bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxytocin Receptor Is Differentially Expressed in Mouse Endometrium and Embryo during Blastocyst Implantation
Authors: BERETSOS PANAGIOTIS , LOUTRADIS DIMITRIS , KOUSSOULAKOS STAUROS , MARGARITIS LOUKAS H. , KIAPEKOU ERASMIA , MASTORAKOS GEORGE , PAPASPIROU IRINI , MAKRIS NIKOLAOS , MAKRIGIANNAKIS ANTONIS , ANTSAKLIS ARIS
Published: February 2007

Abstract:  The oxytocin (OT)‐oxytocin receptor (OTR) system of the mammalian uterus has mainly been studied in relation to its involvement in the onset of labor. The aim of this study was to elucidate the in vivo expression and localization pattern of OTR in the mouse endometrium and embryo during implantation, as well as OTR mRNA expression in the in vitro developing mouse embryo. The expression of OTR or OT was detected immunohistochemically in uterine tissue sections of 5‐ to 8‐week‐old female mice between days 4 and 10 of an established pregnancy. In addition, the expression of OTR mRNA was detected by means of reverse transcription polymerase chain reaction (RT‐PCR) in mouse oocytes and embryos up to the blastocyst stage. The mean ratios of normalized expression levels of OTR gene in all samples were also calculated. The recorded increase in OTR mRNA immediately after fertilization could mean a possible role of OT in this process, as OTR mRNA gradually decreased after the four‐cell stage of pre‐embryonic development. The differential expression of OTR during embryonic apposition and embryonic invasion/placentation in the mouse uterus suggests a potential role of OT in the implantation process of the mouse. It is possible that the interaction of OTR with the hormones included in the ovulation induction regiments utilized today in in vitro fertilization (IVF) could be affecting the receptivity/quality of the implanting endometrium.
Fetal Growth Restriction and Postnatal Development
Authors: ELEFTHERIADES MAKARIOS , CREATSAS GEORGE , NICOLAIDES KYPROS
Published: February 2007

Abstract:  The interaction between genetic constitution and in utero environment determines fetal growth and development and influences the susceptibility to certain disorders in adulthood. Data from both animal and human studies indicate that prenatal and early postnatal malnutrition can program the hypothalamus‐pituitary‐adrenal axis (HPA axis), altering neuroendocrine response to stressors throughout lifetime. Impaired uteroplacental perfusion results in fetal growth restriction (FGR). In FGR there is evidence of chronic hypoxemia and alterations in metabolic, endocrine, and hematological parameters, compatible with starvation. Furthermore, FGR is associated with increased perinatal mortality and in the survivors there is increased susceptibility to diabetes and cardiovascular disease in adulthood. There is evidence that early postnatal growth acceleration, which would normally be considered desirable, may exacerbate metabolic dysfunction in later life.
Sequenced Compared With Simultaneous Anthracycline and Cyclophosphamide in High-Risk Stage I and II Breast Cancer: Final Analysis From INT-0137 (S9313)
Authors: Linden Hannah M. , Haskell Charles M. , Green Stephanie J. , Osborne C. Kent , Sledge George W. , Shapiro Charles L. , Ingle James N. , Lew Danika , Hutchins Laura F. , Livingston Robert B. , Martino Silvana
Published: February 2007

Purpose

We conducted a phase III randomized study of two adjuvant treatment schedules of doxorubicin (A) and cyclophosphamide (C) in early-stage breast cancer to determine if administration of sequential single agents (A → C) results in superior disease-free survival (DFS) and overall survival (OS) versus the same total dose given in combination (AC).

Patients and Methods

High-risk node-negative or low-risk node-positive breast cancer patients received AC given: (arm I) concurrently (AC) doxorubicin 54 mg/m2 and cyclophosphamide 1.2 g/m2 intravenously (IV) every 3 weeks for six cycles; or (arm II) in sequence (A → C) doxorubicin 40.5 mg/m2 IV days 1 and 2 every 3 weeks for four cyles followed by cyclophosphamide 2.4 gm/m2 IV every 2 weeks for three cycles. Total dose and duration were identical, but the intensity of each drug was increased on A → C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics. All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy.

Results

Between 1994 and 1997, 3,176 patients were randomly assigned. Arms were well balanced; 48% of eligible patients were node-negative and 48% were estrogen receptor–positive. No significant differences in OS or DFS were observed; 5-year estimates of OS (95% CI) were 88% (87% to 90%) on AC and 89% (87% to 91%) on A → C. Grade 4 hematologic toxicity was greater on A → C, but nonhematological grade 4 was similar.

Conclusion

The overall result does not support superiority of dose-intense sequenced single agents. The greater toxicity of higher doses of single agents does not support their sequential use.
A Microarray Analysis of the Temporal Response of Liver to Methylprednisolone: A Comparative Analysis of Two Dosing Regimens
Authors: Almon Richard R. , DuBois Debra C. , Jusko William J.
Published: February 2007

