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Abstract. The prevalence of hypovitaminosis D has been recently reevaluated, and diabetes is considered as a risk factor for osteoporosis. We studied the association of the prevalence of hypovitaminosis D with the clinical features of diabetes. We conducted the observational study in 581 Japanese patients with type 2 diabetes mellitus and 51 normal subjects, and analyzed the relationship between serum 25-hydroxyvitamin D (25-OHD) concentration and the clinical features associated with type 2 diabetes. Mean serum 25-OHD concentration in type 2 diabetes patients was 17.0 ± 7.1 ng/ml (Mean ± SD) in winter, and was not statistically different from normal population (17.5 ± 3.6 ng/ml). The prevalence of hypovitaminosis D (<20 ng/ml) was 70.6%. Serum concentrations of 25-OHD were associated with HbA1c (P = 0.013), age (P = 0.070) and serum albumin (P<0.001), but were not related to BMI or the duration of diabetes. The levels of 25-OHD were significantly lower in the population with apparent microvascular complications, although serum creatinine levels were below 2.0 mg/dl. Serum 25-OHD concentrations in the group treated with insulin (15.4 ± 6.5 ng/ml) was lower than those in the patients treated with diet alone (20.8 ± 7.6 ng/ml) and with oral hypoglycemic agents (17.3 ± 7.0 ng/ml). Furthermore, the highest incidence of osteoporotic fracture and/or back deformity was observed in insulin-treated patients with hypovitaminosis D. In conclusion, these results suggest that microvascular complications and insulin treatment in type 2 diabetes patients are associated with the co-existence of hypovitaminosis D, and that hypovitaminosis D in insulin-treated patients is possibly related to the risk of osteoporotic fracture.

Electron-irradiation-induced defects in epitaxially grown 3C-SiC crystals have been studied by electron-spin-resonance (ESR) measurements. The results indicate the presence of an isotropic ESR center that consists of five lines equally spaced at about 1.5 G and has a g value of 2.0029±0.0001. Isochronal and isothermal annealing of electron-irradiated 3C-SiC showed that this center was annealed at three stages (150, 350, and 750 °C) and that the 750 °C stage exhibited first-order reaction with an activation energy of 2.2±0.3 eV.

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The telomere hypothesis postulates stabilization of telomere length and telomerase activation as key events in cellular immortalization and carcinogeneses. Accordingly, telomerase has been suggested as a novel and highly selective target for design of antitumor drugs. Screening of a chemical library including 16 000 synthetic compounds yielded six that strongly inhibited telomerase activity in extracts of cultured human cells, including four isothiazolone derivatives and two unrelated compounds. The most potent inhibitor was 2-[3-(trifluoromethyl)phenyl]isothiazolin-3-one (TMPI), a concentration of 1.0 microM inhibited telomerase activity by 50% according to a telomere repeat amplification protocol (TRAP) assay. Analysis using partially purified telomerase from AH7974 rat hepatoma cells demonstrated noncompetitive inhibition with the telomere-repeat primer and mixed inhibition with the dNTPs; the inhibition constant was 2.5 microM. TMPI did not inhibit eukaryotic DNA polymerase alpha, beta, or human immunodeficiency virus reverse transcriptase (HIV RT). Thus, inhibition by TMPI was highly selective for telomerase. Inhibition by TMPI was quenched by 1 mM of dithiothreitol or glutathione, suggesting that TMPI inhibits telomerase by acting at a cysteine residue. TMPI inhibition of this enzyme may find application as an antineoplastic agent.