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1.
J Vet Intern Med ; 38(2): 971-979, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348783

RESUMO

BACKGROUND: Hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, predisposing them to life-threatening diseases. Varied responses to management strategies suggest the possibility of multiple subtypes. HYPOTHESIS/OBJECTIVE: To identify and characterize HTG subtypes in Miniature Schnauzers through cluster analysis of lipoprotein profiles. We hypothesize that multiple phenotypes of primary HTG exist in this breed. ANIMALS: Twenty Miniature Schnauzers with normal serum triglyceride concentration (NTG), 25 with primary HTG, and 5 with secondary HTG. METHODS: Cross-sectional study using archived samples. Lipoprotein profiles, generated using continuous lipoprotein density profiling, were clustered with hierarchical cluster analysis. Clinical data (age, sex, body condition score, and dietary fat content) was compared between clusters. RESULTS: Six clusters were identified. Dogs with primary HTG were dispersed among 4 clusters. One cluster showed the highest intensities for triglyceride-rich lipoprotein (TRL) and low-density lipoprotein (LDL) fractions and also included 4 dogs with secondary HTG. Two clusters had moderately high TRL fraction intensities and low-to-intermediate LDL intensities. The fourth cluster had high LDL but variable TRL fraction intensities with equal numbers of NTG and mild HTG dogs. The final 2 clusters comprised only NTG dogs with low TRL intensities and low-to-intermediate LDL intensities. The clusters did not appear to be driven by differences in the clinical data. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study support a spectrum of lipoprotein phenotypes within Miniature Schnauzers that cannot be predicted by triglyceride concentration alone. Lipoprotein profiling might be useful to determine if subtypes have different origins, clinical consequences, and response to treatment.


Assuntos
Doenças do Cão , Hiperlipidemias , Hipertrigliceridemia , Cães , Animais , Estudos Transversais , Hipertrigliceridemia/veterinária , Hiperlipidemias/veterinária , Lipoproteínas , Triglicerídeos , Análise por Conglomerados
2.
J Wildl Dis ; 60(2): 519-525, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38087773

RESUMO

Animals colonizing novel environments can encounter novel hazards. Endangered San Joaquin kit foxes (Vulpes macrotis mutica) are found in the cities of Bakersfield and Taft in central California, USA. We documented 66 incidents of kit foxes becoming entangled in sports netting (e.g., soccer nets, batting-cage nets) occurring from the 1980s through 2022. Overall, 25 of the foxes died. Adults were more likely to get entangled in soccer nets, whereas pups (<1 yr) were more likely to get entangled in batting-cage nets. Pups are more likely to die while entangled, probably due to smaller body mass and lower energy reserves. The reasons that kit foxes get entangled in netting were unclear, although incidents involving batting-cage netting and pups may be due to natal dens being located under or near batting cages. At current rates, this hazard is unlikely to limit urban kit fox populations. However, losses of this endangered species should be minimized and the incidents are easily mitigated by dropping or lifting nets when not in use.


Assuntos
Espécies em Perigo de Extinção , Animais , Cidades , População Urbana
3.
Animals (Basel) ; 13(20)2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37893934

RESUMO

The endangered San Joaquin kit fox (Vulpes macrotis mutica; SJKF) occurs in the city of Bakersfield, CA, where several putative competitors also occur, including domestic cats (Felis catus), striped skunks (Mephitis mephitis), raccoons (Procyon lotor), and opossums (Didephis virginiana). We used data from a multi-year (2015-2022) city-wide camera station survey to assess whether the other species were simply sympatric with SJKF or coexisting syntopically (i.e., occurring in the same habitats without apparent competition). Annual detection rates for the other species were not correlated with SJKF rates either within SJKF habitat suitability categories (low, medium, and high) or for all categories combined. Also, detection rates for the other species did not increase in response to a significant decline in SJKF abundance caused by sarcoptic mange. The use of all SJKF habitat suitability categories by the other species and co-detections with SJKF at camera stations indicate high spatial overlap. Interference and exploitative competition between the species are apparently negligible, likely due to similar body sizes and high resource abundance. Thus, SJKF and the other species appear to be coexisting syntopically in the urban environment, resulting in a significant additional SJKF population that facilitates range-wide conservation and recovery of this endangered species.

