A Steady-State Transfer Function Analysis of Portions of the Circulatory System Using Indicator Dilution Techniques

journal articleBiomedical Informatic

A Transfer Function Analysis of Coronary and Renal Circulation Calculated from Upstream and Downstream Indicator-Dilution Curves

journal articleBiomedical Informatic

PreImplantation factor (PIF) protects cultured embryos against oxidative stress: relevance for recurrent pregnancy loss (RPL) therapy

Recurrent pregnancy loss (RPL) affects 2-3% of couples. Despite a detailed work-up, the etiology is frequently undefined, leading to non-targeted therapy. Viable embryos and placentae express PreImplantation Factor (PIF). Maternal circulating PIF regulates systemic immunity and reduces circulating natural killer cells cytotoxicity in RPL patients. PIF promotes singly cultured embryos' development while anti-PIF antibody abrogates it. RPL serum induced embryo toxicity is negated by PIF. We report that PIF rescues delayed embryo development caused by 2 fold the number of embryos reaching the blastocyst stage. Mechanistically, PDI-inhibitor preferentially binds covalently to oxidized PDI over its reduced form where PIF avidly binds. PIF by targeting PDI/TRX at a distinct site limits the inhibitor's pro-oxidative effects. The >3kDa RPL serum increased embryo demise by three-fold, an effect negated by PIF. However, embryo toxicity was not associated with the presence of putative anti-PIF antibodies. Collectively, PIF protects cultured embryos both against ROS, and higher molecular weight toxins. Using PIF for optimizing in vitro fertilization embryos development and reducing RPL is warranted

PreImplantation Factor (PIF) correlates with early mammalian embryo development-bovine and murine models

<p>Abstract</p> <p>Background</p> <p>PreImplantation Factor (PIF), a novel peptide secreted by viable embryos is essential for pregnancy: PIF modulates local immunity, promotes decidual pro-adhesion molecules and enhances trophoblast invasion. To determine the role of PIF in post-fertilization embryo development, we measured the peptide's concentration in the culture medium and tested endogenous PIF's potential trophic effects and direct interaction with the embryo.</p> <p>Methods</p> <p>Determine PIF levels in culture medium of multiple mouse and single bovine embryos cultured up to the blastocyst stage using PIF-ELISA. Examine the inhibitory effects of anti-PIF-monoclonal antibody (mAb) added to medium on cultured mouse embryos development. Test FITC-PIF uptake by cultured bovine blastocysts using fluorescent microscopy.</p> <p>Results</p> <p>PIF levels in mouse embryo culture medium significantly increased from the morula to the blastocyst stage (ANOVA, P = 0.01). In contrast, atretic embryos medium was similar to the medium only control. Detectable - though low - PIF levels were secreted already by 2-cell stage mouse embryos. In single bovine IVF-derived embryos, PIF levels in medium at day 3 of culture were higher than non-cleaving embryos (control) (P = 0.01) and at day 7 were higher than day 3 (P = 0.03). In non-cleaving embryos culture medium was similar to medium alone (control). Anti-PIF-mAb added to mouse embryo cultures lowered blastocyst formation rate 3-fold in a dose-dependent manner (2-way contingency table, multiple groups, X2; P = 0.01) as compared with non-specific mouse mAb, and medium alone, control. FITC-PIF was taken-up by cultured bovine blastocysts, but not by scrambled FITC-PIF (control).</p> <p>Conclusions</p> <p>PIF is an early embryo viability marker that has a direct supportive role on embryo development in culture. PIF-ELISA use to assess IVF embryo quality prior to transfer is warranted. Overall, our data supports PIF's endogenous self sustaining role in embryo development and the utility of PIF- ELISA to detect viable embryos in a non-invasive manner.</p

