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 purpose of this study was to determine if a correlation exists between long-term azidothymidine (AZT) therapy and low pseudocholinesterase concentrations in patients who are infected with the human immunodeficiency virus (HIV). A pilot study was conducted of 10 patients infected with HIV, 5 of whom were receiving AZT. Laboratory tests, including complete blood count (CBC), liver function tests, helper/inducer T lymphocyte numbers (CD4), serum dibucaine numbers, and serum pseudocholinesterase concentrations were examined. Control and study subjects both exhibited normal dibucaine numbers, but the pseudocholinesterase concentrations were significantly lower in the group that was not receiving AZT relative to the AZT treatment group. However, only two patients, neither of whom were receiving AZT, demonstrated low or borderline low pseudocholinesterase concentrations according to laboratory criteria. It is possible that pseudocholinesterase synthesis is significantly inhibited by the HIV disease process and that treatment with AZT partly reverses the inhibition. Associated variables contributing to low pseudocholinesterase concentrations in the HIV-positive patient are explored.
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PMID:The effects of azidothymidine therapy on pseudocholinesterase concentrations in asymptomatic HIV-positive patients. 781 Feb 85

When platelet counts were compared in 1986 and 1992 in 117 anti-HIV antibody positive and negative hemophilia patients, a clear decrease was found in the positive group. In 1992 platelet counts < 150 x 10(9) were present in 23.5% of the positive group in contrast to 5.8% of the negative group. Comparing platelet counts with other clinical parameters, a positive correlation was found with cholinesterase and a negative correlation with IgG in both the positive and negative groups, while negative correlations with beta 2-microglobulin and platelet-associated IgG were found in only the positive group. These findings implicate the chronic liver dysfunction present in hemophilia patients, apart from HIV infection, in the decrease in platelet counts, with immunodeficiency playing an additional role in the positive group. In the treatment of a hemophilia B patient showing decreased platelet counts, these counts increased consistent with the administration of Acyclovir and Zidovudine. It was demonstrated that HSV-1 and HIV-1 antigen are present on the soluble platelets of this patient and are recognized by antibodies in the patient's serum.
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PMID:[Thrombocytopenia in HIV-1 seropositive hemophiliacs]. 831 32

Pseudocholinesterase is a protein for which no function exists in mammals including human beings. To date, no substrate has been identified for this 'enzyme'. Involvement of this protein in the aetiopathogenesis of many diseases, such as hyperlipoproteinaemia, is still actively debated. Here, we propose a theoretical method to immobilize pseudocholinesterase in hepatocytes using antibody bound to liposomes. Conceptually, this approach will have widespread application, especially in blocking human immunodeficiency virus replication in vivo.
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PMID:From pseudocholinesterase to human immunodeficiency virus. 856 42

1. Pentamidine is routinely used to reduce the incidence of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus, but it has been described as inducing pulmonary adverse effects, such as cough and bronchospasm. 2. In this paper we have investigated the effects of pentamidine on guinea-pig isolated main bronchi and human isolated bronchi. Pentamidine induced a concentration-dependent contraction in both preparations with pD2 values of 9.64 +/- 0.07 (n = 8) and 9.73 +/- 0.06 (n = 8) and a maximal effect (Emax) of 40 +/- 4% and 34 +/- 5% of the response to acetylcholine (1 mM) in guinea-pig and human bronchi respectively. Atropine (0.01 to 0.1 microM) and the muscarinic M3 receptor antagonist, hexahydro-siladiphenidol (0.1 and 1 microM) inhibited pentamidine-induced concentration-responses in both preparations in a non-competitive manner, whereas only high concentrations of the M1 receptor antagonist pirenzipine (1 microM) inhibited pentamidine concentration-response curves. 3. The cholinesterase inhibitor, tacrine (1 microM), potentiated the effect of pentamidine; in contrast, morphine inhibited pentamidine-induced responses. 4. The bronchoconstrictor effect of pentamidine on guinea-pig and human isolated bronchi was not modified by the H1 histamine receptor antagonist, mepyramine, by indomethacin or by the neurokinin NK1 and NK2 receptor antagonists, CP-96,345 and SR 48969 respectively, suggesting that neither histamine receptor stimulation, arachidonic acid derivative formation, nor tachykinin release are involved in pentamidine-induced contraction of human and guinea-pig airways. 5. Our overall results suggest that pentamidine induces contraction of guinea-pig and human isolated bronchi through prejunctional cholinergic nerve stimulation.
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PMID:Indirect muscarinic receptor activation by pentamidine on airway smooth muscle. 893 15

