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1.
Res Vet Sci ; 130: 133-138, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32172002

RESUMO

Ovariohysterectomized (OHE) female dogs do not develop the osteopenia and osteoporosis associated with decreasing estrogen in post-menopausal women, possibly due to post-OHE bone mineral density retention through a mechanism that remains unclear. In this study, we aimed to elucidate this mechanism by investigating estradiol (E2) and bone markers. Samples were collected from 56 OHE and 43 intact bitches (0.33 to 17.58 years old) and analyzed for serum E2, osteoclast-secreted cysteine protease cathepsin K (CTK), and N-telopeptide of type I collagen (NTx) by ELISA. OHE and intact bitches showed no significant difference in serum E2 or NTx, and there was no correlation between serum E2 and NTx and age and time since OHE. Intact bitches showed a very low correlation between E2 and NTx, but OHE bitches showed no correlation, and serum CTK was generally undetectable in both groups. Our findings suggest the influence of gonadal hormones on bone metabolism does not work effectively in dogs; this is consistent with a shorter duration of exposure to E2 in bitches (through the 4-to-8-month anestrus phase) than women.


Assuntos
Catepsina K/sangue , Colágeno Tipo I/sangue , Cães/metabolismo , Estradiol/sangue , Peptídeos/sangue , Animais , Biomarcadores/sangue , Feminino , Histerectomia/veterinária , Ovariectomia/veterinária , Estudos Retrospectivos
2.
Can J Vet Res ; 84(1): 37-43, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31949328

RESUMO

This study aimed to determine the effect of a single injection of paracetamol on the sevoflurane minimum alveolar concentration (MAC) response to noxious mechanical stimulation. Seven healthy adult beagles were enrolled in a prospective, randomized, blinded, crossover experimental study. Anesthesia was induced with propofol [11.6 ± 2.4 mg/kg body weight (BW)] and maintained with sevoflurane. The MAC was determined before (MAC-1) and after (MAC-2) treatment with 15 mg/kg BW of intravenous (IV) paracetamol or saline over 15 minutes. Samples for plasma paracetamol determination were collected immediately after IV treatment administration and following MAC-2 determination (123 ± 27 minutes after starting paracetamol administration). The MAC-1 was similar between treatments (1.7% ± 0.4%). There were no differences between control and paracetamol groups at MAC-2 (2.0% ± 0.4% and 1.7% ± 0.5%, respectively; P = 0.285). Paracetamol plasma concentrations after paracetamol administration were 34.5 ± 9.9 µg/mL, decreasing at the end of the procedure (8.5 ± 4.2 µg/mL). In conclusion, 15 mg/kg BW of IV paracetamol did not significantly reduce sevoflurane MAC in healthy dogs.


Assuntos
Acetaminofen/farmacologia , Analgésicos não Entorpecentes/farmacologia , Anestésicos Inalatórios/metabolismo , Cães/metabolismo , Alvéolos Pulmonares/metabolismo , Sevoflurano/metabolismo , Acetaminofen/administração & dosagem , Analgésicos não Entorpecentes/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Animais , Estudos Cross-Over , Método Duplo-Cego , Feminino , Masculino , Propofol/administração & dosagem , Estudos Prospectivos , Distribuição Aleatória
3.
BMC Vet Res ; 15(1): 415, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752848

RESUMO

BACKGROUND: Currently, [18F] altanserin is the most frequently used PET-radioligand for serotonin2A (5-HT2A) receptor imaging in the human brain but has never been validated in dogs. In vivo imaging of this receptor in the canine brain could improve diagnosis and therapy of several behavioural disorders in dogs. Furthermore, since dogs are considered as a valuable animal model for human psychiatric disorders, the ability to image this receptor in dogs could help to increase our understanding of the pathophysiology of these diseases. Therefore, five healthy laboratory beagles underwent a 90-min dynamic PET scan with arterial blood sampling after [18F] altanserin bolus injection. Compartmental modelling using metabolite corrected arterial input functions was compared with reference tissue modelling with the cerebellum as reference region. RESULTS: The distribution of [18F] altanserin in the canine brain corresponded well to the distribution of 5-HT2A receptors in human and rodent studies. The kinetics could be best described by a 2-Tissue compartment (2-TC) model. All reference tissue models were highly correlated with the 2-TC model, indicating compartmental modelling can be replaced by reference tissue models to avoid arterial blood sampling. CONCLUSIONS: This study demonstrates that [18F] altanserin PET is a reliable tool to visualize and quantify the 5-HT2A receptor in the canine brain.


