Comparative medicine最新文献

Pseudoloma neurophilia ( Pn ), the causative agent of the most commonly reported disease of zebrafish, is a microsporidian parasite that confounds research by inducing behavioral and physiologic changes in zebrafish. Although a treatment for P. neurophilia has not been documented in zebrafish, albendazole (ALB) and fumagillin (FUM) have been used to treat microsporidian infections of other fish species. To investigate the efficacy of oral ALB and FUM in the treatment of Pn, we performed a pilot study that demonstrated the safety and palatability of novel gel-based diets containing FUM or ALB in adult AB zebrafish. In a subsequent study, approximately 250 adult AB zebrafish (previously infected with Pn ) were treated with these medicated diets for 4 wk. At 4 different time points (weeks 0, 5, 10, and 16 of the study), fish were euthanized and whole-body qPCR was performed to assess Pn prevalence across treatment and control groups. There was no statistically significant association between treatment group and Pn prevalence at any time point, although potential biologically relevant reductions in Pn prevalence occurred in the combination therapy group at weeks 5 and 16 and in the ALB group at week 5. Based on high-performance liquid chromatography analyses, the medicated diets contained less ALB and more FUM than expected, highlighting the importance of validating medicated feed concentrations to ensure safety, efficacy, and consistency. While Pn remains challenging to eradicate and control, results of this study warrant further investigation into the utility of ALB and FUM as potential treatments for this pathogen.

We previously reported that induced type 1 diabetes mellitus (DM) increases the susceptibility of acute kidney injury in- duced by ischemia-reperfusion injury (IRI) in cynomolgus monkeys. In this follow-up study, we compared the expression of selected markers in the renal tissues of monkeys subjected to bilateral renal IRI with and without diabetes. All tissues were obtained from the original study. Renal biopsies were obtained before and 24 and 48 h after ischemia and were examined for expression of KI-67 (tubular proliferation), Na⁺ /K⁺ ATPase (sodium-potassium pump), TNF-α(tumor necrosis factor-α, inflammation), CD31 (microvessels), CD3 (T-cells), 2 fibrotic markers (fibroblast specific protein-1, FSP-1;α-smooth muscle actin,α -SMA), and cleaved caspase 3 (apoptosis). Generally, the expression of these markers differed in monkeys with and without DM. As compared with non-DM monkeys, DM monkeys had more cells that expressed KI-67 during progression of acute kidney injury (AKI). Na⁺ /K⁺ ATPase expression was clearly present at baseline in the basolateral tubular areas only in the non-DM monkeys. At 48 h, its expression in the basolateral area was not visible in DM monkeys, but was still present in intercellular junctions of non-DM monkeys. The expression of TNF-αwas higher in DM before and 48 h after ischemia. Before and 24 h after ischemia, the number of CD31-positive capillaries was not different between 2 groups, although more collapsed vessels were found at in DM at 24 h. At 48 h, the number of capillaries was less in DM compared with those from non-DM animals. DM monkeys had more interstitial CD3-positive cells than did non-DM monkeys at 24 and 48 h after ischemia. Finally, FSP-1-stained cells were more abundant in DM than non-DM at 24 and 48 h. Our results show that DM aggravates the recovery of renal ischemia/reperfusion injury by affecting tubular proliferation, capillary density, T cell infil- tration and by altering protein and mRNA expression of various genes involved in ion channel, inflammation, and fibrotic change. The results from this observational study demonstrate that DM aggravates the recovery of renal ischemia/reperfusion injury by affecting multiple events including tubular necrosis, proliferation, function, inflammation and by inducing capillary rarefaction in cynomolgus monkeys.

