Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance

Impaired glucose tolerance (IGT) is associated with defects in both insulin secretion and action and carries a high risk for conversion to non-insulin-dependent diabetes mellitus (NIDDM). Troglitazone, an insulin sensitizing agent, reduces glucose concentrations in subjects with NIDDM and IGT but is not known to affect insulin secretion. We sought to determine the role of beta cell function in mediating improved glucose tolerance. Obese subjects with IGT received 12 wk of either 400 mg daily of troglitazone (n = 14) or placebo (n = 7) in a randomized, double-blind design. Study measures at baseline and after treatment were glucose and insulin responses to a 75-g oral glucose tolerance test, insulin sensitivity index (SI) assessed by a frequently sampled intravenous glucose tolerance test, insulin secretion rates during a graded glucose infusion, and beta cell glucose-sensing ability during an oscillatory glucose infusion. Troglitazone reduced integrated glucose and insulin responses to oral glucose by 10% (P = 0.03) and 39% (P = 0.003), respectively. SI increased from 1.3+/-0.3 to 2.6+/-0.4 x 10(-)5min-1pM-1 (P = 0.005). Average insulin secretion rates adjusted for SI over the glucose interval 5-11 mmol/liter were increased by 52% (P = 0.02), and the ability of the beta cell to entrain to an exogenous oscillatory glucose infusion, as evaluated by analysis of spectral power, was improved by 49% (P = 0.04). No significant changes in these parameters were demonstrated in the placebo group. In addition to increasing insulin sensitivity, we demonstrate that troglitazone improves the reduced beta cell response to glucose characteristic of subjects with IGT. This appears to be an important factor in the observed improvement in glucose tolerance.     

The effects of cooperative and individualistic reward on intrinsic motivation

The effects of cooperative versus individualistic reward on students' intrinsic motivation were investigated. The controlling aspects of extrinsic reward may be heightened or produce greater ego threat in the individualistic situation when compared with a group situation. We predicted that students in the cooperative social situation would show higher levels of intrinsic motivation. Fifth-grade students from existing cooperative groups were assigned randomly to receive a tangible reward based on either cooperative or individualistic achievement for completing pattern block designs. Cooperation affected intrinsic motivation positively. Students in the cooperative dyad solved the block designs more quickly, interacted positively, and viewed the task as easier than did those in the individualistic situation, and they reported that their peers were helpful. There was little evidence that the controlling functions of reward or ego-threat were factors in producing the outcome. Some evidence supporting the importance of the social nature of cooperation was provided.     

Effect on normal vaginal flora of three intravaginal microbicidal agents potentially active against human immunodeficiency virus type 1

The effect on normal vaginal flora of three intravaginal microbicides potentially active against human immunodeficiency virus type 1 was examined. Volunteers received dextrin sulfate (D2S), nonoxynol-9 (N-9), or docusate sodium in separate placebo-controlled studies. High vaginal swabs were obtained for bacterial culture before and after microbicide application. D2S did not affect the vaginal flora. However, lactobacilli decreased by > or = 10(2) cfu/mL in 9 (56%) of 16 women given N-9 and in 5 (63%) of 8 women given docusate sodium. Women using N-9 were also significantly more likely to become colonized abnormally (usually with aerobic gram-negative rods) than were those using placebo, as were women using docusate sodium. Women with reduced lactobacilli were less likely to regain normal flora than were those whose lactobacilli were unaffected. However, coliform colonization occurred whether lactobacilli produced H2O2 or not. Continuous use of N-9 could induce susceptibility to urinary and gynecological infection. It is essential that potential microbicides are examined for activity against normal vaginal flora.     

Low-density lipoprotein particle size decreases during normal pregnancy in association with triglyceride increases

OBJECTIVE: To characterize the changes in low-density lipoprotein (LDL) peak particle diameter (diameter of the predominant LDL subclass) in relation to changes in serum triglyceride concentration during successive stages of normal gestation and postpartum. METHODS: Nonfasting venous blood was obtained longitudinally during and after uncomplicated primiparous pregnancy from 10 nonsmoking women with no history of metabolic disorders. Plasma LDL diameter was determined by nondenaturing polyacrylamide gel electrophoresis. Serum concentrations of total cholesterol, triglyceride, apolipoprotein B, apolipoprotein A-I, and LDL-cholesterol were measured. Gestational changes were analyzed by one-way repeated-measures analysis of variance and the paired multiple comparison Student-Newman-Keuls test. Pearson coefficients were computed for correlation of serum lipids and LDL diameter. RESULTS: Low-density lipoprotein diameter decreased progressively with advancing gestation, evident by 16-20 weeks relative to 5-12 weeks. Seven of 10 cases were subclass pattern B (diameter less than 255 A) by term, indicating that small, dense particles predominated. The average diameter decrease from early to late gestation was 13 A. All subjects reverted to subclass pattern A (diameter 255 A or more) by 6-12 weeks postpartum, indicating prevalence of large, buoyant LDL. Low-density lipoprotein diameter correlated inversely with concentrations of serum triglyceride (r = -.61, P < .0001), apo B (r = -.66, P < .0001), cholesterol (r = -.53, P < .001), LDL cholesterol (r = -.45, P < .005), and apo A-I (r = -.39, P < .02). CONCLUSION: Gestational triglyceride increases are accompanied by progressive decreases in LDL diameter in a majority of cases. These changes undergo reversal postpartum and therefore are transient. Small, dense LDL particles have a number of properties capable of altering vascular function. However, the consequences of the gestational LDL size decrease for maternal and fetal metabolism remain unknown.     

