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)

When the plasma glutathione concentration is low, such as in patients with HIV infection, alcoholics, and patients with cirrhosis, increasing the availability of circulating glutathione by oral administration might be of therapeutic benefit. To assess the feasibility of supplementing oral glutathione we have determined the systemic availability of glutathione in 7 healthy volunteers. The basal concentrations of glutathione, cysteine, and glutamate in plasma were 6.2, 8.3, and 54 mumol.l-1 respectively. During the 270 min after the administration of glutathione in a dose of 0.15 mmol.kg-1 the concentrations of glutathione, cysteine, and glutamate in plasma did not increase significantly, suggesting that the systemic availability of glutathione is negligible in man. Because of hydrolysis of glutathione by intestinal and hepatic gamma-glutamyltransferase, dietary glutathione is not a major determinant of circulating glutathione, and it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione.
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PMID:The systemic availability of oral glutathione. 136 56

Plasma membrane-bound 5'-nucleotidase (5'-NT), gamma-glutamyltransferase (gamma-GT) and soluble deoxynucleotidyltransferase (TdT) were studied in peripheral blood cells (PBMN) of 35 individuals, 26 male and 9 female, with circulating anti-HIV antibodies. Twenty-six were drug abusers, 2 were drug abusers and homosexuals and 4 were homosexuals. Three did not fall into any risk group. The surface immunologic phenotype of cells stained with the fluorescent monoclonal antibodies Leu 5, Leu 3, Leu 2, Leu 12, Leu M3, Leu M1, anti-CALLA and anti-HLA-DR was delineated by flow cytometry. While the gamma-GT activity did not change, the lymphocyte 5'-NT activity was significantly less than normal in anti-HIV positive individuals and in anti-HIV negative drug abusers. TdT activity was detectable in 14 anti-HIV positive patients (40%), who did not have clinical AIDS. Of 8 patients with AIDS, 3 had a low level of TdT activity but 5 had cells completely devoid of TdT and 5'-NT activity. 5'-nucleotidase activity and the frequency of Leu 2 suppressor antigen bearing cells were the only independent variables that correlated with AIDS incidence.
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PMID:Enzymatic imbalance in peripheral blood mononuclear cells isolated from individuals with anti-HIV antibodies. 257 Jun 50

One hundred consecutive patients with serum antibodies against HIV 1 were evaluated for the prevalence and the type of liver injury. According to the CDC classification, 16 patients belonged to group II (asymptomatic patients), 47 to group III (persistent generalized lymphadenopathy) and 37 to group IV (11 constitutional disease, 19 secondary infectious diseases, 5 secondary cancers, one chronic lymphoid interstitial pneumonitis and one visceral leishmaniasis). Liver histology was studied in 32 patients. Clinical, biological and histologic abnormalities were assessed according to the clinical group and to the number of T4 lymphocytes. The prevalence of HBV infection was determined by HBV DNA and monoclonal antibodies. Clinical hepatic abnormalities were rare (13 p. 100) and no difference was found between groups. Transaminases or GGT activities were elevated in 60 p. 100 of all cases. Serum GGT activity was higher and serum albumin lower in patients in group IV. HBV infection markers were less frequently found in patients with opportunistic infection (74 p. 100) than in asymptomatic patients (100 p. 100; p less than 0.05). Prevalence of serum HBsAg detected by poly- or monoclonal antibodies was very high (29 p. 100) in all clinical groups. Prevalence of serum HBsAg detected only by monoclonal antibodies (10 p. 100) suggest infection of these patients by an HBV variant. Of the 32 patients undergoing liver histology, only 5 (16 p. 100) had signs of activity. There was no association between clinical or histologic signs and the number of T4 lymphocytes per ml. Alkaline phosphatase, ASAT and GGT activities were higher and serum albumin lower in patients with less than 200 T4 lymphocytes per ml.
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PMID:[Hepatic involvement in HIV 1 virus infection]. 290 Jan 80

A commercially available luminescence enhanced enzyme immunoassay (Amerlite--Amersham International) for carcinoembryonic antigen (CEA) was compared with an established enzyme immunoassay (Monoclonal 1-step Assay--Abbott Laboratories). A reference range for healthy blood donors (n = 272) was established for both kits. The blood donors were not separated into smokers and non-smokers, but were excluded from the reference group if they showed abnormal aminotransferase or gamma-glutamyltranspeptidase serum values. Twenty eight donors were excluded in this way. The test group consisted of 130 known tumour patients, and included pre- and post-operative serum samples. Normal and elevated CEA values were present. All sera were negative for HBsAg, anti-HBsAg and anti-HIV as determined with commercial enzyme immunoassays used routinely in the blood bank. The luminescence enhanced immunoassay gave rise to a reference range (95% confidence limits) of less than 3.91 micrograms/l in comparison with the enzyme immunoassay, which had a reference range of less than 4.12 micrograms/l. The proportion of elevated values in the tumour patient group was 37/130 for the luminescence enhanced enzyme immunoassay and 28/130 for the enzyme immunoassay. The correlation of values from both methods in the blood donor group was good (r = 0.771, n = 272). The CEA levels found in the tumour patient group differed significantly when measured in both kits (Wilcoxon matched-pair signed rank test--c-alpha = -6.52, p less than 0.01, n = 130), the Amersham kit giving the higher results (median values--Abbott 2.35 micrograms/l, Amersham 2.50 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Initial results with a commercial luminescence enhanced enzyme immunoassay for the determination of carcinoembryonic antigen (CEA) in body fluids. 332 Feb 61

