Congenital quadricuspid aortic valve with tetralogy of Fallot and pulmonary atresia

We report the case of a 4-year-old girl who had quadricuspid aortic valve regurgitation with tetralogy of Fallot and pulmonary atresia. This combination is very uncommon. Aortic valve replacement was performed successfully due to aortic regurgitation which had progressed one year after the total repair. The dilated aortic annulus plus quadricuspid aortic valve may result in progressive aortic regurgitation for a short period.     

Epithelium-dependent and -independent inhibitory effects of sivelestat, a neutrophil elastase inhibitor, on substance P-induced contraction of airway smooth muscle in lipopolysaccharide-treated guinea-pigs.

The underlying mechanism involved in the interaction between neutrophil elastase inhibitors and tachykinins has not been elucidated. In this study we have examined the effects of sivelestat, a neutrophil elastase inhibitor, on the in vitro responses of airways from lipopolysaccharide (LPS)-untreated or -treated guinea-pigs to substance P. Substance P (0.01-30 micromol/l) produced concentration-dependent contractions of both tracheal and bronchial ring preparations of LPS-untreated or -treated guinea-pigs. Responsiveness to substance P in these isolated airway preparations was augmented by either epithelium removal or LPS treatment. In epithelium-intact tracheal ring preparations isolated from LPS-untreated guinea-pigs, sivelestat (100 micromol/l) significantly inhibited substance P-induced contractions. The inhibitory action was markedly attenuated by pretreatment with L-NAME (100 micromol/l) or indomethacin (2 micromol/l), and was almost undetected following removal of the epithelium. On the other hand, in bronchial ring preparations isolated from LPS-untreated guinea-pigs, sivelestat had only a very slight effect on substance P-induced contraction of the epithelium-intact preparation, whereas sivelestat greatly inhibited contraction in epithelium-removed bronchial ring preparations. In LPS-treated guinea-pigs, whether the epithelium was intact or not, sivelestat significantly inhibited the substance P-induced contraction of bronchial ring preparations. Pretreatment with L-NAME (100 micromol/l) or indomethacin (2 micromol/l) did not affect the inhibitory effect of sivelestat in bronchial ring preparations. In conclusion, epithelium removal or LPS treatment induced hyperreactivity to substance P in the guinea-pig airway. Sivelestat caused epithelium-, nitric oxide- and prostaglandin-dependent inhibition of the substance P-induced contraction of isolated guinea-pig tracheal ring preparations. In contrast, the inhibitory effect of sivelestat on substance P-induced contraction of guinea-pig bronchial ring preparations is mediated by epithelium-, nitric oxide- and prostaglandin-independent mechanisms. Sivelestat may be effective in reducing the airway hyperresponsiveness to tachykinins induced by epithelial injury as occurs in LPS-mediated inflammatory lung diseases.     

Distinct osteogenic mechanisms of bones of distinct origins

Mammalian bones have three distinct origins (paraxial mesoderm, lateral plate mesoderm, and neural crest) and undergo two different modes of formation (intra-membranous and endochondral). Bones derived from the paraxial mesoderm and lateral plate mesoderm mainly form through the endochondral process. During this process, hypertrophic chondrocytes play a vital role in inducing both osteogenesis and angiogenesis. One of the essential osteogenic factors secreted from hypertrophic chondrocytes is Indian hedgehog (Ihh). In contrast, bones derived from the neural crest mainly form through the intramembranous pro-cess and do not require Ihh. Thus, depending on their origin, bones have distinct signaling properties, which need to be considered in the research and application of bone biology.Presented at the 18th Annual Research Meeting of the Japanese Orthopaedic Association, Kitakyushu, Japan, October 17, 2003     

Coronary artery bypass grafting with combined arterial grafts

Coronary artery bypass grafting with combined arterial graft using the left internal mammary artery (IMA), right IMA, and the right gastroepiploic artery (GEA) was performed in 45 patients with saphenous vein graft (SVG) (29 patients) or without SVG (16 patients) from February 1989 to October 1989. The left IMA was used in all patients, the right IMA was used in 9 patients, and the GEA was used in 43 patients. Perioperative myocardial infarction was noted in two patients who had hospital deaths. Reopening the chest for postoperative bleeding was performed in two patients, and the cerebral accident was noted in one patient. Fourteen patients were operated on without the requirement for blood transfusion. Studied within 3 postoperative months, all arterial grafts were patent though the patency was 97.7% (43/44) in SVG. It is concluded that the combined arterial graft utilizing the IMAs and GEA can be used safely and effectively.     

Detection of proteinous toxins using the Bio-Threat Alert system, part 3: effects of heat pretreatment and interfering substances

We previously reported that the Guardian Bio-Threat Alert (BTA) system could detect (detection limit: about 0.1 μg/ml) staphylococcal enterotoxin B (SEB), botulinum toxins (BTX) A and B, and ricin, with no interference by white-powdered materials or colored matrices. In this study, the capability of the BTA system was further assessed. With 10 min of preheating at 60°C, all toxins could be detected, but with preheating at 80°C, BTX A and B and ricin became undetectable. About 20% SEB could be detected after heating at 80°C, but this detection ability was completely removed after heating at 100°C. The effects of chemicals usually used for decontamination, such as sodium hypochlorite, hydrogen peroxide, formaldehyde, and sodium nitrite, on the detectability of SEB, BTX A, or ricin in the BTA system were also tested. The concentrations giving 50% line intensity for SEB, BTX A, and ricin were 3.1, 11, and 15 μM for sodium hypochlorite and 88, 210, and 60 mM for formaldehyde, respectively. The addition of hydrogen peroxide or sodium nitrite did not decrease the detectability even when used at high concentrations.     

Pressure overload-induced transient oxidative stress mediates perivascular inflammation and cardiac fibrosis through angiotensin II.

Oxidative stress is implicated in the pathogenesis of various cardiovascular diseases. We have shown that in Wistar rats with a suprarenal aortic constriction (AC), pressure overload-induced transient perivascular inflammation (monocyte chemoattractant protein-1 [MCP-1] induction and macrophage accumulation) in the early phase is the determinant of reactive myocardial fibrosis and resultant diastolic dysfunction in the late phase. Thus, we investigated the role of reactive oxygen species production in cardiac remodeling in AC rats. Superoxide production and the footprint of lipid peroxidation were assessed using dihydroethidium staining and immunohistostaining against 4-hydroxy-2-nonenal (4-HNE), respectively. In sham rats, dihydroethidium and 4-HNE signals were scarcely found in the heart. At day 3, AC rats showed dihydroethidium signals mainly in the intramyocardial arterial wall, whereas modest 4-HNE staining was observed diffusely in the myocardium. These signals declined to lower levels by day 14 despite sustained hypertension. Chronic administration of a subdepressor dose of an angiotensin II type 1 receptor blocker candesartan reduced the pressure overload-induced dihydroethidium and 4-HNE signals at day 3. Moreover, candesartan decreased MCP-1 induction and macrophage infiltration at day 3 and prevented myocardial fibrosis at day 14, without affecting left ventricle and myocyte hypertrophy. In conclusion, acute pressure overload induced self-limited superoxide production mainly in the vascular wall. The reactive oxygen species production would contribute to the perivascular inflammation and subsequent myocardial fibrosis. Angiotensin II was suggested to have a pressure-independent effect on the reactive oxygen species production.