Effects of arotinolol on exercise capacity and humoral factors during exercise in normal subjects

Summary A placebo-controlled, double-blind crossover study was undertaken in 10 normal subjects to examine the effects of arotinolol (10 mg bid), a nonselective beta blocker with alpha-blocking activity, on exercise capacity and hormone levels during exercise after a 2-week treatment period. Maximal oxygen uptake (VO₂ max) and blood lactic acid concentration (LA) were measured during progressive exercise testing. An exercise intensity equivalent to 4 mmol/l of LA was used for the constant workload exercise test. Humoral factors were measured after 20 minutes of constant workload exercise. The administration of arotinolol significantly decreased systolic blood pressure and heart rate at rest and during exercise, but diastolic blood pressure did not change. No significant difference was found between arotinolol and placebo with regard to VO₂ max and maximal workload. Plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (NE) levels at rest and during exercise did not differ between the two treatments. In contrast, plasma epinephrine (EN) levels at rest and during exercise were significantly greater with arotinolol. Atrial natriuretic peptide (ANP) at rest did not differ between the two treatments. However, exercise caused a significant increase in ANP after arotinolol treatment. These findings suggest that arotinolol decreases blood pressure and heart rate without affecting exercise capacity.     

Serum markers of liver fibrosis and histologic severity of fibrosis in resected liver

BACKGROUND/AIMS: Serum concentrations of the 7S fragment of type IV collagen (7S collagen), amino-terminal propeptide of type III procollagen (PIIIP), and hyaluronic acid (HA) have been reported to serve as serologic markers of liver fibrosis in hepatitis and cirrhosis. We investigated whether these fibrosis markers reliably reflect histologic changes in the livers of patients with hepatocellular carcinoma. METHODOLOGY: Subjects included 165 patients undergoing liver resection for hepatocellular carcinoma. Most were seropositive for chronic hepatitis B or C. Histopathologic changes in liver tissue resected with the tumor were scored according to Knodell's histologic activity index. Serum was sampled for assays shortly before surgery. RESULTS: Significant correlations were found between hepatitis activity score and 7S collagen, PIIIP, and HA. Concentrations of 7S collagen differed significantly between activity grades, but differences were not significant for PIIIP or HA. Significant correlations were found between fibrosis staging score and all these three markers. When patients were divided according to activity grade, 7S collagen showed stronger correlation with fibrosis staging score than did PIIIP or HA. CONCLUSIONS: The 7S collagen fragment correlated more strongly than PIIIP or HA with stage and activity grade in patients with hepatocellular carcinoma. However, overlapping of results between histologically defined groups appeared to limit clinical diagnostic usefulness of all markers in individual patients.     

Different effects of pravastatin and cerivastatin on the media of the carotid arteries as assessed by integrated backscatter ultrasound.

BACKGROUND: Currently, there are various types of statins used in the treatment of hyperlipidemia and coronary artery disease. The purpose of this study was to compare the effects of a lipophilic statin (cerivastatin) with those of a hydrophilic statin (pravastatin) on the carotid arterial media using integrated backscatter (IB) ultrasound. Cerivastatin (C) has a strong anti-proliferative effect (APE) on smooth muscle cells (SMCs), whereas pravastatin (P) has a weak effect. METHODS AND RESULTS: The IB values in the media of 72 segments of carotid arteries were measured in 36 patients with hyperlipidemia before and after statin therapy or diet for 6 months (C, n=13: P, n=12: diet, n=11). In addition, IB values of 34 segments of carotid arteries were measured in 34 patients without coronary risk factors. Intima - media thickness (IMT) and arterial stiffness (stiffness beta) were measured by conventional echo at the same time. IB values did not significantly change in the P group (12.8+/-3.5 vs 12.7+/-2.7 dB), but decreased in the C group (12.1 +/-2.9 vs 10.0+/-2.7 dB, p<0.01). Also, stiffness beta did not significantly change in the P group (8.3+/-3.1 vs 7.6+/-2.5), but decreased in the C group (10.1+/-4.3 vs 7.9+/-3.3, p<0.05). IB values correlated with age (r=0.70, p<0.01) and stiffness beta (r=0.67, p<0.01) in the 34 patients without coronary risk factors. CONCLUSIONS: Statin therapy with cerivastatin, but not pravastatin, decreased the IB values of the carotid media and arterial stiffness. The difference between these 2 statins may be related to their effective dose range.     

Effect of H. pylori on COX-2 expression in gastric remnant after distal gastrectomy

BACKGROUND/AIMS: Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy. METHODOLOGY: The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically. RESULTS: Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p<0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p<0.001). CONCLUSIONS: H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy.     

