RESUMO
Many people living with HIV/AIDS (PHA) use herbal medicine as one of alternative therapies, where curative options are limited. This study aimed to examine the association between the herbal medicine use and quality of life (QOL) among PHA in northeastern Thailand. Participants were 132 HIV-positive Thai adults who attended the PHA's self-help group meetings from June to July 2002. Health-related QOL scores were measured by self-administered questionnaire from the Medical Outcomes Study-HIV Health Survey. Dimensions of physical function (PF) and mental health (MH) in QOL were assessed. Additional data were collected on herbal medicine use, socio-demographic, psychosocial and HIV-related characteristics. The herbal medicine users had significantly better MH scores than the non-users, while the herbal medicine use was not statistically associated with PF scores. When stratified, herbal medicine users with the following characteristics had significantly better MH scores than the non-users: female, widowed, having no income, reporting any HIV-related symptom, having no instrumental support or receiving subsidies. In conclusion, herbal medicine use was associated with better MH especially among socially vulnerable PHA. This study suggests that herbal medicine has a potential to improve the MH aspect of QOL among socially vulnerable PHA who cannot easily receive antiretroviral therapy in Thailand.
Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Fitoterapia/métodos , Qualidade de Vida/psicologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Feminino , Nível de Saúde , Humanos , Masculino , Saúde Mental , Inquéritos e Questionários , TailândiaRESUMO
We previously reported the protection of hematopoietic cells from methotrexate (MTX) toxicity using an N2-based double copy vector containing serine 31 (S31)-mutated dihydrofolate reductase (DHFR) (DC/SV6S31). To examine whether the use of SFG-based dicistronic vectors will lead to improvement in gene transfer over the DC/SV6 vector, we compared the protection provided by MTX to NIH3T3 cells and hematopoietic progenitor cells infected with these retroviral constructs containing the S31 variant DHFR cDNA. In NIH3T3 cells, the 50% effective dose values of MTX conferred by the SFG vector were 8-fold higher than those obtained with the DC/SV6 vector. DHFR mRNA levels were 22-fold and 38-fold higher than that seen for the DC/SV6 vector according to Northern blot and real-time polymerase chain reaction analysis, respectively. However, DHFR protein expression and DHFR enzyme activity were only 1.5-fold and 2-fold higher in the SFG vector, respectively, indicating that the mRNA from the SFG vector is translated less efficiently than the mRNA generated from the DC/SV6 vector. Furthermore, the degree of MTX protection conferred by each vector in both mouse and human hematopoietic cells was the same. These results indicate that the in vitro transduction efficiency and transgene expression of human DHFR in hematopoietic progenitor cells is equally conferred by both vectors.
Assuntos
Células 3T3/efeitos dos fármacos , Medula Óssea/metabolismo , DNA Complementar/genética , Resistência a Medicamentos/genética , Células-Tronco Hematopoéticas/metabolismo , Metotrexato/farmacologia , Vírus da Leucemia Murina de Moloney/genética , Tetra-Hidrofolato Desidrogenase/genética , Animais , Northern Blotting , Southern Blotting , Western Blotting , Medula Óssea/efeitos dos fármacos , Primers do DNA/química , Regulação Enzimológica da Expressão Gênica , Vetores Genéticos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/análise , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Leucemia/patologia , Masculino , Camundongos , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tetra-Hidrofolato Desidrogenase/metabolismo , Transdução Genética , Células Tumorais CultivadasRESUMO
We have previously shown that transfer of a mutated dihydrofolate reductase (DHFR) confers resistance to methotrexate (MTX) to infected cells. We report herein the construction of a retrovirus vector, DC/SV6S31tk, which carries the herpes simplex virus thymidine kinase gene (HSVtk) as well as the mutated Serine 31 DHFR (S31) cDNA. 3T3 cells infected with DC/SV6S31tk are more resistant to MTX than cells infected with DC/SV6S31, which carries the S31 and Neo gene. In DC/SV6S31tk-infected cells, a fraction of cells (20-40%) were more resistant to MTX compared with DC/SV6S31-infected cells, and these cells survived a 5-day exposure to 200 microM of MTX. The mechanism of this augmented resistance is attributed to the salvage of thymidine by HSVtk, as the augmentation is reversed when dialyzed serum is used for cytotoxicity assays. The cells that survive high-dose MTX selection have high levels of expression of S31 DHFR and HSVtk, although copy numbers of the proviral sequences do not increase significantly. Transduction of cells with the DC/SV6S31tk vector also sensitizes cells to ganciclovir (GCV). Co-expression of a metabolically related gene in a retroviral vector to potentiate the resistance imparted by a drug resistance gene may be useful for gene therapy for cancer patients.