Microarray analyses were performed on livers from adrenalectomized male Wistar rats chronically infused with methylprednisolone (MPL) (0.3 mg/kg·h) using Alzet mini-osmotic pumps for periods ranging from 6 h to 7 d. Four control and 40 drug-treated animals were killed at 10 different times during drug infusion. Total RNA preparations from the livers of these animals were hybridized to 44 individual Affymetrix REA230A gene chips, generating data for 15,967 different probe sets for each chip. A series of three filters were applied sequentially. These filters were designed to eliminate probe sets that were not expressed in the tissue, were not regulated by the drug, or did not meet defined quality control standards. These filters eliminated 13,978 probe sets (87.5%) leaving a remainder of 1989 probe sets for further consideration. We previously described a similar dataset obtained from animals after administration of a single dose of MPL (50 mg/kg given iv). That study involved 16 time points over a 72-h period. A similar filtering schema applied to the single-bolus-dose dataset identified 1519 probe sets as being regulated by MPL. A comparison of datasets from the two different dosing regimens identified 358 genes that were regulated by MPL in response to both dosing regimens. Regulated genes were grouped into 13 categories, mainly on gene product function. The temporal profiles of these common genes were subjected to detailed scrutiny. Examination of temporal profiles demonstrates that current perspectives on the mechanism of glucocorticoid action cannot entirely explain the temporal profiles of these regulated genes.
Leptin Suppresses Ghrelin-Induced Activation of Neuropeptide Y Neurons in the Arcuate Nucleus via Phosphatidylinositol 3-Kinase- and Phosphodiesterase 3-Mediated Pathway
Authors: Kohno Daisuke , Nakata Masanori , Maekawa Fumihiko , Fujiwara Ken , Maejima Yuko , Kuramochi Motoki , Shimazaki Takuya , Okano Hideyuki , Onaka Tatsushi , Yada Toshihiko
Published: February 2007

Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) play a central role in stimulation of feeding. They sense and integrate peripheral and central signals, including ghrelin and leptin. However, the mechanisms of interaction of these hormones in NPY neurons are largely unknown. This study explored the interaction and underlying signaling cross talk between ghrelin and leptin in NPY neurons. Cytosolic Ca2+ concentration ([Ca2+]i) in single neurons isolated from ARC of adult rats was measured by fura-2 microfluorometry. Ghrelin increased [Ca2+]i in 31% of ARC neurons. The [Ca2+]i increases were inhibited by blockers of phospholipase C, adenylate cyclase, and protein kinase A. Ghrelin-induced [Ca2+]i increases were suppressed by subsequent administration of leptin. Fifteen of 18 ghrelin-activated, leptin-suppressed neurons (83%) contained NPY. Leptin suppression of ghrelin responses was prevented by pretreatment with inhibitors of phosphatidylinositol 3-kinase and phosphodiesterase 3 (PDE3) but not MAPK. ATP-sensitive potassium channel inhibitors and activators did not prevent and mimic leptin suppression, respectively. Although leptin phosphorylated signal-transducer and activator of transcription 3 (STAT3) in NPY neurons, neither STAT3 inhibitor nor genetic STAT3 deletion altered leptin suppression of ghrelin responses. Furthermore, orexigenic effect of intracerebroventricular ghrelin in rats was counteracted by leptin in a PDE3-dependent manner. These findings indicate that ghrelin increases [Ca2+]i via mechanisms depending on phospholipase C and adenylate cyclase-PKA pathways in ARC NPY neurons and that leptin counteracts ghrelin responses via a phosphatidylinositol 3-kinase-PDE3 pathway. This interaction may play an important role in regulating ARC NPY neuron activity and, thereby, feeding.
Progesterone Maintains Basal Intracellular Adenosine Triphosphate Levels and Viability of Spontaneously Immortalized Granulosa Cells by Promoting an Interaction between 14-3-3σ and ATP Synthaseβ/Precursor through a Protein Kinase G-Dependent Mechanism
Authors: Peluso John J. , Liu Xiufang , Romak Jonathan
Published: February 2007

The present studies were designed to 1) describe changes in both the mitochondrial membrane potential and ATP content of spontaneously immortalized granulosa cells as they undergo apoptosis, 2) identify some of the downstream events that are activated by progesterone (P4), and 3) relate these downstream events to changes in mitochondrial function and apoptotic cell death. These studies revealed that in response to serum deprivation, the mitochondrial membrane potential initially hyperpolarizes and ATP content increases. That this increase in ATP is required for apoptosis was demonstrated by the finding that oligomycin inhibited the increase in ATP and apoptosis. Piridoxalphosphate-6-azopeyl-2′-4′-disulfonic acid, an inhibitor of purinergic receptors, which are activated by ATP, also inhibited apoptosis due to serum withdrawal. This study provides additional support for ATP’s causative role in apoptosis. Moreover, 8-Br-cGMP, a protein kinase G (PKG) activator, mimicked P4’s action, whereas a PKG antagonist, DT-3, attenuated P4’s suppressive effect on ATP and apoptosis. Finally, DT-3 treatment was shown to attenuate P4-regulated phosphorylation of 14-3-3σ and its binding partner, ATP synthaseβ/precursor and the amount of ATP synthaseβ/precursor that bound to 14-3-3σ. Based on these data, it is proposed that P4 prevents apoptosis in part by activating PKG, which in turn maintains the interaction between ATP synthaseβ/precursor and 14-3-3σ. In the absence of P4-induced PKG activity, we further propose that some ATP synthaseβ precursor dissociates from 14-3-3σ, resulting in its activation and incorporation into the ATP synthase complex, which ultimately results in an increase in ATP and apoptosis.
Determination of Dissociation Constants of Cyclodextrin—Ligand Inclusion Complexes by Electrospray Ionization Mass Spectrometry
Authors: Zhang Huarong , Zhang Hanqi , Jin Weiqun , Ding Lan
Published: February 2007