Assuntos
Encéfalo/metabolismo , Cães/metabolismo , Ketanserina/análogos & derivados , Tomografia por Emissão de Pósitrons/veterinária , Antagonistas da Serotonina/farmacocinética , Animais , Feminino , Radioisótopos de Flúor , Ketanserina/administração & dosagem , Ketanserina/farmacocinética , Modelos Biológicos , Antagonistas da Serotonina/administração & dosagem
4.
Am J Vet Res ; 80(11): 1007-1009, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31644338

RESUMO

OBJECTIVE: To determine the effect of oral administration of gabapentin (20 mg/kg) on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 healthy adult dogs (3 males and 3 females with a mean ± SD body weight of 24.8 ± 1.3 kg). PROCEDURES: Each dog was anesthetized twice. Dogs were initially assigned to 1 of 2 treatments (gabapentin [20 mg/kg, PO] followed 2 hours later by anesthesia maintained with isoflurane or anesthesia maintained with isoflurane alone). A minimum of 7 days later, dogs received the other treatment. The MAC of isoflurane was determined by use of an iterative bracketing technique with stimulating electrodes placed in the maxillary buccal mucosa. Hemodynamic variables and vital parameters were recorded at the lowest end-tidal isoflurane concentration at which dogs did not respond to the stimulus. Effect of treatment on outcome variables was analyzed by use of a paired t test. RESULTS: Mean ± SD MAC of isoflurane was significantly lower when dogs received gabapentin and isoflurane (0.71 ± 0.12%) than when dogs received isoflurane alone (0.91 ± 0.26%). Mean reduction in MAC of isoflurane was 20 ± 14%. Hemodynamic variables did not differ significantly between treatments. Mean time to extubation was significantly less when dogs received gabapentin and isoflurane (6 ± 4 minutes) than when dogs received isoflurane alone (23 ± 15 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of gabapentin 2 hours before anesthesia maintained with isoflurane had a MAC-sparing effect with no effect on hemodynamic variables or vital parameters of dogs.


Assuntos
Anestésicos Inalatórios/farmacocinética , Cães/metabolismo , Gabapentina/farmacologia , Isoflurano/farmacocinética , Alvéolos Pulmonares/efeitos dos fármacos , Administração Oral , Anestésicos Inalatórios/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Feminino , Gabapentina/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Isoflurano/administração & dosagem , Masculino , Alvéolos Pulmonares/metabolismo
5.
J Anim Physiol Anim Nutr (Berl) ; 103(6): 1952-1958, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31529724

RESUMO

The correct assumption of metabolisable energy (ME) requirement is essential for the nutrition consultation and diet formulation. In young dogs, too high energy supply can accelerate growth and thus lead to developmental orthopaedic diseases. The aim of the present study was to collect the data on ME intake and body weight (BW) development in privately owned growing dogs in order to compare these data with the current recommendations. Our hypothesis was that the actual ME intake of healthy young dogs would be lower than the actual recommendation. The data of 493 privately owned puppies (median age at first consultation 21 weeks, the median expected mature BW 30 kg) on ME intake, actual and expected mature BW were collected and compared with recommendations of the Society of Nutrition Physiology (GfE, Meyer and Zentek and NRC). In 243 dogs, there was a follow-up. The actual BW did not deviate systematically from the calculated expected BW (R2  = .929). The ME intake significantly decreased with age (p < .05) and significantly increased with expected mature BW (p < .05). There was no significant interaction between these two parameters (p > .05). Sex had no effect on the ME intake (p > .05). The ME intake of young dogs with a history of skeletal problems or of food allergy did not differ systematically from healthy dogs of similar age and expected mature BW. The ME intake was considerably below NRC recommendations, especially in younger puppies (>8-17 weeks: 78%, >17-26 weeks: 83% of NRC recommendation). A predictive linear equation for ME intake was developed: ME intake (MJ) = (1.063 - 0.565 × [actual BW/expected mature BW]) × actual BW0.75 .


Assuntos
Cães/metabolismo , Ingestão de Energia/fisiologia , Envelhecimento , Ração Animal , Animais , Cães/crescimento & desenvolvimento
6.
Am J Vet Res ; 80(10): 957-962, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31556716

