Bioluminescence microscopy using a short focal-length imaging lens.

Bioluminescence from cells is so dim that bioluminescence microscopy is performed using an ultra low-light imaging camera. Although the image sensor of such cameras has been greatly improved over time, such improvements have not been made commercially available for microscopes until now. Here, we customized the optical system of a microscope for bioluminescence imaging. As a result, bioluminescence images of cells could be captured with a conventional objective lens and colour imaging camera. As bioluminescence microscopy requires no excitation light, it lacks the photo-toxicity associated with fluorescence imaging and permits the long-term, nonlethal observation of living cells. Thus, bioluminescence microscopy would be a powerful tool in cellular biology that complements fluorescence microscopy.

Aldehyde dehydrogenase activity in cancer stem cells from canine mammary carcinoma cell lines.

Increasing evidence suggests that diverse solid tumours arise from a small population of cells known as cancer stem cells or tumour-initiating cells. Cancer stem cells in several solid tumours are enriched for aldehyde dehydrogenase (ALDH) activity. High levels of ALDH activity (ALDH(high)) were detected in four cell lines derived from canine mammary carcinomas. ALDH(high) cells were enriched in a CD44(+)CD24(-) population having self-renewal capacity. Xenotransplantation into immunodeficient mice demonstrated that 1×10(4) ALDH(high) cells were sufficient for tumour formation in all injected mice, whereas 1×10(4) ALDH(low) cells failed to initiate any tumours. ALDH(high)-derived tumours contained both ALDH(+) and ALDH(-) cells, indicating that these cells had cancer stem cell-like properties.

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.

Possible antiarrhythmic activities of trapidil.

Possible antiarrhythmic activities of 5-methyl-7-diethylamino-s-triazolo(1,5-a)pyrimidine (trapidil, Rocornal) were investigated in vitro and in vivo. Trapidil significantly increased the amount of aconitine or ouabain needed for production of ventricular arrhythmias in rats and guinea pigs. Trapidil also produced a significant increase in threshold current of electrical stimuli which induced ventricular tachycardia in dogs under acute myocardial ischemia. Electrophysiological examinations on effects of trapidil on isolated rabbit ventricular muscle cells showed shortening of the action potential duration (APD) and prolongation of the effective refractory period (ERP), resulting in an increase in the ratio of ERP/APD. The results indicate that trapidil will have a possible effectiveness in inhibiting ventricular arrhythmias.

Effect of trapidil on mechanical and electrical activity of isolated rabbit atrium.

Actions of trapidil on mechanical and electrical activities of rabbit right atria were investigated in vitro. Isolated atria had spontaneous contractions. Ca++ (2.7-4.5 mM) concentration-dependently increased force and frequency of atrial contractions, and trapidil (10(-5)-10(-4) g/ml) also did. Trapidil (10(-5)-10(-4) g/ml) showed a tendency to augment the positive inotropic action of Ca++ and significantly enhanced the positive chronotropic action of Ca++. In experiments using conventional microelectrode techniques, trapidil (10(-5)-10(-4) g/ml) concentration-dependently increased the slope of slow diastolic depolarization, the maximal diastolic potentials and the peak potentials in pacemaker potentials of sinoatrial nodal cells, and shortened the cycle length of them. The results indicate pharmacodynamically and electrophysiologically that trapidil produces a positive inotropic and chronotropic effect on isolated rabbit right atria.