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Pharmacokinetic and Phase I Evaluation of Carboplatin in Dogs 总被引:1,自引:1,他引:0
Rodney L. Page DVM MS Margaret C. McEntee DVM Steven L. George PhD Patrick L. Williams PhD Greta L. Heidner DVM Carol A. Novotney DVM Jim E. Riviere DVM PhD Mark W. Dewhirst DVM PhD Donald E. Thrall DVM PhD 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》1993,7(4):235-240
Thirty dogs with spontaneously occurring malignant neoplasms were treated monthly with carboplatin (CBDCA) given as a 30-minute intravenous infusion in a dose escalation study. Twenty-eight dogs were considered evaluable for toxicity. The maximally tolerated dose of CBDCA was conceptually defined as that dose, determined by logistic regression analyses of toxicity data, resulting in a 50% incidence of moderate toxicity (MOD50) or a 5% incidence of severe toxicity (SEV5). Each designated maximally tolerated dose was calculated for the first course of treatment only and for the first and second courses of treatment combined to estimate cumulative drug toxicity. The MOD50 and SEV5 for the first treatment course were 340 and 278 mg/M2, respectively. MOD50 and SEV5 values for the first plus second treatment courses were 327 and 231 mg/M2, respectively. The nadir of neutrophil and platelet counts occurred approximately 14 days after treatment. The mean neutrophil and platelet values for all dogs experiencing myelosuppression during the first two treatment courses were 1541/μL and 62,600/μL, respectively. Nonparametric pharmacokinetic analysis of plasma CBDCA values suggested that half-life (T1/2), area-under-the-curve and total body clearance (CLb) were not dose dependent. Volume of distribution (VDss) significantly increased with dose only between 100 and 150 mg/M2, not between 150 and 300 mg/M2. Dose-independent serum CBDCA pharmacokinetic disposition indicates that detailed investigation of tissue CBDCA distribution would be warranted and may identify novel dosing strategies that could improve the therapeutic index of CBDCA by minimizing toxicity. (Journal of Veterinary Internal Medicine 1993; 7:235–240. Copyright © 1993 by the American College of Veterinary Internal Medicine.) 相似文献
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Abdelwahab SI Hassan LE Sirat HM Yagi SM Koko WS Mohan S Taha MM Ahmad S Chuen CS Narrima P Rais MM Hadi AH 《Fitoterapia》2011,82(8):1190-1197
The in vivo and in vitro mechanistic anti-inflammatory actions of cucurbitacin E (CE) (Citrullus lanatus var. citroides) were examined. The results showed that LPS/INF-γ increased NO production in RAW264.7 macrophages, whereas L-NAME and CE curtailed it. CE did not reveal any cytotoxicity on RAW264.7 and WRL-68 cells. CE inhibited both COX enzymes with more selectivity toward COX-2. Intraperitoneal injection of CE significantly suppressed carrageenan-induced rat's paw edema. ORAC and FRAP assays showed that CE is not a potent ROS scavenger. It could be concluded that CE is potentially useful in treating inflammation through the inhibition of COX and RNS but not ROS. 相似文献
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Large‐scale identification of hot spots for soil carbon demand under climate change and bioenergy production 下载免费PDF全文
Global change scenarios predict an increased risk for declining amounts of soil organic matter (SOM) for Central Germany. Within this region the production of bioenergy is one important strategy to counteract the rising anthropogenic CO2‐emissions. Both issues have a close connection: SOM is an important basis for soil productivity and requires a steady reproduction flux. Bioenergy production requires productive soils and partly consumes plant biomass C. Therefore, the available amount for SOM reproduction is reduced. This study provides a methodology for the large‐scale identification of areas with possible conflicts between bioenergy production and SOM reproduction based on (1) the prediction of climate change impact on SOM reproduction and (2) an analysis of the regional distribution of biogas plants. With the C demand index (CDI) and the capacity index (CAP), two indicators were developed which enable the identification of hot spots of high carbon demand for SOM reproduction due to climate change and the usage of bioenergy. As a result of low data requirements, the indicators are widely applicable and transferable to other large‐scale studies. The proposed methodology was applied to Central Germany as a pilot region. Results indicate a growing demand (10–40%) of fresh organic C from biomass for SOM production in comparison to the current level. The analysis reveals that the bioenergy C demand is not evenly distributed within the study region. It also shows some regional clustering. Furthermore, the analysis identifies certain hot spots of a high C demand, where a high capacity of biogas production may conflict with rising demands for biomass to mitigate climate change effects on SOM storage. The hot spot areas—identified and selected on a large scale—can subsequently be analyzed in more detail on a local to farm scale by using high‐resolution data and models which enable the quantification of soil C dynamics. 相似文献
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Elena Curti Eleonora Carini Greta Bonacini Giovanni Tribuzio Elena Vittadini 《Journal of Cereal Science》2013
High fibre breads were produced adding durum wheat bran fractions of different composition and particle size. Fresh products were characterized for texture, crumb grain, volume, colour, water status (water activity, moisture content, frozen water content, 1H molecular mobility). 相似文献
