Pathogenesis of experimental feline hepatosis

The studies performed have established that in experimental hepatosis, cats show substantial changes in blood morphology, a decrease in the cell transmembrane potential and their impaired ultrastructure. Hepatosis appears as combined dysfunctions of the animal and in subsequent periods of the influence of the etiological factor, inflammatory signs (leukemia and others) appear.     

Babesia canis infection in canine-red blood cell-substituted SCID mice

We have developed a mouse model for Babesia canis infection using severe combined immunodeficiency (SCID) mice whose circulating red blood cells had been substituted with canine red blood cells. Substitution of red blood cells in SCID mice was achieved by repetitive transfusions of canine red blood cells, together with administration of an antimouse red blood cell monoclonal antibody. Following inoculation of canine-red blood cell-SCID mice with B. canis, parasites proliferated in the canine red blood cells that had been transfused into the SCID mice, resulting in much higher parasitaemia than that observed in dogs. In an attempt to demonstrate the utility of this mouse model, three antiprotozoal drugs, diminazene diaceturate, clindamycin and oxytetracycline, were examined for their efficacy to inhibit the growth of B. canis in canine-red blood cell-SCID mice. The mouse model clearly showed that diminazene diaceturate and oxytetracycline were capable of eliminating B. canis from the canine-red blood cell-SCID mice, whereas clindamycin exhibited only a static effect as parasitaemia relapsed upon cessation of drug administration.     

Pathogenesis of Mycobacterium bovis infection in cattle

This paper reviews the pathogenesis of Mycobacterium bovis infection in cattle, focusing on aspects relating to the host rather than the organism. A broad concept of pathogenesis has been considered and information is presented on sources and routes of infection, as well as the immune responses and pathology. In addition, data is presented on the excretion of M. bovis from tuberculous cattle.     

Pathogenesis of pulmonary Cryptococcus neoformans infection in the rat

The pathogenesis of Cryptococcus neoformans pulmonary infection in the rat was studied after intratracheal inoculation. Lungs were examined at various times following infection for histopathology in conjunction with macrophage markers, proliferating cell nuclear antigen (PCNA), and capsular glucuronoxylomannan (GXM) antigen. Serum GXM, immunoglobulin M (IgM) and IgG titers and organ fungal burden were compared with pathological findings. C. neoformans organisms were in the lung parenchyma 2 h postinoculation, and GXM antigen was present in surrounding tissues shortly thereafter. Extrapulmonary dissemination occurred early in infection. Two phases of host cellular inflammatory response were discernible: early local macrophage recruitment at 2 to 4 days followed by granulomatous inflammation, which reached maximum intensity 14 days after infection. The granulomatous phase was preceded by lymphocyte influx with macrophage proliferation and maturation into epithelioid histiocytes; this was paralleled by a shift of yeasts from extracellular to intracellular spaces. Tissue IgG deposits, serum IgG to GXM, and localization of tissue GXM immunoreactivity to epithelioid cells were noted at 2 to 4 weeks. A 10-fold decrease in lung fungal burden occurred 25 days postinfection and was associated with resolving granulomas, fewer proliferating cells, and decreased tissue GXM. The present study demonstrates that (i) C. neoformans penetrates the lung parenchyma shortly after infection; (ii) immunocompetent rats control pulmonary cryptococcosis efficiently, with minimal extrapulmonary dissemination and low levels of serum GXM; and (iii) macrophage activation is likely to play a crucial role in limiting C. neoformans infection in the rat lung.     

Pathogenesis of ocular cytomegalovirus infection in the immunocompromised host

Balb/C nude and C.B-17 SCID mice were inoculated with salivary gland passaged cytomegalovirus (SG-MCMV) intraperitoneally. Dissemination of the virus in the systemic and ocular tissues was studied by the direct immunofluorescence test, and the virus growth in each tissue was titrated in mouse embryonic fibroblasts. The mode of viral spread was assessed by inhibiting macrophage function by silica and administering polyclonal murine anti-MCMV antibody in the circulation. The virus first reached the eyelid, conjunctiva, and cornea. Subsequently, it spread in the outer ocular muscles and chorioretinal layer. Ocular tissues were involved as part of a generalized infection. Abrogation of macrophage function by silica did not affect the outcome of the viral distribution. Administration of antibody prior to and 3 days after the viral infection prevented virus dissemination. Ocular CMV infection occurred initially at the anterior segment of the eye in an immunocompromised host. Free virus, not macrophage-bound virus, disseminated via the bloodstream.     

