Serum Concentrations of a Long-acting Cat Formulation of Transdermal Buprenorphine in C57BL/6 Mice.

Long-acting analgesics such as extended-release buprenorphine are desirable in rodent medicine because they reduce need for administration of additional medication and provide stable drug levels. We measured the serum concentrations of buprenorphine after topical administration of a long-acting transdermal buprenorphine (LAT-bup) solution to female C57BL/6 mice. We hypothesized that LAT-bup dosed topically at 40mg/kg would achieve serum drug concentrations of greater than 1ng/mL, which is considered the therapeutic level for adequate analgesia in rodents. LAT-bup administered at 40mg/kg resulted in serum drug concentrations above 1ng/mL for all mice at time points 2, 4, 24, 48, 72, and 96 h (n = 3/time point), as assessed by liquid chromatography-mass spectrometry. No adverse effects were noted when LAT-bup was dosed at either 30mg/kg or 40mg/kg. We conclude that LAT-bup is easily administered to mice and achieves adequate blood levels for 96 h. Further studies evaluating analgesic efficacy are indicated.

Controls on the epilimnetic phosphorus concentration in small temperate lakes.

Phosphorus (P) is one of the key limiting nutrients for algal growth in most fresh surface waters. Understanding the determinants of P accumulation in the water column of lakes of interest, and the prediction of its concentration is important to water quality managers and other stakeholders. We hypothesized that lake physicochemical, climate, and watershed land-use attributes control lake P concentration. We collected relevant data from 126 lakes in Maine, USA, to determine the major drivers for summer total epilimnetic P concentrations. Predictive regression-based models featured lake external and internal drivers. The most important land-use driver was the extent of agriculture in the watershed. Lake average depth was the most important physical driver, with shallow lakes being most susceptible to high P concentrations; shallow lakes often stratify weakly and are most subject to internal mixing. The sediment NaOH-extracted aluminum (Al) to bicarbonate/dithionite-extracted P molar ratio was the most important sediment chemical driver; lakes with a high hypolimnetic P release have low ratios. The dissolved organic carbon (DOC) concentration was an important water column chemical driver; lakes having a high DOC concentration generally had higher epilimnetic P concentrations. Precipitation and temperature, two important climate/weather variables, were not significant drivers of epilimnetic P in the predictive models. Because lake depth and sediment quality are fixed in the short-term, the modeling framework serves as a quantitative lake management tool for stakeholders to assess the vulnerability of individual lakes to watershed development, particularly agriculture. The model also enables decisions for sustainable development in the watershed and lake remediation if sediment quality is conducive to internal P release. The findings of this study may be applied to bloom metrics more directly to support lake and watershed management actions.

Animal models of craniosynostosis.

BACKGROUND: Various animal models mimicking craniosynostosis have been developed, using mutant zebrafish and mouse. The aim of this paper is to review the different animal models for syndromic craniosynostosis and analyze what insights they have provided in our understanding of the pathophysiology of these conditions. MATERIAL AND METHODS: The relevant literature for animal models of craniosynostosis was reviewed. RESULTS: Although few studies on craniosynostosis using zebrafish were published, this model appears useful in studying the suture formation mechanisms conserved across vertebrates. Conversely, several mouse models have been generated for the most common syndromic craniosynostoses, associated with mutations in FGFR1, FGFR2, FGFR3 and TWIST genes and also in MSX2, EFFNA, GLI3, FREM1, FGF3/4 genes. The mouse models have also been used to test pharmacological treatments to restore craniofacial growth. CONCLUSIONS: Several zebrafish and mouse models have been developed in recent decades. These animal models have been helpful for our understanding of normal and pathological craniofacial growth. Mouse models mimicking craniosynostoses can be easily used for the screening of drugs as therapeutic candidates.

Acrylamide in health and disease.

Acrylamide has been classified as a probable carcinogen and can be ingested, inhaled (e.g. tobacco smoke), or absorbed. Fried, starchy foods are the most prominent sources of exposure. The reaction between asparagine and fructose typically produces the most acrylamide in foods from plant sources. Preparation methods shown to affect acrylamide production include temperature and cooking oil. Hemoglobin adducts present a reliable short term measurement of acrylamide exposure; a variety of methods, predominately LC/MS-MS, have been used for acrylamide detection. Health effects of acrylamide include neurotoxicity and genotoxicity. It is believed that the electrophilic nature of acrylamide will allow it to adduct to thiol groups on nerve axons and proteins that regulate neurotransmitter exocytosis. Presynaptic nitric oxide (NO) may also play a role here. Reproductively, males demonstrate a decrease in sperm count, motility and morphology. Acrylamide produces clastogenic effects while glycidamide (GA), its metabolite, produces mutagenic effects. A number of protective measures against the effects of acrylamide are possible including probiotics, increased use of compounds known to decrease acrylamide production and bioengineering of precursor foods such as potatoes.

[Treatment of advanced and/or metastatic colorectal cancer with bevacizumab in combination with oxaliplatin-based chemotherapy (Folfox7 regimen)]. / Bevacizumab plus oxaliplatine, acide folinique et 5-fluoro-uracile (Folfox7) en première ligne de traitement des cancers colorectaux évolués et/ou métastatiques.

INTRODUCTION: Fundamental research identified new therapy targets implicated in tumor proliferation and angiogenesis which lead to the development of several targeted therapies. Currently, three drugs are used in the treatment of advanced colorectal cancer, cetuximab and panitumumab, two anti epidermal growth factor receptor, and bevacizumab, an anti vascular endothelial growth factor. PATIENTS AND METHODS: We evaluated a treatment with oxaliplatin-based chemotherapy (Folfox7 regimen) and bevacizumab in patients with locally advanced and/or metastatic colorectal cancer. Objectives of the study are the evaluation of the efficacy, toxicity, progression free survival, overall survival and tumor cell expression of the vascular endothelial growth factor by immunochemistry. RESULTS: 47 patients are included in the study during the period between April 2005 and June 2007; 28 men and 19 women. After six cycles of treatment, we achieved 67.3% of objectives responses and 76% of tumor control. The median progression free survival evaluated was 12 months (9.3-14.6 months) and median overall survival 18 months (9-26.9 months). The immunochemistry study of 46 tumours of the study achieved the following results: 13% (0), 17.4% (1+), 23.9% (2+) and 45.7% (3+). A correlation between the vascular endothelial growth factor expression, therapeutic responses and survival has been demonstrated but the difference was not significant in term of survival. Both chemotherapy toxicity and bevacizumab related toxicity are acceptable in our study. CONCLUSION: The fact that vascular endothelial growth factor expression is common in more than 80% of colorectal cancers, lead to recommend the systematic use of bevacizumab with chemotherapy in the treatment of advanced colorectal cancer.