RESUMEN
A 2-month-old male Holstein calf was presented for evaluation of a continuous systolic murmur. A grade V/VI left basilar continuous murmur and a grade IV/VI right basilar continuous murmur was auscultated upon evaluation with increased respiratory effort, wheezes, and crackles. Multimodality diagnostics were performed on this patient for further workup and included transthoracic and transesophageal echocardiography, fluoroscopy guided angiography, and gross necropsy with histopathology. An aortopulmonary window with continuous left-to-right shunting was identified at the level of the left aortic sinus of Valsalva with a severely dilated left coronary artery and left-sided congestive heart failure. This case report outlines the diagnostic workup of a rare congenital heart defect and secondary cardiac abnormalities not previously identified in veterinary literature.
Asunto(s)
Aneurisma , Cardiopatías Congénitas , Seno Aórtico , Aneurisma/veterinaria , Animales , Válvula Aórtica , Vasos Coronarios , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/veterinaria , Masculino , Imagen MultimodalRESUMEN
BACKGROUND: Periodic lack of availability and high cost of commercially produced isotonic fluids for intravenous (IV) use in horses have increasingly led to use of home-made or commercially compound fluids by veterinarians. Data regarding the quality control and safety of compounded fluids would be of benefit to equine veterinarians. OBJECTIVES: To compare electrolyte concentrations, sterility, and endotoxin contamination of commercially available fluids to 2 forms of compounded isotonic crystalloid fluids intended for IV use in horses. METHODS: Prospective study. Two methods of preparing compounded crystalloids formulated to replicate commercial Plasma-Lyte A (Abbott, Chicago, IL) were compared. One formulation was prepared by a hand-mixed method involving chlorinated drinking water commonly employed by equine practitioners, and the other was prepared by means of ingredients obtained from a commercial compounding pharmacy. The variables for comparison were electrolyte concentrations, sterility, and presence of endotoxin contamination. RESULTS: Electrolyte concentrations were consistent within each product but different between types of fluids (P < 0.0001). Hand-mixed fluids had significantly more bacterial contamination compared to commercial Plasma-Lyte A (P = 0.0014). One of the hand-mixed fluid samples had detectable endotoxin contamination. CONCLUSIONS AND CLINICAL IMPORTANCE: Chlorinated drinking water is not an acceptable source of water to compound isotonic fluids for IV administration. Equine practitioners should be aware of this risk and obtain the informed consent of their clients.
Asunto(s)
Composición de Medicamentos/veterinaria , Electrólitos/normas , Caballos , Infusiones Intravenosas/veterinaria , Soluciones Isotónicas/farmacología , Control de Calidad , Animales , Soluciones Cristaloides , Composición de Medicamentos/métodos , Contaminación de Medicamentos , Endotoxinas/análisis , Infusiones Intravenosas/normas , Soluciones Isotónicas/química , Agua/químicaRESUMEN
BACKGROUND: Gestational duration is highly variable in camelids (reference range 330-360 days), and a definition for prematurity has not been established. Anecdotally, it is suggested that crias born outside of this have increased incidence of physical findings of immaturity (tendon laxity, floppy ears, and unerupted teeth) and need increased intensive support in the neonatal period. OBJECTIVES: Low gestational age (<330 days) is associated with physical findings of immaturity, low birth weight, more intensive and expensive care, but not decreased short-term survival. ANIMALS: A total of 130 alpacas presented to the University of Wisconsin. METHODS: Retrospective study of all neonatal crias <1 month of age. RESULTS: Of 130 neonatal alpacas presented, 86 (66%) had gestational age recorded (range 312-393 days). There were 16 (18.6%) crias with gestational age below 330 days. Crias born before 330 days were lighter at birth (mean 6.4 kg, SD 1.3 kg) than those born after 330 days (mean 7.4 kg, SD 1.7 kg, P = .002). Clinically immature crias had lower birth weights (mean 6.5 kg, SD 1.5 kg) than physically mature crias (mean 8.8 kg, SD 3.2 kg, P = .05). Survival rates were similar in all groups (premature 77%, mature 88%, P = .12). However, treatment costs were higher in crias born prior to 330 days with physical findings at birth consistent with immaturity compared with gestationally mature crias and those born prior to 330 days but with a physically mature appearance. CONCLUSIONS: Crias born before 330 days and those with physical findings of immaturity have a good prognosis, but require more intensive care, resulting in higher treatment costs.
