6 research outputs found
Study of the effect of corticotropin releasing hormone (CRH) on the pro/anti-oxidant balance of endothelial cells in the presence of steroid gonadal hormones
No full textAtherosclerosis, a progressive arterial disorder, is characterized by chronic subclinical inflammation of the endothelium. Endothelial tissue integrity is particularly important for transmission of impulses in the arterial wall, regulation of vascular tone, blood pressure, etc, and its disruption has been implicated in the progression of atherosclerosis. Steroid hormones are implicated in the regulation of developmental mechanisms of atherosclerosis. Epidemiological studies indicate that estrogens have a protective effect on the endothelium, as evidenced by lower incidences of atherosclerosis in premenopausal women in comparison to their postmenopausal counterparts. However, the role of androgens in the regulation of the endothelium is not fully elucidated. It is thought that androgens may induce atherosclerosis. However, the current knowledge on how estrogens and androgens participate in the pathophysiology of chronic endothelial inflammation is limited. An important regulator of inflammation is Corticotropin releasing hormone (CRH), a well known stress neuropeptide. In general, CRH participates in inflammation by inducing the secretion of pro-inflammatory cytokines and production of cortizole. According to the literature, CRH is expressed locally in peripheral tissues and regulates cell function through its paracrine and autocrine effects. Our recent studies show that CRH is expressed on the endothelium and exerts a pro-oxidative effect, inducing its adaptation to local stress by modifying pro- and anti- oxidative mechanisms, that constitute important factors of inflammation. Given the limited data about the effect of estrogens and androgens on the homeostasis of cellular oxidative burden of the endothelium and that their effect on locally produced CRH effect is unknown, we designed this study in order to investigate the effect of steroid gonadals on: a) pro- and anti-oxidative mechanisms of macroendothelial cell line EAhy926, in normal conditions and b) the modification of the pro-oxidative role of CRH on the endothelium. The endothelial cell line EAhy926 was incubated for 2h with 17β-estradiol (E2), testosterone and dihydrotestosterone (DHT), alone or in combination with CRH. Our experimental protocol involved the assessment of intracellular reactive oxygen species (ROS) content, activities of endothelial synthase of NO (eNOS), catalase and superoxide dismutase (SOD), as well as the production of nitric oxide (NO), glutathione (GSH) and the Ratio GSH/GSH+GSSG of the macroendothelial cells. In order to evaluate the hormone’s mechanisms of action we used selective inhibitors of the estrogens and androgens receptors. Our findings indicate that E2, acting via ERα and ERβ, exerts a systemic anti-oxidative effect on the vascular endothelium, through regulation of pro- and anti-oxidative mechanisms, while it counterbalances the inhibitory effect of CRH on eNOS activity and NO production, resulting in decreased intracellular oxidative stress. On the contrary, androgens, through androgen receptor (AR), have a pro-oxidative effect, whereby they increase eNOS and SOD activities, as well as NO production, thereby inducing oxidative stress. Moreover, they abolish, similarly to estrogen, the inhibitory effect of CRH on eNOS activity, NO production, and its stimulatory effect on catalase activity enhancing the already increased oxidative stress. The above effects highlight the important role of steroid gonadals in the regulation of redox homeostasis of endothelial cells through modifications on pro- and anti-oxidative mechanisms.