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1.
Artigo em Inglês | MEDLINE | ID: mdl-36543048

RESUMO

Cyathostomins are the most common and highly prevalent parasites of horses worldwide. Historically, the control of cyathostomins has mainly relied on the routine use of anthelmintic products. Increasing reports on anthelmintic resistance (AR) in cyathostomins are concerning. A potential method proposed for detecting emerging AR in cyathostomins has been estimating the egg reappearance period (ERP). This paper reviews the data available for the ERP of cyathostomins against the three major classes of anthelmintics, macrocyclic lactones, tetrahydropyrimidines, and benzimidazoles. Published peer-reviewed original research articles were obtained from three databases (PubMed, CAB Direct and Web of Science) and were evaluated for their inclusion in a systematic review. Subsets of articles were then subjected to a review of ERP data. A total of 54 (of 134) studies published between 1972 and 2022 met the criteria for inclusion in the systematic review. Until the beginning of 2022, there was no agreed definition of the ERP; eight definitions of ERP were identified in the literature, complicating the comparison between studies. Additionally, potential risk factors for the shortening of the ERP, including previous anthelmintic use and climate, were frequently not described. Reports of shortened ERP for moxidectin and ivermectin are frequent: 20 studies that used comparable ERP definitions reported shortened moxidectin and ivermectin ERPs of 35 and 28 days, respectively. It is unclear whether the ERPs of these anthelmintics reduced to such levels are due to the development of AR or some biological factors related to horses, cyathostomin species, and/or the environment. The ERPs for other anthelmintics, such as fenbendazole and pyrantel, were frequently not reported due to established resistance against these drugs. Future research in horses is required to understand the mechanism(s) behind the shortening of ERP for cyathostomins. Based on this systematic review, we propose recommendations for future ERP studies.


Assuntos
Anti-Helmínticos , Doenças dos Cavalos , Animais , Cavalos , Ivermectina/uso terapêutico , Doenças dos Cavalos/parasitologia , Resistência a Medicamentos , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Contagem de Ovos de Parasitas/veterinária , Fezes/parasitologia
2.
Vet Parasitol ; 313: 109851, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521296

RESUMO

This review is aimed to (i) appraise the literature on the use of molecular techniques for the detection, quantification and differentiation of gastrointestinal helminths (GIH) of equids, (ii) identify the knowledge gaps and, (iii) discuss diagnostic prospects in equine parasitology. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews, we retrieved 54 studies (horses: 50/54; donkeys and zebras: 4/54) from four databases. Polymerase chain reaction (PCR) was employed in all of the studies whereas PCR amplicons were sequenced in only 18 of them. Other techniques used (including modifications of PCR) were reverse line blot, quantitative (q)PCR, restriction fragment length polymorphism, nested-PCR, PCR-directed next-generation sequencing, Southern blotting, single strand conformation polymorphism, PCR-enzyme linked immunosorbent assay, matrix-assisted laser desorption/ionisation-time of flight and random amplification of polymorphic DNA. Most of the studies (53/54) used nuclear ribosomal RNA (including the internal transcribed spacers, intergenic spacer, 5.8 S, 18 S, 28 S and 12 S) as target loci while cytochrome c oxidase subunit 1 and random genomic regions were targeted in only three and one studies, respectively. Overall, to date, the majority of molecular studies have focused on the diagnosis and identification of GIHs of equids (i.e. species of Anoplocephala, Craterostomum, cyathostomins, Oesophagodontus, Parascaris, Strongylus, Strongyloides and Triodontophorus), with a recent shift towards investigations on anthelmintic resistance and the use of high-throughput nemabiome metabarcoding. With the increasing reports of anthelmintic resistance in equid GIHs, it is crucial to develop and apply techniques such as advanced metabarcoding for surveillance of parasite populations in order to gain detailed insights into their diversity and sustainable control. To the best of our knowledge, this is the first systematic review that evaluates molecular investigations published on the diagnosis and quantification of equid GIHs and provides useful insights into important knowledge gaps and future research directions in equid molecular parasitology.


