•The GC–MS/MS method uses of 250μl of serum and stable isotope internal standards.•Ten androgens, estrogens and their precursors are measured simultaneously.•The method is sensitivity, provides high ...accuracy, precision, and excellent specificity.•Its applicability is demonstrated on clinical samples from men and women.•This method will help conserve clinical samples from existing biobanks.
Measurement of a large set of sex steroids in clinical epidemiology and laboratory research with reliable methods providing low quantification limits and using a limited volume of blood sample represents a significant challenge. We report a new validated gas chromatography selected reaction monitoring – tandem mass spectrometry assay (GC–MS/MS) for the simultaneous quantification of ten endogenous steroids including progesterone (PROG), dehydroepiandrosterone (DHEA), androstenediol (5-diol), androstenedione (4-dione), testosterone (T), dihydrotestosterone (DHT), androsterone (ADT), 5alpha-androstan-3beta-17beta-diol (3β-diol), estrone (E1) and estradiol (E2). After addition of stable isotope internal standards, the approach involved the combination of liquid–liquid extraction, derivatization and solid-phase extraction for injection into the GC system and multiple reaction monitoring (MRM). The method presents high reproducibility for all analytical parameters in 250μl serum samples. The lower limit of quantification (LLOQ) were of 100pg/ml for DHEA, 50pg/ml for PROG, 5-diol, 4-dione and ADT, 30pg/ml for T, 10pg/ml for 3β-diol and DHT, 5pg/ml for E1, and 1pg/ml for E2. The applicability of the validated method to determine the concentrations of these 10 steroids was successfully tested on serum from men (n=15), premenopausal (n=10) and postmenopausal women (n=20), and is currently used for larger cancer-related epidemiology studies. One of the most considerable advantages over existing methods is the simultaneous determination of ten steroids in a limited volume of serum that will help conserve important clinical samples from existing biobanks.
Consumption of meat, especially beef, is often questioned for its effects on human health, particularly because of the growing prevalence of obesity with which it is associated by some. To help see ...if these are coincidences or co-incidences, the article uses mapping resources, maps were produced from FAO and WHO FaoStat databases, using the Cartes et Données software (Articque) then an additional graphic processing on Adobe Illustrator
Alors que de manière surprenante, l’agriculture reste en marge des négociations et des accords sur la lutte contre les changements climatiques, la FAO propose et porte depuis 2009 le concept ...d’agriculture intelligente face au climat ( climate-smart agriculture CSA). Fondé sur une préoccupation émanant du champ de l’agriculture et de ses institutions, il suscite d’importants débats politiques. À l’instar de nombreux concepts nés ces dernières années à la lisière du monde politique et des communautés scientifiques, il bouscule les frontières et les modes épistémiques. Les acteurs politiques attendent des « evidences », des réponses à leurs questions, des solutions à leurs problèmes, une caution pour crédibiliser les engagements à prendre... alors que la pensée est peu stabilisée et l’univers si incertain. L’espace politique et les interpellations diverses et variées, les comportements émergents mais aussi les critiques formulées par de nombreux acteurs à l’égard de la CSA, conduisent les scientifiques à organiser une série de conférences scientifiques mondiales. En refusant le piège du dogme, de la définition par la norme de ce qui serait ou ne serait pas labellisé « intelligent » et en insistant sur la nécessité de postures critiques, l’enjeu est de ne pas céder à la tentation d’une volatilité extrême des concepts, mais au contraire à faire de la CSA un cadre d’analyse et d’interprétation pertinent et opérationnel pour traiter des liens entre climat et agriculture.
Exploring why the long existing word “territory” is increasingly used to address current sustainability challenges seems a worthwhile effort. Beyond its polysemy, the territory is considered here as ...having both spatial and social characteristics, liaising for instance at the local level between community and landscape. At the local level, the territory contributes to the provision or management of public goods and has the capacity to generate changes. This concept provides an analytical and operational framework for addressing public regulation needs through the strengthening of targeted collective action, through the partial resolution of market and state failures and through the connection between collective and public action. The text finally looks at commonalties and specificities between the two concepts of socio-ecosystem and territory.
Dans un premier temps, sont analysées les raisons qui justifient la mobilisation croissante du mot « territoire » pour répondre aux défis du développement durable. Au-delà d’une polysémie affirmée, ce terme est ici considéré comme ayant une dimension sociale tout autant que spatiale, et faisant ainsi le lien entre les notions de communauté et de paysage. Le territoire contribue à la production et à la gestion de biens publics, ainsi que sa capacité à générer le changement. Ce concept offre un cadre analytique et opérationnel pour saisir les besoins de régulation publique via le renforcement d’actions collectives dédiées, la résolution partielle des défaillances d’État et de marché et les synergies entre actions collectives et publiques. Le texte identifie enfin les similitudes et spécificités des concepts de socioécosystème et de territoire.
