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

The earliest preparations of immunoglobulins (Ig) decreased the susceptibility of agammaglobulinemic patients to infections caused by pneumococci, Haemophilus influenzae, meningococci, streptococci, and Pseudomonas aeruginosa. Intramuscular administration of such preparations was painful and traumatic, especially for children. Ethanol-fractionated Ig could not be administered intravenously (IV) because the IgG molecules tended to aggregate and thus were more likely to produce anaphylactoid reactions. New Ig preparations, isolated at low pH (e.g., pH 4) in the presence of traces of pepsin to inhibit reaggregation, were well tolerated when administered IV. Thus a new era of treatment and prophylaxis of disease using IV Ig (IVIG) was launched. The IVIG preparations revolutionized the management of virtually all immunodeficiency syndromes characterized by failure of antibody responses. Amelioration of antibody deficiency secondary to certain chronic diseases or surgical trauma can be achieved with these preparations. Newer uses of IVIG include treatment of some autoimmune diseases; in some conditions, the beneficial influences may be attributable to antiidiotype antibodies present in the IVIG. Another likely explanation is that IVIG inhibits damage to cells and tissues by antibody-mediated cellular cytotoxicity or blocks phagocytosis that is facilitated by Fc receptor mechanisms. The value of IVIG in preventing infection in patients undergoing bone marrow or organ transplantation and in the treatment and prophylaxis of life-threatening infections in neonates and premature infants also is reviewed.
 ...
PMID:Historic aspects of intravenous immunoglobulin therapy. 187 38

Lipid analyses of the human immunodeficiency virus (HIV) propagated in Hut 78 cells indicated a low total lipid/protein ratio, a high cholesterol/phospholipid molar ratio, and major phospholipids consisting of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and phosphatidylserine; comparable lipid profiles were noted for human erythrocytes and other RNA viruses. Electron spin resonance (ESR) studies of HIV labeled with 5-nitroxide stearate (N-oxy-4',4'-dimethyloxazolidine derivative of ketostearate) showed a low "fluidity" at 37 degrees C, similar to other enveloped RNA viruses and erythrocytes and probably due to the high cholesterol/phospholipid ratio. Ethanol (50%) completely disrupts the envelope, contributing to the rapid inactivation of HIV by ethanol. Contrarily, heating to 57 degrees C causes much less fluidization, and this heating may play a role in the slower viral inactivation at high temperatures. Should a critical minimum ordering in the HIV envelope be necessary for viral stability and infectivity, manipulating the lipid composition or fluidizing the HIV membrane, or both, may provide an untried therapeutic approach.
 ...
PMID:Lipid composition and fluidity of the human immunodeficiency virus. 282 9

Materials commonly employed in the preparation of otologic homografts such as ethanol and formaldehyde are effective in vitro in inactivating human immunodeficiency virus (HIV). However, to our knowledge, the complete permeation of homograft materials with preservative has not been demonstrated. Ethanol and formaldehyde have not been shown to be effective in inactivating the Creutzfeldt-Jakob agent. The literature on sterilization procedures for these agents is reviewed. Standard procedures for preparation of otologic homografts are examined. It is recommended that donor HIV serologic status be determined when otologic homografts must be used. Further research is required to determine the efficacy of otologic homograft sterilization techniques against HIV and Creutzfeldt-Jakob disease.
 ...
PMID:Can acquired immunodeficiency syndrome and Creutzfeldt-Jakob disease be transmitted via otologic homografts? 304 23

The effect of intrauterine exposure to ethanol on lymphocyte development in the neonatal period was studied in C57BI/6J mice. Mice were bred, and then the female mice were assigned to 1 of 3 diet groups, 25% ethanol-derived calories (EDC), pair-fed control, or ad libitum laboratory chow. At birth, all offspring were cross-fostered to surrogate mothers who had been fed laboratory chow. At weekly intervals, the neonatal mice were weighed, and 4 mice from each group were used to assess the development of splenic lymphocytes. The total number of splenocytes was similar in all three groups at each sampling. The number of T-cells, B-cells, and natural killer (NK) cells was measured by flow cytometry. T-cells and NK cells did not vary significantly among the three diet groups. However, the total number of B-cells was decreased for the first 3 weeks of life in the ethanol-exposed animals. The function of the T-cells and B-cells was determined by assessing the response to lipopolysaccharide, pokeweed mitogen, phytohemagglutinin, and concanavalin A. The response to all four mitogens was significantly reduced in the ethanol-exposed animals and did not recover to control levels until 4-5 weeks of life. Ethanol exposure had no significant effect on the kinetics of acquisition of NK lytic function, as assessed by determining the killing of chromium-51 labeled YAC-1 tumor target cells. These data show that prenatal exposure to ethanol causes a transient immunodeficiency in some, but not all compartments of the immune system.
 ...
PMID:In utero exposure to ethanol affects postnatal development of T- and B-lymphocytes, but not natural killer cells. 777 46