RESUMO

OBJECTIVE: To determine the pharmacokinetics of levofloxacin following oral administration of a generic levofloxacin tablet and IV administration to dogs and whether the achieved plasma levofloxacin concentration would be sufficient to treat susceptible bacterial infections. ANIMALS: 6 healthy adult Beagles. PROCEDURES: Levofloxacin was administered orally as a generic 250-mg tablet (mean dose, 23.7 mg/kg) or IV as a solution (15 mg/kg) to each dog in a crossover study design, with treatments separated by a minimum 2-day washout period. Blood samples were collected at various points for measurement of plasma levofloxacin concentration via high-pressure liquid chromatography. Pharmacokinetic analysis was performed with compartmental modeling. RESULTS: After oral administration of the levofloxacin tablet, mean (coefficient of variation) peak plasma concentration was 15.5 µg/mL (23.8%), mean elimination half-life was 5.84 hours (20.0%), and mean bioavailability was 104% (29.0%). After IV administration, mean elimination half-life (coefficient of variation) was 6.23 hours (14.7%), systemic clearance was 145.0 mL/kg/h (22.2%), and volume of distribution was 1.19 L/kg (17.1%). CONCLUSIONS AND CLINICAL RELEVANCE: In these dogs, levofloxacin was well absorbed when administered orally, and a dose of approximately 25 mg/kg was sufficient to reach pharmacokinetic-pharmacodynamic targets for treating infections with susceptible Enterobacteriaceae (ie, ≤ 0.5 µg/mL) or Pseudomonas aeruginosa (ie, ≤ 1 µg/mL) according to clinical breakpoints established by the Clinical and Laboratory Standards Institute.


Assuntos
Antibacterianos/farmacocinética , Cães/metabolismo , Levofloxacino/farmacocinética , Administração Intravenosa , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão/veterinária , Estudos Cross-Over , Feminino , Meia-Vida , Levofloxacino/administração & dosagem , Masculino , Comprimidos
7.
Am J Vet Res ; 80(10): 969-975, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31556717

RESUMO

OBJECTIVE: To determine pharmacokinetic and pharmacodynamic properties of the injectable formulation of dexmedetomidine administered via the oral transmucosal (OTM) route to healthy dogs. ANIMALS: 6 healthy dogs. PROCEDURES: Injectable dexmedetomidine was administered IV (5 µg/kg) or via the OTM route (20 µg/kg) in a blinded, single-observer, randomized crossover study. Dogs received dexmedetomidine and a sham treatment at each administration. Serial blood samples were collected from a catheter in a saphenous vein. Heart rate, respiratory rate, and subjective sedation score were assessed for 24 hours after administration. Plasma samples were analyzed for dexmedetomidine concentrations by use of ultraperformance liquid chromatography-tandem mass spectrometry. RESULTS: For the OTM route, the mean ± SD maximum plasma concentration was 3.8 ± 1.3 ng/mL, which was detected 73 ± 33 minutes after administration. The mean maximum concentration for the IV dose, when extrapolated to the time of administration, was 18.6 ± 3.3 ng/mL. The mean terminal-phase half-life was 152 ± 146 minutes and 36 ± 6 minutes for OTM and IV administration, respectively. After IV administration, total clearance was 8.0 ± 1.6 mL/min/kg and volume of distribution at steady state was 371 ± 72 mL/kg. Bioavailability for OTM administration of dexmedetomidine was 11.2 ± 4.5%. Peak sedation scores did not differ significantly between routes of administration. Decreases in heart rate, respiratory rate, and peak sedation score were evident sooner after IV administration. CONCLUSIONS AND CLINICAL RELEVANCE: OTM administration of the injectable formulation of dexmedetomidine resulted in a similar degree of sedation and prolonged duration of action, compared with results for IV administration, despite relatively low bioavailability.


Assuntos
Dexmedetomidina/farmacocinética , Cães/metabolismo , Hipnóticos e Sedativos/farmacocinética , Administração Intravenosa , Administração através da Mucosa , Administração Oral , Animais , Disponibilidade Biológica , Cromatografia Líquida , Estudos Cross-Over , Dexmedetomidina/administração & dosagem , Feminino , Meia-Vida , Frequência Cardíaca/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Infusões Intravenosas , Masculino , Taxa Respiratória/efeitos dos fármacos
8.
PLoS One ; 14(8): e0220305, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31374084

RESUMO

Calcium and phosphorus requirements for growing dogs can be calculated by different methods. The current standard feeding recommendations are based on experimental data derived from young giant breed puppies. In order to determine the absolute requirement, an extrapolation via metabolisable energy requirement is recommended. Another approach is to calculate the requirement factorially, taking into account the endogenous losses and the amount of calcium and phosphorus retained due to tissue accretion during growth as well as the expected availability of these nutrients. The working hypothesis was that both methods are valid and lead to comparable results in young puppies of a high mature body weight (BW). Yet, deviations for other age and mature BW groups were expected. Thus, the aim of the present study was to compare the results of both methods using exemplary puppies of different age and mature BW groups. The hypotheses could be verified for calcium. The extrapolated requirements overestimate the factorial requirements by up to 59.7% for puppies <60kg mature BW and/or >6 months of age. In case of phosphorus requirement, the deviations between both methods are overall very high in all stages. Taking into account the potentially harmful effects of calcium and phosphorus excess, the feeding recommendations based on the extrapolation should be reconsidered.


