Effects of a High Dose,Aglycone-Rich Soy Extract on Prostate-Specific Antigen and Serum Isoflavone Concentrations in Men With Localized Prostate Cancer

The efficacy and safety of consuming high-dose isoflavone supplements for prostate cancer is not clear. A double-blind, placebo controlled, randomized trial was conducted in 53 men with prostate cancer enrolled in an active surveillance program. The treatment group consumed a supplement containing 450 mg genistein, 300 mg daidzein, and other isoflavones daily for 6 mo. Prostate-specific antigen (PSA) was measured in both groups at baseline, 3 mo, and 6 mo, and serum concentrations of genistein, daidzein, and equol were assessed at baseline and 6 mo in the treatment group. Following the completion of the 6-mo double-blind study, men were enrolled in a 6-mo open label trial with the same isoflavone-rich supplement, and PSA was measured at 3 and 6 mo. PSA concentrations did not change in either group after 6 mo or after 12 mo when the open-label study was included. The 6 mo serum concentrations of genistein and daidzein (39.85 and 45.59 μmol/l, respectively) were significantly greater than baseline values and substantially higher than levels previously reported in other studies. Equol levels did not change. Although high amounts of aglycone isoflavones may result in significantly elevated serum concentrations of genistein and daidzein, these dietary supplements alone did not lower PSA levels in men with low-volume prostate cancer.     

Temocapril treatment ameliorates autoimmune myocarditis associated with enhanced cardiomyocyte thioredoxin expression

OBJECTIVE: Thioredoxin (TRX) is a redox regulatory protein that protects cells from various stresses. Angiotensin-converting enzyme (ACE) inhibitor was reported to enhance endogenous antioxidant enzyme activities. This study was carried out to investigate whether temocapril, a novel non-sulfhydryl-containing ACE inhibitor, reduces the severity of myocarditis via redox regulation mechanisms involving TRX. METHODS AND RESULTS: In normal rat myocytes in vitro and in vivo, Western blot showed that temocapril enhanced cytosolic redox regulatory protein TRX expression, but that neither mitochondrial TRX2 nor antioxidant enzymes, such as copper-zinc superoxide dismutase (Cu/Zn-SOD) or manganese superoxide dismutase (Mn-SOD) expression, was up-regulated by the preconditioning treatment. In rats with experimental autoimmune myocarditis (EAM), the severity of myocarditis and the protein carbonyl contents were less increased in temocapril treatment (10 mg/kg/day, orally) from day 1 to day 21, but not in temocapril treatment from day 15 to day 21. An immunohistochemical study showed that TRX stain was enhanced in infiltrating inflammatory cells and in damaged myocytes. Considering the characteristics of this model that myocardial inflammation begins around day 15 and increases until day 21, temocapril treatment for 3 weeks might be thought of as a preconditioning treatment. CONCLUSIONS: The results suggest that TRX and the redox state modified by TRX may play a crucial role in the pathophysiology of EAM. Temocapril ameliorates myocarditis associated with inducing TRX up-regulation in a preconditioning manner, although the mechanism of TRX up-regulation by temocapril remains to be elucidated.     

Recent decline in hospital mortality among patients with acute myocardial infarction.

BACKGROUND: Many patients with acute myocardial infarction will still die after admission. Recent trends in hospital mortality were analyzed to identify aspects that need improvement. METHODS AND RESULTS: A total of 1,247 patients admitted to Kinki University School of Medicine within 24 h of the onset of infarction were analyzed between 1975 and 2001. The percentage of patients discharged with 100% occlusion decreased gradually from 31.3% during 1975-1982 to 2.1% during 1998-2001, while those with 50% stenosis or less gradually increased from 12.5% to 82.5% during the same period (trends: p < 0.01). The cardiac death rate was 17.1% in 1975-1982, and 7.7% in 1998-2001, showing a significant decrease with time (p < 0.01). This decrease was particularly marked among those admitted within 6 h of the onset of infarction. Death due to cardiac rupture decreased significantly with time (p < 0.001). In contrast, the non-cardiac death rate, amounting to 2.2% on average, did not decline. CONCLUSIONS: Cardiac deaths due to acute myocardial infarction have decreased markedly of late. However, patients must be admitted within 6 h of the onset of infarction to benefit from this improvement. More effort should be made to improve the general care of patients in order to reduce the incidence of non-cardiac death.     

