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1.
Artigo em Inglês | MEDLINE | ID: mdl-38728082

RESUMO

OBJECTIVE: To evaluate the prevalence of red blood cell (RBC) transfusions and factors associated with the need for transfusion in cases of feline urethral obstruction (FUO). Secondarily, to compare survival to discharge in cats receiving an RBC transfusion versus those that did not. DESIGN: Retrospective, multi-institutional study from 2009 to 2019. SETTING: Four university teaching hospitals. ANIMALS: Six hundred twenty-two total occurrences of FUO in 575 cats. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were retrospectively reviewed for pertinent information. The overall prevalence of severe anemia (PCV < 0.20 L/L [<20%]) at presentation was 1.0% (6/622). The prevalence of RBC transfusions during hospitalization was 2.1% (13/622). Cats that received an RBC transfusion weighed significantly less than those that did not (4.9 vs 5.8 kg; P = 0.034) and had a lower PCV at presentation (0.30 L/L [30%] vs 0.41 L/L [41%]; P < 0.001). Hospitalization time (240 vs 72 h) and indwelling urinary catheter time (168 vs 48 h) were significantly longer in cats receiving a transfusion compared with those that did not (P < 0.001). Creatinine concentrations were not significantly associated with transfusion administration, while BUN was higher in cats receiving a transfusion (15.35 mmol/L [43 mg/dL] vs. 11.78 mmol/L [33 mg/dL]; P = 0.043). Transfusion rates were significantly higher in cats undergoing perineal urethrostomy (5.5%) compared with those that did not undergo surgery (0.97%; P < 0.001). The overall survival to discharge rate was 96%. Cats not receiving an RBC transfusion were significantly more likely to survive to discharge than those that did (odds ratio: 14.7, 95% confidence interval: 1.8-37; P < 0.001). CONCLUSIONS: FUO is rarely associated with severe anemia and the need for RBC transfusions. In this study, cats receiving an RBC transfusion were less likely to survive to discharge; therefore, requiring a blood transfusion may be associated with a worse prognosis. In addition, the need for surgical intervention was associated with a higher prevalence of RBC transfusions.


Assuntos
Doenças do Gato , Transfusão de Eritrócitos , Obstrução Uretral , Gatos , Animais , Doenças do Gato/terapia , Doenças do Gato/epidemiologia , Estudos Retrospectivos , Transfusão de Eritrócitos/veterinária , Obstrução Uretral/veterinária , Obstrução Uretral/terapia , Masculino , Fatores de Risco , Feminino , Prevalência , Anemia/veterinária , Anemia/terapia , Anemia/epidemiologia
2.
J Vet Intern Med ; 38(2): 913-921, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38334012

RESUMO

BACKGROUND: Systemic hypertension (SH) is a common cardiovascular disease in older cats that is treated primarily with the calcium channel blocker amlodipine besylate (AML). The systemic effect of AML on the classical and alterative arms of the renin-angiotensin-aldosterone system (RAAS) in cats is incompletely characterized. HYPOTHESIS/OBJECTIVES: To determine the effect of AML compared to placebo on circulating RAAS biomarkers in healthy cats using RAAS fingerprinting. ANIMALS: Twenty healthy client-owned cats. METHODS: Cats were administered amlodipine besylate (0.625 mg in toto) or placebo by mouth once daily for 14 days in a crossover design with a 4-week washout period. Plasma AML concentrations and RAAS biomarker concentrations were measured at multiple timepoints after the final dose in each treatment period. Time-weighted averages for RAAS biomarkers over 24 hours after dosing were compared between treatment groups using Wilcoxon rank-sum testing. RESULTS: Compared to placebo, AML treatment was associated with increases in markers of plasma renin concentration (median 44% increase; interquartile range [IQR] 19%-86%; P = .009), angiotensin I (59% increase; IQR 27-101%; P = .006), angiotensin II (56% increase; IQR 5-70%; P = .023), angiotensin IV (42% increase; -19% to 89%; P = .013); and angiotensin 1-7 (38% increase; IQR 9-118%; P = .015). CONCLUSIONS AND CLINICAL IMPORTANCE: In healthy cats, administration of AML resulted in nonspecific activation of both classical and alternative RAAS pathways.


