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

Tuberculosis (TB) today remains one of the world's most lethal infectious diseases. An estimated one-third of the world's population is infected with the tubercle bacillus-Mycobacterium tuberculosis (Mtb), and 7 to 8 million people develop TB disease each year (27). For purpose of clarity, TB infection (latent TB) is defined as harboring Mtb without evidence of active infection, and TB disease is active infection without Mtb based on clinical and laboratory findings. Recognizing that TB has been one of the most neglected international health problems and that the TB epidemic is rampant in many parts of the world, the World Health Organization (WHO) declared TB to be a global health emergency in 1993 (23). Despite the steady decline in TB cases since this time resulting from the overall implementation of more effective infection control practices, directly observed therapy (DOT), and efforts to control the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) epidemic, preventive and control strategies among other high-risk populations such as the elderly evidently remain a clinical and epidemiological challenge. The geriatric population among all ethnic groups and both genders, represent the largest reservoir of TB infection, particularly in developed nations (9). Clinical features of TB in older adults may be atypical, non-specific, and confused with concomitant age-related diseases (28). Underlying acute or chronic diseases, malnutrition, and the biological changes with aging, can disrupt integumental barriers, impair microbial clearance mechanisms, and contribute to the expected age-associated decline in cellular immune responses to infecting agents such as Mtb. Diagnosis of TB can be difficult and consequently overlooked; this treatable infection may unfortunately be recognized only at autopsy. Furthermore, therapy of TB in the elderly is challenging because of the increased incidence of adverse drug reactions. Optimal treatment of associated chronic diseases, minimization of invasive procedures, limitation of polypharmacy, and adequate nutritional support are essential for this vulnerable population. The institutionalized elderly in addition are especially at high risk for reactivation of latent TB as well as susceptible to new TB infection. This article will discuss the global epidemiology, pathogenesis and immunologic aspects, unique clinical consideration, treatment and prevention of TB, briefly inclusive of the recent published guidelines for targeted tuberculin testing and treatment of latent TB infection as it pertains to the elderly.
 ...
PMID:Tuberculosis in the elderly. 1113 Jan 91

To terminate the reverse transcription of the human immunodeficiency virus type 1 (HIV-1) genome, a final step occurs within the center of the proviral DNA generating a 99-nucleotide DNA flap (6). This step, catalyzed by reverse transcriptase (RT), is defined as a discrete strand displacement (SD) synthesis between the first nucleotide after the central priming (cPPT) site and the final position of the central termination sequence (CTS) site. Using recombinant HIV-1 RT and a circular single-stranded DNA template harboring the cPPT-CTS sequence, we have developed an SD synthesis-directed in vitro termination assay. Elongation, strand displacement, and complete central flap behavior were analyzed using electrophoresis and electron microscopy approaches. Optimal conditions to obtain complete central flap, which ended at the CTS site, have been defined in using nucleocapsid protein (NCp), the main accessory protein of the reverse transcription complex. A full-length HIV-1 central DNA flap was then carried out in vitro. Its synthesis appears faster in the presence of the HIV-1 NCp or the T4-encoded SSB protein (gp32). Finally, a high frequency of strand transfer was shown during the SD synthesis along the cPPT-CTS site with RT alone. This reveals a local and efficient 3'-5' branch migration which emphasizes some important structural fluctuations within the flap. These fluctuations may be stabilized by the NCp chaperone activity. The biological implications of the RT-directed NCp-assisted flap synthesis are discussed within the context of reverse transcription complexes, assembly of the preintegration complexes, and nuclear import of the HIV-1 proviral DNA to the nucleus toward their chromatin targets.
 ...
PMID:Human immunodeficiency virus type 1 central DNA flap: dynamic terminal product of plus-strand displacement dna synthesis catalyzed by reverse transcriptase assisted by nucleocapsid protein. 1123 56

