Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The corticotropin-adrenocortical response to cold pressor challenge was investigated in a study of human immunodeficiency virus (HIV) infection. Data obtained from 16 HIV-1-positive and 28 HIV-1-negative subjects are presented in this report. After the insertion of a venicatheter and following 30 min of rest, the subjects immersed one of their hands in an ice-water mixture for 2 min, and serial blood samples were obtained for the determination of ACTH and cortisol levels. The results show a significant blunting in the ACTH response and marginally lower levels of cortisol, over all time points, in HIV-1-positive subjects compared to that in HIV-1-negative subjects.
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PMID:Abnormal pituitary-adrenocortical response in early HIV-1 infection. 838 Feb 11

Patients with acquired immune deficiency syndrome (AIDS) are reported to have increased basal cortisol and reduced stimulated cortisol release, but the dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis is not yet understood in patients with human immunodeficiency virus (HIV) infection during the advanced stage of disease that precedes the development of AIDS. To understand the status of the HPA axis during this phase of HIV infection, 25 non-AIDS ambulatory patients with advanced HIV infection and without evidence of adrenal or pituitary insufficiency were studied. Ovine corticotropin-releasing hormone was administered (1 microgram/kg BW) intravenously and plasma cortisol and adrenocorticotropin (ACTH) were measured over the following 120 minutes. Based on a standard response curve, obtained from CRH testing of 10 HIV negative volunteers with no HPA abnormalities, 13 patients were found to have normal response (group 1), 6 patients had reduced ACTH and cortisol response (group 2) and 6 patients had normal ACTH with reduced cortisol response (group 3). Basal cortisol and basal ACTH were comparable for control subjects and groups 1, 2, and 3. This suggests that, in advanced non-AIDS HIV patients with no clinical evidence of pituitary or adrenal disease, about 25% (group 2) have reduced pituitary reserve with high basal ACTH and cortisol, and about 25% (group 3) have reduced adrenal reserve with high basal cortisol and inappropriately normal basal ACTH, whereas about 50% (group 1) maintain normal HPA axis activity with increased basal cortisol secretion. The exact physiopathologic mechanism is not yet known, but an enhanced CRH production by the hypothalamus may explain the alterations in the HPA axis in advanced HIV disease.
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PMID:Hypothalamic-pituitary-adrenal function in non-AIDS patients with advanced HIV infection. 848 93

We prospectively studied adrenal function in 51 human immunodeficiency virus-positive male patients, including heterosexuals, homosexuals, and iv drug users, classified according to 1987 CDC criteria as belonging to stages II/III or IVC. Basal serum concentrations of cortisol (F), progesterone (P4) and 17 alpha-hydroxyprogesterone (17 alpha-OHP4) were determined during the two stages. In stage IVC patients, the circadian rhythms of ACTH and F were assessed, and ovine CRH (oCRH) and immediate cosyntropin-stimulating tests were evaluated. Serum concentrations of hormones were analyzed in relationship to the absolute CD4 cell count in all subjects. The mean serum F concentration in stage IVC patients, the mean P4 concentration in stage II/III and IVC patients, and the mean 17 alpha-OHP4 level in stage II/III patients were significantly increased compared to control values (P < 0.0001, P < 0.0001, and P < 0.002, respectively). The mean serum F concentration in stage IVC patients was significantly increased compared to that in stage II/III patients (P < 0.004), and the mean serum 17 alpha-OHP4 concentration in stage II/III patients was significantly increased compared to that in stage IVC patients (P < 0.02). In the 22 stage IVC patients, the circadian rhythms of ACTH and F were normal in all but 7 for ACTH and 5 for F, whereas oCRH test results indicated that 14 of them had reduced or blunted responses. By contrast, cosyntropin stimulation results were normal. CD4 cell counts were significantly negatively correlated with the serum F concentration (P < 0.02). In conclusion, during human immunodeficiency virus infection, the serum F concentration was negatively correlated with CD4 cell counts. Cosyntropin test results were normal, but 63% of the stage IVC men had abnormal responses to oCRH.
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PMID:Hypothalamo-pituitary-adrenal function in human immunodeficiency virus-infected men. 863 5

