Influence of calcium channel blockers in patients with gastrointestinal disease in Japanese community pharmacies.

WHAT IS KNOWN AND OBJECTIVE: Calcium channel blockers (CCBs), which have been widely used for the treatment of hypertension and angina pectoris, decrease lower oesophageal sphincter pressure and, as a result, can exacerbate gastrointestinal disease. In a previous study, increased risk of exacerbation of gastrointestinal disease among elderly patients following treatment with CCBs was identified. The prevalence of gastrointestinal diseases has increased in elderly patients, and it is possible that treatment with CCBs may have undesirably influenced this increase. The change in risk of gastrointestinal disease can be estimated by analysing changes in the prescription of antisecretory drugs as an outcome of exacerbation of gastrointestinal disease caused by CCBs. METHODS: It was hypothesized that patients who were prescribed CCBs would also change their use of antisecretory drugs. From September 2005 to August 2009, a dynamic retrospective cohort study was performed at five community pharmacies in Nagasaki, Japan, to assess alteration of antisecretory drug therapy following treatment with CCBs. Correlations with alterations of antisecretory drug therapy were determined by the Cox proportional hazards model. RESULTS AND DISCUSSION: The proposed study included 260 patients who were prescribed CCBs and 155 controls. During the study period, 53 patients were prescribed CCBs and 13 controls altered their antisecretory drug therapy; the hazard ratio was 2·22 (95% CI 1·25-4·26). WHAT IS NEW AND CONCLUSION: Calcium channel blocker treatment of patients with gastrointestinal disease was associated with alteration in frequency of prescription and an increase in dosage of antisecretory drugs. For clinical management of hypertension, alternative antihypertensive drugs may be considered for patients with gastrointestinal diseases. Further studies are required to determine the influence of CCB therapy on gastroesophageal diseases, suggested by the increase in use of antisecretory drugs.

Increased risk of exacerbating gastrointestinal disease among elderly patients following treatment with calcium channel blockers.

BACKGROUND AND OBJECTIVE: Calcium channel blockers (CCBs) have been widely used for the treatment of hypertension and angina pectoris. It is presumed that CCBs decrease the lower esophageal sphincter pressure and as a result, the risk of gastrointestinal disease may be increased. Since the prevalence of gastrointestinal diseases has increased in elderly patients, it is possible that treatment with CCBs may have contributed to this increase. Therefore, we considered that the risk of exacerbating gastrointestinal disease among elderly patients by CCBs can be estimated by using the prescription ratio of antisecretory drugs as an outcome. METHOD: We hypothesized that patients who are prescribed CCBs would increase the use of antisecretory drugs involving H(2)-receptor antagonists and proton pump inhibitors (PPIs). From January 2001 to December 2005, a dynamic retrospective cohort study was performed at three community pharmacies in Nagasaki city, Japan, to assess the use of antisecretory drugs following treatment with CCBs among elderly patients. The correlation of initiation of antisecretory drugs treatment to maintenance therapy with PPIs was determined by the Cox proportional hazards model. RESULTS: The proposed study includes 303 patients prescribed CCBs and 258 controls. During the study period, 138 patients prescribed CCBs and 66 controls were initiated by giving antisecretory drugs; the hazard ratio was 1.40 (95% confidence interval 1.21-1.63). Eighty two patients taking CCBs and 32 controls were initiated by the maintenance therapy with PPIs; the hazard ratio was 1.48 (95% confidence interval 1.21-1.83). CONCLUSION: Patients who simultaneously initiated the use of antisecretory drugs with CCBs could not be found. Therefore, antisecretory drugs have not been used to prevent the gastrointestinal diseases caused by CCBs. The results obtained in this study suggest that the risk of gastrointestinal disease could be increased by long-term treatment with CCBs for elderly patients.

Stage-specific localization of cytoskeletal actin mRNA in murine seminiferous tubules and intestinal epithelia as demonstrated by in-situ hybridization.

In-situ hybridization experiments have been performed using isoactin (beta and gamma)-specific riboprobes in various tissues of the rat and mouse. Distribution of the grains of actin mRNAs for both beta and gamma types was similar throughout sections of the rat testis. Although both mRNAs were evenly distributed in the seminiferous tubule, extremely heavy labeling was observed in about 10% of the seminiferous tubules that could be identified as stage XII of spermatogenesis. At high magnification, grains of the mRNA were found in the cytoplasm of elongating spermatids and in the Sertoli cell cytoplasm at the adluminal side. Much higher density of the grains of mRNA was observed in the neck region of the spermatids at stage XII. Thus, the dense distribution of cytoskeletal actin mRNAs is stage-specific in the tubule during spermatogenesis in the rat. The high expression of both beta and gamma actin mRNAs was also observed in the epithelial cells of the intestinal crypts.

Tissue-specific expression of the gene for a putative plasma membrane H(+)-ATPase in a seagrass.

A cDNA clone corresponding to the gene (ZHA1) for a putative plasma membrane H(+)-ATPase of a seagrass (Zostera marina L.) was isolated and sequenced. Comparison of the amino acid predicted sequence from the nucleotide sequence of ZHA1 with those encoded by known genes for plasma membrane H(+)-ATPases from other plants indicated that ZHA1 is most similar to the gene (PMA4) for a plasma membrane H(+)-ATPase in a tobacco (84.4%). Northern hybridization indicated that ZHA1 was strongly expressed in mature leaves, which are exposed to seawater and have the ability of tolerate salinity; ZHA1 was weakly expressed in immature leaves, which are protected from seawater by tightly enveloping sheaths and are sensitive to salinity. In mature leaves, in situ hybridization revealed that ZHA1 was expressed specifically in epidermal cells, the plasma membranes of which were highly invaginated and morphologically similar to those of typical transfer cells. Therefore, the differentiation of the transfer cell-like structures, accompanied by the high-level expression of ZHA1, in the epidermal cells of mature leaves in particular may be important for the excretion of salt by these cells.