Cláudio Corrêa Natalini

Spinal Anesthetics and Analgesics in the Horse

In the past 10 years, there have been many recent advances in spinal techniques in horses, both epidural and subarachnoid, to identify drugs or drug combinations that have sensory effects without motor nerve paralysis, thus providing pain control without these horses becoming recumbent. Opioids, alpha-2 agonists, dissociative drugs, and others have been investigated. Many of these drugs, which have serious side effects when injected systemically in horses, have been shown to have useful analgesic effects when injected spinally. Morphine-like opioids have the greatest potential for spinal use as they produce long-lasting analgesia without motor effects. Often the doses used spinally are significantly lower than those needed for systemic effects.

Pharmacokinetics evaluation of soft agglomerates for prompt delivery of enteric pantoprazole-loaded microparticles

Soft agglomerates containing pantoprazole-loaded microparticles were developed with the aim of prompt delivery of gastro-resistant particles. The objective was to evaluate the relative bioavailability in dogs after the oral administration of soft agglomerates. Gastro-resistant pantoprazole-loaded microparticles prepared by spray drying were mixed with mannitol/lecithin spray-dried powder and agglomerated by vibration. One single oral dose (40mg) was administered to dogs. Each dog received either a reference tablet or hard gelatin capsules containing the agglomerates. The plasma profiles were evaluated by non-compartmental and compartmental approaches, and the pharmacokinetic parameters were determined. The agglomerates presented 100% of drug particle loading and a production yield of 80.5%. The amount of drug absorbed after oral dosing was similar after reference or agglomerate administration, leading to a relative bioavailability of 108%. The absorption lag-time was significantly reduced after agglomerate administration (from 135.5+/-50.6 to 15.0+/-2.5min). The agglomerated gastro-resistant pantoprazole-loaded microparticles reduced time to peak plasma. The agglomerates were equivalent to the reference tablets in terms of extent but not in terms of rate of absorption, showing that this formulation is an alternative to single-unit oral dosing with enteric coating and with the advantage of reducing time to effect.

Confecção de um modelo experimental in vitro do espaço subaracnóide eqüino para teste de opióides hiperbáricos

Com o objetivo de avaliar as caracteristicas de distribuicao de agentes hiperbaricos no liquido cerebro-espinhal (LCE) equino, e apresentado um modelo in vitro do espaco subaracnoide confeccionado em policloreto de vinila (PVC) transparente, no qual se adaptou um cateter para a infusao continua de glicose a 10%, morfina hiperbarica, buprenorfina hiperbarica e metadona hiperbarica marcadas com azul de metileno para permitir a visualizacao da distribuicao destas substâncias no LCE. Avaliaram-se a distância alcancada pelos diferentes agentes minuto a minuto e a forma de distribuicao dos mesmos. Todas as substâncias testadas mostraram comportamento de distribuicao vertical a partir da extremidade do cateter, quando se deu o inicio da migracao cranial no LCE, sendo que o avanco maximo registrado foi aos 15 minutos apos o termino da infusao, com migracao de 15cm para glicose a 10%, 13cm para a morfina hiperbarica, 18cm para a buprenorfina hiperbarica e 17cm para a metadona hiperbarica. O modelo proposto mostrou-se eficiente para a avaliacao do comportamento fisico dos agentes hiperbaricos no interior do espaco subaracnoide, oferecendo a possibilidade de teste de substâncias a serem utilizadas pela via subaracnoide de cavalos.

