Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: ZK856 .18
48,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A central aspect of health education campaigns designed to prevent the spread of HIV has been to encourage people to use condoms during sexual intercourse. Little research has, however, been carried out on attitudes towards condoms. The present study investigated the post-AIDS structure of students' attitudes to condoms and examined the association of subjects' age, sex, and experience of use with those attitudes. Subject were students attending a university and a polytechnic in Dundee, Scotland. Out of 600 questionnaires sent out 318 were returned after reminders, a response rate of 53%. Attitudes towards condoms were measured using 8 5-point Likert items. Principal component analysis with varimax rotation produced 3 orthogonal factors accounting for 61.0% of the variance. The factors were labelled Condom Effectiveness (26.3%), Condom Offensiveness (21.0%), and Condom Attractiveness (13.7%). Factor scores were computed by reversing the scoring of items with negative loadings and averaging across items within factors. Condoms were considered quite effective among the present sample (M=4.0, SD+0.6, range=1.5). Subjects also believed, however, that condoms were somewhat offensive (M=3.4, SD=0.6) and unattractive to use (M=2.7, SD=0.8). Women considered condoms more offensive than men (F 1273=11.06, p.001) and subjects who had previously used condoms during sex considered condoms more effective (F1273=4.85, p.05) and less offensive (F1273=12.18, p.001) than those who had never used them. Clearly these concerns about the condom on dimensions of effectiveness, offensiveness and attractiveness might be a barrier to intentions to change behavior and need to be addressed by health education campaigns. Such initiatives must, as Abrams, Abraham, Spears, and Marks (1990) and Abraham, Sheeran, Abrahams, and Spears (in press) point out, be targeted towards the concerns of particular groups such as those examined here. (full text)
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PMID:The postAIDS structure of students' attitudes to condoms: age, sex and experience of use. 234 52

A significant number of patients with AIDS and AIDS-related complex develop neurological complications. Therefore, it is critical that anti-HIV agents penetrate the blood-brain barrier and suppress viral replication in the brain. In an effort to increase the brain delivery of anti-HIV nucleosides, in vitro and in vivo pharmacokinetics of dihydropyridine derivatives of 3'-azido-2',3'-dideoxyuridine (AzddU, AZDU, or CS-87) and 3'-azido-3'-deoxythymidine (AZT, Zidovudine) have been studied. In vitro studies of the prodrugs (AzddU-DHP and AZT-DHP) in human serum, mouse serum, and mouse brain homogenate indicated that the rates of serum conversion from prodrugs to parent drugs are species dependent: mouse brain homogenate greater than mouse serum greater than human serum. Half-lives in human serum, mouse serum, and mouse brain homogenate are 4.33, 0.56, 0.17 h, respectively, for AzddU and 7.70, 1.40, and 0.18 h, respectively, for AZT. In vivo studies of AzddU-DHP and AZT-DHP showed that the prodrugs have areas under the serum concentration-time curves (AUC) similar to those of the parent drugs. The AUC in serum for AzddU following prodrug administration is 25.79 micrograms h/mL, which is similar to the value of 25.83 micrograms h/mL when AzddU was administered. Analogously, the serum AUCs for AZT when AZT-DHP and AZT were administered are 25.38 and 26.64 micrograms h/mL, respectively. However, the brain AUCs for both AzddU and AZT derived from prodrugs, being 11.43 and 11.28 micrograms h/mL, respectively, are greater than the brain AUCs for AzddU (2.09 micrograms h/mL) and AZT (1.21 micrograms h/mL) when the parent drugs were administered. Thus, the relative brain exposure (re) for AzddU (5.47) and AZT (9.32) indicate a significant increase in exposure to the anti-HIV nucleosides following prodrug administrations. The results of extended half-lives of the synthesized prodrugs in human serum along with the higher re values in vivo warrant studies in larger animals to determine the potential usefulness of the prodrugs in humans.
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PMID:Brain targeting of anti-HIV nucleosides: synthesis and in vitro and in vivo studies of dihydropyridine derivatives of 3'-azido-2',3'-dideoxyuridine and 3'-azido-3'-deoxythymidine. 237 45