Asunto(s)
Animales Recién Nacidos/fisiología , Peso Corporal , Camélidos del Nuevo Mundo/fisiología , Edad Gestacional , Nacimiento Prematuro , Animales , Peso al Nacer , Femenino , Embarazo , Estudios RetrospectivosRESUMEN
We have previously reported that Morinda citrifolia (noni) puree modulates neonatal calves developmental maturation of the innate and adaptive immune system. In this study, the effect of noni puree on respiratory and gastrointestinal (GI), health in preweaned dairy calves on a farm with endemic salmonellosis was examined. Two clinical trials were conducted whereby each trial evaluated one processing technique of noni puree. Trials 1 and 2 tested noni versions A and B, respectively. Puree analysis and trial methods were identical to each other, with the calf as the experimental unit. Calves were designated to 1 of 3 treatment groups in each trial and received either: 0, 15 or 30 mL every 12 hr of noni supplement for the first 3 weeks of life. Health scores, weaning age, weight gain from admission to weaning, and weaned by 6 weeks, were used as clinical endpoints for statistical analysis. In trial 1, calves supplemented with 15 mL noni puree of version A every 12 hr had a higher probability of being weaned by 6 weeks of age than control calves (P = 0.04). In trial 2, calves receiving 30 mL of version B every 12 hr had a 54.5% reduction in total medical treatments by 42 days of age when compared to controls (P = 0.02). There was a trend in reduced respiratory (61%), and GI (52%) medical treatments per calf when compared to controls (P = 0.06 and 0.08, respectively). There were no differences in weight gain or mortality for any treatment group in either trial.
Asunto(s)
Enfermedades Gastrointestinales/prevención & control , Factores Inmunológicos/uso terapéutico , Morinda , Fitoterapia , Enfermedades Respiratorias/prevención & control , Infecciones por Salmonella/prevención & control , Destete , Animales , Animales Recién Nacidos , Bovinos , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/prevención & control , Industria Lechera , Suplementos Dietéticos , Femenino , Frutas , Enfermedades Gastrointestinales/microbiología , Medicina Tradicional , Preparaciones de Plantas/uso terapéutico , Enfermedades Respiratorias/microbiología , Salmonella , Infecciones por Salmonella/microbiología , Aumento de Peso/efectos de los fármacosRESUMEN
BACKGROUND: Although adequate colostrum intake and properly used antibiotics can provide much protection for the bovine neonate, increased antibiotic scrutiny and consumer demand for organic products have prompted investigations of natural immunomodulators for enhancing calf health. One plant-based immunomodulator, Morinda citrifolia (noni) fruit, is a well-recognized natural product that has a broad range of immunomodulatory effects. HYPOTHESIS: Neonatal calves fed noni puree would demonstrate whole blood phagocytic capacity in Gram-negative and Gram-positive in vitro assays. ANIMALS: Blood samples from 18 neonatal Holstein bull calves. METHODS: Calves were divided into 2 groups: Group 1 comprised control calves, whereas Group 2 received 30 mL of noni puree twice a day in milk replacer. Day 0 blood samples were obtained between 36 and 48 hours of age before the first feeding of puree. Ethylenediaminetetraacetic acid anticoagulated blood was collected from each calf on days 0, 3, 7, and 14. Bactericidal assays were performed to estimate the percentage killing of Escherichia coli and Staphylococcus epidermidis. RESULTS: Blood samples from noni puree-fed calves displayed significantly more E. coli bacterial killing than did controls on day 14, and although differences were not significant on days 0, 3, and 7, bacterial killing progressively increased over time. There was no significant difference between the groups for S. epidermidis killing. CONCLUSIONS AND CLINICAL IMPORTANCE: The immunomodulatory effect of noni puree may prove valuable in the future as production animal antibiotic use becomes more restricted. Additional clinical trials are warranted to investigate the clinical application of noni puree in promoting calf health.
