bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibin, Activin, and Follistatin in Human Fetal Pituitary and Gonadal Physiology
Authors: BLUMENFELD ZEEV , RITTER MARINA 
Published: July 2010

AbstractBackground: Activin has been previously demonstrated to directly stimulate the synthesis of gonadotropin‐releasing hormone (GnRH) receptors and to increase follicle‐stimulating hormone (FSH) secretion in nonhuman pituitary cell cultures (PCCs). Currently, knowledge of the physiological role of these peptides in primates is still far from complete. Moreover, several results in macaque monkeys failed to support an unequivocal role for inhibin in FSH suppression. Whereas the bioactivity of inhibin and activin has been demonstrated in rat PCCs, no data exist on human pituitary response to these peptides either in vivo or in vitro. Methods: We studied the secretion of FSH and luteinizing hormone (LH) by dispersed human fetal pituitary cells from midtrimester abortions in response to recombinant human (rh‐) activin‐A, inhibin‐A, and other secretagogues. After mechanical and enzymatic dispersion, the human fetal pituitary cells were cultured on an extracellular matrixlikematerial‐coated 24‐well plate. After 3 days' incubation in serum‐containing medium, the PCCs were washed and preincubated for 90 min in serum‐free medium and incubated with activin‐A, inhibin‐A, TGF‐β, follistatin, sex steroids, and GnRH, in quadruplicate. Results: Activin‐A was a potent secretagogue for FSH secretion. GnRH (20 ng/ml) was more potent than rh‐activin‐A for LH secretion. Nevertheless, a significant increase in LH secretion into the medium was brought about by rh‐activin‐A. Inhibin decreased FSH and LH secretion, but the LH response to inhibin was less prominent than that of FSH. GnRH opposed the inhibitory effect of inhibin on LH secretion. In dynamic, short‐term, repetitive exposure of fetal pituitary fragments to rh‐activin‐A (superfusion), we could not receive a similar increase in LH and FSH as in static incubations, as opposed to a short GnRH exposure. In addition to their endocrine, paracrine, and autocrine effects, and in addition to their role as possible markers, the TGF‐β superfamily members may affect embryogenesis and possibly immunomodulation of the embryo and fetus. The role of activin and inhibin as intragonadal regulators is hypothesized. The pro‐αC inhibin precursor may act as an FSH receptor antagonist. Conclusions: Human fetal PCCs express the previously reported physiologic responses to activin and inhibin generated in nonhuman experiments on gonadotropin secretion in vitro and may serve as a physiologic model for studying human gonadotrope responses to the TGF‐β family of peptides.
Design and Conduct of Clinical Trials in Hormone Replacement Therapy
Authors: HOLINKA CHRISTIAN F. 
Published: July 2010

AbstractPostmenopausal hormone replacement therapy represents an area of outstanding importance in preventive medicine that greatly affects personal well‐being as well as public health. The number of women living in the United States who are 50 years or older has been estimated at nearly 50 million.1 Many of those women are likely to be eligible for postmenopausal hormone replacement, which may consist either of estrogen replacement therapy (ERT) in women without a uterus or, more frequently, estrogen/progestin combination therapy (HRT) in women with a uterus. This chapter first presents an overview of general regulatory requirements pertaining to the design and conduct of clinical studies in support of marketing approval for a drug product. These requirements include, but are not restricted to, studies in HRT. The chapter next discusses the design and conduct of clinical trials in support of marketing approval for the indications: treatment of moderate to severe vasomotor symptoms and vulvovaginal atrophy; prevention of osteoporosis; and protection by adjunctive progestin against estrogen‐induced endometrial hyperplasia/cancer in women with a uterus. Finally, data related to the potential cardioprotective action of HRT and its protection against Alzheimer's disease and colon cancer are discussed.
Endometrial Anomalies in Women with Endometriosis
Authors: SHARPE‐TIMMS KATHY L. 
Published: July 2010

