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Clenbuterol is a β2 agonist agent with anabolic properties given by the increase in the muscular mass in parallel to the decrease of the body fat. For this reason, the use of clenbuterol is forbidden by the World Anti-Doping Agency (WADA) in the practice of sport. This compound is of particular interest for anti-doping authorities and WADA-accredited laboratories due to the recent reporting of risk of unintentional doping following the eating of meat contaminated with traces of clenbuterol in some countries. In this work, the development and the validation of an ultra-high pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method for the quantification of clenbuterol in human urine is described. The analyte was extracted from urine samples by liquid-liquid extraction (LLE) in basic conditions using tert butyl-methyl ether (TBME) and analyzed by UHPLC-MS/MS with a linear gradient of acetonitrile in 9min only. The simple and rapid method presented here was validated in compliance with authority guidelines and showed a limit of quantification at 5pg/mL and a linearity range from 5pg/mL to 300pg/mL. Good trueness (85.8-105%), repeatability (5.7-10.6% RSD) and intermediate precision (5.9-14.9% RSD) results were obtained. The method was then applied to real samples from eighteen volunteers collecting urines after single oral doses administration (1, 5 and 10μg) of clenbuterol-enriched yogurts., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Epidemiological and experimental evidence indicates chronic inflammation as a risk factor for colorectal cancer. We investigated whether IL-1B -511C>T (rs16944), IL-1B +3954C>T (rs1143634) and IL1-RN +2018T>C (rs419598) cytokine polymorphisms are correlated with colorectal cancer. Blood samples were obtained from 377 Romanian subjects: 144 patients with sporadic colorectal cancer and 233 healthy controls. Polymorphisms were analyzed by allelic discrimination TaqMan PCR assays with specific probes. The results of our study showed that IL-1RN +2018T>C polymorphism is associated with colorectal cancer. We found that there was a significant difference in the frequency of CC genotype between patients with colorectal cancer and the control group (OR 2.42, 95 % CI: 1.06-5.53, p = 0,034) when TT genotype was used as reference. Furthermore, in a stratified analysis, a positive association was found only for IL-1RN +2018CC genotype, that was limited to early I and II stages (OR 2.72, 95 % CI: 1.05-7.03, p = 0,033). We did not find any association between any of the IL-1B polymorphisms and colorectal cancer. In conclusion this study found that IL-1RN +2018T>C polymorphism is associated with colorectal cancer, mainly for localized disease.

Background: Cytokines and chemokines are involved in cancer development and progression, but their role in colorectal tumorigenesis is still far from well defined. This study investigated the association between five cytokine promoter polymorphisms and risk, stage, and histological grade of colorectal cancer (CRC) in a hospital-based case-control study., Methods: A total of 377 Romanian subjects were included in this study: 144 patients with sporadic colorectal cancer and 233 controls. Cytokine polymorphisms (IL-1B -31T > C, IL-4R -3223C > T, IL-8 -251T > A, IL-10 -1082A > G, and TNF-A -308G > A) were genotyped by allelic discrimination TaqMan PCR assay with specific probes., Results: A significant association was observed for IL-10 -1082A > G polymorphism, the subjects carrying AG genotype were at a lower risk for CRC (OR 0.63, 95% CI: 0.40 - 0.98) when compared with the more frequent AA genotype. Furthermore, in a dominant model the carriers of G allele were protected against CRC (OR 0.64, 95% CI: 0.42 - 0.97). In a stratified analysis the only association between CRC and cytokine polymorphisms was found for carriers of IL-10 -1082G allele and was restricted to poorly differentiated cases (OR 0.36, 95% CI: 0.16 - 0.81). No association was observed for the remaining polymorphisms and CRC risk., Conclusions: This study shows that IL-10 -1082A > G polymorphism may influence CRC risk, the carriers of G allele being protected against CRC in the Romanian population.

Importance of the Field: The major application areas of liquid chromatography (LC) in modern drug discovery are the identification and structural characterization of new potential lead compounds from natural and/or synthetic sources and the determination of their physico-chemical and pharmacokinetic properties., Areas Covered in This Review: Significant advances in terms of LC platforms achieved in the last 5 years are highlighted in this review. Special attention is paid to novel LC strategies used in the discovery of new bioactive molecules and the determination of lipophilicity, pK(a) values, passive drug permeability and in vitro metabolism of new chemical entities., What the Reader Will Gain: Many improvements were achieved in terms of LC instrumentation, columns technology and analytes detection to attain ultra-fast and/or high-resolution chromatographic separations. These advances are particularly beneficial to face the complexity and high number of samples studied in the early phases of the discovery process. Advantages and drawbacks of each strategy are discussed., Take Home Message: LC and ultra high pressure liquid chromatography coupled with mass spectrometry detection constitute the most promising strategies to achieve high-throughput and/or high-resolution analyses in a drug discovery environment.