An increase in serum lactate dehydrogenase (LDH) activity is commonly taken to support the presumptive diagnosis of Pneumocystis carinii pneumonia (PCP), although the LDH level may also be increased in other lung infections and in a variety of extrapulmonary disorders. To assess its diagnostic value in patients with fever, lung infiltrates, and a high prevalence of HIV infection, we compared LDH levels in 42 hospitalized patients with PCP, 71 with disseminated tuberculosis (TB), 40 with pulmonary TB, and 37 with bacterial pneumonia. Peak LDH level was higher (p < 0.05) in patients with PCP (547 +/- 157 U/L) and disseminated TB (569 +/- 338 U/L) than in patients with pulmonary TB (258 +/- 66 U/L) or bacterial pneumonia (331 +/- 139 U/L). However, substantial overlap between groups limited its diagnostic value for individual patients. Expressing LDH as its ratio to simultaneous serum aminotransferases (AST or ALT) did not enhance its discriminatory value. Most patients in each group had abnormalities in other serum enzymes (AST, ALT, alkaline phosphatase, gamma-glutamyltransferase), making an isolated elevation of LDH level uncommon (21% of PCP cases). Serum LDH has a high sensitivity for PCP (100% in this series) but must be interpreted with caution given its lack of specificity.
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PMID:Serum lactate dehydrogenase (LDH) in Pneumocystis carinii pneumonia, tuberculosis, and bacterial pneumonia. 763 77

A previously healthy, now 42-year-old man suddenly fell ill with bouts of septic fever up to 39.5 degrees C, sweats and weight loss without any demonstrable organ involvement. Physical examination on hospitalization 3 weeks after onset of the illness was unremarkable. Blood sedimentation rate at one hour was 123 mm. There was also a moderate increase in gamma-GT and alkaline phosphatase. Routine bacteriological and serological tests failed to discover a causative microorganism. After imaging tests had provided first indication of splenic and hepatic involvement, biopsies of these two organs demonstrated disseminated epithelioid granulomas and Langhans giant cells. Staining and culturing of pelvic crest biopsy tissue showed evidence of Mycobacterium tuberculosis, but there was no evidence of pulmonary involvement. In addition to four-drug tuberculostatic treatment the patient was given glucocorticoids for several weeks to control the fever bouts. Persistent CD4+ T-lymphocytopenia was demonstrated as the cause of the entirely extrapulmonary tuberculosis in this HIV-negative patient. This is an only recently described and so far unexplained syndrome.
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PMID:[Disseminated extrapulmonary tuberculosis in idiopathic CD4-lymphocytopenia]. 782 Dec

An antisense phosphorothioate oligodeoxynucleotide 27-mer complementary to the rev gene mRNA of the human immunodeficiency virus (HIV-1) was administered to rats through intravenous injections and subcutaneous infusions in order to investigate the disposition of this compound. In addition, nonlethal toxic responses of the rat were evaluated. A biphasic plasma clearance with t1/2 alpha of 20-25 min and t1/2 beta of 27-41 hr was observed. Single doses ranging from 35 to 3257 micrograms were examined, and the plasma concentration and area under the plasma concentration-time curve (AUC) were found to be directly proportional to the dose. Continuous subcutaneous infusion of 50 mg over 28 days was also examined. The oligonucleotide is completely eliminated in the urine over 3 days. Electrophoretic analysis demonstrated that the excreted compound has the same mobility and UV-absorbance profile as the administered compound. Measurement of accumulation and distribution into tissues revealed unique tissue-specific rates and extent of oligonucleotide movement into and out of tissues. Results of the chronic infusion study suggest that uptake into tissue is not saturated, even after 28 days of infusion. Analysis of blood plasma from oligonucleotide-treated animals shows a possible transient elevation in levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), but not alkaline phosphatase (AP), gamma-glutamyltransferase (GT), and bilirubin. The data collectively support the potential utility of phosphorothioate oligonucleotides as therapeutic agents in vivo.
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PMID:Pharmacokinetics of an antisense phosphorothioate oligodeoxynucleotide against rev from human immunodeficiency virus type 1 in the adult male rat following single injections and continuous infusion. 806 15

