Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the factors involved in the pathogenesis of thrombocytopenia frequently found in human immuno-deficiency virus (HIV) infection, we studied the clinical and laboratory findings of 35 Japanese HIV-infected hemophiliacs regarding their association with thrombocytopenia. Seventeen HIV-positive patients were thrombocytopenic. They had fewer CD4+ cells and were in more advanced stages of the disease, compared with the 18 patients without thrombocytopenia. We carried out the stepwise regression analysis on 32 patients in the early stage of HIV infection, with the platelet count as the dependent variable, and with the CD8+ cell count, serum cholinesterase, alanine aminotransferase (ALT), CD4+ cell count and white blood cell count as explanatory variables. The CD8+ cell count, serum cholinesterase, and ALT were entered into the regression model as explanatory variables of the platelet count with statistical significance. A positive linear correlation in these 32 patients between the CD8+ cell count and platelet count (r = 0.50, P < 0.01) was noted. We conclude that the decrease of the CD8+ cell count may play a role in the pathogenesis of thrombocytopenia in Japanese hemophiliacs in the early stage of HIV-infection.
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PMID:The association of the platelet count and the peripheral CD8+ cell count in Japanese HIV-infected hemophiliacs. 756 68

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

The relation of small intestinal dysfunction and malnutrition (body composition and serum index parameters of nutrition) was investigated in 36 male patients with AIDS. Mucosal absorptive capacity was assessed by the 25 g D-xylose test. D-xylose absorption (2 h - serum profile and 5 h - urine) classified 17 patients as having impaired and 19 patients as having normal absorption. In both groups body weight, body mass index as well as body composition analysis indicated malnutrition when compared to healthy male controls (n = 340) or asymptomatic HIV-infected patients (n = 26). Patients with abnormal D-xylose test had more severe malnutrition indicated by a lower body cell mass (17.7 +/- 5.4 vs. 22.5 +/- 4.5 kg; p < 0.01) and an increased ratio of extracellular mass to body cell mass (1.99 +/- 0.82 vs. 1.45 +/- 0.46 p < 0.01). Total serum protein, albumin, cholinesterase activity, cholesterol and LDL were significantly diminished in AIDS-patients with abnormal D-xylose test compared to those with normal D-xylose absorption. Intestinal dysfunction indicated by decreased D-xylose Intestinal dysfunction indicated by decreased D-xylose absorption thus represents an important feature of malnutrition and wasting, and patients with abnormal D-xylose absorption have more profound impairment of body composition, visceral proteins and lipids reflecting malnutrition than patients with unaffected intestinal absorption.
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PMID:Intestinal absorption and malnutrition in patients with the acquired immunodeficiency syndrome (AIDS). 829 Dec 78

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

A large number of cycloSal-nucleotide triesters 1-49 have been studied concerning their ability to inhibit cholinesterases of different origins as well as to inhibit HIV replication in cell culture. It was shown that none of the triesters showed inhibitory effects against human acetylcholinesterase (AChE; isolated enzyme) as well as against AChE from beef erythrocytes and calf serum. In contrast, inhibition of butyrylcholinesterase (BChE) has been observed for some triesters in human and mouse serum. cycloSal pronucleotides showed strong competitive inhibition with respect to the substrate acetylcholine chloride (K(i)/K(m): approximately 2 x 10(-5)) and acted by time-dependent irreversible inhibition of the human serum BChE. Detailed studies demonstrated that the inhibitory effect against BChE is dependent on the nucleoside analogue, the substitution pattern of the cycloSal-moiety, and particularly on the stereochemistry at the phosphorus atom. Structural requirements to avoid the inhibition of BChE by cycloSal-nucleotide triesters have been elucidated in the reported study.
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PMID:Interaction of cycloSal-pronucleotides with cholinesterases from different origins. A structure-activity relationship. 1513 62

Chronic brain inflammation is the common final pathway in the majority of neurodegenerative diseases and central to this phenomenon is the immunological activation of brain mononuclear phagocyte cells, called microglia. This inflammatory mechanism is a central component of HIV-associated dementia (HAD). In the healthy state, there are endogenous signals from neurons and astrocytes, which limit excessive central nervous system (CNS) inflammation. However, the signals controlling this process have not been fully elucidated. Studies on the peripheral nervous system suggest that a cholinergic anti-inflammatory pathway regulates systemic inflammatory response by way of acetylcholine acting at the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) found on blood-borne macrophages. Recent data from our laboratory indicates that cultured microglial cells also express this same receptor and that microglial anti-inflammatory properties are mediated through it and the p44/42 mitogen-activated protein kinase (MAPK) system. Here we report for the first time the creation of an in vitro model of HAD composed of cultured microglial cells synergistically activated by the addition of IFN-gamma and the HIV-1 coat glycoprotein, gp120. Furthermore, this activation, as measured by TNF-alpha and nitric oxide (NO) release, is synergistically attenuated through the alpha7 nAChR and p44/42 MAPK system by pretreatment with nicotine, and the cholinesterase inhibitor, galantamine. Our findings suggest a novel therapeutic combination to treat or prevent the onset of HAD through this modulation of the microglia inflammatory mechanism.
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PMID:Galantamine and nicotine have a synergistic effect on inhibition of microglial activation induced by HIV-1 gp120. 1534 4

