Migration behaviour and pathogenesis of five ascarid nematode species in the Mongolian gerbil Meriones unguiculatus.

To understand the characteristic features of the Mongolian gerbil, Meriones unguiculatus, as an animal model of ascarid infections, the migration behaviour and pathogenesis of larvae were investigated in experimentally infected gerbils. Embryonated eggs from each of Toxocara canis, Baylisascaris procyonis, B. transfuga, Ascaris suum, and A. lumbricoides were orally inoculated into gerbils and larvae were recovered from various organs at designated periods. In T. canis-infected gerbils, larvae were present in the liver 3 days after infection and in the skeletal muscle and brain via the heart and lungs at a similar rate. In B. procyonis- and B. transfuga-infected gerbils, larvae were present in the lungs within 24 h after infection, with some having reached the brain by that time. After 24 h, larvae of B. procyonis tended to accumulate in the brain, while those of B. transfuga accumulated in skeletal muscles. In A. suum- and A. lumbricoides-infected gerbils, larvae remained in the liver on day 5 post-infection and elicited pulmonary haemorrhagic lesions, which disappeared 7 days after initial infection. Thereafter, no larvae of any type were recovered. Ocular manifestations were frequently observed in T. canis- and B. procyonis infected gerbils, but were rare in B. transfuga-infected gerbils. In the cases of A. suum and A. lumbricoides, migration to the central nervous system and eyes was extremely rare, and larvae had disappeared by 2 weeks post-infection. Fatal neurological disturbances were observed in B. procyonis-infected gerbils, whereas irreversible non-fatal neurological symptoms were observed in the case of B. transfuga.

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.

Ultrastructural changes and immunohistochemical localization of nitric oxide synthase, advanced glycation end products and NF-kappa B in aorta of streptozotocin treated Mongolian gerbils.

To evaluate the relationship among the induction of nitric oxide synthase (NOS), advanced glycation end products (AGEs) and NF-kappa B for vascular damage 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 and electron microscopical techniques. After STZ treatment, hyperglycemia was confirmed and body weight transiently decreased. Morphological observation revealed no remarkable changs in vascular endothelial cells or vascular smooth muscle cells in the aorta at one week after STZ administration. After 4 weeks increased collagen fibrils were observed in the pericellular spaces of media. At one year after STZ administration, increased collagen fibrils and thickened elastic fibers were found around the vascular smooth muscle cells with vacuolization and increased cytoplasmic organellae compared with non-treated animals of the same age. Immunohistochemically endothelial constitutive NOS (ecNOS) was localized in the endothelium of the aorta of Mongolian gerbils. At one year after STZ administration, the reaction products of iNOS, AGEs and NF-kappa B in vascular endothelial cells and smooth muscle cells were much more greatly increased than at one week and 4 weeks. After STZ administration, the localization of NOS, AGEs and NF-kappa B was observed in the aorta, which suggests these factors play important roles in the pathogenesis of vasculopathy in diabetes mellitus.

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.

Electrophoretic study of lactate dehydrogenase and alkaline phosphatase isoenzymes of the Mongolian gerbil (Meriones unguiculatus).

Lactate dehydrogenase and alkaline phosphatase isoenzymes of the Mongolian gerbil were examined using electrophoretic techniques and were compared with those of the mouse, rat, and guinea pig. Five isoenzymes of lactate dehydrogenase (LDH) were detected in the gerbil with LDH2 and LDH5 being equally dominant. Two bands of alkaline phosphatase (ALP) were distinguished in sera treated with neuraminidase in the gerbil and the relative activity of the cathodic fraction was greater than those of the mouse and rat. Genetic polymorphism was not found among the coat color variants of the Mongolian gerbil. A comparative study on LDH and ALP revealed distinct interspecific differences in the rate of the electrophoretic migration of the respective isoenzymes among the mouse, rat, guinea pig, and the Mongolian gerbil.

Effect of M-711 on experimental skin reactions induced by chemical mediators in rats.

We investigated the mechanism of anti-allergic action of Moku-boi-to (M-711) and effects on the skin reactions induced by chemical mediators as the model of allergic dermatitis. More than 20 mg/kg BW of M-711 significantly suppressed the enhancement of capillary permeability induced by histamine, LTC4, and anti-serum in the rat skin. Anti-histaminic effect of 40 mg/kg BW of M-711 was equipotent to same as the optimal doses of azelastine and diphenhydramine, respectively. As to anti-LTC4 action, 20 mg of M-711 was compared to the optimal dose of diphenhydramine. Those data showed that M-711 has the suppressive effects on the chemical mediators such as histamine and LTC4 and reduced the skin reaction induced by antigen-antibody response.

