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We assessed the usefulness of gerbils as an experimental model for neurologic toxocarosis. Mongolian gerbils, Meriones unguiculatus, infected with Toxocara canis or Toxocara cati (1000 eggs/gerbil) showed progressive neurologic disorders from 50 days after infection in T. canis-infected gerbils or from 120 days after infection in T. cati-infected gerbils. The incidence of the onset was 6 of the 13 gerbils (49%) in the T. canis-gerbils and 5 of the 7 gerbils (71%) in the T. cati-gerbils. Histopathologically, the cerebellum was the most affected in both groups. We observed loss of Purkinje cells, glial nerve fibers, and nerve sheaths. We also found foci consisting of aggregated macrophages scattered in the white matter of the cerebellum. The affected gerbils showed ataxia and ultimately died of cachexia. Our findings suggest that irreversible neurologic toxocarosis in gerbils can be induced by infection with either T. canis or T. cati.

Anti-Thy-1.1 nephritis in the rat is a popular experimental model for mesangial proliferative glomerulonephritis (GN). This model is characterized by direct binding of anti-Thy-1.1 antibody with Thy-1.1 antigen expressed on mesangial cells (MCs) of glomeruli in the rat. A single injection of anti-rat thymocyte serum (ARTS) results in GN with proteinuria and extensive mesangiolysis. Development of mesangiolysis and proteinuria are complement-dependent. We previously demonstrated Thy-1.1 antigen, similar to the rat, in thymocytes, brain cells and MCs of the kidney in the Mongolian gerbil (MG). In this study, we attempted to develop a MG nephritis model, but an injection of ARTS did not induce GN. An additional injection of guinea pig serum as a complement after ARTS injection resulted in anti-Thy-1.1 nephritis in MG. Degeneration of MCs and neutrophil infiltration were observed 1 hr after GP serum injection. Mesangiolysis and fibrin exudation occurred 12 hr after the injection and MC proliferation was apparent 7 days after the injection. In the complement-dependent hemolytic test, MG serum could not hemolyze sheep erythrocytes. These results suggested low activity, or depletion of some factors, in complements of MG serum.

Thoracic paravertebral anesthesia was not believed to accompany numbness in the lumbar nerve region. However, we recently discovered that thoracic paravertebral anesthesia could produce analgesia in the lumbar region. We called this block extended unilateral anesthesia. In this study, appendectomy was attempted in rabbits with extended unilateral anesthesia. After a catheter was inserted into the endothoracic fascia in the paravertebral region on the right side at the level of the 11th thoracic vertebra, a 3-ml dose of 2% mepivacaine was injected repeatedly through the catheter. After an injection of the local anesthetic we could observe motor and sensory paralysis unilaterally from the chest down to the lower limb in all the rabbits, the extended unilateral anesthesia. With this anesthesia, we could accomplish appendectomy. This is the initial report of extended unilateral anesthesia applied to appendectomy in rabbits. We think that this anesthesia could be beneficial in future medical and veterinary use.

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.

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.

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.

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.

This study was designed to clarify the developing mechanism of cardiomyopathy and vasculopathy in streptozotocin-treated Mongolian gerbils. Twenty male Mongolian gerbils (MG; 10-12 weeks old) were used, and 150 mg/kg of streptozotocin (STZ) was injected into the left femoral vein. Six control male MG were injected intravenously with normal saline. The animals showed severe hyperglycemia (up to 330 +/- 96.4 mg/dl) by 1 week after streptozotocin administration. At 1 week after STZ treatment, cardiomyocytes revealed no significant change, but unclear striated structures were demonstrated in cardiomyocytes at 4 weeks. After 1 year, anisocytosis was observed, and in the perinuclear region granular components were stained positively with periodic acid-Schiff reagent. Ultrastructurally, at 4 weeks and 1 year after STZ treatment, cardiomyocytes were irregular in size, and oval amorphous and lysosomal electron-dense bodies were observed in perinuclear and cytoplasmic regions. In coronary arteries, endothelial and medial cells revealed increased vesicles and intercellular collagen fibrils. Capillaries showed slight swelling of endothelial cells associated with the lamellar thickening of basement membrane and collagen fibrils in the perivascular regions. Immunohistochemically, advanced glycation end products (AGE) were observed in the cytoplasm of vascular and heart cells, and ultrastructurally the reaction products were demonstrated in the endoplasmic reticulum and lysosomes of cardiomyocytes and vascular cells in the STZ-treated Mongolian gerbils. AGE may play an important role not only in angiopathy but also in cardiomyopathy of STZ-treated Mongolian gerbils after STZ treatment.

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.

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.

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.

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.

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.

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.

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.

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 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.