To evaluate pituitary and pituitary-dependent target organ function in men infected with the human immunodeficiency virus (HIV), 26 ambulatory HIV-positive men (13 with acquired immunodeficiency syndrome [AIDS]) and nine healthy control men were administered rapid sequential injections of thyrotropin (TSH)-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), ovine corticotropin (ACTH)-releasing hormone (oCRH), and human growth hormone-(GH)-releasing hormone (hGHRH). Blood samples were collected before and for 90 minutes after the injections for immunoassay of pituitary hormones, cortisol, testosterone, and free thyroxine (fT(4)). Data were analyzed for each group of men considering basal, peak, and incremental responses to the releasing hormones, as well as the time course of response of each hormone. Mean basal serum GH concentrations were the same in all groups (control, AIDS, and non-AIDS HIV-positive), but stimulated GH levels were substantially higher at all time points in both groups of HIV-positive subjects. Results for prolactin (PRL) were similar, although stimulated PRL levels were increased significantly only in the AIDS group. The mean basal serum TSH concentration and stimulated TSH levels at 60 and 90 minutes were significantly greater in the AIDS group than in the control group. Basal mean fT(4) concentration in the AIDS group was significantly less than in the control group. Mean basal and stimulated serum (total) testosterone concentrations in all groups were the same. However, basal serum luteinizing hormone (LH) concentrations in both groups of HIV-infected men were significantly greater than in controls; stimulated (peak) LH levels were not different from control levels. Basal and peak stimulated plasma ACTH concentrations were significantly increased in both HIV-infected groups. Basal serum cortisol levels were also greater, on average, in HIV-infected groups, although stimulated (peak) cortisol responses were not different. These results indicate that basal serum concentrations of TSH, LH, ACTH, and cortisol are modestly increased in men with AIDS, and that maximum levels of GH, PRL, TSH, and ACTH stimulated by the releasing hormones are also increased in this group. Measurements obtained in the non-AIDS HIV-infected men showed a pattern generally similar to that obtained in men with AIDS, but less marked. The basis for the increased pituitary activity is unknown; we speculate that it is due to modestly impaired target organ function and to increased hypothalamic stimulation.
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PMID:Anterior pitutiary and pitutiary-dependent target organ function in men infected with the human immunodeficiency virus. 863 49

Current evidence indicates that the neuroendocrine system is the highest regulator of immune/inflammatory reactions. Prolactin and growth hormone stimulate the production of leukocytes, including lymphocytes, and maintain immunocompetence. The hypothalamus-pituitary-adrenal axis constitutes the most powerful circuit regulating the immune system. The neuropeptides constituting this axis, namely corticotrophin releasing factor, adrenocorticotrophic hormone, alpha-melanocyte stimulating hormone, and beta-endorphin are powerful immunoregulators, which have a direct regulatory effect on lymphoid cells, regulating immune reactions by the stimulation of immunoregulatory hormones (glucocorticoids) and also by acting on the central nervous system which in turn generates immunoregulatory nerve impulses. Peptidergic nerves are major regulators of the inflammatory response. Substance P and calcitonin gene-related peptide are pro-inflammatory mediators and somatostatin is anti-inflammatory. The neuroendocrine regulation of the inflammatory response is of major significance from the point of view of immune homeostasis. Malfunction of this circuit leads to disease and often is life-threatening. The immune system emits signals towards the neuroendocrine system by cytokine mediators which reach significant blood levels (cytokine-hormones) during systemic immune/inflammatory reactions. Interleukin-1, -6, and TNF-alpha are the major cytokine hormones mediating the acute phase response. These cytokines induce profound neuroendocrine and metabolic changes by interacting with the central nervous system and with many other organs and tissues in the body. Corticotrophin releasing factor functions under these conditions as a major co-ordinator of the response and is responsible for activating the ACTH-adrenal axis for regulating fever and for other CNS effects leading to a sympathetic outflow. Increased ACTH secretion leads to glucocorticoid production. alpha-melanocyte stimulating hormone functions under these conditions as a cytokine antagonist and an anti-pyretic hormone. The sympathetic outflow, in conjunction with increased adrenal activity. leads to the elevation of catecholamines in the bloodstream and in tissues. Current evidence suggests that neuroimmune mechanisms are essential in normal physiology, such as tissue turnover, involution, atrophy, intestinal function, and reproduction. Host defence against infection, trauma and shock relies heavily on the neuroimmunoregulatory network. Moreover, abnormalities of neuroimmunoregulation contribute to the aetiology of autoimmune disease, chronic inflammatory disease, immunodeficiency, allergy, and asthma. Finally, neuroimmune mechanisms play an important role in regeneration and healing.
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PMID:The immune effects of neuropeptides. 891 48