AbstractEndometriotic lesions are defined by extrauterine growth of endometrial glands and stroma. Retrograde menstruation with subsequent attachment, invasion, and neovascularization are believed to give rise to the endometriotic lesions. As most women exhibit some degree of retrograde menstruation, some other unidentified factor(s) must render certain women susceptible to attachment and growth of ectopic endometrial tissue. A variety of theories have been proposed to account for this susceptibility, including genetic predisposition, aberrant immunological response, and an altered peritoneal environment. Ectopic endometriotic lesions are histologically similar to their putative eutopic precursors, yet significant biochemical differences exist between these two tissues. Less information is available regarding differences between eutopic endometrium from women with or without endometriosis. This report describes anomalies in structure, proliferation, immune components, adhesion molecules, proteolytic enzymes and inhibitors, steroid and cytokine production and responsiveness, and gene expression and protein production that have been identified in eutopic endometrium from women with endometriosis.
Biochemistry and Molecular Biology of Trophoblast Invasion
Authors: BISCHOF P. , MEISSER A. , CAMPANA A. 
Published: July 2010

AbstractCytotrophoblastic cells (CTBs) from first‐trimester placenta form columns of invasive CTBs. This invasive behavior is due to the ability of CTBs to secrete matrix metalloproteinases (MMPs), since tissue inhibitor of MMPs (TIMP) inhibits their invasiveness in the extracellular space. Although CTBs behave like metastic cells, in vivo they are only transiently invasive (first trimester), and their invasion is normally limited only to the endometrium and to the proximal third of the myometrium. This temporal and spatial regulation of trophoblast invasion is believed to be mediated in an autocrine way by trophoblastic factors and in a paracrine way by uterine factors. Several types of regulators have been investigated: hormones, extracellular matrix glycoproteins, and cytokines or growth factors. This review is not intended to be an exhaustive catalogue of potential regulators of trophoblast invasion but is aimed at summarizing the most important categories of factors affecting trophoblast‐endometrium interactions.
Uterine Contractility: Vaginal Administration of the β‐Adrenergic Agonist, Terbutaline
Authors: BULLETTI CARLO , DE ZIEGLER DOMINIQUE , DE MOUSTIER BEATRICE , POLLI VALERIA , BOLELLI GIANFRANCO , FRANCESCHETTI FRANCA , FLAMIGNI C. 
Published: July 2010

AbstractSpontaneous uterine contractility during the menstrual cycle is required for menstruation, gamete transport, and, most likely, embryo nidation. Abnormal uterine contractility has been linked to dysmenorrhea, a condition associated with painful uterine cramping. Based on previous studies with progesterone, we have postulated the existence of a portal system that is responsible for some degree of direct vagina‐to‐uterus transport of administered compounds (i.e., the “first uterine pass effect”). It is possible that treatment with uterorelaxing substances, particularly β‐adrenergic agonists, may alleviate the uterine discomfort that accompanies dysmenorrhea. However, side effects encountered with oral administration of β‐agonists limit their utility. Alternatively, vaginal delivery of β‐agonists could solve this dilemma by enhancing their efficacy and reducing side effects. Therefore, in the current study we used hysterectomy specimens and an in vitro uterine perfusion system to test the vagina‐to‐uterus transport of [3H]terbutaline, a well‐known β‐agonist. With the use of autoradiographic and scintillation counting techniques, our results clearly show progressive diffusion of labeled terbutaline from the rim of vaginal tissue through the uterus during the first 12 hours of perfusion. This indicates that uterine targeting of terbutaline can be accomplished through vaginal administration, suggesting a new therapeutic modality in women's health care.
Contractility of the Nonpregnant Uterus
Authors: DE ZIEGLER D. , BULLETTI C. , FANCHIN R. , EPINEY M. , BRIOSCHI P.‐A. 
Published: July 2010

AbstractRecent renewed interest in uterine contractility stems from the possibility of directly visualizing uterine contractility on images generated by high‐resolution ultrasound probes. During the menstrual cycle, three typical patterns of uterine contractility have been recognized. During the luteofollicular transition and early follicular phase (menses), the contractile event involves all layers of the myometrium and exerts antegrade (from fundus to cervix) expulsive forces. Characteristically, uterine contractions are often perceived by women at the time of menses, sometimes reaching the level of painful cramps (dysmenorrhea). In the late follicular phase, uterine contractility involves only the subendometrial layers of the myometrium and is never perceived by women. The primary function of uterine contractility in the late follicular phase is to facilitate the retrograde (cervix to fundus) transport of sperm towards the distal end of the fallopian tubes where fertilization normally takes place. Finally, the uterus reaches a stage of quiescence after ovulation (under the influence of progesterone) that characterizes the major part of the luteal phase. The present review summarizes our understanding of the physiological role of uterine contractility during the follicular phase and the possible implications in pathological circumstances such as endometriosis and dysmenorrhea.
Assessing Uterine Receptivity in 2001
Authors: FANCHIN RENATO 
Published: July 2010