Assuntos
Anlodipino , Sistema Renina-Angiotensina , Animais , Gatos , Aldosterona , Anlodipino/farmacologia , Anti-Hipertensivos/farmacologia , Biomarcadores , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
3.
Can Vet J ; 64(12): 1143-1148, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38046430

RESUMO

Objective: To retrospectively assess the biological response in cats with pancreatic carcinoma treated with toceranib phosphate. Animals: Twenty-six client-owned cats. Procedure: Patient information from multiple institutions was solicited via an emailed REDCap survey. For inclusion, cats were required to have a confirmed diagnosis of exocrine pancreatic carcinoma either by histopathology, cytology, or both; to have received treatment with toceranib phosphate; and to have adequate follow-up data for analysis. Results: Twenty cats were treated for gross disease and 6 for microscopic disease/incomplete margins. Clinical benefit (complete response, partial response, or stable disease ≥ 10 wk) was observed in 9/20 cats treated in the gross disease setting (45%; complete response: n = 1, stable disease: n = 8). The remaining 11 cats with gross disease did not respond to toceranib phosphate. In the cats with microscopic disease, response was mixed. The median survival time for all cats was 97 d (range: 1 to 1666 d). Conclusion: Toceranib phosphate was well-tolerated and provided modest clinical benefit to a subset of cats treated. Clinical relevance: Although feline exocrine pancreatic carcinoma continues to be a challenging disease to treat, toceranib phosphate appeared to provide potential clinical benefit.


Évaluation rétrospective de l'utilisation du phosphate de tocéranib (Palladia) dans le traitement du carcinome pancréatique félin. Objectif: Évaluer rétrospectivement la réponse biologique chez les chats atteints d'un carcinome pancréatique traités par le phosphate de tocéranib. Animaux: Vingt-six chats appartenant à des clients. Procédure: Les informations sur les patients de plusieurs institutions ont été sollicitées via une enquête REDCap envoyée par courriel. Pour être inclus, les chats devaient avoir un diagnostic confirmé de carcinome pancréatique exocrine, soit par histopathologie, soit par cytologie, soit par les deux; avoir reçu un traitement par phosphate de tocéranib; et disposer de données de suivi adéquates pour l'analyse. Résultats: Vingt chats ont été traités pour une maladie macroscopique et six pour une maladie microscopique/marges incomplètes. Un bénéfice clinique (réponse complète, réponse partielle ou maladie stable ≥ 10 semaines) a été observé chez 9 chats sur 20 traités dans le cadre d'une maladie macroscopique (45 %; réponse complète: n = 1, maladie stable: n = 8). Les 11 chats restants atteints d'une maladie macroscopique n'ont pas répondu au phosphate de tocéranib. Chez les chats atteints d'une maladie microscopique, la réponse était mitigée. La durée médiane de survie pour tous les chats était de 97 jours (écart: 1 à 1666 jours). Conclusion: Le phosphate de tocéranib a été bien toléré et a apporté un bénéfice clinique modeste à un sous-ensemble de chats traités. Pertinence clinique: Bien que le carcinome pancréatique exocrine félin continue d'être une maladie difficile à traiter, le phosphate de tocéranib semble offrir un bénéfice clinique potentiel.(Traduit par Dr Serge Messier).


Assuntos
Antineoplásicos , Doenças do Gato , Humanos , Gatos , Animais , Estudos Retrospectivos , Antineoplásicos/uso terapêutico , Indóis/uso terapêutico , Doenças do Gato/tratamento farmacológico , Neoplasias Pancreáticas
4.
Vet Anim Sci ; 21: 100304, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37664411

RESUMO

Septic peritonitis is a serious medical condition affecting veterinary patients and post-operative care remains controversial. This study aimed to evaluate and compare post-operative outcomes of dogs treated for septic peritonitis with and without surgically placed closed-suction abdominal drains. Medical records were retrospectively searched from the years 2009 through 2019 and one hundred and fifteen dogs with confirmed septic peritonitis treated with exploratory laparotomy were included. Twenty-two dogs had closed suction drains placed and ninety-three dogs were managed without post-operative drainage. Overall survival to discharge rate of patients in this study was 72%. The survival rate of patients with an abdominal drain was 53% compared to 77% in patients without a drain (P < 0.0001). Dogs with a higher APPLEfast score were significantly more likely to have a drain placed at the time of surgery (P = 0.0277). Dogs that had a closed-suction drain were significantly more likely to be given colloidal support compared to dogs managed without drainage (P = 0.0342). Based on this data, closed-suction drainage post-operatively for treatment of septic peritonitis was not associated with a more favorable survival outcome. The use of a severity of illness score, APPLEfast, did not show a correlation between severity of illness and survival outcome but did demonstrate a correlation between illness severity and placement of a closed-suction drain. Closed-suction drainage post-operatively increased the likelihood of receiving colloidal support, but due to the retrospective nature of the study and the lack of standardized post-operative nutritional support, definitive conclusion that post-operative drainage alone led to increased colloidal support cannot be made in this study.

