Circularly polarised luminescence from intramolecular excimer emission of bis-1,8-naphthalimide derivatives.

Chiral excimers exhibit unique photophysical behaviour. However, further molecular design is required along with systematic studies on the effect of spacer groups and solvent polarity. In this study, we prepared four circularly polarised luminescence (CPL)-active molecules that exhibit intramolecular excimer emission. Bis-1,8-naphthalimide (bNI) derivatives D-LybNI, L-LybNI, D-LyMebNI, and L-LyMebNI were prepared with chiral backbones and alkyl linkages between the NI rings with chain lengths of five carbon atoms, suitable for excimer fluorescence. The fluorescence properties were investigated experimentally and theoretically using density functional theory. The molecules exhibited intramolecular excimer fluorescence in polar organic solvents. Mirror-image circular dichroism and CPL spectra were obtained for the D and L forms. D- and L-LyMebNI exhibited relatively large luminescence dissymmetry factors (|glum|) in acetonitrile of 1.9 × 10-3 and 1.6 × 10-3, respectively. Thus, this study demonstrates chiral bNI derivatives with simple synthesis procedures that emit intramolecular excimer fluorescence and have effective CPL properties. These molecules are promising for developing organic molecular systems with bright, highly polarised emission.

Poststreptococcal acute glomerulonephritis in a girl with renal cell carcinoma: possible pathophysiological association.

The severity of the poststreptococcal acute glomerulonephritis is considered to be modulated by the immune response of each individual, although there had been few reports regarding specific factors. Renal cell carcinoma is a cancer frequently associated with paraneoplastic syndrome, characterized by fever, leukocytosis, elevated cytokines, and elevated hormone levels. All of these symptoms resolve after tumor resection. A girl with renal cell carcinoma developed renal failure rapidly, which resolved promptly right after nephrectomy for the carcinoma. She was diagnosed as having poststreptococcal acute glomerulonephritis according to the results of pathological and serological examinations. In addition, elevated serum interleukin-6 level before the surgery was detected. Six and a half years after the diagnosis, the patient's renal function was within normal range and she was tumor free. Because of the quick resolution of her renal dysfunction after the nephrectomy, paraneoplastic syndrome induced by renal cell carcinoma seemed to play a key role in the accentuation of poststreptococcal acute glomerulonephritis.

Effects of diet and time of the day on serum and CSF leptin levels in Osborne-Mendel and S5B/Pl rats.

OBJECTIVE: To characterize the effects of dietary fat on the diurnal variation in serum and cerebrospinal fluid (CSF) leptin levels in Osborne-Mendel (OM) and S5B/Pl rats and quantitate the dose response to lower doses of leptin administered into the third cerebral ventricle. RESEARCH METHODS AND PROCEDURES: Rats were fitted with implanted vascular ports or third ventricular cannulas and fed either laboratory chow or one of two semipurified high-fat or low-fat diets. Leptin and insulin were measured by immunoassay. RESULTS: Serum leptin and insulin levels were positively correlated and had similar patterns of diurnal change. CSF leptin and insulin also had diurnal rhythms, with a peak at 7:00 am, but the diurnal oscillations of leptin and insulin were significantly lower in the S5B/Pl rats than the OM rats. Thus, the ratio of CSF to serum leptin was significantly higher in the S5B/Pl rats than in the OM rats. Dietary fat had no effect on these diurnal patterns. There was a right shift in the dose response to leptin in the OM rats compared with the S5B/P1 rats. S5B/P1 rats treated with leptin had higher signal transduction and translation (STAT-3) mRNA levels compared with pair-fed or saline injected S5B/P1 rats. Hypothalamic suppressors of cytokine signaling mRNA levels were not statistically different between the groups. DISCUSSION: The higher CSF-to-serum leptin ratio in the S5B/P1 rats, the enhanced suppression of food intake and body weight with leptin injections, and the higher STAT-3 activity in these animals suggest that S5B/P1 rats are more sensitive to leptin than OM rats.

Lipoprotein lipase mRNA in white adipose tissue but not in skeletal muscle is increased by pioglitazone through PPAR-gamma.

Lipoprotein lipase (LPL), a key enzyme for triglyceride hydrolysis, is an insulin-dependent enzyme and mainly synthesized in white adipose tissue (WAT) and skeletal muscles (SM). To explore how pioglitazone, an enhancer of insulin action, affects LPL synthesis, we examined the effect of pioglitazone on LPL mRNA levels in WAT or SM of brown adipose tissue (BAT)-deficient mice, which develop insulin resistance and hypertriglyceridemia. Both LPL mRNA of WAT and SM were halved in BAT-deficient mice. Pioglitazone increased LPL mRNA in WAT by 8-fold, which was substantially associated with a 4-fold increase of peroxisome proliferator activated receptor (PPAR)-gamma mRNA (r=0.97, p<0.0001), whereas pioglitazone did not affect LPL mRNA in SM. These results suggest that pioglitazone exclusively increases LPL production in WAT via stimulation of PPAR-gamma synthesis. Since pioglitazone does not affect LPL production in SM, this would contribute to prevent the development of insulin resistance due to lipotoxicity.