Two new classes of lipophilic prodrugs of the antiviral active phosphonate 9-[2-phosphonomethoxyethyl]adenine (PMEA 1) have been prepared and were studied with regard to their hydrolysis properties and biological activity. A first series of compounds was prepared on the basis of the cycloSal nucleotide approach. Because of the surprisingly low hydrolysis stability of these cycloSal-PMEA derivatives, more stable derivatives have to be developed. Instead of using salicyl alcohol, in cycloAmb-PMEA derivatives 2-aminobenzyl alcohols were attached to PMEA 1. The latter compounds showed a considerably higher stability compared to the cycloSal counterparts. Stability studies revealed that all lipophilic prodrugs delivered PMEA selectively by chemical means. All compounds proved to be noninhibiting to acetyl- and butyrylcholinesterase, and some of the phosphonate diesters were found to be more active against HIV compared to the parent PMEA.
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PMID:cycloSal-PMEA and cycloAmb-PMEA: potentially new phosphonate prodrugs based on the cycloSal-pronucleotide approach. 1633 32

Structure-based design and synthesis of novel HIV protease inhibitors are described. The inhibitors are designed specifically to interact with the backbone of HIV protease active site to combat drug resistance. Inhibitor 3 has exhibited exceedingly potent enzyme inhibitory and antiviral potency. Furthermore, this inhibitor maintains impressive potency against a wide spectrum of HIV including a variety of multi-PI-resistant clinical strains. The inhibitors incorporated a stereochemically defined 5-hexahydrocyclopenta[b]furanyl urethane as the P2-ligand into the (R)-(hydroxyethylamino)sulfonamide isostere. Optically active (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[b]furan was prepared by an enzymatic asymmetrization of meso-diacetate with acetyl cholinesterase, radical cyclization, and Lewis acid-catalyzed anomeric reduction as the key steps. A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 A resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance.
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PMID:Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance. 1691 14

Bis-cycloSal-d4T-monophosphates have been synthesized as potentially anti-HIV active "dimeric" prodrugs of 2',3'-dideoxy-2',3'-didehydrothymidine monophosphate (d4TMP). These pronucleotides display a mask-drug ratio of 1:2, a novelty in the field of pronucleotides. Both bis-cycloSal-d4TMP 6 and bis-5-methyl-cycloSal-d4TMP 7 showed increased hydrolytic stability as compared to their "monomeric" counterparts and a completely selective hydrolytic release of d4TMP. The hydrolysis pathway was investigated via 31P NMR spectroscopy. Moreover, due to the steric bulkiness, compound 6 already displayed strongly reduced inhibitor potency toward human butyrylcholinesterase (BChE), while compound 7 turned out to be devoid of any inhibitory activity against BChE. Partial separation of the diastereomeric mixture of 6 revealed strong dependence of the pronucleotides' properties on the stereochemistry at the phosphorus centers. Both 6 and 7 showed good activity against HIV-1 and HIV-2 in wild-type CEM cells in vitro. These compounds were significantly more potent than the parent nucleoside d4T 1 in HIV-2-infected TK-deficient CEM cells, indicating an efficient TK-bypass.
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PMID:Bis-cycloSal-d4T-monophosphates: drugs that deliver two molecules of bioactive nucleotides. 1732 34

The present study was undertaken to investigate the beneficial effect of HIV protease inhibitor Indinavir on memory deficits associated with experimental dementia of Alzheimer disease's (AD) type. Dementia was induced in Swiss albino mice by administration of Celecoxib (100 mg kg(-1) orally, daily for 9 days) or Streptozotocin (3 mg kg(-1) administered intracerebroventricularly on 1st and 3rd day) and the cognitive behaviors of Swiss albino mice were assessed using Morris water maze test. Brain acetyl cholinesterase (AChE) activity was measured by Ell Mann's method. Brain thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively to assess total oxidative stress. Donepezil (0.1 mg kg(-1) i.p.) served as positive control in the present investigation. Celecoxib as well as Streptozotocin (STZ) produced a significant loss of learning and memory. Indinavir (100 and 200 mg kg(-1) orally) successfully attenuated Celecoxib as well as STZ induced cognitive deficits. Higher levels of brain AChE activity, TBARS and lower levels of GSH were observed in Celecoxib as well as STZ treated animals, which were significantly attenuated by Donepezil and Indinavir. Study highlights the potential of Indinavir in memory dysfunctions associated with dementia of AD.
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PMID:Exploitation of HIV protease inhibitor Indinavir as a memory restorative agent in experimental dementia. 1834 89


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