5.
Cells ; 12(9)2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-37174669

RESUMO

A key component of efforts to identify the biological and drug-specific aspects contributing to therapeutic failure or unexpected exposure-associated toxicity is the study of drug-intestinal barrier interactions. While methods supporting such assessments are widely described for human therapeutics, relatively little information is available for similar evaluations in support of veterinary pharmaceuticals. There is, therefore, a critical need to develop novel approaches for evaluating drug-gut interactions in veterinary medicine. Three-dimensional (3D) organoids can address these difficulties in a reasonably affordable system that circumvents the need for more invasive in vivo assays in live animals. However, a first step in developing such systems is understanding organoid interactions in a 2D monolayer. Given the importance of orally administered medications for meeting the therapeutic need of companion animals, we demonstrate growth conditions under which canine-colonoid-derived intestinal epithelial cells survive, mature, and differentiate into confluent cell systems with high monolayer integrity. We further examine the applicability of this canine-colonoid-derived 2D model to assess the permeability of three structurally diverse, passively absorbed ß-blockers (e.g., propranolol, metoprolol, and atenolol). Both the absorptive and secretive apparent permeability (Papp) of these drugs at two different pH conditions were evaluated in canine-colonoid-derived monolayers and compared with that of Caco-2 cells. This proof-of-concept study provides promising preliminary results with regard to the utility of canine-derived organoid monolayers for species-specific assessments of therapeutic drug passive permeability.


Assuntos
Drogas Veterinárias , Animais , Cães , Humanos , Células CACO-2 , Células Epiteliais , Permeabilidade , Organoides
6.
J Feline Med Surg ; 25(2): 1098612X221149348, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36745058

RESUMO

OBJECTIVES: The aim of this study was to evaluate the use of inhalant anesthesia vs sedation for urinary catheter placement in male cats with urethral obstruction. The primary outcome measures were the incidence of complications related to catheterization, the incidence of recurrent urethral obstruction (rUO; both during hospitalization and within 1 year) and survival. The secondary aim of this study was to evaluate the association between baseline serum biochemical concentrations and antispasmodic medications with complications and short-term rUO. METHODS: We carried out a retrospective review of records from a university teaching hospital from 2009 to 2020. Cats were included if diagnosed with a urinary obstruction, based on the presence of a large, painful and non-expressible bladder, a urinary catheter was placed and hospitalization occurred for a minimum of 24 h. Collected baseline data included age, breed, weight, serum biochemical concentrations and if cats underwent sedation or inhalant anesthesia for urethral catheterization. For the comparison of inhalant anesthesia or sedation, univariate logistic regression was used. RESULTS: There was no statistically significant difference in complications or the recurrence of obstruction in cats with urethral obstruction that underwent inhalant anesthesia compared with sedation. All serum biochemical concentrations were significantly associated with survival. Decreased serum ionized calcium was found to be statistically significantly associated with higher complication rates (P = 0.0086), as well as short-term recurrence of obstruction (P = 0.004). Increased serum potassium concentrations were found to be statistically significantly associated with the risk of short-term recurrent urethral obstruction (P = 0.0345). No significant difference was found between the use of antispasmodic medications with short-term recurrence. CONCLUSIONS AND RELEVANCE: No significant difference was found between complications or recurrence rates when comparing the use of inhalant anesthesia to sedation protocols. Baseline serum biochemical data were significantly associated with complications, survival and short-term recurrence rates.


