Comparative medicine最新文献

Often referred to as the silent killer, ovarian cancer is the most lethal gynecologic malignancy. This disease rarely shows any physical symptoms until late stages and no known biomarkers are available for early detection. Because ovarian cancer is rarely detected early, the physiology behind the initiation, progression, treatment, and prevention of this disease remains largely unclear. Over the past 2 decades, the laying hen has emerged as a model that naturally develops epithelial ovarian cancer that is both pathologically and histologically similar to that of the human form of the disease. Different molecular signatures found in human ovarian cancer have also been identified in chicken ovarian cancer including increased CA125 and elevated E-cadherin expression, among others. Chemoprevention studies conducted in this model have shown that decreased ovulation and inflammation are associated with decreased incidence of ovarian cancer development. The purpose of this article is to review the major studies performed in laying hen model of ovarian cancer and discuss how these studies shape our current understanding of the pathophysiology, prevention, and treatment of epithelial ovarian cancer.

Aging is associated with a progressive decline in physical function characterized by decreased mobility, which is an important risk factor for loss of independence and reduced quality of life. Functional testing conducted in animals has advanced our understanding of age-related changes in physical ability and contributed to the development of physiologic measurements that can be used to assess functional changes during aging. The balance beam test is one assessment tool used to measure age-related changes in balance and coordination. The goal of this study is to provide analytical examples and psychometric support of a protocol that has been analyzed to show how the number of successive test runs, foot slips, pauses, and hesitations affect the reliability of the primary outcome measure, which is the time to cross the beam. Our results suggest that conducting more than 1 training session, consisting of greater than or equal to 3 successful training runs, followed by at least one test session with no less than 2 successful runs (that is, runs without pauses or hesitations) provides a psychometrically sound outcome. The data presented here indicate that a psychometric approach can improve protocol design and reliability of balance beam measures in mice.

Melatonin, the circadian nighttime neurohormone, and eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA), which are omega-3 fatty acids (FA) found in high concentrations in fish oil (FO) and plants, abrogate the oncogenic effects of linoleic acid (LA), an omega-6 FA, on the growth of rodent tumors and human breast, prostate, and head and neck squamous cell carcinoma (HNSCC) xenografts in vivo. Here we determined and compared the long-term effects of these inhibitory agents on tumor regression and LA uptake and metabolism to the mitogenic agent 13-[S]-hydroxyoctadecadienoic acid (13-[S]-HODE) in human prostate cancer 3 (PC3) and FaDu HNSCC xenografts in tumor-bearing male nude rats. Rats in this study were split into 3 groups and fed one of 2 diets: one diet containing 5% corn oil (CO, high LA), 5% CO oil and melatonin (2 μg/mL) or an alternative diet 5% FO (low LA). Rats whose diet contained melatonin had a faster rate of regression of PC3 prostate cancer xenografts than those receiving the FO diet, while both in the melatonin and FO groups induced the same rate of regression of HNSCC xenografts. The results also demonstrated that dietary intake of melatonin or FO significantly inhibited tumor LA uptake, cAMP content, 13-[S]-HODE formation, [³H]-thymidine incorporation into tumor DNA, and tumor DNA content. Therefore, long-term ingestion of either melatonin or FO can induce regression of PC3 prostate and HNSCC xenografts via a mechanism involving the suppression of LA uptake and metabolism by the tumor cells.

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by difficulties in restarting the heart, causing significant on-table mortality. Therefore, optimal cardioprotective management during heart valve implantation in sheep is essential. However, little is known about successful cardioprotective management techniques in sheep. This article reports our experience in the cardioprotective management of 20 female sheep that underwent surgical aortic valve replacement with a stented tissue-engineered heart valve prosthesis. During this series of experiments, we modified our cardioprotection protocol to improve survival. We emphasize the importance of total body hypothermia and external cooling of the heart. Furthermore, we recommend repeated cardioplegia administration at 20 min intervals during surgery, with the final dosage of cardioplegia given immediately before the de-clamping of the aorta. To reduce the number of defibrillator shocks during a state of ventricular fibrillation (VF), we have learned to restart the heart by reclamping the aorta, administering cardioplegia until cardiac arrest, and de-clamping the aorta thereafter. Despite these encouraging results, more research is needed to finalize a protocol for this procedure.