Molecular evolution and phylogeny of different human immunodeficiency virus type 1 (HIV1) strains, of a type 2 (HIV2) strain, and of two simian immunodeficiency viruses (SIVAGM and SIVMAC) have been studied by comparing the nucleotide sequences of the two regions of their pol genes which encode the reverse transcriptase (RT) and endonuclease/integrase (EN). The analyses show that the different HIV 1s form one cluster (HIV1 group) and that the SIVs and HIV2 form another (HIV2 group). When the entire genomes of a HIV1, a HIV2, and the two SIVs were compared, the SIVAGM showed a unique pattern of mutation accumulations; that is, the SIVAGM has accumulated more nonsynonymous changes than synonymous changes in the RT and EN regions after its recent divergence from SIVMAC-142, and, furthermore, it has a deletion of approximately 350 bp in the region between the pol and env genes. The SIVAGM was apparently derived from cell cultures infected with a macaque isolate, SIVMAC-251. The contamination provides an opportunity to measure the maximum rate of evolution in the SIVAGM by comparing its DNA sequence to those of SIVMAC-251 and SIVMAC-142. The analysis shows that the rates are given approximately by (1.95 +/- 1.37) x 10(-3)/site/year for one SIVAGM sequence and (5.18 +/- 2.25) x 10(-3)/site/year for another.
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PMID:Molecular evolution of the human and simian immunodeficiency viruses. 246 34

The effects of dose on the pharmacokinetics of 2',3'-dideoxycytidine (DDC), a potent inhibitor of HIV replication, have been studied in rats. DDC was administered intravenously at doses of 10, 50, 100 and 200 mg kg-1. Plasma and urine drug concentrations were determined by HPLC. Non-compartmental pharmacokinetic parameters were calculated by area/moment analysis. DDC plasma concentrations declined rapidly with a terminal half-life of 0.98 +/- 0.18 h (mean +/- s.d.). No statistically significant differences were observed in pharmacokinetic parameters between the four doses. Total, renal and non-renal clearance values were independent of dose and averaged 1.67 +/- 0.24, 0.78 +/- 0.11, and 0.89 +/- 0.27 L h-1 kg-1, respectively. Approximately 50% of the dose was excreted unchanged in urine. Steady state volume of distribution was also independent of dose and averaged 1.2 +/- 0.21 L kg-1. Protein binding of DDC to rat serum proteins was independent of drug concentration with the fraction of drug bound averaging 0.45 +/- 0.12. Thus, the disposition pattern of DDC in the rat is independent of the administered dose even at high doses. Significant interspecies correlations were found for total, renal and non-renal clearance and steady state volume of distribution. Interspecies scaling resulted in superimposable plasma DDC concentration-time profiles from four laboratory animal species and man. Thus, plasma DDC concentrations in humans can be predicted from pharmacokinetic parameters obtained in laboratory animals.
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PMID:Pharmacokinetics of 2',3'-dideoxycytidine in rats: application to interspecies scale-up. 257 44

False positive tests for autonomic neuropathy in HIV-infection and AIDS? Case-control-study of heart rate variation in 62 cases Autonomic neuropathy is said to be common in AIDS. In a cross section study we tested heart rate variability, a simple and sensitive test, in relation to disease severity. The expiratory-inspiratory RR-interval-ratio (RRR) was normal in HIV-infected clinically healthy persons (mean 1.45; n = 10), but progressively lowered in LAS (1.24; n = 12), ARC (1.20; n = 7), AIDS (1.13; n = 20), AIDS with pneumocystis carinii pneumonia (1.07; n = 7) and patients who died within the four month study (1.06; n = 6). The progressive decrease of heart rate variability (from 45% to 6% for group means) is in accord with previous reports. - In a simultaneous case-control study we compared RRR of these 62 patients with those of 62 not HIV infected patients matched for age, sex, resting heart rate and presence of pneumonia. Neither in the six subgroups nor in the total group we found a difference between HIV infected patients and their controls (1.20 +/- 0.18 SD and 1.22 +/- 0.17, respectively; 62 pairs). The decrease of RRR with increasing disease severity in HIV-infected patients was mainly dependent upon increasing heart rate and to a lesser degree upon increasing age. Therefore, a decreased heart rate variability in AIDS is not a specific sign of autonomic neuropathy and likely to be a false positive test result.
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PMID:[False-positive test of autonomic neuropathy in HIV infection and AIDS? Case control study of heart rate variability in 62 HIV positive patients]. 273 26