Several social or recreational drugs singly or together have demonstrated effects on the fetus and neonate, with those effects extending into adulthood. The use of recreational drugs during pregnancy remains a major health problem, with adverse effects including higher rates of fetal distress and demise, lower Apgar scores, growth retardation, and adverse neurodevelopmental outcome. Ethanol has the most profound effects, with physical stigmata of the drug seen in one third of exposed infants. In children without the affected physical appearance, profound neurodevelopmental sequelae have been demonstrated. Other drugs, such as cocaine, heroin, amphetamines, and nicotine, have been associated with impaired fetal growth and acute withdrawal during the neonatal period. Subsequently, these infants and children have an increased risk for altered neurodevelopment and long-term health status. Long-term follow-up and assessment are essential. The risk of neonatal withdrawal or abstinence syndrome is greatest with narcotic drugs but has been found to occur in neonates following exposure to cocaine, nicotine, and amphetamines. Early treatment with tincture of opium, paregoric, or phenobarbital is crucial. Assessment of the overall health status of the infant should include growth parameters, signs and symptoms of infection (especially hepatitis, syphilis, and immunodeficiency viruses), and neurobehavioral function. Such assessments should not be limited to the newborn period, as neurodevelopmental sequelae may not be manifest until later in infancy and childhood. In addition, evaluation of the social milieu is warranted because of the increased risk for neglect and abuse of drug-exposed infants and children. Early intervention, maternal drug rehabilitation treatment, and parenting classes are frequently prescribed, but their efficacy is variable. Further investigations should study the potential benefits of these recommendations.
 ...
PMID:The impact of prenatal drug exposure on the neonate. 954 66

We have developed a novel system to study monocytic function after human immunodeficiency virus type 1 (HIV-1) infection by infecting a series of human macrophage hybridoma cell lines with HIV-1. Since ethanol has detrimental effects on immune function, we investigated the effect of ethanol and its metabolites acetaldehyde and acetate on monocytic function by utilizing one human macrophage hybridoma cell line, clone 43, as well as primary monocytes. Pretreatment of clone 43 and primary monocytes with ethanol and its metabolites resulted in diminished accessory cell function for mitogen-, anti-CD3-, and antigen-induced T-cell proliferation. The decreased accessory cell function was associated with reduced interleukin 1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha production with loss of intracellular cytokine and mRNA production and the induction of transforming growth factor beta. In ethanol-, acetaldehyde-, and acetate-treated HIV-1-infected clone 43 cells (43HIV), there was a more rapid loss (3 days after infection) of accessory cell function at a lower infecting dose of HIV-1 than that in untreated 43HIV cells. We also observed a more rapid loss of surface class II antigen expression in the ethanol-, acetaldehyde-, and acetate-treated 43HIV cells, but no change in surface expression of CD80 or CD86. Ethanol-induced impairment of monocytic function may compound the immunologic defects of AIDS, making the infected individual more susceptible to the complications of the disease.
 ...
PMID:Effect of ethanol on monocytic function in human immunodeficiency virus type 1 infection. 980 36

Neutropenia and impairment of neutrophil function are commonly observed in patients with human immunodeficiency virus (HIV) infections. The HIV regulatory protein Tat is known to exert immunosuppressive effects. Alcohol is known also to be an immunosuppressive factor, and as alcohol abuse is common among HIV infected hosts, both factors may interact in an additive or synergistic fashion to further impair the host defenses of these patients. In order to test this possibility, endotoxin-induced neutrophil beta2-integrins CD11b and CD18 expression, phagocytosis, and hydrogen peroxide generation were examined in normal and HIV-1 Tat-transgenic mice in the absence and presence of ethanol intoxication. Acute ethanol intoxication was induced in mice (body weight of 25+/-1 g) by an intraperitoneal (ip) injection of ethanol (3 g/kg, 20% in normal saline). Thirty min later, the animals were given an ip injection of endotoxin (20 microg in 0.2 ml of saline/mouse). Vehicle-treated controls received an ip injection of saline without ethanol or endotoxin. Two hr after endotoxin administration, the animals were killed to determine neutrophil functions with flow cytometry. The baseline expression of CD11b and CD18 was similar in normal nontransgenic and Tat-transgenic mice. Endotoxin administration significantly up-regulated CD11b and CD18 expression in normal mice. This up-regulation was suppressed in Tat-transgenic mice. Ethanol intoxication inhibited endotoxin-induced CD11b and CD18 expression in normal mice and totally abolished endotoxin-induced CD11b and CD18 expression in Tat-transgenic mice. Neutrophil phagocytic activity in normal and Tat-transgenic mice was similar. Ethanol intoxication produced a similar inhibition of phagocytosis in both study groups. Endotoxin suppressed phagocytosis in normal mice, and this suppression was more pronounced in Tat-transgenic mice. Spontaneous and phorbol myristate acetate (PMA)-stimulated hydrogen peroxide generation by circulating neutrophils (PMNs) were similar in normal and Tat-transgenic mice. Neither ethanol nor endotoxin affected hydrogen peroxide generation by PMNs. These data show that both Tat and alcohol significantly impair PMN function, and this may be a mechanism leading to the increased susceptibility of the HIV-infected host to bacterial infection.
 ...
PMID:The human immunodeficiency virus type I Tat protein potentiates ethanol-induced neutrophil functional impairment in transgenic mice. 988 49

