Pharmacokinetics and pharmacodynamics of dextroketamine alone or combined with midazolam in Caiman crocodilus.

Pharmacokinetics studies of anesthetic agents are important for understanding of the pharmacology and metabolism of anesthetic agents in reptilians. This study was designed to examine the pharmacokinetic and pharmacodynamic properties of intravenous dextroketamine alone or combined with midazolam in Caiman crocodilus. Eight caimans were anesthetized with dextroketamine (10 mg/kg; group D) or dextroketamine and midazolam (10 and 0.5 mg/kg respectively; group DM) into the occipital venous sinus. The pharmacokinetic parameters were calculated by HPLC using a non-compartmental modeling. Serial blood samples were collected at baseline and within 15 and 30 min, and 11.5, 2, 4, 8, 12, 24 and 48 h of drug administration. Sedation status over time differed between groups. All animals in group D (8/8; 100%) showed signs of light sedation at t10. Half (4/8; 50%) of these caimans did not progress to deeper levels of sedation. In spite of light sedation at t10, animals in group DM were deeply sedated within 13.13 ± 7.04 min of anesthetic agent injection. The area under the plasma concentration-time curve (AUC0-48) and half-life of dextroketamine changed significantly after combination with midazolam. Even without significant changes in clearance, the almost two-fold increase in the half-life of dextroketamine suggests a slower rate of elimination.

Pericardiotomy by Transdiaphragmatic Thoracoscopy Singleport in Horses.

Thoracoscopy pericardiotomy consists of endoscopic access to the thoracic cavity to perform the opening of the pericardial sac, described in the equine species only through the intercostal access, and there are no studies addressing the singleport transdiaphragmatic access, so the objective was to develop the pericardiotomy technique by transdiaphragmatic thoracoscopy using a single port. The technique was performed using six cadavers of adult horses, positioned in dorsal decubitus, making it possible to initiate access with an incision in the region proximal to the xiphoid process, for the introduction of an 11 mm endotip trocar, which through the diaphragm reached the thoracic cavity. After accessing the thorax, a rigid endoscope with a working portal was entered, proceeding with the introduction of endoscopic scissors, used to open the pericardium. Pericardiotomy was initiated through the phrenic-pericardial ligament. After the procedure, the corpses were sent for necropsy for evaluation of inadvertent injuries and examination of the diaphragm and pericardium. The access allowed the visualization of the structures of the caudal portion of the thorax, in addition to the visualization and manipulation of the pericardium. The mean surgical time was 24.16 ± 7.03, allowing extensive pericardiotomy. It was concluded that transdiaphragmatic thoracoscopy is an adequate procedure for the visualization and access of the pericardium, as well as the structures present in the caudal region of both hemithoraxes. Therefore, the proposed technique, pericardiotomy by thoracoscopy using a singleport transdiaphragmatic approach, was promising, proving to be a viable alternative for pericardial procedures in the equine species.

Preliminary characterization of a novel form of progressive retinal atrophy in the German Spitz dog associated with a frameshift mutation in GUCY2D.

OBJECTIVE: To describe the clinical, preliminary electroretinographic and optical coherence tomography features of a newly identified form of progressive retinal atrophy (PRA) in German Spitzes, and identify the causal gene mutation. ANIMALS: Thirty-three client-owned German Spitz dogs were included. PROCEDURES: All animals underwent a full ophthalmic examination, including vision testing. In addition, fundus photography, ERG, and OCT were performed. A DNA-marker-based association analysis was performed to screen potential candidate genes and the whole genomes of four animals were sequenced. RESULTS: Initial fundus changes were pale papilla and mild vascular attenuation. Oscillatory nystagmus was noted in 14 of 16 clinically affected puppies. Vision was impaired under both scotopic and photopic conditions. Rod-mediated ERGs were unrecordable in all affected dogs tested, reduced cone-mediated responses were present in one animal at 3 months of age and unrecordable in the other affected animals tested. Multiple small retinal bullae were observed in three clinically affected animals (two with confirmed genetic diagnosis). OCT showed that despite loss of function, retinal structure was initially well-preserved, although a slight retinal thinning developed in older animals with the ventral retina being more severely affected. Pedigree analysis supported an autosomal recessive inheritance. A mutation was identified in GUCY2D, which segregated with the disease (NM_001003207.1:c.1598_1599insT; p.(Ser534GlufsTer20)). Human subjects with GUCY2D mutations typically show an initial disconnect between loss of function and loss of structure, a feature recapitulated in the affected dogs in this study. CONCLUSION: We identified early-onset PRA in the German Spitz associated with a frameshift mutation in GUCY2D.

Potential of Human Neural Precursor Cells in Diabetic Retinopathy Therapeutics - Preclinical Model.

