Pharmacokinetic and Phase I Evaluation of Carboplatin in Dogs

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 (T_1/2), area-under-the-curve and total body clearance (CL_b) were not dose dependent. Volume of distribution (VD_ss) 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.)     

Large‐scale identification of hot spots for soil carbon demand under climate change and bioenergy production

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.     

Effect of the addition of bran fractions on bread properties

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).     

Calcitriol Treatment Attenuates Uric Acid-Induced Kidney Injury via Super Oxide Dismutase-1 (SOD-1) Upregulation and Fibrosis Reduction

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     

Orangutan movement and population dynamics across human-modified landscapes: implications of policy and management

Landscape Ecology - Agricultural expansion is a leading cause of deforestation and habitat fragmentation globally. Policies that support biodiversity and facilitate species movement across farmland...     

A COMPARISON OF RADIOGRAPHIC AND COMPUTED TOMOGRAPHIC FINDINGS IN 31 DOGS WITH MALIGNANT NASAL CAVITY TUMORS

Nasal cavity radiographs and CT images from 31 dogs with nasal cavity cancer were compared. All dogs had abnormal clinical signs relating to -nasal cancer and histologic confirmation of malignant nasal cavity neoplasia. No dog had cyto reductive surgery prior to imaging. All radiographic and CT examinations were abnormal. CT was more accurate than radiographs in identifying unilateral versus bilateral nasal cavity disease and tumor extension into adjacent structures such as the cranial cavity, hard palate, and pterygopala-tine fossa. The improved accuracy of CT in these respects was not of benefit in the confirmation of nasal cavity disease because radiographs were abnormal in every instance. However, CT may be useful for more accurate tumor staging, predicting possible treatment-related complications, and planning of surgery and radiation therapy. It was also determined that one dorsally located radiation therapy portal bounded laterally by the medial ocular canthi, as described in previous reports, would not have been adequate for encompassing all abnormal tissue in 28 of the 31 dogs evaluated.     

A case report of a rapid development of fetal anasarca in a canine pregnancy at term

Veterinary Research Communications - A 5-year-old healthy pluriparous pregnant Flat-coated Retriever bitch was monitored by ultrasound on post-ovulation days 30 and 57: no deviation from normality...     

Sulfhydryl oxidase enhances the effects of ascorbic acid in wheat dough

Various enzyme families such as sulfhydryl oxidase have been successfully applied to bread production although their mechanism of action has not been fully described yet. In this study, we investigated the effects of the recently characterized fungal sulfhydryl oxidase AoSOX1 in fresh and frozen dough alone and in combination with ascorbic acid. The addition of AoSOX1 to an additive-free dough resulted in a weaker and more extensible dough while opposite effects were detected in the presence of ascorbic acid. The hardening of the doughs registered upon the combined use of AoSOX1 and ascorbic acid was dependent on the amount of enzyme used and not on the amount of ascorbic acid. The ability of the sulfhydryl oxidase to enhance the effects of the ascorbic acid system suggests their combined use as a valuable tool to stabilize the structure of fresh and frozen dough.     

Identifying landscape predictors of ocelot road mortality

Landscape Ecology - For depleted wildlife populations, understanding and effectively mitigating the direct and indirect impacts of roads can be a key component of recovery efforts. The ocelot is a...     

Immunoexpression of epithelial membrane antigen in canine meningioma: Novel results for perspective considerations

Epithelial membrane antigen (EMA) is one of the most widely used diagnostic immunohistochemical markers for human meningioma. To date, no published study on EMA expression in formalin‐fixed paraffin‐embedded (FFPE) tissue samples of canine meningioma is available. Here, we describe the results of an immunohistochemical study on 25 FFPE canine meningiomas using a monoclonal anti‐human EMA antibody. All meningiomas showed positive staining for EMA with cytoplasmic pattern, in nine cases associated with membranous staining. Area and intensity of staining were highly variable among cases. No clear relationships between tumour subtype/grade and area/intensity of staining were found. However, epithelial‐like patterns showed a higher affinity for EMA compared to the mesenchymal one. The present study provides the basis to explore the potential diagnostic application of this marker in canine meningioma. To investigate EMA expression in other central nervous system tumours of dogs are necessary to assess the specificity of this marker.