The inclusion complexes of four ligands binding to cyclodextrins (CDs) were studied by electrospray ionization mass spectrometry (ESI-MS) and the dissociation constants of the complexes were obtained. The 1:1 stoichiometric inclusion complex was found in the system of CD and fenbufen or aspirin. The obtained K D values of the inclusion complexes of fenbufen binding to α-CD and to β-CD are 4.38 × 10−4 mol L−1 and 2.12 × 10−4 mol L−1, respectively. The K D values of the inclusion complexes of α-CD-aspirin and β-CD-aspirin are 3.33 × 10−4 mol L−1 and 1.83 × 10−4 mol L−1, respectively. A non-linear least squares regression method was applied to validate the results which were consistent with each other. For the system of tetracycline hydrochloride and CD, the 1:1 and 1:2 stoichiometric inclusion complexes were found in the mass spectra. The K D,1 and K D,2 values of the 1:1 and 1:2 stoichiometric inclusion complexes of α-CD and tetracycline hydrochloride are 4.47 × 10−4 mol L−1 and 6.51 × 10−4 mol L−1, respectively, and those of β-CD and tetracycline hydrochloride are 2.26 × 10−4 mol L−1 and 8.57 × 10−4 mol L−1, respectively. For the system of norfloxacin and CD, besides the 1:1 and 1:2 inclusion complexes, the 1:3 stoichiometric inclusion complex was also found. The K D,1, K D,2 and K D,3 of α-CD and norfloxacin inclusion complexes are 4.61 × 10−4 mol L−1, 6.05 × 10−4 mol L−1 and 1.45 × 10−3 mol L−1, respectively. The three K D values of β-CD and norfloxacin are 1.96 × 10−4 mol L−1, 4.93 × 10−4 mol L−1 and 1.15 × 10−3 mol L−1, respectively.
Mass Spectrometry of β-Ketoesters. Some Evidence of Their Tautomerism
Authors: Allegretti Patricia E. , Castro Eduardo A. , Furlong Jorge J.P.
Published: February 2007

Mass spectrometric evidence of tautomerism is reported for β-ketoesters. The analysis of the corresponding mass spectra has allowed specific the assignment of fragment ions to tautomers. The predictive value of this methodology is supported by the influence of a substitution pattern of these compounds on the equilibria. Experimental data are strongly supported by Austin Model 1 semi-empirical calculations, indicating that mass spectrometry could be resourced as a tool for the investigation of tautomerism of neutral species in the gas phase.
Letter: Electron Ionization-Induced Fragmentation of New Thiochalcone Derivatives
Authors: Nowakowska Zdzislawa
Published: February 2007

Electron ionization mass spectral fragmentation of new (E)-4-chalconylothioalkyl-substituted derivatives of piperidinie, 4-methyl-piperidine, morpholine and piperazine as well as (E)-4-bromoalkylthiochalcones, being substrates of the former compounds, have been studied. Fragmentation pathways have been proposed on the basis of the accurate mass and metastable transition measurements.
A Comparison of Electrospray Ionization and Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry with Nuclear Magnetic Resonance Spectroscopy for the Characterization of Synthetic Co-Polymers
Authors: Alhazmi Abdulrahman M. , Giguère Marie-Soleil , Dubé Marc A. , Mayer Paul M.
Published: February 2007

Electrospray ionization (ESI-MS) and matrix-assisted laser desorption/ionization (MALDI-MS) were used to determine the composition (monomer ratios) and structure (end group analysis) relative to 1H nuclear magnetic resonance (NMR) spectroscopy and theoretical predictions for three different co-polymers: poly(butyl acrylate/vinyl acetate) (PBA/PVAc), poly(methyl methacrylate/vinyl acetate) (PMMA/PVAc) and poly (butyl acrylate/methyl methacrylate) (PBA/PMMA). We found that the ESI results were in excellent agreement with 1H NMR spectroscopy for PBA/PVAc and PBA/PMMA co-polymers, whereas there was more divergence in the case of PMMA/PVAc. In the case of PBA/PMMA co-polymers, a similar distribution of products was observed by ESI-MS and MALDI-MS with the two major product classes differing by their end-groups. One class has hydrogen and dodecylthio end groups while, in the other, the dodecylthio has been replaced by α-cyanoisopropyl from the initiator. The relative abundance of these distributions as a function of co-polymer conversion for a series of reaction conditions was investigated by both ESI and MALDI. MALDI results consistently underestimated (relative to ESI) the butylacrylate monomer ratio in PBA/PMMA and the abundance of co-polymer oligomers terminated by a dodecylthio group from the chain transfer agent.
Plasma Lipoprotein(a) Indicates Risk for 4 Distinct Forms of Vascular Disease
Authors: Jones Gregory T , van Rij Andre M , Cole Jennifer , Williams Michael JA , Bateman Emma H , Marcovina Santica M , Deng Meiying , McCormick Sally PA
Published: February 2007

Background: Increased lipoprotein(a) [Lp(a)] concentrations are predictive for coronary artery disease (CAD). The risk conferred by Lp(a) for other types of vascular disease compared with CAD has not been investigated within a single population. This study aimed to investigate Lp(a) risk association for 4 different types of vascular disease (including CAD) within a predominantly white population.

Methods: We used an Lp(a) ELISA that measures Lp(a) independently of apolipoprotein(a) size to measure plasma Lp(a) in patients [384 CAD, 262 peripheral vascular disease, 184 ischemic stroke (stroke), 425 abdominal aortic aneurysm] and 230 disease-free controls. We then conducted association studies with logistic regression, integrating the potential confounding effects of age, sex, diabetes, plasma lipids, and a history of previous hypertension, hypercholesterolemia, and smoking.

