Could erythropoietin reduce the ovarian damage of cisplatin in female rats?

The aim of this study is to investigate whether erythropoietin (EPO) can reduce the ovarian damage of cisplatin or not. Thirty, female, Wistar-Albino rats were used in the study. Control group (N?=?10): Intraperitoneal saline infusion, Cisplatin group (N?=?10): Intraperitoneal 7?mg/kg cisplatin, Cisplatin?+?EPO group (N?=?10): Intraperitoneal 7?mg/kg cisplatin and subcutaneous 200?IU/kg/day EPO. Serum AMH concentrations were measured by enzyme-linked immunosorbent assay kit of AMH. Follicular counts were evaluated according to mean diameter of the follicles. Ovarian damage; including follicular cell degeneration, vascular congestion, hemorrhage, and inflammation was scored histologically using a graduated scale. Posttreatment AMH levels of cisplatin group were significantly lower than control and cisplatin?+?EPO groups. In cisplatin group, there was a significant decrement in posttreatment AMH level compared to pretreatment AMH level. The total damage score of cisplatin group was significantly higher than scores of control and cisplatin?+?EPO groups. The mean primordial follicle counts of control and cisplatin?+?EPO groups were significantly higher than that of cisplatin group (p?=?.007 and p?=?.003). The results of this study revealed that EPO administration to cisplatin chemotherapy could ameliorate the ovarian damage. Erythropoietin administration to chemotherapeutic agents might suggest to protect ovarian failure and infertility.     

Histomorphometric effects of Kigelia africana (Bignoniaceae) fruit extract on the testis following short-term treatment with cisplatin in male Sprague–Dawley rats

ObjectiveTo investigate the short-term effects of Kigelia africana fruit extract (KAFE) on cisplatin-induced testicular histo-morphometric changes in Sprague–Dawley (SD) rats.DesignThis is an experimental animal study.Materials and methodsFifty-seven male SD rats were acclamatized and grouped into 10 of five rats per group. Each rat was administered either KAFE in 100 and 500mg/kg doses orally or cisplatin 10mg/kg i.p. or normal saline to controls. Experiment was terminated after 28days by i.p. injection of ketamin 50mg/kg. Testicular tissue was processed for histological and morphometric analyses while catalase enzyme activity, lipid peroxidation and glutathione levels were assayed accordingly. Sperm count/motility was also assessed.ResultsCisplatin treatment caused over 37.5% mortality of SD rats. Qualitative histological assessment showed no deleterious changes following treatment with KAFE alone or as a pre-treatment with cisplatin. KAFE post-treatment resulted in focal vacuolar changes in the seminiferous tubules (ST) of the SD rats. Cisplatin-treatment negatively affected the histoarchitecture of the seminiferous tubules with massive loss of spermatogenic cells. There was also a significant reduction in testicular weight/volume, ST diameter and cross-sectional areas (P<0.001) but KAFE positively improved these parameters. KAFE alone and as prophylaxis significantly increased body weight, serum testosterone and follicle-stimulating hormone (P<0.001). It showed a significant elevation in catalase activity, decline in malondialdehyde and up-regulated glutathione levels (P<0.001). These parameters were negatively affected by cisplatin treatment.ConclusionThe cytoprotection against cisplatin-induced testicular damage by KAFE is likely via an antioxidant modulatory pathway. Also, it is possible that KAFE possesses an androgen-stimulating property.     

Pregnancy outcome after IUI for male and idiopathic infertility using a new simplified method for sperm preparation

