Antiplatelet Drugs Plus Thrombolysis in Myocardial Infarction

A breakthrough in platelet inhibition was achieved with the advent of antagonists of the glycoprotein (GP) IIb/IIIa receptors. These receptors are essential to platelet aggregation triggered by any of several different mechanisms. GP IIb/IIIa receptor antagonists, especially the monoclonal antibody abciximab, have been established as adjuncts to angioplasty in acute coronary syndromes. Conjunctive treatment with thrombolysis in myocardial infarction has been studied less extensively. GP IIb/IIIa receptor antagonists appear to be a feasible adjunct to thrombolysis. In particular, the use of abciximab in conjunction with reduced doses of thrombolytics is an attractive approach to achieve early coronary reperfusion with probably acceptable bleeding risk. The eventual role of this combined treatment can only be defined by the large-scale clinical trials that will be performed in the near future.     

Syncytial organization of acanthors of Polymorphus minutus (Palaeacanthocephala), Neoechinorhynchusrutili (Eoacanthocephala), and Moniliformis moniliformis (Archiacanthocephala) (Acanthocephala)

The fine structures of immature and of developed shelled acanthors of three species belonging to the three subgroups of the Acanthocephala were investigated. Acanthors are surrounded by four eggshells (embryonic envelopes) and are composed of three syncytia: a frontal syncytium, a central syncytium, and an epidermal syncytium. Neither a sense organ nor a nervous system has been found. The central syncytium shows a mass of condensed nuclei and 12 decondensed nuclei and gives rise to 10 anterior/posterior subepidermal myofibrillar systems and 2 oblique retractor muscles. Circular muscles are missing. A single decondensed nucleus can be assigned to each of the 12 muscular systems. The epidermal syncytium embeds the other two syncytia and forms the wrinkled epidermis, which shows an extracellular glycocalyx and intrasyncytial condensations. Prominent recurved hooks, which mark the anterior end of each acanthor, and body spines are intraepidermal differentiations. Partly branched tubular infoldings of the epidermal plasma membrane of the acanthor exist and represent precursors of the pore ducts typical of the adult epidermis. Autapomorphies in the ground pattern of the monophylum Acanthocephala are the four eggshells, the early development of three syncytia, the condensed nuclei in the central syncytium, and the differentiation of ten longitudinal muscle bands and two muscle retractors and of intraepidermal hooks and spines. The syncytial organization of the epidermis with intraepidermal skeletal condensations and infoldings of the apical plasma membrane are characteristics inherited from a stem species common to Acanthocephala, Seison, and Rotifera. Received: 25 September 1996 / Accepted: 10 October 1996     

Endogenous brain angiotensin II disrupts passive avoidance behavior in rats

The presence of angiotensinogen, the precursor of angiotensin II (ANG II), in brain tissue and in cerebrospinal fluid (CSF) allows stimulation of endogenous brain ANG II by renin. Passive avoidance tests were performed in female Wistar rats. The animals received an electrical shock after entering a black box on the first experimental day. Avoidance was tested every 24 h for 5 consecutive days. Renin in doses of 0.01 and 0.1 units was injected once into the lateral brain ventricles 2 min before the first test. CSF ANG II increased from 40 to 4547 and 5152 fmol per ml (means), respectively. A dose-dependent disruption of avoidance learning was observed, the frequency to enter the black box increasing from 11% (control) to 29% and 46%, and the latency decreasing from 165 (control) to 143 and 116 sec, respectively. These effects were statistically significant (P less than 0.001) for more than 24 h and returned to control levels after 48 to 120 h. Administration of the converting-enzyme inhibitor SQ 14225 i.v.t. prior to renin injections abolished the renin effects. Injections of renin given 22 h after learning were without effect.     

Quantitative histologic studies of the gonads of sand rats (Psammomys obesus) during the development of diabetes mellitus]

Quantitative-histological investigations (point counting method) are pointed out in 27 male and 15 female sand rats. The animals are divided in the IGT (impaired glucose tolerance), the diabetic and the control group. The LEYDIG cells are in the IGT-group increased, and in the diabetic group decreased. The female sand rats are characterized by the tendency of increase of size and number of follicles in the IGT-group. Corpora lutea are reduced but atretic follicles are increased in the diabetic group. The ovaries are greater in diabetic sand rats.     

Induction of chromosome aberrations and mitotic arrest by cytomegalovirus in human cells

Human cytomegalovirus (CMV) is potentially an effective but often overlooked genotoxic agent in humans. We report here evidence that indicates that infection by CMV can induce chromosome alterations and mitotic inhibition. The frequency of chromosome aberrations induced was dependent on the input multiplicity of infection (m.o.i.) for human lung fibroblasts (LU), but not for human peripheral blood lymphocytes (PBLs) when both cell types were infected at the GO phase of the cell cycle. The aberrations induced by CMV were mostly chromatid breaks and chromosome pulverizations that resembled prematurely condensed S-phase chromatin. Pulverized chromosomes were not observed in LU cells infected with virus stocks that had been rendered nonlytic by UV-irradiation at 24,000 ergs/mm2 or from infection of human lymphocytes. In LU cells infected with UV-irradiated CMV, the frequency of aberrations induced was inversely dependent on the extent of the exposure of the CMV stock to the UV-light. In permissive CMV infection of proliferating LU cells at 24 hr after subculture, a high percentage (greater than 40%) of the metaphase cells were arrested at their first metaphase and displayed severely condensed chromosomes when harvested 48 hr later. A significant increase (p less than 0.05) in the chromosome aberration frequency was also observed. Our study shows that CMV infection is genotoxic to host cells. The types and extent of damage are dependent on the viral genome expression and on the cell cycle stage of the cells at the time of infection. The possible mechanisms for induction of chromosome damage by CMV are discussed.     