Assuntos
Anti-Helmínticos , Helmintos , Doenças dos Cavalos , Animais , Helmintos/genética , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/parasitologia , Cavalos , Patologia Molecular , Strongyloidea , Strongylus
3.
Parasit Vectors ; 14(1): 597, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863271

RESUMO

BACKGROUND: Cyathostomins are the most important and common parasitic nematodes of horses, with > 50 species known to occur worldwide. The frequent and indiscriminate use of anthelmintics has resulted in the development of anthelmintic resistance (AR) in horse nematodes. In this study we assessed the efficacy of commonly used anthelmintics against cyathostomins in Australian thoroughbred horses. METHODS: Two drug efficacy trials per farm were conducted on two thoroughbred horse farms in the state of Victoria, Australia. In the first trial, the horses on Farm A were treated with single and combinations of anthelmintics, including oxfendazole (OFZ), abamectin (ABM), abamectin and morantel (ABM + MOR), moxidectin (MOX) and oxfendazole and pyrantel (OFZ + PYR), at the recommended doses, whereas the horses on Farm B only received MOX, at the recommended dose. The faecal egg count reduction test (FECRT) was used to determine the efficacy and egg reappearance period (ERP) of anthelmintics. Based on the results of the first trial, the efficacies of MOX and a combination of ABM + MOR were reassessed to confirm their activities against cyathostomins. RESULTS: Of the five anthelmintic products tested on Farm A, resistance against OFZ, ABM and OFZ + PYR was found, with efficacies of - 41% (- 195% lower confidence limit [LCL]), 73% (60% LCL) and 82% (66% LCL) at 2 weeks post-treatment, respectively. The FECRT showed high efficacies of MOX and ABM + MOR (100%) at 2 week post-treatment and shortened ERPs for these anthelmintics (ABM + MOR: 4 weeks; MOX: 5 weeks). Resistance to MOX was found on Farm B, with a reduced efficacy of 90% (70% LCL) and 89% (82% LCL) at 2 weeks post-treatment in trials one and two, respectively. CONCLUSIONS: This study provides the first evidence of MOX- and multidrug-resistant (ABM and combinations of anthelmintics) cyathostomins in Australia and indicates the need for continuous surveillance of the efficacy of currently effective anthelmintics and large-scale investigations to assess the ERP for various anthelmintics.


Assuntos
Anti-Helmínticos/farmacologia , Resistência a Múltiplos Medicamentos , Doenças dos Cavalos/epidemiologia , Macrolídeos/farmacologia , Nematoides/efeitos dos fármacos , Infecções por Nematoides/veterinária , Animais , Benzimidazóis/farmacologia , Monitoramento Epidemiológico , Face/parasitologia , Fazendas , Feminino , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/parasitologia , Cavalos , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Masculino , Morantel/farmacologia , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/epidemiologia , Infecções por Nematoides/parasitologia , Contagem de Ovos de Parasitas/veterinária
4.
Parasit Vectors ; 14(1): 444, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479608

RESUMO

BACKGROUND: Strongyloides westeri is found in the small intestine of young horses, mainly in foals up to about 16 weeks of age. The main source of infection for foals is through transmammary transmission, and foals can develop acute diarrhoea, weakness, dermatitis and respiratory signs. The epidemiology of S. westeri in Australia is largely unknown. Further, molecular techniques have never been employed for detection of S. westeri in horses. This pilot study aimed to assess the utility of a molecular phylogenetic method for the detection of S. westeri in the faeces of foals. METHODS: Faecal samples were collected from a foal of less than 2 months of age, and eggs of Strongyloides sp. were detected using the modified McMaster technique. DNA was extracted from purified eggs, and a partial fragment of the small subunit of the nuclear ribosomal DNA (18S) was characterised using polymerase chain reaction, DNA sequencing and phylogenetic methods. RESULTS: Microscopic examination of faeces revealed small ellipsoidal eggs typical of Strongyloides sp. The 18S sequence generated by PCR in this study revealed 98.4% identity with that of a reference sequence of S. westeri available from GenBank. Phylogenetic analyses revealed a polyphyletic clustering of S. westeri sequences. CONCLUSION: This is the first study reporting the detection of DNA of Strongyloides sp. in faeces of a foal using a molecular phylogenetic approach targeting the variable region of 18S rDNA. It is anticipated that this study will allow future molecular epidemiological studies on S. westeri in horses.