Results: Multivariate analyses with Lp(a) concentrations of >45 nmol/L (the 75th percentile value for controls) as the clinical cutoff showed increased Lp(a) concentrations to be a risk factor for all disease groups, with adjusted odds ratios ranging from 1.96 [95% confidence interval (CI) 1.24–3.08] for CAD to 2.33 (95% CI 1.39–3.89) for PVD. The risk conferred by Lp(a) appeared to be independent of other confounders, including exposure to statin/fibrate therapies. Similar odds ratios and CIs between disease groups indicated that increased Lp(a) conferred a similar risk for all groups studied.

Conclusions: Lp(a) constitutes a stable risk factor of similar magnitude for 4 major forms of vascular disease. This association was not altered by exposure to standard lipid-lowering therapy.
Disability Management and Entrepreneurship: Results From a Nationwide Study in Sweden
Authors: Larsson Stig
Published: February 2007

Various factors have meant that employment in welfare states is much more insecure than just a few decades ago. Entrepreneurship has become an important alternative for many people, as a way to increase both security and flexibility. At the end of the 1990s and the start of the 2000s, an average of just over 10,000 people per year received grants in Sweden to start their own business. Of these, just under 10% had some type of ‘work handicap’. This study surveyed a group of new entrepreneurs with disabilities about their entrepreneurial activities. Of those who answered the questionnaire 51% were women. The average age of respondents was 43 years. Only 31.2% reported at follow-up that they were 100% involved in their business. The vast majority of disabled entrepreneurs worked part-time in their firm, which is quite different to the work contribution of entrepreneurs without disabilities. However, the main finding is clear: entrepreneurs with disabilities succeed to roughly the same extent as other entrepreneurs. In terms of disability management programs, entrepreneurship should also be considered as an option for people with disabilities.
A Systematic Review of Workplace Rehabilitation Interventions for Work-Related Low Back Pain
Authors: Williams Renee M. , Westmorland Muriel G. , Lin Chia-Yu , Schmuck Gloria , Creen Marg
Published: February 2007

This article describes the process and outcome of a systematic review that evaluated the effectiveness of workplace rehabilitation interventions for work-related low back pain (LBP). Between 1982 and 2005 CINAHL, MEDLINE, EMBASE and AMED databases were searched for studies of interventions that were provided at the workplace for workers with LBP. Using methodological quality appraisal 5 reviewers scrutinised the articles. A total of 1224 articles were reviewed and 15 articles, consisting of 10 studies, were deemed of sufficient quality to be included. The best evidence was clinical interventions with occupational interventions, as well as early return to work/modified work interventions, were effective in returning workers to work earlier, reducing pain and disability, and decreasing the rate of back injuries. Ergonomic interventions were also found to be effective workplace interventions.
Corporate Integration Agreements and Their Function in Disability Management
Authors: Niehaus Mathilde , Bernhard Dorte
Published: February 2007

The idea of corporate integration of people with disabilities, who often have become impaired in the course of their working career, has been reinforced by the German Social Code Book IX. With the implementation of the Section 83 and 84.2, preventive approaches such as integration agreements have put the emphasis on the role of social partners in the disability management process, that is, on to the employers' representative, the representative body of the disabled employees and the Works Council. A sectoral case study of the automotive industry, funded by the German government, was conducted to evaluate the integration agreement, using both quantitative and qualitative data. This article explores the goal-setting function of the integration agreement and its role in the management process.
Early Work-Related Interventions in a Medical Rehabilitation Setting
Authors: van Lierop Brigitte A.G. , Nijhuis Frans
Published: February 2007

Early work-related interventions are extremely difficult when an employee is on long-term absence and in medical rehabilitation because of a severe illness or injury. The role of the medical rehabilitation setting is often focused on care and cure; there is little focus on work and work resumption. In this respect health care can hinder employees in their work resumption and in their focus on work. In this study, an intervention was undertaken to increase the focus on return to work in the medical rehabilitation setting with the aim of an integrated approach to return to work. The intervention was carried out in eight rehabilitation settings. During implementation, four different organisational models related to the return-to-work activities were recognised, varying from an integration of return-to-work activities within medical rehabilitation to a complete separation of the medical rehabilitation and the return-to-work activities. Every centre reported an increase of work-related activities and an increase in the return-to-work rate of employees was found.
Jørgensen's inequality for metric spaces with application to the octonions
Authors: Markham Sarah , Parker John R
Published: February 2007

Jørgensen's inequality gives a necessary condition for the discreteness of a non-elementary group of isometries of hyperbolic 3-space. The main idea of the proof may be generalised widely but the statement is quite specialised. Here we give a scheme for restating Jørgensen's inequality for Möbius transformations of a metric space. This unifies many previously published versions of Jørgensen's inequality. We then show how this scheme may be applied by giving a version of Jørgensen's inequality for the octonionic hyperbolic plane.
Multiple farthest points on Alexandrov surfaces
Authors: Vîlcu Costin , Zamfirescu Tudor
Published: February 2007

The farthest point mapping on compact surfaces, associating to each point x of the surface the set of absolute maxima of the intrinsic distance from x, is for some surfaces single-valued and a homeomorphism, while for other surfaces it is not single-valued, and not surjective. These two big classes are not very well understood. For instance it is still unknown whether, say in the convex case, the second class is dense. For a C2 metric on both surfaces and the space of surfaces, the first class has, however, nonempty interior. We describe various properties of the sets of critical points, and of relative and absolute maxima of distance functions, and find several connections between them. We see for example that, on smooth surfaces homeomorphic to S2, a point cannot be critical with respect to more than one other point. Sufficient conditions for a surface to belong to the second class will be formulated and a particular Tannery surface belonging to the boundary of both classes will be presented.
Lower bounds for the first eigenvalue of the p-Laplace operator on compact manifolds with nonnegative Ricci curvature
Authors: Zhang Huichun
Published: February 2007