4.
Vet Clin Pathol ; 52(2): 243-251, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37127847

RESUMO

BACKGROUND: There are few reports in dogs that have evaluated the utility of semi-quantitative scoring of bone marrow iron stores in conjunction with reticulocyte hemoglobin (CHr) to identify iron-restricted erythropoiesis due to absolute iron deficiency or iron sequestration. OBJECTIVES: An established system for scoring iron stores in human bone marrow samples was applied to dogs. The objectives were to evaluate interobserver agreement (Κω ), determine marrow iron scores in dogs without detectable hematologic abnormalities, and assess combined interpretation of iron scores and CHr to evaluate for iron-restricted erythropoiesis. METHODS: Four blinded observers independently scored iron in 139 Prussian blue-stained canine marrow samples from 0 (none) to 6 (very heavy), including healthy controls (n = 12), clinically ill dogs with (n = 100) and without (n = 16) detectable hematologic abnormalities, and dogs with experimental nutritional iron deficiency (n = 11). Additional medical record data were available for 118 dogs to evaluate for other evidence of iron deficiency (abnormal CHr, RBC indices, serum iron variables, external blood loss, or nutritional deficiencies). RESULTS: Mean Κω was 0.69 (substantial agreement) for all samples but was 0.44 (moderate agreement) for samples with iron scores <3, indicating distinguishing scores 0-2 may not be reliable. Dogs without detectable hematologic abnormalities had scores from 3-5. Dogs with scores <3 and decreased CHr often had more indicators of iron deficiency vs dogs only having low iron scores or low CHr. CONCLUSIONS: Evaluation of dogs with marrow iron score <3 for external blood loss or nutritional deficiencies is likely clinically worthwhile, particularly if there is also decreased CHr.


Assuntos
Anemia Ferropriva , Doenças do Cão , Deficiências de Ferro , Desnutrição , Humanos , Cães , Animais , Ferro , Eritropoese , Medula Óssea , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/veterinária , Hemoglobinas/análise , Deficiências de Ferro/veterinária , Reticulócitos/química , Desnutrição/veterinária
5.
J Wildl Dis ; 59(2): 269-280, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37018594

RESUMO

Sarcoptic mange epidemics erupted in two of the remaining populations of endangered San Joaquin kit foxes (Vulpes macrotis mutica). Both populations are in urban habitats in the cities of Bakersfield and Taft, California, USA. The risk of disease spread from the two urban populations to nearby nonurban populations, and then throughout the species range, is of considerable conservation concern. To date, mange has not been detected in any nonurban populations despite considerable surveillance effort. The reasons for the lack of detections of mange among nonurban foxes are unknown. We monitored urban kit fox movements using geographic positioning system (GPS) collars to test the hypothesis that urban foxes were not venturing into nonurban habitats. Of 24 foxes monitored December 2018 to November 2019, 19 (79%) made excursions from urban into nonurban habitats from 1-124 times. The mean number of excursions per 30 d was 5.5 (range 0.1-13.9 d). The mean proportion of locations in nonurban habitats was 29.0% (range 0.6-99.7%). The mean maximum distance that foxes traveled into nonurban areas from the urban-nonurban interface was 1.1 km (range 0.1-2.9 km). Mean number of excursions, proportion of nonurban locations, and maximum distance into nonurban habitats were similar between Bakersfield and Taft, females and males, and adults and juveniles. At least eight foxes apparently used dens in nonurban habitats; shared use of dens may be an important mode of mange mite transmission between conspecifics. Two of the collared foxes died of mange during the study and two others had mange when captured at the end of the study. Three of these four foxes had made excursions into nonurban habitats. These results confirm a significant potential for mange to spread from urban to nonurban kit fox populations. We recommend continued surveillance in nonurban populations and continued treatment efforts in the affected urban populations.


