/G/M and complement 3/4 increased. Furthermore, plasma activities of nitric oxide synthase, glutathione peroxidase and total superoxide dismutase and plasma total antioxidative capacity increased. However, plasma concentrations of adrenocorticotropic hormone, aldosterone, cortisol, glucose, urea nitrogen and lactic acid and plasma activities of alanine transaminase, creatine kinase and lactate dehydrogenase decreased. These results indicated that the dietary supplementation of the CHM mixture exerted some positive regulating effects on the nervous system, the endocrine system and the immune system of goats, thus improving the functions of immunity and antioxidation, as well as the digestion and metabolism of nutrients. However, the CHM mixture did not affect their rumen fermentation patterns.Keywords: Chinese herbal medicine, rumen environmental parameter, digestibility, blood indicator, ruminant

Effects of anesthesia with isoflurane on plasma concentrations of adrenocorticotropic hormone in samples obtained from the cavernous sinus and jugular vein of horses.

OBJECTIVE To determine effects of anesthesia on plasma concentrations and pulsatility of ACTH in samples obtained from the cavernous sinus and jugular vein of horses. ANIMALS 6 clinically normal adult horses. PROCEDURES Catheters were placed in a jugular vein and into the cavernous sinus via a superficial facial vein. The following morning (day 1), cavernous sinus blood samples were collected every 5 minutes for 1 hour (collection of first sample = time 0) and jugular venous blood samples were collected at 0, 30, and 60 minutes. On day 2, horses were sedated with xylazine hydrochloride and anesthesia was induced with propofol mixed with ketamine hydrochloride. Horses were positioned in dorsal recumbency. Anesthesia was maintained with isoflurane in oxygen and a continuous rate infusion of butorphanol tartrate. One hour after anesthesia was induced, the blood sample protocol was repeated. Plasma ACTH concentrations were quantified by use of a commercially available sandwich assay. Generalized estimating equations that controlled for horse and an expressly automated deconvolution algorithm were used to determine effects of anesthesia on plasma ACTH concentrations and pulsatility, respectively. RESULTS Anesthesia significantly reduced the plasma ACTH concentration in blood samples collected from the cavernous sinus. CONCLUSIONS AND CLINICAL RELEVANCE Mean plasma ACTH concentrations in samples collected from the cavernous sinus of anesthetized horses were reduced. Determining the success of partial ablation of the pituitary gland in situ for treatment of pituitary pars intermedia dysfunction may require that effects of anesthesia be included in interpretation of plasma ACTH concentrations in cavernous sinus blood.

Responses of Adenohypophyseal Hormones to Substance P Administration in Geldings: Comparison to Responses After Brief Exercise and Sulpiride Administration

Nine adult geldings were used in three experiments to study the possible role of substance P in the prolactin responses to nondopaminergic stimuli. Experiment 1 was performed as an incomplete Latin square design to determine the secretory responses of prolactin, growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to IV administration of substance P. Doses tested and compared to no peptide (0 dose, control) were 62, 125, 250, and 500 μg of substance P. The three highest doses of peptide caused an immediate rise in heart rate, sweating, salivation, rhinorrhea, stretching of hind legs, and defecation. The lowest dose (62 μg) caused minor sweating, some rhinorrhea, and a rise in heart rate. Recovery from these physical responses was complete in approximately 30 minutes. All doses of substance P caused an immediate rise (P < .01) in plasma prolactin concentrations, with the three highest doses producing similar responses, and the 62 μg dose producing a minimal response (P < .05). Concentrations of ACTH (P < .01) and GH (P = .05) also increased after substance P administration; concentrations of LH, FSH, and TSH were unaffected. Experiment 2 compared the effects of brief exercise on hormonal characteristics. Two minutes of trotting increased (P < .01) plasma concentrations of GH, ACTH, and prolactin, as well as LH (P = .055). Experiment 3 determined the relative responses of prolactin to a fixed dose of sulpiride (0.1 mg/kg of body weight). In general, the prolactin responses to substance P were similar to those after exercise, which were both generally less than after sulpiride. These data are consistent with a possible role of substance P in the prolactin response to stressful stimuli.

Environmental enrichment reverses cognitive impairments provoked by Western diet in rats: Role of corticosteroid receptors

AimsPrevious studies demonstrated that the Western diet (WD), which is rich in saturated fat (HFD) and refined sugar (HSU), is related to the impairments of hippocampus-dependent learning and memory and forebrain synaptic plasticity in rodents. The environmental enrichment (EE) has been shown to enhance learning and memory in the HFD-induced cognitive deficits, but the exact mechanism is still not clearly understood. Therefore, the present study aimed to clarify the effects of the EE on spatial memory in WD-fed rats, and to analyze the potential role of corticosteroid receptors in the EE conditioning. Main methodsMale Wistar albino rats were housed in either an enriched or standard environment and fed with the HFD (35% of energy as fat), HSU (100% of carbohydrate as sucrose) or standard rat chow for 4weeks. We used the Morris' water maze test (MWM) to assess the learning and memory performance, and measured plasma levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH), as well as glucocorticoid (GR) and mineralocorticoid receptor (MR) levels in the hippocampus. Key findings: The results showed that HFD-fed rats displayed poorer learning and memory performance evaluated with MWM than controls. The EE reversed the cognitive deficits caused by the HFD. In addition, the EE resulted in an increase of GR and MR levels without affecting plasma CORT and ACTH concentrations. SignificanceBased on these findings, it could be suggested that the EE plays an important role in amelioration of the HFD-induced cognitive impairments, but this intervention is independent of the hypothalamic–pituitary–adrenal axis and hippocampal corticosteroid receptor levels.

Venipuncture does not affect adrenocorticotropic hormone concentration in horses

Increased adrenocorticotropic hormone (ACTH) concentrations in venous blood are an important indicator of pituitary pars intermedia dysfunction (PPID) in horses (van der Kolk and others 1995). However, a physiological response...

Antidepressant-like effects of quercetin in diabetic rats are independent of hypothalamic-pituitary-adrenal axis.

Quercetin, one of the most potent flavonol in the family of flavonoids, has been shown to have benefits against diabetes and its complications. In the present study, we investigated effects of quercetin on depression-like behaviours and hypothalamic-pituitary-adrenal (HPA) axis in diabetic rats. Experimental diabetes was induced by using streptozotocin, and either 50 or 100 mg/kg quercetin was intraperitoneally administered for 21 days. Following the last treatment, animals were subjected to the forced swim test, and subsequently, the blood was obtained by cardiac puncture to measure plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels. A significant increase of the total immobile time, accompanied by a decrease in the immobility latency, which suggests a depressive status, was observed in diabetic animals that was reversed by the treatment of 50 mg/kg quercetin. However, the higher dose of quercetin (100 mg/kg) was ineffective in alleviating depression-like behaviours. The plasma concentrations of ACTH, and total- and free-CORT were not affected by both doses of quercetin. Therefore, we concluded that the antidepressant-like effects of quercetin in diabetes are independent of the HPA axis.