IntroductionIntrauterine insemination (IUI) is a valid treatment for infertility with a cumulative pregnancy rate of 40–90% after 3–10 treatment cycles.DesignWe prospectively studied the efficacy of a new simplified method for motile sperm preparation for IUI for both male causes of infertility, and for those diagnosed with idiopathic infertility.MethodsA prospective clinical trial was performed with 200 couples, with a 2–8 years history of primary infertility. One hundred couples had been diagnosed as idiopathic, while another 100 couples with male factors of infertility. Motile sperm for IUI was prepared by: (A) the classic World Health Organization self-migration (swim-up) method which includes centrifugation, or (B) the proposed simplified swim-up procedure without centrifugation. Both anti-estrogens and HMG had been used for ovarian stimulation. Depending on the cause of infertility, patients were matched one-to-one at the time of IUI, so that when a total of 100 couples had been treated of both causes of infertility, 50/100 women received sperm prepared by method A and 50/100 by method B.ResultsA statistically significant correlation was found between the percentage motile sperm of the original semen sample and the percentage of motile sperm recovered by method A (r = 0.333, P < 0.01) and B (r = 0.400, P < 0.01). A highly significant correlation (r = 0.997, P < 0.001) was found between the two methods. The pregnancy outcome after the proposed IUI procedure was not significantly different after the traditional swim-up sperm preparation.ConclusionsThe simple proposed swim-up method was as effective as the classic swim-up method, regarding the sperm recovery and pregnancy outcome, but in an easier, and faster way.     

Protective effect of alpha lipoic acid on 4-vinylcyclohexene diepoxide induced primary ovarian failure in female rats

ObjectiveThe effects of alpha lipoic acid (ALA) and its possible mechanisms in treating Primary ovarian failure (POF) model was studied with 4 vinylcyclohexene diepoxide (VCD).Material and methodsRats were divided into 4 groups (n = 7) as Control, VCD, VCD + ALA and ALA. POF model was induced by applying VCD intraperitoneally and ALA was administered by oral gavage as 100 mg/day to the VCD + ALA and ALA groups.ResultsAt the end of 42 days, ovarian and uterine tissues were received. The number of primordial and primary follicles were increased and corpus luteum and cystic follicles were decreased in ovarian tissues in VCD + ALA group compared to VCD group. Caspase-3 immunoreactivity in follicular cells was decreased in VCD + ALA group compared to VCD group. eNOS immunoreactivity and eNOS levels were decreased in VCD group and increased in VCD + ALA group while iNOS immunoreactivity and iNOS levels were increased in VCD group, decreased in VCD + ALA group in ovary and uterine tissue. Plasma FSH and LH hormone levels were increased in the VCD but decreased in VCD + ALA group. Estradiol level decreased in the VCD group compared to the other groups. The MDA values were significantly increased in the VCD + ALA group compared to VCD group. In addition, the levels of GSH values were decreased in VCD + ALA group compared to VCD group.ConclusionAlpha lipoic acid treatment of rats with VCD-induced POF had a beneficial effect on reducing ovarian damage by improving histological, immunohistochemical, hormone level and oxidative stress markers. Our results show that ALA is an effective treatment of VCD-induced POF rats.     

Chronic Administration of Sildenafil Modified the Impaired VEGF System and Improved the Erectile Function in Rats with Diabetic Erectile Dysfunction

IntroductionMen frequently develop diabetic erectile dysfunction (DMED), as a result of endothelial dysfunction. DMED patients often have reduced efficacy with phosphodiesterase type 5 inhibitors therapy.AimTo determine whether chronic sildenafil administration can modify the impaired vascular endothelial growth factor (VEGF) system and improve the erectile function in rats with diabetic erectile dysfunction.MethodsA group of Sprague Dawley rats (n = 30) with DMED were induced by intraperitoneal injection of streptozotocin (40 mg/kg) and screened by subcutaneous injection of Apomorphine (100 mg/kg). They were then exposed to either vehicle or sildenafil (prescribed in our hospital, 5 mg/kg and 10 mg/kg, respectively) for 10 weeks. An additional nondiabetic and age-matched control group (n = 10) was also allocated and given the routine diet for the same period. Assessments were performed to both groups at 36 hours after the last dose of sildenafil. Penile intracavernous pressure (ICP), mean arterial pressure (MAP), penile tissue morphology, immunohistologic analysis, and Western blot analysis of VEGF, VEGFR1, and eNOS were determined.Main Outcome MeasureFunctional, morphological, and proteomical changes on penile structures by the chronic Sildenafil (5 mg/kg and 10 mg/kg, respectively) administration were determined.ResultsA significant increase of ICP, ICP/MAP ratio, and area under the curve were observed in the both groups treated by sildenafil (5 mg/kg and 10 mg/kg, respectively), compared with the DMED rats without receiving Sildenafil. Immunohistochemical staining of their penile tissue showed a decrease in VEGF, VEGFR1, and eNOS staining in the controlled group compared with an improvement in the chronic sildenafil administration group. Western blot analysis demonstrated exactly the same results.ConclusionWe demonstrated that daily sildenafil administration can restore the impaired VEGF system in the penis of DMED rats and progressively improve both erectile function and endothelial function, suggesting a potential general mechanism of improved signaling through the VEGF/eNOS signaling cascade. Liu G, Sun X, Dai Y, Zheng F, Wang D, Huang Y, Bian J, and Deng C. Chronic administration of sildenafil modified the impaired VEGF system and improved the erectile function in rats with diabetic erectile dysfunction.     

