Transcriptome changes in newborn goats' skeletal muscle as a result of maternal feed restriction at different stages of gestation

We investigated how feed restriction at 50% of maintenance requirements during different stages of gestation affects the transcriptome of newborn goats' skeletal muscle. Fourteen pregnant dams were randomly assigned into one of the following dietary treatments: animals fed at 50% of maintenance requirement from 8-84 d of gestation and then fed at 100% of maintenance requirement from day 85 of gestation to parturition (RM, n = 6), and animals fed at 100% of maintenance requirement from 8-84 d of gestation and then fed at 50% of maintenance requirement from day 85 of gestation to parturition (MR, n = 8). At birth, samples of offspring's Longissimus muscle were collected for total RNA extraction and sequencing. Our data showed 66 differentially expressed (DE) genes (FDR < 0.05). A total of 6 genes were upregulated and 60 downregulated (FDR < 0.05) in the skeletal muscle of the newborns resulting from treatment RM compared with MR. Our results suggest that the DE genes upregulated in newborn goats' skeletal muscle from the RM group compared to MR, included genes related to satellite cells, and genes that indicates impaired insulin sensitivity and changes in the composition of intramuscular fat. The DE genes upregulated in newborn goats' skeletal muscle from the MR group compared to RM, are also related to impaired insulin sensitivity, as well as a predominantly oxidative metabolism and cellular oxidative stress. However, protective mechanisms against insulin sensitivity and oxidative stress may have been augmented in the skeletal muscle of offspring from MR treatment compared to RM, in order to maintain cellular homeostasis

Electroporation increases antitumoral efficacy of the bcl-2 antisense G3139 and chemotherapy in a human melanoma xenograft

<p>Abstract</p> <p>Background</p> <p>Nucleic acids designed to modulate the expression of target proteins remain a promising therapeutic strategy in several diseases, including cancer. However, clinical success is limited by the lack of efficient intracellular delivery. In this study we evaluated whether electroporation could increase the delivery of antisense oligodeoxynucleotides against bcl-2 (G3139) as well as the efficacy of combination chemotherapy in human melanoma xenografts.</p> <p>Methods</p> <p>Melanoma-bearing nude mice were treated i.v. with G3139 and/or cisplatin (DDP) followed by the application of trains of electric pulses to tumors. Western blot, immunohistochemistry and real-time PCR were performed to analyze protein and mRNA expression. The effect of electroporation on muscles was determined by histology, while tumor apoptosis and the proliferation index were analyzed by immunohistochemistry. Antisense oligodeoxynucleotides tumor accumulation was measured by FACS and confocal microscopy.</p> <p>Results</p> <p>The G3139/Electroporation combined therapy produced a significant inhibition of tumor growth (TWI, more than 50%) accompanied by a marked tumor re-growth delay (TRD, about 20 days). The efficacy of this treatment was due to the higher G3139 uptake in tumor cells which led to a marked down-regulation of bcl-2 protein expression. Moreover, the G3139/EP combination treatment resulted in an enhanced apoptotic index and a decreased proliferation rate of tumors. Finally, an increased tumor response was observed after treatment with the triple combination G3139/DDP/EP, showing a TWI of about 75% and TRD of 30 days.</p> <p>Conclusions</p> <p>These results demonstrate that electroporation is an effective strategy to improve the delivery of antisense oligodeoxynucleotides within tumor cells <it>in vivo </it>and it may be instrumental in optimizing the response of melanoma to chemotherapy. The high response rate observed in this study suggest to apply this strategy for the treatment of melanoma patients.</p

Prevalence of and factors related to tuberculosis in seropositive human immunodeficiency virus patients at a reference center for treatment of human immunodeficiency virus in the southern region of the state of Rio Grande do Sul, Brazil

Objective: In view of the relevance of co-infection with tuberculosis and human immunodeficiency virus, this study was designed to determine tuberculosis prevalence and identify factors related to tuberculosis in patients residing in a region in which both infections are highly prevalent. Methods: All patients treated during 1999 at the HIV/AIDS Clinic of the Universidade Federal do Rio Grande (Rio Grande Federal University) University Hospital were evaluated retrospectively, from the time of human immunodeficiency virus diagnosis, in terms of the incidence of tuberculosis and its relationship to sociodemographic, behavioral and immunological factors. Results: The sample included 204 patients, and tuberculosis prevalence was found to be 27%. The multivariate analysis showed a significant correlation between the development of tuberculosis and being of African descent (odds ratio: 4.76; 95% confidence interval: 1.93-11.72) and an inverse correlation between the development of tuberculosis and the TCD4+ lymphocyte count at the time of human immunodeficiency virus diagnosis (odds ratio: 0.995; 95% confidence interval: 0.993-0.997). When analyzed separately,other variables were found to be potential risk factors: being of the male gender (odds ratio: 2.49; 95% confidence interval: 1.15-5.39); and using illicit drugs (odds ratio: 2.1; 95% confidence interval: 1.02-4.31). Conclusion: The factors responsible for the development of tuberculosis among patients who are human immunodeficiency virus seropositive include immunological, socioeconomic and demographic factors. The high rate of tuberculosis prevalence among the seropositive patients underscores the urgent need to implement strategies that combine rapid identification and prompt treatment of individuals with active or latent infection, as well as of those with whom they have been in contact