Molecular aspects of collagenolysis associated with stress urinary incontinence in women with urethral hypermobility vs intrinsic sphincter deficiency.

AIMS: We aimed to assess the alterations in specific molecular mechanisms associated with collagenolysis and their correlation in cases of stress urinary incontinence (SUI) by urethral hypermobility (UH) and by intrinsic sphincter deficiency (ISD). METHODS: We evaluated the messenger RNA (mRNA) expression of matrix metalloproteinases (MMP1, MMP2, and MMP9), specific tissue inhibitors of metalloproteinases (TIMPs), and associated proteins (TIMP1, TIMP2, and α-2-macroglobulin [A2McG]) in the suburethral tissue of women with SUI (half with SUI by UH and half with SUI by ISD) by reverse-transcriptase quantitative polymerase chain reaction and determined the correlations of the expression of these proteins on each pathological condition. RESULTS: In the suburethral tissue, we found significantly altered MMP2 mRNA levels, being higher in women with ISD than in those with UH. Still, MMP1 and MMP9 exhibited a tendency to a higher expression in women with ISD. Concerning the TIMPs expression, no significant statistical differences were found between women with UH and ISD. When evaluating the MMP/TIMP ratios, we found significant statistical differences between MMP9/TIMP1 and MMP9/A2McG. In fact, the correlations of the expression MMP9 with TIMP1 and A2McG were lost for women with UH. The ratios between MMP1/TIMP1 and MMP1/A2McG were similar, although there was a tendency of higher ratio in ISD for MMP2/TIMP2 and MMP2/A2McG. CONCLUSION: Our results point toward higher collagenolysis in the suburethral tissue of women with SUI by ISD.

Emerging Potential of Natural Products as an Alternative Strategy to Pharmacological Agents Used Against Metabolic Disorders.

BACKGROUND: Human metabolism is an essential biological process that involves the consumption of different substrates to ensure the nutritional and energetic needs of cells. The disruption of this highly regulated system constitutes the onset of several disorders/dysfunctions such as diabetes mellitus, cardiovascular diseases and hypertension. OBJECTIVE: In this review, we propose to discuss promising natural products that can act as modulators of cell metabolism and point towards possible targets to take into account in the development of new therapies against metabolic diseases. METHODS: After having defined our main focus, we undertook an intensive search of bibliographic databases to select the peer-reviewed papers that fits within the review thematic. The information of the screened papers was described in an organized manner through the review and different types of studies were included. RESULTS: Two hundred and seventy papers were included in the review, as well as one reliable website from the World Health Organization. Several articles described that pharmacological agents are commonly used to counteract metabolic disorders. However, in many cases these products are insufficient, represent high costs to health care systems and are associated with several undesirable effects, highlighting the need to search for new therapies. Notably, many papers reported the promising results of natural products in the treatment of several metabolic disorders, constituting a possible alternative or complementary strategy to pharmacological agents. CONCLUSION: The findings of this review confirm that the currently available treatments for metabolic disorders and its associated complications remain far below the expected results.

Antidiabetic Drugs: Mechanisms of Action and Potential Outcomes on Cellular Metabolism.

Diabetes mellitus (DM) is one of the most prevalent chronic diseases and has been a leading cause of death in the last decades. Thus, methods to detect, prevent or delay this disease and its co-morbidities have long been a matter of discussion. Nowadays, DM patients, particularly those suffering with type 2 DM, are advised to alter their diet and physical exercise regimens and then proceed progressively from monotherapy, dual therapy, and multi-agent therapy to insulin administration, as the disease becomes more severe. Although progresses have been made, the pursuit for the "perfect" antidiabetic drug still continues. The complexity of DM and its impact on whole body homeodynamics are two of the main reasons why there is not yet such a drug. Moreover, the molecular mechanisms by which DM can be controlled are still under an intense debate. As the associated risks, disadvantages, side effects and mechanisms of action vary from drug to drug, the choice of the most suitable therapy needs to be thoroughly investigated. Herein we propose to discuss the different classes of antidiabetic drugs available, their applications and mechanisms of action, particularly those of the newer and/or most widely prescribed classes. A special emphasis will be made on their effects on cellular metabolism, since these drugs affect those pathways in several cellular systems and organs, promoting metabolic alterations responsible for either deleterious or beneficial effects. This is a crucial property that needs to be carefully investigated when prescribing an antidiabetic.