Asunto(s)
Alimentación Animal/análisis , Enfermedades de los Bovinos/prevención & control , Dieta/veterinaria , Infecciones por Escherichia coli/veterinaria , Escherichia coli/efectos de los fármacos , Morinda/química , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Bovinos , Enfermedades de los Bovinos/microbiología , Infecciones por Escherichia coli/prevención & control , Masculino , Morinda/inmunología , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
A 17-year-old Quarter horse mare was referred to Cornell University for postmortem examination after 72 hours of encephalopathy that consisted of depression, mania, and blindness. A plasma sample and cerebral spinal fluid demonstrated hyperammonemia. Gross necropsy examination findings included the following: mild icterus, a transmural mass in the glandular portion of the gastric fundus, multiple masses throughout the liver, and a large tumor thrombus in the portal vein. Microscopically, the gastric mass, hepatic masses, and portal vein thrombus were composed of similar neoplastic epithelial cells that formed variably sized acini and branching cords separated by a dense desmoplastic stroma. Throughout the cerebral frontal cortex were numerous Alzheimer type II astrocytes. Hepatic encephalopathy was caused by gastric adenocarcinoma, with metastasis to the liver and the portal vein. The clinical and pathologic lesions from this unique case, as well as hyperammonemia and portal vein thrombosis in the pathogenesis of hepatic encephalopathy, are discussed.
Asunto(s)
Adenocarcinoma/veterinaria , Encefalopatía Hepática/veterinaria , Enfermedades de los Caballos/patología , Neoplasias Hepáticas/veterinaria , Neoplasias Gástricas/veterinaria , Adenocarcinoma/complicaciones , Adenocarcinoma/secundario , Animales , Resultado Fatal , Femenino , Encefalopatía Hepática/etiología , Encefalopatía Hepática/patología , Histocitoquímica/veterinaria , Caballos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/secundario , Vena Porta/patología , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/patologíaRESUMEN
A 5-month-old, female, Aberdeen Angus heifer presented to the veterinary medical teaching hospital for evaluation of slowly progressive hindlimb ataxia. The calf was clinically normal until 4 months of age, following routine pregnancy and delivery. Neurologic examination revealed marked symmetric spastic hindlimb paraparesis. Thoracolumbar radiographs and cerebrospinal fluid (CSF) analysis were unremarkable. A presumptive diagnosis of T3-L3 myelopathy was made, and neurologic status remained static for 3 months with broad-spectrum antibiotic and nonsteroidal anti-inflammatory therapy. Additional diagnostic tests were refused, and a necropsy was performed following euthanasia. A moderately well delineated, reddish-tan, soft mass 18 mm in diameter replaced 80% of the fourth lumbar spinal cord segment. Histologic examination revealed two distinct features: undifferentiated, primitive, polygonal-to-round cells with typical morphologic characteristics of primitive neuroectoderm; and interspersed areas containing myelinated axons and cells with neuronal differentiation. Immunohistochemical examination confirmed the presence of primitive neuroepithelium and cells with neuronal differentiation.
Asunto(s)
Enfermedades de los Bovinos/patología , Neuroblastoma/veterinaria , Neuronas/patología , Neoplasias de la Médula Espinal/veterinaria , Médula Espinal/patología , Animales , Bovinos , Diferenciación Celular , Femenino , Neuroblastoma/patología , Neoplasias de la Médula Espinal/patologíaRESUMEN
A pregnant quarterhorse mare became acutely lame as a result of severe swelling of its right hind leg, thought to have been caused by a fracture or a muscle tear. Diagnostic procedures ruled out a traumatic musculoskeletal cause and a physical examination revealed chronic pastern dermatitis ('scratches'/'grease heel'). Histopathological evaluation of biopsy samples from the right hind leg was consistent with a leucocytoclastic vasculitis, and culture yielded Staphylococcus intermedius. The treatment and infectious causes of pastern dermatitis are discussed.