Assuntos
Raposas , Escabiose , Feminino , Masculino , Animais , Escabiose/epidemiologia , Escabiose/veterinária , Cidades , Ecossistema
6.
Am J Dermatopathol ; 45(1): 56-57, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36484608

RESUMO

ABSTRACT: Perforating osteoma cutis is a benign proliferation of mature bone within the dermis and subcutaneous tissue of the skin with transepidermal elimination. Transepidermal elimination of bone is the hallmark of perforating osteoma cutis and is defined by the breaching of bone through the epidermis. Perforating osteoma cutis is exceptionally rare because only 6 cases have been recorded in the literature at the time of preparation of this report. In this report, we present the case of a 65-year-old female patient with a medical history of nonmelanoma skin cancer, hypertension, hyperlipidemia, and type II diabetes mellitus presented for evaluation of a skin lesion of the posterior lower left leg, which had been present for 1 year. Clinical and histopathologic findings were consistent with the diagnosis of acquired perforating osteoma cutis. Treatment with surgical removal by tangential biopsy has thus far proven to be both diagnostic and therapeutic because no recurrence has been noted as of 6 months.


Assuntos
Diabetes Mellitus Tipo 2 , Ossificação Heterotópica , Osteoma , Dermatopatias Genéticas , Feminino , Humanos , Idoso , Osteoma/cirurgia , Osteoma/diagnóstico , Osteoma/etiologia , Diabetes Mellitus Tipo 2/complicações , Dermatopatias Genéticas/complicações , Ossificação Heterotópica/patologia
7.
Toxicol Pathol ; 50(7): 883-885, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36200573

RESUMO

The hematological impacts of a drug can affect erythropoiesis at the level of the bone marrow, or decrease the life span of the RBC (red blood cell). The most common and recognizable clinical manifestation of either type of drug-induced erythropoietic injury is a decrease in RBC mass, or what is clinically referred to as an anemia. A decrease in RBC production can generally be separated from increased destruction (hemolysis) by evaluation of the hemogram for evidence of regeneration. In most healthy mammalian species, hemolysis will result in a regenerative response characterized by an increase in circulating reticulocytes. Hemorrhage as an alternative cause of a regenerative anemia can generally be excluded by careful clinical evaluation of the animal. Subsequently, the investigation of a drug-induced regenerative anemia should involve a very thorough evaluation of RBC morphology for evidence of immune-mediated destruction, RBC oxidative injury, and fragmentation that can help to identify the underlying pathological mechanism(s) involved.


Assuntos
Anemia , Hemólise , Animais , Eritrócitos/patologia , Eritropoese , Anemia/induzido quimicamente , Anemia/patologia , Reticulócitos , Mamíferos
9.
Animals (Basel) ; 12(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36290113

RESUMO

A population of endangered San Joaquin kit foxes inhabits the urban environment in the city of Bakersfield, California, United States. This population is considered important for the conservation and recovery of this species. In this novel environment, kit foxes encounter a novel competitor, that being non-native red foxes. We examined exploitative and interference competition between these two species. Based on scat analysis, both species consumed similar foods and dietary overlap was high. Red foxes also were found to usurp kit fox dens. Direct mortality to kit foxes from red foxes appears to be rare. Kit foxes and red foxes also appear to overlap spatially, although we found evidence of temporal partitioning of shared space. Based on binary logistic regression modeling, habitat attributes in grid cells used by the two species generally were similar, consistent with the spatial overlap. However, differences in specific attributes indicated that kit foxes are more likely to use areas with smaller open spaces and more human activity compared to red foxes. Competition from red foxes may be mitigated by several factors. Critical resources such as food and dens may be sufficiently abundant such that they are not a limiting factor. Some degree of spatial segregation and temporal partitioning of shared space may reduce interference competition. These factors may facilitate coexistence, and consequently, red foxes do not currently appear to constitute a significant competitive risk to this important population of endangered San Joaquin kit foxes.