Premature ovarian failure and ovarian autoimmunity

Premature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a heterogeneous disorder with a multicausal pathogenesis involving chromosomal, genetic, enzymatic, infectious, and iatrogenic causes. There remains, however, a group of POF patients without a known etiology, the so-called "idiopathic" form. An autoimmune etiology is hypothesized for the POF cases with a concomitant Addison's disease and/or oophoritis. It is concluded in this review that POF in association with adrenal autoimmunity and/or Addison's disease (2-10% of the idiopathic POF patients) is indeed an autoimmune disease. The following evidence warrants this view: 1) The presence of autoantibodies to steroid-producing cells in these patients; 2) The characterization of shared autoantigens between adrenal and ovarian steroid-producing cells; 3) The histological picture of the ovaries of such cases (lymphoplasmacellular infiltrate around steroid-producing cells); 4) The existence of various autoimmune animal models for this syndrome, which underlines the autoimmune nature of the disease. There is some circumstantial evidence for an autoimmune pathogenesis in idiopathic POF patients in the absence of adrenal autoimmunity or Addison's disease. Arguments in support of this are: 1) The presence of cellular immune abnormalities in this POF patient group reminiscent of endocrine autoimmune diseases such as IDDM, Graves' disease, and Addison's disease; 2) The more than normal association with IDDM and myasthenia gravis. Data on the presence of various ovarian autoantibodies and anti-receptor antibodies in these patients are, however, inconclusive and need further evaluation. A strong argument against an autoimmune pathogenesis of POF in these patients is the nearly absent histological confirmation (the presence of an oophoritis) in these cases (< 3%). However, in animal models using ZP immunization, similar follicular depletion and fibrosis (as in the POF women) can be detected. Accepting the concept that POF is a heterogenous disorder in which some of the idiopathic forms are based on an abnormal self-recognition by th

Minilaparotomically Assisted Vaginal Hysterectomy

Endoscopic hysterectomy is increasingly selected as a current trend to minimize invasion, tissue trauma and early recovery. However it has disadvantages of the difficulty to learn and needs expensive equipments. So we developed a new minimally invasive method of vaginal hysterectomy-minilaparotomically assisted vaginal hysterectomy (MAVH) in order to complement the current laparoscopic surgery. The principle of MAVH is based on suprapubic minilaparotomical incision and uterine elevator that allows access and maximal exposure of the pelvic anatomy and an easy approach to the surrounding anatomy enabling division of round ligaments, Fallopian tubes, tuboovarian ligaments, and dissection of bladder peritoneum. After then, the vaginal phase of MAVH is done by the traditional vaginal hysterectomy. We enrolled 75 consecutive cases and in 73 cases thereof MAVH was accomplished successfully. The technique of MAVH is simple and easy to learn and it involves a small incision causing less pain and complications. This practice does not require expensive equipments. MAVH is considered as a safe and effective alternative method for abdominal hysterectomy in most cases

Assessment of endometrial and ovarian characteristics using three dimensional power Doppler ultrasound to predict response in frozen embryo transfer cycles

<p>Abstract</p> <p>Objective</p> <p>To evaluate whether endometrial or ovarian parameters as measured using 3D power Doppler ultrasound would predict the outcome in frozen embryo transfer (FET) cycles.</p> <p>Methods</p> <p>Thirty women with no known gynecological pathology undergoing FET were recruited. The FET was carried out in the natural menstrual cycle 3-4 days after the first positive LH test result. Blood samples for hormonal analysis were collected, and three-dimensional (3D) ultrasonographic examination was performed on the day of the FET and repeated with analysis of the total hCG one week later.</p> <p>Results</p> <p>The demographic, clinical, and embryological characteristics were similar between the pregnant (15/30) and nonpregnant groups (15/30). There were no differences between the groups in endometrial/subendometrial thickness, volume, or vascularization index (VI). The endometrial triple-line pattern was more often present in the pregnant group on the day of the FET (93.3% vs. 40.0%, 95% CI 25.5-81.2%). No differences in the ovaries were observed on the day of the FET. At the second visit, the triple-line pattern was still more often present in those patients who had conceived (91.7% vs. 42.9%, 95% CI 18.5-79.1%), and their corpus luteum was more active as judged by the rise in 17-hydroxyprogesterone and estradiol levels. No differences were observed in the dominant ovarian vasculature.</p> <p>Conclusions</p> <p>According to our results, measurement of power Doppler indices using 3D ultrasound on the day of the FET does not provide any additional information concerning the outcome of the cycle. The existence of the triple-line pattern on the day of the FET seems to be a prognostic sign of a prosperous outcome after FET. The dominant ovary in the pregnant group seems to be already activated one week after the FET.</p