AbstractThe understanding and control of embryo implantation represents the major challenge for assisted reproductive technologies. Along with developments in basic research and efforts to optimize embryo quality, the improvement of noninvasive and reliable methods to assess uterine receptivity constitutes an important step toward meeting such a challenge. Today, ultrasound‐based approaches to evaluate endometrial echogenicity and uterine perfusion and contractility are available for practical use. Increasing evidence indicates that echogenic patterns of the endometrium reflect histologic processes that are involved in the establishment of receptivity. This constitutes a possible explanation for the reported association between premature hyperechogenic patterns of the endometrium and poor implantation rates. Nevertheless, additional studies aiming at correlating further morpho‐biochemical events in the endometrium with its echogenicity patterns are needed. Further, developments in vascular assessment by Doppler, Doppler‐related, and vascular detection technologies will also be instrumental in monitoring and improving vascular changes that lead to uterine receptivity. Finally, data supporting the hypothesis that uterine contractility, as visualized by ultrasound, influences in vitro fertilization‐embryo transfer (IVF‐ET) pregnancy rates encourage further investigation on both the regulation and control of uterine contractions. This article discusses some of the advantages and limitations of ultrasonographic assessments of uterine receptivity in the perspective of the new millennium.
Methods and Devices for the Management of Term and Preterm Labor
Authors: GARFIELD R. E. , MAUL H. , SHI L. , MANER W. , FITTKOW C. , OLSEN G. , SAADE G. R. 
Published: July 2010

AbstractIn this review, we outline studies showing that the uterus (myometrium) and cervix pass through a conditioning step in preparation for labor. This step is not easily identifiable with present methods designed to assess the uterus or cervix. In the uterus, this seemingly irreversible step consists of changes in the electrical properties that make muscle more excitable and responsive and produce forceful contractions. In the cervix, the step consists of softening of the connective tissue components. Progesterone and nitric oxide appear to have important roles in these processes. The progress of labor can be assessed noninvasively using electromyographic (EMG) signals from the uterus (the driving force for contractility) recorded from the abdominal surface. Uterine EMG bursts detected in this manner characterize uterine contractile events during human and animal pregnancy. A low uterine EMG activity, measured transabdominally throughout most of pregnancy, rises dramatically during labor. EMG activity also increases substantially during preterm labor in humans and rats and may be predictive of preterm labor. A quantitative method for assessing the cervix is also described. A collascope estimates cervical collagen content from a fluorescent signal generated when collagen crosslinks are illuminated with an excitation light of about 340 nm. The system has proved useful in rats and humans at various stages of pregnancy and indicates that cervical softening occurs progressively in the last one‐third of pregnancy. In rats, collascope readings correlate with resistance measurements made in the isolated cervix, which may help to assess cervical function during pregnancy and indicate controls and treatments.
Ectopic Pregnancy
Authors: LUCIANO ANTHONY A. , ROY GERARD , SOLIMA EUGENIO 
Published: July 2010

AbstractDuring the past 25 years, the incidence of ectopic pregnancy has progressively increased while the morbidity and mortality have substantially decreased, and the treatment has progressed from salpingectomy by laparotomy to conservative surgery by laparoscopy and more recently to medical therapy. This therapeutic transition from surgical emergency to medical management has been attributed to early diagnosis through the use of sensitive assays for hCG and the high definition of vaginal ultrasound. By using these sensitive diagnostic tools, we are now able to select those patients who are most likely to respond to medical management versus those who are at high risk of rupture and require surgery. Besides being less invasive and associated with significantly lower risks, medical therapy with methotrexate results in significant cost savings, which have been calculated to be approximately $3,000 per treated patient. Our goal is to identify those patients with ectopic pregnancy who are most likely to respond to methotrexate therapy and least likely to develop significant side effects. Recent studies have helped us define the predictors of success with methotrexate treatment in women with ectopic pregnancy. The reported success rates of treating ectopic pregnancy with methotrexate vary from 71% to 100%. The highest success rates have been reported from institutions that have detailed diagnostic and therapeutic protocols, readily available assays for serum hCG levels, high‐resolution vaginal probe ultrasound, and support staff that can closely monitor clinical response. The importance of developing specific protocols to create a clinical environment that supports the effective use of medical therapy for ectopic pregnancy is confirmed by the associated cost savings, decreased morbidity, and patient preference. Modern diagnostic advances and minimally invasive treatments coupled with improved success rates for assisted reproductive technologies should reduce the morbidity and mortality associated with ectopic pregnancy and offer the affected couple a much more optimistic outlook for subsequent reproductive potential.
Role of Exogenous and Endogenous Hormones in Endometrial Cancer
Authors: AKHMEDKHANOV ARSLAN , ZELENIUCH‐JACQUOTTE ANNE , TONIOLO PAOLO 
Published: July 2010