Hyperlipidemia due to a high-fat diet (HFD) is a risk factor for inducing insulin resistance (IR) and adverse effects on pancreatic β-cells in obesity and type 2 diabetes mellitus. This relationship may be due to activation of the hexosaminebiosynthesis pathway. Administration of exogenous glucosamine (GlcN) can increase the end product of this pathway (uridine-5'-diphosphate-N-acetyl-glucosamine), which can mediate IR and protein glycosylation. The objective of this study was to evaluate the effects of oral GlcN and HFD on IR and pancreatic histologic damage in a 22 wk study of 4 groups of male Wistar rats: control group with normal chow diet, HFD group (24%. g/g lard), GlcN group (500 mg/kg^-1 per day of glucosamine hydrochloride in drinking water) and HFD plus oral GlcN. Metabolic variables related to IR that were measured included triglycerides (TG), free fatty acids (FFAs) and malondialdehyde (MDA). Histopathologic evaluation of the pancreas was also performed. The results showed IR in the HFD group, which had increased pancreatic nuclear pyknosis and vacuolization, with fatty infiltration and structural alteration of the islets of Langerhans. TG, FFAs and MDA were higher in serum and pancreatic tissue as compared with the control group. The GlcN group did not develop IR and had only mild nuclear pyknosis with no significant change in the pancreatic content of TG, FFAs and MDA. However, the combined administration of GlcN and HFD attenuated IR and improved TG, FFAs and MDA levels in serum and pancreatic tissue and the pancreatic histopathologic changes, with no significant differences as compared with the control group. These findings suggest that the oral GlcN at a dose of 500 mg/kg^-1 is protective against IR and the pancreatic histologic damage caused by HFD.

Systemic buprenorphine and topical antiseptics such as chlorhexidine are frequently used in research animals to aid in pain control and to reduce infection, respectively. These therapeutics are controversial, especially when used in wound healing studies, due to conflicting data suggesting that they delay wound healing. Low-level laser therapy (LLLT) has been used to aid in wound healing without exerting the systemic effects of therapies such as buprenorphine. We conducted 2 studies to investigate the effects of these common treatment modalities on the rate of wound healing in mice. The first study used models of punch biopsy and dermal abrasion to assess whether buprenorphine HCl or 0.12% chlorhexidine delayed wound healing. The second study investigated the effects of sustained-released buprenorphine, 0.05% chlorhexidine, and LLLT on excisional wound healing. The rate of wound healing was assessed by obtaining photographs on days 0, 2, 4, 7, and 9 for the punch biopsy model in study 1, days 0, 1, 2, 4, 6, 8, 11, and 13 for the dermal abrasion model in study 1, and days 0, 3, 6, and 10 for the mice in study 2. Image J software was used to analyze the photographed wounds to determine the wound area. When comparing the wound area on the above days to the original wound area, no significant differences in healing were observed for any of the treatment groups at any time period for either study. Given the results of these studies, we believe that systemic buprenorphine, topical chlorhexidine, and LLLT can be used without impairing or delaying wound healing in mice.

Ischemic myocardial disease is a major cause of death among humans worldwide; it results in scarring and pallor of the myocardium and triggers an inflammatory response that contributes to impaired left ventricular function. This response includes and is evidenced by the production of several inflammatory cytokines including TNFα, IL1β, IL4, IFNγ, IL10 and IL6. In the current study, myocardial infarcts were induced in 6 mo old male castrated sheep by ligation of the left circumflex obtuse marginal arteries (OM 1 and 2). MRI was used to measure parameters of left ventricular function that include EDV, ESV, EF, SVI, dp/dt max and dp/dt min at baseline and at 4 wk and 3 mo after infarct induction. We also measured serum concentrations of an array of cytokines. Postmortem histologic findings corroborate the existence of left ventricular myocardial injury and deterioration. Our data show a correlation between serum cytokine concentrations and the development of myocardial damage and left ventricular functional compromise.

