89 research outputs found

    Expression and function of G-protein-coupled receptorsin the male reproductive tract

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    This review focuses on the expression and function of muscarinic acetylcholine receptors (mAChRs), α1-adrenoceptors and relaxin receptors in the male reproductive tract. The localization and differential expression of mAChR and α1-adrenoceptor subtypes in specific compartments of the efferent ductules, epididymis, vas deferens, seminal vesicle and prostate of various species indicate a role for these receptors in the modulation of luminal fluid composition and smooth muscle contraction, including effects on male fertility. Furthermore, the activation of mAChRs induces transactivation of the epidermal growth factor receptor (EGFR) and the Sertoli cell proliferation. The relaxin receptors are present in the testis, RXFP1 in elongated spermatids and Sertoli cells from rat, and RXFP2 in Leydig and germ cells from rat and human, suggesting a role for these receptors in the spermatogenic process. The localization of both receptors in the apical portion of epithelial cells and smooth muscle layers of the vas deferens suggests an involvement of these receptors in the contraction and regulation of secretion.Esta revisĂŁo enfatiza a expressĂŁo e a função dos receptores muscarĂ­nicos, adrenoceptores α1 e receptores para relaxina no sistema reprodutor masculino. A expressĂŁo dos receptores muscarĂ­nicos e adrenoceptores α1 em compartimentos especĂ­ficos de dĂșctulos eferentes, epidĂ­dimo, ductos deferentes, vesĂ­cula seminal e prĂłstata de vĂĄrias espĂ©cies indica o envolvimento destes receptores na modulação da composição do fluido luminal e na contração do mĂșsculo liso, incluindo efeitos na fertilidade masculina. AlĂ©m disso, a ativação dos receptores muscarĂ­nicos leva Ă  transativação do receptor para o fator crescimento epidermal e proliferação das cĂ©lulas de Sertoli. Os receptores para relaxina estĂŁo presentes no testĂ­culo, RXFP1 nas espermĂĄtides alongadas e cĂ©lulas de Sertoli de rato e RXFP2 nas cĂ©lulas de Leydig e germinativas de ratos e humano, sugerindo o envolvimento destes receptores no processo espermatogĂȘnico. A localização de ambos os receptores na porção apical das cĂ©lulas epiteliais e no mĂșsculo liso dos ductos deferentes de rato sugere um papel na contração e na regulação da secreção.Fundação de Amparo Ă  Pesquisa do Estado de SĂŁo Paulo (FAPESP)Conselho Nacional de Desenvolvimento CientĂ­fico e TecnolĂłgico (CNPq)Universidade Federal de SĂŁo Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FarmacologiaUNIFESP, EPM, Depto. de FarmacologiaSciEL

    Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry

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    Contains fulltext : 167299.pdf (publisher's version ) (Closed access)Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 x 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 x 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 x 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P </= 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer

    Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry

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    Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≀ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer

    Laser spectroscopy for breath analysis : towards clinical implementation

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    Detection and analysis of volatile compounds in exhaled breath represents an attractive tool for monitoring the metabolic status of a patient and disease diagnosis, since it is non-invasive and fast. Numerous studies have already demonstrated the benefit of breath analysis in clinical settings/applications and encouraged multidisciplinary research to reveal new insights regarding the origins, pathways, and pathophysiological roles of breath components. Many breath analysis methods are currently available to help explore these directions, ranging from mass spectrometry to laser-based spectroscopy and sensor arrays. This review presents an update of the current status of optical methods, using near and mid-infrared sources, for clinical breath gas analysis over the last decade and describes recent technological developments and their applications. The review includes: tunable diode laser absorption spectroscopy, cavity ring-down spectroscopy, integrated cavity output spectroscopy, cavity-enhanced absorption spectroscopy, photoacoustic spectroscopy, quartz-enhanced photoacoustic spectroscopy, and optical frequency comb spectroscopy. A SWOT analysis (strengths, weaknesses, opportunities, and threats) is presented that describes the laser-based techniques within the clinical framework of breath research and their appealing features for clinical use.Peer reviewe

    Expression and function of G-protein-coupled receptorsin the male reproductive tract

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