Assuntos
Anestesia , Doenças do Gato , Obstrução Uretral , Gatos , Animais , Masculino , Estudos Retrospectivos , Parassimpatolíticos , Cateterismo Urinário/veterinária , Obstrução Uretral/veterinária , Anestesia/veterinária
7.
Vet Surg ; 52(2): 249-256, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36382668

RESUMO

OBJECTIVE: The objective of this study was to evaluate the use of linear external skeletal fixation (ESF) applied using minimally invasive techniques in dogs and cats. STUDY DESIGN: Retrospective study. ANIMALS: Forty-nine dogs and 6 cats. METHODS: Medical records of cases with nonarticular tibial fractures, repaired using linear ESF at a single academic institution between July 2010 and 2020, were reviewed. All records of cases that had nonarticular tibial fractures repaired using linear ESF were included. Information was collected regarding signalment, surgical procedures performed, perioperative care, radiographic evaluation, and postoperative complications. RESULTS: Intraoperative imaging was used in 40/55 (72%) of cases. Tibal plateau angle (TPA), tibial mechanical medial proximal and distal tibial angles (mMPTA and mMDTA, respectively) were not affected by intraoperative imaging (P = .344, P = .687, P = .418). A total of 22 (40%) complications occurred. Of these, 18 were considered minor and 4 were considered major. Open fractures had more major complications than closed fractures (P = .019). All fractures reached radiographic union of the fracture. The mean ± SD time to external fixator removal was 71 ± 48 days. CONCLUSION: Linear ESF applied using minimally invasive techniques with or without intraoperative imaging was an effective treatment for nonarticular tibial fractures. CLINICAL SIGNIFICANCE: Closed application of linear ESF should be considered as a minimally invasive option for stabilizing nonarticular tibial fractures.


Assuntos
Doenças do Gato , Doenças do Cão , Fraturas da Tíbia , Gatos , Cães , Animais , Estudos Retrospectivos , Doenças do Gato/diagnóstico por imagem , Doenças do Gato/cirurgia , Placas Ósseas/veterinária , Doenças do Cão/cirurgia , Fraturas da Tíbia/cirurgia , Fraturas da Tíbia/veterinária , Fixação de Fratura/veterinária , Fixadores Externos/veterinária , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/veterinária , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
8.
PLoS One ; 17(12): e0279594, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36548371

RESUMO

Canine splenic hemangiosarcoma (HSA) is an aggressive tumor with a short overall survival time (OST) despite treatment with splenectomy and adjuvant doxorubicin. Modulation of the immune system has been shown to be effective for a variety of human tumors, and may be effective for canine tumors, including HSA. Immunocidin® is a non-specific immunotherapy based on a mycobacterial cell wall fraction. Preliminary work suggests Immunocidin® is safe to give intravenously (IV) in tumor-bearing dogs. This work aimed to evaluate the safety of doxorubicin and Immunocidin® combination in dogs with naturally occurring splenic HSA. A secondary aim of this study was to collect preliminary efficacy data to support a subsequent comprehensive, prospective clinical trial in canine patients with HSA, if the combination of doxorubicin and Immunocidin® was found to be safe. Eighteen dogs with stage II-III splenic HSA were recruited to receive 5 doses of sequential IV doxorubicin and Immunocidin® at two-week intervals following splenectomy. Adverse events (AEs) were graded according to the Veterinary Cooperative Oncology Group v1.1 (VCOG) scheme. Overall survival time was calculated from the date of splenectomy to date of death or loss to follow-up. AEs during administration were infrequent, the most common being hypertension. One patient developed limb and facial twitching and was removed from the study. After infusion, common AEs included lethargy, hyporexia, and diarrhea. One patient developed VCOG grade 5 diarrhea, thrombocytopenia, and anemia. Modifications in the treatment regimen were made to prevent these signs in subsequent patients. The median OST in dogs treated with the combination therapy was estimated at 147 days (range: 39-668 days). Although generally safe, the combination of doxorubicin and Immunocidin® appeared to cause more gastrointestinal effects than doxorubicin alone, and no apparent improvement in OST was noted in this population of dogs.


Assuntos
Doenças do Cão , Hemangiossarcoma , Neoplasias Esplênicas , Animais , Cães , Doenças do Cão/tratamento farmacológico , Doxorrubicina/efeitos adversos , Hemangiossarcoma/tratamento farmacológico , Hemangiossarcoma/veterinária , Imunoterapia , Estudos Prospectivos , Neoplasias Esplênicas/veterinária
11.
Cancers (Basel) ; 14(14)2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35884586

