Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder.

AIM: To characterize purinergic signaling in overactive bladder (OAB). METHODS: Mucosal biopsies were taken by flexible cystoscopy from patients with storage symptoms referred to Urology Departments of collaborating hospitals. Immunohistochemistry (n = 12) and Western blot analysis (n = 28) were used to establish the qualitative and quantitative expression profile of P2Y6 in human mucosa. Participants from the general population provided a mid-stream urine sample. Bioluminescent assays were used to quantify adenosine triphosphate (ATP; n = 66) and adenosine diphosphate (ADP; n = 60) concentrations, which were normalized to creatinine (Cr) concentration. All participants completed a questionnaire (International Consultation on Incontinence Questionnaire - Overactive Bladder) to score urinary symptoms of OAB. RESULTS: P2Y6 immunoreactivity, more prominent in the urothelium (colocalized with the uroepithelial marker pan-cytokeratin), was more greatly expressed in OAB compared to age- and sex-matched controls (benign prostatic hyperplasia) without OAB symptoms. Mucosal P2Y6 was positively correlated only with incontinence (P = .009). Both urinary ATP and its hydrolysis product, ADP, an agonist to P2Y6, were positively correlated with total OAB symptom score (P = .010 and P = .042, respectively). CONCLUSIONS: The positive correlation of P2Y6 only with incontinence may indicate a different phenotype in OAB wet and warrants further investigation. Positive correlations of ATP and ADP with total OAB symptom score demonstrate upregulation in purinergic signaling in OAB; shown previously only in animal models. Further research is required to validate whether purinoceptors are indeed new therapeutic targets for this highly prevalent symptom complex.

New participant stratification and combination of urinary biomarkers and confounders could improve diagnostic accuracy for overactive bladder.

Overactive bladder (OAB) is a highly prevalent symptom complex characterised by symptoms of urinary urgency, increased frequency, nocturia, with or without urge incontinence; in the absence of proven infection or other obvious pathology. The underlying pathophysiology of idiopathic OAB is not clearly known and the existence of several phenotypes has been proposed. Current diagnostic approaches are based on discordant measures, suffer from subjectivity and are incapable of detecting the proposed OAB phenotypes. In this study, cluster analysis was used as an objective approach for phenotyping participants based on their OAB characteristic symptoms and led to the identification of a low OAB symptomatic score group (cluster 1) and a high OAB symptomatic score group (cluster 2). Furthermore, the ability of several potential OAB urinary biomarkers including ATP, ACh, nitrite, MCP-1 and IL-5 and participants' confounders, age and gender, in predicting the identified high OAB symptomatic score group was assessed. A combination of urinary ATP and IL-5 plus age and gender was shown to have clinically acceptable and improved diagnostic accuracy compared to urodynamically-observed detrusor overactivity. Therefore, this study provides the foundation for the development of novel non-invasive diagnostic tools for OAB phenotypes that may lead to personalised treatment.

The Relationship of Pre and Early Postnatal Risk Factors with Breast Cancer.

BACKGROUND: Breast cancer (BC) is the most prevalent cancer in Iranian women and the fifth most common cause of cancer-related death in Iran. Risk factors in the adult life may act during fetus life and after delivery. We conducted a case-control study to find out the relation of in utero and early life exposure and risk of BC. METHODS: A structured questionnaire that covered demographic criteria and BC risk factors in utero was completed for case (732 cases) and control (584 subjects) groups, matched in terms of demographic variants, reproductive issues and socioeconomic status. Odds ratio (OR) and 95% confidence intervals (CI) were computed as measures of association from the logistic models. RESULTS: Having been breast feed for more than 19-24 month (P<0.001, OR 0.03, CI 0.004-0.21) is protective and positive family history of mother (P-value= 0.009, OR 3.4) is a risk factor for BC in adult. CONCLUSION: There is increasing recognition that condition in utero is important for later risks in breast. Emerging evidence suggests an association between intrauterine status and women prenatal condition and their subsequent risk of developing breast cancer. this is the first Iranian study assessing prenatal factors and breast cancer risk in the EMR and it should be followed by the larger group of cases and controls in the future.