The coupling of ultra high-pressure liquid chromatography with a single quadrupole mass spectrometer was investigated for the analysis of several cytochromes P450 (CYP450) substrates and respective metabolites. The effect of numerous operating parameters (e.g. mobile phase pH, flow rate, gradient length, MS acquisition mode, dwell time, polarity switching, etc.) on selectivity, sensitivity and acquisition rate was studied. It was demonstrated that basic pH conditions provided the best compromise in terms of sensitivity and chromatographic selectivity with both acidic and basic compounds. The optimal mobile phase flow rate for UHPLC-MS experiments should be comprised between 300 and 600 microL/min for 2.1mm ID columns, while a higher flow rate generated up to 3-fold loss in sensitivity. It was also demonstrated that the fast polarity switching mode represented a valuable tool to improve throughput, maintaining acceptable performance. Finally, limits of detection were included in the range [1-50 ng/mL] in positive ionization mode and [50-250 ng/mL] in negative ionization mode, for investigated compounds.

A method to perform nanoscale automated CYP450-based drug metabolism studies using a capillary as a reaction vessel is described. In-capillary assays consumed only approximately 30 nL of recombinant human CYP450 solution. Ultrafast analysis of substrates and metabolites was achieved off-line by ultrahigh-pressure liquid chromatography coupled to mass spectrometry. This approach was successfully applied to qualitative metabolism studies of six major CYP450 isozymes and CYP2D6 inhibition experiments.

Variations in the vaginal environment that occur throughout the life span are described. The nature and cybernetics of factors involved in these variations are discussed.

Critical review of eating disorders in girls, based upon five cases:four of anorexia nervosa and one of boulimia, such problems neing accompanied from a gynecologic standpoint by amenorrhea. Interpretation of colpocytologic findings, differing between cases. Suggestion of the central nervous origin of these disorders.

Analytic study of the biochemical factors in the process of pareunia: hormonal factor of embryonic genital crests, responsible for a double sexualization, both genital and encephalic, which stands for the exteriorization of a perfectly determined later behavior; attractive or repulsive exoactones (pheromones) which play a major part in inter-individual attraction. Study of those many exoactones in both sexes; hormonomediation, leading to the intervention of the hypotalamo-adeno-hypophyso-(cortico)-gonadal axis, with such effectors as sexosteroids, the hypothalamo-adenohypophyseal with the prolactin, the neuro-hypopheseal level (vasopressin, ocytocyne), and the epiphyseal level (melatonin), the terminal effector agents appearing either as libido (androgens, P-Rih), or counter-libido (oestrogens, prolactin) with the involvement of two systems of vertical and horizontal libidinization; neuromediation, with the intervention of the catecholaminergic, cholinergic, indolaminergic (serotonin); neuromodulation, with a rise in the endorphin rate when there is an orgasm; very precise enzymatic phenomena (depolymerases appearing in the vaginal content when there is an orgasm), which cannot be ignored any longer.

During experimental female orgasm (or illation), the prominence of five stages which correspond to the orgastic raise. This raise leads to the apparition of very characteristic nodules, which are structured as they group desquamed vaginal cells together with transuded blood cells. Furthermore, the loss of pseudocrystallization of the ovulatory cervical phlegm is to be noted ("fern type crystallization"). An enzymatic explanation for these phenomena, which lead to the intervention of hyaluronidases, may be proposed.

Brief study of vaginal populations, the human vagina being considered as a biotopic cavity. Allusion to dynamic aspects ("vaginal climate", "landscapes") and to various bacterial populations. Introduction of the concept of xenoecies and of facies. This study is preceded by essential definitions of terms widely used in ecology.

The description of a case imported from Chad of an association of Salmonella typhi - Schistosoma haematobium and, in this connection, a new revised general account. The association Salmonella-Schistomas is wide-spread. It corresponds to a salmonello - schistosomo - micro - association by the fixation of precise bacteria in the case of a bacteriemia on the cutaneous surface of male schistosomes in clearly defined places. These Salmonella constitute a permanent antigenic solicitation and they are capable of mobilization and rejection (bacteriuria after passage through the blood-stream) whereas bacteriosis remains asymptomatic. In fact, on the practical level, a clear and absolute distinction must be made between:--the bacteriemia with the concomitant bacteriuria, which are largely physiological in nature, very frequent and originating from various germs, connected with the emunctory function of the kidneys and which can be observed in any subject.--the schistosomal bacteriuria which are specific entities and evidence of a veritable micro-association of a symbiotic nature between the Salmonella and the schistosome, a micro-association which the bacteriuria reveals unexpectedly whereas the clinical symptoms are absent, not clearly discernible or totally misleading.

The various methods and techniques applicable to microbiological gynaecology have been described in detail by the authors: Collected material. DIRECT EXAMINATION: how to prepare the sample, how to chose a directly usable vital stain. The use of non carbolic gentian violet and toluidine blue--a stain that yields a maximum of bacteriological, parasitological and cytologic information--in salin was more particularity recommended by the authors. FINAL PREPARATION: fixation and various stainings. CULTURES: description of the various usable media. CLINICAL AND EPIDEMIOLOGICAL SURVEY: clinical, biotypological, socialogical, psychological, sexological stages and transcription of data on coded cards for ultimate computer processing.