Pseudoloma neurophilia (Pn), the causative agent of the most commonly reported disease of zebrafish, is a microsporidianparasite that confounds research by inducing behavioral and physiologic changes in zebrafish. Although a treatmentfor P. neurophilia has not been documented in zebrafish, albendazole (ALB) and fumagillin (FUM) have been used to treatmicrosporidian infections of other fish species. To investigate the efficacy of oral ALB and FUM in the treatment of Pn, weperformed a pilot study that demonstrated the safety and palatability of novel gel-based diets containing FUM or ALB inadult AB zebrafish. In a subsequent study, approximately 250 adult AB zebrafish (previously infected with Pn) were treatedwith these medicated diets for 4 wk. At 4 different time points (weeks 0, 5, 10, and 16 of the study), fish were euthanized andwhole-body qPCR was performed to assess Pn prevalence across treatment and control groups. There was no statisticallysignificant association between treatment group and Pn prevalence at any time point, although potential biologically relevantreductions in Pn prevalence occurred in the combination therapy group at weeks 5 and 16 and in the ALB group at week 5.Based on high-performance liquid chromatography analyses, the medicated diets contained less ALB and more FUM thanexpected, highlighting the importance of validating medicated feed concentrations to ensure safety, efficacy, and consistency.While Pn remains challenging to eradicate and control, results of this study warrant further investigation into the utility ofALB and FUM as potential treatments for this pathogen.

Cold agglutinin disease (CAD) is a condition involving anemia and its related symptoms; it is caused by autoantibodiesthat bind and agglutinate red blood cells in areas susceptible to hypothermia, such as extremities exposed to cold temperatures.CAD is rare, with 5 to 20 human cases per million individuals. In this report, we describe a case of CAD in a previouslyhealthy and experimentally naïve adult Indian rhesus macaque that was housed indoors and presented with blood in theurine. After our observations of hemoglobinuria and anemia led us to suspect CAD, we demonstrated that the macaque'sblood agglutinated at reduced temperatures. We also noticed that the provision of cold foraging treats triggered episodes ofhemoglobinuria. Further investigation revealed that serum from the macaque agglutinated RBCs in vitro with high thermalamplitude (at or below 30 °C) and had an antibody titer of 8 to 32. The serum contained autoantibodies of the immunoglobulinM (IgM) isotype; agglutinins of the IgG isotype were not detected. The cold-dependent IgM autoantibodies in the serum fromthe affected macaque reacted against a common RBC antigen because RBCs collected from other macaques were bound andagglutinated by the affected animal's IgM under cold conditions. This in vitro binding activity was reversible when the testtemperature was returned to normal body temperature (37 °C). These findings demonstrated cold-dependent RBC-specific IgMagglutinins and led us to a diagnosis of CAD. This is the first documented case of spontaneous CAD in a rhesus macaque.

We previously reported that induced type 1 diabetes mellitus (DM) increases the susceptibility of acute kidney injury inducedby ischemia-reperfusion injury (IRI) in cynomolgus monkeys. In this follow-up study, we compared the expression ofselected markers in the renal tissues of monkeys subjected to bilateral renal IRI with and without diabetes. All tissues wereobtained from the original study. Renal biopsies were obtained before and 24 and 48 h after ischemia and were examinedfor expression of KI-67 (tubular proliferation), Na+/K+ ATPase (sodium-potassium pump), TNF-α (tumor necrosis factor-α,inflammation), CD31 (microvessels), CD3 (T-cells), 2 fibrotic markers (fibroblast specific protein-1, FSP-1; α-smooth muscleactin, α-SMA), and cleaved caspase 3 (apoptosis). Generally, the expression of these markers differed in monkeys with andwithout DM. As compared with non-DM monkeys, DM monkeys had more cells that expressed KI-67 during progressionof acute kidney injury (AKI). Na+/K+ ATPase expression was clearly present at baseline in the basolateral tubular areas onlyin the non-DM monkeys. At 48 h, its expression in the basolateral area was not visible in DM monkeys, but was still presentin intercellular junctions of non-DM monkeys. The expression of TNF-α was higher in DM before and 48 h after ischemia.Before and 24 h after ischemia, the number of CD31-positive capillaries was not different between 2 groups, although morecollapsed vessels were found at in DM at 24 h. At 48 h, the number of capillaries was less in DM compared with those fromnon-DM animals. DM monkeys had more interstitial CD3-positive cells than did non-DM monkeys at 24 and 48 h afterischemia. Finally, FSP-1-stained cells were more abundant in DM than non-DM at 24 and 48 h. Our results show that DMaggravates the recovery of renal ischemia/reperfusion injury by affecting tubular proliferation, capillary density, T cell infiltrationand by altering protein and mRNA expression of various genes involved in ion channel, inflammation, and fibroticchange. The results from this observational study demonstrate that DM aggravates the recovery of renal ischemia/reperfusioninjury by affecting multiple events including tubular necrosis, proliferation, function, inflammation and by inducingcapillary rarefaction in cynomolgus monkeys.