10.
Animals (Basel) ; 12(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36290132

RESUMO

The clinical evaluation of lipid metabolism in equids is often limited to the measurement of total cholesterol and triglyceride concentrations. This provides a limited picture of metabolic state and general health, given the continuous exchange of lipid species between various lipoproteins. Major lipoprotein classes in equids include high-density lipoprotein (HDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and chylomicrons (CM). Unlike large breed horses, donkeys are highly susceptible to hepatic lipidosis. Currently, serum triglyceride concentrations serve as a surrogate marker of hepatic lipid exportation. Both VLDL, indicative of hepatic exportation, and its metabolic end-product, LDL, are rich in triglycerides, and contribute to this value. Diagnostic assays that distinguish VLDL from LDL could be useful in better recognizing the hepatic pathology in donkeys. The compositional differences of lipoproteins across species limit the use of commercially available assays developed for the measurement of human lipoproteins in domestic animals. In this study, we evaluated a high-resolution polyacrylamide gel electrophoresis method (Lipoprint®) for separating major lipoprotein classes and sub-fractionating LDL and HDL based on particle size in a large group of donkeys, and compared the pattern to a representative set of horses. Donkeys proved an HDL-rich species, with HDL accounting for the bulk of all lipoproteins (average 78.45%, SD 6.6%, range 92.2-55%). VLDL accounted for a large portion of the total (average 21.6%, SD 6.6%, range 37.1-7.8%), with minimal amounts of LDL detected. The horses tested had higher proportions of VLDL as compared to donkeys (31.7% and 21.6%, respectively p = 0.00008). The later finding draws into question the purported relationship between VLDL, high triglycerides, and hepatic lipidosis, given the incidence of the disease in donkeys is far higher than in horses.

11.
J Vet Intern Med ; 36(3): 993-1004, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35420224

RESUMO

BACKGROUND: Improved methodology to measure acute phase proteins and determination of lipoprotein particle-size distribution (PSD) could be clinically useful in dogs with systemic inflammatory processes. OBJECTIVES: Evaluate an immunoturbidometric assay for serum amyloid A (SAA) and lipoprotein PSD in dogs with sepsis, nonseptic systemic inflammation, and in healthy controls. Correlate dyslipidemic changes with SAA and C-reactive protein (CRP) concentrations. ANIMALS: Twenty-five dogs with sepsis, 15 dogs with nonseptic systemic inflammation, and 22 healthy controls. METHODS: Prospective, case-control study. Variables included SAA, CRP, and electrophoretic subfractionation of high- and low-density lipoproteins (HDL, LDL). Continuous variables were compared using ANOVA or Kruskal-Wallis tests with linear regression or Spearman's rank correlation used to assess relationships between variables. RESULTS: Median SAA and CRP concentrations were greater in dogs with sepsis (SAA 460 mg/L, interquartile range [IQR] 886 mg/L; CRP 133.2 mg/L, IQR 91.6 mg/L) and nonseptic inflammation (SAA 201 mg/L, IQR 436 mg/L; CRP 91.1 mg/L, IQR 88.6 mg/L) compared to healthy dogs (SAA 0.0 mg/L, IQR 0.0 mg/L; CRP 4.9 mg/L, IQR 0.0 mg/L) P < .0001. A cutoff of >677.5 mg/L SAA was 43.2% sensitive and 92.3% specific for sepsis. Low-density lipoprotein was higher in dogs with sepsis 29.6%, (mean, SD 14.6) compared to 14.4% (mean, SD 5.6) of all lipoproteins in healthy controls (P = .005). High-density lipoprotein was not associated with CRP but was negatively correlated with SAA (rs -0.47, P < .0001). Subfractions of LDL and HDL differed between groups (all P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of SAA using the immunoturbidometric assay evaluated in this study and lipoprotein PSD in dogs with inflammation might help distinguish septic from nonseptic causes of inflammation.


Assuntos
Doenças do Cão , Sepse , Proteínas de Fase Aguda , Reação de Fase Aguda/veterinária , Animais , Biomarcadores , Proteína C-Reativa/análise , Estudos de Casos e Controles , Cães , Inflamação/veterinária , Lipoproteínas , Tamanho da Partícula , Estudos Prospectivos , Sepse/veterinária , Proteína Amiloide A Sérica/metabolismo
12.
Vet Clin Pathol ; 51(1): 119-125, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35224766

RESUMO

BACKGROUND: Reference intervals (RIs) for routine clinicopathologic data in sheep are sparse. The authors sought to establish hematologic and biochemical RIs from a varied ovine population to improve data interpretation for small ruminant veterinarians. OBJECTIVES: The goal of this study was to establish ovine CBC and biochemistry reference intervals by sampling 120 healthy adult sheep, both male and female, from a variety of breeds, located in the Northeastern United States. METHODS: One hundred and eighteen sheep were included in the CBC RI and 121 sheep were included in the biochemistry panel RI. RESULTS: RIs for 42 CBC and biochemistry analytes were established in accordance with the American Society for Veterinary Clinical Pathology and Clinical Laboratory Standards Institute guidelines. CONCLUSIONS: These RIs are provided to assist small ruminant veterinarians with the interpretation of CBC and biochemistry panel results in sheep.


