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Notes: Abstract Vibrio cholerae O139, a causative agent of a large epidemic of cholera-like illness, has suddenly emerged and spread widely over several months. To investigate the characteristics unique to O139, traditional typing techniques for V. cholerae, such as biochemical characteristics, antibiotic susceptibility and detection of toxin production, were performed, with the result that 145 O139 strains, except for two O139 strains isolated from Argentina and Germany, were indistinguishable from O1 strains. Thus, in order to clarify the genetical relatedness among O139 strains, and between O139 and O1 strains, the RAPD (random amplified polymorphic DNA) DNA fingerprinting method was undertaken. Although the RAPD arrays in five O139 isolates from Vellore with one arbitrary primer were slightly different from the other O139 strains, the RAPD patterns of the 145 forty-five O139 strains except for two O139 strains from Argentina and Germany were quite similar to each other, but were different from those of O1 strains, indicating that those O139 epidemic strains are closely related to each other regardless of their place of isolation. Furthermore, the RAPD patterns of the O139 strains resembled those of E1 Tor strains rather than classical strain, and a small change in the RAPD pattern of O139 strains occurred during subculture for 200 generations. These results taken together suggested that O139 V. cholerae have emerged from a common origin associated with the E1 Tor strain.

Notes: Docosahexaenoic acid (C22:6, n-3), a major n-3 fatty acid of the brain, has been implicated in restoration and enhancement of memory-related functions. Because Alzheimer's disease impairs memory, and infusion of amyloid-β (Aβ) peptide (1–40) into the rat cerebral ventricle reduces learning ability, we investigated the effect of dietary pre-administration of docosahexaenoic acid on avoidance learning ability in Aβ peptide-produced Alzheimer's disease model rats. After a mini-osmotic pump filled with Aβ peptide or vehicle was implanted in docosahexaenoic acid-fed and control rats, they were subjected to an active avoidance task in a shuttle avoidance system apparatus. Pre-administration of docosahexaenoic acid had a profoundly beneficial effect on the decline in avoidance learning ability in the Alzheimer's disease model rats, associated with an increase in the cortico-hippocampal docosahexaenoic acid/arachidonic acid molar ratio, and a decrease in neuronal apoptotic products. Docosahexaenoic acid pre-administration furthermore increased cortico-hippocampal reduced glutathione levels and glutathione reductase activity, and suppressed the increase in lipid peroxide and reactive oxygen species levels in the cerebral cortex and hippocampus of the Alzheimer's disease model rats, suggesting an increase in antioxidative defence. Docosahexaenoic acid is thus a possible prophylactic means for preventing the learning deficiencies of Alzheimer's disease.

Notes: 1. Nicorandil is a potent vasodilator combining the effects of a nitrate with an ATP-sensitive potassium channel (KATP) opener. Because the postinfarct remodelled heart has increased vulnerability to subendocardial hypoperfusion, it is possible that the vasodilator effects of nicorandil could cause transmural redistribution of blood flow away from the subendocardium. Alternatively, the KATP channel opening effects of nicorandil could exert a beneficial effect on mitochondrial respiration. Consequently, the present study was performed to examine the effect of nicorandil on energy metabolism in the postinfarct heart.2. Studies were performed in swine in which myocardial infarction produced by proximal left circumflex coronary artery ligation had resulted in left ventricular remodeling. [31P] nuclear magnetic resonance spectroscopy (MRS) was used to examine the myocardial energy supply/demand relationship across the left ventricular wall while the transmural distribution of blood flow was examined with radioactive microspheres. Data were obtained during baseline conditions and during infusion of nicorandil (100 μg, i.v., followed an infusion of 25 μg/kg per min).3. Nicorandil caused coronary vasodilation with a preferential increase in subepicardial flow; however, subendocardial flow also increased significantly. Nicorandil had no significant effect on the rate–pressure product or myocardial oxygen consumption. The ratio of phosphocreatine (PCr)/ATP determined with MRS was abnormally depressed in remodelled hearts (2.01 ± 0.11, 1.85 ± 0.10 and 1.59 ± 0.11 for subepicardium, midwall and subendocardium, respectively) compared with normal (2.22 ± 0.11, 2.01 ± 0.15 and 1.80 ± 0.09, respectively). Nicorandil had no effect on the high-energy phosphate content of normal hearts. However, nicorandil increased the PCr/ATP ratio in the subendocardium of remodelled hearts from 1.59 ± 0.11 to 1.87 ± 0.10 (P 〈 0.05).4. Although nicorandil caused modest redistribution of blood flow away from the subendocardium of the postinfarct left ventricle, this was associated with an increase of the PCr/ATP ratio towards normal. These results suggest that nicorandil exerts a beneficial effect on energy metabolism in the subendocardium of the postinfarct remodelled left ventricle.

