Comparative medicine最新文献

This research aims to establish an experimental surgical model for access to the renal pedicle and kidney and to determine renal length measurement via the kidney/aorta ratio (K/AO) using ultrasound. Fifteen swine underwent ventral median celiotomy with a supraumbilical transverse incision to access the right and left renal pedicles and induce renal ischemia-reperfusion injury (IRR). The kidneys were evaluated using ultrasonography to standardize renal length, aortic diameter, and the K/AO. Assessment was performed at 2 time points: 1 h before and 24 h after the surgery to induce IRR. Blood and urine samples were collected to assess renal function. Histologic evaluation of kidney fragments was also conducted. The proposed abdominal cavity access method proved to be highly efficient for exposing the right and left renal pedicles and inducing IRR. Serum levels of urea, creatinine, calcium, and phosphorus, as well as levels of the urinary protein/urinary creatinine ratio and urinary GGT, did not show significant differences. Acute kidney injury was confirmed through histopathology. The mean lengths of the right and left kidneys were 82.63 and 87.64 mm, respectively. The values of the right and left K/AO were 9.81 and 10.38, respectively. There was no statistically significant difference in the K/AO ratio before and after IRR. The proposed surgical model allowed surgical intervention on the renal pedicles without intra- or postoperative complications. Furthermore, the K/AO could be measured through ultrasonography, establishing a reference for healthy animals.

Malaria is a parasitic disease caused by protozoan species of the genus Plasmodium and transmitted by female mosquitos of the genus Anopheles and other Culicidae. Most of the parasites of the genus Plasmodium are highly species specific with more than 200 species described affecting different species of mammals, birds, and reptiles. Plasmodium species strictly affecting humans are P. falciparum, P. vivax, P. ovale, and P. malariae. More recently, P. knowlesi and other nonhuman primate plasmodia were found to naturally infect humans. Currently, malaria occurs mostly in poor tropical and subtropical areas of the world, and in many of these countries it is the leading cause of illness and death. For more than 100 y, animal models, have played a major role in our understanding of malaria biology. Avian Plasmodium species were the first to be used as models to study human malaria. Malaria parasite biology and immunity were first studied using mainly P. gallinaceum and P. relictum. Rodent malarias, particularly P. berghei and P. yoelii, have been used extensively as models to study malaria in mammals. Several species of Plasmodium from nonhuman primates have been used as surrogate models to study human malaria immunology, pathogenesis, candidate vaccines, and treatments. Plasmodium cynomolgi, P. simiovale, and P. fieldi are important models for studying malaria produced by P. vivax and P. ovale, while P. coatneyi is used as a model for study- ing severe malaria. Other nonhuman primate malarias used in research are P. fragile, P. inui, P. knowlesi, P. simium, and P. brasilianum. Very few nonhuman primate species can develop an infection with human malarias. Macaques in general are resistant to infection with P. falciparum, P. vivax, P. malariae, and P. ovale. Only apes and a few species of New World monkeys can support infection with human malarias. Herein we review the most common, and some less common, avian, reptile, and mammal plasmodia species used as models to study human malaria.

Due to their hematophagous life cycle, hard-bodied ticks including the genus Ixodes are a potential vector for numerous pathogenic organisms including bacteria, protozoa, viruses, and infectious prions. The natural geographic range of several hard tick species, includig Ixodes scapularis, has expanded over recent decades. Consequently, there is an ongoing need to maintain, feed, and propagate ticks for host-pathogen interaction studies to better understand and mitigate their impact on human and animal health. Artificial membrane feeding of hard ticks has advanced in recent years, has study design advantages, and should be used, when possible, to reduce animal use, but it also has several limitations that require the continued use of mammalian hosts including mice, guinea pigs, and rabbits. In this overview, we discuss the best management practices for these relevant species with respect to biosafety, health, and optimal host comfort when used in studies that depend on tick feeding. The capsule-jacket method is preferred over the ear sock-E-collar method of tick feeding on rabbit hosts because of better host health, comfort, and increased study versatility.

Tubulointerstitial fibrosis is a classic histologic feature of chronic kidney disease (CKD) in cats and a final common pathway toward end-stage renal disease. Domesticated cats have been used in models of ischemia-induced renal fibrosis. The objective of this study was to evaluate the performance of 2 variations of a transient unilateral renal ischemia and delayed contralateral nephrectomy model of tubulointerstitial fibrosis in cats. Purpose-bred, young adult, domesticated cats underwent 90 min of surgically induced ischemia to the right kidney followed by delayed contralateral nephrectomy performed 21 d (RI-CN21d group; n = 10) or 90 d postischemia (RI-CN90d group; n = 12). Control cats underwent sham surgery followed by left nephrectomy 21 d after (sham-CN group; n = 3). Renal functional parameters, including glomerular filtration rate and serum creatinine concentration, were evaluated before and after surgeries. The right kidneys were harvested 120 d postischemia/ sham. Renal histology with lesion scoring and histomorphometry for quantification of smooth muscle actin immunolabeling and collagen staining were performed on harvested kidneys. Severe acute kidney injury prompted euthanasia after left nephrectomy in 5/10 (50.0%), 2/12 (16.7%), and 0/3 (0%) of cats in the RI-CN21d, RI-CN90d, and sham-CN groups, respectively. A significant decrease in glomerular filtration rate by day 120, relative to baseline, occurred in cats in the RI-CN21d group (P < 0.001) and RI-CN90d group (P < 0.001) but not the sham-CN group (P = 0.76). All but one cat in the ischemia groups were azotemic at the study end. Kidneys subjected to ischemia had higher interstitial inflammation, tubular atrophy, and fibrosis scores compared with sham-operated kidneys. There were significant increases in smooth muscle actin immunolabeling and collagen staining in these kidneys, relative to the contralateral kidneys. In summary, 90 min of unilateral renal ischemia and delayed contralateral nephrectomy induced histologic and biochemical changes consistent with CKD in cats. A 90-d period between ischemia and nephrectomy resulted in improved survivability of the model.