Assuntos
Doenças dos Cavalos/parasitologia , Filogenia , Strongyloides/genética , Estrongiloidíase/epidemiologia , Estrongiloidíase/veterinária , Fatores Etários , Animais , Antiparasitários/uso terapêutico , Austrália/epidemiologia , Cruzamento , DNA de Helmintos/genética , Fezes/parasitologia , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/epidemiologia , Cavalos , Ivermectina/uso terapêutico , Contagem de Ovos de Parasitas , Projetos Piloto , Strongyloides/classificação , Strongyloides/efeitos dos fármacos , Strongyloides/isolamento & purificação , Estrongiloidíase/tratamento farmacológico
5.
J Vet Intern Med ; 35(2): 1131-1139, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33604912

RESUMO

BACKGROUND: Fibrinogen heterogeneity has been observed in humans and can influence fibrinogen measurements when using the modified Clauss assay. We hypothesized that fibrinogen heterogeneity also exists in horses. OBJECTIVES: To determine whether fibrinogen heterogeneity exists in horses. ANIMALS: Five clinically healthy horses from the university equine teaching herd. METHODS: Presumed fibrinogen was purified from pooled citrated plasma and electrophoresis performed. The purified protein was subjected to Western blotting using sheep antiserum against human fibrinogen, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Gel electrophoresis of nonreduced equine purified protein yielded 2 protein bands (approximately 377 and 318 kDa) that corresponded with the molecular weights of human high molecular weight fibrinogen and low molecular weight fibrinogen fractions, respectively. Electrophoretograms of reduced purified protein, Western blots, and LC-MS/MS supported that the purified nonreduced protein bands were fibrinogen. CONCLUSION: Fibrinogen heterogeneity exists in horses.


Assuntos
Fibrinogênio , Espectrometria de Massas em Tandem , Animais , Western Blotting/veterinária , Cromatografia Líquida/veterinária , Cavalos , Ovinos , Espectrometria de Massas em Tandem/veterinária
6.
Artigo em Inglês | MEDLINE | ID: mdl-35284858

RESUMO

Faecal egg counting techniques (FECT) form the cornerstone for the detection of gastrointestinal parasites in equines. For this purpose, several flotation, centrifugation, image- and artificial intelligence-based techniques are used, with varying levels of performance. This review aimed to critically appraise the literature on the assessment and comparison of various coprological techniques and/or modifications of these techniques used for equines and to identify the knowledge gaps and future research directions. We searched three databases for published scientific studies on the assessment and comparison of FECT in equines and included 27 studies in the final synthesis. Overall, the performance parameters of McMaster (81.5%), Mini-FLOTAC® (33.3%) and simple flotation (25.5%) techniques were assessed in most of the studies, with 77.8% of them comparing the performance of at least two or three methods. The detection of strongyle, Parascaris spp. and cestode eggs was assessed for various FECT in 70.4%, 18.5% and 18.5% studies, respectively. A sugar-based flotation solution with a specific gravity of ≥1.2 was found to be the optimal flotation solution for parasitic eggs in the majority of FECT. No uniform or standardised protocol was followed for the comparison of various FECT, and the tested sample size (i.e. equine population and faecal samples) also varied substantially across all studies. To the best of our knowledge, this is the first systematic review to evaluate studies on the comparison of FECT in equines and it highlights important knowledge gaps in the evaluation and comparison of such techniques.

7.
Vet Clin Pathol ; 49(2): 270-278, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32502315

RESUMO

BACKGROUND: Serum creatinine concentrations are higher in Greyhounds when compared with nonsighthound breeds. Greyhounds might also have higher urine creatinine concentrations compared with other breeds, which could affect urine protein-to-creatinine ratio (UPC) references. OBJECTIVES: We aimed to determine the UPC reference intervals (RIs) in healthy nonracing Greyhounds and compare this with UPC values in a group of healthy nonsighthounds and with the current International Renal Interest Society (IRIS) guidelines. METHODS: The study used an observational cross-sectional design, involving clinically healthy, nonracing Greyhounds (n = 98) and nonsighthound dogs of similar weight, age, and sex (n = 24). Packed cell volumes, total solids, urine protein concentrations, serum and urine creatinine concentrations, urine specific gravity (USG) measurements, and UPCs were determined. Linear regression was used to compare urine creatinine and urine protein concentrations, relative to the USG measurements, between Greyhound and nonsighthound groups. Greyhound UPC RIs were determined using nonparametric methods and compared with UPC values in nonsighthounds and current IRIS guidelines. RESULTS: Mean urine creatinine concentrations, adjusted for USGs, were approximately 22% higher in Greyhounds compared with nonsighthounds (P = .002). Mean urine protein concentration (P = .46) and UPC (P = .1) were not significantly different between Greyhounds and nonsighthounds. The upper limit of the Greyhound UPC RI was 0.20 or 0.42, depending on whether strict or moderate exclusion criteria were applied, respectively. CONCLUSIONS: Greyhounds have higher urine creatinine concentrations than nonsighthounds. Although the suggested RI for UPCs in Greyhounds is slightly lower than the cut-offs recommended in generic canine IRIS guidelines, this difference is not likely to be clinically significant.