This corrects the article DOI: 10.30802/AALAS-CM-22-000095. In the original article entitled "Comparison of Cardiovascular Pathology in Animal Models of SARS-CoV-2 Infection: Recommendations Regarding Standardization of Research Methods," published in Vol 73, Issue 1 (February 2023), the grant information appearing in the Acknowledgments section should read: We acknowledge training support from the National Institutes of Health (T32 OD011089) for IAJ and SM.

Four strains of experimentally naïve mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ [NSG], NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ[NRG], B6.129S(Cg)-Stat1tm1Dlv/J [STAT1-/-], and B6.129S7-Ifngr1tm1Agt/J [IFNγR-/-] housed in a barrier facility developedunusual and seemingly unrelated clinical signs. Young NSG/NRG mice (n = 49, mean age = 4 ± 0.4 mo) exhibited nonspecificclinical signs of moderate-to-severe lethargy, hunched posture, decreased body condition, and pallor. In contrast to the NSG/NRGmice, the STAT1-/- and IFNγR-/-mice (n = 5) developed large subcutaneous abscesses on the head and neck. These micewere euthanized, and samples were collected for culture. NSG/NRG mice had moderate-markedly enlarged livers (20 of49, 40%) and spleens (17 of 49, 35%). The livers contained multiple, variably-sized, tan regions throughout all lobes. Histologyrevealed necrotizing hepatitis (13 of 17, 77%), splenic and hepatic extramedullary hematopoiesis (17 of 17, 100%), glomerularhistiocytosis (6 of 17, 35%), and metritis (6 of 11, 55%) with perivascular inflammation, suggesting hematogenous spreadDifferentials for these lesions included mouse hepatitis virus, ectromelia virus, Pseudomonas aeruginosa, Salmonella spp.,and Clostridium piliforme. Burkholderia gladioli was cultured from liver lesions and subcutaneous abscesses and confirmedwith 16S ribosomal RNA sequencing. After completing systematic testing of the environment, failure of the water autoclavecycle was suspected as the cause of the outbreak. To address the situation, individually ventilated racks were sanitized andnew breeders were purchased; these actions dramatically reduced B. gladioli infections. The current literature contains fewreports of B. gladioli infections in immunocompromised mice, and its typical presentation is torticollis and rolling. B. gladioliinfection is a potential differential for subcutaneous abscesses, hepatitis, and splenomegaly in immunocompromised mice.Careful monitoring of sterilization techniques is essential to prevent such infections in a barrier facility.

The American Association for Laboratory Animal Science endorses the United States Government "Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training" and requires that all papers published in Comparative Medicine report research conducted in conformance with these principles. Research for papers submitted from outside the United States must be in conformance with the guidelines of that country's government. The Editor reserves the right to reject papers reporting results of research not adhering to these principles.

The American Association for Laboratory Animal Science endorses the United States Government "Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training" and requires that all papers published in Comparative Medicine report research conducted in conformance with these principles. Research for papers submitted from outside the United States must be in conformance with the guidelines of that country's government. The Editor reserves the right to reject papers reporting results of research not adhering to these principles.

Swine are commonly used for research on the respiratory system, but various anatomic features of the tracheobronchial tree of swine are poorly defined. The purpose of our study was to acquire normative measurements of the tracheobronchial tree of swine by using chest CT scans, thus laying a foundation for treating or studying airway disorders in this species. In our study, 33 male swine underwent thoracic CT scans; we measured anatomic features of the tracheobronchial tree, including the diameter, length, and angle of various airway structures. We further analyzed the relationships among selected principal parameters. Our data revealed several similarities and differences in anatomy between swine and humans. This information may be useful in future research.