RESUMO

Lipopolysaccharide (LPS) is associated with chronic intestinal inflammation and promotes intestinal cancer progression in the gut. While the interplay between LPS and intestinal immune cells has been well-characterized, little is known about LPS and the intestinal epithelium interactions. In this study, we explored the differential effects of LPS on proliferation and the transcriptome in 3D enteroids/colonoids obtained from dogs with naturally occurring gastrointestinal (GI) diseases including inflammatory bowel disease (IBD) and intestinal mast cell tumor. The study objective was to analyze the LPS-induced modulation of signaling pathways involving the intestinal epithelia and contributing to colorectal cancer development in the context of an inflammatory (IBD) or a tumor microenvironment. While LPS incubation resulted in a pro-cancer gene expression pattern and stimulated proliferation of IBD enteroids and colonoids, downregulation of several cancer-associated genes such as Gpatch4, SLC7A1, ATP13A2, and TEX45 was also observed in tumor enteroids. Genes participating in porphyrin metabolism (CP), nucleocytoplasmic transport (EEF1A1), arachidonic acid, and glutathione metabolism (GPX1) exhibited a similar pattern of altered expression between IBD enteroids and IBD colonoids following LPS stimulation. In contrast, genes involved in anion transport, transcription and translation, apoptotic processes, and regulation of adaptive immune responses showed the opposite expression patterns between IBD enteroids and colonoids following LPS treatment. In brief, the crosstalk between LPS/TLR4 signal transduction pathway and several metabolic pathways such as primary bile acid biosynthesis and secretion, peroxisome, renin-angiotensin system, glutathione metabolism, and arachidonic acid pathways may be important in driving chronic intestinal inflammation and intestinal carcinogenesis.

12.
J Vis Exp ; (179)2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-35156656

RESUMO

Dogs develop complex multifactorial diseases analogous to humans, including inflammatory diseases, metabolic diseases, and cancer. Therefore, they represent relevant large animal models with the translational potential to human medicine. Organoids are 3-dimensional (3D), self-assembled structures derived from stem cells that mimic the microanatomy and physiology of their organ of origin. These translational in vitro models can be used for drug permeability and discovery applications, toxicology assessment, and to provide a mechanistic understanding of the pathophysiology of multifactorial chronic diseases. Furthermore, canine organoids can enhance the lives of companion dogs, providing input in various areas of veterinary research and facilitating personalized treatment applications in veterinary medicine. A small group of donors can create a biobank of organoid samples, reducing the need for continuous tissue harvesting, as organoid cell lines can be sub-cultured indefinitely. Herein, three protocols that focus on the culture of intestinal and hepatic canine organoids derived from adult stem cells are presented. The Canine Organoid Isolation Protocol outlines methods to process tissue and embedding of the cell isolate in a supportive matrix (solubilized extracellular membrane matrix). The Canine Organoid Maintenance Protocol describes organoid growth and maintenance, including cleaning and passaging along with appropriate timing for expansion. The Organoid Harvesting and Biobanking Protocol describes ways to extract, freeze, and preserve organoids for further analysis.


Assuntos
Pesquisa Biomédica , Organoides , Animais , Bancos de Espécimes Biológicos , Cães , Intestinos , Padrões de Referência
13.
J Vet Intern Med ; 36(1): 272-278, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34859924

RESUMO

A 14-year-old male castrated domestic medium-hair cat with diabetes mellitus was evaluated for vomiting, diarrhea, and anorexia. Two weeks before presentation, the cat had been diagnosed with congestive heart failure and started on furosemide. Initial diagnostic testing identified hypokalemia, systemic hypertension, and hypertrophic cardiomyopathy phenotype, and plasma aldosterone concentration was moderately increased. Abdominal ultrasound examination disclosed bilateral adrenomegaly and a right renal mass, and cytology of a needle aspirate of the mass was consistent with malignant neoplasia. The cat was treated with amlodipine and spironolactone. Because of the unusual presentation for hyperaldosteronism, a comprehensive profile of renin-angiotensin-aldosterone system (RAAS) peptides was performed. Results from multiple timepoints indicated persistently and markedly increased plasma renin activity and generalized RAAS upregulation. In addition to the lack of adrenal tumor, the markedly increased plasma renin activity was atypical for primary hyperaldosteronism. These clinical findings are suggestive of primary hyperreninism, a condition previously unreported in cats. The concurrent presence of a renal neoplasm suggests the possibility of a renin-secreting tumor.