Pulmonary infections are a significant cause of morbidity and mortality in patients with alcohol abuse and human immunodeficiency virus (HIV) infection, two immunocompromising conditions that frequently coexist. This study examined the separate and combined effects of in vivo lentiviral infection and in vitro alcohol exposure on alveolar macrophage (AM) production of tumor necrosis factor- alpha (TNF-alpha), a proinflammatory cytokine that is critical to normal pulmonary host defense. AMs, recovered by bronchoalveolar lavage (BAL) from uninfected and simian immunodeficiency virus (SIV)-infected rhesus macaques, at the asymptomatic and terminal stages of infection, were cultured in ethanol 2 h prior to stimulation with lipopolysaccharide (LPS). Median TNF-alpha concentrations were measured 15 h later. Spontaneous TNF-alpha production was similar in all groups examined. LPS increased TNF-alpha protein production similarly in SIV(-) (2, 381 +/- 359 pg/ml) and SIV(+) animals at the terminal stage of infection (2,019 +/- 507 pg/ml). In contrast, cells from SIV(+) asymptomatic animals had a depressed response (763 +/- 304 pg/ml). Ethanol (100 mM) suppressed the LPS-induced AM TNF-alpha response by approximately 50% in both SIV(-) and (+) animals. Ethanol-induced suppression of the TNF-alpha response occurred at a post-transcriptional level. These data suggest that ethanol-induced suppression of the pulmonary TNF-alpha response may further increase the susceptibility to and severity of secondary infectious complications in HIV-infected hosts.
 ...
PMID:In vitro ethanol suppresses alveolar macrophage TNF-alpha during simian immunodeficiency virus infection. 1061 10

While in vitro results at clinically relevant concentrations do not predict abacavir (1592U89) interactions with drugs highly metabolized by cytochrome P450, the potential does exist for a pharmacokinetic interaction between abacavir and ethanol, as both are metabolized by alcohol dehydrogenase. Twenty-five subjects were enrolled in an open-label, randomized, three-way-crossover, phase I study of human immunodeficiency virus-infected male subjects. The three treatments were administration of (i) 600 mg of abacavir, (ii) 0.7 g of ethanol per kg of body weight, and (iii) 600 mg of abacavir and 0.7 g of ethanol per kg. Twenty-four subjects completed the study with no unexpected adverse events reported. Ethanol pharmacokinetic parameters were unchanged with abacavir coadministration. The geometric least squares mean area under the concentration curve extrapolated to infinite time for abacavir increased 41% (from 11.07 to 15.62 microg. h/ml), and the half-life increased 26% (from 1.42 to 1.79 h) in the presence of ethanol (mean ethanol maximum concentration in plasma of 498 microg/ml). The percentages of abacavir dose recovered in urine as abacavir and its two major metabolites were each altered in the presence of ethanol, but there was no change in the total percentage ( approximately 50%) of administered dose recovered in the 12-h collection interval. In conclusion, while a single 600-mg dose of abacavir does not alter blood ethanol concentration, ethanol does increase plasma abacavir concentrations.
 ...
PMID:Pharmacokinetic interaction of abacavir (1592U89) and ethanol in human immunodeficiency virus-infected adults. 1081 29

During the latent phase of human immunodeficiency virus type 1 (HIV-1) infection, CD4+ T cells carrying replication-competent proviral HIV-1 DNA play an important role in persistence of the virus. Several cofactors can induce and or amplify HIV-1 replication and negatively affect disease progression and pathogenesis. Ethanol consumption is an important risk factor for HIV-1 infection, and it has been implicated in increased HIV-1 replication and progression of infection. Because tumor necrosis factor-alpha (TNF-alpha) is an important modulator of HIV-1 replication, in the present study we examined the possible effects of ethanol on TNF-alpha-inducible signaling associated with HIV-1 replication in human CD4+ T cells (Jurkat E6-1). We demonstrate that clinically relevant ethanol concentrations significantly potentiate TNF-alpha-inducible NFkappaB. Although ethanol effectively collaborated with TNF-alpha, by itself it did not have a direct effect on NFkappaB activation. The ethanol-dependent potentiation of TNF-alpha-inducible NFkappaB nuclear translocation was observed to involve the enhanced degradation of IkappaBalpha. Additionally, the ethanol-mediated potentiation of TNF-alpha-inducible NFkappaB activation was abrogated by the known antioxidant pyrrolidinedithiocarbamate, suggesting an important mechanistic role for reactive oxygen species in this process. In correspondence with its effect on NFkappaB, ethanol was also observed to significantly enhance HIV-1 long terminal repeat-dependent transcription induced by TNF-alpha. Overall, the data provide a molecular basis for the possible role of ethanol as a cofactor that can adversely affect HIV-1 infection and pathogenesis.
 ...
PMID:Ethanol enhances TNF-alpha-inducible NFkappaB activation and HIV-1-LTR transcription in CD4+ Jurkat T lymphocytes. 1107 60


1 2 Next >>