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PubMed2004

Perinatal food deprivation induces marked alterations of the hypothalamo-pituitary-adrenal axis in 8-month-old male rats both under basal conditions and after a dehydration period.

Dehydration is a classic homeostatic stressor in rats that leads to a series of endocrine responses including stimulation of the hypothalamo-pituitary-adrenal (HPA) axis. During the last decade, it has been well established that perinatal food restriction is associated with the onset of diseases in adults. Our previous demonstration of long-term alterations in HPA axis activity in both basal conditions and after a 72-hour dehydration period in 4-month-old rats exposed to a 50% maternal food restriction (FR50) in late gestation and lactation prompted us to investigate whether such perinatal undernutrition further affects HPA axis activity in mature animals. As previously described in 4-month-old rats under basal conditions, 8-month-old FR50 rats showed reduced body weight and an enhanced ratio between mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA levels in the hippocampus, as well as increased pro-opiomelanocortin (POMC) mRNA levels in the adenohypophysis. In addition, numerous additional alterations appeared in mature rats. In the hypothalamus, levels of vasopressin (VP) mRNAs were increased both in the paraventricular nucleus (PVN) and in the supraoptic nucleus (SON). In the adenohypophysis, GR and prohormone-convertase 2 (PC2) mRNA levels were significantly increased, whereas prohormone-convertase 1 (PC1) mRNA was not affected by maternal undernutrition. Interestingly, undernourished animals exhibited high plasma levels of total and free corticosterone in spite of normal corticotropin (ACTH) levels, an indication that HPA basal activity is enhanced by maternal undernutrition in 8-month-old animals. Dehydration for 72 h induced a rise in ACTH plasma levels, but did not modify total and free corticosterone plasma levels in 8-month-old FR50 animals. In the adenopituitary, POMC mRNA levels were decreased after dehydration but PC1 mRNA levels were unaffected. The present study indicates that maternal food restriction during the perinatal period dramatically affects the activity of the HPA axis until the age of 8 months. We speculate that higher basal HPA activity and an inadequate HPA response after dehydration in mature animals may contribute to diseases such as hypertension, known to develop with aging in perinatally growth-restricted rats.

Adrenocorticotropic Hormone↗
PubMed2005

Expression analysis of hypothalamic and pituitary components of the growth hormone axis in fasted and streptozotocin-treated neuropeptide Y (NPY)-intact (NPY+/+) and NPY-knockout (NPY-/-) mice.

In the fasted and the streptozotocin (STZ)-induced diabetic male rat, hypothalamic growth hormone (GH)-releasing hormone (GHRH) mRNA levels, and pulsatile GH release are decreased. These changes are believed to be due to a rise in hypothalamic neuropeptide Y (NPY) that inhibits GHRH expression. To directly test if NPY is required for metabolic regulation of hypothalamic neuropeptides important in GH secretion, NPY, GHRH and somatostatin (SRIH) mRNA levels were determined in fasted (48 h) and STZ-treated wild-type (NPY(+/+)) and NPY-knockout (NPY(-/-)) mice by ribonuclease protection assay. In addition, pituitary receptor mRNA levels for GHRH (GHRH-R), ghrelin (GHS-R) and SRIH (sst2) were assessed by RT-PCR. Under fed conditions the GH axis of NPY(+/+) and NPY(-/-) did not differ. In the NPY(+/+) mouse, fasting resulted in a 23% weight loss and >250% increase in NPY mRNA accompanied by a significant reduction in both GHRH and SRIH mRNA. These changes were associated with increases in pituitary expression of GHRH-R and GHS-R and a concomitant suppression of sst2. In the NPY(-/-) mouse, fasting also resulted in a 23% weight loss and comparable changes in GHRH-R and sst2, but failed to alter GHRH, SRIH and GHS-R mRNA levels. Fasting resulted in an overall increase in circulating GH, which reached significance in the fasted NPY(-/-) mouse. Induction of diabetes in NPY(+/+) mice, using a single, high-dose, STZ injection (150 mg/kg), resulted in modest weight loss (5%), and a 158% increase NPY expression which was associated with reciprocal changes in pituitary GHS-R and sst2 expression, similar to that observed in the fasted state, but no change in hypothalamic GHRH or SRIF expression was observed. Induction of diabetes in NPY(+/+) and NPY(-/-) mice, using a multiple, low-dose, STZ paradigm (5 consecutive daily injections of 40 mg/kg), did not alter body weight, hypothalamic neuropeptide expression or pituitary receptor expression, with the exception that sst2 mRNA levels were suppressed and GH levels did rise in the NPY(-/-) mouse. These observations demonstrate that NPY is not required for basal regulation of the GH axis, but is required for fasting-induced suppression of GHRH and SRIH expression, as well as fasting-induced augmentation of pituitary GHS-R mRNA. In contrast to the rat, fasting clearly did not suppress circulating GH levels in mice, but resulted in an overall rise in mean GH levels, similar to that observed in other mammalian species. The fact that many of the fasting-induced changes in the GH axis were observed in the high-dose STZ-treated mice, but were not observed in the multiple, low-dose paradigm, suggests STZ-mediated modulation of GH axis function is dependent on the severity of the catabolic state and not hyperglycemia.