Assuntos
Cálcio na Dieta/análise , Cães/crescimento & desenvolvimento , Necessidades Nutricionais , Fósforo/análise , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Peso Corporal , Cálcio na Dieta/metabolismo , Cães/metabolismo , Cães/fisiologia , Metabolismo Energético , Absorção Intestinal , Fósforo/metabolismo
9.
Vet Anaesth Analg ; 46(5): 605-612, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31395484

RESUMO

OBJECTIVE: To evaluate the cardiovascular effects, pharmacokinetic (PK) data and recovery characteristics of an alfaxalone constant rate infusion (CRI) of different duration in dogs at manufacturer's recommended dose rate. STUDY DESIGN: Experimental, prospective, randomized, crossover study. ANIMALS: Six intact female Beagles. METHODS: Following an intravenous alfaxalone bolus (3 mg kg-1), anaesthesia was maintained using an alfaxalone CRI at 0.15 mg kg-1 minute-1 for 90 (short CRI) or 180 minutes (long CRI). Venous blood samples were collected to determine the PK profile. Cardiovascular variables and recovery characteristics were evaluated. Recovery was scored on a scale ranging from 0, excellent to 4, bad. A mixed-model statistical approach was used to compare the cardiovascular parameters (global α = 0.05). An analysis of variance was performed to compare PK parameters and recovery times between treatments. RESULTS: No significant difference was noted between protocols for any PK parameter. Volume of distribution at steady state (935.74 ± 170.25 versus 1119.15 ± 190.65 mL kg-1), elimination half-life (12 ± 2 versus 13 ± 3 minutes), clearance from the central compartment (26.02 ± 4.41 versus 27.74 ± 5.65 mL kg-1 minute-1) and intercompartmental clearance (8.47 ± 4.06 versus 12.58 ± 7.03 mL kg-1 minute-1) were comparable for short CRI and long CRI. Cardiovascular variables remained within physiological limits. Mechanical ventilation was necessary (short CRI: n = 1, long CRI: n = 4). The manufacturer's recommended dose rate resulted in a light plane of anaesthesia. No significant differences in recovery times and scores were observed between treatments. The quality of recovery was scored as very poor with both protocols. CONCLUSIONS AND CLINICAL RELEVANCE: PK data were similar between long and short infusions of alfaxalone at the manufacturer's recommended dose, with acceptable cardiovascular conditions. Nevertheless, both protocols resulted in a superficial plane of general anaesthesia with poor recovery characteristics.


Assuntos
Anestesia Intravenosa/veterinária , Anestésicos Intravenosos/farmacocinética , Cães/fisiologia , Pregnanodionas/farmacocinética , Período de Recuperação da Anestesia , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/sangue , Anestésicos Intravenosos/farmacologia , Animais , Estudos Cross-Over , Cães/metabolismo , Feminino , Frequência Cardíaca/efeitos dos fármacos , Pregnanodionas/administração & dosagem , Pregnanodionas/sangue , Pregnanodionas/farmacologia , Estudos Prospectivos
10.
J Vet Cardiol ; 24: 58-63, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31405555

RESUMO

INTRODUCTION: The objective of the present study was to evaluate the pharmacokinetics of a compounded sustained-release procainamide formulation in normal dogs. ANIMALS: Six healthy, purpose-bred mixed-breed dogs participated in the study. METHODS: In phase I, two dogs were administered oral procainamide (30 mg/kg), and plasma was obtained to determine plasma concentration ranges and duration. In phase II, six dogs were administered procainamide (30 mg/kg by mouth every 12 hours) to determine the pharmacokinetics of sustained-release procainamide. Serum procainamide concentration was determined using an immunochemistry assay. RESULTS: No adverse clinical effects were noted in any of the dogs studied. The average maximum serum concentration, average serum concentration, and average minimum serum concentration were 10.17, 7.13, and 3.07 µg/mL, respectively. The average time over a 12-h period during which procainamide concentration exceeded 12 µg/mL was 2.35 h, was between 4 and 12 µg/mL was 7.19 h, and was less than 4 µg/mL was 2.46 h. The average times at maximum concentration and minimum concentration were 18.67 and 12.25 h, respectively. CONCLUSIONS: Administration of sustained-release procainamide twice daily achieved targeted plasma concentrations in most dogs. Evaluation of serum trough concentrations should be considered owing to interanimal variability to confirm that serum concentrations are within the reported therapeutic range for an individual patient.


