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101.
Interspecies allometric meta‐analysis of the comparative pharmacokinetics of 85 drugs across veterinary and laboratory animal species 下载免费PDF全文
Q. Huang R. Gehring L. A. Tell M. Li J. E. Riviere 《Journal of veterinary pharmacology and therapeutics》2015,38(3):214-226
Allometric scaling is widely used for the determination of first dosage regimen and the interpolation or extrapolation of pharmacokinetic parameters across many animal species during drug development. In this article, 85 drugs used in veterinary medicine obtained from the Food Animal Residue Avoidance Databank database were selected for allometric scaling analysis. Outlier species were identified by statistical methods. The results showed that 77% and 88% of drugs displayed significant correlations between total systemic clearance (CL) and volume of distribution at steady status (Vss) vs. body weight (P < 0.05) on a log‐log scale, respectively. The distribution of the allometric exponent b for CL and Vss displays approximate normal distribution, with means (0.87 and 0.99) and standard deviations (0.143 and 0.157) for CL and Vss, respectively. Twelve drugs were identified to have at least one outlier species for CL and ten drugs for Vss. The human CL and Vss were predicted for selected drugs by the obtained allometric equations. The predicted CL and Vss were within a threefold error compared to observed values, except the predicted CL values for antipyrine, warfarin and diazepam. The results can be used to estimate cross‐species pharmacokinetic profiles for predicting drug dosages in veterinary species, and to identify those species for which interpolation or extrapolation of pharmacokinetics properties may be problematic. 相似文献
102.
Evidence of shallow fault zone strengthening after the 1992 M7.5 landers, california, earthquake 总被引:1,自引:0,他引:1
Repeated seismic surveys of the Landers, California, fault zone that ruptured in the magnitude (M) 7.5 earthquake of 1992 reveal an increase in seismic velocity with time. P, S, and fault zone trapped waves were excited by near-surface explosions in two locations in 1994 and 1996, and were recorded on two linear, three-component seismic arrays deployed across the Johnson Valley fault trace. The travel times of P and S waves for identical shot-receiver pairs decreased by 0.5 to 1.5 percent from 1994 to 1996, with the larger changes at stations located within the fault zone. These observations indicate that the shallow Johnson Valley fault is strengthening after the main shock, most likely because of closure of cracks that were opened by the 1992 earthquake. The increase in velocity is consistent with the prevalence of dry over wet cracks and with a reduction in the apparent crack density near the fault zone by approximately 1.0 percent from 1994 to 1996. 相似文献
103.
M A Payne A L Craigmill J E Riviere R E Baynes A I Webb S F Sundlof 《Veterinary Clinics of North America: Food Animal Practice》1999,15(1):75-88
During the last one-and-one-half decades, FARAD has established an unparalleled compilation of residue and pharmacokinetic information for veterinary species. In order to fulfill its mission, FARAD has become as much a research project as an educational one. Pressing problems, such as disease-altered kinetics, minor-species drug use, and industrial contaminants in livestock, require the new methods of analysis FARAD is developing. The data upon which this work is based can be greatly augmented by participation by other nations. In the United States, it was the cooperation of both academic and regulatory organizations that made the success of FARAD possible. Similar international cooperation can facilitate use of the FARAD model in other countries for the economic benefit of all participants, enhancement of food safety, and promotion of animal welfare. 相似文献
104.
OBJECTIVE: To determine the efficacy of doxorubicin when used alone in inducing remission in cats with lymphosarcoma. DESIGN: Prospective multi-institutional study of naturally occurring disease. METHODS: Cases were accrued from veterinary institutions in Australia and New Zealand after obtaining consent from informed owners. Cats were treated with doxorubicin every 3 weeks for three treatments. If there was no response to the first dose of doxorubicin or if the cat relapsed during the doxorubicin regimen, the cat was withdrawn from the trial and either euthanased or treated with other agents. Age, breed, gender and anatomic site of the lymphosarcoma (multicentric, alimentary, mediastinal, extranodal) were recorded for each cat. Clinical remission was assessed before each treatment by physical examination, radiography, ultrasonography and computed tomography where appropriate. Complete remission was defined as the disappearance of all clinical signs and clinically detectable tumour. RESULTS: Twenty-one cases were accrued over a 2-year-period but only 19 were available for data analysis. Young Siamese cats were over-represented and all cats with mediastinal tumours were young Siamese. There was a significant difference between the mean ages of cats with mediastinal or multicentric lymphosarcoma (mean +/- SD: 3.5 +/- 3.0 and 4.3 +/- 2.6 years, respectively) and cats with alimentary or extranodal LSA (11.4 +/- 0.9 and 11.0 +/- 0.9 years, respectively). Of 19 cats treated with doxorubicin alone, 6 (32%) had complete remission, 6 (32%) had partial remission and 7 (36%) did not respond. CONCLUSIONS: The results suggest that doxorubicin cannot be recommended as a single agent for treatment of feline lymphosarcoma because of the rather poor remission rate achieved. 相似文献
105.
Tazumi A Maeda Y Buckley T Millar B Goldsmith C Dooley J Elborn J Matsuda M Moore J 《Irish veterinary journal》2009,62(7):456-459
Clinical isolates (n = 63) of Pseudomonas aeruginosa obtained from various sites in 63 horses were compared using ERIC2 RAPD PCR to determine their genetic relatedness. Resulting banding patterns (n = 24 genotypes) showed a high degree of genetic heterogeneity amongst all isolates examined, indicating a relative non-clonal relationship between isolates from these patients, employing this genotyping technique. This study characterised 63 clinical isolates into 24 distinct genotypes, with the largest cluster (genotype E) accounting for 10/63 (15.9%) of the isolates. ERIC2 RAPD PCR proved to be a highly discriminatory molecular typing tool of P. aeruginosa in isolates recovered from horses. With the adoption of several controls to aid reproducibility, this technique may be useful as an alternative to PFGE, particularly in epidemiological investigations of outbreaks where speed may be a significant parameter. This is the first report of clonal heterogeneity amongst P. aeruginosa from horses and demonstrated that ERIC RAPD PCR is a rapid method for the examination of this species in horses, which may be useful in outbreak analysis. 相似文献
106.
