Reinforcing effect of tramadol in the rat.

Tramadol is one of the most commonly prescribed analgesic opioids in various pharmacopeias. Tramadol has been linked to abuse in recent clinical investigations. However, the behavioral effects and neural substrates of the drug have not been well characterized in preclinical studies. As a result, the present study investigated the effects of tramadol on behavioral sensitizations in rats. Its impacts on cellular and molecular alterations in the brain were also investigated. In conditioned place preference (CPP) paradigm, tramadol induced behavioral as well as motor sensitizations. These effects were dramatically reduced by intraperitoneal administration of naltrexone, an opioid receptor antagonist. Tramadol caused changes in several molecular markers (pERK1/2, Δ-FosB, PKCγ, PKMζ GAD67) in the anterior cingulate cortex, which could indicate an increase in excitation within this structure. Tramadol is demonstrated in the present study to be a reinforcing drug in rats, as it increased both behavioral and motor sensitizations. Tramadol's effects are most likely due to the high levels of excitation it causes in the brain, which is mostly caused by the activation of opioid receptors.

MIR-379-5p Expression in Endometrial Cancer and Its Correlation with ROR1 Expression.

OBJECTIVE: To asses miR-379-5p expression in endometrial cancer (EC) and its correlation with ROR1 expression and to investigate the relation between miR-379-5p and ROR1 expressions and the clinicopathological picture of EC. METHODS: Fifty female of EC were joined to this study. The gene expression of miR-379-5p (by quantitative real time-PCR) and ROR1 (by quantitative real time-PCR and immunohistochemistry) were studied in EC and normal nearby endometrial tissue. RESULTS: The gene expression of miR-379-5p was significantly downregulated while that of ROR1 was significantly upregulated in EC tissues compared to adjacent normal endometrial tissues. Furthermore, miR-379 and ROR1 expressions significantly associated with tumor stage (P< 0.045), grade (P< 0.001), myometrial invasion (P <0.001) and LN metastasis (P< 0.034). In addition, miR-3795p and ROR1 gene expression were negatively correlated (r = -0.746, P < 0.001). CONCLUSIONS: In EC, miR-379-5p can be used as a diagnostic marker, and ROR1 could be a potential target of miR-379-5p.

RON, ROR1 and SUSD2 expression in tissues of endometrial carcinoma patients. Clinicopathological and prognostic implications.

Introduction: Endometrial carcinoma is now considered a common female gynecologic cancer with increasing incidence, with 13-25% of patients being still liable to recurrence and metastasis, which needs further studies to detect novel targets and new therapies. The aim of the study was evaluate tissue expression of RON, ROR1 and SUSD2 in endometrial carcinoma and atypical endometrial hyperplasia using immunohistochemistry and correlate their expression with clinical, pathological and prognostic parameters of patients. Material and methods: We included samples from 100 patients with endometrial carcinoma. Sections from paraffin blocks were stained with RON, ROR1 and SUSD2 using immunohistochemistry. Correlations between marker expression, clinicopathological features and prognostic samples were evaluated. Results: Upregulation of RON and ROR1 and downregulation of SUSD2 expression were found in endometrial carcinoma more than atypical endometrial hyperplasia (p < 0.001). High RON and ROR1 expression levels were significantly associated with high grade (p < 0.001), presence of lymph node metastases (p = 0.003), distant metastases (p = 0.009), advanced International Federation of Gynecology and Obstetrics stage (p = 0.002), poor response to therapy (p = 0.046), and lower recurrence-free survival (RFS) rate (p = 0.002), progression-free survival (PFS) rate (p = 0.008), distant metastasis-free survival (DMFS) rate (p = 0.019) and overall survival rate (p < 0.001). Low SUSD2 expression was significantly associated with older patient age (p = 0.002), large tumor size (p = 0.003), high grade (p = 0.005), presence of adnexal invasion (p = 0.023), presence of lympho-vascular invasion (p = 0.021), extent of myometrial invasion (p = 0.002), lower RFS rate (p = 0.008), lower PFS rate (p = 0.023), and lower DMFS rate (p < 0.001). Conclusions: Upregulation of RON and ROR1 and downregulation of SUSD2 lead to promotion of endometrial cancer cell proliferation, migration, epithelial-mesenchymal transition, and invasion.

Naltrexone promotes mechanical allodynia in humans and rats.

Mechanical allodynia has been studied in chronic naltrexone-treated people (N.T.P.) and rats (N.T.R.). After persistent naltrexone administration, patients acquired static and dynamic mechanical allodynia, as measured by von Frey filament (vFf) and brush stimulations. Pregabalin and levodopa administrations in N.T.P. significantly reduced allodynic behaviour, albeit these molecules did not completely stop it. As evidenced by the deployment of the vFf, subchronic treatment with Naltrexone delivered peripherally or intrathecally induced allodynic behaviour in rats. Increased expressions of two pain markers, pERK1/2 and PKCγ, in the spinal dorsal horn laminae were associated with naltrexone-induced allodynic behaviour. After vFf stimulation, pERK1/2 expression was substantially higher (p < 0.001) in superficial spinal dorsal horn laminae than in non-stimulated or naive non-stimulated rats. In addition, when compared to control rats, N.T.R. showed a substantial (p < 0.001) increase in PKCγ expression. PKCγ expression was found to be strong in lamina IIi and laminae III-IV. A cellular mechanism is proposed for the naltrexone effect. In both people and rats, Naltrexone induces static mechanical allodynia, according to this study.