Animals↗
PubMed2005

Age-related changes in hypothalamic-pituitary-adrenal axis activity of male C57BL/6J mice.

As there is little known about age-related changes in the hypothalamic-pituitary-adrenal (HPA) axis of mice, we determined the daily patterns of corticosterone secretion every 2 h, together with adrenocorticotropic hormone (ACTH) release and central HPA axis markers in the morning and evening of 3-, 9- and 16-month-old male C57BL/6J mice. We observed that: (i) corticosterone secretion showed a distinct age-related circadian pattern. During the light period this was expressed by relative hypercorticism in 9-month-old mice and relative hypocorticism in 16-month-old mice. ACTH was elevated at 16 months of age; (ii) mineralocorticoid (MR) and glucocorticoid receptor (GR) mRNA expression in the hippocampus was significantly decreased in 9-month-old mice, whereas in 16-month-old mice, expression was similar to young animals. Circadian variation was modest in all age groups; (iii) the parvocellular hypothalamic paraventricular nucleus (PVN) expressed very high vasopressin mRNA, which was subject to circadian variation in 3- and 9-month-old mice. Furthermore, significant levels of MR mRNA were expressed in the PVN. In conclusion, basal HPA axis activity and expression of its central regulatory markers are age-dependent in mice. This suggests that the capacity to adjust to environmental demands is either a function of age, or depends on different dynamics of the HPA axis.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Sex steroid regulation of the hypothalamo-pituitary-adrenal axis activity in middle-aged mice during endotoxic shock.

Many studies have documented the presence of a sexually dimorphic response of neuroendocrine functions in response to immune signals. The aims of the present study were to evaluate the hypothalamopituitary-adrenal (HPA) axis response to inflammatory stress stimulus in 15-month-old mice, and to determine whether such a response depends on circulating sex steroids. Our results indicate that in the 15-month-old mice: (1) there is a sexual dimorphism in the HPA axis activity in basal condition and after endotoxin treatment with generally higher levels of several parameters of this axis in female than in male mice, (2) gonadectomy alone, followed by sex steroid therapy, modulates HPA axis function in both basal and stress conditions, and (3) whereas estradiol plays a stimulatory role on adrenal function, testosterone inhibits adrenal glucocorticoid production. This study further suggests a clear sexual dimorphism in middle-aged mice injected with endotoxin. These results may be relevant for the treatment of sepsis in aged patients.

Adrenal Cortex↗
PubMed1993

Interferon-alpha stimulates the hypothalamic-pituitary-adrenal axis in vivo and in vitro.

