Effect of different timings of umbilical cord clamping on the level of CD34+ cells in full-term neonates.

Despite the fact that delayed cord clamping (DCC) is recommended by many international organizations, early cord clamping is still widely practiced worldwide. The overarching goal of the DCC practice is to maximize neonatal benefits as achieving higher hemoglobin levels and decreasing the incidence of anemia as well as avoiding the adverse consequences. The current study was conducted to identify the effect of of DCC on the number of CD34+ stem cells in cord blood of full term neonates after two different timings (30 and 60 s after birth). One hundred and three full-term (FT) newborn babies (gestational age 37-40 weeks) delivered by elective cesarean section were randomly assigned into 2 groups: Group 1: babies were subjected to DCC 30 s after birth (50 newborns). Group 2: babies were subjected to DCC 60 s after birth (53 newborns). Neonates in group 2 had significantly higher levels of hemoglobin, hematocrit, total nucleated cells and CD34+ cells compared to those in group 1. The practice of DCC 60 s after birth achieved better CD34+ stem cells transfer in FT neonates than clamping the cord after 30 s.

Anti-IL-6 receptor monoclonal antibody as a new treatment of endometriosis.

Many pro-inflammatory cytokines especially tumor necrotic factor alpha (TNFα), interleukin (IL)-1ß, and IL-6 have crucial role in the pathogenesis of endometriosis. In this study, we investigated the immune-modulatory role of humanized anti-IL-6 receptor monoclonal antibodies in the treatment of endometriosis. This is a prospective, randomized, controlled, blinded study in which Sprague Dawley rats were used as animal model of endometriosis. Animals were randomly divided into two groups, a test group which received tocilizumab (Actemra; Roche, Switzerland) and a control group which received saline. Afterwards, a comparison was done between the eutopic and ectopic endometrium that was excised from both groups, histopathologically and immune-histochemically. Histopathologic assessment and immune-histochemical staining were performed using antibodies against IL-6. Tocilizumab significantly suppressed the volume of endometriotic lesions compared with non-treated rats (P = 0.006) and atrophied the ectopic endometrial-like epithelium (in 42.8% of treated rats vs 0% in the control group). Tocilizumab also decreased the anti-IL-6 receptor immune-histochemical staining intensity in ectopic endometrium (from non to +++ in the test group vs ++ or more in the control group), with no apparent difference in the eutopic one reflecting the down-regulation of IL-6-producing cells in ectopic endometriotic lesions. In rats with induced endometriosis, anti-IL-6 receptor monoclonal antibodies could offer a new horizon of usage of this immune-modulatory biologic drug, used in other autoimmune diseases, in treatment of endometriosis.

Umbilical Cord Blood Mesenchymal Stem Cells as an Infertility Treatment for Chemotherapy Induced Premature Ovarian Insufficiency.

BACKGROUND: Premature ovarian insufficiency (POI) is a challenging disease, with limited treatment options at the moment. Umbilical cord blood mesenchymal stem cells (UCMSCs) have demonstrated promising regenerative abilities in several diseases including POI. MATERIALS AND METHOD: A pre-clinical murine case versus vehicle control randomized study. Two experiments ran in parallel in each of the three groups. The first was to prove the ability of UCMSCs in restoring ovarian functions. The second was to prove improved fertility. A total of 36 mice were randomly assigned; 6 mice into each of 3 groups for two experiments. Group 1 (control), group 2 (sham chemotherapy), group 3 (stem cells). RESULTS: In the first experiment, post-UCMSCs treatment (group 3) showed signs of restored ovarian function in the form of increased ovarian weight and estrogen-dependent organs (liver, uterus), increased follicular number, and a significant decrease in FSH serum levels (p < 0.05) compared to group 2, and anti-Mullerian hormone (AMH) serum levels increased (p < 0.05) in group 3 versus group 2. Immuno-histochemistry analysis demonstrated a higher expression of AMH, follicle stimulating hormone receptor (FSHR) and Inhibin A in the growing follicles of group 3 versus group 2. In the second experiment, post-UCMSCs treatment (group 3) pregnancy rates were higher than group 2, however, they were still lower than group 1. CONCLUSION: We demonstrated the ability of UCMSCs to restore fertility in female cancer survivors with POI and as another source of stem cells with therapeutic potentials.

Vitamin D and corticotropin-releasing hormone in term and preterm birth: potential contributions to preterm labor and birth outcome.