We present some lower bound estimates for the first eigenvalue of p-Laplace operators on compact Riemannian manifolds with quasi-positive (or nonnegative) Ricci curvature in terms of diameter of the manifolds. For compact manifolds with boundary, we consider the Dirichlet eigenvalue problem with some proper hypothesis.
Placental transfer of long-chain polyunsaturated fatty acids (LC-PUFA)
Authors: Koletzko Berthold , Larqué Elvira , Demmelmair Hans
Published: February 2007

Considerable evidence exists for marked beneficial effects of omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) during pregnancy. The omega-3 LC-PUFA docosahexaenoic acid (DHA) is incorporated in large amounts in fetal brain and other tissues during the second half of pregnancy, and several studies have provided evidence for a link between early DHA status of the mother and visual and cognitive development of her child after birth. Moreover, the supplementation of omega-3 LC-PUFA during pregnancy increases slightly infant size at birth, and significantly reduces early preterm birth before 34 weeks of gestation by 31%. In our studies using stable isotope methodologyin vivo, we demonstrated active and preferential materno-fetal transfer of DHA across the human placenta and found the expression of human placental fatty acid binding and transport proteins. From the correlation of DHA values with placental fatty acid transport protein 4 (FATP 4), we conclude that this protein is of key importance in mediating DHA transport across the human placenta. Given the great importance of placental DHA transport for infant outcome, further studies are needed to fully appreciate the effects and optimal strategies of omega-3 fatty acid interventions in pregnancy, dose response relationships, and the potential differences between subgroups of subjects such as women with gestational diabetes or other gestational pathology. Such studies should contribute to optimize substrate intake during pregnancy and lactation that may improve pregnancy outcome as well as fetal growth and development.
Consumption of ω3-fatty acids during perinatal life: role in immuno-modulation and allergy prevention
Authors: Blümer Nicole , Renz Harald
Published: February 2007

Epidemiological data suggest that dietary factors may have a role in recent increases of the prevalence of allergic diseases. One food-related component might be the reduced consumption of ω3-polyunsaturated fatty acids observed especially in the Western societies; yet, clinical trials supplementing ω3-fatty acids to adults with established allergies and bronchial asthma have generally been disappointing. However, it is known that the immature immune system is highly susceptible to immuno-modulatory environmental conditions particularly in the pre- and postnatal period. This review discusses the immuno-modulatory effects of ω3-fatty acids supplementation in the perinatal life phase on the immune system of the child. Evidence exists that perinatal ω3-fatty acid exposure affects T-cells and antigen presenting cells of the neonates likely due to altered eicosanoid metabolism. Although animal experiments strongly suggest a role of maternal ω3-fatty acid intake on allergic immune responses in the offspring, the beneficial effect of ω3-fatty acid supplementation has been studied in a small number of clinical trials. In these studies perinatal supplementation had some positive effects on distinct clinical phenotypes of the atopic syndrome. However, more studies are needed to fully explore the opportunity of perinatal immuno-modulation.
Role of omega 3-fatty acids and multivitamins in gestation
Authors: Hösli Irene , Zanetti-Daellenbach Rosanna , Holzgreve Wolfgang , Lapaire Olav
Published: February 2007

There is a rising interest in a balanced and varied women's diet not only preconceptionally but also during pregnancy and in the breastfeeding period in order to reduce fetal, neonatal, and maternal risks. A decreased intake of omega 3-fatty acids (FA) or deficiencies of micronutrients are a global health problem, not only in developing countries, where micronutrient-rich food and fortified aliments are often not available, and also in the industrialized world. In contrast to data about the daily periconceptionally intake of folate acid that has been shown to reduce substantially the occurrence and recurrence of neural tube defects (NTD), the benefit of other micronutrients is less determinant.

Deficiencies of omega 3-FA may be a contributing factor for severe complications in pregnancy and postpartum. A meta-analysis for the role of omega 3-FA in preeclampsia and maternal postpartum depression is less consistent, some meta-view's results differ substantially or are even contradictory to large observational studies. Further well-designed studies are warranted. A personal interview and counseling concerning the daily diet should be integrated in the preconceptional and in the antenatal care and an individual supplementation should be offered, if indicated.
Does fish oil prevent preterm birth?
Authors: Jørgen Secher Niels
Published: February 2007

A literature review was performed on the effect of fish oil on preterm birth in observational and randomized studies. The only weak effect on preterm birth found in meta-analyses could be caused by the low compliance, and the fact that many women stop supplementation before term together with a fast acting effect on fish oil.
Beneficial effects of a high fibre diet on oocyte maturity and embryo survival in gilts
Authors: Ferguson E M , Slevin J , Hunter M G , Edwards S A , Ashworth C J
Published: February 2007

The present study examined the effects of feeding gilts a high fibre diet from the third post-pubertal oestrus until either day 19 of the same cycle or insemination at the following oestrus on oocyte maturity, embryo survival and associated changes in reproductive hormone concentrations. Gilts fed with the high fibre diet had lower circulating oestradiol concentrations on days 17, 18 and 19 of the cycle and increased LH pulse frequency on day 18. More oocytes recovered on day 19 from gilts receiving the high fibre diet were at metaphase II after 46-h culture in medium containing 10% of their own follicular fluid, despite fewer large (>7 mm) follicles in these gilts when compared with control animals. There was no effect of diet on ovulation rate, corpora lutea size or progesterone concentrations on days 10–12 after insemination, but embryo survival on days 27–29 after insemination was higher in gilts that received the high fibre diet. This study demonstrates that a high fibre diet that increases embryo survival also improves oocyte maturity and provides information on endocrine correlates that may shed light on underlying mechanisms.
Essential fatty acid deficiency induces fatty acid desaturase expression in rat epididymis, but not in testis
Authors: Sæther Thomas , Tran Thien N , Rootwelt Helge , Grav Hans J , Christophersen Bjørn O , Haugen Trine B
Published: February 2007