Risk factors for wound infection following celiotomy in horses

Acute inflammatory polyradiculitis represents an uncommon peripheral nerve complication during HIV infection. The case of an HIV-seropositive patient who was admitted to hospital for a cauda equina syndrome is reported. Despite early application of anticytomegalic medication, a cytomegalovrirus (CMV) infection spread out to the central nervous system (CNS), causing the patient's death. A post-mortem examination confirmed the diagnosis of CMV-encephalomyelomeningoradiculitis. To the authors' knowledge, such a progress of a CMV-related polyradiculitis to an encephalomyelomeningoradiculitis has not yet been described. The clinical features of this case will aid in the recognition of CMV-related neurological complications, and may permit earlier and perhaps more successful treatment.     

Experimental infection of four horses with Ehrlichia phagocytophila

Four clinically healthy horses which were negative for antibodies to Ehrlichia phagocytophila, the agent of bovine ehrlichiosis, were infected experimentally with E phagocytophila-containing bovine leucocytes, administered intravenously. The horses were examined daily for four weeks, and blood samples were collected daily for cytological, haematological and biochemical examination and for a nested polymerase chain reaction (PCR). An indirect immunofluorescence test was used to determine when the horses seroconverted and the duration of positive titres. There were no abnormal clinical, haematological or biochemical findings in any of the four horses and all the PCRs yielded negative results. However, all the horses seroconverted with reciprocal titres of up to 1280, and the positive titres persisted for up to five months.     

Specific immune responses are required to control parasitemia in Babesia equi infection

Horses possessing a normal immune system and spleen often control infection caused by Babesia equi. However, splenectomized horses are unable to control B. equi infection and usually succumb to the infection. To investigate the role of the spleen in the control of B. equi infection in the absence of specific immune responses, two 1-month-old foals with severe combined immunodeficiency (SCID) and two age-matched normal foals were inoculated with B. equi. The SCID foals became febrile seven days postinoculation and developed terminal parasitemias of 41 and 29%. The SCID foals had greater than 50% decreases in indices of total erythrocytes, packed-cell volumes, and hemoglobin concentrations. Both SCID foals were euthanized in extremis at 10 days postinoculation. As expected, the serum of the SCID foals lacked detectable antibodies to B. equi antigens. In contrast, the normal foals inoculated with B. equi produced detectable anti-erythrocyte-stage parasite antibodies by 7 days and controlled clinical disease by 12 days postinoculation. Although SCID foals lack functional T and B lymphocytes, they do possess complement, macrophages, granulocytes, and natural killer cells, as well as a spleen. Therefore, the data indicate that specific immune responses are required to control B. equi parasitemia but are not required for erythrocyte lysis in infected horses. Furthermore, the spleen is not able to control B. equi parasitemia in the absence of specific immune responses to parasite antigens.     

Pathogenesis of heart myofibril lesion in experimental vitamin D-induced cardionecrosis

Multifocal cardionecrosis has been produced in rats by treatment with 3 x 100,000 iu vitamin D3 (calciol). The effects of hypervitaminosis D on rat heart myofibril structure and total protease activity was investigated. Proteolytic enzyme activity of heart muscle homogenate was determined in two independent ways, and was approximately two times higher in the necrotic heart homogenate than in the control rat heart. Electron microscopic examinations showed structural derangements. Myofibrils isolated from necrotic heart exhibited significant changes of ultrastructure in the region of Z-line and I-band. Myofibril enzyme activity (Mg(2+)-ATPase) measurements demonstrated functional deficits as well. Under different conditions of myofibril isolation, it was shown that both ultrastructural and enzymatic lesions appear to be mediated by calcium-activated proteolytic enzymes operating in situ. Our results indicate that the increased proteolytic activity caused by vitamin D treatment leads to the in situ damage of proteins of the heart contractile system.     

