A method for evaluating antianginal drugs in experimental animals: assessment of myocardial ischemia by myocardial pH

This paper describes a method by which antianginal drugs can be evaluated in the dog heart in situ. Myocardial pH was measured continuously by a micro glass pH electrode inserted in the left ventricular endocardial layers of the dog anesthetized with pentobarbital. Occlusion of the left anterior descending coronary artery (LAD) decreased myocardial pH, and release of the LAD restored the pH. The myocardial acidosis induced by ischemia was metabolic in nature and accompanied by a decrease in the levels of adenosine triphosphate and creatine phosphate and an increase in the levels of lactate in the myocardium. Drugs were injected intravenously 30 min after incomplete (partial) occlusion ot the LAD, lasting until 60 min after drug injection. Propranolol, atenolol, and sotalol markedly attenuated the myocardial pH that had been decreased by LAD occlusion. Nitroglycerin, diltiazem, and nicorandil also attenuated the pH, but these drugs were less active in attenuating myocardial acidosis. Dipyridamole, nifedipine, and beta-2 adrenoceptor antagonists were least active in this regard. It is concluded that myocardial pH can be used as an indicator of myocardial regional ischemia and utilized for evaluation of antianginal drugs.     

Attenuation of benzodiazepine-induced passive avoidance deficit by post-training administration of muscimol: interaction with the cholinergic neuronal system

We examined the involvement of GABAergic neuronal systems in benzodiazepine-induced passive avoidance deficit. Chlordiazepoxide impaired the passive avoidance response dose dependently when it was given prior to training. Post-training administration of muscimol improved the performance of chlordiazepoxide-pretreated mice. The effects of muscimol were antagonized completely by the GABAA antagonist, bicuculline, and the muscarinic acetylcholine receptor antagonist, scopolamine, but not by the benzodiazepine receptor antagonist, flumazenil, when the latter was administered immediately after training. It appears from these results that the GABAergic neuronal system plays an important role in the benzodiazepine-induced passive avoidance deficit by interacting with the cholinergic neuronal system.     

Development of a simple image viewer designed for small X-ray field CT equipment 3DX

Objectives To develop a simple image viewer that utilizes image files in general-purpose formats that are written from the original 3DX volume data. Methods We used FLASH MX2004 for Macintosh to develop a simple image viewer. In developing the software for the simple image viewer, we decided that the viewer should provide the following features: (1) be available to both Windows OS and Mac OS, (2) allow interlocking of the 3D images, (3) display image enlargement, and (4) allow distance measurements. The accuracy of the distance measurements was evaluated. Results The procedure was as follows: (1) write 3D images in jpeg format to a folder on i-VIEW; (2) place the folder containing the 3D images into the directory of the simple image viewer software on a PC; (3) start the software and open the window to input the folder name containing the 3D images; and (4) display the 3D images. Our viewer had features such as image enlargement, interlocking 3D images, drawing, and distance measurements. No significant differences were shown between the measurements made by our simple viewer and the actual values of the images in any direction. Conclusions Our image-viewing software for 3DX is beneficial for clinical use.     

An antitumor principle from Euphorbia lathyris

The extract of seeds of Euphorbia lathyris L. showed antitumor activity against Sarcoma 180 ascites in mice. Systematic fractionation of the extract led to the characterization of ingenol-3-hexadecanoate as an active principle, together with an inactive diterpene ingenol-20-hexadecanoate.     

In vivo activity on murine tumors of a novel antitumor compound,N-β-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]phenazine-6-carboxamide sodium salt (NC-190)