On the molecular level, essential fatty acid deficiency (EFAD) has been associated with induced fatty acid (FA) desaturase expression and activity in several tissues. However, there seem to be exceptions. In the present study, we examine the effects of EFAD in the male rat genital tract, combining FA analysis, gene expression studies, and morphological evaluation of epididymal spermatozoa. When feeding 21-day-old Wistar rats, a fat-free diet for 6 weeks, an increase in 18:1n-9 and 20:3n-9 and a concomitant decrease in the 18:2n-6 and 20:4n-6 species are seen in testis, as well as in liver. However, with regard to desaturase expression the rat testis seems to be unresponsive to EFAD conditions, in contrast to other organs studied. In the sexually mature testis none of the desaturases (SCD1, SCD2, D5D, or D6D) are induced in response to lowered contents of polyunsaturated FAs. This also applies to caput epididymis, while EFAD sensitivity is regained in cauda epididymis, where the desaturases are upregulated. The FA profile of epididymal spermatozoa is increasingly affected by EFAD during the transport from testis to cauda epididymis. Furthermore, a significant increase in the number of abnormal spermatozoa is observed in cauda epididymis.
Regulation of chromatin and chromosome morphology by histone H3 modifications in pig oocytes
Authors: Bui Hong-Thuy , Van Thuan Nguyen , Kishigami Satoshi , Wakayama Sayaka , Hikichi Takafusa , Ohta Hiroshi , Mizutani Eiji , Yamaoka Emi , Wakayama Teruhiko , Miyano Takashi
Published: February 2007

Oocyte growth, maturation, and activation are complex processes that include transcription, heterochromatin formation, chromosome condensation and decondensation, two consecutive chromosome separations, and genomic imprinting. The objective of this study was to investigate changes in histone H3 modifications in relation to chromatin/chromosome morphology in pig oocytes during their growth, maturation, and activation. During the growth phase, histone H3 was acetylated at lysines 9, 14, and 18 (K9, K14, and K18), and became methylated at K9 when the follicles developed to the antral stage (oocyte diameter, 90 μm). When the fully grown oocytes (diameter, 120 μm) started their maturation, histone H3 became phosphorylated at serine 28 (S28) and then at S10, and deacetylated at K9, K14, and K18 as the chromosomes condensed. After the electroactivation of mature oocytes, histone H3 was reacetylated and dephosphorylated concomitant with the decondensation of the chromosomes. Histone H3 kinase activity increased over a similar time course to that of the phosphorylation of histone H3-S28 during oocyte maturation, and this activity decreased as histone H3-S10 and H3-S28 began to be dephosphorylated after the activation of the mature oocytes. These results suggest that the chromatin morphology of pig oocytes is regulated by the acetylation/deacetylation and the phosphorylation/dephosphorylation of histone H3, and the phosphorylation of histone H3 is the key event in meiotic chromosome condensation in oocytes. The inhibition of histone deacetylase with trichostatin A (TSA) inhibited the deacetylation and phosphorylation of histone H3, and chromosome condensation. Therefore, the deacetylation of histone H3 is thought to be required for its phosphorylation in meiosis. Although histone H3 acetylation and phosphorylation were reversible, the histone methylation that was established during the oocyte growth phase was stable throughout the course of oocyte maturation and activation.
Gonadotropin-dependent regulation of bovine pituitary adenylate cyclase-activating polypeptide in ovarian follicles prior to ovulation
Authors: Sayasith Khampoune , Brown Kristy A , Sirois Jean
Published: February 2007

To study the regulation of bovine pituitary adenylate cyclase-activating polypeptide (PACAP) in preovulatory follicles prior to ovulation, PACAP cDNA was isolated by RT-PCR. Its open reading frame (ORF) is composed of 531 bp, and encodes for a 176-amino acid protein that bears 76–90% identity with other PACAP homologs. Using bovine preovulatory follicles obtained between 0 and 24 h after human chorionic gonadotropin (hCG) and semiquantitative RT-PCR/Southern blot, we demonstrate that levels of PACAP mRNA were low at 0 h, markedly increased at 6 and 12 h (P<0.05), and declined 18 and 24 h after hCG. Levels of PACAP mRNA were high in the bovine pituitary, testis, intestine and uterus, but moderate to low in other tissues. Analyses performed on isolated preparations of granulosa and theca cells showed a significant increase of PACAP transcripts in both cell types after hCG, whereas primary granulosa cell cultures revealed high levels of PACAP as well as its receptors PAC-1 and VPAC-2 mRNA after forskolin treatment. Overexpression of the catalytic subunit of protein kinase A (PKA) in granulosa cells stimulated, but treatment with H89 or PKA inhibitor protein inhibited PACAP mRNA expression, whereas PACAP overexpression stimulated an increase in abundance of transcripts for PGHS-2, PGES, EP2 receptor, progesterone receptor, and ADAMTS-1, but not for P450-side chain cleavage and P450 aromatase. Thus, this study demonstrates the gonadotropin-dependent regulation of PACAP mRNA in bovine preovulatory follicles, the importance of PKA activation in the expression of PACAP in granulosa cells, and stimulating effect of PACAP on gene expression during the ovulatory process.
Cloning of equine prostaglandin dehydrogenase and its gonadotropin-dependent regulation in theca and mural granulosa cells of equine preovulatory follicles during the ovulatory process
Authors: Sayasith Khampoune , Bouchard Nadine , Doré Monique , Sirois Jean
Published: February 2007