A phase I open-label study of selinexor with paclitaxel and carboplatin in patients with advanced ovarian or endometrial cancers

PurposeSelinexor, a selective inhibitor of nuclear export, monotherapy causes nuclear accumulation of tumor-suppressor proteins and has anti-tumor activity in ovarian and endometrial cancers. The safety and tolerability of oral selinexor plus intravenous carboplatin and paclitaxel chemotherapy (selinexor + CP) was evaluated in this population.Patients and methodsThis phase I, 3 + 3 dose-escalation study assessed 4 selinexor + CP regimens. Patients in cohorts of 3, regardless of disease type, were administered 1 of 4 alternating regimens (selinexor at 30 mg/m² or 60 mg plus CP at AUC 5 and 175 mg/m² or 80 mg/m², respectively) for 6–10 cycles (1 cycle = 21 days), followed by selinexor maintenance. Enrolled patients with ovarian cancer had received 1 prior platinum-based therapy. Patients with endometrial cancer were chemotherapy-naive or had received 1 prior platinum-based therapy. Response was evaluated every 9 weeks.ResultsTwenty-three patients were treated (5 serous ovarian cancer; 18 endometrial cancer, including 6 carcinosarcomas). The most common treatment-related adverse events (TRAEs) were thrombocytopenia (100%), leukopenia (91%), and hyperglycemia (87%). The most common grade 3/4 TRAEs were leukopenia (70%), neutropenia (70%), lymphopenia (61%), anemia (57%), and alanine transaminase increase (43%). One treatment-related dose-limiting toxicity (grade 3 syncope) occurred. Twelve patients achieved a partial response and 1 achieved a complete response. Responses to all four regimens were observed in ovarian and endometrial cancers.ConclusionsCombination selinexor + CP was safe and tolerated in advanced ovarian and endometrial cancers.     

顺铂诱导化疗损伤性卵巢早衰大鼠模型的探讨

目的:探讨顺铂诱导大鼠化疗损伤性卵巢功能早衰大鼠模型的可行性。方法:成熟雌性SD大鼠腹腔注射低、高剂量顺铂4.5 mg/kg(A组)、6.0 mg/kg(B组)和生理盐水(C组),每周1次,共2次,建立大鼠化疗损伤性卵巢早衰模型。检测血清FSH水平及光学显微镜下计数卵巢最大切面原始卵泡、初级卵泡、闭锁卵泡,阴道涂片观察动情周期变化。结果:A、B组大鼠动情周期均明显长于C组(P<0.05),并呈现剂量相关性改变。B组动情周期天数明显长于注射前(P<0.01);血清FSH水平A组与C组相比无统计学意义(P>0.05),B组明显高于A组和C组(P<0.05)。各顺铂组血清FSH水平注射后均较注射前明显升高(P<0.05)。腹腔注射顺铂后,A组、B组大鼠卵巢最大切面原始卵泡数和初级卵泡数均明显降低(P>0.05),而闭锁卵泡数均明显增加(P<0.05),并呈现剂量相关性改变。结论:顺铂可诱导化疗损伤性卵巢早衰。此化疗损伤性卵巢早衰大鼠模型血FSH明显升高,卵巢组织学衰退性改变与人类化疗损伤性卵巢早衰病变过程相似。     

New Methodology for Investigating Ejaculation Dysfunction: Measuring Intraluminal Seminal Vesicle Pressure in Rats with a Telemetric Device

