Role of advanced glycation end-products in obesity-related ovarian dysfunction.

Obesity affects ovarian function, one of the main regulators of female fertility. Tissue levels of the proinflammatory advanced glycation end-products (AGEs) and their receptors (RAGE) are elevated in obesity. AGEs are key contributors to perturbations in the ovarian microenvironment. On this basis, the present review focuses on clinical and experimental studies supporting the role of AGE-RAGE system as a contributor to obesity-related ovarian dysfunction. Particular emphasis has been given to changes in AGEs, RAGE and the anti-inflammatory soluble receptor (sRAGE) levels in obesity state and following dietary interventions (high-fat diet and weight loss). Ovarian sensitivity, in particular granulosa cell function and oocyte meiosis, to the pro-inflammatory AGE-RAGE system as well as the relationship of follicular fluid AGEs and sRAGE to in vitro fertilization outcome are also discussed. Overall, obesity, with its alterations in the AGE-RAGE system, can disrupt the ovarian microenvironment potentially compromising oocyte competence and fertility. This review underscores a critical need to uncover the mechanistic actions of AGE-RAGE system in obesity-related ovarian dysfunction. Clinical and basic studies focusing on elucidating the patterns of accumulation and role of the AGE-RAGE system in human ovarian follicles are key steps in understanding their contribution to the health of human oocytes and embryos.

Modelling the biological half-life and seasonality of ¹4C in Fucus vesiculosus from the east coast of Ireland: implications for the estimation of future trends.

Radiocarbon levels were recorded in Fucus vesiculosus samples collected on a monthly basis over a three-year period at a site on the east coast of Ireland. The resulting data was analysed using a numerical model which estimates the transit times from the Sellafield plant to the sampling location, and the mean availability time of ¹4C in seaweed. With the inclusion of a model parameter allowing for seasonal variability in uptake by the Fucus, good correlation was observed between the predicted and measured concentrations. Future temporal trends of ¹4C Fucus concentrations along the eastern Irish coastline were modelled with the application of three possible prospective discharge scenarios, predicting ¹4C Fucus concentrations to reduce to ambient background levels within 2.5-years of discharges being set to zero. Such projections may prove helpful in assessing the consequences of discharge management and policy making in the context of the OSPAR convention.

Initial clinical experience with Myxo-ETlogix mitral valve repair ring.

OBJECTIVE: Complexity of mitral valve repair for myxomatous disease has led to low adoption. We report initial experience with a new ring designed specifically for myxomatous disease, the Myxo-ETlogix (Edwards Lifesciences LLC, Irvine, Calif). METHODS: From March 15, 2006, through November 19, 2007, 129 patients underwent mitral valve surgery for pure myxomatous disease, and 124 valves (96.1%) were repaired. The Myxo-ETlogix ring was used in 100 cases and the Physio ring (Edwards) in 24. The Myxo-ETlogix design includes a 3-dimensional shape to reduce systolic anterior motion and a larger orifice to accommodate elongated leaflets and decrease need for sliding plasty. Direct mitral valve measurements were made. Sizing was based on A2 height, and choice of ring type was based on unresected leaflet heights. RESULTS: There was no operative mortality or lasting perioperative morbidity. The Myxo-ETlogix group had taller A2, P1, P2, and P3 leaflet segments than the Physio group (P < or = .003). Only 1 sliding plasty was performed for asymmetry in the Myxo-ETlogix group. Predischarge and follow-up echocardiograms (n = 338 in 124 patients) disclosed transient nonobstructive chordal systolic anterior motion in 3 echocardiograms in 3 patients. No patients had 2+ or greater mitral regurgitation. At discharge, 5.7% had 1+ mitral regurgitation; this proportion was 17.3% at last follow-up (mean 6.1 +/- 4.4 months). CONCLUSION: In initial experience with the Myxo-ETlogix ring, nonobstructive systolic anterior motion has been rare and obstructive systolic anterior motion not observed. Ongoing prospective echocardiographic and clinical studies will elucidate the role of this etiology-specific ring.

Retrospective search for evidence of the 1957 Windscale fire in NE Ireland using 129I and other long-lived nuclides.