Assuntos
Creatinina/urina , Doenças do Cão/urina , Cães/urina , Proteinúria/veterinária , Animais , Estudos Transversais , Feminino , Masculino , Proteinúria/urina , Valores de Referência , Urinálise/veterinária
8.
J Vet Emerg Crit Care (San Antonio) ; 30(3): 255-263, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32077234

RESUMO

OBJECTIVE: To assess the in vitro effects of crystalloid and colloid IV fluids on the thromboelastographic (TEG) variables of canine whole blood. DESIGN: In vitro experimental study. SETTING: Veterinary teaching hospital. ANIMALS: Twenty-two healthy dogs. INTERVENTION: Citrated whole blood samples collected from healthy dogs were diluted with 3.4% hypertonic saline (HTS 3.4), 7% hypertonic saline (HTS 7), and 20% mannitol at 8% and 16% dilutions; hydroxyethyl starch 130/0.4 (HES 130/0.4) at 16% dilution; lactated Ringer's solution (LRS) at 16%, 33%, and 66% dilutions; and HTS 7-HES 130/0.4 at 25% and 50% dilutions. Kaolin-activated TEG analysis was concurrently performed on diluted and control (undiluted) samples. MEASUREMENTS AND MAIN RESULTS: Dilution of canine whole blood with LRS compared to control reduced α angle and MA at both 33% (P = 0.009 and P = 0.011, respectively) and 66% dilution (P < 0.001 and P < 0.001, respectively), and prolonged K time at 66% dilution (P = 0.003). At 16% dilution, HTS 3.4, prolonged R time (P = 0.007), while mannitol, a fluid iso osmolar to HTS 3.4, prolonged K time (P = 0.006), reduced α angle (P < 0.001), MA (P = 0.046), and LY60 (P = 0.015). At 8% dilution, HTS 7, a fluid of high osmolarity and tonicity, prolonged R time (P = 0.009) and reduced MA (P = 0.015), while all measured TEG variables were altered at the 16% dilution (P < 0.01 for all variables). HES 130/0.4 reduced α angle (P = 0.031) and MA (P = 0.001) and increased LY60 (P < 0.001) at 16% dilution. Comparing different fluid types, HES 130/0.4 and HTS 3.4 had no to minor, mannitol intermediate, and HTS 7 profound effects on TEG variables (P < 0.05) when compared to LRS at the same dilution. CONCLUSIONS: In vitro dilution of canine whole blood with commonly used IV fluids leads to thromboelastographic changes consistent with hypocoagulability in a dose dependent manner for all fluid types tested. Viscoelastic changes are also influenced by fluid characteristics, specifically tonicity and osmolarity.


Assuntos
Cães/sangue , Derivados de Hidroxietil Amido/farmacologia , Manitol/farmacologia , Substitutos do Plasma/farmacologia , Lactato de Ringer/farmacologia , Solução Salina Hipertônica/farmacologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Masculino , Tromboelastografia/veterinária
9.
Vet Immunol Immunopathol ; 220: 109994, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31877483

RESUMO

Doramapimod (BIRB-796-BS), is an anti-inflammatory compound, acting through p38 MAPK inhibition, but its anti-inflammatory effects have not previously been studied in the horse. Whole blood aliquots from healthy horses diluted 1:1 with cell culture medium were incubated for 21 h with 1 µg/ml of lipopolysaccharide (LPS), lipoteichoic acid (LTA) or peptidoglycan (PGN) in the presence of increasing concentrations of doramapimod (3 × 10-8 M to 10-5 M). Cell bioassays were used to measure TNF-α and IL-1ß activity. Doramapimod significantly and potently inhibited TNF-α and IL-1ß activity induced by all three bacterial toxins. There was no significant difference in IC50 or maximum inhibition of TNF-α or IL-1ß production between any of the toxins. Maximum inhibition of IL-1ß was higher than that of TNF-α for all toxins, and this difference was significant for LPS (P = 0.04). Doramapimod was a potent inhibitor of TNF-α and IL-1ß for inflammation induced by LPS, LTA and PGN, with potency much greater than that of other drugs previously tested using similar methods.