IntroductionEjaculation dysfunction is one of the most common male sexual disorders. Despite its prevalence and adverse impact on patients, little attention has been given to investigating ejaculation dysfunction.AimWe introduce a new method for evaluating ejaculation dysfunction in rats with a telemetric device.MethodsA pressure transducer was surgically implanted in the seminal vesicles of 7-week-old male Sprague–Dawley rats. One week later, the rats were subcutaneously administered tamsulosin 3 μg/kg, and intra-seminal vesicle pressure (ISVP) was recorded in freely moving rats after an injection of apomorphine (80 μg/kg). Same rats repeated experiment with tamsulosin 10 μg/kg, silodosin 1 mg/kg, and normal saline with 3-day intervals.Main Outcome MeasureSexual events were visually identified and recorded. Ejaculation was confirmed by visualization of a copulatory plug in the tip of the penis. We compared the maximal ISVP and area under the curve (AUC) of the ISVP.ResultsAdequate ISVP data were easily recorded and available in 66.6% rats (10/15) over a 6-week telemetric recording period (12 recordings). The mean number of ejaculations during an inspection time of 30 minutes was 1.5 ± 0.1. The maximal ISVP values in rats receiving 3 μg/kg (30.0 ± 5.2 mm Hg) and 10 μg/kg tamsulosin (15.1 ± 1.6 mm Hg) and 1 mg/kg silodosin (12.9 ± 2.2 mm Hg) were significantly lower than that in control rats (61.4 ± 13.4 mm Hg, P < 0.05). The AUC values in rats receiving 3 μg/kg (72.7 ± 18.9 mm Hg × s) and 10 μg/kg tamsulosin (23.5 ± 6.1 mm Hg) and 1 mg/kg silodosin (23.9 ± 8.0 mm Hg) were also lower than that of control rats (162.6 ± 34.3 mm Hg, P < 0.05).ConclusionsTelemetric ISVP assessment is reliable and feasible for investigating apomorphine-induced ejaculation in rats. Tamsulosin (3 μg/kg and 10 μg/kg) and silodosin 1 mg/kg decreased the ISVP during ejaculation.     

Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients with recurrent,platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma

ObjectiveWe examined the safety and efficacy of combining bevacizumab with albumin-bound (ab-) paclitaxel to treat patients with recurrent, platinum-resistant primary epithelial ovarian or peritoneal carcinoma.MethodsPatients had measurable disease per RECIST guidelines, progressing within 6 months after a prior course of platinum-based treatment. Patients received ab-paclitaxel 100 mg/m² given by intravenous infusion over 30 min on days 1, 8, and 15 of a 28-day cycle with bevacizumab 10 mg/kg given on days 1 and 15.ResultsForty-eight patients with an average 1.8 prior lines of treatment participated. The overall response rate was 50% (24/48) (95% CI, 34.8% – 65.1%), with 4 complete and 20 partial responses. Fourteen patients (29%) had stable disease, whereas eight (17%) had progressive disease, and two (4%) were not evaluable. Patients received a median of 6 treatment cycles (range, 1 – 31 cycles). The median progression-free survival was 8.08 months (95% CI, 5.78 – 10.15 months); 6 month progression-free rate was 62.5% (95% CI, 47.8%–77.2%); median overall survival was 17.15 months (95% CI, 13.57 – 23.82 months). Grade 3–4 adverse events included gastrointestinal disorders (18.8%), neutropenia (8.3%), and hypertension (6.3%).ConclusionsAb-paclitaxel with bevacizumab clearly demonstrates antitumor activity and manageable toxicity profile in patients with recurrent, platinum-resistant ovarian carcinoma. This regimen should be evaluated in a larger randomized trial.     

