The metabolism of peptide leukotrienes in the lung may affect their coronary vasoconstrictive effect in anesthetized dogs

The deteriorative effect of peptide leukotrienes (LTs) on the coronary circulation are well known. On the other hand, it has been recognized that some of these prostanoids are metabolized in the pulmonary vascular bed. To clarify the influence of the metabolism of LTs in the lung on their effects to the coronary circulation, we compared the changes of coronary circulation parameters by leukotriene D4 (LTD4) and C4 (LTC4) administered (5 mcg/kg) into the right atrium (RA) and the left atrium (LA) in 8 mongrel dogs. After the administration of LTD4 and LTC4, significant reduction of coronary blood flow (LTD4-RA 65.8 +/- 3.4%, LTD4-LA 54.8 +/- 2.3%, LTC4-RA 64.3 +/- 3.9%, LTC4-LA 66.9 +/- 3.7%) and elevation of coronary vascular resistance (LTD4-RA 130.5 +/- 8.2%, LTD4-LA 157.3 +/- 6.1%, LTC4-RA 138.7 +/- 8.0%, LTC4-LA 129.5 +/- 10.1%) were recognized. The effect of LTD4, administered into the left atrium was significantly greater than that administered into the right atrium (p less than 0.05). The difference between right and left atrial administration was not statistically significant, although a tendency for the effect to be greater with right atrial administration than left was recognized. The LTC4 concentration in aortic blood measured by radioimmunoassay was significantly lower in right atrial administration than left (p less than 0.05). These results suggested that LTD4 was metabolized and inactivated in the lung during its passage through the pulmonary circulation, and LTC4 was not only inactivated but also converted to LTD4 and activated in the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Study on the mechanism of an experimental immunological intrahepatic cholestasis model.

Tuberculin-sensitized guinea pigs were intravenously injected with heat-killed Propionibacterium acnes followed by an intravenous injection of purified protein derivatives 7 day later, resulting in the induction of intrahepatic cholestasis. Using this experimental model, the following results were obtained: (1) Both uptake and release of bile acid were inhibited in the hepatocytes prepared from the cholestasis guinea pigs. (2) The results of the erythritol clearance method indicated that the decrease in bile flow observed in the cholestasis guinea pigs was mostly attributable to the reduced bile excretion from the canaliculi. (3) The decrease in the formation of bile acid independent bile flow was the cause of the decrease in bile flow observed in the cholestasis guinea pigs. (4) There was no change in the permeability of the interhepatocellular tight junction in the cholestasis guinea pigs.     

Effect of natural panting frequency and cheek support on the plethysmographic determination of thoracic gas volume in patients with chronic obstructive pulmonary disease]

The authors studied the effects of natural panting frequency (NF) and the cheek support on the plethysmographic measurement of thoracic gas volume (TGV) in 8 normal subjects (non-smokers) and 46 patients with chronic obstructive pulmonary disease (COPD). The patients were divided into 2 groups according to the degree of airway obstruction (group I; specific airway conductance (SGaw) greater than 0.1 (n = 18), group II; SGaw less than 0.1 (n = 28)). TGV was measured with a pressure-type body plethysmograph (BP). NF was 2.00 +/- 0.43 Hz (mean +/- SD) in control subjects, 1.92 +/- 0.78 Hz in group I, and 1.39 +/- 0.59 Hz in group II, respectively, indicating lower NF in the patients with severe airway obstruction. In control subjects and group I, the differences between TGV at NF and at 0.5-1.0 Hz (TGVNF-TGV1.0) were -0.01 +/- 0.07L, and -0.06 +/- 0.16L, respectively, and cheek support did not alter the difference. On the other hand, in group II, the difference was slightly larger than other groups in spite of the lower NF, and this overestimation was abolished by cheek support (0.13 +/- 0.25L-----0.06 +/- 0.27L, p less than 0.05). These results suggest that, in patients with severe airway obstruction, TGVNF may be overestimated even if NF is relatively low. This overestimation may be mainly due to the extrathoracic airway compliance including the cheek.     