Herpesvirus saimiri has a gene specifying a homologue of the cellular membrane glycoprotein CD59.

Herpesvirus saimiri (HSV) is a T-lymphotropic tumor virus that causes fulminant lymphomas and leukemias in various New World primates other than its natural host, the squirrel monkey (Saimiri sciureus). In the course of completing the nucleotide sequence of its genome, we identified an open reading frame of 363 nucleotides, designated HVS-15, that has no detectable homology to any other viral sequences to date. HVS-15 encodes a 121-amino-acid protein which shows significant similarities to human CD59, a phosphatidyl-inositol-glycan-anchored glycoprotein involved in T-cell activation and restriction of complement-mediated lysis. The predicted HVS-15 gene product is more similar to human CD59 than to the related murine Ly-6 antigens. A nucleotide sequence identity of 64% was found between HVS-15 and the CD59 reading frame, and a 48% identity exists between the corresponding protein sequences. The comparison of the amino acid sequences revealed a number of conserved structural features such as a similar pattern of hydrophobic termini and an identical cysteine skeleton.     

Correlation of the chemical structure of 4-nitroquinolines inactivating human cytomegalovirus and established in vivo carcinogenicity tests

Inactivation of the infectivity of human cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) has been observed following exposure to 4-nitroquinoline 1-oxide (NQO) or its metabolite, 4-hydroxyaminoquinoline 1-oxide (HAQO). The present study of the specificity of the chemical structure of 4-nitroquinolines demonstrated that both the 4-nitro and 1-oxide groups were required for inactivation of virus infectivity. Reduction of the 4-nitro group to a 4-hydroxyamino group enhanced activity, while further reduction to an amino group resulted in loss of activity against virus infectivity. The capacity to inactivate virus was also lost by substitution of the pyridine ring for the quinoline nucleus of NQO. The relationship between the chemical structure and the ability to inactivate viruses studied here correlates well with earlier in vivo carcinogenicity studies of the same group of chemicals.     

Alterations in alanine metabolism in diabetic dogs during short-term treatment with an artificial B cell

Summary The flux rates of plasma glucose and alanine were studied isotopically (6-³H-glucose and U-¹⁴C-alanine simultaneously) in resting chronically diabetic dogs during short-term treatment with an artificial B cell where the insulin was infused into a peripheral vein. Despite perfect blood glucose control and normal glucose flux rates, the concentration and rates of appearance and disappearance of alanine were significantly elevated in the diabetic animals before, during and after an exogenous glucose load. The incorporation of the carbon moiety of alanine into circulating glucose was also increased, but diminished to a near-normal extent when exogenous glucose was given. The plasma clearance rates for alanine in the diabetic dogs were normal throughout the study. It is concluded that normal blood glucose control in diabetes does not necessarily mean normalization of the entire metabolic network. On the basis of peripheral hyperinsulinaemia alanine formation from glucose and branched chain amino acids is elevated in muscle. This may explain increased flux of alanine despite normal blood glucose control.     

Repeated short periods of regional myocardial ischemia: effect on local function and high energy phosphate levels

Summary The effect of recurrent periods of ischemia on the myocardium was investigated in 15 open-chest dogs. Ischemia was produced by 3 minutes of proximal occlusion of the left anterior descending coronary artery. Each occlusion was followed by reperfusion of 3 minutes duration. Forty occlusions with a total of 120 minutes of ischemia were performed, and regional function (sonomicrometry) as well as high energy phosphates (needle biopsies) were determined at the end of the 5th, 20th, and 40th period of ischemia and reperfusion. The first periods of ischemia had a cumulative effect both on regional postischemic function (44% and 59% respectively of preischemic control after 20 occlusions) and on the ATP content, but with increasing number of occlusions the additive effects became smaller (ATP reduction/mol/gww/per occlusion). The ATP breakdown per occlusion was diminished with increasing number of periods of ischemia, and no significant adenosine was measured in the ischemic myocardium. Higher than normal postischemic creatine phosphate levels (9.1 mol/g w w at the 40th reperfusion vs. 6.7 mol/gw w control) indicated a functioning oxidative phosphorylation in the presence of an ATP utilization problem at the sarcomere level, because indicators of the cellular energy level (energy charge, free energy change of ATP hydrolysis) quickly normalized during reperfusion. Stunned myocardium is therefore not a problem of energy supply but rather of energy utilization. Reduced ATP utilization and regional dysfunction are the expressions of the same cellular defect which resides either in the ATP-splitting contractile apparatus or in the electromechanical coupling. Contractile dysfunction during reperfusion protects the heart against subsequent periods of ischemia because ATP turnover is reduced.Parts of the results were presented at the 57th Sessions of the American Heart Association, Miami, Florida/U.S.A. 1984