Corynebacterium bovis, the causative agent of hyperkeratotic dermatitis in immunodeficient mice, is a significant problem in preclinical oncology research. Infection results in lifelong skin colonization and a decrease in successful engraftment of patient-derived xenograft tumor models. The use of antimicrobial agents for C. bovis is controversial in light of reports of poor efficacy and the possibility of selection for resistant strains. The purpose of this study was to describe the antimicrobial susceptibilities of C. bovis isolates obtained exclusively from immunodeficient rodents in order to aid in antimicrobial dose determination. Between 1995 and 2018, 15 isolates were collected from 11 research institutions across the United States. Antimicrobial susceptibility testing was performed for 24 antimicrobials commonly used against gram-positive bacteria. Our results provide an updated understanding of the susceptibility profiles of rodent C. bovis isolates, indicating little variability between geographically and temporally distant isolates. These results will facilitate appropriate antimicrobial use to prevent and treat C. bovis infections in immunodeficient rodents.

Over the last decade, interest in the role of the microbiome in health and disease has increased. The use of germ-free animals and depletion of the microbial flora using antimicrobials are 2 methods commonly used to study the microbiome in laboratory mice. Germ-free mice are born, raised, and studied in isolators in the absence of any known microbes; however, the equipment, supplies, and training required for the use of these mice can be costly and time-consuming. The use of antibiotics to decrease the microbial flora does not require special equipment, can be used for any mouse strain, and is relatively inexpensive; however, mice treated in this manner still retain microbes and they do not live in a germ-free environment. One commonly used antibiotic cocktail regimen uses ampicillin, neomycin, metronidazole, and vancomycin in the drinking water for 2 to 4 wk. We found that the palatability of this mixture is low, resulting in weight loss and leading to removal of mice from the study. The addition of sucralose to the medicated water and making wet food (mash) with the medicated water improved intake; however, the low palatability still resulted in a high number of mice requiring removal. The current study evaluated a new combination of antibiotics designed to reduce the gut microbiota while maintaining body weights. C57BL/6NCrl mice were placed on one of the following drinking water regimens: ampicillin/neomycin/metronidazole/vancomycin water (n = 16), enrofloxacin/ampicillin water ( n = 12), or standard reverse osmosis deionized water (RODI) ( n = 11). During an 8 day regimen, mice were weighed and water consumption was measured. Feces were collected before and after 8 d of treatment. Quantitative real-time PCR (real-time qPCR) for 16S bacterial ribosome was performed on each sample, and values were compared among groups. The combination of enrofloxacin and ampicillin improved water intake, together with a greater reduction in gut flora.

The objectives of this study were to investigate polymorphisms and changes in expression patterns of the genes FGF5, PGAM2, TLR2 and IL10 in V-line, Baladi Black and Baladi Red rabbits. Blood samples were collected from 180 healthy rabbits (n = 60 for each breed) for DNA extraction and DNA sequencing. At 3 mo of age, 20 randomly selected females from each breed were euthanized for gene expression quantification in muscle and spleen samples. PCR-DNA sequencing revealed single nucleotide polymorphisms (SNPs) among the 3 breeds that provided a monomorphic pattern for 3 of the 4 genes analyzed. Linear discriminant analysis (LDA) was used to classify the SNPs of these genes in the 3 breeds. The overall percentage of correctly classified cases for the model was 75%, with percentages of 100% for FGF5, 63% for IL10, and 100% for TLR2. Breed was a significant predictor for gene classification with estimation (1.00). Expression profiles of the genes were higher in V-line as compared with Baladi Black or Baladi Red. The LDA discriminated the 3 breeds using results of the gene expression profile as predictors for classification. Overall, 73% of the cases were correctly classified by gene expression. The identified SNPs, along with changes in mRNA levels of FGF5, PGAM2, TLR2, and IL10, could provide a biomarker for efficient characterization of rabbit breeds and could thus help develop marker assisted selection for growth and immune traits in rabbits.