To produce concentrations of zidovudine (AZT) in plasma and cerebrospinal fluid that would provide constant inhibition of the replication of human immunodeficiency virus (HIV), we gave AZT by continuous intravenous infusion to 21 children ranging in age from 14 months to 12 years who had acquired HIV infection through transfusions or perinatally. All patients were symptomatic before AZT treatment (Class P2 of the Centers for Disease Control); 13 (62 percent) had evidence of neurodevelopmental abnormalities. The mean CD4/CD8 ratio was 0.18; 11 patients had CD4 counts below 0.2 x 10(9) per liter. We administered AZT at four dose levels: 0.5, 0.9, 1.4, and 1.8 mg per kilogram of body weight per hour. The plasma drug concentrations achieved at the respective dose levels were 1.9 +/- 0.3, 2.8 +/- 1.4, 3.1 +/- 1.1, and 4.5 +/- 1.0 microM. The steady-state cerebrospinal fluid:plasma ratio was 0.24 +/- 0.07. The only evidence of toxicity was bone marrow suppression. Transfusion was required in 14 patients because of low levels of hemoglobin (5 mmol per liter [less than 8 g per deciliter]). Dose-limiting neutropenia (less than 0.5 x 10(9) polymorphonuclear leukocytes per cubic millimeter) occurred in most patients who received doses of 1.4 mg per kilogram per hour or more. Improvement in neurodevelopmental abnormalities occurred in all 13 children who had presented with encephalopathy before treatment. Serial measurements of IQ before therapy and after three and six months of continuous therapy with AZT showed that IQ scores, including those for verbal and performance IQ, rose in these 13 patients and in 5 other children who had no detectable evidence of encephalopathy before treatment. Most patients also had increased appetite and weight, decreased lymphadenopathy and hepatosplenomegaly, decreased immunoglobulin levels, and increased numbers of CD4 cells. In some patients the improvement in the features of encephalopathy occurred despite the absence of immunologic improvement. We conclude that AZT is beneficial in children with symptomatic HIV infection, especially those with encephalopathy (which may be subclinical), and that the optimal continuous intravenous dose of AZT in children is between 0.9 and 1.4 mg per kilogram per hour.
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PMID:Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection. 263 49

Fluconazole pharmacokinetics, including absolute bioavailability, were determined for one group of controls (n = 10) and two groups of people with human immunodeficiency virus (HIV) infection (those with CD4+ T-cell counts of less than [n = 4] or greater than [n = 9] 200 cells per mm3). Twenty subjects received four doses of fluconazole; three doses were oral (50, 100, and 400 mg), and one dose was intravenous (either 50, 100, or 400 mg). The other three subjects received one or two doses. The groups were comparable in terms of the weight, body mass index, and estimated creatinine clearance of the subjects, but the people with HIV infection were older. Pharmacokinetic parameters indicated linearity in all subjects; the area under the plasma concentration-time curve and the maximum concentration increased in proportion to the dose. The fraction of an oral dose of fluconazole absorbed approximated unity in all three groups of subjects. The mean (+/- standard deviation) plasma clearance of fluconazole was lowest in the group of subjects with low CD4+ T-cell counts; the value for this group was 0.74 +/- 0.19 liter/h, compared with 0.97 +/- 0.19 liter/h in the group with HIV infection and CD4+ T-cell counts of greater than 200 cells/mm3 and 1.18 +/- 0.23 liter/h in the group of control subjects (P < 0.05). The volume of distribution was lower in those with HIV infection (P = 0.04, corrected for weight). The half-life was longest in people with HIV infection and low CD4+ T-cell counts (P = 0.01). This study has shown that some differences do exist between the pharmacokinetics of fluconazole in people with HIV infection and those in noninfected controls.
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PMID:Pharmacokinetics and bioavailability of fluconazole in two groups of males with human immunodeficiency virus (HIV) infection compared with those in a group of males without HIV infection. 748 28

