Masitinib as a chemosensitizer of canine tumor cell lines: a proof of concept study

Masitinib, a selective tyrosine kinase inhibitor, has previously been shown to enhance the antiproliferative effects of gemcitabine in human pancreatic cancer, demonstrating potential as a chemosensitizer. This exploratory study investigated the ability of masitinib to sensitize various canine cancer cell lines to doxorubicin, vinblastine, and gemcitabine. Masitinib strongly sensitized histiocytic sarcoma cells to vinblastine (>70-fold reduction in IC(50) at 5 μM masitinib), as well as osteosarcoma and mammary carcinoma cells to gemcitabine (>70-fold reduction at 5-10 μM). In addition, several cell lines were sensitized to doxorubicin (2-10-fold reduction at 10 μM). These data establish proof-of-concept that masitinib in combination with chemotherapeutic agents can generate synergistic growth inhibition in various canine cancers, possibly through chemosensitization. The findings justify further investigation into those combinations that may potentially yield therapeutic benefit.     

Boldo (Peumus boldus) cultivated under different light conditions, soil humidity and plantation density

Boldo (Peumus boldus Mol.) is a medicinal plant native to the central zone of Chile and part of the sclerophyll forest. More than 2000 tons of dried leaves exported annually are wild collected. To develop a cultivation system that supports sustainable production of boldo leaves, we have studied growth and harvest of boldo under different light and soil water conditions. The leaf yield per plant as well as the alkaloid and essential oil content were the same for plants grown under shade and for plants exposed to full sun. The only difference between the shaded and the full sun plants was a higher percentage of stem in the harvested product of shade grown plants. This result would permit the intercropping of boldo in forest plantations without affecting the leaf yield and medicinal quality. The excellent adaptation to dry conditions was confirmed, as the different treatments of soil water led to similar leaf yields and plant heights. Plants submitted to water stress produced fewer but longer shoots and contained less essential oil. None of the treatments except water stress affected the medicinal quality requirements of alkaloid or essential oil concentration in the leaves. Wild collected leaves are inexpensive because of low production costs. To be able to compete with wild supplied leaves in the international market, we have evaluated high density plantings as a way to lower costs of a cultivated product by mechanizing harvest. High planting densities led to loweryielding individuals, but leaf yield per area increased. Plant height and the percentage of leaves in the harvested product was the same for densities of 8- and 16 plants m⁻². The leaves produced by cultivated boldo generally fulfill the requirements described in the European Pharmacopoeia. We conclude that boldo can be successfully cultivated under the described cultivation conditions.     

Morphological characters, yields and active principles in wild and cultivated accessions of the Chilean medicinal plant Buddleja globosa Hope

Buddleja globosa is a medicinal shrub native to Chile. Its leaves have been traditionally used for wound and ulcer healing. Different medicinal properties, such as outstanding antioxidant, anti-inflammatory, wound healing and analgesic activities have been shown. Today, all raw materials for pharmaceutical process are coming from wild collection or recently established crops but not from selected plants. Studies of the genetic or environmental variability of the species would permit the optimization of yield and quality factors through the selection of genetic material or suitable production sites and management techniques.To assess which traits are determined genetically some yield related plant and leaf characteristics were studied in three wild populations and the cultivated accessions from the same provenances. The cultivated accessions also included three clones coming from individuals found in rural home gardens. For the cultivation studies individuals were arranged in a randomised block design, and those for the irrigation studies in split plots watered at 20% and 65% field capacity.Plant characteristics such as height and width of the plant, the ratio of both, stem diameter and leaf density differed significantly among natural populations. In leaf characteristics only the presence of stipules showed significant differences. The cultivated progenies or clones may give an idea if these differences among populations are due to environmental or to genetic effects. Compared with other provenances, plants from the coastal provenance Los Ruiles are tallest in both natural populations and cultivated clones and also showed superior leaf yields in spite of their lower leaf density.The hairy leaves may cause allergic reactions at the moment of harvest. This characteristic is not influenced by different irrigation treatments and shows no significant differences between cultivated and wild plants.Because of the significant higher leaf yields per plant in home garden clones we assume that formerly individuals with a higher leaf production were selected for cultivation.     