Notes: 1. To investigate whether the difference in the SA gene expression in the kidneys is causally related to the pathogenesis of hypertension, we reassessed the expression of the SA gene in the kidneys of the spontaneously hypertensive rat (SHR), its stroke-prone substrain (SHRSP) and Wistar-Kyoto (WKY) rat from different sources (SHR/Izm, SHRSP/Izm and WKY/ Izm from Izumo colony; SHR/Crj and WKY/Crj from Charles River Laboratories).2. At the age of 5 weeks, high levels of the SA mRNA were expressed in the kidneys of SHRSP/Izm, SHR/Izm, SHR/Crj and WKY/Izm, while very low levels of the SA mRNA were observed in those of WKY/Crj. At the age of 8 weeks, the expression of the SA mRNA in the kidneys of WKY/Izm was at the same level as in those of SHRSP/Izm and two SHR strains.3. Four genetic markers at the SA locus, an StuI restriction fragment length polymorphism and three microsatellite markers, were not polymorphic among Izumo strains of SHR, SHRSP and WKY rats.4. In situ hybridization showed strong signals of the SA mRNA in the renal proximal tubules, while no positive signals were detected in the glomeruli.5. Because WKY/Izm has normal blood pressure, our observations indicate that a simple difference of the SA gene expression in the kidney cannot be an explanation for the difference of blood pressure between SHR(SP)/Izm and WKY/Izm.

Notes: 1. Myocardial injury has been shown to be associated with successful percutaneous transluminal coronary angioplasty (PTCA). The present study was designed to determine whether uncomplicated successful PTCA results in myocardial injury by measuring coronary sinus (CS) cardiac troponin T (cTnT).2. We measured cTnT in the CS and the femoral vein (FV) in 16 patients with stable angina pectoris who underwent uncomplicated PTCA for stenotic lesions of the left anterior descending artery. Blood samples were drawn from both the CS and FV before and immediately after PTCA and every 4 h for the next 12 h.3. All patients had chest pain and electrocardiographic ST segment elevation or depression during balloon inflation and higher peak elevation of cTnT in the CS than in the FV (0.054±0.059 vs 0.036±0.022 ng/mL; P 〈 0.05). However, all CS cTnT levels were within the normal range over the 12 h period.4. The fact that CS cTnT measurements showed no evidence of uncomplicated PTCA-related myocardial injury led us to conclude that uncomplicated successful PTCA does not cause myocardial injury.

Notes: 1. Low doses of sublingual nifedipine are still used for the treatment of hypertensive crises, although recent studies have raised concerns that sublingual nifedipine may cause serious dose-dependent adverse effects. The present study was performed to test the safety of low-dose sublingual nifedipine administered to elderly hypertensive patients.2. Systemic blood pressure measurements and electrocardiographic (ECG) examinations were performed before and 45–60 min after a 5 mg dose of sublingual nifedipine in 93 consecutive hypertensive patients, 65 years of age or older, who were without coronary artery disease. In 33 patients, the effects of nifedipine on myocardial lactate metabolism were studied during cardiac catheterization.3. In all patients, following nifedipine administration, blood pressure (BP) decreased significantly, while heart rate (HR) increased, and symptoms associated with elevated BP disappeared. However, changes consistent with myocardial ischaemia appeared on the ECG in six of 55 patients with left ventricular hypertrophy (LVH) and in one of 38 patients without LVH, although only two of these seven patients experienced angina-like precordial tightness. Sublingual nifedipine decreased myocardial lactate extraction from 52±13 to 38±19% in 20 patients with LVH (P = 0.02), but myocardial lactate extraction remained stable in 13 patients without LVH (49±7 to 50±5%; NS). The change in lactate extraction was significantly correlated with the percentage change in diastolic arterial pressure (r = 0.77, P 〈 0.001).4. These results suggest that sublingual nifedipine, even at the low dose of 5 mg, may cause myocardial ischaemia in some elderly patients with LVH that is associated with a marked reduction in coronary perfusion pressure.

