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)

Dehydroepiandrosterone (DHEA) and its interconvertible sulfate derivative (DHEA-S) are human androgenic steroids that have been reported to inhibit viral expression and have been associated with a decreased risk of cancer. The relationship between serum DHEA and DHEA-S levels and subsequent progression to AIDS was investigated in a sample of human immunodeficiency virus (HIV)-infected men from the San Francisco Men's Health Study followed prospectively since 1984. Among 108 men seropositive for HIV at study entry and with CD4 lymphocyte counts of 200-499 microliters 24 months later, serum DHEA levels below the lower limit of normal (less than 180 ng/dl) at this later date were predictive of subsequent progression to AIDS (relative hazard = 2.34; 95% confidence interval = 1.18-4.63; P = .01) after controlling for hematocrit, age, and log absolute CD4 cell number in a Cox proportional hazards model. This is the first large prospective cohort in which an endocrinologic variable has been observed to independently predict progression to AIDS. These observations, in addition to recent in vitro data, suggest that DHEA might have a protective effect in HIV infection.
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PMID:Decreased serum dehydroepiandrosterone is associated with an increased progression of human immunodeficiency virus infection in men with CD4 cell counts of 200-499. 168 93

Fatty acids in plasma phospholipids were studied in 35 severely malnourished young children with a median age of 29 mo (range: 9-43 mo), who were either seronegative for human immunodeficiency virus-1 (HIV) (n = 16) or suffered from asymptomatic (stage P-1; n = 12) or symptomatic (stage P-2; n = 7) HIV disease. The malnourished children had significantly lower percentages (% by wt) of phospholipid arachidonic (20:4n-6, AA) and docosahexaenoic (22:6n-3, DHA) acids than 25 age-matched healthy control subjects (AA: 7.05% and 8.70% by wt; DHA: 0.92 and 2.61% by wt, P < 0.001). Body weights of malnourished children did not correlate with linoleic (18:2n-6) and alpha-linolenic (18:3n-3) acid values but were significantly and positively correlated with AA and DHA values (r = 0.40, P = 0.02 and r = 0.63, P < 0.0001, respectively). Plasma concentrations (mg/L) of total phospholipid fatty acids did not differ among seronegative, stage P-1, or stage P-2 patients. Percentage contributions of AA and eicosapentaenoic acid (20:5n-3, EPA) did not differ among those seronegative or in stages P-1 and P-2. In contrast, values of dihomo-gamma-linolenic acid (20:3n-6) were significantly (P < 0.05) lower in stage P-2 (2.38 mg/L) than in either seronegative (3.47 mg/L) or stage P-1 (3.66 mg/L) patients. We conclude that the severely malnourished children developed a depletion of both AA and DHA proportional to the degree of malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-chain polyunsaturated fatty acids in children with severe protein-energy malnutrition with and without human immunodeficiency virus-1 infection. 749 93

Dehydroepiandrosterone (DHEA) is a steroid hormone produced by the adrenal cortex that serves as an intermediary in sex steroid synthesis. DHEA is produced in abundance by humans and most other warm-blooded animals. Based upon previous reports demonstrating the antiviral and immunostimulatory activities of DHEA and DHEA-sulfate (DHEAS) we sought to determine whether introduction of these compounds would affect replication of feline immunodeficiency virus (FIV) in chronically infected cells. When cell number, cell viability, cellular DNA synthesis, and levels of FIV reverse-transcriptase (RT) were measured in cell cultures treated with various dilutions of DHEA or DHEAS it was found that the production of FIV RT was inhibited by DHEA at levels where cellular viability and DNA synthesis were not affected. At the concentrations tested DHEAS did not inhibit FIV replication or impact on cellular viability or proliferation.
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PMID:Dehydroepiandrosterone inhibits replication of feline immunodeficiency virus in chronically infected cells. 754 11

The initial infection with human immunodeficiency virus type 1 (HIV-1) in most individuals usually results in the establishment of a latent or chronic infection before eventual progression toward acquired immunodeficiency syndrome. HIV-1 can also establish a latent or persistent infection in some T cell lines that show minimal constitutive virus expression. However, activation of the T cell lines leading to enhanced HIV-1 replication can be induced by antigens, mitogens, and cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 1, and interleukin-2). Various gene products from other viruses (HTLV-1, HSV, EBV, CMV, HBV, and HHV-6) can also enhance HIV-1 long terminal repeat (LTR)-driven reporter gene activity. On the basis of these observations, it has been proposed that reactivation of latent HIV-1 harbored in chronically infected T lymphocytes, monocytes, or macrophages plays an important role in the pathogenesis of AIDS. So far, there are no drugs or therapy available that can provide protection against HIV-1 latency reactivation. ACH-2, derived from a human T cell line (CEM), is chronically infected with HIV-1, with low levels of constitutive virus expression. ACH-2 can be converted to productive infection by stimulation of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), mitogen or cytokines (TNF-alpha), or infection with HSV. Therefore the ACH-2 cell line is a good candidate for studying the effects of drugs on HIV-1 activation. Previously, we have reported that DHEA and synthetic analogs of DHEA can be modest inhibitors of HIV-1 IIIB replication in phytohemagglutinin-stimulated peripheral blood lymphocyte cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone (DHEA) and an analog of DHEA. 769 6