Bile acids are considered as extremely toxic at the high concentrations reached during bile duct obstruction, but each acid displays variable cytotoxic properties. This study investigates how biliary ...obstruction and restoration of bile flow interferes with urinary and circulating levels of 17 common bile acids. Bile acids (conjugated and unconjugated) were quantified by liquid chromatography coupled with tandem mass spectrometry in serum and urine samples from 17 patients (8 men and 9 women) with biliary obstruction, before and after biliary stenting. Results were compared with serum concentrations measured in 40 age- and sex-paired control donors (20 men and 20 women). The total circulating bile acid concentration increases from 2.7 µM in control donors to 156.9 µM in untreated patients with biliary stenosis. Serum taurocholic and glycocholic acids exhibit 304- and 241-fold accumulations in patients with biliary obstruction compared to controls. The enrichment in chenodeoxycholic acid species reached a maximum of only 39-fold, while all secondary and 6α-hydroxylated species--except taurolithocholic acids--were either unchanged or significantly reduced. Stenting was efficient in restoring an almost normal circulating profile and in reducing urinary bile acids.
These results demonstrate that biliary obstruction affects differentially the circulating and/or urinary levels of the various bile acids. The observation that the most drastically affected acids correspond to the less toxic species supports the activation of self-protecting mechanisms aimed at limiting the inherent toxicity of bile acids in face of biliary obstruction.
The profound transformation of sustainable food systems is a major challenge for agriculture and societies. We must not only solve the problems of malnutrition, but also address all the challenges of ...sustainable development in a comprehensive way. In addition to the recurrent food and nutrition crises that have marked previous decades, changing dietary patterns have created a situation where population supply challenges are compound...
Recent evidence support that androgens play an important role in the etiology of endometrial cancer (EC). Adrenal-derived 11-oxygenated androgens are highly potent agonists of the androgen receptor ...(AR), comparable to testosterone (T) and dihydrotestosterone (DHT) that have not been studied in the context of EC.
We studied a cohort of 272 newly diagnosed postmenopausal EC cases undergoing surgical treatment. Circulating concentrations of seven 11-oxygenated androgens including precursors, potent androgens and their metabolites were established in serum samples collected before and 1 month after surgery using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). Free (unconjugated) and total (free + sulfate and glucuronide conjugates following enzymatic hydrolysis) were analyzed in relation to clinicopathological features, recurrence and disease-free survival (DFS).
Levels of 11-oxygenated androgens were weakly correlated to those of canonical androgens such as testosterone (T) and dihydrotestosterone (DHT), with no evidence of their association with clinicopathological features. Levels of 11-oxygenated androgens declined after surgery but remained higher in overweight and obese compared to normal weight cases. Higher levels of preoperative free 11-ketoandrosterone (11KAST) were associated with an increased risk of recurrence (Hazard ratio (HR) of 2.99 (95%CI=1.09-8.18);
=0.03). Postoperative free 11β-hydroxyandrosterone (11OHAST) levels were adversely associated with recurrence and DFS (HR = 3.23 (1.11-9.40);
=0.03 and 3.27 (1.34-8.00);
=0.009, respectively).
11-oxygenated androgen metabolites emerge as potential prognostic markers of EC.
Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has ...examined this potential association.
Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA.
Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio ORQ4 v. Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered.
This first study of sex steroid hormones and EA provides tentative evidence that androgen:estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.
The non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) is directly conjugated by the UDP-glucuronosyltransferase (UGT) pathway to form EFV-N-glucuronide (EFV-G), but the enzyme(s) ...involved has not yet been identified. The glucuronidation of EFV was screened with UGT1A and UGT2B enzymes expressed in a heterologous system, and UGT2B7 was shown to be the only reactive enzyme. The apparent K(m) value of UGT2B7 (21 microM) is similar to the value observed for human liver microsomes (24 microM), whereas the variant allozyme UGT2B7*2 (Tyr(268)) displayed similar kinetic parameters. Because 3'-azido-3'-deoxythymidine (AZT), one of the most current nucleotide reverse transcriptase inhibitors prescribed in combination with EFV, is also conjugated by UGT2B7, the potential metabolic interaction between EFV and AZT has been studied using human liver microsomes. Glucuronidation of both drugs was inhibited by one another, in a concentration-dependent manner. At K(m) values (25 and 1000 microM for EFV and AZT, respectively), EFV inhibited AZT glucuronidation by 47%, whereas AZT inhibited EFV glucuronidation by 23%. With a K(i) value of 17 microM for AZT-glucuronide formation, EFV appears to be one of the most selective and potent competitive inhibitor of AZT glucuronidation in vitro. Moreover, assuming that concentrations of EFV achieved in plasma (C(max) = 12.9 microM) are in a range similar to its K(i) value, it was estimated that EFV could produce a theoretical 43% inhibition of AZT glucuronidation in vivo. We conclude that UGT2B7 has a major role in EFV glucuronidation and that EFV could potentially interfere with the hepatic glucuronidation of AZT.
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