Asunto(s)
Enfermedades de los Caballos/microbiología , Enfermedades de los Caballos/patología , Infecciones Cutáneas Estafilocócicas/veterinaria , Vasculitis Leucocitoclástica Cutánea/veterinaria , Animales , Femenino , Miembro Posterior , Caballos , Piel/patología , Infecciones Cutáneas Estafilocócicas/patología , Vasculitis Leucocitoclástica Cutánea/microbiología , Vasculitis Leucocitoclástica Cutánea/patologíaRESUMEN
REASONS FOR PERFORMING STUDY: Previous reports of clostridial myonecrosis have either focused on individual case reports or have been small retrospective studies reporting very high mortality rates. OBJECTIVES: The objective of this study was to describe the outcome of cases of clostridial myonecrosis submitted to 2 referral equine hospitals in the United States over a 15 year period. METHODS: A retrospective study of case material selected on the basis of positive Clostridium spp. culture or the identification of Clostridium spp. by specific fluorescent antibody testing from soft tissue wounds was performed at Cornell and Wisconsin. RESULTS: 37 cases of clostridial myonecrosis were documented. Twenty-seven horses survived, 8 were subjected to euthanasia and 2 died during treatment for an overall survival rate of 73%. Twenty-five cases (68%) were associated with Clostridium perfringens alone, 6 cases (16%) with Cl. septicum alone, 4 cases with mixed clostridial infections (11%), 1 case with Cl. sporogenes and 1 with an unspeciated Clostridium spp. The highest survival rate of 81% was documented for those cases from which Cl. perfringens alone was isolated. The most common antecedent condition prior to referral was colic. The myonecrotic lesion occurred within 6-72 h of a soft tissue injection in 34 cases but was associated with a wound or laceration in the remaining 3 cases. Of the 34 cases associated with recent injections, 24 were associated with i.m. injections in the cervical region, 4 in the semimembranosus/semitendinosus region, 3 in the gluteal region, 2 with perivascular leakage of drugs administered into the jugular vein and 1 case developed simultaneously in the gluteal and neck region following injections at both sites. CONCLUSIONS: Clostridial myonecrosis can occur following the i.m. or inadvertent perivascular administration of a wide variety of commonly administered drugs. It is most common in the neck musculature. Aggressive treatment can be associated with survival rates of up to 81% for cases due to Cl. perfringens alone. Survival rates for other Clostridial spp. tend to be lower. POTENTIAL RELEVANCE: A combination of high dose i.v. antibiotic therapy and surgical fenestration/debridement is the best approach to cases of clostridial myonecrosis. With rapid diagnosis and therapeutic intervention, horses may have up to an 81% chance of survival.
Asunto(s)
Gangrena Gaseosa/veterinaria , Enfermedades de los Caballos/mortalidad , Animales , Antibacterianos/uso terapéutico , Clostridium/clasificación , Clostridium/aislamiento & purificación , Desbridamiento , Femenino , Gangrena Gaseosa/epidemiología , Gangrena Gaseosa/mortalidad , Gangrena Gaseosa/terapia , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/terapia , Caballos , Inyecciones Intramusculares/efectos adversos , Inyecciones Intramusculares/veterinaria , Estudios Longitudinales , Masculino , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
L: -FMAU [1-(2-fluoro-5-methyl-beta,L-arabinofuranosyl) uracil] has been shown to be an effective inhibitor of hepatitis B virus (HBV) and duck hepatitis B virus replication in cell culture and duck hepatitis B virus replication in acutely infected Peking ducks. The woodchuck hepatitis virus (WHV) and its natural host, the Eastern woodchuck (Marmota monax), have been established as a predictive model for the evaluation of antiviral therapies against chronic HBV infection. In this report, the antiviral activity of l-FMAU against WHV replication in chronically infected woodchucks is described. Four weeks of once-daily oral administration of L-FMAU significantly reduced viremia, antigenemia, intrahepatic WHV replication, and intrahepatic expression of woodchuck hepatitis virus core antigen (WHcAg) in a dose-dependent manner. At the highest dose administered (10 mg/kg/d), significant reductions of intrahepatic WHV RNA and covalently closed circular (ccc)WHV-DNA levels also were observed. The reduction in viremia was remarkably rapid at the higher doses of L-FMAU, with greater than 1,000-fold reductions in WHV-DNA serum levels observed after as little as 2 to 3 days of therapy. Following the withdrawal of therapy, a dose-related delay in viremia rebound was observed. At the highest doses used, viremia remained significantly suppressed in at least one half of the treated animals for 10 to 12 weeks' posttreatment. No evidence of drug-related toxicity was observed in the treated animals. L-FMAU is an exceptionally potent antihepadnaviral agent in vitro and in vivo, and is a suitable candidate for antiviral therapy of chronic HBV infection.