Assuntos
Doenças do Gato , Hiperaldosteronismo , Hipertensão , Neoplasias Renais , Sarcoma , Aldosterona , Animais , Doenças do Gato/diagnóstico , Doenças do Gato/tratamento farmacológico , Gatos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/veterinária , Hipertensão/veterinária , Neoplasias Renais/veterinária , Masculino , Renina , Sistema Renina-Angiotensina , Sarcoma/veterinária , Regulação para Cima
14.
Vet Clin Pathol ; 50 Suppl 1: 18-28, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34699081

RESUMO

Chronic enteropathies (CEs) in dogs describe a group of idiopathic disorders characterized by chronic persistent or recurrent gastrointestinal (GI) signs. Three major subgroups of CE can be identified by their response to treatment: Food-responsive disease (FRD), antibiotic-responsive disease (ARD), and steroid-responsive disease (SRD). The clinical diagnosis of CE is made by exclusion of all other possible causes of chronic diarrhea and includes histologic assessment of intestinal biopsies. The process of diagnosing canine CE can therefore be very time-consuming and expensive, and in most cases, does not help to identify dogs that will respond to a specific treatment. The development of novel diagnostic tests for canine CE has therefore focused on the accuracy of such tests to predict treatment responses. In this article, several novel assays that have the potential to become commercially available will be discussed, such as genetic tests, perinuclear anti-neutrophil cytoplasmic antibodies (pANCA), antibodies against transglutaminase/gliadin, antibodies against E coli OmpC/flagellin, and micro RNAs.


Assuntos
Doenças do Cão , Doenças Inflamatórias Intestinais , Animais , Biópsia/veterinária , Doença Crônica , Doenças do Cão/diagnóstico , Cães , Escherichia coli , Doenças Inflamatórias Intestinais/veterinária
15.
Am J Physiol Gastrointest Liver Physiol ; 321(6): G668-G681, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34643097

RESUMO

MicroRNA-mediated regulation is critical for the proper development and function of the small intestinal (SI) epithelium. However, it is not known which microRNAs are expressed in each of the cell types of the SI epithelium. To bridge this important knowledge gap, we performed comprehensive microRNA profiling in all major cell types of the mouse SI epithelium. We used flow cytometry and fluorescence-activated cell sorting with multiple reporter mouse models to isolate intestinal stem cells, enterocytes, goblet cells, Paneth cells, enteroendocrine cells, tuft cells, and secretory progenitors. We then subjected these cell populations to small RNA-sequencing. The resulting atlas revealed highly enriched microRNA markers for almost every major cell type (https://sethupathy-lab.shinyapps.io/SI_miRNA/). Several of these lineage-enriched microRNAs (LEMs) were observed to be embedded in annotated host genes. We used chromatin-run-on sequencing to determine which of these LEMs are likely cotranscribed with their host genes. We then performed single-cell RNA-sequencing to define the cell type specificity of the host genes and embedded LEMs. We observed that the two most enriched microRNAs in secretory progenitors are miR-1224 and miR-672, the latter of which we found is deleted in hominin species. Finally, using several in vivo models, we established that miR-152 is a Paneth cell-specific microRNA.NEW & NOTEWORTHY In this study, first, microRNA atlas (and searchable web server) across all major small intestinal epithelial cell types is presented. We have demonstrated microRNAs that uniquely mark several lineages, including enteroendocrine and tuft. Identification of a key marker of mouse secretory progenitor cells, miR-672, which we show is deleted in humans. We have used several in vivo models to establish miR-152 as a specific marker of Paneth cells, which are highly understudied in terms of microRNAs.


Assuntos
Linhagem da Célula , Células Epiteliais/metabolismo , Perfilação da Expressão Gênica , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , MicroRNAs/genética , Transcriptoma , Animais , Biomarcadores/metabolismo , Separação Celular , Células Cultivadas , Biologia Computacional , Cães , Feminino , Citometria de Fluxo , Mucosa Intestinal/citologia , Intestino Delgado/citologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/metabolismo , Organoides , RNA-Seq , Análise de Célula Única
16.
J Vet Intern Med ; 35(5): 2102-2111, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34387901