Age-related changes in barrier function in mouse brain II. Accumulation of serum albumin in the olfactory bulb of SAM mice increased with aging

Brain transfer rate (BTR) and brain to plasma concentration ratio (BPCR) of radiolabelled human serum albumin injected intravenously were calculated to evaluate the brain transfer of serum albumin in the cerebral cortex, the right hemi-brain and the olfactory bulb of senescence accelerated prone mice (SAMP8) and senescence accelerated resistant mice (SAMR1). BTR and BPCR in SAMP8 and SAMR1 were significantly higher in the olfactory bulb than in the cerebral cortex or the right hemi-brain. Age-related significant changes in BTR and BPCR were observed in the olfactory bulb of SAMP8 and SAMR1. These findings suggest that the barrier function to serum albumin in the olfactory bulb of SAMP8 and SAMR1 is not so tight as it is in the cerebral cortex and becomes weaker with age and that the age-related changes are manifested at a younger age in SAMP8 than in SAMR1.     

A Large Retroperitoneal Encapsulation of Bile from a Spontaneous Perforation of the Common Bile Duct

We report a patient with spontaneous rupture of the common bile duct. This is an extremely rare condition which produces free leakage of bile into the peritoneal cavity. There has been no previous report concerning the formation of a large retroperitoneal encapsulation of bile. The preoperative diagnosis in our patient was very difficult and endoscopic retrograde pancreatocholangiography and cystography by ultrasound guidance were helpful.     

Angiogenesis in hepatocellular carcinoma as evaluated by CD34 immunohistochemistry

ABSTRACT— To clarify the relationship between angiogenesis and hepatocarcinogenesis on progression of hepatocellular carcinoma (HCC), we quantitatively evaluated angiogenesis by CD34 immunohistochemistry in liver cirrhosis (LC), adenomatous hyperplasia (AH), and HCC, and proliferative activity estimated by Ki-67 immunohistochemistry. Angiogenesis was evaluated by CD34 immunohistochemistry using monoclonal antibody HPCA-2, and tumor proliferative activity was evaluated using monoclonal antibody MIB-1. We used an image analysis system to assess the microvessel density as the area percentage of the endothelial area. Angiogenesis was generally observed in HCC and there was no significant difference among all clinical stages and histological grades of HCC. On the other hand, the staining of CD34 was partly observed in sinusoids of AH, although no positive staining was seen in any sinusoids of LC. The proliferative activity was significantly correlated with the clinical stage and histological grade of HCC. Our results indicate that the quantitation of angiogenesis does not provide significant prognostic information in HCC, but that it may have diagnostic value in distinguishing HCC from non-HCC. Meanwhile, AH, which is not morphologically diagnosed as cancer, shows positive staining for CD34, suggesting that some portion of AH contains cancerous characteristics.     

Effects of aging on plasma islet amyloid polypeptide basal level and response to oral glucose load.

To delineate the effects of aging on basal and glucose-stimulated secretion of islet amyloid polypeptide (IAPP), we compared the basal level of plasma IAPP and its response to an oral glucose load in elderly subjects with those of young subjects. Plasma IAPP level was determined by radioimmunoassay. Basal level of plasma IAPP in 20 elderly subjects (mean age 63 yr) was 5.3 +/- 0.4 pmol/l, which was not significantly different from 5.0 +/- 0.3 pmol/l in 22 young subjects (mean age 26 yr). Plasma glucose levels after an oral glucose load in elderly subjects (n = 8, mean age 67 yr) and young subjects (n = 8, mean age 29 yr) were within normal limits. However, the plasma glucose response in the aged group was significantly higher than that in the young group. The plasma insulin response to a glucose load in elderly subjects was not different from that in young subjects. The plasma IAPP level in the aged group significantly increased from 5.3 +/- 0.5 to 16.4 +/- 2.3 pmol/l 120 min after the oral glucose load. This result was quite similar to that in the young group whose plasma IAPP level increased from 4.9 +/- 0.5 to 14.1 +/- 1.5 pmol/l 120 min after the glucose load. We concluded that the basal level of plasma IAPP and its response to glucose were not affected by aging.     

Expression of atrial natriuretic polypeptide in ventricles of heart with hypertrophic cardiomyopathy: an immunohistochemical study of endomyocardial specimens]

To investigate the ventricular expression of atrial natriuretic polypeptide (ANP) in human hypertrophic heart, we conducted an immunohistochemical study using endomyocardial biopsy specimens obtained from the right side of the interventricular septum (RVB), left ventricular free wall (LVB), or both of 39 patients with hypertrophic cardiomyopathy (HCM), and 9 control subjects without hypertrophy. No HCM patients had apparent congestive heart failure. ANP was not present in control subjects' RVB or LVB specimens, but was found in HCM patients', showing its characteristic distribution patterns (RVB > LVB, p < 0.05); it was present in 15 of 36 RVB (42%) and 2 of 25 LVB (8%). No clinical data, including echocardiographic, hemodynamic and angiographic data, were directly related to ventricular ANP expression in HCM. According to histological data, however, ANP-present RVB specimens of HCM had larger myocytes, severer fibrosis and myofiber disarray than the specimens without ANP. This indicates that a failing state may not be a prerequisite for ANP expression in human hypertrophic ventricles, but that ventricular ANP expression may occur concomitantly with myocyte hypertrophy as an adaptive response to focal stress due to "histological overloads" such as disarray and fibrosis in HCM, which may be reflected in the characteristic distribution patterns of intraventricular ANP.