Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days. CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200–250 mg/m2 over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h−1; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h × ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200–250 mg/m2. 相似文献
Multi-agent chemotherapy successfully induces remission in most naïve, high-grade canine lymphoma patients; however, disease recurrence is common. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) is an effective rescue protocol used to re-induce remission, but is associated with gastrointestinal toxicity and can be a less desirable option for patients that previously failed vincristine-containing protocols. Therefore, alternative members of the vinca alkaloid family, such as vinblastine, could be potentially advantageous as substitutes for vincristine to reduce gastrointestinal toxicity and chemoresistance. The objective of this study was to report the clinical outcomes and toxicity of 36 dogs with relapsed or refractory multicentric lymphoma treated with a modified MOPP protocol whereby vincristine was replaced with vinblastine (MVPP). The overall response rate to MVPP was 25% with a median progression free survival of 15 days and a median overall survival of 45 days. MVPP at the prescribed doses resulted in modest and transient clinical benefit, but was well tolerated with no treatment delays or hospitalizations secondary to side effects. Given the minimal toxicity, dose intensification could be considered to improve clinical responses. 相似文献
Oral squamous cell carcinoma (OSCC) is the most common oral epithelial malignancy in dogs. It exhibits locally aggressive biological behaviour with the potential to metastasize, and a reported 1-year survival rate of 0% when left untreated. Expression studies suggest that aberrant MAPK signalling plays a key role in canine OSCC tumorigenesis, which is consistent with BRAF and HRAS MAPK-activating mutations reported in some tumours. Several morphological subtypes of canine OSCC have been described, with papillary, conventional, and basaloid as the most common patterns. We hypothesized that mutational differences may underlie these phenotypic variations. In this study, targeted Sanger sequencing and restriction fragment length polymorphism assays demonstrate that up to 85.7% of canine papillary OSCC (n = 14) harbour a BRAF p.V595E mutation. Assessment of neoplastic epithelial cell proliferation using Ki67 immunolabelling (n = 10) confirmed a relatively high proliferation activity, consistent with their known aggressive clinical behaviour. These findings underscore a consistent genetic feature of canine papillary OSCC and provide a basis for the development of novel diagnostic and targeted therapeutic approaches that can improve the quality of veterinary care. 相似文献
During the past two decades with farmer participation in irrigation management moving to center stage, the traditional view of having a centralized control over the water resources for better management has changed. Nevertheless, success of irrigation management transfer depend on a whole set of institutional arrangements or the rules-in-use and the willingness of the users to comply and enforce and/or change the rules in the light of changing circumstances. There are many institutional analyses of water sector, much of them touch on law, policy and administration, and characteristics of the users. The present paper is based on the study carried out to examine the institutional arrangements in one of the water users association that was first in the Maharashtra state. It focuses on the institutional arrangements governing water use and distribution and attempts to elicit the perceptions of the members regarding the rules-in-use. The findings reveal that the WUA has been successful in devising and enforcing the rules for water distribution, fee collection and conflict resolution for over a decade. However, current socio-economic developments such as political heterogeneity have required explicit conflict resolution mechanisms. These issues have now become issues demanding immediate attention and may be use of existing courts or legal institutions to help the WUA sustain in future. 相似文献
Conservation for the Indiana bat (Myotis sodalis), a federally endangered species in the United States of America, is typically focused on local maternity sites; however, the species is a regional migrant, interacting with the environment at multiple spatial scales. Hierarchical levels of management may be necessary, but we have limited knowledge of landscape-level ecology, distribution, and connectivity of suitable areas in complex landscapes.
Objectives
We sought to (1) identify factors influencing M. sodalis maternity colony distribution in a mosaic landscape, (2) map suitable maternity habitat, and (3) quantify connectivity importance of patches to direct conservation action.
Methods
Using 3 decades of occurrence data, we tested a priori, hypothesis-driven habitat suitability models. We mapped suitable areas and quantified connectivity importance of habitat patches with probabilistic habitat availability metrics.
Results
Factors improving landscape-scale suitability included limited agriculture, more forest cover, forest edge, proximity to medium-sized water bodies, lower elevations, and limited urban development. Areas closer to hibernacula and rivers were suitable. Binary maps showed that 30% of the study area was suitable for M. sodalis and 29% was important for connectivity. Most suitable patches were important for intra-patch connectivity and far fewer contributed to inter-patch connectivity.
Conclusions
While simple models may be effective for small, homogenous landscapes, complex models are needed to explain habitat suitability in large, mixed landscapes. Suitability modeling identified factors that made sites attractive as maternity areas. Connectivity analysis improved our understanding of important areas for bats and prioritized areas to target for restoration.
Bahiagrass (Paspalum notatum) is a warm-season grass used primarily in pastures and along highways and other low maintenance public areas in Florida.
It is also used in landscapes to some extent because of its drought tolerance. Bahiagrass can survive under a range of moisture
conditions from no irrigation to very wet conditions. Its well-watered consumptive use has not been reported previously. In
this study, bahiagrass crop coefficients (Kc) for an irrigated pasture were determined for July 2003 through December 2006 in central Florida. The eddy correlation method
was used to estimate crop evapotranspiration (ETc) rates. The standardized reference evapotranspiration (ETo) equation (ASCE-EWRI standardization of reference evapotranspiration task committee report, 2005) was applied to calculate
ETo values using on site weather data. Daily Kc values were estimated from the ratio of the measured ETc and the calculated ETo. The recommended Kc values for bahiagrass are 0.35 for January–February, 0.55 for March, 0.80 for April, 0.90 for May, 0.75 for June, 0.70 for
July–August, 0.75 for September, 0.70 for October, 0.60 for November, and 0.45 for December in central Florida. The highest
Kc value of 0.9 in May corresponded with maximum vapor pressure deficit conditions as well as cloud free conditions and the
highest incoming solar radiation as compared to the rest of the year. During the summer (June to August), frequent precipitation
events increased the cloud cover and reduced grass water use. The Kc annual trend was similar to estimated Kc values from another well-watered warm-season grass study in Florida. 相似文献
Landscape Ecology - In the original publication of the article, the third author name has been misspelt. The correct name is given in this Correction. The original version of this article was revised. 相似文献
Earthworms are recognized to play an important role in the decomposition of organic materials. To test the use of earthworms as an indicator of plant litter decomposition, we examined the abundance and biomass of earthworms in relation to plant litter decomposition in a tropical wet forest of Puerto Rico. We collected earthworms at 0–0.1 m and 0.1–0.25 m soil depths from upland and riparian sites that represent the natural variation in soils and decomposition rates within the forest. Earthworms were hand-sorted and weighed for both fresh and dry biomass. Earthworms were dominated by the exotic endogeic species Pontoscolex corethrurus Müller; they were more abundant, and had higher biomasses in the upland than in riparian sites of the forest. Plant leaf litter decomposed faster in the upland than riparian sites. We found that earthworm abundance in the upper 0.1 m of the soil profile positively correlated with decomposition rate of plant leaf litter. Ground litter removal had no effect on the abundance or biomass of endogeic earthworms. Our data suggest that earthworms can be used to predict decomposition rates of plant litter in the tropical wet forest, and that the decomposition of aboveground plant litter has little influence on the abundance and biomass of endogeic earthworms. 相似文献