Assuntos
Hematologia , Animais , Contagem de Células Sanguíneas/veterinária , Feminino , Masculino , New England , Padrões de Referência , Valores de Referência , Ovinos , Estados Unidos
13.
J Vet Intern Med ; 36(2): 464-472, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35166405

RESUMO

BACKGROUND: Current diagnostic evaluation of transudative effusions rarely aids in identifying an underlying etiology. Lipoproteins in the fluid might reflect the site or nature of vessel involvement. OBJECTIVES: Improve the classification and diagnostic utility of pleural and peritoneal transudates in dogs and cats by investigating lipoprotein patterns in effusions. Compare these patterns with other peritonaeal and pleural fluid variables and underlying diseases. ANIMALS: Samples of transudates and serum from 18 cats and 37 dogs with transudative effusion (total nucleated cell count [TNCC] <5000 cells/µL) were analyzed. METHODS: Lipoprotein fractions, triglyceride, and cholesterol (CHO) concentrations were prospectively determined in paired fluid and serum samples. Standard fluid measurements were retrospectively collected. RESULTS: Two distinct fluid lipoprotein patterns were noted. Fluids rich in VLDL+IDL were associated with chronic kidney disease, acquired portosystemic shunts or protein-losing enteropathy (group I). Fluids rich in denser lipoproteins were associated with underlying heart disease, caudal vena cava syndrome or intracavitary neoplasia (group II). Group I and group II also had significant differences between fluid concentrations of CHO (x̄ = 8 vs 110 mg/dL) and TP (x̄ = 0.6 vs 3.8 g/dL), respectively. Five peritoneal transudates were triglyceride-rich (>100 mg/dL) and associated with pancreatitis. CONCLUSIONS AND CLINICAL IMPORTANCE: Protein-poor (TP <1.5 g/dL) and protein-rich (TP >2.5 g/dL) transudates were associated with distinct lipoprotein patterns and specific groups of disease. Effusions secondary to pancreatitis might be transudative and rich in triglycerides.


Assuntos
Doenças do Gato , Doenças do Cão , Derrame Pleural , Animais , Doenças do Gato/diagnóstico , Gatos , Doenças do Cão/diagnóstico , Cães , Exsudatos e Transudatos , Lipoproteínas , Derrame Pleural/veterinária , Estudos Retrospectivos
14.
Vet Immunol Immunopathol ; 242: 110339, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34715602

RESUMO

Complement-mediated intravascular hemolysis occurs in canine immune-mediated hemolytic anemia (IMHA). Complement inhibitors might enhance treatment of this disease. Dimers of acetylsalicylic acid such as 5,5'-methylenebis(2-acetoxybenzoic acid) (DAS) have been reported to inhibit complement. This study aimed to characterize the pharmacokinetics and safety profile of a single 3 mg/kg IV dose of DAS in 6 healthy mixed-breed dogs. Serum concentrations of DAS and its primary metabolites were measured by liquid chromatography-tandem mass spectrometry at baseline and at 5, 10 and 30 min, and 1, 2, 4, 6, 8, 12, 18 and 24 h post-administration. Additional blood samples were collected 7 and 14 days after drug administration. Complete blood counts, serum chemistry panels, C-reactive protein measurements, coagulation testing and cytokine analyses were used for safety monitoring. Following IV administration of 3 mg/kg DAS, the estimated mean maximum plasma concentration was 54,709 ng/mL. Pharmacokinetic modeling suggested that DAS was eliminated with a half-life value of 8.1 h, equivalent to a clearance of 6.93 L/hr kg and a volume of distribution of 56 mL/kg. Plasma concentrations of the metabolites were measured rapidly (within 15-60 min for M1 and M2 respectively). Overall, the relative exposure to M1 and M2 suggest significant biotransformation of DAS occurred, but DAS was the most abundant circulating species. No adverse clinical reactions were noted following DAS administration and safety studies suggested DAS caused no inflammatory response or coagulation disturbance. Further clinical evaluation of DAS is warranted.