Assuntos
Antiarrítmicos/farmacocinética , Preparações de Ação Retardada/farmacocinética , Cães/metabolismo , Procainamida/farmacocinética , Administração Oral , Animais , Antiarrítmicos/administração & dosagem , Antiarrítmicos/sangue , Preparações de Ação Retardada/administração & dosagem , Cães/sangue , Feminino , Masculino , Procainamida/administração & dosagem , Procainamida/sangue , Valores de Referência
11.
Vet Anaesth Analg ; 46(5): 560-567, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31351807

RESUMO

OBJECTIVE: To investigate the preoperative calming effect of melatonin and its influence on propofol dose for anesthesia induction in dogs. STUDY DESIGN: Prospective, randomized, blinded, placebo-controlled clinical study. ANIMALS: A total of 50 healthy, adult, client-owned dogs scheduled for elective surgery. METHODS: Dogs were equally divided into treatment group M, which received 5 mg kg-1 melatonin, and placebo-control group P (sucrose), both administered orally 2 hours prior to induction of anesthesia. Dogs were subjectively characterized and further designated as skeptical (group S; n = 18) or trustful (group T; n = 32). Behavior, calming effect and vital parameters (pulse rate, respiratory rate, blood pressure, rectal temperature) were evaluated before and after treatment. Propofol dose [mg kg-1 intravenously (IV)] to allow endotracheal intubation and anesthesia induction quality was documented. Data were analyzed using a general linear model and Mann-Whitney U tests. RESULTS: Dogs in group MS (n = 10) were calmer than those in group PS (n = 8) at 90 minutes after drug administration (p = 0.047). Group MT (n = 15) required less propofol (5.98 ± 0.96 mg kg-1) than group PT (n = 17; 7.04 ± 1.82 mg kg-1 IV; p = 0.048) and group MS (9.48 ± 3.22 mg kg-1 IV; p = 0.007). Group PS required 7.69 ± 2.71 mg kg-1 IV. Skeptical dogs showed more reactions during induction (p = 0.013). Vital parameters were within physiological ranges before and after treatment. CONCLUSION AND CLINICAL RELEVANCE: Results showed that melatonin may be used to reduce propofol dose for anesthesia induction in trustful dogs. Skeptical dogs benefitted from the calming properties. Potentially, melatonin could be used to minimize the level of excitement before general anesthesia and to reduce the required propofol dose for induction.


Assuntos
Anestesia Geral/veterinária , Anestésicos Intravenosos/farmacocinética , Depressores do Sistema Nervoso Central/farmacologia , Cães/fisiologia , Melatonina/farmacologia , Propofol/farmacocinética , Anestésicos Intravenosos/administração & dosagem , Animais , Depressores do Sistema Nervoso Central/administração & dosagem , Cães/metabolismo , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Masculino , Melatonina/administração & dosagem , Período Pré-Operatório , Propofol/administração & dosagem , Estudos Prospectivos , Valores de Referência , Taxa Respiratória/efeitos dos fármacos
12.
Mol Biol Rep ; 46(5): 4909-4919, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31264163

RESUMO

Lysyl oxidase (LOX) is an extracellular metalloenzyme which mediates crosslinking of collagen and elastin. It has been reported to play a pivotal role in cancer metastasis especially in women suffering from breast cancer. The present study is the first to evaluate the gene expression levels of LOX by Real time-polymerase chain reaction (Real time-PCR) in dogs with mammary tumor besides molecular cloning and expression of canine lysyl oxidase gene (lox). Real time-PCR studies showed a significant upregulation (threefold higher) of lox in mammary tumor cases as compared to healthy dogs indicating its possible diagnostic and prognostic role in canine mammary tumors (CMTs). Cloning and sequencing of lox gene revealed 1230 bp CDS which is mostly conserved in C-terminal region. Sequence analysis of canine lox showed that it shares 99% homology with the predicted sequence available on NCBI and had greatest identity with the lox gene from cat. Protein structure predicted with homology modelling was validated by Ramachandran plot analysis which revealed most (approximately 95%) of the amino acids in favoured region. Additionally, recombinant lysyl oxidase expressed as His-tagged fusion protein in prokaryotic expression vector (pPROExHTa) was used in an ELISA for detection of circulating protein LOX in serum of CMT subjects. Receiver operating characteristics analysis of the ELISA revealed high sensitivity (90%) and specificity (85%) with histopathology as reference standard. Taken together, we propose LOX as a diagnostic biomarker and a putative prognostic candidate in CMT cases.


Assuntos
Neoplasias Mamárias Animais/diagnóstico , Neoplasias Mamárias Animais/metabolismo , Proteína-Lisina 6-Oxidase/genética , Animais , Biomarcadores Tumorais/metabolismo , Cães/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/cirurgia , Neoplasias Mamárias Animais/genética , Prognóstico , Proteína-Lisina 6-Oxidase/análise , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Proteínas Recombinantes/genética , Transcriptoma/genética
13.
Res Vet Sci ; 125: 309-314, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31351201