AbstractEndometrial carcinoma is the most common cancer of the female reproductive organs in the United States. International comparisons reveal that the incidence of endometrial cancer vary widely between different countries with the highest rates observed in North America and Northern Europe, intermediate rates in Eastern Europe and Latin America, and lowest rates in Asia and Africa. International variation in endometrial cancer rates may represent differences in the distribution of known risk factors, which include obesity, postmenopausal estrogen replacement, ovarian dysfunction, diabetes mellitus, infertility, nulliparity, and tamoxifen use. Most of the risk factors for endometrial cancer can be explained within the framework of the unopposed estrogen hypothesis, which proposes that exposure to estrogens unopposed by progesterone or synthetic progestins leads to increased mitotic activity of endometrial cells, increased number of DNA replication errors, and somatic mutations resulting in malignant phenotype. Although the impact of exogenous hormone replacement was intensively studied during the last two decades, less is known about the effects of endogenous hormones in endometrial cancer. A review of available experimental, clinical, and epidemiologic data suggests that in addition to estrogens, other endogenous hormones, including progesterone, androgens, gonadotropins, prolactin, insulin, and insulin‐like growth factors, may play a role in the pathogenesis of different histopathologic types of endometrial cancer.
Doppler Investigation in Intrauterine Growth Restriction—From Qualitative Indices to Flow Measurements
Authors: FERRAZZI ENRICO , BELLOTTI MARIA , GALAN HENRY , PENNATI GIANCARLO , BOZZO MADDALENA , RIGANO SERENA , BATTAGLIA FREDERICK C. 
Published: July 2010

AbstractIn 1997 we started a collaboration among three groups, combining our experience with Doppler examination of the human fetus, blood flow studies on fetal lamb, and mathematical modeling of human circulation. In preliminary investigations on fetal lambs, the same Doppler method designed for the human fetus was used to measure venous blood flow in the umbilical veins of seven fetal lambs. Doppler measurements and diffusion technique groups for umbilical venous flow were 210.8 ± 18.8 and 205.7 ± 38.5 ml/min/kg, respectively (p= 0.881). In human pregnancy the interobserver variabilities for the vein diameter, mean velocity, and absolute umbilical venous blood were 2.9%, 7.9%, and 12.7%, respectively. A cross‐sectional study allowed us to establish normal reference values. Venous blood flow/kg of estimated fetal weight showed a nonsignificant linear reduction with gestational age, from 128.7 ml/min/kg at 20 weeks to 104.2 ml/min/kg at 38 weeks. In a series of 37 growth‐restricted fetuses, the UV flow per kilogram was significantly lower in the more severe growth‐restricted fetuses (abdominal circumference below the second percentile and abnormal umbilical arterial p.i.) than in normal comparable fetuses (p < 0.001). In a series of 140 normal fetuses, we calculated that the absolute blood flow rate in the ductus venosus (DV) increases significantly with advancing gestational age from 20 to 38 weeks of gestation (from 23.2 ± 9.6 ml/min to 43.5 ± 21.5 ml/min). This means that the percentage of umbilical blood flow shunted through the DV decreases significantly during gestation (from 50% at midgestation to 20% at 38 weeks). In a series of 45 growthrestricted fetuses, delivered because of nonreactive fetal heart rate (group 2) and for other reasons but still with a normal heart rate pattern (group 1), we measured the ductal inlet diameter. In these fetuses, the diameters at the ductal isthmus, normalized for the dimension of the abdominal circumference (inlet diameter/abdominal circumference), were significantly larger (group 1 = 6.8 ± 2.3; group 29.4 ± 2.8) than in the control group (6.1 ± 0.3). This means that in this subset of fetuses the amount of blood shunted can be increased as a compensatory mechanism.
Ethical Issues in Selecting Embryos
Authors: RHODES ROSAMOND 
Published: July 2010

