BACKGROUND The emerging controversy concerning the causal role of atherosclerosis in the development of aortic aneurysms was examined using the accumulated clinical and autopsy data obtained during a 20-year follow-up of a cohort of more than 8,000 men of Japanese ancestry in Hawaii. METHODS AND RESULTS Analyses of 174 clinical incident events indicated that there were two types of aneurysmal disease, 151 aortic aneurysms and 23 aortic dissections. The baseline risk factors that predicted the clinical aortic aneurysms were the same factors that predicted aortic atherosclerosis in the same cohort, namely, high blood pressure, high serum cholesterol, and cigarette smoking. These same risk factors were also significantly associated with the occurrence of 27 aortic aneurysms among 293 autopsied men. The less common aortic dissections had an age-specific incidence pattern indicative of an innate susceptibility precipitated by an exposure to another factor. This pattern was consistent with the findings that the incidence of aortic dissections was predicted mainly by baseline high blood pressure. CONCLUSIONS From the perspective of prevention, it appears that the risk factors for aortic atherosclerosis and probably atherosclerosis itself are necessary elements in the causal pathway for the great majority of aortic aneurysms in this cohort.

A synthetic extract, prepared from 44 pure chemicals on the basis of the analytical data on the leg meat extract of the boiled snow crab, Chionoecetes opilio, satisfactorily reproduced the taste of the natural extract except for a slight lack of body and mildness. A series of taste panel assessments on synthetic extracts prepared by omitting or adding extractive component(s) were carried out by a triangle difference test and changes in taste profile were assessed. Only 12 components, Ala, Arg, Glu, Gly, glycine betaine, AMP, CMP, GMP, Na+, K+, Cl-, and P04s-, were found to contribute more or less toward producing the characteristic taste of the snow crab.

Transient receptor potential (TRP) melastatin 8 (TRPM8) is a temperature-sensing ion channel mainly expressed in primary sensory neurons (Ad-fibers and C-fibers in the dorsal root ganglion). In this report, we characterized ), a novel and selective TRPM8 antagonist, to assess its therapeutic potential against frequent urination in rat models with overactive bladder (OAB). In calcium influx assays with HEK293T cells transiently expressing various TRP channels, KPR-5714 showed a potent TRPM8 antagonistic effect and high selectivity against other TRP channels. Intravenously administered KPR-5714 inhibited the hyperactivity of mechanosensitive C-fibers of bladder afferents and dose-dependently increased the intercontraction interval shortened by intravesical instillation of acetic acid in anesthetized rats. Furthermore, we examined the effects of KPR-5714 on voiding behavior in conscious rats with cerebral infarction and in those exposed to cold in metabolic cage experiments. Cerebral infarction and cold exposure induced a significant decrease in the mean voided volume and increase in voiding frequency in rats. Orally administered KPR-5714 dose-dependently increased the mean voided volume and decreased voiding frequency without affecting total voided volume in these models. This study demonstrates that KPR-5714 improves OAB in three different models by inhibiting exaggerated activity of mechanosensitive bladder C-fibers and suggests that KPR-5714 may provide a new and useful approach to the treatment of OAB. SIGNIFICANCE STATEMENTTRPM8 is involved in bladder sensory transduction and plays a role in the abnormal activation in hypersensitive bladder disorders. KPR-5714, as a novel and selective TRPM8 antagonist, may provide a useful treatment for the disorders related to the hyperactivity of bladder afferent nerves, particularly in overactive bladder.

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