Effects of ZCR-2060 on Allergic Airway Inflammation and Cell Activation in Guinea-pigs

Abstract— The effects of 2-(2-(4-(diphenylmethyl)-1-piperadinyl) ethoxy) benzoic acid malate (ZCR-2060) on allergic airway inflammation and inflammatory cell activation in guinea-pigs were studied. Allergic airway inflammation was induced by inhalation of antigen into actively-sensitized animals and the increase in inflammatory cells into bronchoalveolar lavage fluid (BALF) was measured. Aeroantigen-induced infiltration of inflammatory cells, especially eosinophils and neutrophils, in BALF gradually increased, and reached a peak at 6 or 9 h after the challenge. ZCR-2060 (1 mg kg^?1 p.o.) clearly inhibited the increase of eosinophil numbers in BALF. Moreover, the effect of ZCR-2060 on inflammatory cell activation in terms of chemotaxis and superoxide generation in-vitro was studied. ZCR-2060 (10^?6-10^?4 m ) inhibited the platelet-activating factor (PAF)-induced chemotaxis of eosinophils and neutrophils, but did not inhibit the leukotriene B₄-induced chemotaxis of eosinophils and the formyl-Met-Leu-Phe-induced chemotaxis of neutrophils. PAF-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages was inhibited by ZCR-2060 (10^?6-10^?4 m ). However, ZCR-2060 did not affect phorbol myristate acetate-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages. These results indicate that ZCR-2060 inhibits allergic airway inflammation, and PAF-induced inflammatory cell activation in guinea-pigs. ZCR-2060 may prove useful for the treatment of allergic airway inflammation or allergic disorders, especially inflammatory cell infiltration and activation.     

An Unusual Variant of Chromosome 16 in Three Generations

An unusual variant of chromosome 16, 16p+, in three generations is described. This is the first clinical report of 16p+ in Japan.     

A combination of preductal aortic coarctation and type B dissection: Report of a case

(Received for publication on Sept. 12, 1996; accepted on May 12, 1997)     

Reduction of myocardial infarct size by early intracoronary thrombolysis as assessed by serum cardiac myosin light chains and left ventricular function

Cardiac myosin light chains are released from the infarcted myocardium soon after the onset of infarction, and the level of myosin light chains in the serum reflects infarct size, regardless of the presence of early coronary reperfusion. In this study, we used serum myosin light chains and assessed changes in left ventricular function to evaluate the effects of intracoronary thrombolysis on infarct size, with special reference to the interval between the onset of infarction and the time of reperfusion. Forty patients with acute myocardial infarction who underwent coronary angiography and intracoronary thrombolysis for the left anterior descending artery (LAD) early after the onset of infarction were categorized in four groups: in group A (n = 9) the LAD was already patent at the start of intracoronary thrombolysis, in group B (n = 12) antegrade flow in the LAD was achieved within three hours of the onset of symptoms, in group C (n = 10) antegrade flow was achieved later than three hours after the onset of symptoms, and in group D (n = 9) antegrade flow in the LAD was not achieved. The peak appearance time of creatine phosphokinase (CPK) in group D was significantly later than in the other groups. The total release of CPK in group C (3,119 +/- 414 IU/l) was greater than that in group A (1,332 +/- 346 IU/l) (p less than 0.01), but the total CPK release in group D (2,525 +/- 525 IU/l) was not statistically different from those of any other group. In all four groups myosin light chain I appeared in the serum from the first day on and reached their peak values between the third and fifth days. The peak values of myosin light chain I were 14.7 +/- 2.1 ng/ml for group A, 16.3 +/- 2.3 ng/ml for group B, 24.6 +/- 2.4 ng/ml for group C, and 25.1 +/- 1.8 ng/ml for group D. The peak myosin light chain levels in groups A and B were less than those in groups C and D. Twenty-nine of the 40 patients had no previous episodes of infarction, and these 29 patients were classified in two groups according to the Forrester's subset class on the first day: four of seven patients in group D were in subsets II, III or IV; whereas, the majority of patients in groups A, B and C were in subset I.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of Kearns-Sayre syndrome with impaired respiratory regulation]

We reported a case of Kearns-Sayre syndrome with impaired respiratory regulation. A 55-year-old male was admitted to our hospital complaining of chronic progressive external ophthalmoplegia, limb muscle weakness and dyspnea. On admission, because arterial blood gas analysis showed marked alveolar hypoventilation, ventilatory response was measured and diminished chemosensitivity to both hypoxia and hypercapnia was found. His vital capacity and forced expiratory volume in 1 second were slightly decreased, and a chest X-ray film revealed a moderate degree of elevation of the bilateral diaphragm. Therefore, we considered that the diminished response to hypoxia and hypercapnia in this case was caused by an impairment of the respiratory center, as well as chemoreceptors and also the presence of respiratory muscular weakness.     

Active cutaneous anaphylaxis (ACA) in the mouse ear.

Active cutaneous anaphylaxis (ACA) was studied in the ear of female BALB/c mice. Mice were immunized with ovalbumin in the presence of aluminium hydroxide gel or complete Freund's adjuvant (CFA). Two weeks after the immunization, ACA was elicited in the mouse ear by injecting 10 microliters of antigen solution intradermally into the ear lobe. ACA was assessed by the amount of extravasated dye, which was given intravenously just after the antigen injection. Antiallergic drugs (tranilast, ketotifen and azelastine), antihistamines (chlorpheniramine, diphenhydramine and mequitazine), beta-stimulants (isoproterenol and salbutamol), theophylline and glucocorticoids (hydrocortisone, prednisolone and dexamethasone) inhibited the reaction significantly. These drugs inhibited both ACA in mice immunized with alum-precipitated antigen and ACA in mice injected with CFA-emulsified antigen similarly. ACA in the mouse ear might be a useful tool for studying drugs for allergy.