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: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV is the most significant risk factor for many opportunistic infections like tuberculosis. In this study, we designed an isatinimino lead compound as a novel non-nucleoside reverse transcriptase inhibitor with antimycobacterial properties for the effective treatment of AIDS and AIDS-related tuberculosis. Among the compounds sythesized, 1-cyclopropyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-7[[N4-[3'-[(4,6-dimethylpyrimidin-2-yl)benzenesulfonamido-4-yl]imino-1'-(5-fluoroisatinyl)]methyl]-3-methyl N1-piperazinyl]-3-quinoline carboxylic acid (9) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV (EC50: 12.1 microg/ml), and Mycobacterium tuberculosis (MIC: 1.22 microg/ml).
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PMID:Synthesis, anti-HIV and antitubercular activities of isatin derivatives. 1664 36

In sub-Saharan Africa, the position of efavirenz as a first-line nonnucleoside reverse transcriptase inhibitor remains to be discussed. We report here the 6-month efficacy and tolerance of an efavirenz-containing highly active antiretroviral therapy in a large cohort of HIV-1-infected adults. Seven hundred forty highly active antiretroviral therapy-naive adults (74% women; 14% with positive serum HBs antigen and 21% with abnormal baseline transaminase value) started zidovudine + lamivudine + efavirenz. At month 6, 1.2% of them were dead, 87% had undetectable viral load, and 7% had abnormal transaminase value. From months 1 to 6, the percentage of women who were actually using a contraceptive method increased from 58% to 80% (65% intramuscular progesterone and 35% oral estrogen/progesterone combination). The incidence of pregnancy was 2.6/100 woman-years (95% confidence interval, 0.67-4.51), and 86% of pregnant women voluntarily interrupted the pregnancy with no intervention on our part. Before month 6, only 0.8% of patients permanently discontinued efavirenz for severe adverse effects (neurologic, 0.6%; cutaneous, 0.1%; and hepatic, 0.1%). The leading cause of severe morbidity was tuberculosis. Considering the very high hepatic and cutaneous tolerance, efavirenz could be considered as a valuable first-line drug for women of childbearing age who agree to use contraception in sub-Saharan Africa, provided that the risk of teratogenicity should be closely monitored.
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PMID:Tolerance and acceptability of an efavirenz-based regimen in 740 adults (predominantly women) in West Africa. 1676 90

HIV is the most significant risk factor for many opportunistic infections like tuberculosis, bacterial infections etc. In this paper, we designed aminopyrimidinimino isatin lead compound as a novel non-nucleoside reverse transcriptase inhibitor with broad-spectrum chemotherapeutic properties for the effective treatment of AIDS and AIDS-related opportunistic infections. Compound 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7[[N(4)-[3'-(4'-amino-5'-chloroben-zylpyrimidin-2'-yl)imino-1'-(5-methylisatinyl)] methyl]N(1)-piperazinyl]-3-quinoline carboxylic acid (10) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV-1 replication (EC(50): 9.4 microg /ml), M. tuberculosis (MIC: 3.13 microg /ml) and various pathogenic bacteria (MIC's: 1.22 microg /ml).
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PMID:Aminopyrimidinimino isatin analogues: design and synthesis of novel non- nucleoside HIV-1 reverse transcriptase inhibitors with broad-spectrum anti-microbial properties. 1678 23

Macrophages play an essential role in the immune response to Mycobacterium tuberculosis (Mtb). Previous transcriptome surveys, by means of micro- and macroarrays, investigated the cellular gene expression profile during the early phases of infection (within 48 hr). However, Mtb remains within the host macrophages for a longer period, continuing to influence the macrophage gene expression and, consequently, the environment in which it persists. Therefore, we studied the transcription patterns of human macrophages for up to 7 days after infection with Mtb. We used a macroarray approach to study 858 human genes involved in immunoregulation, and we confirmed by quantitative real-time reverse transcriptase polymerase chain reaction (q-rt RT-PCR) and by enzyme-linked immunosorbent assay the most relevant modulations. We constantly observed the up-regulation in infected macrophages versus uninfected, of the following genes: interleukin-1 beta and interleukin-8, macrophage inflammatory protein-1 alpha, growth-related oncogene-beta, epithelial cell-derived neutrophil-activating peptide-78, macrophage-derived chemokine, and matrix metalloproteinase-7; whereas macrophage colony-stimulating factor-receptor and CD4 were down-regulated in infected macrophages. Mtb is able to withstand this intense cytokine microenvironment and to survive inside the human macrophage. Therefore we simultaneously investigated by q-rt RT-PCR the modulation of five mycobacterial genes: the alternative sigma factors sigA, sigE and sigG, the alpha-crystallin (acr) and the superoxide dismutase C (sodC) involved in survival mechanisms. The identified host and mycobacterial genes that were expressed until 7 days after infection, could have a role in the interplay between the host immune defences and the bacterial escape mechanisms.
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PMID:Gene expression profiling of human macrophages at late time of infection with Mycobacterium tuberculosis. 1689 54