Assuntos
Aspirina/análogos & derivados , Compostos Benzidrílicos/farmacocinética , Animais , Aspirina/farmacocinética , Cromatografia Líquida/veterinária , Cães , Infusões Intravenosas/veterinária , Cinética
15.
Vet Med (Auckl) ; 12: 177-185, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168973

RESUMO

Two 8-week-old Finnish Lapphund dogs presented with pain on manipulation, abnormal long bone conformation, retrognathism, and stunted growth compared to their litter mates. Multiple long bone fractures were evident on radiographs. Clinical pathology showed an atypically normal serum alkaline phosphatase activity for dogs this age. Due to poor quality of life, the dogs were humanely euthanized and subjected to a complete necropsy. On necropsy, all bones were soft and easily broken. Histologic examination revealed that the secondary spongiosa was diminished with abnormal bony trabeculae embedded in abundant loose vascular stroma. No Haversian canals were observed and the cortices contained abundant woven bone separated by fibrovascular tissue consistent with the diagnosis of osteogenesis imperfecta (OI). Inbreeding of the sire and female offspring led to a suspicion of recessive inheritance and the particular genetic collagen disorder remains to be identified in this breed.

16.
Vet Pathol ; 58(5): 809-828, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33769136

RESUMO

Tumor grading is a method to quantify the putative clinical aggressiveness of a neoplasm based on specific histological features. A good grading system should be simple, easy to use, reproducible, and accurately segregate tumors into those with low versus high risk. The aim of this review is to summarize the histological and, when available, cytological grading systems applied in veterinary pathology, providing information regarding their prognostic impact, reproducibility, usefulness, and shortcomings. Most of the grading schemes used in veterinary medicine are developed for common tumor entities. Grading systems exist for soft tissue sarcoma, osteosarcoma, multilobular tumor of bone, mast cell tumor, lymphoma, mammary carcinoma, pulmonary carcinoma, urothelial carcinoma, renal cell carcinoma, prostatic carcinoma, and central nervous system tumors. The prognostic relevance of many grading schemes has been demonstrated, but for some tumor types the usefulness of grading remains controversial. Furthermore, validation studies are available only for a minority of the grading systems. Contrasting data on the prognostic power of some grading systems, lack of detailed instructions in the materials and methods in some studies, and lack of data on reproducibility and validation studies are discussed for the relevant grading systems. Awareness of the limitations of grading is necessary for pathologists and oncologists to use these systems appropriately and to drive initiatives for their improvement.


Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias da Bexiga Urinária , Animais , Carcinoma de Células de Transição/veterinária , Neoplasias Renais/veterinária , Gradação de Tumores , Prognóstico , Reprodutibilidade dos Testes , Neoplasias da Bexiga Urinária/veterinária
17.
J Dairy Sci ; 103(2): 1956-1968, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31864738

RESUMO

Postpartum dairy cows experience a heightened inflammatory state coinciding with the time of greatest nutrient deficit. Nutrient availability is sensed on the cellular level by nutrient sensing kinases, such as the PI3K/AKT/mTOR (mTOR) pathway, a key orchestrator of immune cell activation and inflammatory balance. Our objective was to determine the responsiveness of this pathway to inflammatory stimulation with and without nutrient supplementation ex vivo. Blood samples were collected from Holstein cows (n = 14) at -42, -14, 7, 21, and 42 d relative to calving. Control samples and samples pretreated with a mixture of amino acids, glucose, and insulin (AAM) were stimulated with 100 ng/mL E. coli lipopolysaccharide (LPS; LPS, AAMLPS) or left unstimulated (control, AAM). After 1 h, ratios of mean fluorescence intensity for phosphorylated to total protein of AKT and mTORC1 substrates S6RP and 4EBP1 were analyzed in polymorphonuclear cells (PMN), and monocytes by flow cytometry. A separate aliquot was stimulated with LPS for 2 h and relative mRNA abundance of IL10, IL12A, IL12B, and TNFA in whole blood leukocytes from 10 cows was measured by reverse-transcription quantitative PCR. Repeated measures ANOVA was performed with fixed effects of time, treatment, and their interaction. Cells had different ratios of pathway proteins with PMN having the highest phosphorylation of AKT, S6RP, and 4EBP1. Stimulation with LPS consistently activated mTOR signaling in PMN regardless of nutrient supplementation except for postpartum 4EBP1, which increased in response to nutrients alone. In monocytes, AKT baseline phosphorylation was lower and activation could not be induced by either treatment, whereas activation of 4EBP1 responded to nutrient supplementation. Treatment with LPS increased phosphorylation of S6RP in both innate immune cell types. Nutrient supplementation increased baseline IL10 expression and decreased baseline as well as LPS-induced IL12B and TNFA expression. We conclude that the mTOR pathway in bovine innate immune cells can be differentially activated in response to inflammatory stimulation and nutrient supplementation in monocytes versus PMN. Effects of nutrient supplementation on cytokine mRNA abundance are likely specific to immune cell type.