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Gunanti Mahasri Umi Hafidloh Fungky P. Pratama Dicky Rahmawan Sri Subekti Putri D. Wulansari Muhamad Amin 《Journal of fish diseases》2020,43(10):1133-1143
The marine leech, Zeylanicobdella arugamensis, is a major threat to aquaculture in grouper-producing countries including Indonesia. This study aimed at investigating prevalence, intensity and histopathology of the ectoparasite in humpback and hybrid groupers cultured in different rearing systems. A total of 260 groupers (60 humpback groupers and 200 hybrid groupers) were used for samples. The marine leech was observed on skin, fins, gills and mouth, followed by histopathological assay on the skin tissue. The results showed that prevalence of the leech in both groupers was higher when they were cultured in the floating net cages compared with the hatchery, p < .05. Furthermore, humpback grouper had a higher prevalence than hybrid grouper when they were cultured in a similar system, p < .05. Meanwhile, there was no significant difference in intensity between the two groupers, p > .05. Within the hybrid groupers, the highest prevalence was obtained from hybrid groupers reared in the earthen ponds. Histopathological studies showed that the infected groupers exhibited inflammation, congestion and erosion of the epidermis layer. Hybrid grouper had more severe histopathological lesions in the skin tissues. These results suggested that species and type of aquaculture system had significantly determined the prevalence, intensity and severity of lesion in Z. arugamensis infestation. 相似文献
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Zainal A. Muchlisin Putri I. Sarah Dhea F. Aldila Kartini Eriani Iwan Hasri Agung S. Batubara Firman M. Nur Mustaqim Mustaqim Cut Ruhul Muthmainnah Abinawanto Abinawanto Martin Wilkes 《Aquaculture Research》2020,51(4):1700-1705
Cryoprotectant is the crucial factor in the cryopreservation process. In general, there are two types of cryoprotectant, permeating and non‐permeating cryoprotectants. Dimethyl sulfoxide (DMSO) and egg yolk are common permeating and non‐permeating cryoprotectants respectively. Hence, the objective of the present study was to determine the best proportion of DMSO and egg yolk for the cryopreservation of Rasbora tawarensis sperm. A completely randomized experimental design was used in this study which involves two types of cryoprotectant and their combination at different concentrations, namely 5% DMSO, 5% egg yolk, 5% DMSO + 5% egg yolk and 2.5% DMSO + 2.5% egg yolk. Every treatment was conducted in three replicates. Combination of 5% DMSO + 5% egg yolk gave the best results cryoprotectant treatment had significant effects on sperm motility, fertilization and hatching rate of the R. tawarensis eggs (p < .05). It is concluded that the best proportion of cryoprotectants for sperm cryopreservation in this species is 5% DMSO + 5% egg yolk. 相似文献
7.
Muhammad Mansyur Romi Nur Arfian Wiwit Ananda Wahyu Setyaningsih Rachma Greta Perdana Putri Mohammad Juffrie Dwi Cahyani Ratna Sari 《Iranian Biomedical Journal》2021,25(6):417
Background:Hyperuricemia induces nephropathy through the mediation of oxidative stress, tubular injury, inflammation, and fibrosis. The high uric acid level is associated with the reduction of vitamin D levels. However, the reno-protective effects of this vitamin in hyperuricemia condition remain unknown. This study aimed to elucidate calcitriol treatment in a uric acid-induced hyperuricemia mice model. Methods:Uric acid (125 mg/kg BW) was administered intraperitoneally for 7 (UA7) and 14 (UA14) days. Calcitriol (0.5 g/kg BW) was intraperitoneally injected for the following seven days, after 14 days of uric acid induction (UA14VD7 group). The control group received NaCl 0.9%, by the same route. Serum creatinine was measured using calorimetric method, and uric acid levels were assessed using enzymatic calorimetric assay. Tubular injury and fibrosis were assessed using PAS and Sirius red staining. RT-PCR and qRT-PCR were carried out for the analyses of SOD-1, Collagen-1, and TGF-1 mRNA expression in the kidney. Immunostaining of SOD-1 was performed to detect its expression in the kidney. Results:Uric acid and creatinine levels markedly increased in UA14 groups, followed by an exacerbation of tubular injury. RT-PCR revealed the upregulation of Collagen-1 and TGF-1, along with the downregulation of SOD-1. Calcitriol treatment attenuated the injury with reducing uric acid and creatinine levels, as well as tubular injury. This was associated with lower Collagen-1 and TGF-1 mRNA expression compared to the UA7 and UA14 groups. SOD-1 was upregulated in epithelial cells in the UA14VD7 group. Conclusion:Calcitriol treatment after uric acid induction may attenuate kidney injury through upregulation of SOD-1 and downregulation of Collagen-1 and TGF-1 gene expression. Key Words: Fibrosis, Hyperuricemia, Kidney injury, Superoxide dismutase-1, Vitamin D 相似文献
8.
Anhar Azwir Putri Dwi Hilda Advinda Linda Atika Veby Amimi Syovia Aldo Wahyu Ruchi Widya 《Journal of Crop Science and Biotechnology》2021,24(4):441-448
Journal of Crop Science and Biotechnology - This study aims to elucidate the molecular characterization of Trichoderma strains isolated from rice soil rhizosphere from paddy cultivation in West... 相似文献
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Seaman Dave J. I. Voigt Maria Bocedi Greta Travis Justin M. J. Palmer Stephen C. F. Ancrenaz Marc Wich Serge Meijaard Erik Bernard Henry Deere Nicolas J. Humle Tatyana Struebig Matthew J. 《Landscape Ecology》2021,36(10):2957-2975
Landscape Ecology - Agricultural expansion is a leading cause of deforestation and habitat fragmentation globally. Policies that support biodiversity and facilitate species movement across farmland... 相似文献