A multicenter open-label randomized phase II trial of paclitaxel plus EP-100, a novel LHRH receptor-targeted,membrane-disrupting peptide,versus paclitaxel alone for refractory or recurrent ovarian cancer

ObjectiveThis randomized open-label phase II study evaluated the safety and clinical activity of EP-100 plus weekly paclitaxel in patients with recurrent ovarian cancer expressing positive LHRH receptor.MethodsIn a limited “run-in” dose escalation phase for EP-100, six patients were treated with ascending dose levels (13 mg/m², 20 mg/m², 30 mg/m²). In the randomized phase, patients received weekly paclitaxel (80 mg/m² intravenously) plus twice weekly EP-100 (30 mg/m² intravenously; combination arm) or weekly paclitaxel alone (80 mg/m² intravenously; paclitaxel arm). The primary study endpoint was overall response rate (ORR).ResultsForty-four patients were then randomized to either the experimental combination arm (n = 23) or the standard of care paclitaxel monotherapy arm (n = 21). The ORR was 35% (95%CI 16%–57%) for the combination arm and 33% (95% CI 15%–57%) for the paclitaxel arm. An interesting observation from an unplanned analysis was that a subset of patients with target liver lesions showed a greater overall response rate to the combination (69%) compared to paclitaxel alone (16%). The frequency of treatment-related grade 3–4 adverse events was similar between treatment arms: 48% vs 43% for the combination and paclitaxel arms, respectively.ConclusionsORR in the EP-100 combination arm was similar to that in the group treated with paclitaxel alone; however, a subset of patients with liver metastases appeared to benefit from the combination. The addition of EP-100 did not appear to augment the adverse event profile of paclitaxel and was well tolerated.     

Clomiphene citrate alone,in combination with metformin or in combination with pioglitazone as first line therapy in induction of ovulation in infertile women with polycystic ovary syndrome,a randomized controlled trial

Study objectiveTo compare the efficacy of clomiphene citrate (CC) alone, combined CC and metformin and combined CC and pioglitazone as first line therapy for induction of ovulation and achievement of pregnancy in overweight and obese infertile women due to polycystic ovary syndrome (PCOS).DesignA randomized controlled trial.SettingThe infertility clinic of Ain Shams University maternity hospital.Materials and methods106 overweight and obese women complaining of infertility due to PCOS were randomly assigned to receive ovulation induction using CC, 100 mg daily for 5 days beginning on the third day of spontaneous or induced menses, either alone (Group 1) in combination with metformin, 850 mg twice daily, (Group 2) or in combination with pioglitazone, 30 mg daily, (Group 3). Folliculometry was started from cycle day 9 and repeated every 2 days. hCG (10000 IU) was given intramuscular when at least one follicle ?18 mm was formed. Serum β-hCG was measured 16 days after hCG injection to diagnose pregnancy.Main outcome measureBiochemical pregnancy rate.ResultsThere were no statistically significant differences between the three study groups regarding the biochemical pregnancy rates (7.4% (2/27), 11.1% (3/27) and 18.5% (5/27) for groups 1, 2 and 3, respectively) and the number of women who succeeded to have mature follicles (74.1% (20/27), 74.1% (20/27) and 81.5% (22/27) for groups 1, 2 and 3, respectively).ConclusionThere is no potential benefit from adding pioglitazone or metformin to CC while inducing ovulation in overweight and obese women complaining of infertility due to PCOS. Further larger extended trials are needed to assess using insulin sensitizers for longer duration which could give a better chance to evaluate the cumulative effect of these drugs.     

Phase II study of interval debulking surgery followed by intraperitoneal chemotherapy for advanced ovarian cancer: A Kansai Clinical Oncology Group study (KCOG9812)