Prophylactic treatment of experimental canine babesiosis (Babesia canis) with doxycycline

A single subcutaneous injection of imidocarb at 6 mg kg-1 gave 2 weeks protection against experimental inoculation of Babesia canis merozoites in Beagle dogs. The prophylactic effect was evaluated by daily measurements of parasitaemia, rectal temperature, haematological values and specific antibodies.     

Pathogenesis of multiple sclerosis. Work-hypotheses and experimental data

In spite of a history of more than 100 years, the pathoaetiology of multiple sclerosis is still unknown today. Research is based on three working hypotheses, i.e. on an immunopathological disease origin, on the conception that MS, as an infectious disease, is caused by a specific pathogen (slow virus infection) and on the assumption of a disturbance of basal metabolism or utilisation. The present position of the scientific foundation of the working hypotheses is presented in detail and supplemented by the results of our own investigations. Of particular interest are the geomedical studies which show that MS occurs more frequently in temperate climatic regions. In Europe, a latitude of 46 degrees forms a conspicuous boundary; in the USA this boundary is found at 38 degrees. North of this line there is a morbidity rate of 30 to 60 patients per 100 000 inhabitants, while south of it 15 cases at most per 100 000 inhibitants are found. Asia, especially in China and Japan, and tropical countries, where Multiple Sclerosis is practically unknown in the native populations, are exceptions. The observation that immigrants from areas with a low MS incidence into regions with a high risk of MS fall ill with the disease after years remains also unexplained. These peculiarities have given rise to the consideration whether there is a still unknown factor in the soil of high-risk areas or a specific pathogenic spectrum. In this connection, the question is also discussed whether the risk of MS in northern countries is associated with the excessive consumption of animal fat. The possible therapeutic and prophylactic significance of unsaturated fatty acids is emphasized. Our own results with the Schilling-test, determination of gastric acids, rubella titres in serum and cerebrospinal fluid, the immunofluorescence test of the serum and CSF, determination of tissue antigens (HLA) in families with multiple incidence of Multiple Sclerosis are discussed. On evaluation of a large series of patients, it is striking that Multiple Sclerosis and juvenile diabetes seem to be mutually exclusive (Schrader). Likewise, in MS statistics no other immunopathologic disease such as rheumatic diseases or bronchial asthma was found. Interestingly, also in 400 MS patients examined, hyperuricaemia or gout, which are widespread among the populace, were not found in a single case.     

Natural Babesia infection sought in black and Norway rats trapped in five Egyptian Governorates

Babesiosis is a protozoal disease caused by members of the genus Babesia transmitted by the ixodid ticks. It is a parasite of various mammalian hosts as bovine (B. bovis), equine (B. equi), rodent (B. microti), canine (B. canis) and others. Human cases of babesiosis have been reported from several countries including Egypt. It is now well established that man may become infected (Fulminating or Subclinical) with several species of Babesia without prior splenectomy. In this paper, a total of 398 Rattus rattus and 90 R. norvegicus were trapped in Suez, Ismailia, Port Said, North Sinai and South Sinai Governorates. Blood films were taken from the atil after a simple cut of its end. The films were fixed in acetone free methyl alcohol and stained with Giemsa stain as usual. The results showed that all rats trapped in Ismailia had Babesia infection, then decreased in North Sinai, Port Said, South Sinai and was zero in Suez. As double infection. Trypanosoma lewisi was found in rats trapped in Port Said, North Sinai and South Sinai. But none had Theileria infection. The medical and veterinary importance of these results were discussed.     

Experimental infection with Babesia divergens in cattle persistently infected with bovine virus diarrhoea virus

Nine Norwegian Red cattle, aged 7-14 months, persistently infected with bovine virus diarrhoea virus (BVDV) were inoculated with a Swedish strain of Babesia divergens. Six persistently infected cattle of the same age and breed were kept as controls. Blood and serum samples were collected regularly during the observation period. Rectal temperatures were recorded every morning for 25 days post infection, and the animals were examined clinically on a daily basis. Sera were examined for antibodies to B. divergens by indirect immunofluorescence antibody test (IFAT). Eight of the infected animals developed fever of 2-5 days duration. Babesia divergens organisms appeared in the erythrocytes of all infected animals on the day after inoculation. The parasitaemia lasted for 4-11 days. One animal had a transient haemoglobinuria. Compared with the control group, there was a 20% decrease in the haematocrit. There was a transient lymphopenia and thrombocytopenia during the period of fever. There were no differences in mean numbers of neutrophils between the two persistently infected groups. Compared with cattle free of BVDV, the persistently infected cattle had consistently lower total leucocyte count that was mainly due to decreased mean numbers of neutrophils and monocytes. All infected animals develop antibodies > or = 1:1280 between day 7 and 10 post infection. The magnitude of the antibody response was considerably lower than that of BVDV-free animals inoculated with the same strain and dosage of B.divergens.     

