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.     

Lymphoepithelial cyst in the pancreas: A case report

A case of lymphoepithelial cyst in the pancreas was reported. A 64-year-old man without any specific compalints was found to have a cystic lesion in the anterior portion of the pancreas, as revealed by ultrasonography of the abdomen at an annual medical examination in 1988. This was dissected easily from the pancreas. Histologically, it was diagnosed to be a benign lymphoepithelial cyst in the pancreas. Cysts of this type are rare, and their histogenesis is also not well understood.     

Health benefits associated with exercise habituation in older Japanese men

BACKGROUND AND AIMS: The purpose of this study was to compare the effects of exercise habituation (3-32 years, mean 13.2 years) on physical vitality among five different groups. METHODS: One hundred and two independent, community-dwelling elderly Japanese men, aged 64.6 +/- 6.6 years, were recruited as subjects. The vital age test battery consisted of various coronary heart disease risk factors and physical fitness elements. RESULTS: The results of analysis of variance revealed that vital age as an index of physical vitality was youngest in joggers (47.9 yr, N=18), intermediate in trekkers (55.8 yr, N=20) and walkers (59.1 yr, N=18), and oldest (69.6 yr, N=20) in patients with ischemic heart disease (IHD). The difference between chronological age and vital age was approximately 15 years (p<0.05) in joggers, and 8 years (p<0.05) in trekkers and walkers. The vital age of sedentary persons (N=26) was only 1.9 years (NS) younger than their chronological age, which was similar to the difference (vital age of 64.1 +/- 8.5 yr vs chronological age of 65.7 +/- 5.4 yr) previously observed in similarly aged exercising IHD patients. CONCLUSIONS: These results indicate that exercise habituation significantly affects the overall health status of most individuals, irrespective of mode of exercise. Among the three modes of exercise, jogging may be most beneficial. Furthermore, regularly exercising coronary patients may have physical vitality similar to that of sedentary men.     

Spontaneous loss of hepatitis B surface antigen in chronic carriers, based on a long-term follow-up study in Goto Islands, Japan

Annual mass examination was performed between 1972 and 1997 in Tomie-town, Goto Islands, Japan, where hepatitis B virus (HBV) infection is very prevalent. In the present study, the incidence of spontaneous loss of hepatitis B surface antigen (HBsAg) in HBsAg carriers was determined in this area. Three thousand and nineteen inhabitants were tested for HBsAg two or more times in our annual surveys. Among them, 131 (4.3%) were defined as chronic HBsAg carriers based on the persistence of HBsAg for 1 or more years. These 131 subjects were followed for 12.2 ± 7.6 years. During the follow-up period, spontaneous loss of HBsAg occurred in 38 (29%) of the 131 carriers, with a yearly incidence of 2.5%. This loss was seen more frequently in carriers aged 40 years or more on enrollment than in those aged less than 40 years during the same observation periods (P = 0.0141), irrespective of sex or the results of liver function tests. The values for liver function test results were similar before and after loss of HBsAg in these carriers. Stored serum samples were available for later analysis of HBV-DNA by polymerase chain reaction in 32 carriers with loss of HBsAg. The HBV-DNA sequence was detected in 26 (81%) and 2 of the 32 carriers (6%) before and after loss of HBsAg, respectively. These results indicate that spontaneous loss of HBsAg, largely attributable to clearance of viremia, occurs age-dependently in chronic carriers. Received: July 23, 1999 / Accepted: September 24, 1999     

Endothelin-1(1-31) levels are increased in atherosclerotic lesions of the thoracic aorta of hypercholesterolemic hamsters

