RESUMEN
Neoplastic lesions were observed in untreated aged Sprague Dawley (SD) rats throughout their lifespan starting at 5 weeks. Their mean survival times were 89 to 105 weeks of age. The total tumor incidences were 70 to 76.7% and 87 to 95.8% in males and females, respectively. The common neoplasmas were pituitary adenoma and adrenal pheochromocytoma in both sexes, testicular Leydig cell tumor in males and mammary gland tumors, thyroidal C-cell adenoma and uterine stromal polyp in females.
Asunto(s)
Envejecimiento , Neoplasias/veterinaria , Enfermedades de los Roedores/epidemiología , Adenoma/epidemiología , Adenoma/veterinaria , Neoplasias de las Glándulas Suprarrenales/epidemiología , Neoplasias de las Glándulas Suprarrenales/veterinaria , Animales , Femenino , Tumor de Células de Leydig/epidemiología , Tumor de Células de Leydig/veterinaria , Masculino , Neoplasias Mamarias Animales/epidemiología , Neoplasias/epidemiología , Feocromocitoma/epidemiología , Feocromocitoma/veterinaria , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/veterinaria , Pólipos/epidemiología , Pólipos/veterinaria , Ratas , Ratas Sprague-Dawley , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/veterinaria , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/veterinaria , Neoplasias Uterinas/epidemiología , Neoplasias Uterinas/veterinariaRESUMEN
A 12-month oral repeated dose toxicity study of (+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was conducted in beagle dogs. Male and female dogs were given the drug orally for 12 months at doses of 0 (control), 3, 17.5 and 100 mg/kg. After discontinuation of the treatment, a 2-month recovery test was also conducted. No effects related to the treatment were observed on survival and water consumption. Mydriasis, vomiting and a decrease in body weight or a suppression of its weight gain were seen in the 17.5 and 100 mg/kg groups. Salivation and a decrease in food consumption were seen in the 100 mg/kg group. Ophthalmologic examination confirmed the mydriasis in the 17.5 and 100 mg/kg groups. Electrocardiographic and hematological examinations and urinalysis showed no abnormalities attributable to the treatment. Blood chemical examination revealed increases in GPT and ALP in the 17.5 and 100 mg/kg groups, increases in GOT and triglyceride and a decrease in total protein in the 100 mg/kg group. Pathological examination disclosed hepatocellular hypertrophy and concentric lamellar bodies derived from the smooth-ER in the 100 mg/kg group, and hyperplasia of smooth-ER, an increase in number of lysosomes and bile pigments in the bile capillary, hepatocyte and stellate cells of Kupffer in the 17.5 and 100 mg/kg groups. The recovery test showed that the above-mentioned changes were satisfactorily reversible or the degree and frequency of these changes were lowered. The serum concentrations of NS-21 and its active metabolite. RCC-36, in the treated groups were increased in a dose-dependent manner. No treatment-related effects were seen in the 3 mg/kg group. These results show that the NOAEL (no observed adverse effect level) of NS-21 is 3 mg/kg for 12-month oral toxicity in dogs.
Asunto(s)
Fenilacetatos/toxicidad , Trastornos Urinarios/tratamiento farmacológico , Administración Oral , Animales , Perros , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Estructura Molecular , Fenilacetatos/química , Fenilacetatos/uso terapéutico , Factores de Tiempo , Incontinencia Urinaria/tratamiento farmacológicoRESUMEN
A repeated dose toxicity study of prulifloxacin, a new antibacterial agent, was conducted in beagle dogs. Male and female dogs were given the test material orally for 13 weeks at doses of 0 (control), 20, 100 and 500 mg/kg. After discontinuation of the treatment, a 5-week recovery test was also conducted. Vomiting, salivation and decreased body weight gain or reduced body weight were seen in the 100 and 500 mg/kg groups. In the 500 mg/kg group, tremor, paresis of posterior limb associated with prone or sitting position and decreased food consumption were also observed. There were no treatment-related effects on survival and water consumption. Ophthalmoscopic, electrocardiographic and hematologic examinations, and urinalysis failed to show any abnormalities attributable to the treatment. Blood chemical examination showed increased GPT and decreased beta- and gamma-globulins in the 100 and 500 mg/kg groups, and increased GOT in the 500 mg/kg group. In pathological examination, cavitations and erosions were seen in the humeral and femoral articular cartilages in the 100 and 500 mg/kg groups. The above-mentioned changes were satisfactorily reversible except for erosions in the humeral and femoral articular cartilages in the 100 and 500 mg/kg groups. No toxicological findings were seen in the 20 mg/kg group. The results show that the NOAEL of prulifloxacin is 20 mg/kg for 13-week repeated dose toxicity in dogs.
