Retinoic acid and fibroblast growth factor-2 play a key role on modulation of sex hormones and apoptosis in a mouse model of polycystic ovary syndrome induced by estradiol valerate.

OBJECTIVE: The main goal of the present study is to investigate the effects of retinoic acid and fibroblast growth factor-2 on serum levels of FSH and LH, histology, and apoptosis in the mouse model of Poly Cystic Ovary Syndrome (PCOS). MATERIALS AND METHODS: 80 female NMRI mice have been randomly divided into eight groups. Group 1 received normal saline as a control, and Group 2 received estradiol valerate (EV) at 4 mg/100 g of body weight. Moreover, Groups 3-4 were administered with RA (a dose of 0.05 µg/µl) and FGF2 (a dose of 0.01 µg/kg), respectively. Groups 5 and 6 respectively received the EV plus the RA (0.05 µg/µl) and FGF2 (0.01 µg/kg). Group 7 received the RA and FGF2 at doses corresponding to healthy mice, and Group 8 received the EV plus the RA + FGF2 (similar to previous doses). RA and FGF2 were injected three times per week for four weeks. Finally, histological and immunohistological parameters of the ovary were evaluated. RESULTS: The study revealed that both single and combined injection of fibroblast growth factor-2 (FGF2) and retinoic acid (RA) in groups 5, 6, and 8 significantly reduced follicular diameters compared to group 2. Measurements confirmed that simultaneous injection of RA and FGF2 into polycystic mice significantly increased antral follicles, corpus luteum (CL), epithelial thickness, and oocyte diameter as well as decreased cystic follicles. Positive TUNEL cells that were considerably increased in the antral follicle of group 2 significantly decreased in the RA and FGF2 recipient groups, either alone or in combination. Besides, the injection of FGF2 increased preantral follicles and CL. CONCLUSION: The findings of the present investigation reveal that injection of RA and FGF2 has both protective and ameliorative effects that can promise new therapies for women with PCOS.

Comparison effects of olive leaf extract and oleuropein compounds on male reproductive function in cyclophosphamide exposed mice.

Spermatogenesis is a complicated process in which sperm is susceptible to various chemotherapy drugs such as cyclophosphamide (CP). As olive leaf extract (OLE) and its active ingredient, oleuropein, have variousantioxidant, anti-apoptotic, and anti-inflammatory properties the aim of the present study was to investigate the effects of OLE and oleuropein on male reproductive function focusing antioxidative effects and histological modifications in the testes of CP-exposed mice. In order to do this, 80 NMRI male mice were divided into eight groups including control group, group received CP, group received OLE, group received oleuropein, group received OLE following CP exposure, group received oleuropein following CP exposure, group received OLE plus oleuropein and group received OLE plus oleuropein following CP exposure. In all groups CP (single dose of 100 mg/kg (, OLE (100 mg/kg for consequence 28 days) and oleuropein (100 mg/kg for consequence 28 days) were injected intraperitoneally. Moreover, testis histology, sperm parameters and serum levels of LH, FSH, MDA and antioxidant capacity were investigated. Results showed that CP caused oxidative state and abnormal changes in sperms and testes. Besides, treatments with oleuropein and OLE led to mitigate the harmful effects of CP on the male reproductive system. In conclusion, our findings showed that olive's compounds can diminish the hazardous effects of CP on spermatogenesis in mice.

Exploring Changes in Thalamus Metabolites as Diagnostic Biomarkers in Idiopathic Generalised Epilepsy Patients Using Magnetic Resonance Spectroscopy.

