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2.  Subtypes of Benign Breast Disease as a Risk Factor for Breast Cancer: A Systematic Review and Meta-Analysis Protocol 
Breast cancer is a multifactorial disease. Benign breast disease (BBD) is one of the most important risk factors for breast cancer. The etiology of BBD is unknown. It is divided into nonproliferative and proliferative diseases. The selection of studies will be based on titles, abstract screening, inclusion and exclusion criteria, and quality assessment. Previous studies have shown that all types of BBD increase the risk of breast cancer, but the risk degree is different for each one. Accurate risk estimation of breast cancer in each category can be very important for proper clinical management. This systematic review and meta-analysis will be conducted on observational studies (traditional case control, nested case control, case cohort, and cohort) published in the Web of Science (ISI), PubMed (MEDLINE), Scopus, Google Scholar, and the key journals of this field such as Breast Cancer Research and Treatment and Cancer Research from January 2000 to June 2015. Reference lists and gray literature will be reviewed too. All the initial retrievals will be performed by 2 researchers independently. The data extraction form will consist of general information concerning the studies, study eligibility, method, risk of bias assessment, and results—including odds ratios, risk ratios, rate ratios, and hazard ratios. The PRISMA and MOOSE guidelines will be used to report our findings. Registration Details: PROSPERO-42016035243
PMCID: PMC5775989
Fibrocystic breast disease; Mammary dysplasia; Breast neoplasms; Risk factors; Systematic review
3.  Inhibition of the CatSper Channel and NOX5 Enzyme Activity Affects the Functions of the Progesterone-Stimulated Human Sperm 
Low levels of reactive oxygen species (ROS) and calcium are necessary for sperm function. NADPH oxidase 5 (NOX5) is a membrane enzyme which produces ROS. This enzyme is dependent on calcium for its activity. We investigated the importance of NOX5 and an important calcium channel (CatSper) on sperm function.
This laboratory in-vitro study was done in Shiraz, Iran, 2016. Normal semen samples (n=24) were washed and diluted to 20×106 sperm/mL. The diluted samples were divided into 8 groups, containing Ham’s F-10 (control group), 2 µM of NNC (CatSper channel inhibitor), 1 µM DPI (NOX5 inhibitor), and NNC+DPI. The other 4 groups were the same as the 1st ones, except that they contained 1 µM of progesterone. Motility assessment was done by VT–Sperm 3.1. Acrosome status was monitored with acrosome-specific FITC-PSA using fluorescent microscopy. Sperm viability was assessed by Eosin Y. Statistical analysis was performed using SPSS 16 software. The comparison between the groups was done using the one-way ANOVA, followed by Tukey. A P<0.05 was considered significant.
The percentage of motile sperm, sperm velocity, and viability decreased significantly in the groups containing NNC. DPI reduced sperm progressive motility only in the progesterone-stimulated condition. Progesterone induced acrosome reaction, but this effect was inhibited by NNC and DPI.
CatSper had a prominent role in the motility, acrosome reaction, and viability of the human sperm. The function of NOX5 was important only in the stimulated sperm. We conclude that CatSper has a more prominent role than NOX5 activity. The functional relation between NOX5 and CatSper is not clear but is very probable.
PMCID: PMC5775990
NOX5 protein; Human; CatSper; Progesterone; Sperm; Acrosome reaction
4.  Regression of Nonalcoholic Fatty Liver Disease with Zinc and Selenium Co-supplementation after Disease Progression in Rats 
Studies have shown that zinc and selenium deficiency is common in nonalcoholic fatty liver disease (NAFLD). However, the effects of zinc and selenium co-supplementation before and/or after disease progression on NAFLD are not clear enough. The aim of this study was to compare the effects of zinc and selenium co-supplementation before and/or after disease progression on NAFLD prognosis.
Materials and Methods:
Forty male Sprague–Dawley rats (197±4 g) were randomly assigned to 4 dietary groups: normal-fat diet (NFD; receiving 9% of calories as fat), high-fat diet (HFD; receiving 82% of calories as fat), supplementation before disease progression (S+HFD), and supplementation after disease progression (HFD+S). The diets were implemented over a 20-week period in all the groups. Biochemical and histologic parameters were compared between the 4 groups, and between-group comparisons were also carried out.