RESUMO

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly prescribed in dogs, but the ideal dosage is unknown. HYPOTHESIS/OBJECTIVES: In dogs with cardiac disease, a dose-response relationship exists for ACEIs with respect to long-term outcome. ANIMALS: One hundred forty-four dogs with cardiac disease, 63 with current or prior congestive heart failure. METHODS: Retrospective medical record review. Cox proportional hazards models were used to determine variables associated with 2-year survival or survival from first-onset congestive heart failure (CHF). RESULTS: Median initial ACEI dosage was 0.84 (interquartile range [IQR], 0.56-0.98) mg/kg/day, and 108/144 (75%) of dogs received q12h dosing. No clinically relevant changes in renal function test results, serum electrolyte concentrations, or blood pressure occurred between initial prescription of ACEI and first reevaluation (median, 14 days later). In univariable analysis, higher ACEI dose was associated with increased survival from first-onset CHF (P = .005), and within the subgroup of dogs in CHF at the time of ACEI prescription, higher ACEI dose was associated with improved survival at 2 years (P = .04). In multivariable analysis, q12h dose frequency of ACEI (hazard ratio [HR], 0.30; 95% CI, 0.10-0.88; P = .03) and higher serum potassium concentration at visit 1 (HR, 0.39; 95% CI, 0.16-0.97; P = .04) were predictive of 2-year survival. The ACEIs were well-tolerated, with only 8/144 (5.6%) dogs having ACEI dose decreased or discontinued because of adverse effects. CONCLUSIONS AND CLINICAL IMPORTANCE: Twice daily dose frequency might optimize the cardioprotective benefit of ACEIs.


Assuntos
Doenças do Cão , Insuficiência Cardíaca , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Doenças do Cão/tratamento farmacológico , Cães , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/veterinária , Potássio , Modelos de Riscos Proporcionais , Estudos Retrospectivos
17.
Vet Surg ; 50(7): 1427-1433, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34251686

RESUMO

OBJECTIVE: Identify acceptable implant corridors in the normal canine thoracic vertebrae (T) from T1 to T9. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Computed tomographic (CT) studies of normal canine thoracic spines (n = 39). METHODS: CT imaging studies of normal T1-T9 canine spines were evaluated by five independent observers. Each identified a proposed corridor, measured the width, length, and angle off mid-sagittal that the corridor occupied. RESULTS: CT studies were from 39 dogs weighing 3.19-60 kg (mean 10.72, SD 9.9 kg). Vertebral corridors ranged in average width from 3.8 to 5.2 mm, the widest being located at T1. They ranged in average length from 13.3 to 17.5 mm, shortest being T1 and longest being T6. The angle of corridors varied the most between individual vertebrae at T1-T3. The average corridor angles were: T1 = 38°, T2 = 32°, T3 = 27°, T4 = 26°. T5-T9 angle ranged from 23° to 24°. CONCLUSION: The average dimensions of corridors measured in dogs weighing 3.1-60 kg were consistent with those of commercially available cortical screws and pins. CLINICAL SIGNIFICANCE: Corridor trajectories identified in this population can be achieved from a dorsal approach between T5 and T9. A dorsal approach for implant placement would be challenging for T1-T4 due to the variability found in these vertebrae as well as regional anatomical constraints.


Assuntos
Vértebras Torácicas , Tomografia Computadorizada por Raios X , Animais , Pinos Ortopédicos , Cães , Estudos Retrospectivos , Vértebras Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/veterinária
18.
Vet Surg ; 50(5): 1076-1086, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33955036

RESUMO

OBJECTIVE: To determine the influence of plating systems on the clinical outcomes in dogs treated for ilial fractures. DESIGN: Retrospective study. ANIMALS: Fifty-nine dogs (63 hemipelves). METHODS: Radiographs and medical records of dogs with ilial fractures presented to Iowa State University between 2003 and 2019 were reviewed. After fracture reduction, fractures were fixed with a locking plate system (LPS) or non-locking plate system (NLS). Perioperative, long-term complications, and follow-up data were recorded. The frequency of implant failure and pelvic collapse were compared using a logistic and linear regression analysis, respectively. Where the univariate test was statistically significant, a multivariate analysis across categories was performed to identify statistically different categories. RESULTS: LPS and NLS implants were used in 25/63 and 38/63 hemipelves, respectively. Median follow-up time was 8 weeks (3-624 weeks). Implant failure occurred in 18/63 (29%) of fracture repairs, consisting of 17 with NLS and 1 with LPS. Revision surgery was recommended in five cases of implant failure, all with NLS. The probability of implant failure was higher when fractures were fixed with NLS (p = .0056). All other variables evaluated did not seem to influence outcome measures. CONCLUSION: The variable with the most influence on the outcomes of dogs treated for ilial fractures consisted of the fixation method (NLS vs. LPS). Fractures repaired with NLS were nearly 20 times more likely to fail than those repaired with LPS. CLINICAL RELEVANCE: Surgeons should consider repairing ilial body fractures in dogs with LPS to reduce the risk of short-term implant failure.


