Treatment of partial seizures and seizure-like activity with felbamate in six dogs     

Ruehlmann D  Podell M  March P 《The Journal of small animal practice》2001,42(8):403-408

Six dogs with partial seizures or partial seizure-like activity were treated with the antiepileptic drug felbamate between 1993 and 1998. All dogs had a history and results of diagnostic testing suggestive of either primary (idiopathic) or occult secondary epilepsy. Dogs ranged between four months and eight years of age at the onset of seizure activity. The median time period between onset of the first seizure and the start of felbamate therapy was 3.8 months (range 0.75 to 36 months). Median duration of therapy was nine months (range two to 22 months). All dogs experienced a reduction in seizure frequency after felbamate administration. Median total number of seizures post-treatment was two (range 0 to 9). Two dogs had an immediate and prolonged cessation of seizure activity. Steady-state trough serum felbamate concentrations measured at two weeks, and one, 12 and 22 months after the commencement of therapy in four dogs ranged between 13 and 55 mg/litre (median 35 mg/litre). Reversible haematological adverse effects were detected in two dogs, with one dog developing concurrent keratoconjunctivitis sicca. These results suggest that felbamate can be an effective antiepileptic drug without life-threatening complications when used as monotherapy for partial seizures in the dog.  相似文献   

Immunohistochemical detection of PrP in the medulla oblongata of sheep: the spectrum of staining in normal and scrapie-affected sheep     

Ryder SJ  Spencer YI  Bellerby PJ  March SA 《The Veterinary record》2001,148(1):7-13

Sections of the medulla oblongata from the brains of sheep were examined for prion protein (PrP) by immunohistochemistry. On the basis of the morphology and neuroanatomical distribution of the deposits, distinct disease-associated patterns of PrP deposition were identified in scrapie-affected sheep, suggesting at least four distinct phenotypes of scrapie. In addition, clearly defined patterns of PrP deposition, readily distinguished from the disease-associated PrP deposits, were identified in some normal sheep from scrapie-free flocks. In five sheep, believed to be preclinically affected by scrapie, PrP deposition of a disease-specific type but of restricted distribution was identified, demonstrating the sensitivity of the technique for the diagnosis of scrapie. The neuroanatomical distribution of these early PrP deposits suggest that the route of entry of the scrapie agent into the brain is via parasympathetic motor neurons in the vagus nerve which innervate the gastrointestinal tract.  相似文献   

Refinement of an orthotopic lung cancer model in the nude rat   总被引：5，自引：0，他引：5  

March TH  Marron-Terada PG  Belinsky SA 《Veterinary pathology》2001,38(5):483-490

Over 85% of people with lung cancer eventually succumb to this disease, largely because current chemotherapies are ineffective. The testing and validation of promising new approaches generally rely on achieving responses with cell lines in vitro or in tumor xenografts in nude mice. However, quite often the results seen with these models are not recapitulated in the clinic, thus necessitating the need for better animal models of lung cancer for preclinical testing of new therapies. One promising model is that of orthotopic lung cancer, where xenografts of human lung cancer are established in lungs of immunodeficient rodents. The problems associated with this model include poor rates of engraftment, limited tumor multiplicity, and a heightened risk for surgical trauma. The purpose of our study was to develop an efficient approach to engraftment of orthotopic tumors throughout the lungs of the Rowett nude rat. Initially, we augmented immunosuppression in the rats with whole-body X-irradiation and then used orotracheal cannulas to intratracheally instill human cancer cells from the Calu-6 cell line. This protocol produced a low rate of engraftment and low tumor multiplicity. The hypothesis that slight disruption of the pulmonary epithelium or the surfactant layer would allow better tumor engraftment was tested by coadministration of either pancreatic elastase or ethylenediaminetetraacetic acid (EDTA) along with the cell instillations. Lung tumor engraftment was evaluated 8 weeks after instillation. The inclusion of elastase or EDTA with the Calu-6 cells resulted in an 80-100% engraftment rate, respectively. Coadministration of EDTA resulted in significantly larger and greater numbers of tumors/lung than those in elastase-treated animals. Temporal studies demonstrated that small nodules were scattered throughout the lung parenchyma 5 weeks after instilling Calu-6 cells and EDTA. These nodules grew to coalesce and form large masses that effaced >75% of the parenchyma at 9 weeks postinstillation. The refinements made through our studies have led to the development of an orthotopic lung cancer model that should facilitate the evaluation of novel therapies designed to treat or impede lung cancer development.  相似文献   