Helminthiasis due to hookworm infestations in humans and Haemonchus contortus in sheep cause untold levels of disease and economic losses worldwide. Drug resistance is an ever-growing problem with pathogenic helminths. Thus, there is a critical need for new treatment strategies for hookworms and H. contortus that depends on animal models. Because hook- worms and H. contortus are obligate parasites, they can only be maintained using live animals. This review describes use of the Syrian golden hamster to propagate hookworms and Mongolian gerbil to propagate H. contortus.

Domestic swine (Sus scrofa domesticus) are important translational models for cardiovascular transplant studies. This can be attributed to the anatomic and physiologic similarities of their cardiovascular system to humans. Transplant studies frequently employ clinically relevant immunosuppression regimens to prevent organ rejection postoperatively. Immunosuppression can lead to opportunistic infection, including presentations that are novel or poorly described in immunocompetent hosts. In this study, we describe the first case of Mycoplasma hyorhinis -induced endocarditis affecting the pulmonary valve in a juvenile, immunosuppressed pig following a partial heart transplantation procedure. Clinical signs of infection began at 15 d postoperation, were consistent with a variety of infectious agents, including Mycoplasma hyorhinis, and included lethargy, respiratory signs, and elevated white blood cell counts. By 28 d post procedure, lameness and soft tissue swelling around the left tarsus developed. Joint fluid obtained by arthrocentesis was PCR positive for Mycoplasma hyorhinis and negative for other tested pathogens. Despite antimicrobial treatment, the transplanted pulmonary valve developed leaflet thickening, stenosis, and insufficiency starting at 30 d after the procedure. At 86 d posttransplantation, the pig reached experimental endpoints and was humanely euthanized for necropsy and histopathology. The pulmonary valve had numerous dark red vegetative expansions of all 3 leaflets. Postmortem testing of a vegetative lesion was positive for Mycoplasma hyorhinis, confirming the etiologic agent responsible for endocarditis. Mycoplasma hyorhinis -induced endocarditis of an orthotopic transplanted pulmonary valve has yet to be described in swine. This case report demonstrates that infections following immunosuppression may present with novel or undercharacterized clinical signs.

An in-house genotyping facility should aim to be more cost-effective than outsourced service and more reliable than genotyping performed by short-term employees or students of individual research groups. Reliable genotyping allows efficient and economical management of mice colonies and promotes accurate and reproducible research results. Here we provide a detailed description of our approach to establishing a genotyping core facility, relying on automated PCR assembly and high-resolution melting (HRM) analysis (first derivative). The workflow we devised was tightly managed by purpose-designed applications developed using MATLAB App Designer that allowed straightforward work planning, ensured sample tracking throughout the process, and provided a platform for reliable data analysis and generation of genotyping reports. We successfully transitioned PCR product analysis of more than 250 different target genes from standard gel electrophoresis to the more advanced HRM analysis. About 23% of the target genes required a redesign of primers to adapt to our protocol. The process was highly universal, and only 2% of the target genes required deviation from the standard PCR method to a more restricted protocol that reduces the amplification of nonspecific products. We currently run more than 1,000 PCR reactions weekly, of samples taken at weaning or experimental endpoint, and assemble a large variety of target genes in every PCR plate. We also showed that genotyping of blastocytes instead of embryos can serve as quality control of cryopreservation. Thus, our genotyping protocol promotes the 3Rs (Replacement, Reduction, and Refinement) principles. Our refined genotyping process facilitates cost-effective colony management, replaces tissue types as well as traditional methods with advanced ones, and provides reliable results in a timely manner. MATLAB codes and related data are available in supplementary materials and online.

Human infection with dengue virus (DENV) results in significant morbidity and mortality around the world. Current methods to investigate virus-associated changes in insect feeding behaviors are largely restricted to video analysis of feeding events outside of the host or intravital microscopy. Electropenetrography, a method originally developed for plant-feeding insects, offers a promising alternative by allowing high-resolution recording of voltage changes across the insect bite interface. We compared recordings from DENV-infected Aedes aegypti mosquitoes feeding on uninfected mice and uninfected A. aegypti feeding on DENV-infected mice to controls of uninfected A. aegypti feeding on uninfected mice. We found significant mosquito behavioral changes in both DENV-infected groups compared with controls including longer feeding times and longer preingestion probing events for A. aegypti feeding on DENV-infected mice and a higher number of sequential probing events in DENV-infected A. aegypti feeding on uninfected mice. By recording mosquito feeding and probing events beneath the surface of the skin, we have been able to both confirm and add new dimensions to previous findings regarding DENV-associated behavior changes in A. aegypti. This provides a foundation for increasingly in-depth studies focusing on the transmission of the DENV between vectors and hosts.