Several animal models are used to study Mycobacterium tuberculosis (MTB) infections, but none is a fully ideal model of human disease. The American cotton rat is an excellent model for the study of several human viral and bacterial respiratory infectious diseases, but until now has not been reported to be a model with MTB infection. Preliminary experiments were designed in which two species of cotton rats (Sigmodon hispidus and Sigmodon fulviventer) received respiratory challenges with M. tuberculosis via either intranasal or aerosol inoculation. Granulomatous disease, often with central necrosis, developed in the lungs, spleen, and lymph nodes of infected animals. The number of MTB bacilli in the lungs increased logarithmically until reaching a plateau in the second month after aerosol inoculation. There were differences in response to infection between the two species, with S. fulviventer demonstrating greater mortality than S. hispidus. Cytokine gene expression analysis by reverse transcriptase polymerase chain reaction (RT-PCR) was performed on both normal appearing and granulomatous lung tissue from infected animals. Many cytokine genes were more highly expressed in the focal areas of inflammation. Cotton rats provide another valuable tool in future research with tuberculosis.
Tuberculosis (Edinb) 2007 Mar
PMID:The American cotton rat: a novel model for pulmonary tuberculosis. 1697 21

Tuberculosis associated with HIV infection continues to be an important problem throughout the world. Since the advent of HAART, the medication of HIV-infected patients who have to receive concomitant treatment for tuberculosis has become a difficult task. The two main problems faced by clinicians include the significant pharmacokinetic interactions between rifamycins, a cornerstone in antituberculosis therapy, and protease inhibitors and nonnucleoside reverse transcriptase inhibitors, which are essential components of antiretroviral combination regimens, as well as the best moment to initiate antiretroviral therapy in patients with tuberculosis. The therapy of choice for patients with no previous antiretroviral experience includes an antituberculous regimen with rifampin and an efavirenz-based antiretroviral regimen. No dose adjustments of these drugs seem to be necessary. Nevirapine can be an alternative to efavirenz in this situation. For patients who cannot take efavirenz, either due to resistance or intolerance, rifabutin and a boosted protease inhibitor can be coadministered, with the necessary dose adjustments. No definite recommendations can be given regarding the optimal timing of antiretroviral therapy, but a delay of two months after initiation of antituberculosis therapy would be advisable and seems to be safe in most patients.
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PMID:Antiretroviral therapy in AIDS patients with tuberculosis. 1707 82

HIV and tuberculosis (TB) are leading global causes of mortality and morbidity, and yet effective treatment exists for both conditions. Rifamycin-based antituberculosis therapy can cure HIV-related TB and, where available, the introduction of highly active antiretroviral therapy (HAART) has markedly reduced the incidence of AIDS and death. Optimal treatment regimens for HIV/TB co-infection are not yet clearly defined. Combinations are limited by alterations in the activity of the hepatic cytochrome P450 (CYP) enzyme system, which in particular may produce subtherapeutic plasma concentrations of antiretroviral drugs. For example, protease inhibitors often must be avoided if the potent CYP inducer rifampicin is co-administered. However, an alternative rifamycin, rifabutin, which has similar efficacy to rifampicin, can be used with appropriate dose reduction. Available clinical data suggest that, for the majority of individuals, rifampicin-based regimens can be successfully combined with the non-nucleoside reverse transcriptase inhibitors nevirapine and efavirenz. Most available HAART regimens in areas that have a high burden of TB contain one or the other of these drugs as a backbone. However, significant questions remain as to the optimal dose of either agent required to ensure therapeutic plasma concentrations, especially in relation to particular ethnic groups. The timing of HAART initiation after starting antituberculosis therapy continues to be controversial. Debate centres upon whether early initiation of HAART increases the risk of paradoxical reactions (immune reconstitution-related events) and other adverse events, or whether delay greatly elevates the risk of disease progression. Further prospective clinical data are needed to help inform practice in this area.
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PMID:Tuberculosis and HIV co-infection: a practical therapeutic approach. 1718 73