Biodeposit production and benthic loading by farmed mussels and associated tunicate epifauna in Prince Edward Island

An experimental study was done to evaluate the biodeposition dynamics associated with mussels and two fouling tunicates, Ciona intestinalis and Styela clava, in mussel aquaculture in Prince Edward Island (PEI), eastern Canada. The presence of C. intestinalis on small constructed mussel socks increased biodeposition by a factor of about 2 relative to mussel socks without tunicates. S. clava were small and had a negligible effect on total biodeposition from mussel socks although they increased sedimentation rates relative to that of abiotic control socks. Sinking rates of faecal pellets from large C. intestinalis varied between 1.39 and 6.54 cm s^− 1 (LSMean = 2.35 cm s^− 1). Using biodeposit production and sinking rates and hydrological data obtained in the present study, footprints of benthic loading due to mussel and tunicate biodeposition for a typical mussel farm in PEI were modelled using Shellfish-DEPOMOD. The results show benthic loading below longlines with C. intestinalis to be ca. 2 times greater than those from lines with only mussels with rates of up to 15.2 g m^− 2 d^− 1. However, given the greater settling rate of C. intestinalis biodeposits relative to mussel biodeposits, the extent of the footprint (≥ 1 g m^− 2 d^− 1) is similar or even more restrained.     

超富集植物对稀土元素吸收转运解毒与分异的研究进展

稀土是重要的战略资源,在现代高科技行业和农业生产中发挥着重要的作用。随着稀土需求量的与日俱增,稀土矿山开发加剧,产生了大面积的稀土废弃尾砂地进而污染农田,对当地生态环境和居民健康构成威胁。植物采矿是指在金属污染地上种植超富集植物,在恢复植被和修复污染土壤的同时,还可通过收割地上部实现金属回收利用,是一种原位和低成本的污染土壤修复手段。探究超富集植物重金属富集机理是实现植物采矿的基础,但相对于Ni、Zn、As等超富集植物的研究,稀土超富集植物吸收转运和耐受稀土机制的研究仍然缺乏。本文结合近年国内外研究,从植物富集稀土的四个关键过程综述超富集植物对稀土的吸收、转运和分布解毒机制以及与稀土分异之间的关系,并提出超富集植物中稀土分异的概念模型。     

Pharmacokinetics of masitinib in cats

Masitinib is the first veterinary drug recently approved in Europe to treat mast cell tumours in dogs (Hahn et al. JVIM, Masivet). This inhibitor is selective and highly efficient in blocking c-Kit, PDGFR, and Lyn tyrosine kinase activities. It showed good efficacy and acceptable toxicity in several animal studies such as mice, rats, rabbits and dogs (Dubreuil P, et al. submitted, and Hahn et al. (J Vet Intern Med 22(6):8, 2008)). C-kit is a tyrosine kinase receptor that plays a critical role in the biology of mast cells including differentiation, survival, migration and cytokine/mediator release. Mast cells are involved in a number of allergy-and immune-related diseases in cats such as asthma (Reinero Carol et al. Vet Immunol Immunopathol 121(3–4):9, 2008), inflammatory bowel disease, (Janeczko et al. Vet Mic 128(1–2):15, 2008), and feline mast cell tumours (Rassnick et al. J Am Vet Med Assoc 232(8):1200–1205, 2008). Therefore, there might be a strong rationale to use masitinib in these indications. Here, we report the results of a preliminary pharmacokinetic study of masitinib in cats which showed a good bioavailability of ~60% in both sexes. We propose that an oral dose of 10–15 mg/kg masitinib is appropriate to achieve adequate plasma concentrations.     

Correlates of diet quality in the Quebec population

OBJECTIVE: To determine the correlates of a high-fat diet in urban, suburban and rural areas of Quebec, Canada. DESIGN: A secondary analysis of data collected as part of a 5-year multi-factorial, multi-setting, community-intervention project. SETTING: Urban, suburban and rural settings of the province of Quebec, 1997. SUBJECTS: Data were analysed from a sample of 5214 participants (2227 males, 2987 females). A food-frequency questionnaire was completed and a global index of food quality was calculated. Logistic regression was used to identify correlates of a diet high in total fats, saturated fat and cholesterol. RESULTS: In both genders, lower level of education, smoking status, French and English languages compared with other languages spoken at home, and a rural environment were associated with poor diet quality. Having no intention to eat low-fat dairy products more often was associated with a high-fat diet. In men, obesity (body mass index >/=30 kg m(-2)) and absence of reported health problems were correlates of a high-fat diet, while, in women, lower physical activity was a correlate. CONCLUSIONS: Future health interventions in Quebec should target people with low education, smokers and those living in a rural environment. Obese men and sedentary women should have access to specific dietetic resources.     