Summary A novel antitumor compound, N--dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of >200% in life span (ILS), and 75% of the mice were alive on day 30, when the optimal dose (50 mg/kg, days 1–5) was given. Additionally, the compound had significant activities against i.p. inoculated mouse L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma, sarcoma 180, mouse hepatoma MH134, and rat Yoshida sarcoma and Yoshida ascites hepatoma AH130. The optimal dose resulted in a >280% ILS with a 30-day survival of 50% in mice with L1210 leukemia (100 mg/kg, days 1–5), a 156% ILS in mice with B16 melanoma (50 mg/kg, days 1–5), a 98% ILS with a 90-day survival of 25% in mice with M5076 reticulum cell sarcoma (25 mg/kg, days 1, 5, 9, and 13), a >300% ILS with a 60-day survival of 50% in mice with sarcoma 180 (50 mg/kg, days 3–10), a 148% ILS with a 60-day survival of 25% in mice with MH134 (25 mg/kg, days 1–5), a 129% ILS with a 60-day survival of 12.5% in rats with Yoshida sarcoma (12.5 mg/kg, day 3–10), and a >161% ILS with a 60-day survival of 50% in rats with AH130 (6.3 mg/kg, days 3–10). In the experiments with s.c. inoculated tumors, NC-190 not only inhibited tumor growth, but also increased the life span of mice with Lewis lung carcinoma or B16 melanoma. The 60-day survivors accounted for 60% and 30% in mice with Lewis lung carcinoma and B16 melanoma, respectively. The compound significantly inhibited the spontaneous lung metastasis of Lewis lung carcinoma by more than 90% when eight daily i.v. injections were given. NC-190 was active by the i.p., s.c., and i.v. routes. Five consecutive daily i.p. doses (days 1–5) were more effective than a single dose (day 1), two doses (days 1 and 5), or three doses (days 1, 5, and 9). NC-190 warrants further study as a potential antineoplastic agent against human neoplasms, as it has a broad spectrum of antitumor activity and inhibits metastasis.Abbreviations ILS increase in life span - MST median survival time - MMC mitomycin C - ADM adriamycin - CPA cyclophosphamide - 5-FU 5-fluorouracil     

A New Indole Alkaloid Glycoside from the Leaves of Palicourea marcgravii

A new indole alkaloid glucoside, named palicoside, has been isolated from the leaves of PALICOUREA MARCGRAVII (Rubiaceae) collected in Brazil. The structure was established by spectroscopic methods and its chemical conversion to strictosamide.     

Immunosuppressive effect of restraint stress on the initiation of allergic rhinitis in mice

BACKGROUND: Exposure to acute stressors modulates both innate and acquired immune function. However, little is known about whether stress has the potential to modulate the pathogenesis of allergic rhinitis. OBJECTIVES: To determine the effects of acute restraint stress on the initiation of allergic rhinitis in a murine model. METHODS: CBA/J mice were repeatedly intranasally sensitized with phospholipase A2 (PLA2) from honeybee venom without adjuvant. Restraint stress was applied using uniform cylinders once a week for a continuous 8-hour period, on five occasions in total. Production of PLA2-specific antibodies and degree of nasal and blood eosinophilia were compared between stressed and control mice. RESULTS: Repeated intranasal sensitization with PLA2 induced PLA2-specific IgE and marked eosinophilia in both the nose and blood in CBA/J mice. Exposure to restraint stress significantly inhibited production of PLA2-specific IgE, IgG1 and IgG2a. Conversely, the stress exerted no significant effect on eosinophilia. CONCLUSIONS: Exposure to acute restraint stress inhibits antigen-specific antibody production, but not local or systemic eosinophilia. The results of this study suggest that acute stress has the potential to modulate the initiation of allergic rhinitis.     

HEREDITARY HEMORRHAGIC TELANGIECTASIA WITH MALIGNANT LYMPHOMA An Autopsy Case

A 60-year-old Japanese woman was diagnosed at autopsy as having had hereditary hemorrhagic telangiectasia (HHT) associated with systemic hemangiomas. In her repoduction period, premenstrual epistaxis frequently occurred. At the age of 60, the patient died of malignant lymphoma. At autopsy, multiple telangiectatic spots were noted on the face, limbs and trunk. The paraaortic lymph nodes, which were enlarged and irregularly conglomerated, were histologically diagnosed as malignant lymphoma of the diffuse large cell type. Submucosal telangiectatic lesions were found in the gastrointestinal system from the oral cavity to the rectum. Cavernous hemangiomas were present in various visceral organs including the liver, spleen, small and large intestines, rectum, appendix, uterus, and jejunal and colonic mesenteries. There was an arteriovenous fistula in the left lung. Examination of her family pedigree showed that the patient had an autosomal dominant trait of inheritance. The pathogenesis of the systemic visceral hemangiomas observed in this patient was considered to be similar to that of hamartoma.