Kinetics of Decomposition of the 1-Methyl-1-nitroso-3-phenylurea Derivatives

The kinetics of decomposition of the 3-substituted-phenyl-1-nitroso-1-methylureas was studied under a certain pH and various temperatures. It was observed that the rate of decomposition is first order in concentration of the nitroso compound under the constant pH and that the more the electron withdrawal of the ring substituent, the larger is the rate of decomposition. From the temperature dependence of the rate, the apparent enthalpy and entropy of activation were determined. The sequence of the rate of decomposition of this series of compounds was found to be governed largely by the variation of the entropy rather than that of the enthalpy of activation.     

Increase in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Had a Strong Impact on the Development of Type 2 Diabetes in Japanese Individuals with Impaired Insulin Secretion: The Saku Study

Our aim was to assess the impact of increase in homeostasis model assessment of insulin resistance (HOMA-IR) on the development of type 2 diabetes in Japanese individuals with impaired insulin secretion (IIS). This study included 2,209 participants aged 30–69 without diabetes at baseline who underwent comprehensive medical check-ups between April 2006 and March 2007 at Saku Central Hospital. Participants were classified into eight groups according to the combination of baseline IIS status (non-IIS and IIS) and category of HOMA-IR change between the baseline and follow-up examinations (decrease, no change/small increase, moderate increase, and large increase). Type 2 diabetes was determined from fasting and 2 h post-load plasma glucose concentrations at the follow-up examination between April 2009 and March 2011. At baseline, 669 individuals (30.3%) were classified as having IIS. At follow-up, 74 individuals developed type 2 diabetes. After adjusting for confounding factors including baseline HOMA-IR values, the multivariable-adjusted odds ratios (95% confidence intervals) for type 2 diabetes in the non-IIS with a decrease (mean change in HOMA-IR: −0.47), non-IIS with a moderate increase (mean change in HOMA-IR: 0.28), non-IIS with a large increase (mean change in HOMA-IR: 0.83), IIS with a decrease (mean change in HOMA-IR: −0.36), IIS with no change/small increase (mean change in HOMA-IR: 0.08), IIS with a moderate increase (mean change in HOMA-IR: 0.27), and IIS with a large increase (mean change in HOMA-IR: 0.73) groups, relative to the non-IIS with no change/small increase (mean change in HOMA-IR: 0.08) group were 0.23 (0.04, 1.11), 1.22 (0.26, 5.72), 2.01 (0.70, 6.46), 1.37 (0.32, 4.28), 3.60 (0.83, 15.57), 5.24 (1.34, 20.52), and 7.01 (1.75, 24.18), respectively. Moderate and large increases in HOMA-IR had a strong impact on the development of type 2 diabetes among individuals with IIS in this Japanese population.     

Reduction in Adiposity, β-Cell Function,Insulin Sensitivity,and Cardiovascular Risk Factors: A Prospective Study among Japanese with Obesity

Background

A reduction in adiposity may be associated with an improvement in insulin sensitivity and β-cell function as well as cardiovascular disease (CVD) risk factors; however, few studies have investigated these associations in a longitudinal setting.

Methods

To investigate these associations over a 1-year period, we conducted an observational analysis of 196 Japanese subjects with obesity in the Saku Control Obesity Program. We investigated the relations between changes in adiposity (body mass index [BMI], waist circumference, subcutaneous fat area [SFAT], and visceral fat area [VFAT]) and changes in HbA1c, fasting plasma glucose (FPG), insulin sensitivity index (ISI), the homeostasis model assessment β cell function (HOMA-β), lipids, and blood pressure.

Results

All adiposity changes were positively associated with HbA1c and FPG changes. Reductions in BMI and VFAT were associated with HOMA-β reduction. Reductions in all adiposity measures were associated with an improvement in the ISI. Changes in most adiposity measures were positively associated with changes in blood pressure and lipid levels, except for LDL.

Conclusion

The present findings provide additional supportive evidence indicating that a reduction in adiposity may lead to an improvement in insulin sensitivity and the reduction of CVD risk factors in obese individuals.     

(-)-Semivioxanthin, a new abscisic active compound against Hinoki cypress leaves isolated from Cryptosporiopsis abietina

The new naphthopyrone, (-)-semivioxanthin (1) was isolated from Cryptosporiopsis abietina. The structure of 1 was determined as the reversed optical isomer of semivioxanthin by comparing its spectroscopic data with those of semivioxanthin. Compound 1 exhibited abscisic activity against Hinoki cypress leaves and antifungal activity against Cladosporium herbarum.     

Insect Sterilization Activity of the 1-Methyl-1-nitroso-3-phenylurea Derivatives

The sterilization activity of the 3-substituted-phenyl-1-methyl-1-nitrosoureas was examined by a feeding test on house fly adults. This series of compounds exhibited toxicity as well as sterility, but, for some compounds, the toxicity was reduced to minimum still retaining the high sterility at lower dose levels in bait. It was suggested that the sterilization activity is dependent on physicochemical properties such as chemical reactivity and solubility in the insect body.     

Microarray Analysis of Perinatal-Estrogen-Induced Changes in Gene Expression Related to Brain Sexual Differentiation in Mice

Sexual dimorphism of the behaviors or physiological functions in mammals is mainly due to the sex difference of the brain. A number of studies have suggested that the brain is masculinized or defeminized by estradiol converted from testicular androgens in perinatal period in rodents. However, the mechanisms of estrogen action resulting in masculinization/defeminization of the brain have not been clarified yet. The large-scale analysis with microarray in the present study is an attempt to obtain the candidate gene(s) mediating the perinatal estrogen effect causing the brain sexual differentiation. Female mice were injected with estradiol benzoate (EB) or vehicle on the day of birth, and the hypothalamus was collected at either 1, 3, 6, 12, or 24 h after the EB injection. More than one hundred genes down-regulated by the EB treatment in a biphasic manner peaked at 3 h and 12-24 h after the EB treatment, while forty to seventy genes were constantly up-regulated after it. Twelve genes, including Ptgds, Hcrt, Tmed2, Klc1, and Nedd4, whose mRNA expressions were down-regulated by the neonatal EB treatment, were chosen for further examination by semiquantitative RT-PCR in the hypothalamus of perinatal intact male and female mice. We selected the genes based on the known profiles of their potential roles in brain development. mRNA expression levels of Ptgds, Hcrt, Tmed2, and Nedd4 were significantly lower in male mice than females at the day of birth, suggesting that the genes are down-regulated by estrogen converted from testicular androgen in perinatal male mice. Some genes, such as Ptgds encoding prostaglandin D2 production enzyme and Hcrt encording orexin, have been reported to have a role in neuroprotection. Thus, Ptgds and Hcrt could be possible candidate genes, which may mediate the effect of perinatal estrogen responsible for brain sexual differentiation.