Optimal use of anthelmintics in children is of major public health importance because the parasites involved probably infect over 2 billion persons, and most are especially common and debilitating in children. Well targeted drug delivery, particularly via community chemotherapy, can substantially decrease aggregate morbidity and mortality and also improve growth rates, physical fitness and activity, cognitive and school performance, and social well-being. The drugs discussed here include the benzimidazoles (albendazole, levamisole and mebendazole), pyrantel, praziquantel, oxamniquine, ivermectin, diethylcarbamazine and some traditional medicines. The parasitic infections discussed are hookworm, ascariasis, trichuriasis, strongyloidiasis, schistosomiasis and lymphatic filariasis; onchocerciasis and loiasis are also mentioned briefly. Dosage regimens and effectiveness, including combination treatment, are discussed. Mechanisms by which parasites may cause or aggravate malnutrition and retard development are shown, along with examples of nutritional and functional improvement at various ages due to antiparasitic treatment. Improvement in appetite is likely to be the single most important mechanism through which a variety of physiological improvements occur. We recommend community treatment of girls and women of childbearing age in areas with widespread hookworm and anaemia, because effective treatment can reduce the incidence of low birthweight, mortality in infancy and pregnancy, and stunted growth and morbidity in children and adults. Treatment of moderate-to-severe anaemia improves appetite, growth and cognitive and school performance in children, and also improves work and social capacity and productivity in children and adults. Since treatment for helminth infections may also decrease both the probability of contracting HIV infection and the rate of viral replication in those infected with both types of organisms, large-scale treatment and control of helminths and treatment of individual cases when diagnosed are now truly urgent.
 ...
PMID:Optimising the benefits of anthelmintic treatment in children. 1151 81

In collaboration with the Dutch Institute for Health Care Improvement (CBO) and on the basis of recent developments, new guidelines have been developed for the diagnosis and treatment of HIV-infected patients. The most important recommendations are: Treatment of adult patients is indicated if HIV load > 30,000 RNA copies/ml, or when CD4+ cell count is < 350 x 10(6) cells/l. Treatment of children is indicated if HIV load > 5,000 copies/ml, even when CD4+ cell count is > 500 x 10(6) cells/l. Optimal antiretroviral treatment consists of a combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and one protease inhibitor, or a combination of two NRTIs and one non-nucleoside reverse transcriptase inhibitor. Patients on antiretroviral treatment should be monitored every 3 months. Undetectable HIV load should be the target of first- or second-line antiretroviral treatment. In order to prevent HIV transmission from mother to child, prescription of antiretroviral drugs after the first three months of pregnancy is indicated in pregnant women with a detectable HIV load. Prophylaxis of opportunistic infections can be discontinued if CD4+ cell count recovers above 200 x 10(6)/l. In case of exposure to HIV due to a needle or other occupational accident or unsafe sexual contact, post-exposure prophylaxis should be offered after careful risk evaluation. Preferably, vaccination to prevent pneumococci infections, influenza, hepatitis A or hepatitis B should be given when CD4+ cell count is > 200 x 10(6)/l.
 ...
PMID:[CBO guidelines 'Antiretroviral therapy in the Netherlands']. 1153 75

During the HIV-1 replication process, interactions between the RNA sequence, named TAR RNA, and the viral protein, Tat, permit a fast and efficient transcription of viral DNA into RNA. Based on the NMR structure of TAR RNA from the PDB, two Peptidic Nucleic Analog- (PNA) based molecules were designed by molecular modelling, the first one targeting G32 U31 and the second targeting U31 C30 free loop bases. Before designing the molecules, the flexibility of the TAR RNA was evaluated by molecular dynamics (MD). The molecules studied are composed of three domains: an arginine, a linker, and two PNA bases. First, molecules were designed and the linker length was optimized to fit the TAR RNA; second, a MD simulation on the TAR RNA molecule complex was performed to validate the molecular structure. Optimal molecules were synthesized and tested on infected cells. The experimental results support the choices made in the design of the molecules.
 ...
PMID:Interaction of new PNA-based molecules with TAR RNA of HIV-1: molecular modelling and biological evaluation. 1155 87

Human immunodeficiency virus type 1 (HIV-1) protease activity is targeted at nine cleavage sites comprising different amino acid sequences in the viral Gag-Pol polyprotein. Amino acid polymorphisms in protease and in regions of Gag, particularly p7(NC) and the C-cleavage site between p2 and p7(NC), occur in natural variants of HIV-1 within infected patients. Studies were designed to examine the role of natural polymorphisms in protease and to identify determinants in Gag that modulate protease processing activity. Closely related Gag-Pol regions from an HIV-1-infected mother and two children were evaluated for processing in an inducible expression system, for protease activity on cleavage-site analogues, and for impact on replication by recombinant viruses. Gag-Pol regions displayed one of three processing phenotypes based on the appearance of Gag intermediates and accumulation of mature p24(CA). Gag-Pol regions that were processed rapidly to produce p24(CA) resulted in high-level replication by recombinant viruses, while slow-processing Gag-Pol variants resulted in recombinant viruses that replicated with reduced kinetics in both T cell lines and peripheral blood mononuclear cells. Direct impact by Gag sequences on processing by protease was assessed by construction of chimeric Gag-Pol regions and by site-directed mutagenesis. Optimal protease activity occurred when Gag and Pol regions were derived from the same gag-pol allele. Heterologous Gag regions generally diminished rates and extent of protease processing. Natural polymorphisms in novel positions in p7(NC) and the C-cleavage site have a dominant effect on protease processing activity. Accumulation of Gag products after processing at the C site appears to delay subsequent cleavage and production of mature p24(CA).
 ...
PMID:Naturally occurring amino acid polymorphisms in human immunodeficiency virus type 1 (HIV-1) Gag p7(NC) and the C-cleavage site impact Gag-Pol processing by HIV-1 protease. 1187 16