There were significant differences in the average food dietary intake (P<0.001), weight (P<0.001), fasting blood sugar (P=0.005), triglyceride (P<0.001), total cholesterol (P<0.001), low-density lipoprotein cholesterol (P=0.002), high-density lipoprotein cholesterol (P=0.001), alanine aminotransferase (P<0.001), and aspartate aminotransferase (P<0.001) between the 4 dietary groups. Serum triglyceride and total cholesterol were significantly lower in the HFD+S Group than in the S+HFD Group (P<0.001 and P=0.003, respectively). Fat accumulation was significantly reduced in the HFD+S Group (P<0.001).
Zinc and selenium co-supplementation after disease progression improved biochemical and histologic parameters in an experimental model of NAFLD.
PMCID: PMC5775991
Fatty liver; Trigelycerids; Lipid profile; Selenium; Zink; Cholestrol
5.  Effects of the Oral Ingestion of Probiotics on Brain Damage in a Transient Model of Focal Cerebral Ischemia in Mice 
Probiotics are microorganisms that may influence brain function via altering brain neurochemistry. New research evidence suggests that probiotic bacteria might protect tissue damage through diminishing the production of free radicals and/or inflammatory cytokines. Therefore, this study was designed to evaluate the effects of probiotic bacteria on the prevention or reduction of brain damage in an experimental model of stroke in mice.
In this study, 30 male BLC57 mice were randomly divided into 6 equal groups. Focal cerebral ischemia was induced via middle cerebral artery occlusion for 45 minutes, followed by 24 hours of reperfusion, in the mice. Probiotics at a concentration of 107 CFU/mL were administered by oral gavage daily for 14 days before ischemia. Infarct size, neurological outcome, and biochemical markers were measured 24 hours after brain ischemia. Statistical analysis were performed using the one-way ANOVA and/or Kruskal–Wallis ANOVA on rank by Sigma Stat (2.0; Jandel Scientific) software.
Our results indicated that pretreatment with probiotics significantly reduced infarct size by 52% (P=0.001) but could not improve neurological function (P=0.26). Moreover, the administration of probiotics significantly decreased the malondialdehyde content (P=0.001) and the tumor necrosis factor-alpha level (P=0.004) in the ischemic brain tissue.
The findings of the present study showed that probiotic supplements might be useful in the prevention or attenuation of brain ischemic injury in patients at risk of stroke. Probiotics may open new therapeutic alternatives for the prevention of stroke. More preclinical and clinical studies are, however, needed to clarify their efficacy in cerebral stroke.
PMCID: PMC5775992
Probiotics; Focal cerebral ischemia; Tumor necrosis factor-alpha; Mice
6.  Radioprotective Efficacy of Lutein in Ameliorating Electron Beam Radiation-induced Oxidative Injury in Swiss Albino Mice 
Lutein, a carotenoid compound, has previously been studied for its antioxidant and medicinal properties as well as the moderate protection it confers against gamma radiation. This study aimed at evaluating the effects of lutein against radiation-induced hematological and biochemical changes in mice.
The optimized dose of the compound was orally administered for 15 days, and the mice were irradiated (6 Gy) on day 15 after the administration of the compound. The groups were divided (6 mice in each group) into normal control, radiation control, gallic acid control, 10% DMSO control, lutein control, and irradiated groups pretreated with gallic acid, 10% DMSO, and lutein. Gallic acid was used to maintain a standard since it is a proven radioprotector. Within 24 hours post irradiation, the animals were anesthetized and sacrificed. The hematological, biochemical, and antioxidant changes were determined using suitable methods. Data were analyzed by the Kaplan–Meier curve (log-rank test) and ANOVA (the Tukey test). The independent t test was used to compare the independent groups. SPSS (ver. 16) was employed.
Maximum survival was observed with a dose of 250 mg/kg b.wt lutein. The total leukocyte count and the percentage lymphocyte count exhibited a significant decline in the irradiated groups pretreated with gallic acid and lutein in comparison to their controls, whereas the percentage granulocyte count showed a significant rise. Antioxidant activity had markedly declined in the irradiated groups, indicating oxidative stress. Lutein pretreatment reduced the damage and maintained the antioxidant system.
The present study suggests a protective role for lutein in palliating radiation-induced oxidative changes and maintaining the antioxidant system in vivo.