Increase of Bone Mass and Mechanical Strength in Rats after Treatment with a Novel Bisphosphonate,YM175, for Two Years

Abstract: We have evaluated the relationship between bone mass and mechanical properties of bone from male and female rats treated with YM175, a novel bisphosphonate, for 104 weeks. YM175 [disodium (cycloheptylamino) methylenediphosphonate monohydrate] was given via the drinking water at a concentration of 0, 0.005, 0.015, 0.05, or 0.15%. Since the mortality in the male 0.15% group exceeded the exclusion criteria (75%) at week 88, this group was omitted from the study. Mean daily intake of YM175 was 2.2-22.1 mg/kg for males and 3.6-104 mg/kg for females. After the treatment, mechanical properties and ash weight of the humerus were determined. In males, 0.015 and 0.05% of YM175 (6.6–22.1 mg/kg) significantly increased failure load of the midshaft. In females, failure load and stiffness of the midshaft tended to be increased by YM175 (up to 104 mg/kg). Furthermore, ultimate compressive load at the humeral metaphysis treated with the highest dose of YM175 was 2- or 3.5-fold greater than that of untreated male or female control. Ash weight of the humerus was increased dose-dependently and was positively correlated with failure load of the midshaft. These findings indicate that treatment for 2 years with YM175 increased bone mass and mechanical strength without blocking bone mineralization.     

Water-curable and biodegradable prepolymers.

In an attempt to develop biodegradable polymers which can be shaped in situ and adhere to living tissues, we synthesized esterurethane prepolymers which can be cured upon contact with water in living tissues. First, D,L-lactide polymerization or D,L-lactide-epsilon-caprolactone (50:50) copolymerization was carried out using ethylene glycol or poly(ethylene glycol) as initiator to obtain hydroxyl-terminated biodegradable polyesters. They were then reacted with an excess of diisocyanate such as hexamethylene diisocyanate, toluylene diisocyanate, and diphenylmethane diisocyanate to introduce a reactive isocyanate group to both of the end groups of the polyesters. The isocyanate-terminated prepolymers could be cured in the presence of water and the cured polymers were degraded by hydrolysis both in vitro and in vivo. It was found that the presence of appropriate amounts of hydrophilic units in the main chain was essential for giving a high curing rate and a high degradation rate for the biodegradable urethane prepolymers. The tissue responses to the cured polymers were not severe.     

The efficacy of fluconazole in treating prosthetic valve endocarditis caused byCandida glabrata: Report of a case

A case of active prosthetic valve infective endocarditis (PVE) due toCandida glabrata was successfully treated by the systemic administration of fluconazole. A 66-year-old Japanese man with infective endocarditis of unknown etiology underwent aortic and mitral valve replacement to treat severe aortic and mitral regurgitation associated with multiple organ failure. Postsurgical cultures of arterial blood were repeatedly positive forC. glabrata, and therefore fluconazole was administered either intravenously or orally at a dose of 400 mg/day for 46 days. During that time the signs of inflammation including fever such as an elevated white blood cell count and the presence of C-reactive protein (CRP) all improved while the blood cultures became negative. Fluconazole is thus considered to be effective in treating PVE caused byC. glabrata. When administering this treatment, it is also important to monitor the patient's renal and liver function.     

Assembly of synthetic cellulose I.

Cellulose microfibrils with an electron diffraction pattern characteristic of crystalline native cellulose I have been assembled abiotically by means of a cellulase-catalyzed polymerization of beta-cellobiosyl fluoride substrate monomer in acetonitrile/acetate buffer. Substantial purification of the Trichoderma viride cellulase enzyme was found to be essential for the formation of the synthetic cellulose I allomorph. Assembly of synthetic cellulose I appears to be a result of a micellar aggregation of the partially purified enzyme and the substrate in an organic/aqueous solvent system favoring the alignment of glucan chains with the same polarity and extended chain conformation, resulting in crystallization to form the metastable cellulose I allomorph.