Light-activated merocyanine 540 (pMC540) has been shown in our earlier studies to be effective against certain types of tumor cells and viruses, including human immunodeficiency virus (HIV-1). To test the potential extracorporeal and systemic use of pMC540, its toxicity was investigated in DBA/2 mice, pigs, and dogs. The lethal dose in DBA/2 mice after an i.p. injection was 370 mg/kg, and the 50% lethal dose (LD50) was 320 mg/kg; however, following i.v. administration, the lethal dose and the LD50 dose were 240 and 160 mg/kg, respectively. Tritium-labeled MC540 was used to study the biodistribution of pMC540 in DBA/2 mice. Almost 70% of the injected radioactivity was excreted within 6 h of injection. After 1 week, the pMC540 was almost completely cleared, with only 1.89% of the activity remaining, and had a plasma half-life of 23 h. Pigs injected with an accumulated dose of 10 mg/kg and followed for a period of 30 days did not show adverse signs of toxicity as monitored by SMAC-28 analysis, CBC profile, and blood-coagulation studies. A dog injected with a single dose of 20 mg/kg showed induction of the hepatic enzymes glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (AST); however, serum levels of gamma-glutamyl transpeptidase (GGT) remained unchanged. The data presented herein may serve to identify certain drug-dose limitations in the systemic use of pMC540.
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PMID:Biodistribution and toxicity of photoproducts of merocyanine 540. 845 86

We report the case of a young HIV seropositive patient with severe hemophilia A who presented rapid liver failure related to his chronic C hepatitis. The patient had been receiving factor VIII:C clotting factor concentrates (mean 60,000 U/year) since 1975. In 1984 alanine aminotransferase presented abnormal levels. The CD4 lymphocyte count in 1991 was normal and ultrasonographic scan showed normal liver morphology. In 1991 the patient were found to be seropositive for HCV antibodies as detected by the ELISA method and confirmed by the RIBA method. One year later, a progressive increase in policlonal gamma-globulin and a decrease in the CD4+ lymphocyte count to below 500/muL were detected in concomitance with ultrasonographic evidence of a progressive increase in the longitudinal diameters of the liver and spleen and signs of liver inhomogeneity. A significant inverse correlation was observed between the increase in the longitudinal diameter of the liver and the decline in albumin levels, and between the increase in the longitudinal diameter of the liver and the drop in platelet count. Elevated levels of ammonemia, gamma-glutamyl transpeptidase, alkaline phosphatase and IgA were detected. Moreover, decreased levels of the C4 and C3 complement fractions were documented. At this time (1994), esophagogram and esophagogastroscopy evidenced varicosities in the lower esophageal section (stage F1). The patient died in 1995 March at the age of 29 years of sudden septic shock related to Pseudomonas aeruginosa infection.
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PMID:Rapid liver failure related to chronic C hepatitis in an HIV seropositive hemophilic patient with severe immunodepression. 887 Mar 78

The relationship between ritonavir plasma concentration, efficacy, and tolerance was evaluated in 31 children with advanced HIV infection who were receiving a triple therapy with ritonavir as protease inhibitor. Median CD4+ lymphocyte count and median viral load before the initiation of ritonavir-containing combination therapy were 1320 cells/mL and 5 log10 copies/mL, respectively. Ritonavir was given at a dose ranging from 300 to 450 mg/m2 twice daily. The median follow-up of triple therapy was 19 months. Response was defined as a drop of viremia of more than 1 log. Plasma drug levels were determined twice during the observation period: after at least 4 weeks and after 3 months of combined treatment. Samples were collected before (residual) and 2 hours (T2) after drug intake. Cholesterol, triglycerides, alanine transaminase, aspartate transaminase, and gamma-glutamyl transpeptidase were assessed at the same time. The median values of ritonavir residual and T2 levels were 1.64 mg/L and 5.9 mg/L at observation 1 and 3.35 mg/L and 6.29 mg/L at observation 2, respectively. According to virologic response, median residual concentrations of ritonavir were 3.17, 2.52, and 1.04 mg/L for the complete, the partial, and the no-response groups. The authors observed a wide intersubject variability of ritonavir concentrations with an increase in residual levels between the two observation periods. Residual levels were correlated with virologic response whereas there was no direct association between T2 levels and long-term response. Patients with complete or partial response displayed statistically significantly higher residual concentrations than the no-response group. No correlation could be demonstrated between elevated plasma drug concentrations and abnormal cholesterol or triglycerides values. These results emphasize the importance of a sustained high ritonavir concentration to achieve optimal treatment efficacy. Furthermore, these results prove the clinical benefit of therapeutic drug monitoring and could potentially improve patient evaluation in terms of treatment efficacy, compliance, and viral resistance.
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PMID:Relationship between efficacy, tolerance, and plasma drug concentration of ritonavir in children with advanced HIV infection. 1094 79


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