PMCID: PMC5775993
Antioxidants; Carotenoids; Lutein; Oxidative stress
7.  Antiproliferative Effects of Pancratium Maritimum Extracts on Normal and Cancerous Cells 
Plants are an important natural source of compounds used in cancer therapy. Pancratium maritimum contains potential anti-cancer agents such as alkaloids. In this study, we investigated the anti-proliferative effects of P. maritimum extracts on MDA-MB-231 human epithelial adenocarcinoma cell line and on normal lymphocytes in vitro.
Leaves, flowers, roots, and bulbs of P. maritimum were collected and their contents were extracted and diluted to different concentrations that were applied on MDA-MB-231 cells and normal human lymphocytes cell in vitro for different intervals. Cells viability, proliferation, cell cycle distribution, apoptosis, and growth were evaluated by flow cytometry and microscopy. Parametric unpaired t-test was used to compare effects of plant extracts on treated cell cultures with untreated control cell cultures. IC50 was also calculated.
P. maritimum extract had profound effects on MDA-MB-321 cells. It inhibited cell proliferation in a dose- and time-dependent manner. The IC50 values were 0.039, 0.035, and 0.026 mg/ml after 48, 72, and 96 hours of treatment with 0.1 mg/ml concentration of bulb extract, respectively. Those values were 0.051 and 0.03 mg/ml after 72 and 96 hours for root extract, respectively, and 0.048 mg/ml after 96 hours for flower extract. There were no significant effects of P. maritimum bulb extracts on normal lymphocytes proliferation.
P. maritimum extract has anti-proliferative effects on MDA-MB-231 cell line in vitro. The effects imply the involvement of mechanisms that inhibits cell growth and arresting cells at S and G2/M phases. Cyclin B1, Bcl-2, and Ki67 expression was also affected.
PMCID: PMC5775994
MDA-MB-231; Pancratium maritimum; Gene Expression; Cell Proliferation; Lymphocytes
8.  Evaluation of Psychopathology and Quality of Life in Patients with Anogenital Wart Compared to Control Group 
Anogenital warts (AGW) are one of the most common venereal diseases. Psychosocial complications and quality of life (QoL) of AGW patients have been considered only in recent years. Herein, the QoL and psychopathology in patients with AGW are evaluated. In total, 37 AGW patients and 37 healthy controls were recruited in the present cross-sectional study. All participants were provided with the symptom checklist 90-R (SCL-90-R) and short-form (SF-36) questionnaires. All analyses were performed using the SPSS software, version 16.0.1 for Windows. QoL was not significantly different between the study groups (P=0.12). The data showed that mental health, general health, and social functioning were significantly decreased in AGW patients (P<0.05). In addition, AGW patients were significantly more depressed and anxious than the control group (P=0.01 and P=0.04, respectively). AGW has adverse effects on psychological and QoL elements of the infected individuals. Psychological factors should be carefully considered when treating a patient with the HPV virus; hence, referral to a psychiatrist seems mandatory in these cases.
PMCID: PMC5775995
Anogenital wart; Quality of life; Psychopathology; Condylomata acuminate
9.  The Effect of Prophylactic Infusion of Combined Ephedrin and Phenylephrine on Maternal Hemodynamic after Spinal Anesthesia for Cesarean Section: A Randomized Clinical Trial 
Several techniques have been proposed to prevent hypotension in obstetric patients. Ephedrine and phenylephrine are individually used to prevent maternal hypotension; however, each has its own drawbacks. Some researchers have reported that the infusion of combined ephedrine and phenylephrine immediately after spinal anesthesia for cesarean delivery reduces the incidence of maternal hypotension. Other studies have indicated that the combination is not superior to the infusion of an individual agent. The present study aimed to evaluate the effect of prophylactic infusion of ephedrine and phenylephrine before the induction of spinal anesthesia for cesarean section on maternal hemodynamic. In a randomized, double-blinded clinical trial study, 90 pregnant women that underwent elective cesarean delivery under spinal anesthesia were recruited. Before the spinal anesthesia, the infusion of combined ephedrine and phenylephrine during 15 minutes (study group) or serum NaCl 0.9% (placebo group) was performed. Hemodynamic parameters and fetal blood gas were recorded. The data were analyzed using the SPSS software, version 16.0. The results showed that hypotension and bradycardia after spinal anesthesia were less in the study group. The need for vasopressors and inotropes to treat hypotension, nausea, and vomiting were higher in the placebo group. First- and fifth-minute Apgar scores were higher in the study group. The prophylactic infusion of low-dose ephedrine and phenylephrine before spinal anesthesia for cesarean delivery can be used to decrease the frequency and severity of maternal hypotension and its side effects to the mother and neonate. Trial Registration Number: IRCT201401277013N6
