Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone.

A rhodium-catalyzed intramolecular reductive aldol-type cyclization is described to give ß-hydroxylactones with high diastereoselectivities. The stereoselectivity of this cyclization is highly solvent dependent and can give syn- or anti-ß-hydroxylactones with high diastereoselectivity. This methodology was also applied to the synthesis of a chiral necic acid lactone which is a structural component of the pyrrolizidine alkaloid monocrotaline.

Administration of angiotensin-converting enzyme inhibitors is associated with slow progression of mild aortic stenosis in Japanese patients.

It is almost unknown which demographic factors or medications affect the progression of aortic stenosis (AS) in Japanese patients with mild AS. We identified a total of 194 patients with native tricuspid valvular AS, defined as a continuous-wave Doppler determined peak aortic valve jet velocity of ≥ 2.0 m/s, in whom echo Doppler studies were repeated at an interim of at least 6 months. Annualized change in peak jet velocity was calculated, and effects of age, sex, diabetes mellitus, blood pressure, serum low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels, and use of statins and antihypertensive agents on the progression of AS were retrospectively evaluated. Peak aortic valve jet velocity was 2.36 ± 0.79 m/s (mean ± SD) and annualized increase in peak aortic valve jet velocity was 0.17 ± 0.32 m/s/year for all the studied patients. The increase in peak aortic valve jet velocity was lower in patients taking angiotensin-converting enzyme inhibitors (ACE-Is) than in those not taking ACE-Is (0.04 ± 0.22 vs. 0.20 ± 0.32 m/s/year, P < 0.05). Such protective associations were not observed for other first-line antihypertensive agents and statins. Multiple linear regression analysis revealed that ACE-I treatment, decrease in left ventricular ejection fraction, and higher peak aortic valve jet velocity at the first echocardiogram were associated with slower progression of AS. Administration of ACE-Is was associated with the slow progression of mild AS in Japanese patients. Prospective study to assess this hypothesis is needed.

Increased interleukin-18 expression in nonrheumatic aortic valve stenosis.

BACKGROUND: It is unknown whether interleukin-18 (IL-18) participates in the pathophysiology of nonrheumatic aortic stenosis (NR-AS). METHODS: We examined IL-18 expression in human NR-AS valves by immunohistochemistry and Western blot analysis. RESULTS: Immunohistochemistry revealed that NR-AS valves showed increased IL-18 expression compared with controls. IL-18 receptor was also expressed in NR-AS valves. Western blot analysis showed that IL-18 was expressed as an active form in NR-AS valves. Furthermore, increased IL-18 expression was correlated with the advanced clinical severity of NR-AS. CONCLUSIONS: IL-18 was expressed in the aortic valves and up-regulated in NR-AS valves. IL-18 may contribute to the pathophysiology of NR-AS.

Loop diuretic precipitated beriberi in a patient after pancreaticoduodenectomy: a case report.

Upper gastrointestinal tract surgery and diuretic use are 2 unrecognized causes of thiamine (vitamin B1) deficiency. Upper gastrointestinal tract surgery decreases the thiamine absorption, and diuretic use increases urinary excretion of thiamine. We present a case of a patient with a history of pancreaticoduodenectomy who had development of beriberi by diuretic use. A 68-year-old man was referred to our hospital because of pretibial pitting edema, foot numbness, and gait disturbance. He had a history of pancreaticoduodenectomy 8 years before and had been taking loop diuretics for 2 months. He had signs of polyneuropathy and hyperkinetic heart. Beriberi was suspected, and thiamine supplementation was started immediately. Edema disappeared within several days, and signs of polyneuropathy gradually subsided. Because diuretics enhance urinary thiamine excretion, practitioners should use caution for thiamine deficiency when they prescribe diuretics for patients who have a history of upper gastrointestinal surgery and potentially have latent thiamine deficiency.