INTRODUCTION: Idiopathic generalised epilepsy (IGE) refers to a group of epilepsies resulting from the activation of neurons in the whole brain. This study aimed to evaluate the metabolite changes in thalamus as diagnostic biomarkers in IGE patients compared to healthy individuals using magnetic resonance spectroscopy (MRS) technique. METHODS: The MRS was performed on 35 IGE patients (26 women and 11 men) with average age of 32 (ranged from 18 to 43) and 35 healthy individuals (13 women and 22 men) with average age of 31 (ranged from 21 to 50) as the control group. The levels of N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) were measured using MRS. The NAA/Cr and NAA/Cho ratios were calculated for all participants. These values were statistically compared using t-test between the groups. RESULTS: The NAA had significant lower values in IGE patients, 9.6 (SD = 0.8) and 9.9 (SD = 0.7) for right and left thalamus, respectively, compared to 10.9 (SD = 0.9) and 10.7 (SD = 0.9) in control group. The Cr values in the left side of thalamus were significantly higher in IGE patients (6.7 [SD = 0.8] versus 5.8 [SD = 0.5]); however, there was no difference in right thalamus. Measurements showed no difference for amounts of Cho between the groups in both sides of thalamus. The NAA/Cr ratio was 1.48 (SD = 0.14) and 1.48 (SD = 0.16) for right and left thalamus, respectively, in IGE patients in comparison with 1.83 (SD = 0.2) and 1.86 (SD = 0.26) in controls. There was no meaningful variation between the NAA/Cho ratio of the right and left thalamus among the groups. CONCLUSION: Thalamic NAA, Cr and NAA/Cr ratio values in IGE patients showed statistical differences compared to healthy individuals. Evaluating metabolites variations in thalamus using MRS is suggested for differentiating IGE patients from healthy individuals.

Effect of hydroalcoholic Allium atroviolaceum L. on the pathology of testicular tissue in cyclophosphamide-treated mice.

BACKGROUND: The most important side effects of Cyclophosphamide, as an anticancer broad-spectrum drug, are the negative effects on the reproduction and fertility because of oxidative stress. Considering the antioxidant properties of medicinal plants, especially those of the Allium genus, this paper studied the effect of hydroalcoholic extract of Allium atroviolaceum L. on the pathology of testicular tissue in CP-treated mice. METHODS: Groups of this experimental study consisted of normal saline recipients; three groups receiving A. atroviolaceum extract at 50, 100, 200 mg/kg; three groups receiving A. atroviolaceum extract at 50, 100, and 200 mg/g and 6.6 mg/kg of Cyclophosphamide; and a group given Cyclophosphamide at 1.6 mg/kg. All injections were performed intra-peritoneally. After 30 days, the testicular histological profile as well as the number of spermatozoa, the number of primary and round spermatocytes, and the number of spermatogonia were investigated. RESULTS: Cyclophosphamide treatment significantly reduced the lumen diameter, the seminiferous tubule diameter, the epithelial thickness, as well as decreased the quantity of spermatozoa and round and primary spermatocytes compared to the control group. Cyclophosphamide groups treated with A. atroviolaceum extract at 50, 100 and 200 mg/kg in a significant manner improved these variables (P < 0.001). CONCLUSION: A. atroviolaceum extract can significantly improve Cyclophosphamide-induced toxicity and pathological process on testicular tissue. It seems that this plant, with high antioxidant capacity, can be considered a complementary therapy for Cyclophosphamide to prevent undesirable effects on the reproductive system.

Biological Effects of Magnetic Resonance Imaging on Testis Histology and Seminiferous Tubules Morphometry.

OBJECTIVES: Spermatogenesis is a regular and lengthy process in which the function of testicular cells may potentially be influenced by several extrinsic and intrinsic stressors, including environmental factors such as magnetic resonance imaging (MRI) waves and radiation. Our study aimed to investigate the effects of MRI waves and fields on the testicular histology and morphometry of seminiferous tubules in mice. METHODS: The experiment was conducted on 40 adult Naval Medical Research Institute mice. The control group was located in the center of the MRI bore while it was turned off, while the exposed group was exposed to the active scanner for 36 minutes once a week for three weeks. Our study included four groups: group I (control group at one hour after last exposure), group II (experimental group at one hour after last exposure), group III (control group at 35 days after last virtual exposure), and group IV (experimental group at 35 days after last exposure). We then assessed the tube and lumen diameters, as well as epithelium thickness of the seminiferous tubules. RESULTS: Our data showed that MRI waves partially reduced testicular weight one hour after the last exposure (group II) compared to group I (p = 0.240). On the other hand, in group II the Johnson's score (score 10, complete spermatogenesis and perfect tubules) was 87.5% which was slightly less than recorded in groups I, III, and IV (91.4%, 92.2%, and 90.5%, respectively). Furthermore, the MRI in group II revealed induces vacuolization in the epithelium, arrest in primary spermatocytes in the pachytene stage as well as disruption in the testicular parenchyma. CONCLUSIONS: Long-term exposure to MRI waves has deleterious effects on the male reproductive system, fertility parameters, and the quantity of germ cells in the seminiferous tubules with the exception of the number of round spermatid cells and epithelial thickness. All these effects were reversible after a new period of spermatogenesis.

