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At least 703 records · Page 39Linked to original sources
PubMed2004

Nonhuman primate models for islet transplantation in type 1 diabetes research.

Insulin-dependent diabetes mellitus is an autoimmune disease that causes a progressive destruction of the pancreatic beta cells. As a result, the patient requires exogenous insulin to maintain normal blood glucose levels. Both the pancreas and the islets of Langerhans have been transplanted successfully in humans and in animal models, resulting in full normalization of glucose homeostasis. However, insulin independence, transient or persistent, was documented in only a small fraction of cases until recently. The chronic immunosuppression required to avoid immunological rejection appears to be toxic to the islets and adds the risk of lymphoproliferative disease reported earlier. For islet transplantation to become the method of choice, it is essential first to identify islet-friendly immunosuppressive regimens and/or to develop methods that induce donor-specific tolerance and improve islet isolation and transplantation protocols. Indeed, researchers have already successfully allografted islets in the presence of nonsteroidal immunosuppression in a process known as the Edmonton protocol. An alternative method, gene therapy, could replace these other methods and better meet the insulin requirement of an individual without requiring pancreatic or islet transplantation. This alternative, however, requires animal models to develop and test clinical protocols and to demonstrate the feasibility of preclinical trials. Nonhuman primates are ideally suited to achieve these goals. The efforts toward developing a nonhuman primate diabetic model with demonstrable insulin dependence are discussed and include pancreatic and islet transplant trials to reverse the diabetic state and achieve insulin independence. Also described are the various protocols that have been tested in primates to circumvent immunosuppression by using tolerance induction strategies in lieu of immunosuppression, thus exploring the field of donor-specific tolerance that extends beyond islet transplantation.

Animals↗
PubMed2004

Nonhuman primate models in type 1 diabetes research.

The recent success of "steroid-free" immunosuppressive protocols and improvements in islet preparation techniques have proven that pancreatic islet transplantation (PIT) is a valid therapeutic approach for patients with type 1 diabetes. However, there are major obstacles to overcome before PIT can become a routine therapeutic procedure, such as the need for chronic immunosuppression, the loss of functional islet mass after transplantation requiring multiple islet infusion to achieve euglycemia without exogenous administration of insulin, and the shortage of human tissue for transplantation. With reference to the first obstacle, stable islet allograft function without immunosuppressive therapy has been achieved after tolerance was induced in diabetic primates. With reference to the second obstacle, different strategies, including gene transfer of antiapoptotic genes, have been used to protect isolated islets before and after transplantation. With reference to the third obstacle, pigs are an attractive islet source because they breed rapidly, there is a long history of porcine insulin use in humans, and there is the potential for genetic engineering. To accomplish islet transplantation, experimental opportunities must be balanced by complementary characteristics of basic mouse and rat models and preclinical large animal models. Well-designed preclinical studies in primates can provide the quality of information required to translate islet transplant research safely into clinical transplantation.

Animals↗
PubMed1987

Effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine and recombinant human beta interferon alone and in combination on simian varicella virus infection in monkeys.

Treatment of viral infections with combinations of antiviral agents may permit administration of reduced doses of either or both drugs. Lowered doses may reduce associated toxicity. Intravenous administration of substantial doses of either human recombinant beta interferon (rHuIFN-beta) or 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) prevents development of simian varicella virus infection in African green monkeys. Daily doses of 2 X 10(6) U of rHuIFN-beta/kg inhibited clinical disease in monkeys inoculated with simian varicella virus, and doses of DHPG between 20 and 60 mg/kg per day were necessary for similar antiviral effects. Intravenous administration of combinations of rHuIFN-beta and DHPG permitted an approximately 100-fold reduction in the effective dose of rHuIFN-beta and a 10-fold reduction in the effective dose of DHPG. Analysis of data relating to viremia by using the method of the median-effect principle showed the combination of rHuIFN-beta and DHPG was strongly synergistic in treatment of this infection.

Acyclovir↗
PubMed1973

Differences in clinical and convalescent-phase antibodies of Rhesus monkeys infected with monkey pox, tanapox, and Yaba poxviruses.

Complement-fixing and complement-fixing inhibiting (CFI) antibodies were demonstrated in the clinical and convalescent stages, respectively, of rhesus monkeys infected with either monkey poxvirus, Tanapoxvirus, or Yaba poxvirus. Specificity of the CFI antibody was confirmed by its failure to cross-react with heterologous poxvirus antigens and by experiments demonstrating the CFI test as being antigen dependent. Serum containing CFI antibody neutralized homologous poxvirus but failed to agglutinate antigen-coated, tanned red blood cells. The application of CFI test as a seroepidemiologic tool for studies of poxvirus infection of man and simian monkeys and the biologic role of CFI antibody in pathogenesis were discussed.

Animals↗
PubMed1975

Pathology of pulmonary acariasis in Baboons (Papio sp.).

Pulmonary acariasis is one of the important and more frequently observed spontaneously occurring diseases in African baboons (Papio sp.). It has been found more frequently in baboons in their native habitat than in those in captivity. Prevalence also varies with the sites of captivity. Histopathologic changes occurring in the lungs due to infection with Pneumonyssus santos diasi and P. mossambicensis are described.

Animals↗
PubMed1955

Virus meningo-encephalitis in Austria. III. Pathogenic and immunological properties of the virus.

