Inflammatory cytokines are suspected to play an important role in the pathophysiology of left ventricular (LV) remodeling. We investigated whether high-sensitivity C-reactive protein (CRP) (hs-CRP) is a predictor for LV remodeling in patients with acute myocardial infarction (AMI) with successful reperfusion, and also whether such a situation can be avoided by the administration of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). The subjects were 139 patients with an initial attack of anterior myocardial infarction successfully treated by reperfusion therapy. They were randomly divided into the following two groups: an angiotensin (AG) group (91 patients treated with ACEI/ARB) and a NON-AG group (48 patients not treated with ACEI/ARB). Levels of hs-CRP, creatine kinase, human atrial natriuretic polypeptide, brain natriuretic peptide (BNP), fasting blood glucose, serum lipids, fibrinogen, fibrin degradation product, prothromloin time, and activated partial thromboplastin time were measured immediately after 1, 2, 3, and 7 days, and 1 months after the onset of AMI. ACEI or ARB administration lowered hs-CRP levels and prevented the development of LV remodeling. Peak CRP levels significantly correlated with BNP levels during the acute stage (r = +0.54, P < 0.0001), end-diastolic volume index (r = +0.78, P < 0.0001), end-systolic volume index (r = +0.36, P = 0.0405), ejection fraction (r = -0.45, P = 0.0052), left ventricular end-diastolic diameter (r = +0.61, P < 0.0001), cardiac output (r = -0.52, P = 0.0005), cardiac index (r = -0.41, P = 0.0099), and systolic pulmonary arterial pressure (r = +0.48, P = 0.0017) 1 month after the onset of AMI in the NON-AG group but not in the AG group. Logistic multivariate analysis revealed that peak CRP alone was an independent risk factor for the development of LV remodeling in the NON-AG group (odds ratio = 1.79, P = 0.002). These results suggest that hs-CRP is a useful factor for predicting LV remodeling. Furthermore, ACEI or ARB administration to AMI patients showing increased hs-CRP levels during the early stage of the disease could prevent LV remodeling.

ObjectiveDiabetic patients with severe autonomic nervous disorder show delayed gastric emptying accompanied by diabetic gastroparesis, which decreases the electric activity of the stomach associated with gastric motility. It is reported that epalrestat, an aldose reductase inhibitor, is useful for treating diabetic neuropathy. Therefore, we evaluated whether this drug improves the decreased gastric motility in diabetic patients.Methods The present study evaluated the electrogastrograms (EGG) and autonomic nervous activity in 15 healthy volunteers (N group), and in 15 diabetic patients before and after the administration of epalrestat (DM group). Autonomic nervous activity was evaluated by spectral analysis of heart rate variability.The EGGs were recorded before and after oral administration of epalrestat (3 months or more) in the DMgroup. Results The dominant frequency of EGGwas 3 cycles/min (cpm) in the N group. However, these 3 cpm waves disappeared with bradygastria, and postprandial increases in the peak powers of EGGwere not observed in the DMgroup. Both the amplitude of 3 cpmwaves and the postprandial peak powers were significantly increased after the administration of epalrestat. The parameters of autonomic nervous activities (LF power, HF power, and the LF/HFratio) were significantly lower in the DMgroup before the administration of epalrestat than in the N group. However, these parameters were improved after the administration of epalrestat. Conclusion Since gastroparesis is a form of diabetic dysautonomia, complication by gastroparesis may influence blood sugar control and the absorbance of oral antidiabetics.Epalrestat significantly increased the amplitude of 3 cpm waves on EGGand improved the spectral analytical parameters of heart rate variability. These findings suggest that epalrestat is useful for the treatment of diabetic gastroparesis. (Internal Medicine 42: 655-664, 2003)

Studies were made on whether ammonia, which is an obligatory intermediate of amino acid metabolism, depresses the food intake of rats fed a low-casein (basal) diet containing imbalanced amino acid mixtures (imbalanced diets). Bilateral lesions in the prepyriform cortex caused normalization of food intake of rats fed amino acid-imbalanced diets, confirming the work of Leung and Rogers (Am. J. Physiol. 221:929-935, 1971). Unlike normal rats, animals with prepyriform cortical lesions consumed as much of a diet containing 3% NH4Cl as they did of the basal diet. However, like normal rats, they rejected a diet containing a mixture of keto acids. Unilateral injection of NH4Cl into prepyriform cortical areas reduced the food intake to a greater extent than injection of NaCl into these areas or injection of NH4Cl into other parts of the brain. These results suggest that ammonium ions influence the appetite through their effect on prepyriform cortical areas.

Synthetic LRH was infused into normal women and women with obesity and anorexia nervosa to determine the distribution volume (DV), metabolic clearance rate (MCR) and half disappearance time (t\m=1/2\)of plasma LRH.In normal women, the DV of LRH was 12.1 \m=+-\0.9 (mean \ m=+-\se) 1, the MCR was 1478.9 \m=+-\39.8 ml/min (28.5 \m=+-\1.2 ml/min/kg body weight) and the initial t \ m=1/ 2\ was 5.6 \m=+-\0.4 min.In obese patients the DV (20.6 \ m=+-\ 1.5 1) was significantly higher than that in normal subjects (P < 0.005), but the MCR and t\m=1/2\were not significantly different from those in normal subjects.In patients with anorexia nervosa the DV and MCR were 6.5 \m=+-\1.1 l and 621.8 \m=+-\110.5 ml/min (17.9 \ m=+-\2.4 ml/ min/kg body weight), respectively, which were both significantly lower than those in normal subjects (P < 0.02), while the t\m=1/2\(7.3 \m=+-\0.1 min) was longer than in normal subjects (P < 0.02).These data suggest that 1) the abnormal responses of some hormones to provocation tests observed in obese patients and patients with anorexia nervosa should be evaluated in consideration of changes in the DV and metabolic clearance of hormones in these conditions, and 2) in patients with anorexia nervosa changes in MCR and t \ m=1/ 2\ may reflect low metabolism of LRH.Various endocrine and metabolic abnormalities have been found in obese subjects (Beck et al. 1964;Copinschi et al. 1967) and underweight subjects (Frankel & Jenkins 1975). As we previously reported, the release of some pituitary hormones in response to various stimuli is impaired in obese patients (Chikamori 1976), and elevation of the plasma growth hormone (GH) level and decrease in luteinizing hormone (LH) secretion are noted in many patients with anorexia nervosa (Nishimura et al. 1979). These abnormalities in hormone secre¬ tion have been considered as secondary changes due to change in the body weight or dysfunction of the hypothalamo-pituitary axis. However, the plasma concentration of a hormone reflects a ba¬ lance between the rates of its secretion and meta¬ bolism, and thus endocrine function should be evaluated on the basis not only of the plasma concentration but also of metabolic clearance of the hormone released from the endocrine gland.For investigation of this problem, it is necessary to study changes in the distribution volume (DV) and metabolic clearance rate of hypothalamic or pituitary hormones in patients with obesity and anorexia nervosa. At present few purified pituitary hormones are available for iv injection into hu¬ mans, but hypothalamic releasing hormone is read¬ ily available.The metabolic clearance of synthetic luteinizing hormone releasing hormone (LRH) in normal sub¬ jects has been studied (Miyachi et al. 1973;Keye et al. 1973), but litüe is known about changes in metabolic clearance of LRH in diseased states (Pimstone et al. 1977). Therefore, we studied the DV, metabolic clearance rate (MCR) and half disap-