Background : We conducted a case-control study to examine the impact of coronal heart disease (CHD) risk factors on calcium oxalate (CaOX) stone formation. Methods : Variables included body mass index (BMI), current alcohol use, smoking habit, hypertension, hypercholesterolemia, diabetes mellitus, and hyperuricemia. Data sufficient for analysis were obtained for 181 CaOX stone formers and 187 controls.Results : Seven of 181 stone formers (3.9%) had a history of CHD compared with none of 187 control subjects ( P = 0.007). In univariate logistic regression analysis, smoking habit (OR 4.41, 95% CI 2.85-6.84, P < 0.0001), hypertension (OR 4.24, 95% CI 2.61-6.91, P < 0.0001), hypercholesterolemia (OR 3.03, 95% CI 1.77-5.20, P < 0.0001) and BMI (OR 1.10, 95% CI 1.04-1.17, P = 0.007) reached statistical significance. In a multivariate logistic regression analysis, smoking habit (OR 4.29, 95% CI 2.68-6.86, P < 0.0001), hypertension (OR 3.57, 95% CI 2.11-6.07, P < 0.0001), and hypercholesterolemia (OR 2.74, 95% CI 1.51-5.00, P = 0.001) reached statistical significance, while BMI (OR 1.06, 95% CI 0.99-1.12, P = 0.09) did not. Conclusions : CaOX stone formers are significantly associated with several CHD risk factors, including smoking habit, hypertension, hypercholesterolemia, and obesity.

To investigate the mechanism that controls circadian rhythms in the mammalian retina, we examined the mRNA expression rhythms of serotonin N-acetyltransferase (NAT), the mammalian clock gene rPer2 and a clock-controlled gene Dbp in the retina of rats with lesions of the suprachiasmatic nucleus (SCN), the master clock in mammals. Northern blot analyses showed that retinal NAT mRNA still exhibited the circadian expression in the SCN-lesioned rats, whereas the lesion abolished the rhythms of rPer2 and Dbp mRNAs. These findings suggest that the mammalian retina has two circadian oscillatory mechanisms: one can generate rhythmicity independent of the SCN and the other requires the SCN to maintain circadian oscillation.

These results demonstrated a good transfer of allopurinol from mother to fetus and suggested the possibility of intrauterine treatment to inhibit fetal brain damage resulting from increased oxygen free radicals.

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Oxaliplatin, a third-generation platinum-based chemotherapeutic agent, displays unique acute peripheral neuropathy triggered or enhanced by cold, and accumulating evidence suggests that transient receptor potential ankyrin 1 (TRPA1) is responsible. TRPA1 is activated by oxaliplatin via a glutathione-sensitive mechanism. However, oxaliplatin interrupts hydroxylation of a proline residue located in the N-terminal region of TRPA1 via inhibition of prolyl hydroxylase (PHD), which causes sensitization of TRPA1 to reactive oxygen species (ROS). Furthermore, PHD inhibition endows cold-insensitive human TRPA1 (hTRPA1) with ROS-dependent cold sensitivity. Since cysteine oxidation and proline hydroxylation regulate its activity, their association with oxaliplatin-induced TRPA1 activation and acquirement of cold sensitivity were investigated in the present study. A high concentration of oxaliplatin (1 mM) induced outward-rectifier whole-cell currents and increased the intracellular Ca2+ concentration in hTRPA1-expressing HEK293 cells, but did not increase the probability of hTRPA1 channel opening in the inside-out configuration. Oxaliplatin also induced the rapid generation of hydrogen peroxide, and the resultant Ca2+ influx was prevented in the presence of glutathione and in cysteine-mutated hTRPA1 (Cys641Ser)-expressing cells, whereas proline-mutated hTRPA1 (Pro394Ala)-expressing cells showed similar whole-cell currents and Ca2+ influx. By contrast, a lower concentration of oxaliplatin (100 μM) did not increase the intracellular Ca2+ concentration but did confer cold sensitivity on hTRPA1-expressing cells, and this was inhibited by PHD2 co-overexpression. Cold sensitivity was abolished by the mitochondria-targeting ROS scavenger mitoTEMPO and was minimal in cysteine-mutated hTRPA1 (Cys641Ser or Cys665Ser)-expressing cells. Thus, high oxaliplatin evokes ROS-mediated cysteine oxidation-dependent hTRPA1 activation independent of PHD activity, while a lower concentration induces cold-induced cysteine oxidation-dependent opening of hTRPA1 via PHD inhibition.