The successful therapeutic use of interferon-alpha (IFN-alpha) in myeloproliferative disorders offered the possibility to test its acute and long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis in humans. ACTH and cortisol plasma concentrations were measured in 8 patients hourly starting from 4 p.m. through 12 p.m. on three occasions. The first time all patients were studied before initiation of therapy, when the vehicle was injected alone. The patients were studied again on day 1 of IFN-alpha therapy (5 million units) and once more after 3 weeks of therapy. On the control day, plasma concentrations of ACTH and cortisol were in the range expected for this time of day. In contrast, after the first administration of IFN-alpha a significant stimulation of the HPA axis was observed. After 3 weeks of IFN-alpha therapy, no significant stimulation of the HPA axis occurred after administration of IFN-alpha. IFN-alpha-induced adaptive changes in the HPA axis were also indicated by a significantly enhanced ACTH and cortisol response to exogenously administered supramaximal doses of corticotropin-releasing hormone (CRH) when the patients had been on IFN-alpha treatment for 3 weeks. To determine the exact locus of the IFN-alpha action, in vitro experiments were performed using rat hypothalamic organ and primary pituitary and adrenal cell culture systems. Thereby a significant stimulation of hypothalamic CRH secretion and rat adrenal corticosterone production was observed after INF-alpha at concentrations of 5 x 10(-8) M or 10(-7) M respectively. In contrast, no direct IFN-alpha effect on pituitary ACTH secretion could be observed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1994

In vivo and in vitro effects of arginine-vasopressin receptor antagonists on the hypothalamic-pituitary-adrenal axis in the rat.

Arginine-vasopressin (AVP) is regarded as a potent stimulator of pituitary adrenocorticotropin (ACTH) secretion and participates therefore in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis function in concert with the physiological activator of the axis, hypothalamic corticotropin-releasing hormone (CRH). We examined the effects of AVP and/or three synthetic V1b receptor antagonists on the activity of the HPA axis in vivo and in vitro in the rat. AVP was injected intravenously to Sprague-Dawley rats (1 microgram/rat) through an indwelling jugular catheter. AVP stimulated ACTH release, with maximal effect 10 min after injection. Intravenous injection of three V1b antagonists, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-ethyltyrosine, 4-valine] arginine vasopressin (d(CH2)5[Tyr(Et2)]VAVP (WK 1-1), 9-desglycine[1-(beta-mercapto-beta,beta- cyclopentamethylenepropionic acid), 2-O-ethyltyrosine, 4-valine] arginine vasopressin desGly9d(CH2)5 [Tyr(Et2)]-VAVP (WK 3-6), and 9-desglycine [1-(beta-mercapto-beta,beta- cyclopentamethylenepropionic acid),2-D-(O-ethyl)tyrosine, 4-valine ] arginine vasopressin des Gly9d(CH2)5[D-Tyr(Et2)]VAVP (AO 3-21), prevented AVP-stimulated ACTH secretion. Explanted rat hypothalami incubated in vitro with graded concentrations of AVP (10(-14)-10(-5) M) secreted immunoreactive CRH (iCRH) in a concentration-dependent fashion. Maximal stimulatory effect occurred at the concentration of 10(-6) M. Incubation of hypothalami with WK 1-1, WK3-6, or AO 3-21 (10(-6) M) prevented AVP-stimulated iCRH secretion. Results suggest that AVP plays a relevant, multiple role in the activation of the HPA axis in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1994

Hypothalamic-pituitary-adrenocortical axis changes in the rat after long-term treatment with the reversible monoamine oxidase-A inhibitor moclobemide.

