Novel drug delivery methods for improving efficacy of endometriosis treatments.

Abstract: Erratum to “Subject and clinician experience with the levonorgestrel-releasing intrauterine system” [Contraception 77(2008) 22–29]B Jeffrey T. Jensen⁎, Anita L. Nelson, Antonio C. Costales Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239, USA Department of Public Health and Preventive Medicine, Oregon Health and Science University, Portland, OR 97239, USA Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA 90502, USA Medical Affairs, Women’s HealthCare, Bayer HealthCare Pharmaceuticals, Inc., Wayne, NJ 07470, USA

Abstract: Pharmacotherapy has a key role in endometriosis treatment and management, however, a significant proportion of patients have only intermittent or limited benefits with current treatment options. Th...

Abstract: Endometriosis is common in reproductive-age women and its pathology is to increase proliferation and migration to enhance epithelial-to-mesenchymal transition progression (EMT). However, treatments are currently limited, so it is important to explore new therapeutic drugs. Hence, in this study, we investigate the therapeutic effect of fucoidan (FC) on the progression and mechanisms of endometriosis. The cell viability of endometrial cell lines End1/E6E7 and Vk2/E6E7 treated with different concentrations of FC were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell counting. Cell migration was evaluated using wound-healing assay. In an in vivo experiment, female Balb/c mice received surgically induced endometriosis followed by different concentrations of fucoidan for 6 weeks. High-frequency ultrasound imaging was applied to detect subsequent lesion growth. The results demonstrated that fucoidan inhibited the viability and migration ability of End1/E6E7 and Vk2/E6E7 cells. Additionally, the administration of fucoidan reduced the volume and weight of endometriotic lesions, decreased inflammatory cytokines and vascular endothelial growth factor (VEGF) of serum and lesions, and improved EMT proliferation and apoptosis-related protein expression. For the first time, fucoidan indicated anti-proliferative and anti-inflammatory effects as well as inhibited EMT progression and induced apoptosis, improving endometriosis.

Abstract: Reproductive efficiency of farm animals has central consequences on productivity and profitability of livestock farming systems. Optimal reproductive management is based on applying different strategies, including biological, hormonal, nutritional strategies, as well as reproductive disease control. These strategies should not only guarantee sufficient reproductive outcomes but should also comply with practical and ethical aspects. For example, the efficiency of the biological- and hormonal-based reproductive strategies is mainly related to several biological factors and physiological status of animals, and of nutritional strategies, additional factors, such as digestion and absorption, can contribute. In addition, the management of reproductive-related diseases is challenged by the concerns regarding the intensive use of antibiotics and the development of antimicrobial resistant strains. The emergence of nanotechnology applications in livestock farming systems may present innovative and new solutions for overcoming reproductive management challenges. Many drugs (hormones and antibiotics), biological molecules, and nutrients can acquire novel physicochemical properties using nanotechnology; the main ones are improved bioavailability, higher cellular uptake, controlled sustained release, and lower toxicity compared with ordinary forms. In this review, we illustrate advances in the most common reproductive management strategies by applying nanotechnology, considering the current challenges of each strategy.

Abstract: In past two decades poly lactic-co-glycolic acid (PLGA) has been among the most attractive polymeric candidates used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. In particular, PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. This manuscript describes the various fabrication techniques for these devices and the factors affecting their degradation and drug release.

Abstract: studydesign,size,duration: This guideline was produced by a group of experts in the field using the methodology of the Manual for ESHRE Guideline Development, including a thorough systematic search of the literature, quality assessment of the included papers up to January 2012 and consensus within the guideline group on all recommendations. To ensure input from women with endometriosis, a patient representative was part of the guideline development group. In addition, patient and additional clinical input was collected during the scoping and review phase of the guideline.

Abstract: A healthy 25-year-old woman presents with worsening dysmenorrhea, pain of recent onset in the left lower quadrant, and dyspareunia She has regular menstrual cycles, and her last menstrual period was 3 weeks before presentation How should this patient be evaluated and treated?

Abstract: Regulatory T (Treg) cells are a developmentally and functionally distinct T cell subpopulation that is engaged in sustaining immunological self-tolerance and homeostasis. The transcription factor Foxp3 plays a key role in Treg cell development and function. However, expression of Foxp3 alone is not sufficient for conferring and maintaining Treg cell function and phenotype. Complementing the insufficiency, Treg-cell-specific epigenetic changes are also critical in the process of Treg cell specification, in regulating its potential plasticity, and hence in establishing a stable lineage. Understanding how epigenetic alterations and Foxp3 expression coordinately control Treg-cell-specific gene regulation will enable better control of immune responses by targeting the generation and maintenance of Treg cells.

Abstract: Naturally occurring CD4 + regulatory T cells (T R ) that express CD25 and the transcription factor FoxP3 play a key role in immune homeostasis, preventing immune pathological responses to self and foreign Ags. CTLA-4 is expressed by a high percentage of these cells, and is often considered as a marker for T R in experimental and clinical analysis. However, it has not yet been proven that CTLA-4 has a direct role in T R function. In this study, using a T cell-mediated colitis model, we demonstrate that anti-CTLA-4 mAb treatment inhibits T R function in vivo via direct effects on CTLA-4-expressing T R , and not via hyperactivation of colitogenic effector T cells. Although anti-CTLA-4 mAb treatment completely inhibits T R function, it does not reduce T R numbers or their homing to the GALT, suggesting the Ab mediates its function by blockade of a signal required for T R activity. In contrast to the striking effect of the Ab, CTLA-4-deficient mice can produce functional T R , suggesting that under some circumstances other immune regulatory mechanisms, including the production of IL-10, are able to compensate for the loss of the CTLA-4-mediated pathway. This study provides direct evidence that CTLA-4 has a specific, nonredundant role in the function of normal T R . This role has to be taken into account when targeting CTLA-4 for therapeutic purposes, as such a strategy will not only boost effector T cell responses, but might also break T R -mediated self-tolerance.