Fasting increases gene expressions of uncoupling proteins and peroxisome proliferator-activated receptor-gamma in brown adipose tissue of ventromedial hypothalamus-lesioned rats.

Uncoupling proteins (UCPs) are supposed to be involved in diet-induced thermogenesis. Their activities are usually elevated by feeding and reduced by fasting in normal animals. To investigate whether fasting affects the expression of UCPs mRNA in brown adipose tissue (BAT) of bilateral ventromedial hypothalamus (VMH)-lesioned rats, we determined the gene expression of UCP1, UCP2 or UCP3 in BAT of VMH-lesioned rats and examined oxygen consumption in these rats under fed or 48-h fasted conditions. Northern blotting revealed no difference in the expression of UCPs mRNA in BAT between VMH-lesioned and sham-operated rats under the fed condition, however, expressions were increased markedly in BAT of VMH-lesioned rats under the fasted condition. Under the fed condition, no difference in oxygen consumption was observed between VMH-lesioned and sham-operated rats. Under the fasted condition, oxygen consumption decreased in both rats, however, it decreased in VMH-lesioned less than in sham operated rats. To explore the mechanism that fasting elevated BAT UCPs mRNA in VMH-lesioned rats, we measured peroxisome proliferator-activated receptor (PPAR)-gamma mRNA and protein in BAT, because PPAR-gamma agonist can elevate UCPs mRNA levels in BAT. Under the fed condition, no differences in the expression of PPAR-gamma mRNA and protein content were observed between in BAT of VMH-lesioned and sham-operated rats. Under the fasted condition, however, both increased in BAT of VMH-lesioned rats. These results suggest that VMH-lesions enhance the gene expression of UCPs in BAT under long-term fasting as a defensive reaction to inhibit the reduction of body temperature through an increase in PPAR-gamma activity.

Impaired ascorbic acid metabolism in streptozotocin-induced diabetic rats.

Ascorbic acid (AA) metabolism in streptozotocin (STZ)-induced diabetic rats was determined by examining urinary excretion, renal reabsorption, reductive regeneration, and biosynthesis of AA at 3 and 14 days after STZ administration. AA concentrations in the plasma, liver, and kidney of the diabetic rats were significantly lower than those of controls on d 3, and decreased further as the diabetic state continued. Hepatic AA regeneration significantly decreased in the diabetic rats on d 3 in spite of increased gene expressions of AA regenerating enzymes and was further reduced on d 14. Hepatic activity of L-gulono-gamma-lactone oxidase, a terminal enzyme of hepatic AA biosynthesis, also decreased significantly on d 3 and decreased further on d 14. Urinary excretion of AA was significantly increased on d 3, with an increase in urine volume but no change in gene expressions of renal AA transporters (SVCT1 and SVCT2). Urinary excretion of AA was normalized on d 14. The results suggest that impaired hepatic and renal regeneration, as well as increased urinary excretion and impaired hepatic biosynthesis of AA, contributed to the decrease in AA in plasma and tissues of STZ-induced diabetic rats.

Distinct role of adiposity and insulin resistance in glucose intolerance: studies in ventromedial hypothalamic-lesioned obese rats.

It remains unclear whether adiposity plays an important role in glucose intolerance independently of insulin resistance. We investigated whether adiposity and insulin resistance had distinct roles in glucose intolerance in rats. We examined glucose tolerance and insulin resistance using ventromedial hypothalamic (VMH)-lesioned rats in the dynamic and the static phases of obesity (2 and 14 weeks after lesioning, respectively). Rats were fed either normal chow or a fructose-enriched diet (60% of total calories). The intravenous glucose tolerance test (IVGTT) was performed by bolus injection of glucose solution (1 g/kg) and blood sampling after 0, 5 10, 30, and 60 minutes. Insulin resistance was evaluated from the steady-state plasma glucose (SSPG) value during continuous infusion of glucose, insulin, and somatostatin. SSPG was not increased in VMH-lesioned rats in the dynamic phase of obesity, but increased markedly in the static phase. The area under the glucose curve (glucose AUC) during IVGTT was increased in VMH-lesioned rats in the static phase, but not in the dynamic phase, when compared with their sham-operated counterparts. A fructose-enriched diet for 2 or 14 weeks increased SSPG values to a similar extent in both sham-operated and VMH-lesioned rats without inducing excess adiposity, but glucose intolerance was only developed in the obese rats. The plasma leptin level, an excellent indicator of adiposity, was significantly related to the glucose AUC independently of the insulin level. Insulin resistance or increased adiposity alone is not sufficient to impair glucose tolerance, but increased adiposity plays an important role in the development of glucose intolerance in an insulin-resistant state.