RESUMO

Vilazodone (VLZ) is a drug approved for the treatment of major depressive disorder in humans but no data are available for dogs. The present study aimed to evaluate the pharmacokinetics of a single oral 40 mg dose of VLZ in healthy Labrador dogs (n = 6) in fasted and fed conditions. Dogs were randomly divided in two (n = 3) groups in a cross-over study design (2 × 2). Group I was administered with VLZ at 40 mg/dog after fasting over-night. Group II was fed prior to and after administration of the same dose. A two-week wash-out period was observed. Plasma samples collected underwent LC-MS/MS analysis. VLZ concentrations were quantified in dogs' plasma in two different windows of time: 30 min to 10 h for the fasted group and 4 h to 35 h for the fed group. The values for t1/2λz were statistically different between the groups (fed, 4.6 ±â€¯1.1 h vs fasted, 1.7 ±â€¯0.2 h). Tmax drastically changed between the groups (fed, 10 h vs fasted, 1.5 h), while Cmax did not significantly vary (fed, 39.4 ±â€¯5.6 ng/mL vs fasted, 38.7 ±â€¯4.8 ng/mL). The AUC value was always statistically higher in the fed group. As a result, the average relative oral fasted bioavailability of VLZ was low, 28.8 ±â€¯6.1%. In conclusion, feeding can affect the pharmacokinetics of VLZ in the dog.


Assuntos
Antidepressivos/farmacocinética , Cães/metabolismo , Jejum/metabolismo , Cloridrato de Vilazodona/farmacocinética , Animais , Cromatografia Líquida , Estudos Cross-Over , Feminino , Masculino , Distribuição Aleatória , Espectrometria de Massas em Tandem
14.
Vet Anaesth Analg ; 46(5): 568-578, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31326349

RESUMO

OBJECTIVE: To develop a population pharmacokinetic model for propofol target-controlled infusion (TCI) in dogs and to evaluate its performance for use in the clinical setting. STUDY DESIGN: Prospective clinical study. ANIMALS: A group of 40 client-owned dogs undergoing general anaesthesia for magnetic resonance imaging. METHODS: Propofol was administered to 26 premedicated dogs and arterial blood samples were collected during the infusion and over 240 minutes after terminating the infusion. Propofol concentrations were measured by high-performance liquid chromatography. A population pharmacokinetic analysis was performed using a nonlinear mixed-effects modelling approach, allowing inter- and intra-individual variability estimation and quantitative evaluation of the influence of the following covariates: weight, body condition score, age, size-related age (Age_size), sex, premedication type, size and contrast agent administration. A final model was obtained using a stepwise approach in which individual covariate effects on each pharmacokinetic variable were incorporated. The performance of the developed TCI model was subsequently evaluated while inducing and maintaining anaesthesia in 14 premedicated dogs and assessed by comparing predicted and measured concentrations at specific time points. RESULTS: Propofol pharmacokinetics was best described by a three-compartment model. Weight, Age_size, premedication and sex showed significant pharmacokinetic effects. Addition of the significant covariate/variable associations to the final model resulted in a reduction of the objective function value from 285.53 to -22.34. The median values of prediction error and absolute performance error were 3.1% and 28.4%, respectively. Induction targets between 4.0 and 6.5 µg mL-1 allowed intubation within 5.0 ± 0.9 minutes. Anaesthesia was achieved with targets between 3.0 and 6.5 µg mL-1. Mean time to extubation was 9.7 ± 2.6 minutes. All dogs recovered smoothly and without complications. CONCLUSIONS AND CLINICAL RELEVANCE: Overall predictive performance of the pharmacokinetic model-driven infusion developed was clinically acceptable for administering propofol to dogs in routine anaesthesia.


Assuntos
Anestesia Geral/veterinária , Anestésicos Intravenosos/farmacocinética , Cães/fisiologia , Propofol/farmacocinética , Anestésicos Intravenosos/administração & dosagem , Animais , Cães/metabolismo , Feminino , Masculino , Modelos Psicológicos , Propofol/administração & dosagem , Estudos Prospectivos
15.
BMC Vet Res ; 15(1): 145, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088464

RESUMO

BACKGROUND: Melatonin regulates metabolism and metabolism related hormones in mammalians. Castration has some adverse effects on the metabolic hormones of dog. This study was conducted to determine the effects of oral melatonin administration on metabolic hormones, as well as to compare changes of these hormones after administration of melatonin in castrated and intact dogs. Twenty healthy mixed breed mature male dogs were divided randomly into four groups (n = 5): melatonin (3 mg/10 kg(, castrated, castrated and melatonin treated, and negative control. Blood sample was collected from jugular vein weekly for 1 month. RESULTS: T3 and T4 hormones had a significant decrease within 1 month following administration of melatonin. No significant change was observed in concentration of FT3 and FT4 hormones. Leptin and ghrelin hormones also had a significant decrease in this period. Leptin and ghrelin had a more significant decrease in "non-castrated and melatonin treated" group compared to "castrated and melatonin treated" group. Galanin had a significant decrease but this neurotransmitter had no significant change in "non-castrated and melatonin treated" group in comparison to "castrated and melatonin treated" group. CONCLUSIONS: It seems that daily administration of melatonin capsule in all dogs can probably decrease concentration of T3 and T4 hormones and balance other metabolic hormones following castration. METHODS: The dogs underwent castration, melatonin treatment and blood sampling.