Asunto(s)
Antivirales/farmacología , Arabinofuranosil Uracilo/fisiología , Expresión Génica/efectos de los fármacos , Genes Virales/genética , Virus de la Hepatitis B de la Marmota/crecimiento & desarrollo , Virus de la Hepatitis B de la Marmota/genética , Hepatitis B Crónica/virología , Replicación Viral/efectos de los fármacos , Animales , Antígenos de Superficie/análisis , Arabinofuranosil Uracilo/análogos & derivados , Replicación del ADN/efectos de los fármacos , ADN Circular/antagonistas & inhibidores , ADN Viral/antagonistas & inhibidores , ADN Viral/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Antígenos de la Hepatitis/análisis , Virus de la Hepatitis B de la Marmota/efectos de los fármacos , Virus de la Hepatitis B de la Marmota/inmunología , Antígenos de la Hepatitis C/análisis , Marmota , ARN Viral/metabolismo , Factores de Tiempo , Viremia/prevención & controlRESUMEN
The medical approach to treatment of cholangiohepatitis and cholelithiasis in 9 horses is described. Seven horses were treated successfully and returned to normal use, with a minimum follow-up period of 12 months. Long-term antimicrobial therapy was believed to be critical in those cases that survived, with a median treatment duration of 51 days (range 17-124 days). Treatment failure was associated with severe periportal and bridging hepatic fibrosis from biopsy material obtained at admission in 2 horses, one of whom also presented with hyperammonaemic hepatic encephalopathy. Transabdominal ultrasound was used diagnostically in each case to obtain hepatic biopsy material for histopathology and bacterial culture, to evaluate hepatic size and echogenicity and to identify and monitor the dissolution of hepatoliths. Histologically, all horses had evidence of suppurative cholangiohepatitis with varying degrees of periportal and bridging fibrosis. Discrete hyperechoic calculi were identified in 4 cases, but all horses had ultrasonographic evidence of biliary obstruction with numerous dilated bile ducts. Aerobic and anaerobic cultures of liver biopsy material were negative from 7 horses, but 2 different species of Escherichia coli were obtained from one horse, and Bacteroides vulgatus and Escherichia coli were isolated from another. In all 7 horses that survived, clinical recovery was seen before normalisation of biochemical indices of hepatobiliary function including gammaglutamyl transaminopeptidase (GGT), alkaline phosphatase (AP), bile acids and serum bilirubin. Serum GGT levels were monitored extensively as a marker of hepatobiliary disease and actually increased during the initial period of clinical improvement in horses that recovered. Supportive medical therapy with i.v. fluids was also a critical part of the therapy of several cases in this report, both acutely and in the management of chronic cases that deteriorated clinically during treatment. Previous therapeutic failures may well be related to treatment periods of inadequate duration, and the authors recommend that antimicrobial therapy should be continued until GGT values are normal.
Asunto(s)
Colangitis/veterinaria , Colelitiasis/veterinaria , Fluoroquinolonas , Hepatitis Animal/tratamiento farmacológico , Enfermedades de los Caballos/tratamiento farmacológico , Animales , Antiinfecciosos/uso terapéutico , Cefalosporinas/uso terapéutico , Colangitis/complicaciones , Colangitis/tratamiento farmacológico , Colelitiasis/tratamiento farmacológico , Combinación de Medicamentos , Enrofloxacina , Femenino , Hepatitis Animal/complicaciones , Caballos , Masculino , Quinolonas/uso terapéutico , Sulfadiazina/uso terapéutico , Resultado del Tratamiento , Acetato de Trembolona/análogos & derivados , Acetato de Trembolona/uso terapéutico , Trimetoprim/uso terapéuticoRESUMEN
Seventeen cases of severe hypokalemia (serum or plasma potassium < or = 2.1 mEq/L) in association with profound muscle weakness and recumbency in lactating dairy cattle were included in a retrospective study. The cattle were from 15 different farms. Eleven of the 17 animals were recumbent at presentation while the remaining six became recumbent within 6 hours of admission. Both multiparous cows (n = 11) and first calf heifers (n = 6) were included. The median days in milk was 21 (range: 5 to 110), and chronic, recurrent ketosis (15 of the 17 cases) was the most common preexistent condition. Potential musculoskeletal and neurologic causes of recumbency were ruled out on the basis of physical examination and ancillary diagnostics. Ten of the 17 animals were euthanized and underwent full necropsy examination that demonstrated ischemic muscle damage and varying degrees of hepatic lipidosis. Aggressive potassium supplementation was instituted in all 17 cases either orally, intravenously, or by a combination of both routes. In the seven individuals that survived, potassium supplementation was administered orally and intravenously in five, orally only in one, and intravenously only in one.