PMCID: PMC5775996
Cesarean Section; Anesthesia; Spinal; Hypotension; Ephedrine; Phenylephrine
10.  Classic versus Inguinal Approach for Obturator Nerve Block in Transurethral Resection of Bladder Cancer under Spinal Anesthesia: A Randomized Controlled Trial 
Single spinal anesthesia in transurethral resection of bladder tumor (TURBT) has been reported to be unable to prevent obturator nerve stimulation and adductor muscle contraction, which can cause complications like bladder perforation. The present study aimed to compare the effectiveness of the classic and inguinal approaches for obturator nerve block (ONB ). Seventy patients with cancers of the lateral wall of the bladder, scheduled to undergo TURBT at Imam Reza Hospital (Tabriz, Iran) during a 6-month period as of June 2016, were randomly allocated to groups of inguinal and classic methods (n=35). After the infusion of 500 mL of normal saline, spinal anesthesia was commenced using 3 mL (15 mg) of bupivacaine. Then ONB was performed using 10 mL of 1% lidocaine via the inguinal or classic approach in the inguinal group or the classic group, respectively. The success rate, defined as lack of post-block contraction with stimulation or during surgery, number of puncture attempts, time of block onset, and patient and surgeon satisfaction, was compared between the 2 methods using SPSS, version 19.
The success rate of ONB was significantly higher in the inguinal group (97.1% vs. 71.4%; P=0.003). The number of puncture attempts in the classic group was more than that in the inguinal group (3.71±1.10 vs. 1.66±0.68, respectively; P<0.001). The block onset time was shorter in the inguinal group (1.5±0.66 min vs. 2.9±1.18 min; P<0.001). Dissatisfaction of the patient (19 cases vs. 2 cases) and the surgeon (10 cases vs. no case) was higher in the classic group (P<0.001).
Compared to the classic approach, the inguinal approach for ONB appeared to be an easily performable, effective block with a high success rate, rapid onset, and good patient and surgeon satisfaction. Trial Registration Number: IRCT 201608171772N21
PMCID: PMC5775997
Obturator nerve block; Urinary bladder neoplasms; Transurethral resection; Inguinal approach; Classic approach
11.  Pachydermoperiostosis in a Patient with Crohn’s Disease: Treatment and Literature Review 
Pachydermoperiostosis (PDP) is a rare disorder characterized by pachydermia, digital clubbing, periostitis, and an excess of affected males. It is the primary form of hypertrophic osteoarthropathy (HOA) and there are some rare associations of PDP with other disorders. Here we describe a patient with Crohn’s disease associated with PDP. A 26-year-old man, who was a known case of Crohn’s disease, referred with diffuse swelling in the upper and lower limbs and cutis verticis gyrata since 7 years ago. PDP was suspected and endocrinological and radiological studies were conducted for the evaluation of underlying disease. He was prescribed celecoxib, low-dose prednisolone, and pamidronate to control the swelling, periostitis, azathiopurine, and mesalazine according to gastrointestinal involvement. In conclusion, it is important to identify this condition since a misdiagnosis might subject the patient to unnecessary investigations.
PMCID: PMC5775998
Pachydermoperiostosis; Cutis verticis gyrata; Crohn’s disease; Pamidronate
12.  Atypical Kawasaki Disease Presenting with Hemiparesis and Aphasia: A Case Report 
Kawasaki disease (KD) is an inflammatory vasculitis. KD is classified into two groups based on clinical characteristics criteria, namely classic and incomplete. Cerebral vascular abnormality, especially arterial ischemic stroke (AIS) is very rare and unusual in KD. Here, we report a 4-year-old boy who was referred to our tertiary pediatric center with abrupt right hemiparesis and aphasia. At admission time, he had febrile illness and was toxic. On physical examination, we found unilateral left submandibular lymphadenopathy. On neurologic examination, we obtained right sided hemiparesis with hemiparetic gait and aphasia. His deep tendon reflexes (DTRs) of right extremities were exaggerated and his sensory system was intact. Based on these features, some differential diagnoses were suggested, such as acute encephalitis with focal signs, brain abscess, cerebral vasculitis, hemorrhagic insults, and ischemic stroke, etc. After a complete evaluation, especially brain MRI and MRA, our diagnosis was arterial ischemic stroke (AIS) following atypical KD. Based on these findings, we administered intravenous immunoglobulin (IVIG 2 gm/kg) and oral high dose aspirin (100 mg/kg/d). He responded to these anti-inflammatory treatments dramatically.