The effects of the reversible monoamine oxidaseA (MAOA) inhibitor moclobemide on the rat hypothalamic-pituitary-adrenocortical (HPA) axis were studied. The time-course experiments showed that moclobemide, given via the drinking water (4.5 mg/kg/day), produces significant decreases (p < 0.05) in adrenal weight after 5 (-23%) and 7 weeks (-16%) of treatment. It was found that long-term moclobemide treatment had neuroanatomically distinct effects on corticosteroid receptor expression. Hippocampal mineralocorticoid receptor (MR) levels were upregulated at 2 (+65%), 5 (+76%) and 7 (+19%) weeks of treatment. Glucocorticoid receptor (GR) levels in this limbic brain structure were slightly up-regulated by 10% at 5 weeks, and indistinguishable from controls after 2 and 7 weeks of treatment. After 5 weeks of treatment, MR levels were unchanged in the hypothalamus, and increased by 44, 24 and 28% in the neocortex, amygdala and anterior pituitary, respectively. GR concentrations were elevated by 24 and 14% in the hypothalamus and anterior pituitary, respectively, whereas neocortical and amygdaloid receptor levels were not altered. After 5 weeks of moclobemide treatment, marked decreases in [125I]Tyr0-ovine corticotropin-releasing hormone ([125I])-oCRH binding capacity and proopiomelanocortin (POMC) mRNA content were observed in the anterior pituitary. Regarding the functional implications of long-term anti-depressant treatment, moclobemide treatment (5 weeks, 4.5 mg/kg/day) significantly attenuated stress (30-min novel environment)-induced plasma ACTH (-35%) and corticosterone (-29%) levels; no changes were observed in basal plasma ACTH and corticosterone levels. In conclusion, this study shows that moclobemide has a concerted influence on multiple elements of the HPA axis manifesting functionally as a reduced neuroendocrine responsiveness to stress. In previous experiments, it was found that the structurally and pharmacologically distinct antidepressant amitriptyline after long-term administration also attenuated HPA axis activity. We postulate that an adjustement of HPA axis activity may be regarded as a common denominator for clinically efficacious antidepressant drugs.

Adrenal Cortex↗
PubMed1994

Sex differences in the hypothalamo-pituitary-adrenal axis response to inflammatory and neuroendocrine stressors. Evidence for a pituitary defect in the autoimmune disease-susceptible female Lewis rat.

Susceptibility to inflammatory disease in infantile Lewis (LEW/N) female rats seems to be related to their impaired hypothalamo-pituitary-adrenal (HPA) axis response to different inflammatory stimuli, while the relative resistance to this type of disease in Fischer (F344/N) female rats is apparently due to their potent HPA axis response to the same stimuli. In the present study, we attempted to elucidate whether there is an impairment in the HPA axis response in the juvenile female LEW/N rat to inflammatory and noninflammatory stimuli, and also to determine whether the endogenous sex-steroid environment influences the HPA axis function in both strains of rats. For these purposes, juvenile F344/N and LEW/N rats of both sexes were submitted to different treatments: (a) inhalation of normal atmosphere or ether vapors for 1 min (Ether); (b) i.p. injection of vehicle alone or containing CRH (0.5 microgram/rat), arginine vasopressin (AVP; 5 micrograms/rat, angiotensin II (AII; 5 micrograms/rat), insulin (INS; 0.3 IU/rat), bacterial lipopolysaccharide (LPS; 100 micrograms/rat) or snake venom (SV; 100 micrograms/rat). Rats were then killed at different time intervals (in min) after treatments: 20 for Ether, AVP and CRH, 30 for AII, 45 for INS, 60 for SV and 120 for LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1996

Interleukin 6 modulates interleukin-1-and stress-induced activation of the hypothalamic-pituitary-adrenal axis in male rats.

This study examined the interaction between interleukin 6 (IL-6) and IL-1 and between IL-6 and stress on the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Coadministration of IL-6 (100 ng/rat) with IL-1 (20 or 100 mg/ rat) resulted in synergistic stimulation of the HPA axis, as determined by increased plasma levels of ACTH and corticosterone (CORT) which were greater in rats that received both cytokines than in rats receiving either cytokine alone. Concomitant administration of IL-6 (100 ng/rat) with exposure to a novelty stressor also synergistically stimulated the activation of the HPA axis, as IL-6-treated rats subjected to novelty stress had greater increases in plasma levels of ACTH and CORT than vehicle-treated rats exposed to novelty stress or rats receiving IL-6 alone. However, concomitant administration of IL-6 (100 ng/rat) did not significantly affect restraint stress induced elevation of plasma levels of ACTH and CORT, although IL-6 tended to prolong restraint stress induced elevation of plasma levels of CORT. These findings indicate a modulatory role for IL-6 stimulated HPA axis activity in response to IL-1 or a novelty psychological stressor, but not for restraint stress.