AbstractPeople involved in assisted reproduction frequently make decisions about which of several embryos to implant or which of several embryos to reduce from a multiple pregnancy. Yet, others have raised questions about the ethical acceptability of using sex or genetic characteristics as selection criteria. This paper reviews arguments for rejecting embryo selection and discusses the subject of choosing offspring in terms of the centrality of liberty and autonomous choice in ethics. It also presents a position on the acceptable scope of embryo selection and the professional responsibilities of those who practice reproductive medicine.
Effect of Reynolds Number, Turbulence Level and Periodic Wake Flow on Heat Transfer on Low Pressure Turbine Blades.
Authors: SUSLOV DMITRY , SCHULZ ACHMED , WITTIG SIGMAR 
Published: July 2010

Abstract: The development of effective cooling methods is of major importance for the design of new gas turbines blades. The conception of optimal cooling schemes requires a detailed knowledge of the heat transfer processes on the blade's surfaces. The thermal load of turbine blades is predominantly determined by convective heat transfer which is described by the local heat transfer coefficient.Heat transfer is closely related to the boundary layer development along the blade surface and hence depends on various flow conditions and geometrical parameters. Particularly Reynolds number, pressures gradient and turbulence level have great impact on the boundary layer development and the according heat transfer. Therefore, in the present study, the influence of Reynolds number, turbulence intensity, and periodic unsteady inflow on the local heat transfer of a typical low pressure turbine airfoil is experimentally examined in a plane cascade.
Pharmacological Interventions against Aging through the Cell Plasma Membrane
Authors: ZS.‐NAGY IMRE 
Published: July 2010

AbstractAs was shown in a recent review by this author (Ann. N.Y. Acad. Sci., 928:187‐199, 2001), oxyradicals cannot be considered only as harmful by‐products of the oxidative metabolism, but living cells and organisms implicitly require their production. This idea is supported by numerous facts and arguments, the most important of which is that the complete inhibition of the oxyradical production by KCN (or by any block of respiration) kills the living organisms long before the energy reserves would be exhausted. This new theoretical approach not only helps our understanding of the normal functions of the living organisms, such as the basic memory mechanisms in the brain cells, but also helps in identifying the site‐specific, radical‐induced damaging mechanisms that represent the undesirable side effects of oxygen free radicals. First of all, these effects make the cell plasma membrane vulnerable and cause a series of intracellular functional disorders, as described by the membrane hypothesis of aging (MHA). The logical way for any antiaging intervention therefore should be to increase the available number of loosely bound electrons inside the plasma membrane that are easily accessible for OH•free radical scavenging. The present review summarizes the available knowledge regarding the theory of the use of membrane‐related antiaging pharmaca, like centrophenoxine (CPH), tested in both animal experiments and human clinical trials. A modified, developed version of CPH coded as BCE‐001 is also reported.
Coenzyme Q10 Protects the Aging Heart against Stress
Authors: ROSENFELDT FRANKLIN L. , PEPE SALVATORE , LINNANE ANTHONY , NAGLEY PHILIP , ROWLAND MICHAEL , OU RUCHONG , MARASCO SILVANA , LYON WILLIAM , ESMORE DONALD 
Published: July 2010

AbstractWith aging of the population, increasing numbers of elderly patients are presenting for cardiac surgery. However, the results in the elderly are inferior to those in the young. A likely contributing factor is an age‐related reduction in cellular energy production in the myocardium during surgery, which is known to induce aerobic and ischemic stress. The lipophilic antioxidant and mitochondrial respiratory chain redox coupler, coenzyme Q10 (CoQ10), has the potential to improve energy production in mitochondria by bypassing defective components in the respiratory chain as well as by reducing the effects of oxidative stress. We hypothesized that CoQ10 pretreatment prior to stress could improve the recovery of the myocardium after stress.