In order to examine the relationship between malnutrition and tuberculosis development in vivo, a malnourished guinea pig model fed with a low casein (5%) diet was developed. After being fed with the low casein diet, the guinea pigs were infected with Mycobacterium (M.) tuberculosis Kurono strain by aerosol infection, and seven weeks later were subjected to histopathologic examination, colony-forming unit (CFU) assay, fluorescence-activated cell sorter (FACS) analysis and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12 and inducible nitric oxide synthase (iNOS) mRNA. Another group of guinea pigs were vaccinated subcutaneously with 10(6) CFU BCG Tokyo for three weeks and then similarly infected by aerosol. Eighty-eight% (7/8) of the malnourished guinea pigs succumbed to mycobacterial infection within 85 days after infection, while the malnourished guinea pigs vaccinated with BCG Tokyo survived. CFU assay showed that lung and splenic CFUs were higher in the low casein diet-fed groups than in the control diet (20% casein)-fed groups, although both groups had significantly lower CFUs after vaccination with BCG Tokyo (p<0.01). Examination of lung histopathology revealed that pulmonary granulomas were large and disorganized in the groups fed the low casein diet. The number of visible lesions on the surfaces of the fixed lungs in guinea pigs fed control diet+BCG and low casein diet+BCG was low significantly. Pan T-, CD4-, CD8- and Mac antigen-positive cells were also recognized in the infected lung tissues of low casein-fed guinea pigs and Pan T-, CD4- and Mac antigen-positive cells increased after vaccination with BCG Tokyo. Expression of IFN-gamma, TNF-alpha, IL-12 and iNOS mRNA was also recognized in the infected lung tissues of low casein-fed guinea pigs and IFN-gamma and TNF-alpha mRNA expression was enhanced with BCG vaccination. These results indicate that malnutrition exacerbates mycobacterial infection and that malnourished infected hosts may be protected by BCG vaccination.
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PMID:BCG vaccination enhances resistance to M. tuberculosis infection in guinea pigs fed a low casein diet. 1734 51

To understand the predominant HIV subtype and drug-resistant viruses in northwest Ethiopia, isolates from 92 antiretroviral drug-naive HIV-1-infected tuberculosis patients were analyzed. Of these patients, 90 (97.8%) were found to be infected with viral subtype C. Other isolates had subtype A (1.1%) and subtype D (1.1%). No primary mutations were associated with protease inhibitor drug resistance. One case (1.1%) had the reverse-transcriptase mutation, V75I. Two patients (2.2%) had the G190A mutation, which confers resistance to the nonnucleoside reverse transcriptase inhibitor, nevirapine. Our study demonstrates that subtype C is the major HIV-1 subtype in northwest Ethiopia. Our results also reveal that the population in the study area had been exposed to antiretrovirals and that treatment-naive patients had drug resistance mutations. Thus, our results emphasize the need for routine drug resistance monitoring in northwest Ethiopia.
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PMID:Molecular epidemiology of HIV type 1 in treatment-naive patients in north Ethiopia. 1745 46

Glycoprotein Si was the major protein to determine infection and immunogenicity of Infectious bronchitis virus (IBV). The S1 glycoprotein gene of IBV isolates were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and proved to be S1 gene by sequencing. The E. coli-mycobacterium expression shuttle plasmid pR-alpha-S1 was constructed by inserting the S1 gene to the pRR3 with human mycobacterium tuberculosis HSP70 promoter and a signal peptide. Then the plasmid pR-alpha-S1 was introduced into mycobacterium bovis BCG by electroporation to construct a recombinate strain rBCG-Sl. The S1 protein could be highly expressed in M. smegmatis mc2 155 when induced by heating and was detected by ELISA and Western blot assays using monoclonal antibody against S1 glycoprotein of IBV. 6 week-old SPF chicken were subcutaneously immunized with 10(6) cfu rBCG-S1 and each chick was immunized three times at 3 week intervals with the same antigen used for the primary immunization. The protective immunity of rBCG-S1 was identified in vaccinated chickens. Results from the protection test showed the two immunizations with rBCG-S1 could provide protection for chickens from the challenge with virulent nephropathogenic IBV strain X. Haemagglutination inhibition titers were also increased in chickens immunized with the expressed rBCG-S1, and significantly higher titers were detected after challenge. These data indicate that the rBCG-S1 could be used as candidate of a live vector vaccine for NIBV.
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PMID:[Construction of recombinant BCG bearing S1 glycoprotein of nephropathogenic IBV and study on its immunogenicity on chickens]. 1755 43


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