PMCID: PMC5775999
Mucocutaneous lymph node syndrome; Stroke; Child; Vasculitis; Kawasaki disease
13.  Effects of Folic Acid on Appetite in Children with Attention Deficit Hyperactivity Disorder (ADHD) Treated with Methylphenidate: A Randomized Double-Blind Clinical Trial 
The highly effective medications in treating attention deficit hyperactivity disorder (ADHD) symptoms are stimulants like methylphenidate. However, they have adverse effects like reduced appetite. We investigated the effects of folic acid on reduced appetite caused by the use of methylphenidate in children with ADHD.
This randomized double-blind clinical trial evaluated 70 outpatients, aged between 6 and 12 years, with a diagnosis of ADHD. The children were recruited from the Outpatient Child and Adolescent Psychiatric Clinic of Golestan Hospital (Ahwaz, Iran) between 2016 and 2017. The study subjects were randomly assigned to 2 groups: Group 1 received an average dose of methylphenidate (1 mg/kg) plus folic acid (5 mg/d) and Group 2 received an average dose of methylphenidate (1 mg/kg) plus a placebo (5 mg of sucrose) for 8 weeks. Assessments, comprising the Conners Parent Questionnaire, anthropometric measurements, and appetite questionnaire, were conducted by a psychiatrist at baseline and then at 2, 4, 6, and 8 weeks after the medication was started using repeated measure analysis. The data were analyzed with the Mann–Whitney U and ANOVA tests using the SPSS statistical software (v. 18.0).
Age and gender were not associated with the groups. Weight, height, and the body mass index were not changed during the study in both groups. ADHD symptoms significantly decreased in both groups during the trial; however, no difference was observed between the groups. Moreover, appetite was significantly improved in Group 1. Both medications were well tolerated.
It seems that folic acid improved the reduced appetite caused by the use of methylphenidate in our children with ADHD. Trial Registration Number: IRCT2016040927304N1
PMCID: PMC5776000
Attention deficit disorder with hyperactivity; Methylphenidate; Folic acid; Clinical trial; Appetite
14.  Papillary Carcinoma of Thyroid with Nasal Cavity Metastases: A Case Report 
Papillary thyroid carcinoma (PTC) is one of the most commonly diagnosed types of differentiated carcinoma of the thyroid. It is stated that lung is the most common site of metastasis followed by bone. The incidence of paranasal sinus (PNS) metastasis is fairly uncommon in case of thyroid carcinoma. To the best of our knowledge, no case of metastatic PTC to nasal cavity has been reported. In this case report, we present the first case of papillary carcinoma of the thyroid with nasal cavity metastases in a 55-year-old female. The patient underwent surgical treatment and the mass was completely removed and sent for pathology. The pathology report revealed that it was metastatic papillary cell carcinoma. Surgical approach is usually difficult in view of the cosmetic and functional concerns, but may be considered in selected cases. As described herein, this rare type of metastasis was successfully removed and the patient was symptoms free after 1-year follow-up.