Threonine 82 in the regulatory chain is important for nucleotide affinity and for the allosteric stabilization of Escherichia coli aspartate transcarbamoylase

Changes in the kinetic properties of voltage-activated sodium currents (I(Na)) were studied in rat retinal ganglion cells during in vivo differentiation. Whole-cell recordings from cells maintained as retinal slices or whole-mounts were examined using the patch-clamp technique in the perforated patch mode. Voltage-clamp recordings revealed significant ontogenetic modifications in key properties of I(Na) and the present study described for the first time the detailed time course of such alterations. I(Na) was first expressed on embryonic day 17/18 (E17/18). Current density increased during development from an average of -81 pA/pF on E17/18 to a maximum of -747pA/pF on postnatal day 10/12 (P10/12). Simultaneously, the activation of I(Na) shifted towards more negative potentials, reflected by a shift in the potential of half-activation from -14.1 mV on E17/18 to - 37.5 mV on P10/12. No significant changes in these parameters were observed after P10/12. Steady-state inactivation shifted first towards more positive potentials, reflected by a shift in the potential of half-inactivation from -51 mV on E17/18 to -38 mV on P3/5, but shifted back towards more negative values thereafter (-44 mV in the adult). The most striking feature of I(Na) in rat RGCs was a transient slowing of I(Na) kinetics that was never described before. Time to peak and decay time constants increased between E20 and P5, resulting in slow and broad sodium currents within a developmental period that is characterized by intensive synaptogenesis in the target structures of retinal ganglion cells and maximum retinal ganglion cell death. Thereafter, time to peak and decay time constants decreased again to values found before E20, resulting in rapid sodium spikes. In conclusion, sodium currents in rat retinal ganglion cells displayed substantial electrophysiological changes during pre- and postnatal development. These changes in the sodium system had different temporal time patterns, indicating that they may play specific roles during the development of the visual system.     

Colon cancer cell vaccine prepared with replication-deficient vaccinia viruses encoding B7.1 and interleukin-2 induce antitumor response in syngeneic mice

The objective of this study was to evaluate the clinical efficacy and cost effectiveness of inpatient and outpatient laparoscopic lumbar diskectomy (LLD) compared with laminectomy (LAM) in the surgical treatment of disabling L5-S1 disk herniation. Sixty-two adults underwent surgery for herniated L5-S1 intervertebral disks (31 LLD and 31 LAM). Operative blood loss (EBL) (milliliters), operative time (ORT) (minutes), hospital stay (LOS), and rehabilitation time to normal activity (REHAB) (days), recurrent symptoms, postoperative morbidity, percent pain free, and hospital patient charges were calculated. Thirty LLD patients (97%) had immediate relief of disk pain. Morbidity after LLD included transient urinary retention (one) and rectus hematoma (one). One LAM patient had a pseudomeningocele. Among patients observed for > or =6 months, with a median follow up time of 34 months, 22 of 25 LLD patients (88%) returned to normal activity, while 12 of the LAM group (52%) were disabled (p = 0.004). Functional outcome was improved by LLD for workers compensation patients followed > or =6 months, with 86% LAM disabled, vs. 10% LLD (p = 0.001). Sixteen LLD patients (52%) and 18 (58%) of the LAM group needed postoperative physical therapy. Four LLD patients recurred; three required reoperation. Four LAM patients had surgery for recurrent disk herniation. ORT was longer for LLD than LAM (210 vs. 158 minutes, median, p < 0.05). EBL and REHAB time were significantly reduced with LLD, vs. LAM. With a median follow-up of 34 months, 58% of LLD and 39% of LAM patients followed > or =6 months were pain free. Outpatient LLD (n = 9) reduced LOS (1 day vs. 2 days and 4 days, p < 0.01) and lowered patient charges ($4,405 vs. $5,723 and $7,192, p < 0.01) compared with inpatient LLD (n = 23) and LAM, respectively. LLD is a safe, cost-effective, minimally invasive alternative to LAM for treating herniated L5-S1 disks. Compared with LAM, LLD reduces EBL, LOS, REHAB time, and patient charges, improves function, and increases long-term pain relief. Cost effectiveness is optimized when LLD is performed as outpatient surgery.     

Glutathione-binding proteins of Setaria digitata: antibody responses in human infected with Wuchereria bancrofti

Glutathione-s-transferase activity was determined in filarial parasites. The activity was detected in adult stages of cattle parasite Setaria digitata. It was absent in other stages of Setaria and also in infective larval stages of Wuchereria bancrofti and Brugia malayi. The activity was enhanced about twenty five fold following purification of adult setaria extracts on glutathione agarose column. Antibody (IgG and IgM) levels to the affinity purified proteins (SdGBP) were detected predominantly (90%) in Wuchereria bancrofti infected individuals compared with normal residents of endemic regions. IgA and IgE responses could not be detected. Filarial sera in contrast to non-filarial caused reduction in the enzymatic activities of Sd GBP. Microfilaraemic sera after diethylcarbamazine treatment resulted in enhanced reduction of enzymatic activity.     

Is chromium supplementation effective in managing type II diabetes?

The results of a recent placebo-controlled intervention trial in China show beneficial effects of chromium supplementation in type II diabetes. Before extrapolating the results to Western populations, however, large-scale placebo-controlled studies in Westerners are necessary to confirm the positive results.