Effect of M-711 on experimental asthma in rats.

We experimentally demonstrated the anti-asthmatic effects of M-711, the dry extract of a Chinese herb medicine called Mokuboi-to, using the rat model of allergic asthma. Allergic asthma was induced by the antigen-antibody reaction in the rats and they showed anaphylactic symptoms accompanied with hypotension and depression of respiratory function. More than 20 mg/kg body weight of M-711 was effective in relieving the asthmatic symptoms like methylephedrine. It could lessened the suppress of respiration and provided a good improvement. It also reduced a drop of the blood pressure and improved it quickly. Its ingredients alone were much less effective than M-711 as the total. Those data suggested that M-711 was effective for alleviating allergic asthma in the present study and that its action was provided by interaction of all ingredient raw herbs of M-711.

Effect of rearing conditions on encephalomyocarditis (EMC) virus-induced diabetes in mice.

To compare the incidence in the diabetic syndrome in mice reared under sterile and non-sterile conditions, both conventional and SPF DBA/2 N male mice were inoculated intraperitoneally with two doses (10(4) TCID50/0.1 ml or 10(5) TCID50/0.1 ml) of encephalomyocarditis (EMC) virus M variant. The incidence of diabetic symptoms was higher in mice reared under sterile conditions than under non-sterile conditions. It appeared that a difference in animal rearing conditions would affect the sensitivity to EMC virus in mice.

Decrease in mitogen-induced lymphocyte proliferative responses in cats infected with feline immunodeficiency virus.

The blastformation tests using concanavalin A and pokeweed mitogen were carried out on peripheral blood lymphocytes obtained from cats infected with feline immunodeficiency virus (FIV). The infected cats included those showing multiple chronic disease, those with a single mild sign, and one with no clinical sign. The infected cats showed significantly lower mitogenic responses of peripheral lymphocytes to both mitogens and lower lymphocyte counts as compared to uninfected healthy cats. These immunologic alterations in the infected cats may be closely related to the development of immunodeficiency-like disorders associated with FIV.

Kidney complications in EMC virus-induced diabetes in conventional DBA/2 male mice.

Conventional DBA/2 male mice of about 9 weeks of age were inoculated by intraperitoneally injecting EMC virus M variant (10(4) TCID50/0.1 ml/animal) which is passaged in mice. The mice which tested positive for glycosuria and hyperglycemia were examined histopathologically 2 or 5 months after inoculation. The kidneys were examined for thickening of Bowman's capsule and the mesangial matrix. These changes were more clearly observable 5 months after inoculation than they were 2 months after inoculation.

Renal lesions in a strain of spontaneously diabetic WBN/Kob rats.

In WBN/Kob strain rats, only males spontaneously develop hyperglycemia, glycosuria, hypoinsulinemia and glucose intolerance from about nine months of age. The kidneys of male rats of this strain were histopathologically studied to evaluate the changes which appeared as complications of diabetes mellitus. Thickening of the basement membrane, increase of the mesangial matrix and fibrin-cap lesions were noted in the glomeruli. Armanni-Ebstein degeneration was occasionally found in the tubules. Linear deposition of plasma components such as IgG and albumin in the basement membrane of the glomeruli, tubules and Bowman's capsule characterized the immunohistological pattern. These findings are similar to the findings in diabetic nephropathy in humans. Since the onset of diabetes mellitus in the strain is slow and symptoms are generally mild, insulin administration is usually not necessary for survival. This strain, therefore, appears to be an important animal model for the study of complications of diabetes in humans.

Spontaneous diabetes-like syndrome in WBN/KOB rats.

Spontaneous hyperglycemia, glycosuria, hypoinsulinemia, and glucose intolerance were observed in some WBN/Kob rats, at about 9 months of age, and in all at the age of 17 months. Females did not present this pathology. Histopathologic examination of the pancreas revealed severe changes in male rats at the age of 3 months. Between 3 and 6 months of age a distinct infiltration of inflammatory cells was found around islets and among adjacent acinar cells. At the same time, marked fibrosis was seen around the pancreatic ducts and blood vessels. With advancing age the fibrous tissue gradually invaded extensive areas of the pancreas where also the islets became involved in fibrotic degeneration. At 17 months of age and later, an obvious decrease in islet number and size (less than 50 mu in diameter) was observed, even in relatively unaffected areas of the organ. Frequent bilateral cataracts began to appear at about 15 months of age. Opacities were first observed in the periphery of the lens, then increased rapidly in intensity and extended centripetally. Nineteen-month-old male rats were hypersensitive to exogenous insulin, but showed no significant decrease in blood glucose level when treated with oral tolbutamide. These results suggest that these rats suffered from a decreased insulinogenic response.