Role of CT scan in theranostic and management of traumatic spinal cord injury.

Traumatic spinal cord injury (TSCI) is a condition with suffering of neural structures from acute trauma with short-term or permanent sensory and motor problems. This study was conducted with the aim of determining the prevalence of TSCI in Tehran with emphasis on demographic characteristics of patients and to evaluate the effect of computed tomography (CT) in determining fracture type and severity grade of injury among TSCI patients. In a cross-sectional study, all TSCI and spinal fracture patients (N = 520) who referred to the main trauma center in Tehran, Iran, in 2013 and 2014 were selected. Radiography and CT scan were prepared and reported blindedly by two radiologists. Majority of the patients was 21-30 years male, married and their most common occupation was car driver. A significant difference was observed between gender and etiology (P = 0.001). The main etiology was traffic accident followed by falling from height. While the most common location of injury for males was thoracic vertebrae followed by lumbar vertebrae; for females it was lumbar followed by thoracic. Majority of patients had ASIA (American Spinal Injury Association) impairment scale of E (normal), followed by B (sensory incomplete). Most of the cases were hospitalized less than one week. Age of the patient and duration of hospitalization had a significant association (P = 0.015). The results showed that in traumatic spinal cord events, traffic accident and falling from height are the main etiologies; hence, authorities in Iranian health system could consider preventive policies to decline the load and TSCI effects in hospitals and population.

Radioprotective effects of Silymarin on the sperm parameters of NMRI mice irradiated with γ-rays.

Free radicals and reactive oxygen species (ROS) are generated using various endogenous systems or from external sources such as exposure to different physiochemicals. Ionizing radiation damage to the cell can be caused by the direct or indirect effects of radiotherapy processes. Silymarin (SM), a flavanolignan compound, has been identified as a natural potent antioxidant with cytoprotection activities due to scavenging free radicals. The aim of the present study was to evaluate the radioprotective effect of SM on sperm parameters of mice induced by γ-rays. A total number of 40 adult, male NMRI mice were randomly divided into four equal groups. The control group was neither treated with SM nor irradiated by γ-rays. The second group was only irradiated with 2Gy of γ-rays. The third group was firstly treated with 50mg/kg of SM for 7 consecutive days, and one day later, last injections were irradiated by 2Gy of γ-rays. The fourth groups received only 50mg/kg of SM for 7 consecutive days. All the animals were treated intraperitoneally. Histopathological and morphometrical examinations were performed. The data were analyzed using ANOVA and Tukey post hoc test. A value of p<0.05 was considered significant. The results showed that in the radiation-only group when compared with those treated with SM and irradiated, a significant different was observed in testicular parameters and DNA damage (p<0.05). In conclusion, SM can be considered as a promising herbal radioprotective agent in complementary medicine which may play an important role to protect normal spermatocytes against possible effects of γ-radiation-induced cellular damage.

Color doppler indices of proximal and distal parts of middle cerebral artery in fetuses with intrauterine growth restriction.

INTRODUCTION: Intrauterine growth restriction (IUGR) is a major clinical issue for pregnant women. The purpose of this study was to evaluate color Doppler indices of the proximal and distal parts of the middle cerebral artery (MCA) of the fetus. METHODS: In this cross-sectional study, 350 pregnant patients, with gestation age of 32-40 who were suspected to have intrauterine growth restriction, participated. The patients were referred for color Doppler sonography at the Imam Reza Hospital (Kermanshah, Iran) from May 2011 to September 2012. The following indices were measured for the proximal and distal part of the MCA: pulsatility index (PI), resistive index (RI), fetal heart rate (FHR), systolic to diastolic (S/D) ratio, and peak systolic velocity (PSV). The data were analyzed applying Tukey's-test, Paired-Samples t-test, and simple linear regression analysis using SPSS 19. RESULTS: Average age of the mother, the frequency of pregnancy, and fetus gestational age were 27.79±0.17 years, 2.09±1.3, and 34.19±2.52 weeks, respectively. For gestation age of <36weeks, all Doppler indices of the distal part of the fetus MCA were significantly different from those of proximal part (p<0.05). Comparing indices of gestation age <36 weeks with those of >36 weeks, significant difference was found between the Doppler indices of the proximal parts as well as for the distal parts (p<0.05). CONCLUSION: Measurement of fetus MCA indices may depend to the sampling location; however, this needs further investigation in order to find a clear probe location.