Assuntos
Anti-Inflamatórios/farmacologia , Toxinas Bacterianas/antagonistas & inibidores , Naftalenos/farmacologia , Pirazóis/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Bioensaio , Linhagem Celular , Cavalos , Interleucina-1beta/sangue , Lipopolissacarídeos/farmacologia , Camundongos , Peptidoglicano/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ácidos Teicoicos/farmacologia , Fator de Necrose Tumoral alfa/sangue
10.
Parasit Vectors ; 12(1): 188, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036059

RESUMO

BACKGROUND: Equine gastrointestinal nematodes (GINs) have been the subject of intermittent studies in Australia over the past few decades. However, comprehensive information on the epidemiology of equine GINs, the efficacy of available anthelmintic drugs and the prevalence of anthelmintic resistance (AR) in Australasia is lacking. Herein, we have systematically reviewed existing knowledge on the horse GINs recorded in Australia, and main aspects of their pathogeneses, epidemiology, diagnoses, treatment and control. METHODS: Six electronic databases were searched for publications on GINs of Australian horses that met our inclusion criteria for the systematic review. Subsets of publications were subjected to review epidemiology, diagnoses, pathogeneses, treatment and control of GINs of horses from Australia. RESULTS: A total of 51 articles published between 1950 to 2018 were included. The main GINs reported in Australian horses were cyathostomins (at least 28 species), Draschia megastoma, Habronema muscae, H. majus, Oxyuris equi, Parascaris equorum, Strongyloides westeri and Trichostrongylus axei across different climatic regions of Queensland, New South Wales, Victoria, and Western Australia. Nematodes are diagnosed based on the traditional McMaster egg counting technique, though molecular markers to characterise common GINs of equines were characterised in 1990s. The use of anthelmintic drugs remains the most widely-used strategy for controlling equine GIN parasites in Australia; however, the threshold of faecal egg count that should trigger treatment in horses, remains controversial. Furthermore, anthelmintic resistance within GIN population of horses is becoming a common problem in Australia. CONCLUSIONS: Although GINs infecting Australian horses have been the subject of occasional studies over the past few decades, the effective control of GIN infections is hampered by a generalised lack of knowledge in various disciplines of equine parasitology. Therefore, coordinated and focused research is required to fill our knowledge gaps in these areas to maximise equine health and minimise economic losses associated with the parasitic infections in Australia.


Assuntos
Trato Gastrointestinal/parasitologia , Nematoides/isolamento & purificação , Infecções por Nematoides/veterinária , Doenças Parasitárias em Animais/epidemiologia , Animais , Anti-Helmínticos/uso terapêutico , Fezes/parasitologia , Cavalos , Nematoides/classificação , Infecções por Nematoides/epidemiologia , New South Wales/epidemiologia , Contagem de Ovos de Parasitas , Doenças Parasitárias em Animais/diagnóstico , Queensland/epidemiologia , Vitória/epidemiologia , Austrália Ocidental/epidemiologia
11.
Biochim Biophys Acta Mol Basis Dis ; 1865(9): 2125-2137, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31029826