Muscular dystrophy in female dogs     

Shelton GD  Liu LA  Guo LT  Smith GK  Christiansen JS  Thomas WB  Smith MO  Kline KL  March PA  Flegel T  Engvall E 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2001,15(3):240-244

The most common form of muscular dystrophy in dogs and humans is caused by mutations in the dystrophin gene. The dystrophin gene is located on the X chromosome, and, therefore, disease-causing mutations in dystrophin occur most often in males. Therefore, females with dystrophin deficiency or other forms of muscular dystrophy may be undiagnosed or misdiagnosed. Immunohistochemistry was used to analyze dystrophin and a number of other muscle proteins associated with muscular dystrophy in humans, including sarcoglycans and laminin alpha2, in muscle biopsy specimens from 5 female dogs with pathologic changes consistent with muscular dystrophy. The female dogs were presented with a variety of clinical signs including generalized weakness, muscle wasting, tremors, exercise intolerance, gait abnormalities, and limb deformity. Serum creatine kinase activity was variably high. One dog had no detectable dystrophin in the muscle; another was mosaic, with some fibers normal and others partly dystrophin-deficient. A 3rd dog had normal dystrophin but no detectable laminin alpha2. Two dogs could not be classified. This study demonstrates the occurrence of dystrophin- and laminin alpha2-associated muscular dystrophy and the difficulty in clinical diagnosis of these disorders in female dogs.  相似文献   

Has bovine somatotropin (BST) an effect upon drug disposition? Comparative studies in goats and cattle with sulphadimidine and antipyrine after parenteral administration of BST,zeranol and proligestone     

R. F. WITKAMP  S. M. NIJMEIJER  C. T. M. VAN DUIN  M. M. BEVERS  TH. WENSING†  H. VAN GOGH  A.S.J.P.A.M. VAN MIERT 《Journal of veterinary pharmacology and therapeutics》1989,12(2):163-178

Daily subcutaneous BST injection in lactating cows, bulls and castrated male dwarf goats did not induce significant changes in the pharmacokinetic parameters of antipyrine (AP) and sulphadimidine (SDD). Similarly, no changes were obtained after injection of slow-release BST formulations in lactating cows and non-lactating female goats. In contrast to androgenic hormones, both zeranol and proligestone had no effect upon the disposition of AP and SDD, although both synthetic hormones did induce enhanced plasma somatotropin concentrations. In goats, metabolic effects induced by zeranol and BST included significant reductions in plasma urea values, whereas plasma creatinine levels were somewhat lower after daily BST administration.  相似文献   

Pharmacokinetics and toxicity of bromide following high-dose oral potassium bromide administration in healthy Beagles     

March PA  Podell M  Sams RA 《Journal of veterinary pharmacology and therapeutics》2002,25(6):425-432

The pharmacokinetics of a multidose regimen of potassium bromide (KBr) administration in normal dogs was examined. KBr was administered at 30 mg/kg p.o. q 12 h for a period of 115 days. Serum, urine, and cerebrospinal fluid (CSF) bromide (BR) concentrations were measured at the onset of dosing, during the accumulation phase, at steady-state, and after a subsequent dose adjustment. Median elimination half-life and steady-state serum concentration were 15.2 days and 245 mg/dL, respectively. Apparent total body clearance was 16.4 mL/day/kg and volume of distribution was 0.40 L/kg. The CSF:serum BR ratio at steady-state was 0.77. Dogs showed no neurologic deficits during maintenance dosing but significant latency shifts in waves I and V of the brainstem auditory evoked response were evident. Following a subsequent dose adjustment, serum BR concentrations of approximately 400 mg/dL were associated with caudal paresis in two dogs. Estimated half-life during the accumulation phase was shorter than elimination half-lives reported in other studies and was likely related to dietary chloride content. The range of steady-state concentrations achieved suggests individual differences in clearance and bioavailability between dogs. The described protocol reliably produced serum BR concentrations that are required by many epileptic patients for satisfactory seizure control.  相似文献   