Can glyburide be advocated over subcutaneous insulin for perinatal outcomes of women with gestational diabetes? A systematic review and meta-analysis.

PURPOSE: To obtain precise findings from published studies about the efficacy and safety of glyburide versus subcutaneous insulin in patients with gestational diabetes mellitus (GDM). METHODS: We searched PubMed, Cochrane Library, Web of Science, and Scopus, up to January 2019, for relevant studies that compared glyburide with subcutaneous insulin for patients with GDM. We extracted maternal and neonatal outcomes from included studies, performed meta-analysis, evaluated heterogeneity, assessed the risk of bias of included studies, and conducted subgroup and sensitivity analyses. RESULTS: A total of 24 studies (11 randomized controlled trials (RCTs) and 13 observational cohort studies) with a total of 24,517 women were included in the present study. The pooled estimate showed that glyburide significantly decreased the need for cesarean section (OR = 0.87, 95% CI [0.82, 0.92], p < 0.0001), fasting blood glucose (MD - 5.63 mg/dL, 95% CI [- 10.97, - 0.28], p = 0.04), and Apgar score at 5 min (MD - 0.30, 95% CI [- 0.36, - 0.23], p < 0.001) than insulin. However, glyburide significantly increased the risk of neonatal hypoglycemia (OR = 1.42, 95% CI [1.03, 1.95], p = 0.03) and neonatal intensive care unit admission duration (NICU) (MD 4.26 days, 95% CI [2.65, 5.86], p < 0.01) compared to insulin. The overall results did not favor either group in terms of macrosomia (OR = 1.14, 95% CI [0.92, 1.41], p = 0.25) and large for gestational age (LGA) (OR = 1.38, 95% CI [0.99, 1.92], p = 0.06). While subgroup analysis of RCTs showed that maternal hypoglycemia and LGA rates were significantly higher in glyburide than insulin and cesarean section rates were comparable between both compared groups. CONCLUSION: Our study suggests that glyburide is an effective and well-tolerated drug compared to insulin in the management of women with GDM, provided neonates are monitored for hypoglycemia and Apgar score. In addition, glyburide was associated with lower cesarean sections, which may add to the potential clinically benefits of glyburide compared to insulin.

Association of miRNA - 320 expression level and its target gene endothelin-1 with the susceptibility and clinical features of polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance (IR). MicroRNAs (miRNAs) are small noncoding RNA associated with ovarian follicle development and female fertility. The objective of this study was to investigate the role of miRNA- 320 and its target gene endothelin-1 (ET-1) as a noninvasive biomarker of PCOS and to evaluate its possible relationship with IR as well as clinic-morphological features of PCOS. METHODS: Case-control study enrolled 60 patients with PCOS and 40 control group. We subdivided our PCOS women according to homeostasis model assessments of insulin resistance (HOMA-IR) to PCOS women with and without IR.ET-1 levels were measured by ELISA. We estimated the serum expression level of miRNA- 320 by real-time polymerase chain reaction. RESULTS: Our results revealed that serum miR-320 expression level was lower in PCOS patients compared to controls, in particular, PCOS women with IR. Moreover, it was negatively correlated to its target gene; ET-I as well as fasting serum insulin (FSI), HOMA-IR, PCOS phenotype; hirsutism score, ovarian volume and antral follicle count (AFC). In the PCOS group, linear regression analysis revealed that only hirsutism and HOMA-IR was the main predictor of expression levels of miRNA - 320 among other clinical and laboratory biomarkers of PCOS. The sensitivity and specificity of serum miR-320 expression levels in diagnosis PCOS was 80, and 97.5% respectively. CONCLUSION: The Expression serum levels of miR-320 were lower in PCOS compared to control and it could be a noninvasive diagnostic biomarker of PCOS.

Evaluation of protocol of management of morbidly adherent placenta in maternity Zagazig university hospital

Background: Morbidly adherent placenta (MAP) defines the abnormal adherence of the placenta to the underlying uterine wall. It has a rising incidence world-wide. The risk of placental abnormalities increases in the presence of uterine scars due to cesarean delivery or gynecologic procedures. It may lead to massive obstetric hemorrhage resulting in serious complications such as DIC, transfusion related complications. Aim: Evaluation of protocol of management of patients with morbidly adherent placenta at Maternity Zagazig University Hospital and its effect on pregnancy outcome to find the best method of management to decrease associated morbidity and mortality.Patients and methods: This cohort study conducted on 120 patients diagnosed as having morbidly adherent placenta and were admitted to Zagazig University Hospitals.Results: In our study there were 48 cases (40%) managed by CS only and 72 cases (60%) managed by hysterectomy.Conclusion: well-planned caesarean hysterectomy with placenta left in situ adopting multidisciplinary approach is the recommended management option for MAP