The accident at Windscale in October 1957 resulted in the release to the atmosphere of a large quantity of radioactivity. The presented work is a retrospective search for evidence of contamination from the accident in the northeastern region of Ireland. A lake yielding a high-resolution sedimentary record was identified near the northeast coast of Ireland. This site was used to reconstruct the history of radionuclide input to the region, based on the analysis of a set of cores extracted from the lake. A chronology for sediment accumulation within the lake was established using radioisotopic dating techniques (including 270Pb). High-resolution gamma and alpha spectrometry techniques were used to quantify concentrations of 137Cs, 239,240Pu and 241Am, all of which were released during the accident. The primary radioactive component of the release was 131I (T1/2 = 8 days), but this short-lived isotope has long since decayed. However, 129I (T1/2 = 1.57 x 10(7) years) was also released during the accident, and in a known ratio to 131I. Recent advances in accelerator mass spectrometry now make it feasible to measure 129I at ultra-trace level and thereby retrospectively reconstruct 131I deposition. Clearly resolved concentration profiles for 137Cs, 239,240Pu and 241Am in the lake cores reflect known historical fallout trends. The data suggest that any contamination from the Windscale fire that might have reached this catchment has been overwritten by input from the testing of nuclear weapons in the atmosphere. A time-series for 129I in lake sediment shows that concentrations in recent sediments are approximately 10 times greater than concentrations recorded in strata corresponding to the period of maximum fallout of other radionuclides from atmospheric testing of nuclear weapons (1964). These recent increases in 129I are attributed to increased emissions from the nuclear industry. The study yields no evidence of any enhancement in radioisotope concentrations, over and above global fallout, in strata dated to 1957, and we conclude that contamination from the Windscale fire had negligible impact on the northeastern region of Ireland.

Stereotactic breast biopsy: a six-year surgical experience.

A retrospective review was done of all stereotactic breast biopsies performed at the Central Baptist Hospital Breast Center from February 1994 through December 1999. A total of 1,080 biopsies were performed in 1,026 patients, all by surgeons working independently. Masses were biopsied in 54% and calcifications in 40%. Eighteen percent of biopsies were malignant. The most common benign diagnosis was fibrocystic disease (72%), followed by fibroadenoma (19%), lymph node (2%), and papilloma (2%). The most common malignant diagnosis was invasive ductal carcinoma (40%) followed by ductal carcinoma in situ (32%) and mixed invasive and in situ ductal carcinoma (19%). A prebiopsy BI-RADS mammographic Category III was associated with a 2% incidence of malignancy; Category IV--17%; Category V--90%. Atypical ductal hyperplasia on stereotactic biopsy was upgraded to a malignant diagnosis after reexcision in 19% of the cases. The false-negative rate was 0.4% (sensitivity 99%) and the complication rate was 3%, mostly related to bleeding. Stereotactic biopsy is a safe and accurate technique for the minimally-invasive diagnosis of abnormal mammograms.

Müllerian inhibitory substance induces growth of rat preantral ovarian follicles.

Müllerian inhibitory substance (MIS), also known as anti-Müllerian hormone, is best known as the hormone that regulates the regression of the Müllerian duct in males. In females, MIS is expressed in granulosa cells of preantral and early antral follicles. The specific MIS type II receptor is present in granulosa and theca cells of these small, growing follicles. Because the role of MIS in preantral follicle development is unknown, we have evaluated the effect of MIS on the growth, differentiation, and apoptosis of intact preantral follicles in a serum-free culture system. In this system, treatment with FSH induces an increase in both follicle diameter, cell number, and follicle cell differentiation based on increased inhibin-alpha synthesis. Of interest, treatment with MIS enhances the effect of FSH both on follicle diameter and cell number. Although treatment with activin A also enhances FSH effects on follicle growth, treatment with transforming growth factor (TGF)-ss inhibits the FSH effects on follicle growth. Based on in situ staining of fragmented DNA, MIS was found to have no effect on follicle cell apoptosis, unlike its proapoptotic action on Müllerian ducts. In contrast to MIS and activin, TGF-ss was a potent proapoptotic factor for preantral follicles in culture. Analysis of inhibin-alpha expression of cultured preantral follicles further indicated that in contrast to activin, treatment with MIS did not enhance FSH-stimulated follicle differentiation. Thus, MIS is a unique factor that promotes preantral follicle growth but not preantral follicle cell differentiation and apoptosis.

Forgiveness. A concept analysis.

This article provides an operational definition of forgiveness as a first step in the systematic analysis of the concept. Using the method described by Walker and Avant (1995), the authors identify the attributes and characteristics of forgiveness and its theoretical and practical implications for nursing. Sample cases from clinical practice help illustrate the concept further. Further nursing research needs to test the theoretical relationships between forgiveness and nursing practice outcomes.

Evaluating the spiritual perspectives of homeless men in recovery.

The purpose of this study was to describe the self-reported spiritual perspectives of 100 homeless male residents living in a communal shelter. The residents, in recovery from substance addiction, were asked to complete Reed's 10-item Spiritual Perspective Scale (SPS) as part of their initial health database. Their responses were described within the context of their participation in 12-Step recovery programs, demographic characteristics, and perceived health status. Findings suggest that spirituality is an important health component for this population.

In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats.

