Characterization of circulating steroids and endocannabinoids levels in obese subjects by liquid chromatography tandem mass spectrometry

Nowadays obesity can be defined as a global epidemic. The precise identification of circulating biomarkers involved in this pathology could be essential to early diagnose potential co-morbidities and to better address the development of future therapeutic strategies. Published evidences show that circulating steroid hormones and endocannabinoids might have a role in the physiopathology of obesity; however, a precise and reliable quantification of these molecules is still lacking. In the first part of the present thesis, we developed a sensitive, specific and accurate quantification method for nine steroid hormones using a liquid chromatography tandem mass spectrometry (LC-MS/MS) system. This method has been used first for a comparative study with immunoassays, currently used in the clinical practice to quantify these molecules and then to redefine circulating reference intervals in healthy subjects. Furthermore, we measured circulating steroid hormones in three groups of subjects: normo-weight, over-weight and obese, defining different steroid hormones profiles depending on the obesity state. The role of circulating endocannabinoids in humans is still unclear, however there are several evidences concerning their involvement in obesity. In the second part of the thesis, we determined changes of circulating endocannabinoids in obese patients after a weight loss induced by bariatric surgery, currently the most effective long-term treatment for obesity, using LC/MS-MS. We measured basal and dynamic endocannabinoids plasma levels in 12 patients with severe obesity before, one month after and six months after the Roux-en-Y gastric bypass intervention, currently one of the most performed types of bariatric surgery. All together the findings illustrated in this thesis project will help better define the role of steroid hormones and endocannabinoids in the framework of obesity in humans and the role that each type of molecule might have in its pathophysiology.

Construções e redefinições: as toxoplasmoses

Esta tese tem como objeto o processo de redefinição da categoria diagnóstica infecção/doença Toxoplasmose. É um estudo qualitativo, inserido no campo science studies, de abordagem crítica reformista e de natureza empírico-analítica. Vincula-se à linha de pesquisa intitulada Instituições, saberes e práticas em saúde e ao projeto Os médicos e a ciência do Instituto de Medicina Social da Universidade do Estado do Rio de Janeiro. As unidades de análise foram: 1) Agentes envolvidos na produção do conhecimento científico em nível local; 2) Documentos normativos locais; 3) Documentos normativos nacionais e internacionais; 4) Instituição: Laboratório Reconhecer do Centro de Biociências e Biotecnologia (CBB), da Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF/Darcy Ribeiro). Como técnicas de pesquisa foram utilizadas a observação etnográfica, entrevistas e pesquisa documental da produção científica. Os pressupostos foram de que essa redefinição seja decorrente de uma construção (Hacking, 1999; Latour, 1997, 2000, 2001) e realizada em uma arena transepistêmica (Knor-Cetina, 1981). Foram acrescidos a esses conceitos, os de referência circulante (Latour, 2001) e os da taxonomia dos elementos dos objetos da ciência laboratorial, ou seja, os conceitos idéias, marcas e coisas (Hacking, 1992). Considerando essa dinâmica, as redefinições em relação a essa infecção/doença estariam em um período de pouca estabilização, embora elas não se definiriam completa e eternamente pela dependência que possuem do invólucro espaço-temporal (Latour, 2001) e da referência circulante.

ANT on the PISA trail: following the statistical pursuit of certainty

The OECD’s Programme for International Student Assessment (PISA) is increasingly depended upon by education policy makers to provide reliable measures of their country’s education system against international benchmarks. PISA attempts to provide efficient, scientific and technical means to develop educational policies which achieve optimal outcomes (Berg &Timmermans, 2000, p. 31). This kind of scientific evidence is seen by policy makers as being free of prejudice and ideology. Science is expected to represent the truth, state universal facts and make predictions.Thus PISA seeks to rank countries’ performances, work out future scenarios and offer policy direction. By what means does PISA gain knowledge and speak with confidence about diverse cultures and distant nations? How does it acquire a ‘voice from nowhere’ (Haraway, 1988; Suchman, 2000), and become a modern-day Oracle that countries might consult for policy advice? Modelled on early actor-network accounts of laboratory life, this ethnography traces how PISA knowledge comes to be made, guided by interview data with two ‘insiders’ in the ‘PISA laboratory’. It traces the translations and the circulating reference that turn PISA into a ‘centre of calculation’. It highlights how human and non-human entities are imbricated in the assembling of scientific facts and argues for a suspension of the divide between ‘science’ and ‘politics’. In the process, the paper offers an empirical instantiation of how some concepts from actor-network theory may be applied in the field of education policy, and ponders the implications of such an understanding for evidence based policy making.

Remarks on currency and banking; having reference to the present derangement of the circulating medium in the United States.

Mode of access: Internet.

Remarks on currency and banking : having reference to the present derangement of the circulating medium in the United States /

Mode of access: Internet.

Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer

Circulating tumour cells (CTCs) have attracted much recent interest in cancer research as a potential biomarker and as a means of studying the process of metastasis. It has long been understood that metastasis is a hallmark of malignancy, and conceptual theories on the basis of metastasis from the nineteenth century foretold the existence of a tumour "seed" which is capable of establishing discrete tumours in the "soil" of distant organs. This prescient "seed and soil" hypothesis accurately predicted the existence of CTCs; microscopic tumour fragments in the blood, at least some of which are capable of forming metastases. However, it is only in recent years that reliable, reproducible methods of CTC detection and analysis have been developed. To date, the majority of studies have employed the CellSearch™ system (Veridex LLC), which is an immunomagnetic purification method. Other promising techniques include microfluidic filters, isolation of tumour cells by size using microporous polycarbonate filters and flow cytometry-based approaches. While many challenges still exist, the detection of CTCs in blood is becoming increasingly feasible, giving rise to some tantalizing questions about the use of CTCs as a potential biomarker. CTC enumeration has been used to guide prognosis in patients with metastatic disease, and to act as a surrogate marker for disease response during therapy. Other possible uses for CTC detection include prognostication in early stage patients, identifying patients requiring adjuvant therapy, or in surveillance, for the detection of relapsing disease. Another exciting possible use for CTC detection assays is the molecular and genetic characterization of CTCs to act as a "liquid biopsy" representative of the primary tumour. Indeed it has already been demonstrated that it is possible to detect HER2, KRAS and EGFR mutation status in breast, colon and lung cancer CTCs respectively. In the course of this review, we shall discuss the biology of CTCs and their role in metastagenesis, the most commonly used techniques for their detection and the evidence to date of their clinical utility, with particular reference to lung cancer.

Decrease in circulating glucose, insulin and leptin levels and improvement in insulin resistance at 1 and 3 months after gastric bypass

Background: Hyperglycemia, insulin resistance and hyperleptinemia are some of the consequences of obesity. Gastric bypass for morbid obesity provides gastric restriction with decreased energy absorption. To confirm and extend previous reports in the literature, We evaluated the plasma glucose, serum insulin and leptin and insulin resistance of patients preoperatively and 1 and 3 months after Roux-en-Y gastric bypass (RYGBP).Methods: We determined body mass index (BMI), plasma glucose (glucose-oxidase method), serum leptin (immunoassay) and insulin (chemiluminescent immunometric assay), and insulin resistance index (IRI) by Homeostasis Model Assessment (HOMA) of 20 patients with morbid obesity both preoperatively and 1 and 3 months after RYGBP.Results: Patients showed a mean decrease in weight of 8 kg/month. Glycemia was above reference levels in 65% of the preoperative patients but dropped significantly 1 month postoperatively, serum insulin and leptin levels and the HOMA index also decreasing significantly in the same period. The percentage of patients with preoperative elevated serum insulin and leptin relative to reference levels decreased significantly following RYGBP. We also observed a weak but significant correlation between BMI and glucose, BMI and insulin, and leptin and insulin.Conclusions: the beneficial effects of bariatric surgery are already noticeable 1 month postoperatively, the reduction in insulin levels being more important for leptin reduction than decreased BMI. Leptin appeared to be subject to multifactorial control and showed a larger reduction than body weight.

Specific components found in circulating immune complexes (CIC) in paracoccidioidomycosis

Circulating immune complexes (CIC) from 15 paracoccidioidomycosis (PCM) patient sera and from 20 healthy control sera were analysed. After CIC precipitation, solubilization and acid treatment, only a little reactivity to P. brasiliensis antigens was found in the free antibodies from PCM-CIC. This result has suggested that there were antibodies with a high affinity bound to fungus components. Dissociated CIC were fractionated in a column of Sephacryl S300 and the fractions that probably contained antigens were pooled and applied to an affinity column, prepared with mouse anti-gp43 monoclonal antibody. Using ECL-Western blotting assay two polypeptide with apparent mass of 43 and 62 kDa were found.

Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality

Context: IGF-I plays a central role in metabolism and growth regulation. High IGF-I levels are associated with increased cancer risk and low IGF-I levels with increased risk for cardiovascular disease. Objective: Our objective was to determine the relationship between circulating IGF-I levels and mortality in the general population using random-effects meta-analysis and dose-response metaregression. Data Sources: We searched PubMed, EMBASE, Web of Science, and Cochrane Library from 1985 to September 2010 to identify relevant studies. Study Selection: Population-based cohort studies and (nested) case-control studies reporting on the relation between circulating IGF-I and mortality were assessed for eligibility. Data Extraction: Data extraction was performed by two investigators independently, using a standardized data extraction sheet. Data Synthesis: Twelve studies, with 14,906 participants, were included. Overall, risk of bias was limited. Mortality in subjects with low or high IGF-I levels was compared with mid-centile reference categories. All-cause mortality was increased in subjects with low as well as high IGF-I, with a hazard ratio (HR) of 1.27 (95% CI = 1.08–1.49) and HR of 1.18 (95% CI = 1.04–1.34), respectively. Dose-response metaregression showed a U-shaped relation of IGF-I and all-cause mortality (P = 0.003). The predicted HR for the increase in mortality comparing the 10th IGF-I with the 50th percentile was 1.56 (95% CI = 1.31–1.86); the predicted HR comparing the 90th with the 50th percentile was 1.29 (95% CI = 1.06–1.58). A U-shaped relationship was present for both cancer mortality and cardiovascular mortality. Conclusions: Both low and high IGF-I concentrations are associated with increased mortality in the general population.

A system of elocution, with special reference to gesture, to the treatment of stammering, and defective articulation ...

AMERICANA COLL./JVK-NON-CIRCULATING MATERIAL.

Septic Shock Sera Containing Circulating Histones Induce Dendritic Cell–Regulated Necrosis in Fatal Septic Shock Patients

International audience