RESUMO

Cardiac metabolism affects systemic energetic balance. Previously, we showed that Krüppel-like factor (KLF)-5 regulates cardiomyocyte PPARα and fatty acid oxidation-related gene expression in diabetes. We surprisingly found that cardiomyocyte-specific KLF5 knockout mice (αMHC-KLF5-/-) have accelerated diet-induced obesity, associated with increased white adipose tissue (WAT). Alterations in cardiac expression of the mediator complex subunit 13 (Med13) modulates obesity. αMHC-KLF5-/- mice had reduced cardiac Med13 expression likely because KLF5 upregulates Med13 expression in cardiomyocytes. We then investigated potential mechanisms that mediate cross-talk between cardiomyocytes and WAT. High fat diet-fed αMHC-KLF5-/- mice had increased levels of cardiac and plasma FGF21, while food intake, activity, plasma leptin, and natriuretic peptides expression were unchanged. Consistent with studies reporting that FGF21 signaling in WAT decreases sumoylation-driven PPARγ inactivation, αMHC-KLF5-/- mice had less SUMO-PPARγ in WAT. Increased diet-induced obesity found in αMHC-KLF5-/- mice was absent in αMHC-[KLF5-/-;FGF21-/-] double knockout mice, as well as in αMHC-FGF21-/- mice that we generated. Thus, cardiomyocyte-derived FGF21 is a component of pro-adipogenic crosstalk between heart and WAT.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Peso Corporal , Dieta Hiperlipídica , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Fatores de Crescimento de Fibroblastos/genética , Humanos , Fatores de Transcrição Kruppel-Like/genética , Leptina/sangue , Masculino , Complexo Mediador/genética , Complexo Mediador/metabolismo , Camundongos , Camundongos Knockout , MicroRNAs/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Obesidade/etiologia , Transdução de Sinais
12.
Child Maltreat ; 24(2): 127-136, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30522344

RESUMO

Child protection systems that implement differential response (DR) systems screen to route referrals to an investigation response (IR) or alternative response (AR). AR responses emphasize family engagement, assessment of family needs, and service linkage. Usually, AR state-level policy does not require child welfare staff to make a maltreatment determination. Jurisdictions implement DR systems differently, leading to variations in the proportion of AR cases, risk levels of cases served, and the ways families access and use services. County data from the National Child Abuse and Neglect Data System were analyzed for six states from 2004 to 2013 that implemented DR. Variation in county-level AR rates were associated with county-level re-report rates using regression models with risk adjustments for socioeconomic and other county characteristics. Counties had 3% fewer re-reports overall for each percentage increase in AR use; higher levels of AR use are related to lower levels of re-reporting. When county AR and IR cases were analyzed separately, increasing rates of AR were associated with lower re-report rates for IR cases, but higher re-report rates for AR cases. Findings for the AR and IR subgroup must be interpreted with caution as a number of technical factors may be driving these results.


Assuntos
Maus-Tratos Infantis/prevenção & controle , Serviços de Proteção Infantil/estatística & dados numéricos , Criança , Maus-Tratos Infantis/estatística & dados numéricos , Pré-Escolar , Sistemas de Dados , Humanos , Recidiva , Fatores de Risco
13.
Sci Signal ; 11(560)2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30538174

RESUMO

Increased abundance of GRK2 [G protein-coupled receptor (GPCR) kinase 2] is associated with poor cardiac function in heart failure patients. In animal models, GRK2 contributes to the pathogenesis of heart failure after ischemia-reperfusion (IR) injury. In addition to its role in down-regulating activated GPCRs, GRK2 also localizes to mitochondria both basally and post-IR injury, where it regulates cellular metabolism. We previously showed that phosphorylation of GRK2 at Ser670 is essential for the translocation of GRK2 to the mitochondria of cardiomyocytes post-IR injury in vitro and that this localization promotes cell death. Here, we showed that mice with a S670A knock-in mutation in endogenous GRK2 showed reduced cardiomyocyte death and better cardiac function post-IR injury. Cultured GRK2-S670A knock-in cardiomyocytes subjected to IR in vitro showed enhanced glucose-mediated mitochondrial respiratory function that was partially due to maintenance of pyruvate dehydrogenase activity and improved glucose oxidation. Thus, we propose that mitochondrial GRK2 plays a detrimental role in cardiac glucose oxidation post-injury.