Η αθηροσκλήρωση συνιστά μία εξελισσόμενη αρτηριακή διαταραχή που χαρακτηρίζεται από χρόνια υποκλινική φλεγμονή του ενδοθηλίου. Η ενδοθηλιακή ακεραιότητα είναι ιδιαιτέρως σημαντική για τη μεταβίβαση των απαραίτητων ερεθισμάτων στο αρτηριακό τοίχωμα, τη ρύθμιση του αγγειακού τόνου, την πίεση του αίματος, κλπ, και η διαταραχή αυτής της ακεραιότητας έχει συσχετισθεί με την ανάπτυξη της αθηροσκλήρωσης. Τα στεροειδή των γονάδων επηρεάζουν τους μηχανισμούς ανάπτυξης της αθηροσκλήρωσης. Επιδημιολογικές μελέτες υποδηλώνουν ότι τα οιστρογόνα ασκούν προστατευτική δράση στο ενδοθήλιο αφού, σε σύγκριση με προεμμηνοπαυσιακές γυναίκες, η συχνότητα της αθηροσκλήρωσης αυξάνει μετά την εμμηνόπαυση. Ο ρόλος των ανδρογόνων στη λειτουργία του ενδοθηλίου δεν είναι πλήρως κατανοητός. Υπάρχει διάχυτη αλλά μη τεκμηριωμένη αντίληψη ότι τα ανδρογόνα προάγουν την αθηροσκλήρωση. Ωστόσο, οι γνώσεις μας για τη συμμετοχή ανδρογόνων και οιστρογόνων στην παθοφυσιολογία της χρόνιας φλεγμονής του ενδοθηλίου είναι περιορισμένες. Σημαντικός ρυθμιστικός παράγοντας του φαινομένου της φλεγμονής είναι η εκλυτική ορμόνη της κορτικοτροπίνης (CRH), γνωστό νευροπεπτίδιο του στρες. Συμμετέχει γενικά στη διαδικασία της φλεγμονής επάγοντας την έκκριση προ-φλεγμονωδών κυτοκινών και την παραγωγή της κορτιζόλης. Βιβλιογραφικά δεδομένα δείχνουν ότι η CRH εκφράζεται τοπικά σε περιφερικούς ιστούς και ασκεί ρυθμιστικό ρόλο στη λειτουργία των κυττάρων μέσω παρακρινικής και αυτοκρινικής δράσης. Πρόσφατες παρατηρήσεις μας έδειξαν ότι η CRH εκφράζεται στο ενδοθήλιο και ασκεί προ-οξειδωτική δράση, επάγοντας την προσαρμογή του στο τοπικό στρες μέσω της τροποποίησης των προ- και αντι-οξειδωτικών μηχανισμών, οι οποίοι αποτελούν σημαντικό στοιχείο της φλεγμονώδους διαδικασίας. Επειδή δεδομένα για την επίδραση οιστρογόνων και ανδρογόνων στην ομοιόσταση του κυτταρικού οξειδωτικού φορτίου στο ενδοθήλιο είναι περιορισμένα, και η επίδρασή τους στη δράση της τοπικά παραγόμενης CRH άγνωστη, σχεδιάσαμε την παρούσα μελέτη με στόχο τη διερεύνηση της επίδρασης των στεροειδών των γονάδων: α) στους προ- και αντι-οξειδωτικούς μηχανισμούς μακροενδοθηλιακών κυττάρων, της σειράς EAhy926, σε βασικές συνθήκες και β) στη μεταβολή του προ-οξειδωτικού ρόλου της CRH στο ενδοθήλιο. Στα μακροενδοθηλιακά κύτταρα τα οποία επωάσθηκαν για 2 ώρες παρουσία 17β-οιστραδιόλης (Ε2), Τεστοστερόνης και Διυδροτεστοστερόνης (DHT), μόνων ή σε συνδυασμό με CRH, μετρήθηκαν: α) η συγκέντρωση των ελευθέρων ριζών οξυγόνου (ROS), β) η ενεργότητα της ενδοθηλιακής συνθετάσης του ΝΟ (eNOS), της καταλάσης και της δισμουτάσης του υπεροξειδίου (SOD), γ) η συγκέντρωση του μονοξειδίου του αζώτου (ΝΟ) και της γλουταθειόνης (GSH) και υπολογίστηκε ο λόγος GSH/GSH+GSSG. Για την εκτίμηση του μηχανισμού δράσης των ορμονών χρησιμοποιήθηκαν εκλεκτικοί ανταγωνιστές των οιστρογονικών και ανδρογονικών υποδοχέων αντίστοιχα. Τα αποτελέσματά μας έδειξαν ότι η Ε2, δρώντας μέσω των υποδοχέων ERα και ERβ, ασκεί συστηματική αντιοξειδωτική δράση στο αγγειακό ενδοθήλιο, μέσω επίδρασης στο σύνολο των προ- και αντι-οξειδωτικών μηχανισμών, ενώ εξουδετερώνει την ανασταλτική επίδραση της CRH στη δραστικότητα της eNOS και την παραγωγή του ΝΟ οδηγώντας σε ελάττωση του κυτταρικού οξειδωτικού φορτίου. Σε αντίθεση με τα οιστρογόνα, τα ανδρογόνα, δρώντας μέσω του ανδρογονικού υποδοχέα (AR), ασκούν προ-οξειδωτική δράση μέσω της αύξησης της δραστικότητας της eNOS, της παραγωγής ΝΟ, της δραστικότητας της SOD, και μείωση της δραστικότητας της καταλάσης, αυξάνοντας το ενδοκυτταρικό οξειδωτικό φορτίο. Παράλληλα, εξουδετερώνουν, όπως και τα οιστρογόνα, την ανασταλτική επίδραση της CRH στη δραστικότητα της eNOS και την παραγωγή του ΝΟ και επιπρόσθετα τη διεγερτική της επίδραση στη δραστικότητα της καταλάσης ενισχύοντας το ήδη αυξημένο ενδοκυτταρικό οξειδωτικό φορτίο. Οι ως άνω επιδράσεις τεκμηριώνουν τη σημαντική επίδραση των στεροειδών του φύλου στη ρύθμιση της οξειδοαναγωγικής ισορροπίας των ενδοθηλιακών κυττάρων μέσω της τροποποίησης των προ- και αντι-οξειδωτικών μηχανισμών