PURPOSE: This study aimed to evaluate a cell therapy strategy with human neural precursor cells (hNPCs) to treat diabetic retinopathy (DR) in Wistar rats induced to diabetes by injecting streptozotocin. MATERIAL AND METHODS: The Wharton's jelly mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate to develop neurospheres and obtain the hNPCs. The animals were divided into three groups: non-diabetic (ND) n = four, diabetic without treatment (DM) n = nine, and diabetic with cell therapy (DM + hNPCs) n = nine. After 8 weeks of diabetes induction and DR characteristics installed, intravitreal injection of hNPCs (1 × 106 cell/µL) was performed in the DM + hNPCs group. Optical Coherence Tomography (OCT) and Electroretinography (ERG) evaluations were conducted before and during diabetes and after cell therapy. Four weeks posttreatment, histopathological and immunohistochemistry analyses were performed. RESULTS: The repair of the retinal structures in the treated group (DM + hNPCs) was observed by increased thickness of neuroretinal layers, especially in the ganglion cell and photoreceptor layers, higher ERG oscillatory potentials (OPs) amplitudes, and transplanted hNPCs integration into the Retinal Pigment Epithelium. CONCLUSIONS: The results indicate that hNPCs reduced DR progression by a neuroprotective effect and promoted retinal repair, making them potential candidates for regenerating the neuroretinal tissue.

A morphometric study of the canine skull and periorbita and its implications for regional ocular anesthesia.

OBJECTIVE: A hypothetical relationship between canine cranial length and the length of the periorbita could be used for intraconal anesthetic volume estimation. STUDY SUBJECTS: Forty-one canine cadaver heads and one macerated dog skull. PROCEDURES: Inion and nasion points were recognized in the macerated skull and used as landmarks for cranial length measure. Thirty cadavers classified as dolichocephalic, mesaticephalic and brachycephalic were distributed in three study groups. Anatomic references of the skull shapes were recognized and parameters measured: body weight (BW), cranial length (Lcr ) and length of the periorbita (Lpo ). Results were compared and statistical analyses were performed to find correlations between BW and the skull parameters. Contrast medium was injected in another 11 cadavers with a total volume calculated based on Lcr (10 cadavers) or BW (one cadaver) and then submitted to computerized tomography examination to compare techniques, estimate the capacity of the intraconal space of the periorbita and to illustrate practical implications. RESULTS: There is a positive correlation between BW and Lpo (P < 0.001) as well as between Lcr and Lpo (P < 0.0001). Linear regression of the variable BW predicts only 71% of the variable Lpo (r2 = 0.71), whereas the variable Lcr predicts 88% (r2 = 0.88) of Lpo . CONCLUSIONS: This study demonstrated a mathematical relation between Lcr and Lpo . A method for calculating anesthetic solution volumes based on canine morphometric features is presented. The formula 0.1 mL/cm Lcr to calculate total intraconal anesthetic volume is suggested.

Characterization of a novel form of progressive retinal atrophy in Whippet dogs: a clinical, electroretinographic, and breeding study.

OBJECTIVE: To describe a form of progressive retinal atrophy (PRA) in Whippets including clinical, electroretinographic, optical coherence tomographic changes and pedigree analysis. ANIMALS STUDIED: Client-owned Whippet dogs (n = 51) living in Brazil. PROCEDURES: All animals were submitted for routine ophthalmic screening for presumed inherited ocular disease, which included the following: visual tests, such as obstacle course tests, in scotopic and photopic conditions, cotton ball test, dazzle reflex, ocular fundus evaluation by indirect ophthalmoscopy followed by fundus photography. Additionally, electroretinography (ERG) and optical coherence tomography (OCT) were performed in 24 and four dogs, respectively. RESULTS: Sixteen dogs were diagnosed with PRA. Vision deficits in dim light were detected in dogs examined at a young age associated with nystagmus. Funduscopic changes included the development of multifocal retinal bullae from 6 months of age. Retinal thinning became apparent later, at which time the bullae were no longer detected. OCT examination of selected young dogs revealed that the retinal bullae were due to separation between photoreceptors and the retinal pigment epithelium, and of dogs with more advanced disease confirmed the development of retinal thinning. Electroretinography in young dogs revealed a negative ERG due to a lack of b-wave in both scotopic and photopic recordings. With progression, the ERG became unrecordable. Pedigree analysis suggested an autosomal recessive mode of inheritance. CONCLUSION: The retinal dystrophy reported here in Whippet dogs has a unique phenotype of an initial lack of ERG b-wave, development of retinal bullae then a progressive generalized retinal degeneration.