Masitinib is safe and effective for the treatment of canine mast cell tumors

Background: Activation of the KIT receptor tyrosine kinase is associated with the development of canine mast cell tumors (MCT). Hypothesis/Objective: To evaluate the efficacy of masitinib, a potent and selective inhibitor of KIT, in the treatment of canine MCT. Animals: Two hundred and two client‐owned dogs with nonmetastatic recurrent or nonresectable grade II or III MCT. Methods: Double‐blind, randomized, placebo‐controlled phase III clinical trial. Dogs were administered masitinib (12.5 mg/kg/d PO) or a placebo. Time‐to‐tumor progression (TTP), overall survival, objective response at 6 months, and toxicity were assessed. Resulsts: Masitinib increased overall TTP compared with placebo from 75 to 118 days (P= .038). This effect was more pronounced when masitinib was used as first‐line therapy, with an increase in the median TTP from 75 to 253 days (P= .001) and regardless of whether the tumors expressed mutant (83 versus not reached [P= .009]) or wild‐type KIT (66 versus 253 [P= .008]). Masitinib was generally well tolerated, with mild (grade I) or moderate (grade II) diarrhea or vomiting as the most common adverse events. Conclusions and Clinical Importance: Masitinib is safe and effective at delaying tumor progression in dogs presenting with recurrent or nonresectable grade II or III nonmetastatic MCT.     

Influence of vitamin E on organic matter fermentation,ruminal protein and fatty acid metabolism,protozoa concentrations and transfer of fatty acids

Vitamin E (Vit. E) is discussed to influence ruminal biohydrogenation. The objective of this study was to investigate the influence of a Vit. E supplementation on rumen fermentation characteristics, ruminal microbial protein synthesis as well as ruminal organic matter fermentation. Furthermore, we aimed to investigate the influence of Vit. E supplementation on short‐chain fatty acids (SCFA) and protozoa concentrations in the rumen and, in addition, on transfer rates of middle‐chain and long‐chain fatty acids into the duodenum in lactating dairy cows. Eight rumen and duodenum fistulated German Holstein cows were assigned to either a group receiving 2,327 IU/d Vit. E (138.6 IU/kg DM DL‐α‐tocopherylacetate; n = 4) or a control group (23.1 IU/kg DM; n = 4). Neither ruminal protein synthesis nor organic matter fermentation was influenced by treatment. Vit. E did not act on the concentrations of short‐chain fatty acids and protozoa in rumen fluid. Duodenal flow of C13:0 (1.3 versus 0.2 g/d, p = 0.014) and iso‐C14:0 (1.0 versus 0.5 g/d, p = 0.050) was higher in the Vit. E group. We observed a trend for higher duodenal flows for C12:0 (1.6 versus 0.9 g/d, p = 0.095) and anteiso‐C15:0 (12.2 versus 8.9 g/d, p = 0.084). Transfer rate of C12:0 tended to be higher in the Vit. E group (125.61 versus 73.96, p = 0.082). No other transfer rates were affected by treatment. Further studies are necessary to investigate the influence of Vit. E on rumen microbiota and their fatty acid production as well as on the impact of different doses of Vit. E supplementation on variables of protein synthesis efficiency.     

Early transformation and transfer processes in a Technosol developing on iron industry deposits

Large surface areas covered with man‐made materials are subject to pedogenetic evolution. However, pedogenetic processes in the resulting Technosols are seldom fully assessed. This work was conducted to identify and characterize the processes occurring on deposits of industrial technogenic materials. A former settling pond of the iron and steel industry where a forest has established since termination of the industrial activity approximately 50 years ago was chosen. A 2‐m deep pit was opened, and a series of layers of the soil profile were sampled. The macro‐ and micro‐structure were studied, and soil samples were analysed for structural, chemical and mineralogical assessment (chemical analyses, X‐ray diffraction, infrared and Mössbauer spectroscopies, scanning and transmission electron microscopies coupled with energy dispersion spectrometry). Results showed that the profile was composed of a succession of sub‐horizontal layers arranged in two groups according to their structure and composition, linked to the composition of the industrial effluent. Group 1 was composed of iron‐, carbonate‐ and aluminosilicate‐rich layers exhibiting a compact structure. Group 2 contained manganese‐rich layers with a friable structure. Pedogenetic processes of various intensities were detected at different depths. Besides an accumulation of organic matter at the surface, transformations of minerals were recorded all along the soil profile, with weathering, leaching and precipitation of new phases. Phenomena occurred primarily in specific zones, such as cracks and interfaces between two layers. In conclusion, the soil maintained characteristics of the original industrial material and displayed several stages of pedogenesis, which were controlled chronologically by climatic and biological factors.