Assuntos
Bovinos/fisiologia , Suplementos Nutricionais/análise , Imunidade Inata , Inflamação/veterinária , Lipopolissacarídeos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Aminoácidos/metabolismo , Animais , Bovinos/imunologia , Estudos de Coortes , Citocinas/genética , Escherichia coli/química , Feminino , Inflamação/induzido quimicamente , Monócitos/metabolismo , Neutrófilos/metabolismo , Nutrientes , Fosforilação , Período Pós-Parto , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
18.
Vet Clin North Am Equine Pract ; 35(3): 433-455, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31672198

RESUMO

Given the stoic nature of donkeys and their hybrids, it is important to consider the significance of diagnostic testing modalities that can provide objective health status information beyond the basic physical examination findings. However, clinical pathology assays are also fraught with significant limitations because the results for donkeys, mules, and hinnies can be difficult to interpret, and transference of data from the horse is not always applicable. This article presents considerations for sample collection, storage, analysis, and interpretation strategies for clinical pathology testing of donkeys and their hybrids based on the limited information available in the literature.


Assuntos
Equidae , Doenças dos Cavalos/patologia , Animais , Cavalos , Patologia Clínica
20.
J Biol Chem ; 294(43): 15623-15637, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31434739

RESUMO

Defects in the Fanconi anemia (FA) DNA damage-response pathway result in genomic instability, developmental defects, hematopoietic failure, cancer predisposition, and metabolic disorders. The endogenous sources of damage contributing to FA phenotypes and the links between FA and metabolic disease remain poorly understood. Here, using mice lacking the Fancd2 gene, encoding a central FA pathway component, we investigated whether the FA pathway protects against metabolic challenges. Fancd2-/- and wildtype (WT) mice were fed a standard diet (SD), a diet enriched in fat, cholesterol, and cholic acid (Paigen diet), or a diet enriched in lipid alone (high-fat diet (HFD)). Fancd2-/- mice developed hepatobiliary disease and exhibited decreased survival when fed a Paigen diet but not a HFD. Male Paigen diet-fed mice lacking Fancd2 had significant biliary hyperplasia, increased serum bile acid concentration, and increased hepatic pathology. In contrast, female mice were similarly impacted by Paigen diet feeding regardless of Fancd2 status. Upon Paigen diet challenge, male Fancd2-/- mice had altered expression of genes encoding hepatic bile acid transporters and cholesterol and fatty acid metabolism proteins, including Scp2/x, Abcg5/8, Abca1, Ldlr, Srebf1, and Scd-1 Untargeted lipidomic profiling in liver tissue revealed 132 lipid species, including sphingolipids, glycerophospholipids, and glycerolipids, that differed significantly in abundance depending on Fancd2 status in male mice. We conclude that the FA pathway has sex-specific impacts on hepatic lipid and bile acid metabolism, findings that expand the known functions of the FA pathway and may provide mechanistic insight into the metabolic disease predisposition in individuals with FA.


Assuntos
Bile/metabolismo , Dieta , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/deficiência , Metabolismo dos Lipídeos , Fígado/metabolismo , Caracteres Sexuais , Animais , Colesterol/metabolismo , Dano ao DNA , Doenças do Sistema Digestório/metabolismo , Suscetibilidade a Doenças , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Comportamento Alimentar , Feminino , Regulação da Expressão Gênica , Cinética , Metabolismo dos Lipídeos/genética , Masculino , Camundongos
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