ObjectiveIntraperitoneal chemotherapy (IP) is known to be effective after optimal primary debulking surgery (PDS) for ovarian cancer (OC). Here, we conducted a phase II study to investigate its effectiveness after interval debulking surgery (IDS).MethodsThirty-seven patients with FIGO stage IIIB-IV and suboptimal (≥ 1 cm diameter) residual disease after PDS were enrolled. Carboplatin (AUC 4 IV, Day 1) and cisplatin (50 mg/m² IV, Day 3) were given q21d for 3 cycles. After IDS, paclitaxel (175 mg/m² IV Day 1 or 60 mg/m² IV Days 1, 8, and 15, since 2000) and cisplatin (75 mg/m² IP Day 2) were given q21d for 4 cycles. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS) and adverse events (CTCAE ver. 2.0). Clinical manifestations at first recurrence and subsequent treatment were also surveyed.ResultsOf the 37 patients, high-grade, serous adenocarcinoma was found in 33. Stages IIIB, IIIC, and IV were found in 2, 24, and 11 patients, respectively. After IDS, 23 patients had no macroscopic residual tumor. No patients had permanent enterostomy, febrile neutropenia, or platelet transfusion. The treatment protocol was completed in 22 patients, and discontinued in 5 due to IP catheter-related complications. Median PFS and OS were 22 and 57 months, respectively. Among the 28 patients with recurrence, 10 had no intraperitoneal disease at first recurrence. Among the 8 patients who underwent surgical cytoreduction, 6 had no residual tumor, while 2 had a < 1-cm-diameter residual tumor.ConclusionIP after IDS for patients with initially suboptimally debulked OC was effective.     

Outcome and reproductive function after cumulative high-dose combination chemotherapy with bleomycin, etoposide and cisplatin (BEP) for patients with ovarian endodermal sinus tumor

ObjectiveThe aim of this study was to investigate the outcome and reproductive function of patients with ovarian endodermal sinus tumor (EST) after cumulative high-dose combination chemotherapy with bleomycin, etoposide and cisplatin (BEP).MethodsBetween 1995 and 2006, 1034 patients with the diagnosis of ovarian cancer were treated at a single institution. Among these patients, 51 had a confirmed diagnosis of malignant ovarian germ cell tumor (MOGCT) including 20 cases of EST. We retrospectively reviewed those patients with EST, who received BEP as adjuvant chemotherapy. The doses were 15 mg/day of bleomycin on days 1 to 3, 100 mg/m²/day IV of etoposide on days 1 to 3 and 20 mg/m²/day of cisplatin on days 1 to 5. The median number of total cycles was six (range between three and nine).ResultsThe median age of the patients with EST was 18 years (range 5 to 36). All except two were nulliparous. The overall survival rate was 90% at a median follow-up of 70 months. Two patients (10%) had disease recurrence in the pelvis. Of the 15 patients who were treated with fertility-sparing surgery, all had regular menstruation following the completion of adjuvant chemotherapy, and two of these patients had pregnancies with live birth deliveries and no complications.ConclusionIn patients with EST, the cumulative high-dose BEP regimen resulted in excellent overall survival and did not seem to impair ovarian function.     

Ultrasonographic markers of endometrial receptivity of letrozole and clomiphene citrate in unexplained infertile women

ObjectiveTo compare endometrial receptivity of letrozole and clomiphene citrate.Study designA prospective comparative study.Subjects120 women with unexplained infertility undergoing superovulation.InterventionSixty patients underwent ovulation induction using 5 mg letrozole compared with another 60 patients using 100 mg clomiphene citrate.Main outcomeThe endometrial thickness, the endometrial volume, uterine artery and spiral artery Doppler indices at 7 days after HCG administration.ResultsThe mean age, parity and duration of infertility in both groups of patients were similar. There was a significant difference in the endometrial thickness, endometrial volume, and spiral artery Doppler indices between the two groups one week after HCG administration. No difference was found in the uterine artery Doppler indices in both groups. The pregnancy rate was higher in the letrozole group but it was statistically insignificant.ConclusionLetrozole (5 mg) showed a significantly better endometrial response than 100 mg of clomid.     

Astragalus polysaccharides and astragaloside IV ameliorates cyclophosphamide-induced mouse model of overactive bladder