Growth differentiation factor (GDF)-9 is a cystine knot-containing hormone of the transforming growth factor-beta superfamily produced by the oocyte. In GDF-9 null mice, follicle development is arrested at the primary stage and GDF-9 treatment in vitro enhances preantral follicle growth. Immature female rats were treated with recombinant GDF-9 for 7 or 10 days. At 10 days, treatment with GDF-9 augmented ovarian weights, concomitant with an increase in the number of primary and small preantral follicles by 30 and 60%, respectively. Furthermore, the number of primordial follicles was decreased by 29%, but the number of large preantral follicles was not affected. In contrast, treatment with FSH increased the number of small and large preantral follicles by 36 and 177% but did not influence the number of primary and primordial follicles. Immunoblot analysis showed an increase of CYP17, a theca cell marker, in the ovarian homogenate after treatment with GDF-9 but not FSH. The present results indicate that in vivo treatment with GDF-9 enhances the progression of primordial and primary follicles into small preantral follicles. Thus, GDF-9 treatment could provide an alternative approach to stimulate early follicle development in addition to the widely used FSH that acts mainly on the development of more advanced follicles.

Autocrine and paracrine Müllerian inhibiting substance hormone signaling in reproduction.

Members of the transforming growth factor beta (TGFbeta) superfamily are polypeptide growth factors that exhibit diverse effects on normal cell growth, adhesion, mesenchymal-epithelial interactions, cell differentiation, and programmed cell death. This chapter will discuss the work of ourselves and others on one member of this large superfamily, Müllerian inhibiting substance (MIS, or anti-Müllerian hormone, AMH) and its role in reproductive tract development and the adult gonad. Using recombinant MIS protein, it is possible to begin unraveling the molecular mechanism of duct involution in the embryo. Our recent results suggest that MIS triggers cell death by altering mesenchymal-epithelial interactions. In addition to the developmental effects of MIS in secondary sexual differentiation, expression studies of the MIS ligand and the MIS type II receptor (MISIIR) suggest a potential regulatory role for MIS in adult germ cell maturation and gonadal function. Recent data from others suggest that MIS may act in a paracrine manner to block differentiation of interstitial cells of the adult gonad by repressing all or some steps of steroidogenesis. Our studies are highly suggestive of direct repression of steroidogenic enzyme gene expression by activation of the MIS signaling pathway. Thus, for the first time, an opportunity to define fully target genes and components of the MIS signaling pathway may be possible.

Dizygotic twinning is not linked to variation at the alpha-inhibin locus on human chromosome 2.

Natural multiple pregnancy in women leading to dizygotic (DZ) twins is familial and varies across racial groups, suggesting a genetic predisposition. Mothers of DZ twins have a higher incidence of spontaneous multiple ovulation and elevated FSH concentrations. FSH release is controlled by feedback of inhibin peptides from the ovary, and immunization against inhibin alpha-subunit results in an increased ovulation rate in animals. The inhibin alpha-subunit is therefore a candidate gene for mutations that may increase the frequency of DZ twinning. Restriction digests of a PCR product from exon 1 with the enzyme SpeI detects a C/T polymorphism at bp 128 with two alleles of 447 and 323/124 bp. The polymorphism was typed in 1,125 individuals from 326 pedigrees with 717 mothers of spontaneous DZ twins. The alpha-inhibin locus mapped within 3 centimorgans of D2S164, and linkage with DZ twinning was excluded [decimal log odds ratio (LOD) score, -2.81 at theta = 0]. There was complete exclusion of linkage (LOD, less than -2) of a gene conferring relative risk 1.8 (lambdas, >1.8) across the chromosome, except at the p-terminus region and a small peak (maximum LOD score, 0.6) in the region of D2S151-D2S326. Analysis using either recessive or dominant models excluded linkage with DZ twinning in this population (LOD score, less than -2.5) across chromosome 2. We conclude that dizygotic twinning is not linked to variation in the alpha-inhibin locus. The results also suggest that mutations in other candidates on chromosome 2, including the receptor for FSH and the betaB-inhibin subunit (INHBB) cannot be major contributors to risk for DZ twinning.

Hormonal regulation of early follicle development in the rat ovary.

Although earlier studies focused on the hormonal regulation of antral and preovulatory follicles, recent studies indicate the importance of the hormonal control mechanism for preantral follicles. The endocrine hormone FSH is not only a survival factor for early antral follicles but also a potent growth and differentiation factor for preantral follicles. In addition, KGF secreted by theca cells and c-kit ligand secreted by granulosa cells play paracrine roles in the regulation of preantral follicle growth and development. Furthermore oocyte-derived GDF-9 promotes the growth and differentiation of early follicles by acting on somatic cells in the follicle. It is likely that the genetic makeup of an oocyte could determine the secretion of oocyte hormones which would, in turn, regulate the growth and differentiation of the surrounding somatic cells of that follicle. A better understanding of the hormonal mechanisms underlying early follicle development could provide a refined culture system for the in vitro maturation of fertilizable oocytes and future design of fertility and contraceptive agents.