Adrenal Glands↗
PubMed1995

Evidence that activation of the hypothalamo-pituitary-adrenal axis by electrical stimulation of the noradrenergic A1 group is not mediated by noradrenaline.

The paraventricular nucleus (PVN) of the hypothalamus, where the CRF-containing neurosecretory cells controlling the hypothalamo-pituitary-adrenal (HPA) axis are located, receives a dense noradrenergic innervation from the A1 group of the caudal ventrolateral medulla. In the present study we studied the relationship between release of noradrenaline (NA) in the PVN and activation of the HPA axis in response to electrical stimulation of the A1 region. In the urethane-anesthetized male rat, extracellular NA in the PVN was monitored on line by electrochemical recording while the activity of the HPA axis was estimated by measurement of ACTH in blood samples. A 1 min, 10 Hz stimulation evoked a significant increase of extracellular NA in the PVN as well as an ACTH surge in blood. The NA and ACTH response evoked by stimulation in the 3- to 14-Hz range were found to be frequency dependent. However, whilst the NA response increased in an exponential manner with respect to frequency, the ACTH response appeared to plateau between 10 and 14 Hz. Specific lesions of the noradrenergic terminals in the PVN, by bilateral local administration of 6-hydroxydopamine, markedly reduced the ACTH response to stimulation. Intracerebroventricular injection of desmethylimipramine, a NA uptake inhibitor, enhanced the increase in extracellular NA evoked by submaximal stimulation about 2.5-fold but did not modify the corresponding ACTH response. Combined intracerebroventricular injection of alpha- and beta-adrenergic antagonists, phentolamine and propanolol respectively, did not prevent the ACTH response evoked by stimulation. Following stimulation of the caudal ventrolateral medulla, the ACTH response thus appears to result from the stimulation of the A1 noradrenergic group projecting to the PVN. However, the inability of pharmacological manipulations which enhance or block central noradrenergic transmission to influence the ACTH response suggests that the noradrenergic endings in the PVN originating from the A1 group use a transmitter other than NA to activate the HPA axis at the PVN level.

Adrenocorticotropic Hormone↗
PubMed1997

Increased vasopressinergic activity as a possible compensatory mechanism for a normal hypothalamic-pituitary-adrenal axis response to stress in BALB/c nude mice.

A bidirectional relationship between the immune and neuroendocrine systems is now widely accepted. Since it is well known that the thymus plays an important role in the regulation of the immune function, we decided to explore whether a lack of the thymic function may influence hypothalamic-pituitary-adrenal (HPA) axis activity. Eight-week-old female mice of both strains, nude and control BALB/c, were used to study: (a) the in vivo response of the HPA axis to several stress stimuli acting at either the hypothalamic (insulin administration and ether vapor inhalation), pituitary (CRH and vasopressin injections) or adrenal (ACTH treatment) level and (b) the in vitro response of hypothalamic fragments to high KCl (48 mM) stimulation. The results indicate that: (1) basal plasma ACTH and vasopressin levels were significantly (p < 0.05) higher in nude than in control BALB/c mice, whereas basal plasma corticosterone concentrations were similar in both strains of mice; (2) although no significant strain-related difference in the stress-induced ACTH secretion in plasma was found, hypothalamic stimuli were able to induce a significantly (p < 0.05) higher secretion of glucocorticoid in plasma in nude than in control BALB/c mice; (3) the pattern of in vitro hypothalamic CRH release was similar in both strains of animals; however, basal AVP output and that stimulated by 48 mM KCl were significantly (p < 0.05) higher in nude than in control hypothalamic fragments, and (4) whereas hypothalamic CRH, pituitary ACTH and adrenal glucocorticoid contents were similar in both strains, hypothalamic AVP content was significantly (p < 0.05) higher in athymic than in control mice. In summary, our results indicate that nude mice have an increased vasopressinergic function which could contribute to a normal HPA axis activity; thus, adult athymic mice of BALB/c origin could compensate, due to their increased vasopressinergic function, for a robust glucocorticoid release to protect themselves immediately after aggression. It remains to be determined whether this enhanced vasopressinergic function is a result of an early adrenal insufficiency due to congenital deficiency of thymic factors known to stimulate HPA axis function.