ObjectivePrevious studies have shown that Astragalus polysaccharides (APS) and Astragaloside IV (AS-IV) protect against inflammation-related cell damage and exhibit immune enhancement. Since urothelial injury may result in an overactive bladder (OAB), the aim of this study was to investigate the efficacy of APS and AS-IV on urothelial injury in an experimental animal model.Materials and methodsThe effects of APS and AS-IV on the proliferation and migration of primary human urothelial cells (HUCs) or primary human fibroblast cells (HFCs) were assessed using an in vitro wounding model and colorimetric thiazolyl blue assays. Sixty virgin female mice were randomized into five groups: group 1–saline-injected plus treatment with H₂O, group 2–cyclophosphamide (CYP) plus treatment with H₂O, group 3–CYP plus treatment with solifenacin succinate (SS; 10 mg/kg), group 4–CYP plus treatment with AS-IV (100 mg/kg), and group 5–CYP plus treatment with APS (100 mg/kg). Cystometry assessment was conducted and cell junction-associated protein zonula occludens-2 (ZO-2) expression was measured. Voiding interval values (time between voids) were assessed in mice under anesthesia. Lastly, immunohistochemistry analysis was used to confirm the location and level, respectively, of ZO-2 expression.ResultsAPS and AS-IV did not influence the cell viability but increased migration in HFCs compared with the controls. The OAB mice showed significantly lower voiding interval values. Voiding interval values were significantly higher in the CYP plus treatment with APS (100 mg/kg) and AS-IV (100 mg/kg) groups than in the CYP-induced OAB group. Additionally, the expression of ZO-2, a tight junction protein, was increased in the CYP plus treatment APS (100 mg/kg) and AS-IV (100 mg/kg) groups compared with the CYP-induced OAB group.ConclusionThese findings suggest that APS and AS-IV modulate urothelial wound healing, which ameliorates urinary frequency of mice treated with CYP. APS or AS-IV may have the potential benefit of acting as urothelial wound healing modulators.     

A multicenter,double-blind,randomized, placebo-controlled study of rifaximin for the treatment of bacterial vaginosis

ObjectiveTo compare efficacy and tolerability between different regimens of rifaximin vaginal tablets and a placebo for treatment of bacterial vaginosis.MethodsIn a prospective study carried out at 13 sites in 3 European countries between August 2009 and October 2010, White, non-pregnant, premenopausal women with bacterial vaginosis were randomly assigned to receive rifaximin at 100 mg for 5 days (100 mg/5 days), 25 mg/5 days, or 100 mg/2 days, or placebo. Women were assessed at 7–10 and 28–35 days. Diagnosis and cure were based on Amsel criteria and Nugent score. Fisher exact test was used to compare cure rates.ResultsAmong 114 women recruited, 103 were evaluable for drug efficacy. Therapeutic cure rate at first follow-up was higher in the rifaximin 25 mg/5 days (48%, P = 0.04), 100 mg/2 days (36.0%), and 100 mg/5 days (25.9%) groups than in the placebo group (19.0%). At second follow-up, therapeutic cure rate was 28.0%, 14.8%, and 4.0% in the respective groups versus 7.7% in the placebo group. No difference in adverse events was observed.ConclusionRifaximin at 25 mg/5 days showed better therapeutic cure rates and maintenance of therapeutic cure after 1 month versus placebo. All treatment regimens were well tolerated.EudraCT number: 2009-011826-32.     

The Impact of Maternal Body Mass Index on In Vitro Fertilization Outcomes

ObjectiveTo examine the effect of body mass index on gonadotropin dose requirements for ovarian stimulation, as well as other clinical outcomes in women undergoing in vitro fertilization.MethodsWe performed a retrospective cohort study involving 752 women undergoing a total of 951 IVF or IVF-ICSI cycles at a private fertility clinic between January 2007 and May 2011. The 951 treatment cycles were divided into three groups according to the weight of the women involved: normal weight (BMI < 25 kg/m², 461 cycles), overweight (25 ≤ BMI < 30 kg/m², 277 cycles), and obese (BMI ≥ 30 kg/m², 179 cycles). Total gonadotropin dose requirements and clinical IVF cycle outcomes (cycle cancellation, clinical pregnancy, and live birth) were compared between the three BMI groups. We performed multivariable analyses, adjusting for potential confounders such as age at cycle start, day 3 serum FSH level, smoking, presence of polycystic ovary syndrome, and duration of infertility.ResultsThere were no significant differences between the three BMI groups for any of the IVF cycle outcomes measured, including the total FSH dose required for ovarian stimulation. The likelihood of cycle cancellation, clinical pregnancy, and live birth were not significantly different between normal weight, overweight, and obese women.ConclusionObese women did not require significantly higher doses of gonadotropins for ovarian stimulation than normal weight individuals. At our centre, female obesity did not significantly affect the clinical outcomes of IVF treatment. However, given the conflicting results of existing studies, the effect of maternal obesity on IVF outcomes remains unclear.     

