Techniques of orthotopic renal transplantation. II. Size-matched porcine grafts in monkey recipients

ABSTRACT Purpose As a classical xenotransplantation model, porcine kidneys have been transplanted into the lower abdomen of non-human primates. However, we have improved upon this model by using size-matched grafting in the orthotopic position. The beneficial aspects and surgical details of our method are reported herein. Methods Donors were two newborn pigs (weighting 5 to 6 kg) and recipients were two cynomolgus monkeys (weighting, approximately, 7 kg). After bilateral nephrectomy, kidneys were cold-transported in Euro-Collins solution. The porcine kidney was transplanted to the site of a left nephrectomy and fixed to the peritoneum. Results Kidneys transplanted to the lower abdomen by the conventional method were more susceptible to torsion of the renal vein (two cases). In contrast, early-stage blood flow insufficiency did not occur in orthotopic transplants of theleft kidney. Conclusions Size-matched porcine-primate renal grafting using our method of transplanting tothe natural position of the kidneys contributes to stable post-transplant blood flow to the kidney.

Comparative safety assessments of the biosimilar APZ001 and Erbitux in pre-clinical animal models

Purpose: To evaluate the toxicity of Erbitux as well as its biosimilar APZ001 antibody (APZ001) in pre-clinical animal models including mice, rabbits and cynomolgus monkeys. Methods: We performed analysis of normal behavior activity, autonomic and non-autonomic nervous functions, nervous-muscle functions, nervous excitability and sensorimotor functions on CD-1 mice. Subsequently, we studied that effects of APZ001 and Erbitux on respiratory system, cardiovascular system and kidney in Cynomolgus monkey models and performed local tolerance experiments on New Zealand rabbits. Results: The comparisons between APZ001 and Erbitux showed no significant differences in mice autonomic nervous system, nervous muscle functions, non-autonomic nervous functions, nervous excitability and sensorimotor functions between treated and untreated group (p>0.05). APZ001 and Erbitux showed negative effect on CD-1 mice in the present of pentobarbital sodium anesthesia (p>0.05). Single administrations of high, medium or low doses of APZ001 did not lead to monkey urine volume alterations (p>0.05). In human tissues, APZ001 and Erbitux showed positive signals in endocardium, lung type II alveolar epithelial cell and surrounding vessels, but showed negative results in kidney and liver tissues. No hemolysis phenomenon and serious side-effects in vessels and muscles were observed in rabbits when administrated with APZ001 and Erbitux respectively. Conclusion: The safety comparisons between APZ001 antibody and Erbitux showed that these two antibodies showed highly similarities in mice, rabbits and cynomolgus monkey animal models in consideration of pharmaceutical effects, indicating APZ001 might be a suitable substitute for Erbitux.(AU)

Clinic, morphometric, and haematologic evaluation of captive Cynomolgus macaques (Macaca Fascicularis) / Avaliação clínica, morfométrica e hematológica de macacos Cynomolgus (Macaca Fascicularis) cativos

Characterization of biological parameters is essential to assess the sanitary conditions of animal breeding, especially when it comes to closed colonies, such as this study. Data from biometrics, semiologic and hematological evaluation were compared between sex and age groups. Adult animals have become longer in stature over the years in captivity and adult females show considerably smaller and lighter than adult males. The tails of males were significantly higher in adult males. The average temperature was 38.5°C. Heart rate remained homogeneous in the three age groups of both sexes and did not vary among age groups as observed in respiratory rate (RR), which may have been due to physical restraint and anesthesia with ketamine hydrochloride. The RR was significantly higher in juvenile animals. With the exception of eosinophilia, present in adults, all hematologic findings were within normal limits. These data indicate that the condition of the captive colony closed under study, as well as the adopted management does not produce anomalous results or unsatisfactory on clinical parameters and biometric analysis.