The mammalian ovulatory process is accompanied by a gonadotropin-dependent increase in follicular levels of prostaglandin E2 (PGE2) and PGF2α, which are metabolized by 15-hydroxy prostaglandin dehydrogenase (PGDH). Little is known about ovarian PGDH regulation in non-primate species. The objectives of this study were to characterize the structure of equine PGDH and its regulation in follicles during human chorionic gonadotropin (hCG)-induced ovulation. The full-length equine PGDH was obtained by RT-PCR, 5′- and 3′-rapid amplification of cDNA ends (RACE). Its open reading frame encodes a 266-amino acid protein that is 72–95% homologous to other species. Semi-quantitative RT-PCR/Southern blot were used to study PGDH regulation in follicles isolated 0–39 h post-hCG. Results showed that PGDH mRNA expression was low in follicles obtained at 0 h, increased at 12 and 24 h (P < 0.05), and decreased at 36-h post-hCG. This induction of expression was biphasic, with elevated abundance of transcripts at 12 and 33 h post-hCG (P < 0.05) in mural granulosa and theca cells. Immunohistochemistry and immunoblotting confirmed regulated expression of PGHD protein in both cell types of preovulatory follicles after hCG. High levels of PGDH mRNA were observed in corpus luteum and other non-ovarian tissues tested, except kidney, muscle, brain, and heart. Thus, this study is the first to report the gonadotropin-dependent regulation of PGDH during ovulation in a non-primate species. PGDH induction was biphasic in theca and mural granulosa cells differing from primates in which this induction was monophasic and limited to granulosa cells, suggesting species-specific differences in follicular control of PGDH expression during ovulation.
Reproductive role of prolactin
Authors: Bachelot Anne , Binart Nadine
Published: February 2007

The biological actions of prolactin (PRL), a polypeptide hormone, are mostly related to lactation and reproduction. These actions have been clarified by studies of PRL and PRL-deficient receptor mice, which have a clear phenotype of reproductive failure at multiple sites. This review aims to summarize current knowledge about PRL and its receptor, role in reproductive axis and presents information of hyperprolactinemia in reproductive medicine. Our understanding of the physiology and transduction pathway of PRL has largely increased in the past 20 years with the cloning of PRL and its receptor gene.
Expression of extracellular matrix metalloproteinase inducer and matrix metalloproteinases during mouse embryonic development
Authors: Chen Li , Nakai Masaaki , Belton Robert J , Nowak Romana A
Published: February 2007

Mouse embryo implantation is a highly invasive and controlled process that involves remodeling and degradation of the extracellular matrix of the uterus. Matrix metalloproteinases (MMPs) are the main proteinases facilitating this process. Extracellular matrix metalloproteinase inducer (EMMPRIN) can stimulate the production of MMPs and is required for successful implantation in the mouse. The aims of the present study were to examine the expression profiles of mRNA and proteins for EMMPRIN and MMPs in the developing mouse embryo in vitro, and to study whether EMMPRIN protein induces the production of MMPs by mouse blastocysts. EMMPRIN mRNA, detected by RT-PCR, was present at all stages of embryo development from the one-cell to the blastocyst outgrowth. EMMPRIN protein, observed by confocal microscopy, was present on the cell surface at the same stages of development as was the mRNA. Of seven MMPs studied, murine collagenase-like A (Mcol-A), murine collagenase-like B (Mcol-B) and gelatinase A (MMP-2) mRNAs were detected only in blastocyst outgrowths by RT-PCR. Gelatinase B (MMP-9) mRNA was detected both in expanded blastocysts and blastocyst outgrowths. MMP-2 and -9 proteins were detected in the cytoplasm of outgrowing trophoblast cells. Collagenase-2 (MMP-8), collagenase-3 (MMP-13), or stromelysin-1 (MMP-3) mRNAs were not present at any stage of pre- or peri-implantation mouse embryo development. Quantitative RT-PCR analyses showed that recombinant EMMPRIN protein did not stimulate MMP-2 or -9 expression by mouse blastocyst outgrowths. These data suggest that EMMPRIN may regulate physiological functions other than MMP production by mouse embryos during implantation.
Evaluation of Sca-1 and c-Kit As Selective Markers for Muscle Remodelling by Nonhemopoietic Bone Marrow Cells
Authors: Wong Sharon H.A. , Lowes Kym N. , Bertoncello Ivan , Quigley Anita F. , Simmons Paul J. , Cook Mark J. , Kornberg Andrew J. , Kapsa Robert M.I.
Published: February 2007

Bone marrow (BM)-derived cells (BMCs) have demonstrated a myogenic tissue remodeling capacity. However, because the myoremodeling is limited to approximately 1%–3% of recipient muscle fibers in vivo, there is disagreement regarding the clinical relevance of BM for therapeutic application in myodegenerative conditions. This study sought to determine whether rare selectable cell surface markers (in particular, c-Kit) could be used to identify a BMC population with enhanced myoremodeling capacity. Dystrophic mdx muscle remodeling has been achieved using BMCs sorted by expression of stem cell antigen-1 (Sca-1). The inference that Sca-1 is also a selectable marker associated with myoremodeling capacity by muscle-derived cells prompted this study of relative myoremodeling contributions from BMCs (compared with muscle cells) on the basis of expression or absence of Sca-1. We show that myoremodeling activity does not differ in cells sorted solely on the basis of Sca-1 from either muscle or BM. In addition, further fractionation of BM to a more mesenchymal-like cell population with lineage markers and CD45 subsequently revealed a stronger selectability of myoremodeling capacity with c-Kit/Sca-1 (p < .005) than with Sca-1 alone. These results suggest that c-Kit may provide a useful selectable marker that facilitates selection of cells with an augmented myoremodeling capacity derived from BM and possibly from other nonmuscle tissues. In turn, this may provide a new methodology for rapid isolation of myoremodeling capacities from muscle and nonmuscle tissues.