Notes: 1. The present study was designed to test the hypotheses whether platelet degranulation across the coronary bed is detectable during non-ischaemic periods in patients with vasospastic angina (VSA) and whether the exogenous nitric oxide (NO) donor nitroglycerin (GTN) is able to modify platelet degranulation, reflecting an impaired endothelial production of NO.2. We studied 13 patients with VSA and 10 controls. The time course of coronary sinus (CS) plasma 5-hydroxytryptamine (5-HT) levels was evaluated every 4 h before and after intravenous infusion of GTN over a period of 40 h. Coronary sinus plasma 5-HT levels were significantly higher at any measured time point in patients with VSA compared with control and were significantly decreased in patients with VSA following treatment with GTN, but not in controls. Femoral artery plasma 5-HT levels remained almost constant throughout the study. The ratio of CS:aorta 6-keto-prostaglandin F1α was significantly and inversely correlated with the transcardiac plasma 5-HT difference only in patients with VSA (r=−0.68; P 〈 0.02; n= 13).3. The time course of CS 5-HT levels confirmed significant platelet degranulation across the coronary bed supplied by the spasming artery in patients with VSA and this was modified by GTN. The present data suggest that platelet degranulation occurs during non-ischaemic periods in patients with VSA and that prostacyclin biosynthesis may be a compensatory response to an impaired endothelial release of NO, limiting the degree of the effects of platelet degranulation.

Notes: 1. Serum hepatocyte growth factor (HGF) is considered to be a potent marker of vascular endothelial injury. The present study was designed to examine serum HGF levels in atrial fibrillation and after successful direct current (DC) cardioversion.2. We measured serum HGF levels before and 7 days and 1 month after DC cardioversion in 39 patients with atrial fibrillation in whom sinus rhythm was maintained for at least 7 days after DC cardioversion and in 30 age- and sex-matched normal control subjects with sinus rhythm. We also measured acetylcholine-induced changes in forearm blood flow (FBF) using venous occlusive plethysmography in 10 patients.3. Serum HGF levels were significantly higher in the atrial fibrillation patients (both lone atrial fibrillation and with underlying heart disease) than in the controls (0.16 ± 0.07 vs 0.10 ± 0.04 ng/mL; P 〈 0.001). Seven days after successful DC cardioversion, the patients' serum HGF levels had decreased significantly (0.16 ± 0.07 vs 0.12 ± 0.06 ng/mL; P 〈 0.05) and in the 24 patients maintaining sinus rhythm 1 month after DC cardioversion, serum HGF levels decreased to control values (0.10 ± 0.08 ng/mL at 1 month). Serum HGF levels of the 15 patients who had relapsed into atrial fibrillation 1 month after DC cardioversion tended to decrease 7 days after DC cardioversion, but increased again 1 month after DC cardioversion. Percentage changes in FBF between baseline and the highest dose of acetylcholine before and after DC cardioversion were 180 ± 98 and 323 ± 196%, respectively (P = 0.0051). The rate of increase in FBF at the highest dose of acetylcholine between before and after DC cardioversion correlated negatively with the rate of decrease in serum HGF levels between before and after DC cardioversion (r = −0.837; P = 0.0025).4. This study is the first to demonstrate that serum HGF levels increase in atrial fibrillation and decrease after successful DC cardioversion. This may reflect the fact that atrial fibrillation induces vascular endothelial injury.

Notes: 1. The aim of the present study was to determine whether the vasorelaxant effect of atrial natriuretic peptide (ANP) is, in part, endothelium dependent in humans.2. We used veno-occlusive plethysmography to measure forearm blood flow (FBF) during intra-arterial infusions of ANP (4, 8, 16, 32 pmol/min per dL forearm tissue volume) before and after the inhibition of nitric oxide (NO) synthesis by NG-monomethyl-L-arginine (L-NMMA; 100 μmol) in seven normal healthy subjects.3. Atrial natriuretic peptide caused a dose-dependent increase in FBF both before and after L-NMMA and significantly reduced the plasma concentration of angiotensin (Ang) II. Administration of L-NMMA significantly diminished the increase in FBF in response to ANP infusion (P 〈 0.05).4. These results suggest that the forearm vasodilatative response to ANP is modulated, in part, by an endothelium-derived NO-mediated mechanism associated with a decrease in AngII caused by ANP.