Biotransformation of rifabutin, an antibiotic used for treatment of tuberculosis in patients infected with the human immunodeficiency virus (HIV), and its interactions with some macrolide and antifungal agents were studied in human intestinal and liver microsomes. Both liver and enterocyte microsomes metabolized rifabutin to 25-O-deacetylrifabutin, 27-O-demethylrifabutin, and 20-, 31-, and 32-hydroxyrifabutin. The same products (except 25-O-deacetylrifabutin) were formed by microsomes from lymphoblastoid cells that contained expressed CYP3A4. The apparent Michaelis-Menten constant (Km); approximately 10 to 12 mumol/L) and maximal velocity (Vmax; approximately 100 pmol/min/mg of protein) values for CYP-mediated metabolism were similar in liver and enterocyte microsomes. Deacetylation of rifabutin (Km approximately 16 to 20 mumol/L and Vmax approximately 50 to 100 pmol/min/mg of protein) was catalyzed by microsomal cholinesterase. Clarithromycin, ketoconazole, and fluconazole inhibited CYP-mediated metabolism of rifabutin in enterocyte microsomes equally or more potently than in liver microsomes but had no effect on cholinesterase activity. Azithromycin did not inhibit in vitro metabolism of rifabutin. This study provides evidence that CYP3A4 and cholinesterase are major enzymes that biotransform rifabutin in humans and that intestinal CYP3A4 contributes significantly to rifabutin presystemic first-pass metabolism and drug interactions with macrolide and antifungal agents.
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PMID:Metabolism of rifabutin in human enterocyte and liver microsomes: kinetic parameters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents. 916 17

Although FDA-approved Alzheimer's disease (AD) treatment strategies (cholinesterase inhibitors and memantine) offer proven benefits, providers recognize unmet needs beyond what is currently available. Consequently there is a significant use of anecdotal yet unproven combinations for treating AD in practice. Based on the best evidence, combination drug therapy is the standard of care for treating other medical conditions such as malignancies, human immunodeficiency virus (HIV), and hypertension. We review recent combination drug therapy studies in AD. To date, the best evidence-based combination strategy is for moderate-to-severe AD, in which the addition of memantine to stable donepezil therapy was found to benefit cognition, behavior, and function. In milder stages of AD, the benefit of combination drug therapy has not been demonstrated. This review highlights the urgent need to systematically test additional rational drug combinations and the need for future trials to enroll adequate sample sizes and utilize relevant and sensitive outcome measures.
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PMID:Combination drug therapy for Alzheimer's disease: what is evidence-based, and what is not? 1594 60

A century has passed since the discovery of the first neurotransmitter, acetylcholine, in 1914. Extensive research on acetylcholine and its function has provided us with important options to treat the formerly intractable neuromuscular disease myasthenia gravis (MG). In the first days of treatment for MG, acetylcholine esterase inhibitors are administered, which is only a symptomatic therapy. After overwhelming developments in immunology, the immunological mechanisms of MG at the molecular or genetic level were recognized. Destruction of the acetylcholine receptors through autoimmune attacks plays a pivotal role in the evolution of MG. Thus, a mainstay of the newly developing treatments for MG are effective immunosuppression or immunomodulation. However, these therapeutic approaches are still "symptomatic", and target immunological rather than specific myasthenic symptoms. Immunomodulation may result in fatal immunodeficiency. From this point of view, although they are somewhat removed from first-line MG treatment (cholinesterase inhibitors), future drug development should focus on the cancellation of autoimmunity in MG patients.
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PMID:[Myasthenia gravis and acetylcholine]. 2480 68