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M Petrella

Publications and source records attributed to M Petrella.

11 recordsLinked to original sources
PubMed2004

Rationale for maintenance of the M184v resistance mutation in human immunodeficiency virus type 1 reverse transcriptase in treatment experienced patients.

The M184V substitution in HIV-1 RT develops rapidly following initiation of therapy with 3TC and confers high-level phenotypic resistance to this drug both in vitro and in vivo. Interestingly, the presence of M184V is also associated with alteration of several mechanisms relating to RT function that include decreased RTprocessivity, reduced nucleotide-dependent primer unblocking, increased fidelity, hypersensitization to other NRTIs, impaired viral fitness, and delayed appearance of mutations in RT that are responsible for resistance to thymidine analogues (i.e. thymidine-associated mutations or TAMs). In addition, M184V may affect viral transmission and immunological response. Collectively, these factors might explain the residual antiviral effect and clinical benefit observed with continued use of 3TC in combination therapy regimens following the emergence of M184V.

Amino Acid Substitution↗
PubMed2001

HIV drug resistance and implications for the introduction of antiretroviral therapy in resource-poor countries.

The development and transmission of HIV drug-resistant viruses is of serious concern and has been shown to significantly diminish the effectiveness of antiretroviral therapy. In addition, cross-resistance between drugs of the same class can seriously limit therapeutic options and may potentially be most problematic in resource-poor settings where new drugs are not widely available. Strategies based on avoidance of virological failure are therefore essential for the long-term success of therapy. In this regard, regionally adapted programs to facilitate proper adherence with therapy need to be urgently implemented, concomitant with expanded access to new antiretroviral drugs. The value of genotypic resistance testing as a prognostic tool to help guide therapeutic decisions has been established. However, the relatively high cost of this novel technology does not warrant its routine utilization at this time in resource-poor countries. Lastly, the genetic barrier of the antiretroviral agents that are prescribed is also an important consideration that needs to be integrated with knowledge of HIV-1 subtypes, drug pharmacology, and medical management of concurrent illnesses. The selection of appropriate first-line antiretroviral combination regimens may be an even more important consideration in developing than developed countries, given that options in the aftermath of treatment failure may be more limited in such settings.

Antiretroviral Therapy, Highly Active↗
PubMed1991

Modification of mitogen-induced proliferation of murine splenic lymphocytes by in vitro tocopherol.

The effect of alpha-tocopherol on in vitro proliferation of murine splenic lymphocyte cultures supplemented with various concentrations of the vitamin has been measured at sub-optimal, optimal and supra-optimal levels of the T-cell mitogen Concanavalin A (Con A). In the concentration range (1-25 micrograms/ml), tocopherol enhanced proliferation when administered up to 24 hours after exposure to sub-optimal and optimal concentrations of Con A; however, at supra-optimal levels of the mitogen, it appeared to inhibit proliferation. In the concentration range 50-100 micrograms/ml, tocopherol supplementation only enhanced proliferation in response to sub-optimal concentration of Con A. The spontaneous proliferation of lymphocytes in the absence of mitogens was increased by tocopherol supplementation at all concentrations tested. In contrast, there appeared to be only slight stimulation of B-cell proliferation in response to optimal concentration of bacterial lipopolysaccharide (LPS) by lower levels of vitamin E. Tocopherol supplementation of cultures over a broad range of concentrations (0.5-100 micrograms/ml) had no significant effect on cell viability before onset of proliferation at 18 hours after exposure to Con A, nor was there evidence of earlier onset of DNA synthesis in response to mitogen in the presence of 5 micrograms/ml of the vitamin. Although macrophage depletion of cultures impaired proliferation induced by Con A, tocopherol supplementation continued to stimulate proliferation at optimal and sub-optimal levels of mitogen.

Animals↗
PubMed1987

Humoral immune response of mice injected with tocopherol after exposure to X-radiation.

Serum haemagglutination (HA) titers have been determined for irradiated and non-irradiated mice responding to injection of two different concentrations of sheep red blood cells (SRBC) 24 to 48 hours after irradiation and immediate intraperitoneal injection of 2.5 mg DL alpha-tocopherol, the emulsifying vehicle, or saline. Mice maintained on tocopherol-deficient diets for 8 weeks post-weaning and those on regular diets exhibited increased IgG titers during peak response when injected with vitamin E. This partially alleviated the radiation-depression of the primary immune response induced by the smaller SRBC injection. This stimulatory effect was most significant in mice maintained on vitamin E-deficient diets. The HA titers of irradiated and non-irradiated mice maintained on normal rations were determined following a 10-fold increase in the SRBC inoculation. Antibody titer was greater following injection of the higher concentration of SRBC but post-irradiation injection of tocopherol immediately or 24 hours after irradiation did not enhance immune response. At the higher SRBC concentration maximum observed HA titers decreased with increasing dose of radiation; however, tocopherol had no significant dose-reducing effect. Tocopherol toxicity as manifested by depressed HA titers was observed occasionally in non-irradiated mice challenged with the higher concentration of SRBC.

Animals↗
PubMed1974

Contribution to the standardisation of a gas chromatographic method for the analysis of an oestrogenic and progestational combination.

An experimental procedure is described in order to standardize a gaschromatographic method proposed for a collaborative study organised by the F.I.P. Committee for Laboratories and Official Drug Control Services, on the analysis of some oestro-progestinic formulations. The assayed combination was a standard mixture of lynestrenol, mestranol and d, 1-alpha-tocopherol: testosterone was included as internal standard; two combinations, differing only in the internal standard content as specified in the text, were used. The variability of the instrumental factor was investigated performing some sets of single experiments, each consisting of 5 successive injections of the same standard mixture, on the same day. For each single experiment and for each substance the mean value Rm of the ratios R (R=area of the peak for compound cpi/area of the peak of the internal standard) was estimated with its relative standard deviation (% s.d.). For each set of experiments the % s.d. values were elaborated, following the Bartlett test, in order to obtain the sigma intra % value for each set, as a measure of the instrumental factor. An experimental evidence was observed for the relationship existing between the instrumental factor value (sigma intra %) and the internal standard content, in the operating conditions fixed for the present gas chromatographic analysis, a lowering of the instrumental factor beeing observed with the higher level of testosterone content (internal standard) in the mixture.

Chromatography, Gas↗
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Age Factors↗