MicroRNAs-Based Imaging Techniques in Cancer Diagnosis and Therapy.

Cancer is one of the most serious global health concerns in different populations. Several studies indicated that there are many potentially promising cellular and molecular targets for cancer therapy within cancer cells and their microenvironment. Among different cellular and molecular targets involved in cancer pathogenesis, microRNAs (miRNAs) are well known as key targets for cancer therapy. miRNAs are one of main classes of non-coding RNAs. These molecules play important roles in different critical processes of cancer pathogenesis. Hence, this makes miRNAs as a suitable tool for cancer diagnosis and therapy. There are different approaches for monitoring miRNAs in cancer patients. Some conventional approaches including next-generation sequencing, real-time polymerase chain reaction (PCR), northern blotting, and microarrays could be used for assessment of miRNAs expression. Some studies revealed that the utilization of these approaches associated with various limitations. Recently, it has been revealed that molecular imaging techniques are powerful tools for monitoring of different cellular and molecular targets involved in various diseases such as cancer. These techniques help investigators to investigate and monitor miRNAs functions through assessing different targets by fluorescent proteins, bioluminescent enzymes, molecular beacons, as well as various nanoparticles. Therefore, utilization of molecular imaging techniques could assist investigators to better monitor and more effectively treat patients during different phases of malignancy. Here, we give a review on the current state of miRNAs-based imaging techniques in cancer diagnosis and therapy. J. Cell. Biochem. 118: 4121-4128, 2017. © 2017 Wiley Periodicals, Inc.

Efficacy of Multidetector-Row Computed Tomography as a Practical Tool in Comparison to Invasive Procedures for Visualization of the Biliary Obstruction.

INTRODUCTION: Recently, multidetector computed tomography (MDCT) has been introduced into clinical practice. MDCT has become the noninvasive diagnostic test of choice for detailed evaluation of biliary obstruction. AIM: the main objective of the present study was to evaluate the diagnostic value of MDCT compared to invasive procedures for detecting biliary obstruction causes. MATERIAL AND METHODS: Since February 2009 until May 2011 fifty biliary obstruction patients based on clinical, laboratory or ultrasonographic findings, were evaluated by Multidetector-row computed tomography. The causes of biliary obstruction, which was identified using. MDCT were classified into three categories: calculus, benign stricture, and malignancy. Final diagnosis was conducted based on percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangiopancreatography, biopsy, or surgery. The MDCT diagnosis and were compared with the final diagnosis. RESULTS: A correct diagnosis of causes of biliaryobstruction was made on the basis of MDCT findings for 44 of the total 50 patients. Two patients with chronic pancreatitis were incorrectly diagnosed with a pancreatic head adenocarcinoma on the basis of MDCT findings. One patient with biliary stone was incorrectly diagnosed with a periampullary adenocarcinoma on the basis of MDCT findings. The Sensitivity, specificity and accuracy of MDCT in the diagnosis of causes of biliary obstruction were 94.12% and87.87% and94.6% respectively. CONCLUSION: Based on the findings of this study MDCT has an excellent image quality, providing valuable information about the biliary tree and other abdominal organs. The use of advanced image processing, including maximum intensity projection and multiplanar reconstruction (especially coronal or sagittal reformatted images), allows superior visualization of the biliary tree and vascular structures. Three-dimensional reconstruction images complement axial images by providing a more anatomically meaningful display of the lesion and its relationship to adjacent structures, and accurate determining the craniocaudal extent of the lesion. High accuracy, wide availability and ease of use, make the MDCT the imaging modality of choice for evaluation of biliary obstruction.

Evaluation of mouse embryos produced in vitro after electromagnetic waves exposure; Morphometric study.

