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.     

Subjective ratings of sleepiness--the underlying circadian mechanisms

Previous field and laboratory studies have revealed that there is a diurnal variation in subjective sleepiness that is different in form to that of objective sleepiness and many measures of performance efficiency. The worst subjective sleepiness occurs at the trough in the circadian temperature rhythm, the least subjective sleepiness about 7 h before the peak in temperature. A series of forced desynchronization experiments, in which the endogenous circadian oscillator controlling the temperature rhythm ran at a different period to the sleep/wake cycle, revealed that these findings can be explained by postulating subjective sleepiness to be under the control of both factors, with minimum sleepiness occurring at the peak in temperature in terms of the temperature cycle and about 6 h after waking in terms of the sleep/wake cycle.     

A comparison of Nd:YAG laser damage thresholds for PMMA and silicone intraocular lenses

Power density producing damage at a probability of 0.5 (ie, damage threshold, DT-50) was determined for PMMA (with/without UV absorber) and Silicone intraocular lenses. Scattered light from a collinear diagnostic He:Ne beam was one of four damage monitors deployed to enhance the sensitivity of the system. In order of increasing laser resistance the following results were obtained: injection molded PMMA (1.9/GW/cm2) Silicone (2.63 GW/cm2) Lathe-cut PMMA (4.47 GW/cm2), Lathe-cut PMMA with UV absorber (8.32 GW/cm2), Cast-molded PMMA (12.30 GW/cm2). An analysis of variance revealed interclass differences significant at the .01 level. Cast-molded PMMA was the most laser-resistant IOL material.     

Immunohistochemical characterization of extracellular matrix in the developing human cornea

Collagen, fibronectin and laminin are important components of the extracellular matrix of the human cornea. We used the immunofluorescence technique with polyclonal antibodies directed against these proteins and to bullous pemphigoid antigen (BPA), in order to study their distribution in human corneas from 8 weeks of gestation to term and in adult corneas. Immunoreactivity was observed with antibodies to type I collagen in the limbus and the corneal stroma at 8 weeks of gestation. At 11 weeks of gestation it was found in epithelial basement membrane (EBM) and Descemet's membrane (DM) and continued thus throughout fetal and adult life. Type II collagen was not detected in fetal or adult cornea. Type III collagen was detected during 8-20th weeks of gestation in the EBM, DM and stroma. After 27th weeks of gestation, type III collagen could no longer be detected in the central cornea. Type IV collagen was detected in the EBM as early as 8 weeks of gestation and remained positive throughout fetal and adult life. Descemet's membrane was negative for type IV collagen at 8 weeks of gestation and became positive thereafter. Immunostaining for fibronectin in DM was negative at 8 weeks of gestation, followed by patchy staining of corneal stroma and EBM up to the age of 37 weeks of gestation. Staining in the EBM was negative or variable up to 70 years of age, and then became positive again in a 77 year old individual. Staining for LN was positive in the EBM after 8 weeks of gestation. Staining was negative in DM at that age, but became positive after 9 weeks of gestation. Staining for BPA was negative at 8-9 weeks of gestation, then gradually became positive.     

Synthesis and bacterial mutagenicity of the cyclopenta oxides of the four cyclopenta-fused of isomers of benzanthracene

Many polycyclic aromatic hydrocarbons containing peripherallyfused cyclopenta rings are believed to be activated primarilyby epoxidation of the cyclopenta ring. The cyclopenta epoxidesof a series of four cyclopenta benzanthracene derivatives, benz[e]aceanthrylene-5,6-oxide,benz[j]ace-anthrylene-1,2-oxide, benz(l)anthrylene-1,2-oxideand benz[k]acephenaceanthrylene-4,5-oxide were synthesized fromtheir parent hydrocarbons by formation of the bromohydrin followedby dehydrobromination, and characterized by u.v. – vis,and ¹H n.m.r. spectroscopy and mass spectrometry. The mutagenicityof these compounds was investigated in the Ames plate incorporationassay with Salmonella typhimurium strain TA98. All the oxideswere active without exogenous metabolic activation (170–320His⁺ revertants per nanomole) and also toxic above 0.5 µg/plate.Addition of S9 protein did not increase, and generally decreased,the mutagenicity of the oxides, while toxicity was largely unchanged.These results are consistent with the postulated role of cyclopentaoxides as major contributors to the mutagenicity of the parentcompounds in the Ames assay.     

Immunological mechanisms giving rise to latency of herpes simplex virus in the spinal ganglia of the mouse

In the model of genital herpes simplex virus (HSV)-infection of mice, early latency could be induced by passive immunization with HSV-specific antibodies and, to a lesser degree, by adoptive transfer of immune lymphocytes prepared from spleen and draining lymph nodes of genitally infected syngeneic mice. Conversely, spontaneously occurring latency was inhibited by treatment of the animals with cyclophosphamide (Cph) and, to a lesser degree, with cyclosporin A (CyA). Whereas the effect of CyA could be compensated by passively administered HSV-specific antibodies, that of Cph could not. Apparently specific antibodies cooperate with a non-specific proliferating cell type, probably macrophages and/or NK-cells, as could be demonstrated by significantly reduced antibody effect in silica-treated mice. Moreover, F(ab)₂ fragments, in contrast to complete antibody molecules, were inactive. HSV-specific antibodies and also immune lymphocytes had little effect on virus production in the mucous membranes, immune lymphocytes being at least as active as antibodies. It is therefore not probable that latency is induced by attenuation of the peripheral disease. It can rather be concluded that the neuron itself is the target for the action of specific antibodies, cooperating in turn with macrophages and/or NK cells.With support of the Deutsche Forschungsgemeinschaft, Schn 174/6-3     

Intra-arterial thrombolysis for acute limb ischemia: a three-year experience

Peripheral arterial thromboembolism and thrombosis of arterial grafts continue to threaten viability of extremities. Percutaneous intra-arterial thrombolysis (IAT) and angiodilatation have afforded limb salvage in some of these patients. Proper patient selection appears to be the hallmark of success with IAT. During a recent three-year period, we used IAT in 32 extremities in 28 patients who had acute arterial insufficiency. Before IAT, 16 extremities were painful at rest, and 16 had incapacitating claudication. The overall success rate was 38%, but some degree of thrombolysis occurred in 88%. Limb salvage was achieved in 27 of 32 extremities (84%). Only five of 17 limbs (29%) with arterial graft thrombosis required no operation or an operation of lesser magnitude than predicted before IAT. Of six extremities with native arterial embolism, four (67%) were completely cleared with IAT. Major complications occurred in eight cases (25%), with two IAT-related deaths (6%). This study suggests that IAT is best reserved for individuals with acute limb ischemia caused by arterial embolus, those whose degree of ischemia would tolerate a 24-hour trial of IAT, and those whose femoral or tibial runoff is not likely to require remedial operation.     

Stellenwert der Second-look-Laparotomie im Behandlungsschema des progredienten Ovarialkarzinoms

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