Search

This study evaluates the influence of streptozotocin-induced diabetes on the kinetic disposition and metabolism of mexiletine (MEX) enantiomers in rats. Animals in the control (n = 6 for each blood collection time), diabetic (single intravenous dosage of 45 mg x [(kg body mass).sup.-1] of streptozotocin), and insulin-treated groups (diabetic rats treated daily with 2 IU insulin) received by gavage a single dose of 10 mg x [(kg body mass).sup.-1] racemic MEX. MEX enantiomers and the metabolites hydroxymethylmexiletine (HMM) and p-hydroxymexiletine PHM) were analyzed by LC-MS/MS. Statistical analysis was based on a serial sacrifice design, and parameter estimation was performed using a Bayesian modeling procedure. Area under the curve (AUC) for the (-)-(R) enantiomers of MEX, HMM, and PHM did not differ between the control and diabetic groups. However, AUC for (+)-(S)-MEX and (+)-(S)-HMM were lower in the diabetic than in the control group. Insulin treatment recovered glucose levels to normal and the (+)-(S)-MEX AUC and (+)-(S)-HMM AUC became similar to the AUCs observed in the nondiabetic animals. Key words: mexiletine, enantiomers, metabolites, pharmacokinetics, diabetes, insulin, rats. Cette etude evalue l'influence du diabete induit par la streptozotocine sur la disposition cinetique et le metabolisme des enantiomeres de la mexiletine (MEX) chez le rat. Les animaux des groupes controle (n = 6a chaque prelevement sanguin), diabetique (une seule dose i.v. de 45 mg x [(kg de masse corporelle).sup.-1] de streptozotocine) et traite a l'insuline (diabetique traite quotidiennement avec 2 UI d'insuline) ont recu par gavage une seule dose de 10 mg x [(kg de masse corporelle).sup.-1] d'un melange racemique de MEX. Les enantiomeres de MEX et leurs metabolites, la hydroxymethylmexiletine (HMM) et la p-hydroxymexiletine (PHM), ont ete analyses par LC-MS/MS. L'analyse statistique a ete basee sur des donnees issues d'un protocole de sacrifice seriel et l'estimation parametrique a ete realisee par une modelisation Bayesienne. Les aires sous la courbe (ASC) des enantiomeres (-)-(R) de MEX, de HMM et de PHM ne differaient pas significativement entre les groupes controle et diabetique. Toutefois les ASC de (+)-(S)-MEX et (+)-(S)-HMM etaient plus faibles chez le groupe diabetique comparativement au groupe controle. Le traitement a l'insuline permettait de retablir les niveaux normaux de glucose et les ASC de (+)-(S)-MEX et de (+)-(S)-HMM similaires a ceux des animaux non diabetiques. [Traduit par la Redaction] Mots-cles: mexiletine, enantiomeres, metabolites, pharmacocinetique, diabete, insuline, rats., Introduction Mexiletine (MEX; 1-(2,6-dimethylfenoxi)-2-aminopropane), a drug available as a racemic mixture of (-)-R and (+)-(S) enantiomers, is used clinically for alleviating neuropathic pain in diabetes (Andriaensen et al. 2005). The [...]

The study attempts to evaluate the C-Peptide levels after autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) among newly diagnosed type 1 diabetes mellitus. The results indicate that C-Peptide levels increased significantly following HSCT and patients exhibited insulin independence with good glycemic control.

Abstract Background Many studies reported that brief interventions are effective in reducing excessive drinking. This study aimed to assess the efficacy of a protocol of brief intervention for college students (BASICS), delivered face-to-face, to reduce risky alcohol consumption and negative consequences. Methods A systematic review with meta-analysis was performed by searching for randomized controlled trials (RCTs) in Medline, PsycInfo, Web of Science and Cochrane Library databases. A quality assessment of RCTs was made by using a validated scale. Combined mean effect sizes, using meta-analysis random-effects models, were calculated. Results 18 studies were included in the review. The sample sizes ranged from 54 to 1275 (median = 212). All studies presented a good evaluation of methodological quality and four were found to have excellent quality. After approximately 12 months of follow-up, students receiving BASICS showed a significant reduction in alcohol consumption (difference between means = −1.50 drinks per week, 95% CI: -3.24 to −0.29) and alcohol-related problems (difference between means = −0.87, 95% CI: -1.58 to −0.20) compared to controls. Conclusions Overall, BASICS lowered both alcohol consumption and negative consequences in college students. Gender and peer factors seem to play an important role as moderators of behavior change in college drinking. Characteristics of BASICS procedure have been evaluated as more favorable and acceptable by students in comparison with others interventions or control conditions. Considerations for future researches were discussed.

