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.     

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.     

Are left-sided gallbladders really located on the left side?

OBJECTIVE: The aim of this investigation was to establish the association between left-sided gallbladders and right-sided round ligaments. SUMMARY BACKGROUND DATA: The left-sided gallbladder is a rare anomaly and has been classified into two types: 1) gallbladder migration to the left side and 2) development of a second gallbladder with atrophy of the original one. Recently, left-sided gallbladders were reported to be associated with right-sided round ligaments. METHODS: The authors reviewed 3 patients treated in their departments and 15 patients reported in the literature diagnosed as having left-sided gallbladders accompanied by right-sided round ligaments. RESULTS: Although the gallbladders of all 18 patients were located at the normal site, they were diagnosed as being left sided because of the right-sided round ligaments. This anomaly was accompanied by abnormal intrahepatic portal venous branching, which could be classified into two types. In eight patients, the first branch of the portal vein ran to the posterior segment and then the portal vein formed a trunk of the left and right anterior portal veins. The latter portal vein formed the umbilical portion and finally joined the right-sided round ligament (trifurcation type). In five, the portal vein diverged normally to form the left and right portal veins, then the latter branched to form the anterior and posterior segments, and finally the anterior branch joined the round ligament (bifurcation type). In the other five, the branching type could not be determined. CONCLUSIONS: A right-sided round ligament causes a gallbladder at the normal site to be located on the left side. This anomaly should not be diagnosed as a left-sided gallbladder but as a right-sided round ligament. Recognition of this anomaly clinically is important when performing hepatectomy, because it is always associated with abnormal intrahepatic portal venous branching.     

Focal nodular hyperplasia of the liver: arterial angio-CT and microangiography.

To differentiate focal nodular hyperplasia (FNH) from other hepatic tumors, especially hepatocellular carcinoma, we evaluated the hemodynamics of histologically proved FNH in three patients, two by arterial angio-CT and one by microangiography of the resected specimen. These studies demonstrated the centrifugal blood supply of FNH (early filling of central tumor vessels radiating to periphery, and lobulated tumor stains with central low density area in the late phase), which could not be demonstrated by dynamic CT or hepatic angiography. Arterial angio-CT is useful as a further study, when differential diagnosis of FNH is uncertain by other imaging techniques.     

Influence of limonene and laurocapram on percutaneous absorption of nonsteroidal anti-inflammatory drugs.

The promoting effect of cyclic monoterpenes, 1% limonene (CAS 5989-27-5) and 1% cineole (CAS 470-82-6), on percutaneous absorption of nonsteroidal anti-inflammatory drugs was investigated in the rats. Compared with 1% laurocapram, drug absorption from the gel ointments was significantly more enhanced by addition of 1% limonene, while without any enhancer only ibuprofen penetrated across the skin in the limited amount. When using formulation with propylene glycol or 50% propylene glycolethanol solution, instead of carboxyvinyl polymer gel, percutaneous absorption significantly decreased and neither limonene nor cineole or laurocapram were capale to promote percutaneous absorption of flufenamic acid to sufficient serum level. Cineole and limonene were also evaluated in permeation experiments in vitro. Enhancement ability of limonene in the gel oinment was approximately 5 times higher comparing with enhancement ratio of cineole, while in 100% propylene glycol enhancement ability of both cyclic monoterpenes was equal. Good correlation was observed between in vivo and in vitro experiments. Evaluation of solubility proved that in the gel ointment simulated as water-ethanol solution were relatively best condition for percutaneous absorption of flufenamic acid when comparing with propylene glycol or 50% propylene glycol-ethanol solution.