Asunto(s)
Enfermedades de los Bovinos/patología , Hipopotasemia/veterinaria , Debilidad Muscular/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/tratamiento farmacológico , Femenino , Hipopotasemia/tratamiento farmacológico , Hipopotasemia/patología , Debilidad Muscular/tratamiento farmacológico , Debilidad Muscular/patología , Potasio/administración & dosificación , Potasio/uso terapéutico , Soluciones para Rehidratación/uso terapéutico , Factores de RiesgoRESUMEN
Microscopic examination of Gram-stained tissue specimens collected from severe corneal ulcers in 2 horses revealed large gram-positive rods suggestive of Clostridium spp. Clostridium perfringens was isolated from specimens collected from horse 1; anaerobic organisms were not detected in specimens from horse 2. Aerobic bacterial culture revealed Aeromonas hydrophila and Enterobacter cloacae in specimens collected from horses 1 and 2, respectively. An insect exoskeleton was presumed to be the underlying cause of ulceration in horse 1. Cause of ulceration in horse 2 was not determined. Antibiotics used to treat the corneal infections included ticarcillin disodium-clavulanic acid injected one time subconjunctivally and chloramphenicol applied topically at frequent intervals. Horse 2 also received penicillin or trimethoprim-sulfadiazine. Small leukomas were the only lesion remaining between 2 and 7 months after initial evaluation. Chloramphenicol applied topically appears to be an effective treatment against clostridial corneal infections in horses.
Asunto(s)
Bacterias Aerobias/aislamiento & purificación , Infecciones por Clostridium/veterinaria , Úlcera de la Córnea/veterinaria , Infecciones Bacterianas del Ojo/veterinaria , Enfermedades de los Caballos , Administración Tópica , Aeromonas hydrophila/aislamiento & purificación , Animales , Cloranfenicol/administración & dosificación , Cloranfenicol/uso terapéutico , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/microbiología , Úlcera de la Córnea/tratamiento farmacológico , Úlcera de la Córnea/microbiología , Quimioterapia Combinada , Enterobacter cloacae/aislamiento & purificación , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/veterinaria , Cuerpos Extraños en el Ojo/complicaciones , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Infecciones Bacterianas del Ojo/microbiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/veterinaria , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/etiología , Enfermedades de los Caballos/microbiología , Caballos , Insectos , Pomadas , Soluciones Oftálmicas , Penicilinas/administración & dosificación , Penicilinas/uso terapéuticoRESUMEN
Preclinical aspects of a potent anti-hepatitis B virus (HBV) L-nucleoside, 1-(2-fluoro-5-methyl-beta-L-arabino-furanosyl)uracil (L-FMAU) are described. L-FMAU was prepared from L-ribose derivatives via either L-xylose or L-arabinose. L-FMAU shows potent antiviral activity against hepatitis B virus (EC50 5.0 microM in H1 cells) with high selectivity in vitro. L-FMAU is not incorporated into mitochondrial DNA and no significant lactic acid production was observed in vitro. L-FMAU is phosphorylated by thymidine kinase as well as deoxycytidine kinase, ultimately to the triphosphate, which inhibits HBV DNA polymerase as the mechanism of antiviral action. Preliminary in vivo toxological studies suggest no apparent toxicity for 30 days at 50 mg/kg/day in mice and for 3 months in woodchucks (10 mg/kg/day). L-FMAU also has respectable bioavailability in rats. L-FMAU shows potent anti-HBV activity in vivo against woodchuck hepatitis virus in chronically infected woodchucks and there is no significant virus rebound after cessation of the drug treatment.
Asunto(s)
Antivirales/farmacología , Arabinofuranosil Uracilo/análogos & derivados , Virus de la Hepatitis B/efectos de los fármacos , Animales , Antivirales/toxicidad , Arabinofuranosil Uracilo/química , Arabinofuranosil Uracilo/farmacología , Arabinofuranosil Uracilo/toxicidad , Disponibilidad Biológica , Línea Celular , Desoxicitidina Quinasa/metabolismo , Evaluación Preclínica de Medicamentos , Patos , Infecciones por Hepadnaviridae/tratamiento farmacológico , Infecciones por Hepadnaviridae/virología , Virus de la Hepatitis B del Pato/efectos de los fármacos , Virus de la Hepatitis B de la Marmota/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Ácido Láctico/sangre , Ácido Láctico/metabolismo , Dosificación Letal Mediana , Marmota , Ratones , Fosforilación , Ratas , Timidina Quinasa/metabolismoRESUMEN
A nine-year-old Holstein cow that developed recurrent ruminal tympany and an abnormal forelimb gait and posture ultimately became recumbent and unable to rise, and was euthanased. A postmortem examination demonstrated numerous schwannomas affecting peripheral nerves and several thoracic and abdominal viscera.