Tramadol effects on clinical variables and the mechanical nociceptive threshold in horses / Efeitos do tramadol sobre variáveis clínicas e limiar nociceptivo mecânico em equinos

This study assessed the clinical effects and the mechanical antinociceptive potential of intravenous (IV) tramadol in horses.A blinded and randomized study was designed with 7 horses treated with 1 (Tr1), 2 (Tr2) or 3 (Tr3) mg kg-1 of tramadol IV. The heart rate, respiratory rate (fR), arterial pressure, degree of sedation, gastrointestinal motility (GI), behavior changes and the mechanical nociceptive threshold (MNT) were evaluated. The MNT was determined with von Frey device method.Tr3 had a significant increase in their fR and more pronounced behavioral changes than other treatments.The Tr1 showed a significant increase in arterial pressure. The GI reduced significantly, mainly in Tr2. The tramadol did not change the MNT of the horses.The clinical alterations observed with the different treatments were considered mild and transitory, being most evident in Tr2. However the tramadol did not have any analgesic effect with any of the doses evaluated.

Avaliaram-se os efeitos clínicos e o potencial antinociceptivo mecânico de diferentes doses de tramadol administradas por via intravenosa (IV) em equinos. Sete animais foram tratados com 1 (Tr1), 2 (Tr2) ou 3 (Tr3) mg kg-1de tramadol IV em um estudo cruzado do tipo cego e randomizado. Foram avaliados frequência cardíaca, frequência respiratória, temperatura retal, pressão arterial, nível de sedação, motilidade gastrointestinal, alterações comportamentais e limiar antinociceptivo mecânico (Von Frey). As principais alterações evidenciadas pela administração do tramadol concentram-se no aumento na frequência respiratória em Tr3, aumento significativo da pressão arterial em Tr1 e redução da motilidade gastrointestinal, mais pronunciada em Tr2. O tramadol não promoveu alteração significativa no limiar nociceptivo mecânico. As alterações clínicas observadas nos diferentes tratamentos foram consideradas leves e transitórias. Diante dos resultados, pode-se concluir que o tramadol não apresentou efeito antinociceptivo passível de ser avaliado pelo método empregado no presente estudo, em nenhum dos tratamentos.

Topical and intraluminal Carolina Rinse Solution in p44/42 and p38 MAP Kinase activation profile in rabbit jejunum after ischemia and reperfusion / Uso tópico e intraluminal da Solução de Carolina Rinse no perfil de ativação das MAP quinases p44/42 e p38 no jejuno de coelhos após isquemia e reperfusão

The effects of topical and intraluminal Carolina Rinse Solution (CRS) in p44/42 (ERK 1/2) and p38 MAPK activation profile, in rabbit jejunum after ischemia and reperfusion (I/R), were investigated in this study. Fifteen New Zealand rabbits were allocated in three groups: Sham-operated (A), Ischemia and reperfusion (B) and CRS (C). Groups B and C were subjected to one hour of ischemia and two hours of reperfusion. In group C, ten minutes prior to reperfusion, the bowel lumen was filled with CRS, and the segment was immersed in CRS until reperfusion onset. Ischemia and reperfusion stimulated the phosphorylation of the p44/42 MAPK and p38 MAPK pathways in some layers of jejunum. Progressive activation of p44/42 MAPK was chiefly localized in the crypts of Lieberkühn, circular and longitudinal muscle layers, whereas p38 MAPK was prominently activated in myenteric plexus and both muscle layers. The results of this research indicate that the chosen model of topical and intraluminal CRS does not interfere in p44/42 and p38 MAPK activation profile in rabbit jejunum subjected to I/R.

Os efeitos do uso tópico e intraluminal da Solução de Carolina Rinse (CRS), no perfil de ativação das MAP quinases p44/42 (ERK 1/2) e p38, no jejuno de coelhos após isquemia e reperfusão (I/R), foram investigados neste estudo. Quinze coelhos da raça Nova Zelândia foram alocados em três grupos: Instrumentado (A), Isquemia e Reperfusão (B) e CRS (C). Os grupos B e C foram submetidos a uma hora de isquemia e duas horas de reperfusão. No grupo C, dez minutos antes da reperfusão, o lúmen do segmento isolado foi preenchido com CRS e o segmento foi imerso em CRS até o início da reperfusão. A isquemia e reperfusão resultou em estímulo da fosforilação das MAP quinases p44/42 e p38 em algumas camadas do jejuno. A ativação progressiva de p44/42 ocorreu principalmente nas criptas de Lieberkühn e camadas musculares longitudinal e circular, enquanto p38 foi ativada principalmente no plexo mioentérico e em ambas as camadas musculares. Os resultados deste trabalho indicam que o modelo escolhido de uso tópico e intraluminal de CRS não interfere no perfil de ativação das MAP quinases p44/42 e p38 no jejuno de coelhos submetidos à I/R.