Amelioration of virulent Babesia bovis infection in calves by administration of the nitric oxide synthase inhibitor aminoguanidine

The expression of synaptosomal-associated protein (SNAP-25), neural growth-associated protein (GAP-43) and neural cell adhesion molecule (NCAM) were studied in mouse olfactory cells and axons for 2 weeks following unilateral bulbectomy. The olfactory cells and axons in the control olfactory epithelium were positive for SNAP-25 but levels decreased in the atrophic olfactory epithelium 3 days after bulbectomy. There was no expression of SNAP-25 in the olfactory epithelium on the bulbectomy side 7 days after bulbectomy, indicating that this protein may be a good marker for the degeneration of olfactory cells. The expression of NCAM was still found in the atrophic olfactory epithelium at 7 days after bulbectomy, while the expression of NCAM in the olfactory epithelium of the bulbectomy side was stronger than that on the control side at 14 days after bulbectomy. The expression of GAP-43 in the olfactory axonal bundles of the bulbectomy side at 3 and 4 days after bulbectomy was stronger than that on the control side. These results suggest that upregulation of NCAM may be related to the regeneration of the olfactory cells, with upregulation of GAP-43 probably playing a role in axonal regeneration after bulbectomy.     

Medical therapy of experimental infection stones

Eighty-seven basal cell carcinomas were treated by surgical excision. Sites of removal were allowed to heal by secondary intention. Advantages of this method include histologic monitoring of the adequacy of incision, a less formidable surgical procedure, and a cosmetically acceptable scar.     

Identification of persistent infection in experimental syphilis by PCR

The studies described herein were designed to evaluate the usefulness of the PCR in detecting persistent syphilitic infection. Three groups of animals were used: a nonimmune group infected with Treponema pallidum (NI/TP), a nonimmune group injected with heat-killed treponemes (NI/HKTP), and an immune and reinfected group (I/TP). All animals were inoculated with similar numbers of organisms distributed at 10 sites on the clipped back and in both testes. The persistence of the treponemes was examined by PCR and the rabbit infectivity test (RIT). The kinetic studies and statistical analysis of their results demonstrated that the rate of bacterial clearance from the NI/TP group was very low and incomplete at 4 months after infection. It was significantly different from those of both the NI/HKTP (P < 0.001) and I/TP (P < 0.05) groups. No statistically significant differences in treponemal elimination were found between the NI/HKTP and I/TP groups. PCR can detect the DNA of dead organisms, but the latter are eliminated by the host relatively quickly (15 to 30 days) as compared to elimination of live treponemes (>120 days). PCR results correlated well with RIT results. These data suggest that PCR-positive specimens obtained from an untreated patient(s) or collected weeks after treatment indicate persistent infection. They also show that the process of elimination of T. pallidum from primary sites of infection is prolonged and incomplete.     

Ultrastructural characteristics of Babesia odocoilei in vitro

Babesia odocoilei continuously cultured in white-tailed deer (Odocoileus virginianus) erythrocytes was examined by transmission and scanning electron microscopy. Merozoites, trophozoites, intermediate-stage forms, and dividing forms were observed. Merozoites possessed a single nucleus, inner membrane complex, rhoptries, free ribosomes, rough endoplasmic reticulum, and single membrane-bound vesicles. Trophozoites lacked an inner membrane complex and rhoptries. Intermediate stages were characterized by distinct segments of inner membrane complex. Dividing forms ranged from cells with an elongated nucleus to mature daughter cells joined by a ringlike structure. Babesia odocoilei was characterized by its close proximity to the erythrocyte membrane, membranous structures resembling feeding organelles, and reproduction via a method resembling budding sensu stricto.