Assuntos
Cães/metabolismo , Galanina/sangue , Grelina/sangue , Leptina/sangue , Melatonina/farmacologia , Orquiectomia/veterinária , Hormônios Tireóideos/sangue , Administração Oral , Animais , Estudos de Casos e Controles , Masculino , Melatonina/administração & dosagem , Orquiectomia/efeitos adversos
16.
Vet Anaesth Analg ; 46(3): 375-383, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30981587

RESUMO

OBJECTIVE: To measure plasma methadone concentrations in bitches and the umbilical cords of their puppies after systemic or epidural administration. STUDY DESIGN: Prospective, randomized, clinical study. ANIMALS: A total of 27 healthy pregnant female dogs undergoing caesarean section, 4.3 ± 2.3 years of age and weighing 19.9 ± 13.2 kg. METHODS: The dogs were randomly divided into three groups: 1) intramuscular methadone (0.3 mg kg-1) (group MET; n = 9); 2) epidural methadone (0.1 mg kg-1) (group METEPI; n = 9); and 3) epidural lidocaine (4.4 mg kg-1) [group CON (control group); n = 9]. Ten minutes before induction, methadone was administered intramuscularly to the group MET dogs. Anaesthesia was induced with propofol and maintained with isoflurane. Cardiovascular and respiratory parameters were monitored throughout the anaesthesia. After induction, epidural anaesthesia was administered to dogs in groups METEPI and CON. Before any treatment (T0) and, as soon as the last foetus was removed from the uterus (T1), venous blood samples were collected from each dog into heparinized tubes; the umbilical cords were collected and stored at -80 °C until pharmacological analysis was carried out. The samples were analysed using ultra performance liquid chromatography. RESULTS: The cardiorespiratory parameters of the bitches and of the puppies at birth, and the Apgar scores did not differ significantly between groups. At T1 both the median maternal methadone plasma concentration and the median methadone umbilical cord concentration were higher in group MET compared to group METEPI (p = 0.0018 and p = 0.004, respectively). The maternal plasma concentration was higher than the concentration in the umbilical cords (p = 0.05) in group METEPI but not in group MET (p = 0.25). CONCLUSIONS AND CLINICAL RELEVANCE: Epidural methadone (0.1 mg kg-1) administered to bitches undergoing caesarean section is associated with lower umbilical cord methadone concentrations as compared with intramuscularly administered methadone at higher dosages (0.3 mg kg-1).


Assuntos
Analgésicos Opioides/sangue , Anestesia/veterinária , Cesárea/veterinária , Cães/sangue , Metadona/sangue , Cordão Umbilical/metabolismo , Analgésicos Opioides/administração & dosagem , Anestesia Epidural/veterinária , Animais , Cães/metabolismo , Feminino , Injeções Intramusculares , Isoflurano/administração & dosagem , Metadona/administração & dosagem , Gravidez , Propofol/administração & dosagem , Distribuição Aleatória
17.
Res Vet Sci ; 124: 233-238, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30933891

RESUMO

PURPOSE: Promising results have been described for antibodies binding vascular endothelial growth factor (VEGF) in patients with corneal neovascularization. Whether veterinary patients would also benefit from this therapeutic approach has not been investigated yet. We examined binding properties of anti-human VEGF antibodies bevacizumab (Avastin®) and aflibercept (Zaltrap®) for canine, feline, and equine VEGF. METHODS: Human, equine, feline, and canine VEGF were analyzed for sequence similarity using the "Basic Local Alignment Search Tool" (BLAST). Western-blot analysis and ELISA were used to assess binding properties. RESULTS: BLAST analysis revealed a sequence homology of canine, feline, and equine VEGF to human VEGF-A of 93%, 92%, and 89%, respectively. Western-blot analysis showed immunoreactivity of bevacizumab with human, canine, and feline VEGF, but not with equine VEGF. Aflibercept recognized VEGF of all tested species. ELISA data indicated that bevacizumab and aflibercept bind canine VEGF in a dose-dependent manner. Feline VEGF was bound by bevacizumab and aflibercept in a dose-independent manner. ELISA study further confirmed the lack of bevacizumab binding to equine VEGF, and yielded also a dose-independent binding by aflibercept. CONCLUSIONS: Bevacizumab and aflibercept turned out to bind VEGF with species-specific differences. Further studies are required to investigate their efficacy and safety under clinical conditions.