Effect of Magnesium Sulfate Added to Tincture of Opium and Buprenorphine on Pain and Quality of Life in Women with Dysmenorrhea: A Prospective, Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Adding magnesium sulfate (MgSO4) to opioid receptor agonists increases the opioid analgesic effects via blocking this receptor. The current study aimed to evaluate the effectiveness of adding MgSO4 to tincture of opium (TOP) and buprenorphine (BUP) on pain and quality of life (QOL). METHODS: In prospective, randomized, double-blind, placebo-controlled clinical trial, one hundred and sixty-three women with secondary dysmenorrhea caused by endometriosis were selected using a respondent-driven sampling (RDS) and assigned into six groups using block randomization. Patients received 50 mg/kg MgSO4 in 100 ml saline by micro set in six monthly menstrual periods and completed the visual analogue scale (VAS) and QOL Questionnaire (QOLQ). Data were analyzed by repeated measures analysis of variance (ANOVA) and hierarchical regression. FINDINGS: The primary outcomes showed that pain scores in magnesium (MAG) + opium tincture (OT) [F = 5.7(1,162), P = 0.004] and MAG+ BUP [F = 4.5(1,162), P = 0.006] groups showed a significant decrease compared with control group. Also, QOL scores in MAG + OT [F = 4.8(1,162), P = 0.005] and MAG + BUP [F = 5.9(1,162), P = 0.003] showed a significant increase. However, there was no significant difference between the two groups (P = 0.140) and the changes did not persist until follow-up (P = 0.810). Secondary outcomes indicated that the low scores of the two components of QOL including physical and psychological components were predictors of pain (P = 0.011, Beta > 3.09). CONCLUSION: Simultaneous use of MAG with opioids is associated with pain reduction and the improvement of QOL. However, this hypothesis requires careful handling in a randomized controlled trial.

Effects of autologous platelet-rich plasma on implantation and pregnancy in repeated implantation failure: A pilot study.

BACKGROUND: Repeated implantation failure (RIF) is a major challenge in reproductive medicine and despite several methods that have been described for management, there is little consensus on the most effective one. OBJECTIVE: This study was conducted to evaluate the effectiveness of platelet-rich plasma in improvement of pregnancy rate in RIF patients. MATERIALS AND METHODS: Twenty women with a history of RIF who were candidates for frozen-thawed embryo transfer were recruited in this study. Intrauterine infusion of 0.5 ml of platelet-rich plasma that contained platelet 4-5 times more than peripheral blood sample was performed 48 hrs before blastocyst transfer. RESULTS: Eighteen participants were pregnant with one early miscarriage and one molar pregnancy. Sixteen clinical pregnancies were recorded and their pregnancies are ongoing. CONCLUSION: According to this study, it seems that platelet-rich plasma is effective in improvement of pregnancy outcome in RIF patients.

Effects of acupuncture for initiation of labor: a double-blind randomized sham-controlled trial.

PURPOSE: This double-blind randomized controlled trial was conducted to evaluate whether use of acupuncture could initiate labor at term and thus reduce post-term induction. METHODS: Between 2010 and 2011, a total of 80 women at 38 weeks of gestation or greater were randomized to acupuncture and sham acupuncture groups. Acupuncture points LI4, SP6 and BL67 were needled bilaterally. The primary outcome was initiation of labor. The time from acupuncture to delivery, mode of delivery, fetal and maternal outcome and Apgar scores were recorded. The trial is registered at irct.ir, number IRCT201111218151N1. RESULTS: Eighty women were randomized and 75 women completed the study procedure. Age, BMI, parity and gestational age were similar in both groups. Spontaneous labor was initiated in 94.7 % of acupuncture group and 89.2 % of sham acupuncture group (p = 0.430). There were no statistically significant difference between groups for time from enrollment to delivery (p = 0.06). CONCLUSION: According to this study, it seems that acupuncture was not effective in labor initiation compared to sham acupuncture.

Effects of gabapentin on postoperative pain, nausea and vomiting after abdominal hysterectomy: a double blind randomized clinical trial.

PURPOSE: Gabapentin has demonstrated analgesic effects in some studies. This double blind randomized clinical trial (RCT) was conducted to evaluate whether the pre-emptive use of gabapentin 600 mg could reduce postoperative pain, nausea and vomiting, and meperidine consumption in patients after hysterectomy. METHODS: Between 2009 and 2010, a total of 170 patients who were candidates for abdominal hysterectomy were assessed for eligibility to enter the study. Thirty patients were excluded for different reasons; and 140 included patients were randomly assigned to one of two groups according to the method of treatment, gabapentin or placebo, in a double-blind manner before hysterectomy. Postoperatively, the pain was assessed on a visual analogue scale (VAS) at 1, 4, 8, 12 and 24 h at rest. Meperidine intramuscularly was used to treat postoperative pain on VAS score and patients demand. Total meperidine and anti emetic drug consumption in the first 24 h after surgery was also recorded. The trial is registered at irct.ir, number IRCT201106186829N1. RESULTS: Patients in the gabapentin group had significantly lower VAS scores at all time intervals, than those in the placebo group. The total meperidine consumed in the gabapentin group was significantly less than in the placebo group. Postoperative nausea and vomiting (PONV) and anti emetic drug consumption were significantly decreased in gabapentin group. CONCLUSION: Pre-emptive use of gabapentin 600 mg orally, significantly decreases postoperative pain and PONV, and also rescues analgesic and anti emetic drug requirements in patients who undergo abdominal hysterectomy.