We studied two monoclonal antibodies (MAbs 9-11 and 41-1) which are specific for dominant and conserved epitopes located on HIV-1 transmembrane Gp41. These MAbs recognize both Gp41 and a synthetic HIV-1 envelope peptide (39GC) which is a fragment of Gp41. The interactions between MAbs 9-11 and 41-1 and 39GC either coupled to a sensor chip or to alkaline phosphatase were investigated using BIAcore technology. The association and dissociation rate constants as well as the affinity constants were determined. BIAcore technology allows real-time determination of the interaction between two molecules without the need for any labeling, neither isotopic nor enzymatic. The peptide 39GC was immobilized by coupling to dextran on the BIAcore biosensor through a disulfide bond with a cysteine residue added to the N-terminus of the synthetic peptide. The two native cysteine residues located in the loop of Gp41 were protected by ethylcarbamoyl residues (CONHC2H5); this chemical modification prevented the formation of the S-S bridge and in particular the internal loop. We specifically studied the interaction between the MAbs and either the protected peptide or the peptide whose cysteine residues had been deprotected in situ by alkaline treatment. The results showed that MAb 41-1 recognized 39GC either protected (Ka = 7.6 x 10(6) M-1) or unprotected (Ka = 1.48 x 10(8) M-1), whereas MAb 9-11 recognized only the unprotected form (Ka = 2.18 x 10(8) M-1). Our results suggest that the epitope MAb 9-11 is directed against a part of the peptide sequence which includes the two native cysteines. The difference in affinity observed for MAb 41-1 between the protected and the unprotected forms of 39GC was found to be due to a lower rate of dissociation for unprotected 39GC; these results illustrate the importance of peptide conformation on antibody recognition and might be explained by a conformational change due to reconstitution of the internal loop following deprotection of the thiol groups. MAbs 9-11 and 41-1 also recognized 39GC conjugated to alkaline phosphatase and deprotected. We observed a difference between the rate constants for MAb 41-1 binding to free peptide and its binding to the peptide-enzyme conjugate which might be due to changes in peptide flexibility. In contrast, the rate constants of MAb 9-11 were the same in both experiments, suggesting that the rigidity of the internal loop prevents changes in 9-11 epitope conformation.
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PMID:Effect of HIV-1 peptide presentation on the affinity constants of two monoclonal antibodies determined by BIAcore technology. 751 68

Cytopenia is a common complication of human immunodeficiency virus (HIV) infection and can affect different hematopoietic lineages, including erythropoiesis, lymphopoiesis, thrombopoiesis, and granulopoiesis. Stem cell factor (SCF), a cytokine expressed by bone marrow stromal cells, is a multipotential growth factor acting on early progenitor cells of most hematopoietic lineages. Therefore, we investigated the serum SCF levels in 74 HIV-infected persons without active secondary infection at different stages of HIV infection [Centers for Disease Control (CDC) stages A through C]. Circulating SCF levels were determined by enzyme-linked immunosorbent assay and were found to be significantly elevated in CDC stage A as compared with normal controls (7.18 +/- 1.94 ng/mL v 3.95 +/- 0.91 ng/mL, P = .04). However, in CDC groups B and C, SCF levels were lower than in CDC group A (3.29 +/- 0.75, P = .162, and 1.95 +/- 0.39, P = .005, respectively). Serum levels greater than 1.8 ng/mL were associated with a longer survival (P = .0037) in 74 HIV type 1 (HIV-1)-seropositive patients monitored for up to 114 weeks, suggesting that this cytokine may be directly associated with the disease course. A Cox proportional hazards model showed SCF to be an independent prognostic factor for survival (risk ratio for death, 0.73; 95% confidence interval, 0.56 to 0.95; P = .019). Serum SCF levels decreased on follow up in 24 of 38 patients or remained below 0.4 ng/mL in 10 of 38 patients from whom a second blood sample was collected after a mean interval of 44 weeks. To determine potential regulatory factors of SCF expression by stromal cells, we exposed cultured fibroblasts to various cytokines. Only interleukin-4 (IL-4) upregulated SCF mRNA. As IL-4 is modulated during early HIV disease, it may be a key regulator of SCF secretion. Further studies are required to elucidate the mechanism of SCF action and regulation in patients with HIV infection.
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PMID:Serum levels of stem cell factor are increased in asymptomatic human immunodeficiency virus-infected patients and are associated with prolonged survival. 754 Aug 85

A total number of 283 long distance truck drivers and their assistants (loaders) who ferry goods between Kenya and Zaire were included in a cross-sectional study between September 1991 and April 1992. 26% of the study subjects were seropositive for HIV-1 and none were HIV-2 seropositive. Countries of birth and residence were significantly associated with HIV infection (chi square = 23.6, p = 0.0006). Significant associations were also found between HIV seropositivity and level of secondary school education and above (OR = 3.4, 95% CI = 1.01-11.55); being circumcised, which was more protective (OR = 0.38, 95% CI = 0.19-0.76); a history of many years of driving (chi square = 9.3, p = 0.0254); and income (OR = 11.13, 95% CI = 1.35-91.95). When a stepwise multiple logistic regression model was fitted to all the variables observed to be significant in the univariate analysis, the following risk factors attained statistical significance: lack of circumcision (OR = 3.75); income greater than Ksh. 2000 (OR = 7.24); being employed in long distance driving more than 11 years (OR = 3.98); and secondary school education and above (OR = 4.06, 95% CI = 1.18-13.98). Reference for all the above odds ratios was 1.
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PMID:Epidemiology of HIV infection among long distance truck drivers in Kenya. 758 47


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