Assuntos
Placas Ósseas/veterinária , Doenças do Cão/cirurgia , Fixação Interna de Fraturas/veterinária , Fraturas Ósseas/veterinária , Ílio/lesões , Animais , Cães , Feminino , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Ílio/cirurgia , Masculino , Radiografia , Estudos Retrospectivos , Resultado do Tratamento
19.
Vet Surg ; 50(5): 1065-1075, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33955568

RESUMO

OBJECTIVE: To determine radiation exposure to surgical personnel and to evaluate the accuracy of a modified percutaneous lag screw fixation technique for sacroiliac luxation (SIL) under fluoroscopic guidance in dogs. STUDY DESIGN: Cadaveric experimental study. SAMPLE POPULATION: Seventeen beagle cadavers with iatrogenic SIL. METHODS: Seventeen beagles with iatrogenic SIL underwent reduction and stabilization with 3.5-mm screws. Hypodermic needles (14 gauge) and fluoroscopy were used to orient two Kirschner wires for temporary stabilization and to guide drilling of glide and pilot holes using cannulated drill bits. Duration of surgery and radiation exposure were recorded. Postoperative computed tomographic evaluation of screw position and angulation was performed. RESULTS: Average time for fixation was 15.85 minutes (range, 6.37-33.5). Cumulative radiation doses of 0.4 mrem for the dominant arm of the assistant and 0 mrem for the primary surgeon were recorded. The mean dorsoventral and craniocaudal screw angles were 0.68° ± 3.4° (range - 5.4° to 9.5°) and 1.9° ± 3.2° (range - 4.3° to 9.1°), respectively. Sixteen of the 17 dogs had 100% sacral screw purchase, with the remaining case achieving 93.4% purchase. CONCLUSION: Fluoroscopy-assisted percutaneous placement of 3.5-mm cortical screws in lag fashion performed with 14-gauge needles in conjunction with Kirschner wires and cannulated drill bits yielded repeatable accurate screw placement with low levels of ionizing radiation exposure to the surgical team. CLINICAL SIGNIFICANCE: The described technique may be a viable method for minimally invasive osteosynthesis fixation of SIL with low levels of radiation exposure to the surgical team. These results provide evidence to support further evaluation of radiation exposure in clinical cases and can aid in study design and sample size determination.


Assuntos
Doenças do Cão/cirurgia , Fluoroscopia/veterinária , Fixação Interna de Fraturas/veterinária , Luxações Articulares/veterinária , Exposição à Radiação , Articulação Sacroilíaca , Animais , Parafusos Ósseos/veterinária , Cadáver , Cães , Fixação Interna de Fraturas/métodos , Tomografia Computadorizada por Raios X
20.
AAPS J ; 23(3): 59, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33907906

RESUMO

This review is a summary of factors affecting the drug pharmacokinetics (PK) of dogs versus humans. Identifying these interspecies differences can facilitate canine-human PK extrapolations while providing mechanistic insights into species-specific drug in vivo behavior. Such a cross-cutting perspective can be particularly useful when developing therapeutics targeting diseases shared between the two species such as cancer, diabetes, cognitive dysfunction, and inflammatory bowel disease. Furthermore, recognizing these differences also supports a reverse PK extrapolations from humans to dogs. To appreciate the canine-human differences that can affect drug absorption, distribution, metabolism, and elimination, this review provides a comparison of the physiology, drug transporter/enzyme location, abundance, activity, and specificity between dogs and humans. Supplemental material provides an in-depth discussion of certain topics, offering additional critical points to consider. Based upon an assessment of available state-of-the-art information, data gaps were identified. The hope is that this manuscript will encourage the research needed to support an understanding of similarities and differences in human versus canine drug PK.


Assuntos
Proteínas de Transporte/metabolismo , Doenças do Cão/tratamento farmacológico , Cães/fisiologia , Modelos Biológicos , Drogas Veterinárias/farmacocinética , Animais , Transporte Biológico/fisiologia , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Modelos Animais , Especificidade da Espécie , Drogas Veterinárias/uso terapêutico
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