Immunological studies in human immunodeficiency virus (HIV)-positive patients suggest that the disease progression is accompanied by a defective production of type 1 cytokines (interleukin-2 (IL-2) and IL-12], an increased production of type 2 cytokines (IL-4, IL-6, and IL-10), and an increased production of IgE. HIV infection is also associated with activation of the hypothalamo-pituitary-adrenal axis function and increased plasma and urinary cortisol concentrations. As cortisol is involved in the physiological regulation of cytokines, a study was conducted to examine cytokine patterns in two groups of hypercortisolemic patients, one with normal sensitivity to glucocorticoids and the other with glucocorticoid resistance. Ten HIV-infected patients with normal receptor affinity to glucocorticoids (AIDS-C), 10 HIV-infected patients with low receptor affinity to glucocorticoids (AIDS-GR), and 20 healthy subjects were studied. Receptor characteristics of peripheral blood mononuclear cells were evaluated by [3H]dexamethasone binding. Serum cortisol and urinary free cortisol were measured by RIA. Serum ACTH and IgE were measured by immunoradiometric assay, and IL-2, IL-4, and IL-10 cytokines and interferon-gamma were measured by enzyme-linked immunosorbent assay. AIDS-C patients showed low IL-2 and high IL-4, IL-10, and IgE concentratios; conversely, AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations. Thus, in HIV infection, elevated cortisol levels suppress cell-mediated immunity and stimulate humoral immunity, whereas this response is not detected in cortisol-resistant patients. These findings indicate that cortisol and its receptors are critically involved in the regulation of immune function in HIV infection.
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PMID:Glucocorticoids and the immune function in the human immunodeficiency virus infection: a study in hypercortisolemic and cortisol-resistant patients. 932 49

Many patients with acquired immune deficiency syndrome (AIDS) have symptoms consistent with adrenal insufficiency, but only a small subset of these patients meet criteria for adrenal insufficiency during a short corticotropin (ACTH) stimulation test. We hypothesized that patients with AIDS and symptoms of adrenal insufficiency who produce normal amounts of cortisol in response to administration of 0.25 mg cosyntropin may nevertheless produce lower amounts of cortisol in a course of 24 hours than comparably sick AIDS patients without symptoms of adrenal insufficiency or comparably sick patients without AIDS. We studied four groups of male patients: AIDS patients with symptoms suggestive of adrenal insufficiency but with a normal response to cosyntropin (group I), AIDS patients without symptoms suggestive of adrenal insufficiency (group II), human immunodeficiency virus (HIV)-negative patients with serious acute or chronic illness (group III), and healthy subjects (group IV). The following variables were examined: age, CD4 cell count, Acute Physiologic and Chronic Health Evaluation (APACHE) score, serum cortisol and plasma ACTH at baseline; serum cortisol at 30 and 60 minutes after intravenous administration of 0.25 mg cosyntropin; and 24-hour urinary free cortisol. The four groups had a similar mean age and baseline plasma ACTH and serum cortisol levels. However, a change in cortisol from baseline to 30 and 60 minutes after administration of cosyntropin was significantly smaller in both groups of AIDS patients than in the sick patients without AIDS and normal subjects. There were also differences noted between the two groups of AIDS patients: both baseline and stimulated levels of cortisol tended to correlate directly with ACTH levels in patients without symptoms of adrenal insufficiency, while this relationship appeared to be inverse in patients with symptoms suggestive of adrenal insufficiency (r = -.57 to -.7, P < .05 to .14). The 24-hour urinary free cortisol levels were similar among all groups, but correlated strongly with baseline and stimulated serum cortisol levels only in patients with AIDS and symptoms of adrenal insufficiency (r = .8 to .9, P < .002 to .015). We conclude that (1) AIDS patients with and without symptoms of adrenal insufficiency may have either normal adrenal function or somewhat suboptimal adrenal reserve as demonstrated by a blunted cortisol response during the short ACTH stimulation test in comparison to HIV-negative comparably sick patients or healthy subjects; and (2) 24-hour urinary free cortisol is not a useful test for detection of subtle abnormalities of adrenal function in patients with AIDS.
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PMID:Twenty-four-hour urinary free cortisol in patients with acquired immunodeficiency syndrome. 962 68

To overcome the low oral bioavailability of the highly potent and selective antiretroviral agent (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA), a new lipophilic ester derivative, i.e., the bis(isopropyloxycarbonyloxymethyl)-ester [bis(POC)-PMPA], was prepared. The usefulness of bis(POC)-PMPA as an oral prodrug for PMPA was investigated in the intestinal mucosa Caco-2 cell monolayer model. The total transport of bis(POC)-PMPA was 2.7%, whereas it was less than 0.1% for PMPA. Bis(POC)-PMPA was considerably metabolized inside the epithelial cells, since the majority of the compound was recovered after transport in the form of the monoester metabolite [mono(POC)-PMPA]. In contrast, bis(POC)-PMPA was relatively resistant to degradation at the luminal side of the Caco-2 cells. Pharmacokinetic studies with mice showed that the oral bioavailability of bis(POC)-PMPA (calculated from the curves of the concentration of free PMPA in plasma) was 20%. Neither bis(POC)-PMPA nor mono(POC)-PMPA could be recovered in plasma, suggesting the efficient release of the active drug PMPA after oral administration of bis(POC)-PMPA. Severe combined immunodeficient (SCID) mice infected with Moloney murine sarcoma virus (MSV) and treated orally with bis(POC)-PMPA for 5 or 10 days (dosages, 50, 100, or 200 mg of PMPA equivalent per kg of body weight per day) showed a significant delay in MSV-induced tumor appearance and tumor-associated death. The antiviral efficacy of oral bis(POC)-PMPA was related to the dosage and treatment period and was not significantly different from that of subcutaneous PMPA given at an equivalent dose. The favorable pharmacokinetic profile, marked antiviral efficacy, and low toxicity make bis(POC)-PMPA an attractive oral prodrug of PMPA that should be further pursued in clinical studies with patients infected with human immunodeficiency virus or hepatitis B virus.
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PMID:Antiretroviral efficacy and pharmacokinetics of oral bis(isopropyloxycarbonyloxymethyl)-9-(2-phosphonylmethoxypropyl)adenine in mice. 966 Sep 84