Assuntos
Inibidores da Angiogênese/metabolismo , Bevacizumab/metabolismo , Gatos/metabolismo , Cães/metabolismo , Cavalos/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Humanos , Ligação Proteica
18.
Theriogenology ; 131: 41-46, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30939355

RESUMO

The main aim of this study was to investigate the effect of pyometra on glycosylation of proteins in the uterine tissues from female dogs, using western blotting with selected lectins (Sambucus nigra agglutinin - SNA and Maackia amurensis agglutinin - MAL II). In addition protein pattern of examined tissues was also evaluated. The study was performed on 10 female dogs undergoing ovariohysterectomy because of pyometra and 10 clinically healthy female dogs, undergoing elective spaying (ovariohysterectomy). Uterine tissue samples of 1 cm2 were taken from the middle region of each uterine horn in both group of animals immediately after ovariohysterectomy. Tissue samples were homogenized and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting with SNA and MAL II. SDS-PAGE analysis showed differences between pyometra samples and controls in the amount of obtained protein fractions and the protein content in the individual fractions. Five protein (with a molecular weight of 193.78 kDa, 103.18 kDa, 77.67 kDa, 70.39 kDa, and 53.00 kDa) were found only in the pyometra samples. The remaining fractions differed in intensity of staining, which indicated differ abundance of a given protein. The results of western blotting with SNA and MAL II demonstrated that the pattern obtained from densitometric analysis differs between adequate healthy and pyometra samples with regard to the amount of protein fraction obtained as well as the intensity of staining of particular fraction. The pyometra tissues contained seven SNA-binding proteins (with a molecular weight 189.94 kDa, 165.51 kDa, 100.94 kDa, 59.42 KDa, 41.32 kDa, 35.16 kDa, and 32.6 kDa) that were not in the healthy tissues. Of the nine remaining fractions, six showed significantly higher (P < 0.05) intensity of staining in the healthy uterine tissues. In turn, the MAL II-binding protein with a molecular weight 75.85 kDa, 51.12 kDa, and 49.98 kDa were found only in the pyometra samples. Of the 28 remaining fractions, ten demonstrated significantly higher (P < 0.05), and five fractions had significantly lower (P < 0.05) intensity of staining in the pyometra tissues. The results obtained indicate that proteins in uterine tissues from female dogs with pyometra are differently glycosylated compared to normal uterine tissues. These findings provide the basis for further studies of the possible role of glycosylation in the pathogenesis of canine pyometra.


Assuntos
Doenças do Cão/metabolismo , Cães/metabolismo , Piometra/veterinária , Útero/metabolismo , Animais , Feminino , Glicosilação , Piometra/metabolismo
19.
Metabolomics ; 15(2): 15, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30830416

RESUMO

INTRODUCTION: We recently identified variances in serum metabolomic profiles between fasted diabetic and healthy dogs, some having similarities to those identified in human type 1 diabetes. OBJECTIVES: Compare untargeted metabolomic profiles in the non-fasted state. METHODS: Serum from non-fasted diabetic (n = 6) and healthy control (n = 6) dogs were analyzed by liquid chromatography-high resolution mass spectrometry. RESULTS: Clear clustering of metabolites between groups were observed, with multiple perturbations identified that were similar to those previously observed in fasted diabetic dogs. CONCLUSION: These findings further support the development of targeted assays capable of detecting metabolites that may be useful as biomarkers of canine diabetes.


Assuntos
Diabetes Mellitus/metabolismo , Diabetes Mellitus/veterinária , Cães/metabolismo , Animais , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Análise por Conglomerados , Cães/sangue , Metaboloma , Metabolômica/métodos , Espectrometria de Massas em Tandem
20.
J Vet Med Sci ; 81(5): 712-716, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-30918224

RESUMO

Phosphofructokinase-1 (EC:2.7.1.11, PFK-1) catalyzes the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate using adenosine triphosphate and is a key regulatory enzyme of glycolysis. Mammalian PFK-1 isozymes are composed of three kinds of subunits (PFK-M, -L, and -P), with different properties. It has been suggested that the proportion of PFK-1 subunits in different organs is based on the organ energy metabolism. In this study, we analyzed the activity and subunit composition of canine PFK-1. We found that, in dogs, the skeletal muscle only has PFK-M, the liver mainly has PFK-L, and the brain expresses all of them. The knowledge of the composition of PFK-1 could provide useful information for determination of the differences in glycolysis in various organs of dogs.


Assuntos
Cães/metabolismo , Isoenzimas/metabolismo , Fosfofrutoquinase-1/metabolismo , Animais , Encéfalo/enzimologia , Feminino , Fígado/enzimologia , Masculino , Músculo Esquelético/enzimologia , Fosfofrutoquinase-1/química , Distribuição Tecidual
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