RB Rivkin L Legendre D Deibel JE Tremblay B Klein K Crocker S Roy N Silverberg C Lovejoy F Mesple N Romero MR Anderson P Matthews C Savenkoff A Vezina JC Therriault J Wesson C Berube RG Ingram 《Science (New York, N.Y.)》1996,272(5265):1163-1166
Models of biogenic carbon (BC) flux assume that short herbivorous food chains lead to high export, whereas complex microbial or omnivorous food webs lead to recycling and low export, and that export of BC from the euphotic zone equals new production (NP). In the Gulf of St. Lawrence, particulate organic carbon fluxes were similar during the spring phytoplankton bloom, when herbivory dominated, and during nonbloom conditions, when microbial and omnivorous food webs dominated. In contrast, NP was 1.2 to 161 times greater during the bloom than after it. Thus, neither food web structure nor NP can predict the magnitude or patterns of BC export, particularly on time scales over which the ocean is in nonequilibrium conditions. 相似文献
107.
R Cauble Da Silva LB TW Barbee P Celliers C Decker RA London JC Moreno JE Trebes AS Wan F Weber 《Science (New York, N.Y.)》1996,273(5278):1093-1096
X-ray lasers (XRLs) have experimental average gains that are significantly less than calculated values and a persistently low level of spatial coherence. An XRL has been used both as an injected signal to a short XRL amplifier and as an interferometer beam to measure two-dimensional local gain and density profiles of the XRL plasma with a resolution near 1 micrometer. The measured local gain is in agreement with atomic models but is unexpectedly spatially inhomogeneous. This inhomogeneity is responsible for the low level of spatial coherence observed and helps explain the disparity between observed and simulated gains. 相似文献
108.
JE Lupton 《Science (New York, N.Y.)》1996,272(5264):976-979
An extensive helium plume in the north central Pacific emanates from Loihi Seamount on the flanks of Hawaii. The maximum helium signal is found at a depth of about 1100 meters, the same depth as the near-field plume directly above Loihi Seamount. Although this helium plume is strongest near Hawaii, where the 3He/4He ratio at a depth of about 1100 meters reaches values 28 percent above the atmospheric ratio, it can be detected quite clearly at latitude 24°N, over 400 kilometers to the north. Excess 3He is also present on the same isopycnal between 15°N and 20°N at 135°W, some 2000 kilometers east of the Hawaiian Islands. 相似文献
109.
C Aurich T Gerlach JE Aurich H-O Hoppen J Lange N Parvizi 《Reproduction in domestic animals》2002,37(6):335-340
In the non‐breeding season, LH release is reduced via dopaminergic systems in the ram. On the other hand, our previous studies demonstrated an opioidergic inhibition of LH release in stallions outside the breeding season. Thus, in the present study we investigated the dopaminergic regulation of LH and prolactin secretion in stallions, considering interactions between dopamine and opioids. To achieve this, stallions (n=8) were treated with the dopamine antagonist sulpiride (0.6 mg/kg), the opioid antagonist naloxone (0.5 mg/kg), sulpiride plus naloxone or saline in December, March and June. Two hours after the respective treatments, they received a GnRH agonist. Sulpiride induced a significant prolactin release which was most pronounced in December, indicating seasonal variations in the inhibition of prolactin secretion by dopaminergic systems. Prolactin concentrations were not changed by naloxone. Neither during nor outside the breeding season, a dopaminergic regulation of LH release could be demonstrated. In contrast, naloxone caused a significant (p < 0.05) LH release, confirming an opioidergic inhibition of LH release. In conclusion, opioidergic regulation of LH and dopaminergic inhibition of prolactin secretion undergo seasonal changes. Neither during nor outside the breeding season, dopaminergic effects on LH release exist in the stallion. 相似文献
110.
Changes in use of both stored and newly synthesized sources of carbon (C) and nitrogen (N) were investigated during rooting of leafy cuttings of Larix x eurolepis A. Henry. We used dual (13)C and (15)N long-term labeling of reserves of stock plants and followed isotope dilution of the labels in the cuttings to determine the respective proportions of C and N derived from stock plant reserves (Q(C,old), Q(N,old)) and from newly synthesized sources (Q(C,new), Q(N,new)). We also assessed their partitioning into the growing needles and roots. Because rooting development occurred over several months, destructive harvests were made during three periods (t(0): April 9; t(1): May 15 to June 5; t(2): June 12 to June 26). Total C content (Q(C)) of cuttings did not change with time, whereas total N content (Q(N)) decreased significantly between t(0) and t(2). In rooted cuttings, unlike unrooted cuttings, total N concentration decreased less markedly in needles and in the lower stem component between t(1) and t(2) than between t(0) and t(2). The lower stem of rooted cuttings contained more Q(N,old) than that of unrooted cuttings and showed lower C:N and (13)C:(15)N ratios. The increase in Q(N,new) in the lower stem was positively correlated with rooting status. At t(1), new roots appeared and grew mainly at the expense of Q(C,new) and Q(N,old). By t(2), root growth was mainly dependent on new assimilates. We conclude that in leafy cuttings the initial amount of N reserves, rather than C reserves, may constitute a limiting factor for rooting. 相似文献