A caracterização de parâmetros biológicos é imprescindível para avaliar as condições sanitárias de uma criação animal, principalmente quando se trata de colônias fechadas, como a do referido estudo. Assim, com o intuito de avaliar os dados fisiológicos de primatas cativos mantidos neste sistema de criação, o trabalho aqui exposto avaliou dados biométricos, semiológicos e hematológicos de um total de 72 macacos Cynomolgus (Macaca fascicularis) no período de dois anos consecutivos, visando garantir as características originais intrínseca da espécie. Os dados provenientes da biometria, avaliação semiológica e hematológica foram comparadas entre sexos e faixas etárias. Os animais adultos se tornaram de estatura menos longelínea ao longo dos anos em cativeiro e as fêmeas adultas se mostram consideravelmente menores e mais leves que os machos adultos. As caudas dos machos foram significativamente maiores nos machos adultos. A média da temperatura foi de 38.5ºC. A frequência cardíaca manteve-se homogênea nas três faixas etárias de ambos os sexos e não apresentou variação entre as faixas etárias como observado na frequência respiratória (FR), fato que pode ter sido em decorrência da contenção física e da anestesia com cloridrato de cetamina. A FR foi significativamente mais elevada em animais juvenis. Com exceção da eosinofilia, presente nos adultos, todos os resultados hematológicos estiveram dentro dos parâmetros de normalidade. Estes dados indicam que a condição de cativeiro da colônia “fechada” sob estudo, bem como o manejo adotado não produz resultados anômalos ou insatisfatórios sobre os parâmetros clínicos e biométricos analisados.

Clinic, morphometric, and haematologic evaluation of captive Cynomolgus macaques (Macaca Fascicularis) / Avaliação clínica, morfométrica e hematológica de macacos Cynomolgus (Macaca Fascicularis) cativos

Characterization of biological parameters is essential to assess the sanitary conditions of animal breeding, especially when it comes to closed colonies, such as this study. Data from biometrics, semiologic and hematological evaluation were compared between sex and age groups. Adult animals have become longer in stature over the years in captivity and adult females show considerably smaller and lighter than adult males. The tails of males were significantly higher in adult males. The average temperature was 38.5°C. Heart rate remained homogeneous in the three age groups of both sexes and did not vary among age groups as observed in respiratory rate (RR), which may have been due to physical restraint and anesthesia with ketamine hydrochloride. The RR was significantly higher in juvenile animals. With the exception of eosinophilia, present in adults, all hematologic findings were within normal limits. These data indicate that the condition of the captive colony closed under study, as well as the adopted management does not produce anomalous results or unsatisfactory on clinical parameters and biometric analysis.(AU)

A caracterização de parâmetros biológicos é imprescindível para avaliar as condições sanitárias de uma criação animal, principalmente quando se trata de colônias fechadas, como a do referido estudo. Assim, com o intuito de avaliar os dados fisiológicos de primatas cativos mantidos neste sistema de criação, o trabalho aqui exposto avaliou dados biométricos, semiológicos e hematológicos de um total de 72 macacos Cynomolgus (Macaca fascicularis) no período de dois anos consecutivos, visando garantir as características originais intrínseca da espécie. Os dados provenientes da biometria, avaliação semiológica e hematológica foram comparadas entre sexos e faixas etárias. Os animais adultos se tornaram de estatura menos longelínea ao longo dos anos em cativeiro e as fêmeas adultas se mostram consideravelmente menores e mais leves que os machos adultos. As caudas dos machos foram significativamente maiores nos machos adultos. A média da temperatura foi de 38.5ºC. A frequência cardíaca manteve-se homogênea nas três faixas etárias de ambos os sexos e não apresentou variação entre as faixas etárias como observado na frequência respiratória (FR), fato que pode ter sido em decorrência da contenção física e da anestesia com cloridrato de cetamina. A FR foi significativamente mais elevada em animais juvenis. Com exceção da eosinofilia, presente nos adultos, todos os resultados hematológicos estiveram dentro dos parâmetros de normalidade. Estes dados indicam que a condição de cativeiro da colônia “fechada” sob estudo, bem como o manejo adotado não produz resultados anômalos ou insatisfatórios sobre os parâmetros clínicos e biométricos analisados.(AU)

Dormancy models for Mycobacterium tuberculosis: A minireview

Dormancy models for Mycobacterium tuberculosis play important roles in understanding various aspects of tuberculosis pathogenesis and in the testing of novel therapeutic regimens. By simulating the latent tuberculosis infection, in which the bacteria exist in a non-replicative state, the models demonstrate reduced susceptibility to antimycobacterial agents. This minireview outlines the models available for simulating latent tuberculosis both in vitro and in several animal species. Additionally, this minireview discusses the advantages and disadvantages of these models for investigating the bacterial subpopulations and susceptibilities to sterilization by various antituberculosis drugs..(AU)