Assuntos
Apoptose , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Glucose/química , Insuficiência Cardíaca/prevenção & controle , Isquemia/fisiopatologia , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Alanina/química , Alanina/genética , Alanina/metabolismo , Animais , Quinase 2 de Receptor Acoplado a Proteína G/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Masculino , Camundongos , Mitocôndrias/patologia , Miócitos Cardíacos/patologia , Oxirredução , Consumo de Oxigênio , Fosforilação , Mutação Puntual , Serina/química , Serina/genética , Serina/metabolismo , Transdução de Sinais
14.
Vet Clin Pathol ; 47(3): 458-463, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30102411

RESUMO

BACKGROUND: The reference intervals (RIs) for the renal biomarkers urea and creatinine, in Greyhounds, are higher than those for non-sighthound breeds. A recent study has demonstrated a higher concentration of another biomarker of renal function, symmetric dimethylarginine (SDMA), in Greyhounds compared with other dog breeds, and thus a breed-specific RI for serum SDMA may be appropriate for Greyhounds. Greyhounds appear to be predisposed to renal disease, and the establishment of an appropriate RI for SDMA may improve the ability to identify early renal dysfunction in this breed. OBJECTIVES: The aim of this study was to establish an RI for serum SDMA in nonracing Greyhounds and to determine whether the RI for Greyhounds is different from that of non-sighthound breeds. METHODS: Blood samples were collected from 101 clinically healthy, nonracing Greyhounds for serum SDMA measurements. Results from Greyhounds were compared with serum SDMA concentrations measured in a group of non-sighthound dogs (n = 24) of similar weight, age, and sex, and with a previously established canine serum SDMA RI. RESULTS: The serum SDMA RI for Greyhounds was 6.3-19.9 µg/dL (0.31-0.99 µmol/L). Greyhounds had a significantly higher mean value (13.1 µg/dL) than that of the non-sighthound dogs (10.2 µg/dL) (P < .001), and the RI of Greyhounds was different from previously established canine RIs for SDMA. CONCLUSION: This study supports the use of a Greyhound-specific RI for SDMA. Using previously established canine RIs for this breed could result in the overdiagnosis of renal disease.


Assuntos
Arginina/análogos & derivados , Cães/sangue , Animais , Arginina/sangue , Feminino , Masculino , Valores de Referência , Especificidade da Espécie
15.
J Vet Emerg Crit Care (San Antonio) ; 28(2): 85-105, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29533512

RESUMO

OBJECTIVE: To review the current literature with respect to the physiology, pathophysiology, and measurement of lactate. DATA SOURCES: Data were sourced from veterinary and human clinical trials, retrospective studies, experimental studies, and review articles. Articles were retrieved without date restrictions and were sourced primarily via PubMed, Scopus, and CAB Abstracts as well as by manual selection. HUMAN AND VETERINARY DATA SYNTHESIS: Lactate is an important energy storage molecule, the production of which preserves cellular energy production and mitigates the acidosis from ATP hydrolysis. Although the most common cause of hyperlactatemia is inadequate tissue oxygen delivery, hyperlactatemia can, and does occur in the face of apparently adequate oxygen supply. At a cellular level, the pathogenesis of hyperlactatemia varies widely depending on the underlying cause. Microcirculatory dysfunction, mitochondrial dysfunction, and epinephrine-mediated stimulation of Na+ -K+ -ATPase pumps are likely important contributors to hyperlactatemia in critically ill patients. Ultimately, hyperlactatemia is a marker of altered cellular bioenergetics. CONCLUSION: The etiology of hyperlactatemia is complex and multifactorial. Understanding the relevant pathophysiology is helpful when characterizing hyperlactatemia in clinical patients.


Assuntos
Hiperlactatemia/veterinária , Ácido Láctico/sangue , Animais , Biomarcadores , Humanos , Hiperlactatemia/fisiopatologia
16.
J Vet Emerg Crit Care (San Antonio) ; 28(2): 106-121, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29533517

RESUMO

OBJECTIVE: To review the current literature pertaining to the use of lactate as a prognostic indicator and therapeutic guide, the utility of measuring lactate concentrations in body fluids other than blood or plasma, and the clinical management of hyperlactatemia in dogs, cats, and horses. DATA SOURCES: Articles were retrieved without date restrictions primarily via PubMed, Scopus, and CAB Abstracts as well as by manual selection. HUMAN AND VETERINARY DATA SYNTHESIS: Increased plasma lactate concentrations are associated with increased morbidity and mortality. In populations with high mortality, hyperlactatemia is moderately predictive in identifying nonsurvivors. Importantly, eulactatemia predicts survival better than hyperlactatemia predicts death. Consecutive lactate measurements and calculated relative measures appear to outperform single measurements. The use of lactate as a therapeutic guide has shown promising results in people but is relatively uninvestigated in veterinary species. Increased lactate concentrations in body fluids other than blood should raise the index of suspicion for septic or malignant processes. Management of hyperlactatemia should target the underlying cause. CONCLUSION: Lactate is a valuable triage and risk stratification tool that can be used to separate patients into higher and lower risk categories. The utility of lactate concentration as a therapeutic target and the measurement of lactate in body fluids shows promise but requires further research.