Asunto(s)
Antiinfecciosos/toxicidad , Dioxolanos/toxicidad , Fluoroquinolonas , Piperazinas/toxicidad , Quinolonas/toxicidad , Administración Oral , Alanina Transaminasa/sangre , Animales , Antiinfecciosos/administración & dosificación , Aspartato Aminotransferasas/sangre , beta-Globulinas/metabolismo , Peso Corporal/efectos de los fármacos , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Dioxolanos/administración & dosificación , Perros , Discinesia Inducida por Medicamentos/etiología , Femenino , Masculino , Piperazinas/administración & dosificación , Quinolonas/administración & dosificación , gammaglobulinas/metabolismoRESUMEN
Renal toxicity of prulifloxacin, a new antibacterial agent, was investigated in rats of both sexes. The animals were given prulifloxacin orally for 28 days at a dose of 3000 mg/kg. Tubular nephrosis in which crystalline substances appeared primarily within tubules was observed from the second day of administration, and a large number of brown circular crystals were found in the urinary sediment from the first day of administration. Electron microscopic observation revealed a close resemblance of the ultrastructural characteristics between the intratubular crystalline substance and the urinary brown circular crystal, and the tubules were occasionally occluded by the crystalline substances. Infrared spectral analysis and X-ray microanalysis indicated that the brown circular crystal consisted of NM394, an active metabolite of prulifloxacin. These results suggested that NM394, which was filtered into the primary urine, may be precipitated as crystals on the process of water reabsorption in the tubules. And then most of the crystals would be washed out as crystalluria particles, and some of crystals retained and caused the obstructive uropathy.
Asunto(s)
Antiinfecciosos/toxicidad , Dioxolanos/toxicidad , Fluoroquinolonas , Riñón/efectos de los fármacos , Piperazinas/toxicidad , Quinolonas/toxicidad , Administración Oral , Animales , Antiinfecciosos/administración & dosificación , Antiinfecciosos/metabolismo , Cristalización , Dioxolanos/administración & dosificación , Dioxolanos/metabolismo , Femenino , Riñón/patología , Necrosis Tubular Aguda/inducido químicamente , Necrosis Tubular Aguda/metabolismo , Necrosis Tubular Aguda/patología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/metabolismo , Túbulos Renales/ultraestructura , Masculino , Piperazinas/administración & dosificación , Piperazinas/metabolismo , Piperazinas/orina , Quinolonas/administración & dosificación , Quinolonas/metabolismo , Quinolonas/orina , Ratas , Ratas Sprague-DawleyAsunto(s)
Astrocitoma/veterinaria , Parálisis/veterinaria , Ratas Sprague-Dawley , Enfermedades de los Roedores , Neoplasias de la Médula Espinal/veterinaria , Animales , Astrocitoma/complicaciones , Miembro Anterior , Masculino , Parálisis/etiología , Ratas , Neoplasias de la Médula Espinal/complicacionesRESUMEN
An intracranial epidermoid cyst was identified within the fourth ventricle of a male 10-month-old beagle dog. The cyst, which exhibited a multilocular structure, was lined by a stratified squamous epithelium and filled with desquamated keratin. In the region of the roof of the fourth ventricle, choroid plexus adherent to the cyst wall and secondary compression of the cerebellum were also seen.
Asunto(s)
Encefalopatías/veterinaria , Enfermedades de los Perros/patología , Quiste Epidérmico/veterinaria , Animales , Encefalopatías/patología , Enfermedades Cerebelosas/patología , Enfermedades Cerebelosas/veterinaria , Plexo Coroideo/patología , Perros , Quiste Epidérmico/patología , MasculinoRESUMEN
Simultaneous administration of monensin and tiamulin to pigs resulted in enhanced myotoxicity. Skeletal muscles of tongue, diaphragm and legs were preferentially affected, whereas the masseter, longissimus thoracis and cardiac muscles, including the left auricle, were spared. Histochemical examination revealed an involvement of both type I and II fibers of skeletal muscles.