Two virus strains were isolated from the central nervous systems of two fatal human cases during an epidemic of encephalomyelitis in Austria. Monkeys, mice, and chick embryos proved susceptible; rabbits and guinea-pigs were refractory. The experimental disease in monkeys was characterized by acute meningo-encephalomyelitis, which was localized particularly in the grey matter of the brain stem, the cerebellum, the medulla, and the anterior horns of the spinal cord. The virus produced discrete lesions on the chorioallantoic membrane of the chick embryo. In monkeys, viraemia was demonstrated for a period of at least 6-8 days before the development of the clinical illness.The virus was shown to be closely related to that of Russian spring-summer encephalitis. Neutralizing and complement-fixing antibodies could be demonstrated in patients' sera.

Animals↗
PubMed2004

Outbreak of Mycobacterium bovis in a conditioned colony of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques.

We describe a tuberculosis outbreak caused by Mycobacterium bovis in a conditioned colony of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques. Animals in five rooms were exposed, but most (16/27) infections were confined to the room that housed a mixed population of cynomolgus and rhesus macaques. In this room, rhesus (8/8) and cynomolgus (10/11) macaques naturally exposed to M. bovis were infected at nearly identical rates (Fisher exact test, 2-tailed P = 1). The clinical signs of disease and pathologic lesions in infected macaques, however, were moderately different between the two species. Rhesus macaques were more likely (5/8) to exhibit clinical signs of persistent coughing and inappetance, and had more severe pulmonary lesions. By contrast, clinical signs of disease were seen in only 1 of 19 cynomolgus macaques, and overall, the pulmonary lesions were often focal and less severe, although some still had severe involvement of the lungs similar to that seen in rhesus macaques. These differences should be taken into consideration when developing or evaluating a tuberculosis-screening program. On the basis of observations made during this outbreak, we recommend that alternative screening methods such as the PRIMAGAM test and the ESAT-6 ELISA, be incorporated into the screening program to aid in the identification of infected animals.

Animals↗
PubMed1978

Experimental infection of marmosets with hepatitis A virus.

Saguinus mystax marmosets were experimentally infected with two strains of human hepatitis A virus. One of these strains of HAV was successfully subpassaged in this species of marmosets. In another experiment, the 1.32 and 1.41 g/cm3 buoyant density species of HAV derived from an infected chimpanzee stool were shown to be infectious in three species of marmosets. The value of the marmoset as an experimental model for hepatitis A infection was demonstrated by these studies.

Animals↗
PubMed1988

The apparent reversal of a wasting syndrome by nutritional intervention in Saguinus mystax.

One hundred eighty sexually mature Saguinus mystax were imported from Peru in six lots over a period of 1 year. Within 1 year after arrival, the mortality was 60% and the majority of the tamarins showed signs similar to "wasting marmoset syndrome" (WMS). In an effort to improve the survival rate, an open formula diet replaced the commercial closed formula diet that had been fed since arrival of the tamarins. The open formula diet contained 26.2% crude protein, 12.3% ether extract, 43.3% nitrogen free extract and 5.9% crude fiber on a dry matter basis. The diet was evaluated on the basis of palatability, weight gain, mortality, digestibility, nitrogen balance, serum biochemical parameters and blood counts. The mean daily consumption on an as-is basis was 44.8g or 335 Kcal gross energy/Kg of body wt./day. During the 3 month open formula diet evaluation period average weight increased by 56g (p less than .05), mortality decreased demonstratively, and alopecia and chronic diarrhea were nearly eliminated. Mean daily gross energy intake for S. mystax (335 Kcal/Kg of body wt/day) was substantially greater than previously reported values for callitrichids. WMS signs observed in the S. mystax colony were controlled by providing what appears to be an adequate diet.

Animal Feed↗
PubMed1977

Chronic bile duct cannulation of rhesus macaques (Macaca mulatta) without causing biliary fistulas.

Two surgical procedures were used for establishing chronic bile duct cannulations in rhesus macaques (Macaca mulatta) while maintaining an intact enterohepatic circulation for use in metabolism studies. One procedure resulted in the formation of biliary fistulas in all of the animals, whereas the other procedure allowed successful maintenance of the macaques without fistulation for up to 8 months after surgery. The possible importance of pressure against bile outflow in the development of the fistulas was discussed.

Animals↗
PubMed1977

The olive babbon (Papio anubis) as an animal model for research in affective disorders of man.

Efforts were made to develop an animal model for studies of the role of biogenic amines in a group of human "mood" diseases including mania and depression. Subadult, male olive baboons (Papio anubis), both normal and psychologically disturbed individuals, were anesthetized and administered 18O-enriched air for 60-130 minutes. Afterwards blood, urine, and cerebrospinal fluid were collected every hour, for 10 hours. The samples were subsequently fragmentographically analyzed for labelled metabolites of serotonin, dopamine, and norepinephrine. The results showed that significant incorporation of 18O was found in all metabolities studied, with a peak after about 4 hours. The effect of chlorpromazine injection on 18o-incorporation was also measured. It was found that chlorpromazine caused a faster rise in labelling and indicated the stimulation of dopamine turnover in the brain. The usefulness of the animal model and the in vivo labelling technique for biogenic amine determination in the brain was demonstrated by the fact that the technique was subsequently used in human patients with neurologic disease.

Affective Symptoms↗