Activation of protein kinase C and nicotinamide adenine dinucleotide phosphate oxidase in leukocytes of spontaneously hypertensive rats.

The involvement of oxidative stress in polymorphonuclear leukocytes (PMN) in the pathogenesis of hypertension remains to be elucidated. We analyzed the generation of reactive oxygen species (ROS) by the circulating and peritoneally infiltrating PMN from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Flow cytometric analysis revealed that ROS generation by PMN from SHR was higher than that from WKY before (at 6 weeks of age) and after (at 16 weeks of age) the onset of hypertension. In vivo, ROS generation by PMN from SHR, but not that by PMN from WKY, was significantly suppressed by 10-week treatment with 50 mg/kg/day carvedilol, and this treatment did not affect blood pressure. Western blotting analysis revealed that protein kinase C alpha (PKCalpha), but not PKCbetaI or betaII, was activated more strongly in PMN from SHR than in PMN from WKY. Furthermore, expression of p47phox of nicotinamide adenine dinucleotide phosphate oxidase, but not of p67phox, in PMN from SHR was higher than that in PMN from WKY. These results suggest that ROS generation by PMN is principally enhanced in SHR through activation of PKCalpha and p47phox.     

Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed.

Anthocyanins, which are responsible for a variety of bright colors (including red, blue, and purple) in fruits, vegetables, and flowers, are consumed as dietary polyphenols. Anthocyanin-containing fruits are thought to decrease coronary heart disease and are used in anti-diabetic preparations. Diabetes is associated with a variety of cardiovascular complications that may be mediated by endothelial dysfunction, and so this study was designed mainly to characterize the influence of a synthesized anthocyanidin derivative (HK-008) over acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the glucose level as effectively as the same dose of glibenclamide. The aortic relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was greatly inhibited by glibenclamide (10 microM), and also significantly inhibited by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused, preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10 microM), and this enhancement was significantly attenuated by indomethacin (10 microM). The ACh-induced mesenteric relaxation was impaired by an increase in oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1 U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly suppressed by HK-008 (10 microM). These results suggest that HK-008 increases endothelium-induced relaxation by suppressing oxidative stress or modulating prostanoids signaling. This compound may therefore be useful against certain cardiovascular disorders.     

Allergic Predisposition Among Infants with Bronchiolitis

Allergic predisposition among infants with bronchiolitis was examined. The number of infants with serum IgE exceeding mean +1 SD was 31/70 (44.3%). The rate of positive radioallergosorbent test (RAST) scores of 1 or more to mites, egg white, or milk was 31/71 (43.7%) and that of scores over 2 was 11/71 (15.5%). Eosinophils and/or mast cells were found in their nasal smears on several occasions. These results indicated that allergic predisposition may be observed among infants with bronchiolitis.     

A patient with lambda type light-chain disease associated with Crow-Fukase syndrome and autoimmune thrombocytopenia]

A 67-year-old woman, who presented polyneuropathy, pleural effusion, ascites and sclerosing changes in the ribs, was admitted to our hospital on June 17, 1987. On admission, cerebrospinal examination showed a marked protein-cell dissociation and a delay in nerve conduction velocity. Bence-Jones protein was detected in urine, and the immunohistochemical study of biopsied bone marrow of the rib revealed lambda-chain positive plasmacytoma. Serum immunoelectrophoresis, however, showed no monoclonal gamma-globulinemia. From the findings described above, she was diagnosed as having Crow-Fukase syndrome associated with lambda-type light chain disease. Even with a therapy by prednisolone, platelet counts progressively declined to 10,000/ml3. Bone marrow aspiration showed normal number of megakaryocytes. Since platelet-associated IgG was increased to 452 ng/1.0 x 10(8) plt, a diagnosis of autoimmune thrombocytopenia was considered. Melphalan and cyclophosphamide to plasmacytoma resulted in a marked improvement of platelets. In addition, the level of platelet-associated IgG returned to normal range. Polyneuropathy, however, didn't respond to those therapies. It was suggested that both Crow-Fukase syndrome and thrombocytopenia were closely concerned with plasmacytoma but developed in a different manner.     

Anti-allergic effect of bryonolic acid from Luffa cylindrica cell suspension cultures.

The anti-allergic activity of bryonolic acid (1) isolated from the cultured cells of Luffa cylindrica L. (Cucurbitaceae) was compared with that of glycyrrhetinic acid (2), the aglycone of glycyrrhizin from licorice. Compound 1, when administered to rats intraperitoneally at a dose of 600 mg/kg, inhibited homologous passive cutaneous anaphylaxis more strongly than 2 at the same dose. Compound 1 also significantly inhibited delayed hypersensitivity in mice which could not be inhibited by 2. In contrast to 2, 1 showed not only little toxicity but no visible side effects on mice, without impairing the activity of the hepatic enzyme (4,5 beta-dihydrocortisone:NADP+ delta 4-oxidoreductase) involved in steroid catabolism.     

Three-dimensional assessment of urinary stone on non-contrast helical computed tomography as the predictor of stonestreet formation after extracorporeal shock wave lithotripsy for stones smaller than 20 mm

The incidence of stonestreet formation after extracorporeal shock wave lithotripsy (ESWL) rises with increasing stone burden. However, stonestreet after ESWL is often experienced even in stones smaller than 20 mm. To examine whether the non-contrast helical computed tomography (CT) data could predict stonestreet formation in these stones, 53 radiopaque stones of 5-20 mm treated with ESWL were evaluated. Maximal dimension was measured on plain radiograph. From an attenuation value histogram graphed from the CT data, total stone volume and mean attenuation value were calculated. Seven stonestreets longer than 25 mm developed. There was no significant difference in maximal dimension and total stone volume between stones that did and stones that did not develop stonestreet. Mean attenuation value was the sole significant predictive factor. Application of mean attenuation value with cut-off level of 650 HU would anticipate stonestreet formation with a sensitivity of 85.7% and a specificity of 71.7%. The estimated risk of stonestreet formation is high in the treatment of stones with higher mean attenuation value.     

Effects of gender on prognosis of patients with known or suspected coronary artery disease undergoing contrast-enhanced dobutamine stress echocardiography.

BACKGROUND: Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease (CAD) undergoing contrast-enhanced dobutamine stress echocardiography (CE-DSE) have not been completely determined. METHODS AND RESULTS: Follow-up (30+/-17 months) data for 581 men and 309 women with known or suspected CAD who underwent CE-DSE (mean age: 66 years) were obtained. Hard cardiac events included cardiac death and nonfatal myocardial infarction. Total cardiac events included hard cardiac events, unstable angina, congestive heart failure, and late revascularization (>3 months). Cardiac events occurred in 123 male and 50 female patients. Positive results for CE-DSE were associated with worse prognosis in both men and women (2-year total event free rate: 73.5% vs 88.2% in men, p<0.0001, 80.3% vs 91.3% in women, p<0.01). Addition of CE-DSE results, including abnormal left ventricular end-systolic volume response and left ventricular ejection fraction at peak stress <50%, to the clinical and rest echocardiography model provided incremental information for predicting total cardiac events (increase in chi-square value for the model from 60 to 72, p<0.001) in men and (increase in chi-square value for the model from 17 to 32, p<0.001) in women. CONCLUSIONS: CE-DSE provides incremental information for predicting future cardiac events in both men and women.