Disruption of the linkage among the immune, nervous, and endocrine systems may contribute to the pathology and symptoms of acquired immunodeficiency syndrome (AIDS). We investigated the role of human immunodeficiency virus (HIV) in altering these linkages via induction of corticotropin (ACTH) by lymphocytes. Cultured T lymphocytes (H9 cell line) were infected with HIV-1, after which ACTH production was measured and characterized at various time intervals by immunofluorescence and Western blotting. We report a coordinate expression of ACTH and p24 HIV core protein in H9 cells. Also, the kinetics of HIV-induced ACTH production by H9 T lymphoma cells are demonstrated using three different strains of HIV as well as UV-inactivated HIV. ACTH production corresponded with the appearance of p24 antigen and was maximal 35 days after infection. UV-inactivated HIV and the viral envelope protein, gp120, were also able to induce ACTH production in these cells, indicating that viral replication was not required for the ACTH induction. The HIV-induced ACTH was synthesized de novo and had the size and biological activity of pituitary ACTH. Inhibition of ACTH in HIV-infected lymphocyte cultures by anti-ACTH antiserum enhanced viral p24 expression. The significance of lymphocyte ACTH in AIDS is not clear, but these results suggest that it may restrict HIV replication and possibly infection.
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PMID:Human immunodeficiency virus induction of corticotropin in lymphoid cells. 985 80

Multidrug antiretroviral regimens that include human immunodeficiency virus-1 (HIV-1) protease inhibitors are associated with distinct lipodystrophy, hypertriglyceridemia, hyperinsulinemia, and deposition of visceral abdominal adipose tissue. To determine whether these findings are related to abnormalities of adrenal function, we compared the hypothalamic-pituitary-adrenal axes of HIV-positive patients who had evidence of protease inhibitor-associated lipodystrophy (PIAL), control volunteers (CON), and patients with Cushing's syndrome (CS). To elucidate the metabolic consequences of the observed lipodystrophy, we measured basal serum lipids and compared glucose and insulin concentrations during an oral glucose tolerance test. Spontaneous plasma cortisol showed normal diurnal variation in PIAL. Cortisol levels were similar in CON and PIAL, and levels in these groups were less than those in CS at all times of the night or day (P < 0.005). Ovine CRH-stimulated morning plasma cortisol levels were similar in PIAL and CON. ACTH was significantly greater in PIAL than CON (P < 0.05) at 0, 15, and 30 min after CRH stimulation. Urinary free cortisol in PIAL (mean +/- SD, 76 +/- 51 nmol/day) was significant lower than those in CON (165 +/- 64 nmol/day; P < 0.001) and CS (1715 +/- 1203 nmol/day; P < 0.001). However, 17-hydroxycorticosteroid excretion was significantly greater in PIAL (43 +/- 23 micromol/day) than in CON (17 +/- 8 micromol/day; P < 0.001), although lower than that in CS (74 +/- 47 micromol/day; P < 0.01). Scatchard analysis revealed normal glucocorticoid receptor number and affinity in PIAL. Serum triglycerides were significantly greater in PIAL (6.57 +/- 5.63 mmol/L) than in CS (1.78 +/- 0.83 mmol/L; P < 0.001) or CON (1.36 +/- 0.84 mmol/L; P < 0.001). Although triglyceride levels were significantly correlated with body mass index for CON and CS, these were not correlated for PIAL. During an oral glucose tolerance test, similar glucose and insulin values were found in PIAL and CS that were greater (P < 0.05) than CON values at 30, 60, 90, and 120 min. We conclude that the lipodystrophy associated with use of HIV-1 protease inhibitors is a syndrome of increased intraabdominal adiposity with concomitant dyslipidemia and insulin resistance, but without total body weight gain and is distinct from any known form of hypercortisolism. Although urinary cortisol disposition seems to be altered in HIV-infected patients who are being treated with multidrug regimens that include protease inhibitors, the decreased free cortisol and increased 17-hydroxycorticosteroid excretion appear to be unlikely explanations for the observed lipodystrophy. The cause remains to be elucidated.
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PMID:Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy. 1037 88


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