The effect of extended release tolterodine used for overactive bladder treatment on female sexual function
No full textABSTRACT Introduction Overactive bladder (OAB) is a common condition, especially in middle aged women, requiring long term therapy with anticholinergics to maintain symptoms relief. The aim of the study was to determine the effect of tolterodine extended release (ER) used for OAB treatment on the sexual function of women. Materials and Methods Between August 2010 and August 2014, 220 women with confirmed OAB, attended Urogynecology Outpatient Clinic and were prospectively enrolled in this study. 158 women were evaluated, with a comprehensive history, physical examination, urodynamic studies and Female Sexual Function Index (FSFI) questionnaire. 73 patients of group A (control group) received no treatment and 85 patients of group B received an anticholinergic regimen – tolterodine ER 4mg once daily. Data were evaluated again in accordance with FSFI after three months, using SPSS software. Results A statistically significant increase was noted in group B in domains of desire (pre-treatment 2.5±0.2 to 4.5±0.2 post-treatment), arousal (3.1±0.2 to 3.1±0.2 respectively), lubrication (3.4±0.3 to 4.3±0.3 respectively), orgasm (3.5±0.3 to 4.5±0.3 respectively), satisfaction (2.6±0.2 to 4.2±0.3 respectively) and pain (2.4±0.2 to 4.6±0.4 respectively) after three months treatment with tolterodine ER. In group A there were no statistically significant changes in pre and post treatment values (p>0.05). Total FSFI score for group B was significantly higher after tolterodine treatment (26.5±1.5) compared to pre-treatment values (17.4±1.4, p0,05) respectively. Conclusions This preliminary study demonstrates that treatment of OAB with tolterodine ER was found to have positive effect on sexual function of patients with OAB
The effect of extended release tolterodine used for overactive bladder treatment on female sexual function
No full textAssessment of anthropometric and metabolic parameters of patientes in outpatient follow up diagnosed with glomerular proteinuria
No full textOrientador: Maria Almerinda Vieira Fernandes Ribeiro AlvesDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução: A síndrome nefrótica é uma condição clínico-laboratorial caracterizada por proteinúria maciça, hipoalbuminemia, hiperlipidemia e edema. O edema é uma manifestação clínica comum e dificulta a avaliação e monitoramento do estado nutricional. A maioria das técnicas de aferição, utilizadas rotineiramente para avaliar o estado nutricional, tem limitações na sua aplicação. Objetivo: O objetivo desse estudo foi monitorar a avaliação corporal em pacientes com diagnóstico de proteinúria glomerular em acompanhamento ambulatorial, comparando os resultados obtidos por meio de parâmetros antropométricos e correlacionando-os com o estado clínico e dados laboratoriais. Métodos: Foram incluídos, entre 2008 e 2011, 47 pacientes adultos (>18 anos), em acompanhamento ambulatorial com proteinúria e doença glomerular comprovada por biópsia renal. Os pacientes foram avaliados no início do acompanhamento (T0) e após 6 meses (T6 n=25) de acompanhamento. Para avaliar os efeitos do nível de albumina sérica nos parâmetros avaliados o grupo foi dividido em pacientes normoalbuminêmicos (n=14) e hipoalbuminêmicos (n=11) de acordo com a presença de albuminemia18 years), in outpatient follow-up with proteinuria and renal biopsy-proven glomerular disease. Patients were evaluated in the