Long-term trends of radiocesium activity concentrations in vegetation in Irish semi-natural ecosystems.

137Cs activity concentrations were determined in vegetation from four Irish blanket bog ecosystems during the summer months of 1989-1997. The dominant and abundant vegetation species were sampled at each site and the data were used to estimate long-term trends of 137Cs activity concentrations. A general decline in the 137Cs activity concentrations in vegetation was observed from all sites sampled. The fastest and most consistent long-term rates of 137Cs decline were observed in the bryophyte and lichen vegetation group with 137Cs effective half-life (T ef) values of 2.2 to 10.7 y. The ericoid group with the exception of one case also showed a significant long-term decline in 137Cs activity concentrations with T ef values of 3.5 to 12.4 y as did the rush species Juncus squarrosus (T ef range 9.3 to 12.8 y). The sedge and grass groups showed the slowest and the least consistent rates of 137Cs decline, with T ef values of 2.9 to 59.8 y. Preliminary evaluation of 137Cs activity concentrations in sheep from some of the studied sites suggests that the decline found in vegetation is reflected in sheep.

The regulation of apoptosis in preantral ovarian follicles.

Less than 1% of ovarian follicles ever mature to ovulation. The remainder undergo atretic degeneration via apoptosis during development. Though the regulation of antral and preovulatory survival has been studied for many years, very little is known about the regulation of survival and development of preantral follicles. This review discusses recent findings regarding preantral follicle development with emphasis on the regulation of preantral follicle apoptosis.

Initial and cyclic recruitment of ovarian follicles.

Mammalian ovaries consist of follicles as basic functional units. The total number of ovarian follicles is determined early in life, and the depletion of this pool leads to reproductive senescence. Each follicle develops to either ovulate or, more likely, to undergo degeneration. The dynamics of ovarian follicle development have interested endocrinologists and developmental biologists for many years. With the advent of assisted reproductive techniques in humans, the possibility of regulating follicle development in vivo and in vitro has gained clinical relevance. In this review, we focus upon key branching points during the development of ovarian follicles as well as factors involved in determining the eventual destiny of individual follicles. We discuss inconsistencies in the literature regarding the definitions of follicle recruitment and selection and propose to name the two major steps of follicle development as initial and cyclic recruitment, respectively. Because some of these disparities have arisen due to differences in the animal systems studied, we also compare the development of the ovarian follicles of both humans and rats. We also review the status of knowledge of several puzzling clinical issues that may provide important clues toward unlocking the mechanisms of follicle development.

Alcoholics Anonymous and nursing. Lessons in holism and spiritual care.

Alcoholic Anonymous (AA) is a worldwide, million-member organization that has assisted countless alcoholics to achieve sobriety through a spiritual program of recovery from alcoholism. Based on spiritual principles known as the "Twelve Steps" and "Twelve Traditions," AA has provided a model for other recovery programs such as Narcotics Anonymous (NA), Gamblers Anonymous (GA), and Sex and Love Addicts Anonymous (SLAA). Recovery in AA appears to involve a process of self-transcendence. In recent years, nursing scholars have increasingly explored the concepts of self-transcendence and spirituality as they apply to nursing theory and practice. This article explores the roots and spiritual dimensions of 12-step recovery programs. It further explores the ways in which theoretical and clinical knowledge about the delivery of spiritual care interventions may be gained from an understanding of AA's spiritual approach to recovery.

Keratinocyte growth factor promotes the survival, growth, and differentiation of preantral ovarian follicles.

OBJECTIVE: To determine the effect of treatment with keratinocyte growth factor (KGF) on the survival of cells in cultured preantral follicles and on the growth and differentiation of preantral follicles. DESIGN: Preantral follicles (140-150 microm) were dissected mechanically from the ovaries of 14-day-old rats and cultured for 24 hours with and without KGF. Genomic DNA was extracted, labeled with [32P]-dideoxyadenosine triphosphate, and fractionated through agarose gels. For growth studies, the follicles were cultured individually in 96-well dishes. After 72 hours, the follicles were collected and their protein or DNA content was evaluated and their inhibin-alpha content was determined. RESULT(S): Keratinocyte growth factor suppressed apoptosis in cultured preantral follicles by 60%. Treatment with KGF or FSH increased follicle diameter by 8% and 16%, respectively, and combined treatment with KGF and FSH increased follicle diameter by 26%. Western blot analysis demonstrated increased expression of inhibin-alpha content after treatment with KGF (2-fold), treatment with FSH (4-fold), and combined treatment with FSH and KGF (12-fold), demonstrating the effect of KGF on preantral follicle differentiation. CONCLUSION(S): Treatment with KGF promotes the survival, growth, and differentiation of cultured preantral follicles. Keratinocyte growth factor produced by theca cells may play a role in the progression of early follicle development.