BACKGROUND: Poor maternal vitamin D status and elevated circulating corticotropin-releasing hormone (CRH) are associated with preterm birth. It is not known if these risk factors are independent or interrelated. Both are associated with inflammation. METHODS: We measured maternal circulating 25-hydroxyvitamin D (25-OH-D) and CRH from 97 samples collected from 15 early-preterm, 31 late-preterm, 21 early-term, and 30 term births. The potential involvement of vitamin D in the regulation of inflammation was evaluated by Q-PCR in human uterine smooth muscle (UTSM) cell line. RESULTS: Maternal 25-OH-D was lowest in early-preterm births (22.9 ± 4.2 ng/ml versus 34.4 ± 1.4 ng/ml; p = .029). Circulating CRH was high in early-preterm births (397 ± 30 pg/ml). Late-preterm (304 ± 13 pg/ml) and early-term births (347 ± 17 pg/ml) were not different from term births (367 ± 19 pg/ml), after accounting for gestational age. Maternal circulating 25-OH-D and CRH were not associated in term births. In preterm births, 25-OH-D below 30 ng/ml was associated with higher CRH. Vitamin D treatment of UTSM significantly reduced mRNA for leptin and IL-6 receptors. Deletion of vitamin D receptor from UTSM promoted the expression of the cox2 inflammatory marker. CONCLUSION: Early-preterm birth showed a syndrome of high maternal CRH and low vitamin D status.

Human Mesenchymal Stem Cells Partially Reverse Infertility in Chemotherapy-Induced Ovarian Failure.

INTRODUCTION: Chemotherapy is the most commonly used modality to treat human cancers; however, in many cases it causes irreversible ovarian failure. In this work, we plan to evaluate the restorative function of human bone marrow mesenchymal stem cells (BMSCs) in a chemotherapy-induced ovarian failure mouse model. METHODS: Acclimatized 4 to 6 week-old female mice (C57BL/6) were assigned randomly to a vehicle-treated control group (group 1), chemotherapy-treated group followed by vehicle alone (group 2), or chemotherapy-treated group followed by stem cell intraovarian injection (group 3). Outcomes were evaluated using immunohistochemistry (IHC), serum hormonal assays, and estrous cycle monitoring and breeding potential. RESULTS: Post BMSCs administration, group 3 promptly showed detectable vaginal smears with estrogenic changes. Increase in total body weight, ovarian weight, and weight of estrogen-responsive organs (uterus and liver) was observed at 2 weeks and continued to end of the experiment. Hematoxylin and Eosin histological evaluation of the ovaries demonstrated a higher mean follicle count in group 3 than in group 2. Group 3 had lower follicle-stimulating hormone (FSH) levels ( P = .03) and higher anti-Müllerian hormone serum (AMH) levels ( P = .0005) than group 2. The IHC analysis demonstrated higher expression of AMH, FSH receptor, inhibin A, and inhibin B in growing follicles of group 3 versus group 2. Tracking studies demonstrated that human BMSCs evenly repopulated the growing follicles in treated ovaries. Importantly, breeding data showed significant increases in the pregnancies numbers, 2 pregnancies in group 1 and 12 in group 3 ( P = .02). CONCLUSIONS: Intraovarian administered BMSCs are able to restore ovarian hormone production and reactivate folliculogenesis in chemotherapy-induced ovarian failure mouse model.

The genetic diversity of metronidazole susceptibility in Trichomonas vaginalis clinical isolates in an Egyptian population.

Trichomoniasis is the most common curable sexually transmitted disease worldwide. Resistance to metronidazole in treating trichomoniasis is a problematic health issue. We aimed to determine the minimum lethal concentration (MLC) of metronidazole for Trichomonas vaginalis isolates detected in Mansoura, Egypt and studied the genotypic profile of these isolates. Vaginal swab specimens were obtained from 320 symptomatic and 100 asymptomatic females, for whom clinical examination, vaginal discharge wet mount, Giemsa stain, and culture in modified Diamond's media were performed. Metronidazole susceptibility testing by an aerobic tube assay was performed. Both sensitive and resistant isolates were examined by PCR amplification followed by restriction fragment length polymorphism (RFLP). Trichomonas vaginalis was identified in 49/420 (11.7%) using either culture or PCR, while wet mount and Giemsa stain detected the parasite in 8.1 and 7.6% of participants, respectively. After 48 h incubation, most isolates were sensitive to metronidazole with a minimal lethal concentration (MLC) of 1 µg/ml. Mild resistance was observed in two isolates with MLCs of 64 µg\ml and mild to moderate resistance was observed in an additional two isolates with MLCs of 128 µg/ml. The four isolates that demonstrated low to moderate metronidazole resistance displayed a unique genotype band pattern by RFLP compared to the other 45 samples that were metronidazole sensitive. Our results highlight the presence of in vitro metronidazole tolerance in a few T. vaginalis isolates in Mansoura, Egypt that may lead to the development of drug resistance as well as the possibility of an identifying RFLP pattern in the isolates.

