Practice Points - Pharmacological therapy of female urinary incontinence

Background: Although not a life threatening condition, UI is a common problem in women that produces embarrassing and debilitating symptoms, severely affects the quality of life and represents a significant public health problem. The bladder and urethra in women constitute a functional unit that is controlled by a complex interplay between the central and peripheral cholinergic and noradrenergic nervous systems and local regulatory factors. A substantial part of urethral tone in women is also mediated through the effect of estrogen on urethral mucosal function. Theoretically, detrusor instability can be improved by agents that decrease detrusor contractility and genuine stress incontinence by agents that increase outlet resistance. Objectives: To review the use of various drugs in treatment of female urinary incontinence [UI] and present the current evidencebased recommendations. Methods: Systemmatic review of literature Results: The strength of evidence for the use of such agents, however, varies from data obtained from pharmacological and physiological experiments to those derived from clinical studies. Hence, the use of some of the currently prescribed drugs for treatment of female UI is founded more on tradition than on evidence based on results from controlled clinical trials. There is also an urgent medical need for a new smooth muscle agent for treating UI in women because current drug therapy of UI is either inadequate or ineffective. Therefore, further clinical experience with drugs that selectively modulate the electrophysiological properties and the intracellular pathways of the smooth muscles of the lower urinary tract in women as therapeutic agents for UI is awaited with interest

Genetics of pelvic organ prolapse: crossing the bridge between bench and bedside in urogynecologic research

An increasing number of scientists have studied the molecular and biochemical basis of pelvic organ prolapse (POP). the extracellular matrix content of the pelvic floor is the major focus of those investigations and pointed for potential molecular markers of the dysfunction. the identification of women predisposed to develop POP would help in the patients' management and care. This article includes a critical analysis of the literature up to now; discusses implications for future research and the role of the genetics in POP.Universidade Federal de São Paulo, Dept Gynecol, Div Urogynecol & Reconstruct Pelv Surg, BR-04038031 São Paulo, BrazilAin Shams Univ, Fac Med, Dept Obstet & Gynecol, Cairo, EgyptUniversidade Federal de São Paulo, Dept Gynecol, Div Urogynecol & Reconstruct Pelv Surg, BR-04038031 São Paulo, BrazilWeb of Scienc

DESIGN, SYNTHESIS AND BIOLOGICAL ESTIMATION OF INNOVATIVE PYRAZOLES AS ANTICANCER AGENTS TARGETING CDK2

CDK2, which exhibits an indispensable role as an organizer of cell growth, is the powerfully studied protein Kinases objective of anticancer suppressors. The present study was dedicated to design (pharmacophore, docking, and binding energy) and to prepare an inspired derivatives of pyrazole and pyrazolo[1,5-d]pyrimidine as promising anticancer agents, which can act by targeting CDK2. The promising compounds were selected according to their fit-value and binding energy scores. The anticancer activity against MCF-7 was tested for the prepared compounds and compounds 2, 3b, and 7b showed expressive activity with IC50 1.75, 0.89 and 1.32 µM respectively. The CDK2 evaluation was carried out to estimate the efficiency of the prepared compounds as promising inhibitors. The results revealed that compound 3b with effective inhibitory activity against tumor growth and with its potent inhibition against the CDK2 enzyme with percent inhibition 86 would be a prospective anticancer agent. The prepared compounds with high biological activity could be used as lead inhibitors for the CDK2 kinase domain

Mixed urinary incontinence : international urogynecological association research and development committee opinion

Background and aim The definition as well as the treatment of women with mixed urinary incontinence (MUI) is controversial. Since women with MUI are a heterogeneous group, the treatment of MUI requires an individual assessment of the symptom components: stress urinary incontinence, urinary urgency, urgency urinary incontinence, urinary frequency, and nocturia. The purpose of this paper is to summarize the current literature and give an evidence-based review of the assessment and treatment of MUI. Methods A working subcommittee from the International Urogynecological Association (IUGA) Research and Development (R&D) Committee was formed. An initial document addressing the diagnosis and management of MUI was drafted based on a literature review. After evaluation by the entire IUGA R&D Committee, revisions were made, and the final document represents the IUGA R&D Committee Opinion on MUI. Results This R&D Committee Opinion reviews the literature on MUI and summarizes the assessment and treatment with evidence-based recommendations. Conclusions The diagnosis of MUI encompasses a very heterogeneous group of women. The evaluation and treatment requires an individualized approach. The use of validated questionnaires is recommended to assess urinary incontinence symptoms and effect on quality of life. Conservative therapy is suggested as a first-line approach; if surgery is contemplated, urodynamic investigation is recommended. Women undergoing surgical treatment for MUI need to be counselled about the possibility of persistence of urinary urgency, frequency and urge incontinence even if stress urinary incontinence is cured

An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction

Next to existing terminology of the lower urinary tract, due to its increasing complexity, the terminology for pelvic floor dysfunction in women may be better updated by a female-specific approach and clinically based consensus report. This report combines the input of members of the Standardization and Terminology Committees of two International Organizations, the International Urogynecological Association (IUGA) and the International Continence Society (ICS), assisted at intervals by many external referees. Appropriate core clinical categories and a subclassification were developed to give an alphanumeric coding to each definition. An extensive process of 15 rounds of internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). A terminology report for female pelvic floor dysfunction, encompassing over 250 separate definitions, has been developed. It is clinically based with the six most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different specialty groups involved in female pelvic floor dysfunction. Female-specific imaging (ultrasound, radiology, and MRI) has been a major addition while appropriate figures have been included to supplement and help clarify the text. Ongoing review is not only anticipated but will be required to keep the document updated and as widely acceptable as possible. A consensus-based terminology report for female pelvic floor dysfunction has been produced aimed at being a significant aid to clinical practice and a stimulus for research