OBJECTIVE: The novel vaso-constricting 31-amino acid-length endothelin-1 [ET-1(1-31)] is selectively produced by human mast cell chymase via its action on big ET-1. However, the pathological role of ET-1(1-31) in atherosclerosis remains unclear. The aim of this study was to clarify vasoconstrictive response and expression of ET-1(1-31) in atherosclerotic aorta. METHODS AND RESULTS: Syrian golden hamster, was used for preparing the atherosclerotic models by the administration of a high cholesterol diet (HC), treatment with the nitric oxide synthase inhibitor (Nomega-nitro-L-arginine methylester, L-NAME) alone, or both (HC and L-NAME) for 40 weeks. Early atherosclerosis was observed in the case of HC or L-NAME alone treatments respectively and severe atherosclerosis was observed in the case of combined HC and L-NAME treatment. Vasoconstriction induced by ET-1(1-31) was not altered by the atherosclerotic changes, but the expression pattern of ET-1(1-31) was different at each stage of the atherosclerotic aorta. ET-1(1-31) was observed rarely in normal aortas or in early atherosclerotic lesions, but ET-1(1-31) expression was dramatically increased in aortic neointima and adventitia in a state of atherosclerosis with severe inflammation. CONCLUSION: ET-1(1-31) might play in a role of promoting atherosclerosis, and especially be involved in inflammatory mediation during the progression of atherosclerosis.     

Phenotyping of malignant hematopoietic cells

Summary 1255 cases of leukemia-lymphoma were tested between 1972 and 1984 by multiple marker analysis. Routine leukemia phenotyping was performed using standard morphological and cytochemical techniques in combination with clinical and histo-pathological information; the main emphasis was put on immunological surface marker analysis using erythrocyte rosette assays, TdT and a large panel of poly- and monoclonal antibody tests. The 1255 cases were divided into these major types and subtypes: 349 cases of ALL and related immature T- and Burkitt-lymphomas (cALL, pre B-ALL, B-ALL and Burkitt-lymphomas, T-ALL and immature, mostly leukemic T-lymphomas, Null-ALL), 454 cases of mature T- and B-cell malignancies (T-CLL, mycosis fungoides, Sezary-syndrome, T-lymphomas, B-CLL, hairy cell leukemia, multiple myeloma, B-lymphomas), 263 cases of acute myeloid leukemias (AML, AMMoL/AMoL), 182 cases of chronic myeloid leukemias (CML in chronic phase, CMoL, CML in blast crisis), 6 cases of erythroleukemia and 1 case of megakaryoblastic leukemia. A simplified classification scheme which has been used in our laboratories is presented. Phenotyping is of diagnostic, prognostic and therapeutic relevance, most evidently for patients with ALL. Routine leukemia phenotyping should be performed with highly standardized techniques and reagents and by combining information from several fields in the multiple marker analysis. New areas of leukemia research might become very useful for the routine procedure of phenotyping.Abbreviations ALL acute lymphoblastic leukemia - AML acute myeloblastic leukemia - AMMoL acute myelomonoblastic leukemia - AMoL acute monoblastic leukemia - cALL common ALL - CLL chronic lymphocytic leukemia - CML chronic myelocytic leukemia - CML-BC CML in blastic crisis - CMoL chronic monocytic leukemia     

Health-related quality of life of outpatients with systolic and isolated diastolic dysfunction

Background The impact of isolated diastolic dysfunction (IDD) and systolic dysfunction (SD) on health-related quality of life (HRQOL) is unknown. Methods and Results To evaluate HRQOL in patients with IDD and SD under treatment, information on outpatients aged 60-84 years was extracted from the records of 4,500 consecutive individuals who underwent echocardiographic examination at Sado General Hospital. The medical records of these patients were reviewed and a questionnaire, including the Medical Outcome Study Short Form 36, was mailed to 71 IDD and 99 SD patients; answers were obtained from 66 and 91 patients, respectively. The HRQOL of patients with cardiac dysfunction was impaired even when echocardiographic parameters improved with treatment. Patients with IDD showed an impairment of HRQOL similar to those with SD. Compared with males, female patients had a larger and more significant reduction in the physical and mental components of the HRQOL score. These scores correlated positively with exercise capacity in patients with IDD or SD. Conclusions Impaired HRQOL, in both its mental and physical components, is a serious problem for IDD and SD patients under treatment. Because exercise intolerance may underlie the reduced HRQOL, improving exercise capacity could be an important target for managing outpatients with heart failure. (Circ J 2008; 72: 1436 - 1442).