Adrenocorticotropic Hormone↗
PubMed1982

Age-associated change in QRS axis: intrinsic or extrinsic ageing?

Human ageing is most usefully conceptualised as an interaction between intrinsic and extrinsic processes. Comparison of age-associated trends in populations living under different environmental conditions provides a method of recognising the effects of extrinsic influences. This paper compares the age-associated trend in mean frontal plane QRS axis in the male adult population of Pukapuka with the trend observed in an age-matched sample from a British population. The Pukapukans show no rise in mean blood pressure with age and have other features placing them at low risk of coronary heart disease. Although the British population showed the shift to the left in mean QRS axis characteristic of economically advanced populations there was no change in mean QRS axis with age among the Pukapukans. The conclusion is drawn that the shift with age in QRS axis observed in advanced populations is extrinsic in origin but is not necessarily a manifestation of coronary heart disease.

Adult↗
PubMed1976

Left axis deviation: a spectrum of intraventricular conduction block.

The effects of left axis shift (greater than -30 degrees) on intraventricular conduction time (IVCT) were studied in 63 subjects in whom electrocardiograms before and after appearance of the left axis shift were available. Subjects with electrocardiographic evidence of left or right ventricular hypertrophy, left or right bundle branch block, myocardial infarction, pre-excitation and those receiving antiarrthymic drugs were excluded. The IVCT increased by an average of 25 msec when the QRS axis shifted to -30 degrees or beyond. When the individual AQRS was related to the IVCT a linear correlation (r = -0.8) was observed. It appears that a continuum relation between the AQRS and the IVCT exists throughout the counterclockwise range of +90 degrees to -90 degees. In all leftward shifts in AQRS from from +90 degrees there is a prolongation in IVCT. Our observations indicate that all leftward shifts in AQRS, including the extreme left axis shift (left anterior hemiblock), represent a spectrum of intraventricular conduction block.

Adult↗
PubMed2000

The insulin-like growth factor axis: A review of atherosclerosis and restenosis.

Insulin-like growth factors I and II (IGF-I and -II) and their regulatory proteins are secreted by cells of the cardiovascular system. They are growth promoters for arterial cells and mediators of cardiovascular disease. IGFs are bound to IGF binding proteins (IGFBPs), which modulate IGF ligand-receptor interaction and consequently to IGF action. IGFBPs are in turn posttranslationally modulated by specific proteases. This dynamic balance (IGFs, IGFBPs, and IGFBP proteases) constitutes the IGF axis and ultimately determines the extent of IGF-dependent cellular effects. Dysregulated actions of this axis influence coronary atherosclerosis through effects on vascular smooth muscle cell growth, migration, and extracellular matrix synthesis in the atherosclerotic plaque. IGF-I promotes macrophage chemotaxis, excess LDL cholesterol uptake, and release of proinflammatory cytokines. Endothelial cells also receive the effects of IGFs stimulating their migration and organization forming capillary networks. Neointimal hyperplasia of restenosis after coronary artery injury is also modulated by the IGF axis. IGFs stimulate vascular smooth muscle cell proliferation and migration to form the neointima and upregulate tropoelastin synthesis after disruption of the elastic layer. Understanding IGF axis regulation establishes a scientific basis for strategies directed to limit or reverse plaque growth and vulnerability in atherosclerosis and in the neointimal hyperplasia of restenosis.

Arteriosclerosis↗
PubMed2006

Intervention at the level of the neuroendocrine-immune axis and postoperative pneumonia rate in long-term alcoholics.