Disclosure of potential conflicts of interest is found at the end of this article.
Identification of Long-Term Repopulating Potential of Human Cord Blood-Derived CD34−flt3− Severe Combined Immunodeficiency-Repopulating Cells by Intra-Bone Marrow Injection
Authors: Kimura Takafumi , Asada Rumiko , Wang Jianfeng , Kimura Takashi , Morioka Miho , Matsui Kazuo , Kobayashi Katsuya , Henmi Kae , Imai Shiro , Kita Masakazu , Tsuji Takashi , Sasaki Yutaka , Ikehara Susumu , Sonoda Yoshiaki
Published: February 2007

Recently, we have identified human cord blood (CB)-derived CD34-negative (CD34−) severe combined immunodeficiency (SCID)-repopulating cells (SRCs) using the intra-bone marrow injection (IBMI) method (Blood 2003;101:2924). In contrast to murine CD34− Kit+Sca-1+Lineage− (KSL) cells, human CB-derived Lin−CD34− cells did not express detectable levels of c-kit by flow cytometry. In this study, we have investigated the function of flt3 in our identified human CB-derived CD34− SRCs. Both CD34+flt3+/− cells showed SRC activity. In the CD34− cell fraction, only CD34−flt3− cells showed distinct SRC activity by IBMI. Although CD34+flt3+ cells showed a rather weak secondary repopulating activity, CD34+flt3− cells repopulated many more secondary recipient mice. However, CD34−flt3− cells repopulated all of the secondary recipients, and the repopulating rate was much higher. Next, we cocultured CD34−flt3− cells with the murine stromal cell line HESS-5. After 1 week, significant numbers of CD34+flt3+/− cells were generated, and they showed distinct SRC activity. These results indicated that CB-derived CD34−flt3− cells produced CD34+flt3− as well as CD34+flt3+ SRCs in vitro. The present study has demonstrated for the first time that CB-derived CD34− SRCs, like murine CD34− KSL cells, do not express flt3. On the basis of these data, we propose that the immunophenotype of very primitive long-term repopulating human hematopoietic stem cells is Lin−CD34−c-kit−flt3−.

Disclosure of potential conflicts of interest is found at the end of this article.
Effects of Physical Training on Functional Status in Patients With Prolonged Mechanical Ventilation
Authors: Chiang Ling-Ling , Wang Li-Ying , Wu Chin-Pyng , Wu Huey-Dong , Wu Ying-Tai
Published: February 2007

Background and Purpose. Patients requiring prolonged mechanical ventilation (PMV) are frequently deconditioned because of respiratory failure precipitated by the underlying disease, the adverse effects of medications, and a period of prolonged immobilization. The effects of 6 weeks of physical training on the strength of respiratory and limb muscles, on ventilator-free time, and on functional status in patients requiring PMV were examined. Subjects. Thirty-nine patients with PMV were initially enrolled in the study and were assigned to either a treatment group (n=20) or a control group (n=19). Three subjects in the treatment group and 4 subjects in the control group died during the 6-week intervention period and thus their data were excluded from the final analysis. Methods. Subjects in the treatment group received physical training 5 days a week for 6 weeks. Strength of respiratory and limb muscles, ventilator-free time, and functional status, which was measured by the Barthel Index of Activities of Daily Living (BI) and Functional Independence Measure (FIM), were examined at baseline and at the third and sixth weeks of the study period. Results. Respiratory and limb muscle strength improved significantly at the third and sixth weeks in the treatment group compared with baseline measurements. Total BI and FIM scores increased significantly in the treatment group and remained unchanged in the control group. Effect sizes of the BI and FIM scores were 2.02 and 1.93, respectively, at the sixth week. Discussion and Conclusion. The results show that a 6-week physical training program may improve limb muscle strength and ventilator-free time and thus improve functional outcomes in patients requiring PMV. [Chiang LL, Wang LY, Wu CP, et al. Effects of physical training on functional status in patients with prolonged mechanical ventilation. Phys Ther. 2006;86:1271–1281.]
Combined Use of Repetitive Task Practice and an Assistive Robotic Device in a Patient With Subacute Stroke
Authors: Frick Ellen M , Alberts Jay L
Published: February 2007

Background and Purpose. This case report describes a training program comprising repetitive task practice (RTP) and robotic therapy for a patient with subacute stroke and resultant impaired upper-extremity function. Case Description. A 63-year-old man with right-sided hemiplegia resulting from a hemorrhagic stroke received a combined intervention of RTP and robotic therapy for 4 hours per day for 3 weeks. Clinical and kinetic evaluations were performed before and after intervention. Outcomes. Following the combined intervention, clinical improvements in hand function were observed, maximum grip force decreased slightly, and interlimb coupling decreased. Discussion. An intervention of RTP with robotic therapy may be an effective method to improve upper-extremity function following stroke. Furthermore, the case suggests that improvements in strength are not necessary for improved dexterous function, provided that a minimal level of strength is present.