Effect of exogenous insulin on glucose kinetics in rats with noninsulin-dependent diabetes

Noninsulin-dependent diabetes (NIDD) was induced in adult female rats by neonatal administration of streptozotocin. Despite elevated basal plasma glucose values in the postabsorptive state (196 +/- 16 mg/100 mL as compared to 118 +/- 7 in the controls), the glucose disappearance rate measured after the intravenous glucose load was not significantly lower in the diabetic than in control rats. In contrast, in vivo glucose-induced insulin release was drastically reduced, thus suggesting that endogenous insulin was more effective on the target tissues of the diabetic rats. Glucose kinetics (glucose production, utilization, and clearance) in response to intravenous insulin injection were studied in anesthetized postabsorptive diabetic and control female rats using [6-3H] glucose. With a maximal dose of insulin (0.5 U/kg body weight) no difference in blood glucose-lowering effect of insulin was found between the 2 groups. With 2 submaximal insulin doses (0.15 and 0.3 U/kg body weight), glucose production was inhibited more rapidly and more efficiently in diabetic rats than in control rats: 2 minutes after the 0.15 U/kg insulin injection, endogenous glucose production fell by 79 +/- 5% in the diabetics while being unchanged in the controls and the maximal decrease of glucose production after the same insulin injection was significantly greater in the diabetic rats (79 +/- 5% at 2 minutes) compared to the controls (33 +/- 4% at 6 min). The rise of glucose clearance in response to insulin was not significantly different in the 2 groups. These findings are discussed in view of the increased insulin clearance rate in these diabetic females.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analyse de données d’expression transcriptomiques rythmées par des gènes-horloge : approche méthodologique et optimisation

Background

In microarray data, wide-scale correlations are numerous and increase the number of genes correlated to a test condition (phenotype, mutation status, etc.) either positively or negatively. Several methods have been developed to limit the effect of such correlations on the false discovery rate, but these may reject too many genes that have a mild or indirect impact on the studied condition. We propose here a simple methodology to correct this spurious effect without eliminating weak but true correlations.

Results

This methodology was applied to a microarray dataset designed to distinguish heterozygous BRCA1 mutation carriers from non-carriers. As our samples were collected at different times in the morning, we evaluated the effect of correlations due to circadian rhythm. The circadian system is a well-known correlation network, regulated by a small number of period genes whose expression varies throughout the day in predictable ways. The downstream effects of this variation on the expression of other genes, however, are incompletely characterized. We used two different strategies to correct this correlation bias, by either dividing or multiplying the expression of correlated genes by the expression of the considered period gene according to the sign of the correlation between the period gene and correlated gene (respectively positive or negative).

Conclusions

We observed a linear relationship between the number of false-positive/negative genes and the strength of the correlation of the candidate gene to the test condition. BRCA1 was highly correlated to the period gene Per1; our correction methodology enabled us to recover genes coding for BRCA1-interacting proteins which were not selected in the initial direct analysis. This methodology may be valuable for other studies and can be applied very easily in case of well-known correlation networks.     

Does intraoperative transfusion during total knee arthroplasty reduce the need for transfusion after surgery?: A preliminary retrospective cohort study

ObjectivesAfter total knee arthroplasty (TKA), many patients experience anemia due to blood loss. To prevent postoperative anemia and allogeneic blood transfusion after TKA, we used prophylactic allogeneic or autologous blood transfusion intraoperatively. This study evaluated the effects of prophylactic transfusion during TKA.Materials and methodsThis retrospective cohort study included 579 patients receiving scheduled unilateral TKA. We allocated the patients into three groups, the prophylactic allogeneic transfusion (Group AL), prophylactic autologous transfusion (Group AT), and no prophylactic transfusion with intra-articular tranexamic acid administration (Group C) groups. After propensity score matching, we compared the rate of postoperative allogeneic blood transfusions until three days after TKA, postoperative hemoglobin and hematocrit levels until four days after TKA, and the side effects in each groups.ResultsThe postoperative allogeneic blood transfusion rates were statistically higher in group AL and AT than in group C (18.2% and, 18.9% vs 2.3%, respectively; P < 0.000). The postoperative hemoglobin and hematocrit levels were statistically lower in group Auto than in group C (P < 0.0001), but the levels in group AL were not different from those of group C (P = 0.493 vs. P = 0.384 respectively). In addition, the side effects were statistically higher in group AL and AT than in group C.ConclusionProphylactic intra-operative transfusions did not reduce the rates of allogeneic transfusions and produced more side effects and hypotension after surgery than intra-articular tranexamic acid administration with no prophylactic transfusion in patients undergoing TKAs.