Preventive effect of renin-angiotensin system inhibitors on new-onset atrial fibrillation in hypertensive patients: a propensity score matching analysis.

It is still controversial whether treatment with renin-angiotensin system (RAS) inhibitors reduces the risk of incident atrial fibrillation (AF). This longitudinal observational study was performed to investigate the confounder-independent effects of RAS inhibitors on new-onset AF in hypertensive patients. Among 1263 consecutive hypertensive patients who underwent echocardiography, 964 eligible patients (mean age, 63 years) were enrolled as the study population. Forty-nine patients developed new-onset AF during the follow-up period (mean: 4.6 years). Kaplan-Meier analysis showed that the cumulative AF event rate was lower in patients receiving RAS inhibitors than in patients without these drugs, but the difference between these two groups was not significant (P=0.057). Since the use of RAS inhibitors was influenced by concomitant diabetes, chronic kidney disease and left ventricular hypertrophy, propensity score matching (1:1) was employed to minimize the influence of selection bias for RAS inhibitors. Clinical and echocardiographic parameters showed no significant differences between the propensity score-matched groups with and without RAS inhibitor therapy (both n=326), but the cumulative AF event rate was significantly lower in the group receiving RAS inhibitors (P=0.013). Univariate and multivariate Cox regression analyses also revealed that RAS inhibitor therapy was associated with a significantly lower risk of new-onset AF during the follow-up period. In conclusion, this propensity score matching study demonstrated that the incidence of new-onset AF was lower in hypertensive patients receiving RAS inhibitor therapy.

Aberrant branch of the bronchoesophageal artery resembling patent ductus arteriosus in a dog.

An anomalous shunt between the bronchoesophageal artery and pulmonary artery was diagnosed in a 1-year- old, 3.5 kg female Miniature Dachshund by selective contrast angiography. A cardiac murmur had been observed in the dog during examination at another hospital. The machinery murmur was auscultated at the left side of the base of the heart. Although thoracic radiography revealed mild cardiomegaly, the characteristic findings of patent ductus arteriosus (PDA), including as aortic arch enlargement and pulmonary artery enlargement were not observed. Echocardiography demonstrated shunting of blood flow presumably from the arterial duct at the pulmonary artery carina. Based on the above findings the case was diagnosed as PDA. Angiocardiography was performed to confirm the diagnosis in preparation for surgical treatment, but later we confirmed that the shunt vessel was not PDA, but apparently a branch of the bronchoesophageal artery. The shunt vessel was branching in a complicated manner and shunted to the pulmonary artery.

Modulation of the immune system by the autonomic nervous system and its implication in immunological changes after training.

This review examines the role of the autonomic nervous system in the regulation of the immune system to understand the alteration of immunological parameters under the influence of stressors and exercise. Sympathetic innervation in secondary lymphoid organs plays a major role in immune regulation. Catecholamine released from the nerve terminal serves as the major mediator when bound to adrenergic receptors present on immunocompetent cells. Experiments using chemical and surgical denervation, catecholamine knock-out mice, and receptor antagonist and agonists revealed several important points. Sympathetic nerve activity is generally suppressive for the immunocompetent cells in the blood stream except neutrophils. Sympathetic activity facilitates detachment of T cells and NK cells from blood vessels without affecting functional adhesion molecule expression. Th1 cells express more beta 2 adrenergic receptors than Th2 cells, indicating a greater influence of sympathetic activity on Th1 response. Sympathetic action was also shown to regulate the production of chemokines. Taken together, the sympathetic nervous system does not simply suppress the immune system but might help organize the immune response sequentially and spatially by modulating the distribution of immunocompetent cells.

Effects of endurance training on the size and blood flow of the arterial conductance vessels in humans.

The aim of the present study was to determine non-invasively the effects of endurance training on both the size and blood flow of the arterial conductance vessels during exercise by men. Twelve healthy male subjects were assigned to either an exercise-trained group (ET, n = 7) or a sedentary control group (S, n = 5). The ET group underwent cycle-endurance training for 8 weeks (80% VO2max, 40 min day-1, 5 days week-1). The S group led normal lives during the 8-week period. Before and after the training period, cross-sectional areas (CSA) of the ascending and abdominal aorta were measured by echography. Measurements were taken in the semisupine position on a cycle ergometer fitted with a backrest, at rest and during 40, 60 and 80% VO2max of exercise. In addition, Doppler ultrasonographic velocity and flow in the ascending aorta were simultaneously measured. The CSA of the ascending and abdominal aorta after training were significantly larger than those before training in the ET group. Although there were no significant differences in the peak and mean velocities in the ascending aorta before and after the training in the ET group, the blood flow in the ascending aorta during exercise after training was significantly larger than that found before training at each relative intensity. There were no significant differences in any of the Doppler echographic parameters in the S group. These findings suggest that the arterial conductance vessels can be morphologically altered in an adaptive response to the endurance training. Furthermore, the dilation of the conductance vessels with endurance training contributes to an increase in blood flow to the exercising muscles without a rise in blood velocity. In other words, the arterial conductance vessels adapt to maintain adequate blood velocity and shear stress.

A new synthesis of inosine from 5-amino-1-beta-D-ribofuranosyl-4-imidazole-carboxamide.

Inosine was prepared (15% yield) by treatment of 5-amino-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (AICA-riboside) with chloroform in the presence of sodium methoxide. This ring closure can be reasonably explained by assuming the formation of dichlorocarbene from chloroform and alkali. Carbon tetrachloride or hexachloroethane as a carbene source was more effective for the ring closure of AICA-riboside, giving inosine in 48% and 51% yields respectively.

Synthesis of guanosine and its derivatives from 5-amino-1-beta-D-ribofuranosyl-4-imidazolecarboxamide. III. Formation of a novel cycloimidazole nucleoside and its cleavage reactions.

A new cycloimidazole nucleoside, 5-(1 inch -benzamido-1 inch-hydroxymethylene) amino-2', 1 inch-anhydro-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (III) was synthesized by reaction of 5-amino-1-beta-D-ribofuranosyl-4-imidazolecarboxamide (AICA-riboside) with benzoyl isothiocyanate followed by methylation with methyl iodide. The structure of III was elucidated on the basis of its nmr spectra and chemical reactions. Of special interest are reactions of III with various nucleophiles. For example, guanosine (IX) was obtained by amination of III wtih ammonia in 72% yield. Analogous reactions of III with methylamine and dimethylamine gave N2-methylguanosine (X) and N2-dimethylguanosine (XI), respectively. Refluxing of III in alkaline solution afforded xanthosine (VII). The probable mechanism of formation and facile ring-opening of III is also discussed.

Synthesis of guanosine and its derivatives from 5-amino-1-beta-D-ribofuranosyl-e-imidazolecarboxamide. IV. A new route to guanosine via cyanamide derivative.

4-Cyanamido-5-imidazolecarboxamide (IV) was prepared by brief treatment of 5-(S-methylisothiocarbamoyl) amino-4-imidazolecarboxamide (V) with alkali. Compound VI was converted in an alkaline solution to either guanine (VII) or isoguanine (VIII), depending on the concentration of alkali. This procedure was applied to the synthesis of 2',3'-0-isopropylideneguanosine (XVI) from the riboside of 5-(N'-benzoyl-S-methylthiocarbamoyl) amino-4-imidazolecarboxamide (IX), PROviding a new route to XVI.