A novel antifungal protein with its N-terminal sequence bearing similarity to the C-terminal sequences of peroxidases was isolated from French bean legumes. The protein, which possessed a molecular weight of 37 kDa, was adsorbed on Affi-gel blue gel and CM-Sepharose. The protein exhibited peroxidase activity with a Km of 58 microM and a Vmax of 3.36 U/nmol. Optimal peroxidase activity was found at 22 degrees C and pH 4. It exerted antifungal activity against a variety of fungal species including Coprinus comatus, Mycosphaerella arachidicola, Fusarium oxysporum and Botrytis cinerea. It inhibited the activities of alpha-glucosidase and beta-glucosidase but was without any inhibitory effect on HIV-1 reverse transcriptase.
 ...
PMID:Isolation of a novel peroxidase from French bean legumes and first demonstration of antifungal activity of a non-milk peroxidase. 1213 13

Nucleoside reverse transcriptase inhibitors (nucleoside analogues) are a central component of HAART regimens. Optimal adherence to and activity of the "nucleoside analogue backbone" is required to preserve the utility of the more cross-resistant protease inhibitor and nonnucleoside analogue components of a highly active regimen, and a systematic approach to nucleoside analogue sequencing is needed to preserve the clinical activity of this class. As HIV treatment strategies move toward the long-term management of a chronic infection, treatment issues such as convenience, safety, and tolerability become even more important. Acute and chronic safety issues associated with individual drug classes are a growing concern. Because adherence is linked to convenience and tolerability, new agents with favorable safety profiles, low pill burdens, and little or no selection for drug resistance will be required to ensure long-term viral suppression.
 ...
PMID:Adherence, resistance, and timing: current issues in the use of new therapies. 1222 92

Genotype-based resistance assays are commonly used to aid treatment in HIV-infected individuals failing antiretroviral therapy. The relationship between genotype and antiretroviral therapy comes mostly from in vitro assays of the response to a single drugs although there is a need for a prediction of clinical response to combination therapy. We have compared three different methods of analysing genotype data as a predictor of clinical response in a small clinical cohort of highly antiretroviral-experienced individuals failing therapy. No method performed well beyond 8 weeks into a new therapeutic regimen. A model based on the number of 'primary' mutations was statistically significant, but a multiple regression model, which identified specific mutations explained threefold more variation in response. Optimal prediction in this dataset was given by a model obtained from a classification tree analysis, in which genotype at amino acid sites 135 and 202 were combined with amino acid site 184, which explained over 50% of the deviance in the data and had a classification success of 86%.
 ...
PMID:Association of antiretroviral resistance genotypes with response to therapy--comparison of three models. 1248 81

The leishmaniases are protozoan diseases caused by Leishmania parasites. The first-line treatment of its visceral forms is pentavalent antimony (meglumine antimoniate or sodium stibogluconate), but toxicity is frequent with this drug. Moreover antimony unresponsiveness is increasing in Leishmania infantum and L. donovani foci, both in immunocompetent and in immunosuppressed patients. Amphotericin B is a polyene macrolide antibiotic that binds to sterols in cell membranes. It is the most active antileishmanial agent in use. Its infusion-related and renal toxicity may be reduced by lipid-based delivery. Liposomal amphotericin B (AmBisome); Gilead Science, Paris, France) seems to be less toxic than other amphotericin B lipid formulations (Amphocil); Liposome Technology Inc., Menlo Park, CA, USA, Amphotec); Ben Venue Laboratories Inc., Bedford, OH, USA). Optimal drug regimens of AmBisome) vary from one geographical area to another. In the Mediterranean Basin, a total dose of 18 mg/kg (3 mg/kg on days 1-5 and 3 mg/kg on day 10) could be used as first-line treatment of visceral leishmaniasis in immunocompetent patients. In immunocompromised patients, especially those co-infected with HIV, relapses are frequent with AmBisome), as with other drugs.
 ...
PMID:Liposomal amphotericin B in the treatment of visceral leishmaniasis in immunocompetent patients. 1266 28


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>