INTRODUCTION: Today, the use of electromagnetic waves in medical diagnostic devices, such as magnetic resonance imaging (MRI), has increased, and many of its biological effects have been reported. The aim of the present study was to assess the biological effects of 1.5 Tesla (T) magnetic resonance imaging (MRI) on fertility and reproductive parameters. METHODS: Eighty adult male and female NMRI mice (NMRI: Naval Medical Research Institute) of age 6-8 weeks were studied and randomly divided into two study and control groups. After confirmation of pregnancy, the mice in the study group were exposed to the MRI (1.5 T) machine's waves over the next three weeks, once a week for 36 minutes. One day and thirty-five days after the last radiation, the mice were killed in order to do the in vitro fertilization (IVF) by neck beads' displacement and the impact on the evolution of embryos, and its quality was studied. Data were analyzed using SPSS version 20 and the significance level of less than 0.05 was considered. RESULTS: Embryo morphometry showed that the total diameter and the cytoplasm diameter of the study group embryos suffered significant reduction compared to the control group, 1 day after the last irradiation (p < 0.05), but the diameter of the perivitelline space of this group's embryos had a significant increase (p < 0.05). The qualitative results during 35 days after irradiation showed that morphologically parameters of the embryos in the study group had no significant differences from the control group. CONCLUSION: Exposure to MRI irradiation can transiently disturb the development of mouse embryos and fertility, but these effects are reversible 35 days after the last irradiation.

Prognostic investigations of B7-H1 and B7-H4 expression levels as independent predictor markers of renal cell carcinoma.

In order to evaluate the correlation of B7-H4 and B7-H1 with renal cell carcinoma (RCC), we analyzed B7-H1 and B7-H4 expressions and their clinical significance by immunohistochemical method. Our result indicated that B7-H4-positive staining was detected in 58.13 % of RCC tissues (25 tissues tumors), and there were 18 tissues of patients without detectable B7-H4. Furthermore, 21 cases (48.83 %) were B7-H1-positive. Positive tumor expressions of B7-H4 and B7-H1 were markedly related to advanced TNM stage (P = 0.001; P = 0.014), high grade (P = 0.001; P = 002), and larger tumor size (P = 0.002; P = 024) in RCC tissues than patients with B7-H4-negative and B7-H1-negative in RCC tissues. The patients with B7-H1 and B7-H4-positive expressions were found to be markedly correlated with the overall survival of the patients (P < 0.05) and tended to have an increased risk of death when compared with negative expression groups. Univariate analysis showed that B7-H4 and B7-H1 expressions, TNM stage, high grade, and tumor size were significantly related to the prognosis of RCC. Furthermore, multivariate analysis showed that B7-H4 and B7-H1 expressions decreased overall survival. The adjusted HR for B7-H1 was 2.83 (95 % CI 1.210-2.971; P = 0.031) and also was 2.918 (95 % CI 1.243-3.102; P = 0.006) for B7-H4 that showed these markers were independent prognostic factors in RCC patients. The expressions of B7-H1 and B7-H4 in RCC patients indicate that these markers may be as a predictor of tumor development and death risk. Further investigations can be helpful to confirm B7-H1 and B7-H4 roles as an independent predictor of clinical RCC outcome.

Diagnostic efficacy of sonography for diagnosis of ovarian torsion.

OBJECTIVES: Misdiagnosing ovarian torsion is now suggested as an important issue in clinical setting. The aim of this study was to determine the diagnostic accuracy of sonography for ovarian torsion. Methods : In this study 323 women with acute pelvic pain with highly suspected ovarian torsion signs and symptoms attending Imam Reza Medical Center in Kermanshah between 2011 through 2012 were included and underwent a transabdominal sonography (2-5 MHz probes). Then findings of sonography were compared with laparatomy. Results : The ultrasound correctly diagnosed 72.1% of ovarian torsion and missed 27.9% of them (false negatives). However, one free subject (0.4%) was misclassified as ovarian torsion (false positive). There was a strong correlation between sonography and laparatomy with a kappa value of 84.0%. The sensitivity and specificity of sonography were 72.1% and 99.6%, respectively. Sonography had a positive predictive value of 96.9%, a negative predictive value of 95.9%, and a total accuracy of 96.0% for detection of ovarian torsion. CONCLUSION: Sonography appears to be an excellent method to evaluate patients with suspected ovarian torsion. Abnormal blood flow detected by sonography is highly predictive of ovarian torsion and is therefore useful in the diagnosis of this phenomenon.