Dehydroepiandrosterone (DHEA) is a naturally occurring adrenal steroid reported to have immunomodulatory and antiviral activity in cellular and animal models as well as modest in vitro antiretroviral activity against human immunodeficiency virus (HIV). A phase I dose-escalation study was performed to evaluate the safety and pharmacokinetics of DHEA in subjects with symptomatic HIV disease and an absolute CD4 lymphocyte count between 250 and 600 cells/microliters. Thirty-one subjects were evaluated and monitored for safety and tolerance. The oral drug was administered three times daily in doses ranging from 750 mg/day to 2,250 mg/day for 16 weeks. Some immunological and virological parameters were monitored as well. The drug was well tolerated and no dose-limiting side effects were noted. Dose proportionality was evidenced neither by the serum DHEA nor by DHEA-S time-concentration curves for the three dosing groups. However, the study cohort appeared to consist of two subpopulations with markedly different bioavailability for a given DHEA dose. No sustained improvements in CD4 counts nor decreases in serum p24 antigen or beta-2 microglobulin levels were observed. However, serum neopterin levels decreased transiently by 23-40% at week 8 compared with baseline in all dosing groups. DHEA was well tolerated by patients with mild symptomatic HIV disease; evaluation of this agent for efficacy in HIV disease would require randomized, controlled trials.
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PMID:An open-label dose-escalation trial of oral dehydroepiandrosterone tolerance and pharmacokinetics in patients with HIV disease. 809 87

LP-BM5 retrovirus infection and hormone synthesis modulate many physiological systems that could affect physical activity. Infection induced oxidative damage and immunodeficiency of female mice which hormone supplement prevented. Therefore, the effects of retrovirus infection and hormone supplementation were assessed on physical activity using a computerized video system. Retroviral infection increased activity when stationary while lowering average speed and resting time. Hormone supplementation partially modified changes due to murine AIDS. Dehydroepiandrosterone (DHEA) or melatonin (MLT) supplementation restored the average speed; ambulatory time and distance traveled of retrovirus infected mice. MLT as well as the combination of DHEA + MLT increased body movement, but decreased average speed and distance traveled. Thus, retrovirus infection had significant effects on physical activity. Further studies into the relationship between the DHEA and/or MLT and physical activity will assert the contribution of these hormones to the treatment of murine AIDS.
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PMID:Physical inactivity of murine retrovirus infected C57BL/6 mice is prevented by melatonin and dehydroepiandrosterone. 979 Jan 72

Patients treated with relatively high doses of DHEA (dehydroepiandrosterone) are showing modest viral load reductions. This is an important finding because DHEA is readily available in health food stores as an alternative treatment for various conditions, and it is inexpensive. Laboratory tests have shown it to modestly inhibit HIV and FIV (feline immunodeficiency virus), and low levels of DHEA were associated with faster disease progression. Patients are cautioned to only use pharmaceutical-grade DHEA that has been specifically manufactured for human use.
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PMID:DHEA: modest viral load reduction in patients. 1136 54

Dehydroepiandrosterone (DHEA) and its analogue, 16alpha-bromoepiandrosterone (alpha-epi-Br), may have activity against viral and parasitic infections, including human immunodeficiency virus (HIV) and Cryptosporidium parvum. Therefore, we evaluated its antimalarial effects on Plasmodium falciparum and Plasmodium berghei. In vitro, chloroquine (CQ)-sensitive and resistant strains of P. falciparum parasitized red blood cells were incubated with escalating doses of alpha-epi-Br or CQ. In vivo, 62 rats were infected with P. berghei and treated with CQ or alpha-epi-Br. At the highest doses tested against a CQ-sensitive strain, parasitemias decreased from 25.4% in the saline control group to 4.3% and 4.8% in the alpha-epi-Br and CQ groups, respectively (P < 0.05). Against two CQ-resistant strains, parasitemias decreased from 22.3-28.8% and 24.8-30% in the CQ and saline groups, respectively, to 2.5-2.7% in the alpha-epi-Br groups (P = 0.003). In vivo, on Day 4, parasitemias decreased from 23% in the saline group to 9-12% and 12% in the in alpha-epi-Br and CQ groups, respectively (P < 0.05). These data demonstrate that alpha-epi-Br shows activity against CQ-sensitive and resistant strains of P. falciparum in vitro. At the doses tested against P. berghei in vivo in rats, alpha-epi-Br is comparable to CQ.
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PMID:16alpha-bromoepiandrosterone, a dehydroepiandrosterone (DHEA) analogue, inhibits Plasmodium falciparum and Plasmodium berghei growth. 1142 78