Assuntos
Hiperlactatemia/veterinária , Ácido Láctico/sangue , Animais , Biomarcadores , Humanos , Hiperlactatemia/sangue , Especificidade da Espécie
17.
J Vet Emerg Crit Care (San Antonio) ; 27(3): 362-368, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28267896

RESUMO

OBJECTIVE: To describe the treatment of persistent supraventricular tachycardia (SVT) in a young horse in endurance training. CASE SUMMARY: A 6-year-old Arab gelding in endurance training presented for a dysrhythmia and decreased performance. SVT was diagnosed and conversion to a normal sinus rhythm was achieved following administration of a constant rate infusion of amiodarone. However, reversion to SVT occurred shortly after initiation of ridden exercise. A second attempt to convert the dysrhythmia with amiodarone failed, but normal sinus rhythm was achieved with transvenous electrical cardioversion (TVEC). Postmortem examination of the heart revealed extensive fibrous replacement of most of the left atrial myocardium; these changes likely provided the structural substrate for the dysrhythmia. The underlying cause of the fibrosis was not identified. NEW OR UNIQUE INFORMATION PROVIDED: SVT is a form of supraventricular tachyarrhythmia rarely diagnosed in the horse. A recent report has described sudden death of a horse following attempted conversion of SVT with oral flecainide acetate. In the present report, we describe short-term conversion of SVT in a horse using intravenous amiodarone with no significant adverse effects. When the dysrhythmia recurred, the animal was donated for teaching purposes and conversion was achieved with TVEC. Normal sinus rhythm persisted for 2 weeks until the horse was euthanized for postmortem evaluation of the heart. Intravenous amiodarone or TVEC could be considered as treatments for supraventricular tachyarrhyhmias other than atrial fibrillation in the horse.


Assuntos
Doenças dos Cavalos/terapia , Condicionamento Físico Animal , Taquicardia Supraventricular/veterinária , Amiodarona/administração & dosagem , Animais , Antiarrítmicos/administração & dosagem , Morte Súbita , Cardioversão Elétrica/veterinária , Emergências/veterinária , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/fisiopatologia , Cavalos , Masculino , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatologia , Taquicardia Supraventricular/terapia
18.
Vet Clin North Am Equine Pract ; 31(3): 587-600, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26612749

RESUMO

Neonatal encephalopathy is the most common neurologic condition affecting newborn foals and shares similarities with perinatal asphyxia syndrome of human infants. In many cases of neonatal encephalopathy there is no obvious episode of acute or chronic hypoxia and other mechanisms likely play a role in the pathogenesis. Increased concentrations of neuroactive progestagens are found in affected foals; whether these molecules are protective, as has been suggested, or play a role in the pathogenesis is unknown. Neurologic diseases other than neonatal encephalopathy affect foals occasionally and should be considered when evaluating sick foals with clinical signs of neurologic dysfunction.


Assuntos
Animais Recém-Nascidos , Doenças do Sistema Nervoso Central/veterinária , Sistema Nervoso Central/crescimento & desenvolvimento , Doenças dos Cavalos/diagnóstico , Animais , Doenças do Sistema Nervoso Central/diagnóstico , Cavalos
19.
Vet Clin North Am Equine Pract ; 30(2): 399-413, viii, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25016498

RESUMO

Admission blood lactate concentration is widely used as a prognostic indicator in equine medicine and can be a useful indicator of disease severity but typically fails to completely discriminate survivors from nonsurvivors. Increased admission lactate concentrations in adult horses typically return to normal within 12 to 24 hours. Lactate concentrations in neonatal foals are higher than adult concentrations for the first 24 to 72 hours of life. Serial measures reflecting both the magnitude and duration of hyperlactatemia might enable more accurate prognostication and provide insight into disease pathogenesis and could be a valuable therapeutic guide.


Assuntos
Doenças dos Cavalos/sangue , Cavalos/sangue , Ácido Láctico/sangue , Animais , Animais Recém-Nascidos , Estado Terminal
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