Abstract Background To identify the most appropriate cut-off points of fasting glycemia for the screening of diabetes mellitus type 2 (DM2) with the comparison of the properties of capillary glycemia (CG) and venous blood plasma glycemia (PG) in a population of Japanese origin from the community of Mombuca, Guatapará - SP, Brazil. Methods This was a population-based descriptive cross-sectional study conducted on a sample of 131 individuals of both genders aged 20 years or more (66.8% of the target population). CG was measured with a glucometer in a blood sample obtained from the fingertip and PG was determined by an enzymatic method (hexokinase) in venous blood plasma, after a 10-14 hour fast in both cases. Data were analyzed by the receiver operating characteristic (ROC) curve in order to identify the best cut-off point for fasting glycemia (CG and PG) for the diagnosis of DM, using the 2-hour plasma glycemia > 200 mg/dl as gold - standard. Results The ROC curve revealed that the best cut-off point for the screening of DM was 110 mg/dl for CG and 105 mg/dl for PG, values that would optimize the relation between individuals with positive and false-positive results. The area under the ROC curve was 0.814 for CG (p < 0.01) and 0.836 for PG (p < 0.01). Conclusions The cut-off points of 105 mg/dl(5.8 mmol/l) for PG and of 110 mg/dl(6.1 mmol/l) for CG appear to be the most appropriate for the screening of DM2 in the population under study, with emphasis on the fact that the value recommended for CG is 5 mg/dl higher than that for PG, in contrast to WHO recommendations.

We proposed a Bayesian analysis of pseudo-compositional data in presence of a latent factor, assuming a spatial structure. This development was motivated by a dataset containing information on the number of newborns of primiparous mothers living in each of the microregions of the state of Sao Paulo, Brazil, in the year of 2015, stratified by the age of the mothers (15-18, 19-29 and 30 years or more). Considering that data on newborns are not stochastically distributed among the three age groups, but they are explained in relation to women's population structure, we adopted the expression "pseudo-compositional data" to refer to this data structure. The hypothesis of interest establishes that the age of the first pregnancy is associated with the economic conditions of the geographic area where the mother lives. The incidence of poverty was included as an independent variable. Additive log-ratio (alr) and isometric log-ratio (ilr) transformations were considered, as is usually done in the analysis of compositional data. The model included a random effect related to the spatial effect assumed to have a conditional autoregressive structure. A Bayesian Markov Chain Monte Carlo (MCMC) simulation procedure was used to get the posterior summaries of interest. The model based on the (ilr) transformation was well fitted to the data, showing that in the microregions with the highest incidence of poverty, there are higher proportions of women who have their first child in adolescence, while in the microregions with the lowest incidence of poverty, there are higher proportions of women who have their first child after the age of 30 years. From these results it is possible to conclude that this Bayesian approach was very useful in the estimation of the parameters of the proposed model. The proposed method should have a broad application to other problems involving pseudo-compositional data. [ABSTRACT FROM AUTHOR]

Population‐based studies on blood donation prevalence and its association with sociodemographic and behavioural factors are scarce, but remain the best approach to assess correlates of donation, including those which could be the target for donor recruitment campaigns. This study describes the population of primary healthcare users from the public system in a medium‐sized Brazilian municipality to investigate the association of blood donation practice with other sociodemographic factors. A stratified, representative sample of primary healthcare users at 12 healthcare facilities in Ribeirão Preto, São Paulo, Brazil, were invited to participate. Analysis focused on demographic and psychosocial factors including, sex, age, marital status, socioeconomic status, educational level, health insurance, self‐perception of health, religious beliefs, and blood donation history. Blood donors, self‐defined ineligible donors, and never donors were compared. Multiple correspondence analysis (MCA) was used to assess positively and negatively associated variables in the dataset. MCA was conducted on respondents' age and monthly household income to assess dimensionality of other questionnaire responses. Of a total of 1,055 study participants, 79.7% were females and the mean age was 40.6 years. Blood donation practice was reported by 246 participants (23.3%), 669 (63.4%) had never donated, and 140 (13.3%) reported being unable to donate blood. Graphical presentation of the MCA showed that male, older age groups, those who have health insurance, and with higher socioeconomic and educational level are more likely to donate blood. Poor or average self‐perception of health, lower socioeconomic status, and divorced or widowed marital status were associated with self‐defined inability to donate blood. Thus, our results are useful to understand the multifactorial nature of blood donation behaviour. Our findings provide guidance for targeted recruitment campaigns focused on relevant contextual factors. The focus on reducing barriers to blood donation according to sociodemographic groups can be a relevant strategy to expand the donor base. [ABSTRACT FROM AUTHOR]