Dynamics of plasma free amino acids in rainbow trout (Oncorhynchus mykiss under variety of dietary conditions     

Chutima Tantikitti  B. E. March 《Fish physiology and biochemistry》1995,14(3):179-194

Plasma amino acid profiles in the systemic circulation of rainbow trout acclimated to diets containing different protein sources, with and without supplementation with free amino acids, were monitored for up to 120 hours after consumption of the diets. Plasma concentrations of lysine, methionine, and isoleucine increased more rapidly after feeding a diet supplemented with these amino acids in free form and, depending upon the increase in plasma concentration, remained at concentrations above those in fish fed the basal diet for at least 24h after feeding. Dietary supplementation with isoleucine increased plasma concentrations of leucine and valine as well as of isoleucine. Maximum plasma concentrations for most amino acids were attained between 12 and 24h postprandial. Dietary inclusion of gelatin caused more rapid elevations in plasma glycine and serine than did free glycine. Feeding at three hour intervals resulted in stable plasma concentrations of individual amino acids in contrast to the fluctuations occurring when fish were fed once daily. Frequent feeding favoured a higher proportion of protein to lipid in body composition.  相似文献   

Utilization of dietary starch and glucose tolerance in juvenile chinook salmon (Oncorhynchus tshawytscha) of different strains in seawater     

Carol Nelson Mazur  D. A. Higgs  E. Plisetskaya  B. E. March 《Fish physiology and biochemistry》1992,10(4):303-313

Juvenile chinook salmon of three strains responded to inclusion of 28.7% of gelatinized starch in the diet with different degrees of reduction in growth rate and feed efficiency relative to control fish of the respective strains fed a low-starch, high-lipid diet of similar protein (46%) and estimated metabolizable energy content (16 mJ/kg). The productive protein value of the diet was not reduced to the same extent by the high intake of starch. Carcasses of fish fed the high-starch diet contained higher concentrations of protein and lower concentrations of lipid than control fish. The accumulation of liver glycogen in response to the high-starch diet differed among strains. Glucose tolerance curves also varied among strains but were poorly correlated with plasma concentrations of insulin. Tolerance to glucose loading was improved in fish previously fed the high-starch diet.  相似文献   

Self-trapping of dark incoherent light beams     

Z Chen  M Mitchell  M Segev  TH Coskun  DN Christodoulides 《Science (New York, N.Y.)》1998,280(5365):889-892

"Dark beams" are nonuniform optical beams that contain either a one-dimensional (1D) dark stripe or a two-dimensional (2D) dark hole resulting from a phase singularity or an amplitude depression in their optical field. Thus far, self-trapped dark beams (dark solitons) have been observed using coherent light only. Here, self-trapped dark incoherent light beams (self-trapped dark incoherent wavepackets) were observed. Both dark stripes and dark holes nested in a broad partially spatially incoherent wavefront were self-trapped to form dark solitons in a host photorefractive medium. These self-trapped 1D and 2D dark beams induced refractive-index changes akin to planar and circular dielectric waveguides. The experiments introduce the possibility of controlling high-power coherent laser beams with low-power incoherent light sources such as light emitting diodes.  相似文献   

Reticulocytosis in response to dietary antioxidants     

B E March  V Coates  J Biely 《Science (New York, N.Y.)》1969,164(886):1398-1399

Alpha-tocopheryl acetate, 1, 2, dihydro-6-ethoxy-2, 2, 4-trimethylquinoline, and butylated hydroxytoluene increased the number of circulating reticulocytes when added to the diet of chickens. Hematocrit values were not reduced and erythrocyte life-spans were not shortened by the antioxidants. The reticulocytosis is attributed to delayed loss of reticular material from the maturing erythrocytes. components.  相似文献