Opinions and Practice of US-Based Obstetrician-Gynecologists regarding Vitamin D Screening and Supplementation of Pregnant Women.

Vitamin D deficiency/insufficiency is prevalent among pregnant women. Recommendations for adequate levels of circulating 25-hydroxyvitamin D and appropriate vitamin D supplementation during pregnancy differ between the Institute of Medicine and the Endocrine Society. Obstetrician-gynecologists must make clinical decisions in this environment of uncertain guidance. An online questionnaire regarding physician practice patterns for screening and supplementing pregnant women was administered to 225 randomly selected practicing obstetrician-gynecologists of whom 101 (45%) completed the questionnaire. A majority indicated that vitamin D insufficiency was a problem in their patient population (68.4%) and that most of their pregnant patients would benefit from vitamin D supplementation (66.3%). Half (52.5%) would recommend vitamin D supplementation during pregnancy to some patients, but only 16.8% to all. Only one in four (25.8%) routinely screen their pregnant patients for vitamin D status. Physicians who indicated that vitamin D status was a problem in their patient population were more likely to screen routinely (32.8% versus 9.7%, P = 0.002) and believe their patients would benefit from supplementation (91.2% versus 16.1%, P = 0.001). Opinion regarding supplementation levels and indicators of adequacy were split between the two competing recommendations, suggesting that clinical practice will likely remain variable across physicians, with uncertain public health consequences.

Magnetic nanoparticles as a new approach to improve the efficacy of gene therapy against differentiated human uterine fibroid cells and tumor-initiating stem cells.

OBJECTIVE: To study whether efficient transduction and subsequent elimination of fibroid tumor-initiating stem cells during debulking of tumor cells will aid in completely eradicating the tumor as well as decreasing the likelihood of recurrence. DESIGN: Case control study. SETTING: Research laboratory. PATIENT(S): None. INTERVENTION(S): Magnetic nanoparticles (MNPs) complexed to adenovirus (Ad-GFP) or (Ad-LacZ) used to transfect differentiated human fibroid cells in vitro. MAIN OUTCOME MEASURE(S): Rate of transduction and tumor growth inhibition. RESULT(S): We have developed a localized nonsurgical adenovirus-based alternative for the treatment of uterine fibroids that combines viral-based gene delivery with nanotechnology for more efficient targeting. Magnetic nanoparticles complexed to adenovirus, in the presence of an external magnetic field, accelerate adenovirus transduction. We observed a statistically significant increase in transduction efficiency among differentiated human fibroid cells at two different multiplicities of infection (MOI), 1 and 10, respectively, with MNPs as compared with adenovirus alone. Human fibroid stem cells transfected with Ad-LacZ expressed ß-galactosidaze at a MOI of 1, 10, and 50 at 19%, 62%, and 90%, respectively, which were statistically significantly enhanced with MNPs. CONCLUSION(S): When applied with adenovirus herpes simplex thymidine kinase, magnetofection statistically significantly suppressed proliferation and induced apoptosis in both cell types. Through the use of magnetofection, we will prove that a lower viral dose will effectively increase the overall safety profile of suicide gene therapy against fibroid tumors.

Atypical Presentations of Molar Pregnancy: Diagnostic Roles of Imaging, ß-Human Chorionic Gonadotropin Measurement, and p57 Immunostaining.

In modern practice , the diagnosis of molar pregnancy is made at an early gestational age. The opportunity to diagnose gestational trophoblastic disease (GTD) using sonography alone occurs less frequently. The classic appearance of a "snowstorm" in the endometrial cavity and bilateral theca lutein cysts still applies to the diagnosis of second-trimester GTD. The diagnosis of first-trimester GTD requires increased clinical suspicion. If the sonographic appearance of the pregnancy is atypical, GTD should be included in the differential diagnosis. Additional nonimaging criteria such as serial quantitative ß-human chorionic gonadotropin levels, pathologic examination, and p57 (cyclin-dependent kinase inhibitor 1C protein) immunostaining can accurately confirm the diagnosis of GTD.