Intravenous 15% isoflurane lipid nanoemulsion for general anesthesia in dogs

OBJECTIVEnTo investigate the efficacy of a new intravenous (IV) nanoemulsified isoflurane formulation for maintenance of general anesthesia in dogs.nnnSTUDY DESIGNnProspective, crossover, experimental study.nnnANIMALSnSeven healthy, mature, mixed-breed dogs, three male and four female, weighing 11.5xa0±xa01.5xa0kg.nnnMETHODSnAnesthesia was induced with propofol for instrumentation. Measurements were obtained before administration of either inhaled isoflurane (Iso-I) or IV 15% isoflurane-loaded lipid nanoemulsion (Iso-nano). The minimum alveolar concentration (MAC) of isoflurane was determined using the up-and-down technique. A tail clamp was applied every 15xa0minutes for a total time of 90xa0minutes and isoflurane administration was adjusted according to the response. Data were recorded at 30, 60 and 90xa0minutes for end-tidal isoflurane concentration (Fe´Iso), end-tidal carbon dioxide partial pressure (PeCO2), inspired isoflurane concentration (FIIso), arterial hemoglobin oxygen saturation (SaO2), peripheral hemoglobin oxygen saturation (SpO2), respiratory rate (fR), heart rate (HR), arterial blood pH, PaCO2, PaO2, base excess (BE), bicarbonate (HCO3-), systemic arterial pressure (sAP), and biochemical variables of blood urea nitrogen, alanine aminotransferase, creatine kinase and creatinine.nnnRESULTSnNo significant differences between treatments were detected for HR, fR, SaO2 or any biochemical variables (p > 0.05). In the Iso-nano treatment, sAP was significantly decreased throughout the study. Significant decreases in pH, PeCO2, BE and HCO3- were measured in the Iso-nano treatment. Isoflurane MAC was significantly lower in the Iso-nano than the Iso-I treatment. The dose of isoflurane (gxa0hour-1) required to maintain general anesthesia did not differ significantly between treatments.nnnCONCLUSIONS AND CLINICAL RELEVANCEnAdministration of 15% isoflurane-loaded lipid nanoemulsion IV was effective in maintaining general anesthesia in dogs but did not reduce the amount of isoflurane necessary to maintain general anesthesia. Significant hypotension and nonrespiratory acidosis occurred with the injectable form.

High-resolution melting analysis for detection of a single-nucleotide polymorphism and the genotype of the myostatin gene in warmblood horses

OBJECTIVE To develop a high-resolution melting (HRM) assay to detect the g.66493737C>T polymorphism in the myostatin gene (MSTN) and determine the frequency of 3 previously defined g.66493737 genotypes (T/T, T/C, and C/C) in warmblood horses. SAMPLES Blood samples from 23 horses. PROCEDURES From each blood sample, DNA was extracted and analyzed by standard PCR methods and an HRM assay to determine the MSTN genotype. Three protocols (standard protocol, protocol in which a high-salt solution was added to the reaction mixture before the first melting cycle, and protocol in which an unlabeled probe was added to the reaction mixture before analysis) for the HRM assay were designed and compared. Genotype results determined by the HRM protocol that generated the most consistent melting curves were compared with those determined by sequencing. RESULTS The HRM protocol in which an unlabeled probe was added to the reaction mixture generated the most consistent melting curves. The genotypes of the g.66493737C>T polymorphism were determined for 22 horses (16 by HRM analysis and 20 by sequencing); 14, 7, and 1 had the T/T, T/C, and C/C genotypes, respectively. The genotype determined by HRM analysis agreed with that determined by sequencing for 14 of 16 horses. The frequency of alleles T and C was 79.5% and 20.5%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that HRM analysis may be a faster and more economical alternative than PCR methods for genotyping. Genotyping results might be useful as predictors of athletic performance for horses.

Anestesia por isofluorano em eqüinos submetidos à infusão contínua de medetomidina ou xilazina

Eight horses under inhalant general anesthesia with isoflurane (1MAC) and continuous infusion of xylazine (0.35mg kg-1h-1) or medetomidine (3.5µg kg-1h-1) were evaluated for heart rate and rhythm, respiratory rate, arterial blood pressure, arterial blood gas analysis and temperature immediately before the beginning of the continuous infusion (T0) and in intervals of 10 minutes after the beginning of the continuous infusion (T10 to T60). Heart rate and temperature decreased and mean arterial pressure increased. PaCO2 (in GM) increased and GM showed a higher paO2 than GX. We conclude that equipotent doses of continuous infusion of medetomidine and xylazine during inhalant general anesthesia with isoflurane in horses promote slight and equivalent cardiocirculatory, respiratory, thermic and arterial blood gases changes.