Although prior studies suggest reduced androgen levels in women with acquired immune deficiency syndrome wasting, little is known regarding the regulation of adrenal and ovarian androgen secretion in such patients. We investigated ovarian and adrenal function in 13 human immunodeficiency virus-infected women with acquired immune deficiency syndrome wasting and 21 age- and body mass index-matched healthy control subjects studied in the early follicular phase. Subjects received hCG (5000 U, im) on d 1 and Cosyntropin (0.25 mg, i.v.) on d 3 after dexamethasone (1 mg, orally, at 2400 h) pretreatment on d 2. At baseline, human immunodeficiency virus-infected subjects demonstrated significantly reduced T [18 +/- 2 vs. 25 +/- 2 ng/dl (0.6 +/- 0.1 vs. 0.9 +/- 0.1 nmol/liter); P = 0.02], free T [1.5 +/- 0.1 vs. 2.4 +/- 0.2 pg/ml (5.3 +/- 0.5 vs. 8.3 +/- 0.6 pmol/liter); P = 0.001], androstenedione [119 +/- 6 vs. 162 +/- 14 ng/dl (4.16 +/- 0.20 vs. 5.66 +/- 0.48 nmol/liter); P = 0.02], and dehydroepiandrosterone sulfate [0.96 +/- 0.17 vs. 1.55 +/- 0.19 microg/ml (2.6 +/- 0.5 vs. 4.2 +/- 0.5 micromol/liter); P = 0.047] levels compared with the control subjects. T [8 +/- 2 vs. 6 +/- 2 ng/dl (0.3 +/- 0.1 vs. 0.2 +/- 0.1 nmol/liter); P = 0.48], free T [0.5 +/- 0.2 vs. 0.4 +/- 0.1 pg/ml (1.7 +/- 0.7 vs. 1.5 +/- 0.5 pmol/liter); P = 0.85], 17 hydroxyprogesterone [0.5 +/- 0.2 vs. 0.7 +/- 0.2 microg/liter (1.6 +/- 0.6 vs. 2.0 +/- 0.6 nmol/liter); P = 0.63], and androstenedione [-1 +/- 12 vs. 8 +/- 11 ng/dl (-0.03 +/- 0.42 vs. 0.28 +/- 0.39 nmol/liter), P = 0.61] responses to hCG were not different between the groups. Cortisol responses were increased and dehydroepiandrosterone sulfate responses were decreased in the human immunodeficiency virus-infected vs. control subjects after ACTH stimulation. The ratio of DHEA to cortisol was significantly decreased at 60 (71 +/- 11 vs. 107 +/- 10; P = 0.02) and 90 (63 +/- 8 vs. 102 +/- 9; P = 0.004) min post-ACTH in the human immunodeficiency virus-infected patients compared with control subjects. Baseline urinary free cortisol levels were not different between the groups [36 +/- 9 vs. 36 +/- 5 microg/24 h (99 +/- 26 vs. 100 +/- 13 nmol/d)]. The DHEA to cortisol ratio correlated with the CD4 count (r = 0.67; P = 0.01). These data demonstrate significant shunting of adrenal steroid metabolism away from androgenic pathways and toward cortisol production in human immunodeficiency virus-infected women with the wasting syndrome. In contrast, our data suggest intact ovarian androgen responsivity to hCG stimulation. Further studies of the mechanism of adrenal steroid shunting and the efficacy of androgen replacement in human immunodeficiency virus-infected women are necessary.
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PMID:Mechanisms of androgen deficiency in human immunodeficiency virus-infected women with the wasting syndrome. 1154 36

Dehydroepiandrosterone sulfate (DHEAS) is the most abundant circulating steroid hormone in humans and can readily be converted to its parent steroid DHEA by tissue sulfatases. Yet, a biologic function for these steroids has not been defined. The link between DHEA and aging has been raised by: (1) its well documented age-related decline, and (2) a preventive effect of DHEA on numerous age-related illnesses: ischemic heart-disease, cognitive impairment, immunodeficiency, malignancies, osteoporosis. These effects have been suggested by epidemiological studies in humans. Animal studies support a protective effect of DHEA on these age-related diseases. However, it remains unknown whether these results in animals can be transposed in humans, because adrenal secretion of DHEA seems to be particular to primates. In humans, only a few studies have been performed. The effects of oral supplementation with DHEA have, so far, focused on the possible metabolic effects of DHEA. A few studies have shown: the absence of any side-effects; no change in body-weight; conflicting results on body-composition and lipids and no effect on insulin-tolerance. The latest study showed a beneficial effect on well-being but these results need to be confirmed.
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PMID:Dehydroepiandrosterone (DHEA) and aging. 1537 10


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