Intraductal papillary adenoma: Usefulness of magnetic resonance cholangiopancreatography in the diagnosis of cystic branch-duct dilatation of the pancreas

A 70-year-old woman with gastric cancer was referred to our hospital for further evaluation of a cystic mass in the head of the pancreas. Endoscopic ultrasonography (EUS) showed a mural nodule in the cystic mass. Endoscopic retrograde cholangio pancreatography (ERCP) revealed a cystic lesion with a filling defect caused by obstruction with mucus. Magnetic resonance cholangiopancreatography (MRCP) allowed visualization of the entire configuration of the cystic lesion despite the presence of mucus. Pancreatic juice was positive for K-ras point mutation. Pancreatoduodenectomy was performed, with a diagnosis of intraductal papillary adenoma or adenocarcinoma with gastric cancer. Pancreatography of the resected specimen showed a cystic lesion in the uncinate process, consistent with the MRCP findings. Histological examination revealed an intraductal papillary adenoma. MRCP is very useful for demonstrating the total configuration of cystic lesions and is not impeded by impacted mucin. Nevertheless, because of its lower spatial resolution, this noninvasive modality is of limited value in detecting mural nodules. At present, therefore, surgical indications for cystic lesion of the pancreas should be determined by comprehensively analyzing: size and sequential changes in size of the cyst; presence of mural nodules, cytologic examination for presence of malignant cells, and/or K-ras point mutation in pure pancreatic juice.     

Unusual left ventricular dilatation without functional or biochemical impairment in normotensive extremely overweight Japanese professional sumo wrestlers

To explore the physiologic limit of left ventricular (LV) enlargement, we performed echocardiography and air displacement plethysmography to respectively assess LV dimension and function and the body composition of Japanese professional sumo wrestlers. After excluding subjects with cardiovascular disease, hypertension, plasma brain natriuretic peptide (BNP) > or =17.9 pg/ml, diabetes mellitus, or asthma, 331 subjects (mean +/- SD age, 21.6 +/- 3.7 years; height 179.2 +/- 5.3 cm; weight 1,17.9 +/- 21.5 kg; percent fat, 29.6 +/- 6.6%) were analyzed. LV end-diastolic dimension averaged 58.4 +/- 3.7 mm and was within the generally regarded normal limit (< or =54 mm) in 14.5% of subjects, but was > or =60 mm in 41.1% of subjects. LV septal and posterior wall thicknesses were 10.3 +/- 0.9 and 10.2 +/- 0.9 mm, respectively. Peak E- and A-wave velocities, E/A ratio, LV fractional shortening, and BNP were 96 +/- 16 and 51 +/- 13 cm/s, 2.0 +/- 0.7, 33.5 +/- 4.5%, and 3.1 +/- 3.7 pg/ml, respectively. LV end-diastolic dimension was not correlated with these indexes of LV function or with plasma BNP levels, but was significantly correlated with height, weight, body surface area, fat-free mass, and fat mass. These results show that among very large, highly trained, professional athletes, LV end-diastolic dimension frequently exceeds the traditionally accepted upper limit of normal for the general population. This increase in LV end-diastolic dimension may thus represent an extreme example of the physiologic adaptation of the athlete's heart.     

Expression of GPIV and Naka antigen on monocytes in Naka-negative subjects whose platelets lack GPIV

Summary. The platelet antigen Nak^a was once considered to be a platelet-specific alloantigen and is carried on platelet membrane glycoprotein (GP) IV. Recent studies suggest that Nak^a-negative subjects lack platelet GPIV. GPIV is an important adhesive receptor and expressed on the surface of monocytes as well as of platelets. In the present study, flow cytometry was used to detect GPIV and Nak^a antigen on the surface of monocytes. Nak^a antigen was expressed on monocytes as well as on platelets in Nak^a-positive subjects ( n = 6) (P-GPIV-positive subjects). To our surprise, monocytes of Nak^a-negative subjects ( n = 7) (P-GPIV-negative subjects) having no anti-Nak^a antibody in their serum expressed GPIV and Nak^a antigen to almost the same degree as did the monocytes of P-GPIV-positive subjects. Competitive experiments using OKM5 (a monoclonal antibody against GPIV) and anti-Nak^a antibody showed that the epitope of anti-Nak^a antibody on monocytes was very close to that of OKM5. In two P-GPIV-negative subjects having anti-Nak^a antibody in their serum, GPIV and Nak^a antigen were not expressed on the surface of either monocytes or platelets. These results indicate that the GPIV molecules and Nak^a antigen are expressed on the surface of monocytes in the majority of P-GPIV-negative subjects, but that in a very few P-GPIV-negative subjects neither GPIV nor Nak^a antigen is expressed on the surface of their monocytes. We hypothesize that P-GPIV-negative subjects who carry neither GPIV nor Nak^a antigen on their monocytes produce anti-Nak^a antibody as a result of transfusion or pregnancy.