RATIONALE: Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit (ICU) stay. Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal (HPA) axis and immunity. OBJECTIVES: The aim of this study was to evaluate HPA intervention with low-dose ethanol, morphine, or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients. METHODS: In this randomized, double-blind controlled study, 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence. Nonalcoholic patients were included but only as a descriptive control. Perioperative intervention with low-dose ethanol (0.5 g/kg body weight per day), morphine (15 mug/kg body weight per hour), ketoconazole (200 mg four times daily), and placebo was started on the morning before surgery and continued for 3 d after surgery. Blood samples to analyze the neuroendocrine-immune axis were obtained on the morning before intervention and on Days 1, 3, and 7 after surgery. MEASUREMENTS AND MAIN RESULTS: In long-term alcoholic patients, all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio. All interventions decreased the pneumonia rate from 39% to a median of 5.7% and shortened intensive care unit stay by 9 d (median) compared with the placebo-treated long-term alcoholic patients. CONCLUSIONS: Intervention at the level of the HPA axis altered the immune response to surgical stress. This resulted in decreased postoperative pneumonia rates and shortened intensive care unit stay in long-term alcoholic patients.

APACHE↗
PubMed1992

The relationship between personality and DSM-III axis I disorders in the population: results from an epidemiological survey.

OBJECTIVE: The aim of this study was to assess the relationships between specific personality disorders and DSM-III axis I conditions in a community sample. METHOD: A total of 810 subjects were examined by psychiatrists in the second stage of the Eastern Baltimore Mental Health Survey, part of the Epidemiological Catchment Area Program of the National Institute of Mental Health. A semistructured examination, the Standardized Psychiatric Examination, was employed to assess axis I and axis II conditions. Scales for compulsive and antisocial personality disorders were derived from DSM-III criteria. The relationships between scores on these personality disorder scales and the presence of generalized anxiety disorder, alcohol use disorders (alcohol abuse and alcohol dependence), and simple phobia were evaluated by using logistic regression. RESULTS: Higher compulsive personality scores were associated with a greater odds of generalized anxiety disorder and simple phobia but a smaller odds of alcohol use disorders. In contrast, higher antisocial personality scores were associated with a greater odds of alcohol use disorders but a smaller odds of generalized anxiety disorder. There was no relationship between antisocial personality scores and simple phobia. CONCLUSIONS: Personality disorders have specific relationships to axis I conditions, which suggests different vulnerabilities but also different protective influences.

Adolescent↗
PubMed1993

Interleukin-1 beta: a putative mediator of HPA axis hyperactivity in major depression?

OBJECTIVE: There is extensive evidence that major depression, and particularly melancholia, is characterized by hypothalamic-pituitary-adrenal (HPA) axis hyperactivity as well as systemic immune activation, which may be accompanied by increased interleukin-1 beta production. Interleukin-1 beta is known to enhance HPA axis activity during an immune response. This study investigated whether interleukin-1 beta production is related to HPA axis activity in depressed subjects. METHOD: The subjects were 28 inpatients with major or minor depression and 10 normal comparison subjects. The authors measured 1) the subjects' cortisol levels after an overnight 1-mg dexamethasone suppression test (DST) and 2) mitogen-stimulated supernatant interleukin-1 beta production by peripheral blood mononuclear cells. RESULTS: Statistically significant positive correlations between interleukin-1 beta production and post-DST cortisol values were found in the study group as a whole and in the depressed and normal subgroups separately. CONCLUSIONS: It is suggested that constituents of the immune response (such as interleukin-1 beta) in major depression may contribute to HPA axis hyperfunction in that illness.

Adult↗
PubMed1995

Axis II diagnoses among volunteers for HIV testing and counseling.

OBJECTIVE: The authors' goal was to investigate the rate of personality disorders (axis II diagnoses in DSM-III-R) among adults at risk for AIDS. METHOD: The Personality Disorder Examination was administered to 260 volunteers for HIV testing and counseling. RESULTS: Thirty-seven percent of the subjects who subsequently tested seropositive for HIV and 20% of those who tested seronegative were given DSM-III-R axis II diagnoses on the Personality Disorder Examination. Thirty percent of the HIV-positive subjects who knew their serostatus before they were tested were given DSM-III-R axis II diagnoses. CONCLUSIONS: The meaningful rates of axis II diagnoses that preexisted determination of HIV status and the relation of these diagnoses to subsequently determined serostatus underscore the importance of adequately assessing the occurrence of personality disorder in individuals at risk for HIV infection.

AIDS Serodiagnosis↗