first assesment (T0) and after 6 months (T6 n=25) for the monitoring. To assess the effects of serum albumin on the evaluated parameters, the group was divided into normoalbuminemic and hypoalbuminemic patients in accordance with the presence of albumin <3,0g/dL. All patients underwent anthropometric evaluated and body composition calculation (% body fat, MAC= mid-arm circumference, MAMC= mid-arm muscle circumference and MAMA = mid-arm muscle area), Watson Formula (estimate total body water), Body Shape Index (ABSI - The body shape index) and biochemical examinations during follow-up. Renal function was estimated by the Cockroft-Gault equation corrected by the body surface simplified MDRD and CKD-Epi. Results: The patients who started up with hypoalbuminemia after 6 months evolved into a normoalbuminemia situation (p<0.05). Most patients showed no difference in the total estimated volume of water, even among patients with hypoalbuminemia that evolved with normal albumin. In relation to body evaluation, there was no change in BMI during the study. Patients in the group hipoalbuminemic, regardless of gender were classified as overweight both at baseline and after 6 months of follow-up. In normoalbuminemic group, patients were classified as obese. We can see that there is a cardiovascular risk in both group when they were valued at ABSI (p<0.05). As expected, the percentage of body fat was higher in females than males. No changes were observed during the follow up period. The estimated GFR held by CG, MDRD and CKD-Epi remained unchanged during the follow up period (T0 x T6). As expected compared to MDRD and CKD-Epi also a significant increase in the glomerular filtration rate estimated by the Cockroft Gault. There was no change in the parameters evaluated in relation to food intake. Conclusion: Our data showed that the anthropometric assessment by skinfold used in conjunction with other simple measures of body assessment as a cardiovascular risk (ABSI) in proteinuric patients, even in nephrotic levels, with little or no edema in attendance in use diuretics, hypotensive and diet, was satisfactoryMestradoClinica MedicaMestra em Clínica Médic
17‐β estradiol attenuates the pro‐oxidant activity of corticotropin‐releasing hormone in macroendothelial cells
No full textBridging Andrology and Oncology: Prognostic Indicators of Cancer Among Infertile Men
No full textApproximately 7% of males globally suffer from male infertility, which is becoming more widely acknowledged as a clinical indicator of potential health hazards as well as a cause of reproductive failure. Among these, cancer has become a significant worry due to mounting evidence that spermatogenesis impairment is associated with increased risk of prostate, testicular, and other cancers. Male infertility may be an early clinical manifestation of systemic genomic instability due to shared biological pathways, such as Y-chromosome microdeletions (AZF regions), germline DNA repair defects, mutations in tumor suppressor genes (e.g., BRCA1/2, TP53), mismatch repair gene mutations (e.g., MLH1, MSH2), and dysregulated epigenetic profiles. This narrative review covers the most recent research on prognostic markers of cancer in infertile men. These include molecular biomarkers such as genetic, epigenetic, and proteomic signatures; endocrine and hormonal profiles; and clinical predictors such as azoospermia, severe oligozoospermia, and a history of cryptorchidism. The possibility of incorporating these indicators into risk stratification models for precision medicine and early cancer surveillance is highlighted. For this high-risk group, bridging the domains of andrology and oncology may allow for better counseling, earlier detection, and focused therapies
