Ebola hemorrhagic fever (EHF): mechanism of transmission and pathogenicity.

Hemorrhagic fevers represent a wide spectrum of viral infectious diseases, out-breaking mostly as epidemics, some of them being highly lethal. They range from those caused by bunyaviridae, associated with renal or pulmonary syndromes and those recently emerging and caused by the filoviridae family of thread-like viruses. Among the latter, Ebola hemorrhagic fever (EHF) bears the highest mortality and morbidity rates. One form of the disease has been documented only in monkeys. The human form, has occurred mainly in areas surrounding rain forests in central Africa. Patients present with signs of hemorrhagic diathesis, fever, diarrhea and neurological disorders, leading sometimes to confusion with local endemic diseases. Fatal victims of the disease die of dehydration. Poor hygienic conditions facilitate the spread of the virus. Biologically, the virus seems to target both the host blood coagulative and immune defense systems. Intensive epidemiologic search have failed to establish the definitive natural host of the virus. Twice, with a 19-year interval, major outbreaks have taken place in the Democratic Republic of the Congo. The second major outbreak in the northwestern city of Kikwit in April 1995 will serve here to elucidate the mechanism of the viral infection.

Localization of extracellular matrix and mitogen-activated protein kinase (MAPK) in aorta of streptozotocin treated Mongolian gerbils.

To evaluate the relationship among the extracellular matrix (ECM) and mitogen-activated protein kinase (MAPK) family for the vascular damages in hyperglycemia, we injected Mongolian gerbils intravenously with 150 mg/kg streptozotocin (STZ) and observed over the next one year the resulting aortic changes by immunohistochemical techniques. After STZ treatment, hyperglycemia was confirmed. At 4 weeks after STZ administration morphological observation revealed increased stromal components among the vascular smooth muscle cells (SMCs). Immunohistochemically, extracellular matrices such as fibronectin and laminin were localized in the aorta at 4 weeks and one year after STZ administration. The reaction products of MAPK in vascular SMCs were more increased at one year than at 4 weeks after STZ administration. After STZ administration, the increase of ECM and MAPK was observed in the aorta, which suggests these factors play important roles in the pathogenesis of macrovasculopathy in diabetes mellitus.

Differential susceptibility to Brugia pahangi infection in Mongolian gerbils (Meriones unguiculatus) of different coat colour.

The influence of intraspecific host variables on the response to parasitic infections is an important aspect of host-parasite relationships, yet little is known about this aspect of filariasis for lack of a model. This study presents coat colour mutants of the Mongolian gerbil (Meriones unguiculatus) as potential new models for research into the effects of host genetic variation on response to filarial infection. Peak level of microfilaraemia, eosinophil response, body weight and degree of splenomegaly in gerbils infected with Brugia pahangi varied with agouti, albino, and black coat colour. These results suggested that coat colour-related genes might influence host immune response to developmental stages of the parasite and eosinophil-mediated reaction might cause host damage.

Nafamostat mesilate, a synthetic protease inhibitor, attenuated hypercoagulability in a canine model of hemorrhagic shock.

Hypercoagulability is known to occur in the early phase of hemorrhagic shock. The prolongation of excessive clot formation after recovery from a shock state leads to the formation of microthrombi or disseminated intravascular coagulation which disturbs microcirculation, damaging organ function. The aim of the present study is to investigate the beneficial effect of a synthetic protease inhibitor, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate (nafamostat mesilate), in the attenuation of hypercoagulability in hemorrhagic shock. A model of hemorrhagic shock that simulates the clinical course of injured patients was created in anesthetized dogs. The animals were divided into two groups: a control group (group-C, n = 9) and an experimental group (group-E, n = 9). Animals received saline or 0.2 mg/kg of nafamostat mesilate respectively when their mean arterial pressure declined to 50 mmHg. The serum concentration of hydroxytryptamine (5-HT), prothrombin time (PT), and activated partial thromboplastin time (APTT) were determined as indicators of platelet activity and blood coagulation. In group-C, serum 5-HT was elevated significantly at 60 min after hemorrhagic shock but not so in group-E. The APTT at 30 and 60 min was shorter in group-C than in group-E. The PT at 30 min was also shorter in group-C. Plasma fibrin degradation products (FDP) increased at 60 min after the induction of shock in group-C. The results indicate that inadequate tissue perfusion in shock stimulates blood coagulation and that nafamostat mesilate might be beneficial in decreasing excessive blood coagulation.