Protective effects of hydrogen-rich saline in preeclampsia rat model

Hydrogen has been reported as a novel antioxidant to selectively reduce levels of toxic reactive-oxygen species (ROS). We investigated the effects of hydrogen-rich saline on the prevention of oxidative injuries in N(omega)-nitro-l-arginine methyl ester (l-NAME) induced rat model of preeclampsia (PE). Sprague-Dawley rats (n = 50) were randomized into five groups: non-pregnant; normal pregnancy; pregnancy + hydrogen saline, 5 ml/kg, intraperitoneal (i.p.); pregnancy + l-NAME, 60 mg/kg (i.p.); pregnancy + l-NAME + hydrogen saline rats. Terminations of pregnancy were performed on day 22 of gestation, when the placentas and kidneys were microscopically inspected; tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and malonyldialdehyde (MDA) were assessed; and the mean systolic BP, level of proteinuria, resorptions, and pups birth weights were recorded. It was found that the pups of hypertensive gravid rats treated with hydrogen-rich saline presented fewer number of resorptions than those of the group of pregnancy + l-NAME, 60 mg/kg i.p. (P < 0.05). Additionally, hydrogen-rich saline treatment decreased the blood and placental MDA, proteinuria and the pro-inflammatory cytokine TNF-α, IL-1β in the placental tissues compared with those in L-NAME-treated rats (all P < 0.05). The mean systolic BP showed no significant difference except on day 22 of gestation (P < 0.05). The preventive administration of hydrogen significantly attenuated the severity of PE, which might be ascribed to a reduction in inflammation response and oxidative stress. It could be concluded that hydrogen can be an effective antioxidant in the management of PE.     

Anti-Müllerian Hormone in Female Adolescent Cancer Patients Before,During, and After Completion of Therapy: A Pilot Feasibility Study

Study ObjectiveAlkylating agents are implicated in premature ovarian insufficiency. To optimize counseling regarding future ovarian function in survivors of adolescent cancer, we describe anti-Müllerian hormone (AMH) levels in female adolescents at diagnosis, during, and shortly after completion of chemotherapy.Design, Setting, Participants, Interventions, and Main Outcome MeasuresThis was a prospective single-institution study. Participants were a mixed population of newly diagnosed postmenarchal female adolescents with malignancy. AMH was performed at diagnosis (T1), 6 months from diagnosis (T2), at end of therapy or 12 months [T3, whichever came first], 1 year after the end of therapy or 24 months from diagnosis [T4, whichever came first], and 18 months from the time of diagnosis (T5). All patients had baseline pelvic ultrasound examinations. Presence of menses and hot flashes were recorded at each time point.ResultsSixteen participants with a median age at diagnosis of 14.3 years (range 12-17 years) were followed for 18.2 months (range, 14-24 months). Oncology diagnoses included leukemia, lymphoma, and sarcoma. Ten patients (62.5%) received alkylating agents with a median cumulative dose of 3041 mg/m² (range, 2639-6478 mg/m²) of cyclophosphamide. Almost half (n = 7; 44%) experienced amenorrhea during treatment with resumption of menses in 6 of 7 patients (85%). Fifteen of 16 (94%) participants showed a decline in mean AMH levels by 6 months (T2) from diagnosis (15.8 IU/mL at T1 vs 6.5 IU/mL at T2; P = .003) and 12 of 15 (80%) showed at least some recovery of AMH (mean AMH at T4 = 13.2 IU/mL compared with 6.5 IU/mL at T2; P = .02). There was no difference in the mean decline nor recovery of AMH in those who did, vs did not receive cyclophosphamide.ConclusionTo our knowledge, this is the largest series to date in adolescents showing that AMH is uniformly suppressed during cancer therapy and short-term recovery occurs in just more than half of the patients by 18-24 months. The contribution of short-term AMH measurements in predicting long-term ovarian function remains to be defined. Long-term follow-up with serial AMH levels is required to help predict those at risk for premature ovarian insufficiency.