PMCID: PMC5776001
Thyroid neoplasms; Carcinoma; Papillary; Nasal cavity; Neoplasm metastasis
15.  Tubercular Mycobacterial Spindle Cell Pseudotumour: A Case Report 
Pseudotumour is a benign inflammatory lesion. Mycobacterial spindle cell pseudotumour (MSP) is a rare pseudotumour. It is a benign proliferation of spindle-shaped histiocytes containing acid-fast mycobacterium, commonly reported in immunocompromised patients. MSP is usually associated with mycobacterium avium complex (MAC). Here, we present the case of a 38-year-old gentleman with acquired immune deficiency syndrome (AIDS) who presented with low-grade fever for 1-month duration. Clinically, he had generalised lymphadenopathy. Chest X-ray showed miliary infiltration in bilateral lung fields. Lymph nodal biopsy showed spindle-shaped histiocytes filled with acid-fast bacilli on Ziehl-Neelsen (ZN) stain, suggestive of MSP. Immunohistochemical (IHC) stains were positive for CD68, S-100 and negative for CD31, which are consistent with MSP. Polymerase chain reaction (PCR) of the biopsy tissue was positive for MTB. Highly active antiretroviral therapy (HAART) was continued and anti-tubercular therapy (ATT) was started. The fever resolved within two weeks and there was a resolution of lymph nodal swelling by 6 weeks. The diagnosis of MSP associated with mycobacterium tuberculosis (MTB) makes our case interesting. It is of utmost importance to differentiate MSP from Kaposi’s sarcoma (KS) and other pseudotumours and to know whether it is of tubercular or non-tubercular origin, as the treatment is entirely different.
PMCID: PMC5776002
Acquired immunodeficiency syndrome; Biopsy; Mycobacterium tuberculosis (MTB); HIV; Spindle cell
16.  Isolated Peritoneal, Mesenteric, and Omental Hydatid Cyst: A Clinicopathologic Narrative Review 
Hydatid disease (HD) is caused by Echinococcus granulosus and is endemic in many parts of the world. This parasitic tapeworm can produce cysts in almost every organ of the body, with the liver and lung being the most frequently targeted organs. Peritoneum, omentum, and mesentery are among these unusual locations, which can cause diagnostic challenge and treatment delay. This review provides information on the reported cases of the peritoneal, omental, and mesenteric hydatid cyst in the world during the last 20 years. During the last 20 years, there have been 49 published cases of hydatid cysts in the peritoneum, mesentery, and omentum. Among the reported cases in the English literature, the most common presenting symptom has been chronic abdominal pain and the method of primary diagnosis has been ELISA and ultrasonography. The best treatment modalities have been surgical excision, with and without adjuvant therapy, with albendazole and scolicidal agents. The published follow-up studies showed a low recurrence rate.
PMCID: PMC5684372
Hydatid cyst; Peritoneum; Omentum; Mesentery; Echinococcosis
17.  Topical Effects of Artemisia Absinthium Ointment and Liniment in Comparison with Piroxicam Gel in Patients with Knee Joint Osteoarthritis: A Randomized Double-Blind Controlled Trial 
Pain alleviation and improvement of functional status are the main objectives in the treatment of osteoarthritis. Artemisia absinthium (AA) was used traditionally in reducing pain and inflammation. The aim of the present study was to compare the effects of topical formulations of AA and piroxicam gel (PG) among patients with knee osteoarthritis.
In total, 90 outpatients aged 30-70 years with the diagnosis of primary osteoarthritis in at least one knee were enrolled in a randomized double-blind clinical trial. The patients referred to the Rheumatology Clinic at Shahid Beheshti Hospital in Hamadan province during 2012-2013. The patients were randomly assigned into three groups, 30 patients per group, and respectively received AA ointment (AAO) 3%, AA liniment (AAL) 3%, and PG; three times daily (TID) for 4 weeks. The patients were visited at baseline, week 4, and week 6. The effectiveness criteria were pain severity which was assessed with a 10-point visual analog scale (VAS), the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) for total pain score (WTPS), total physical function score (WTPFS), and total stiffness score (WTSS). Repeated measure ANOVA, paired t test and post hoc were used to compare variables. Statistical analysis was performed using the SPSS software, version 13.0 (SPSS Inc., Chicago, Illinois).
All groups had similar patient demographics. The administration of PG significantly improved all tested criteria with no recurrence after discontinuing the treatment protocol. AAO alleviated all tested factors except for WTSS. Alleviation was comparable to PG. AAL only reduced pain factors (VAS, WTPS) in week 4 with recurrence in week 6.
Administration of Artemisia ointment may have beneficial effects in the treatment of osteoarthritis. Trial Registration Number: IRCT201202123109N3
PMCID: PMC5684373
Artemisia absinthium; Osteoarthritis; Piroxicam
18.  Adherence to the CONSORT Statement in the Reporting of Randomized Controlled Trials on Pharmacological Interventions Published in Iranian Medical Journals 
Among manuscripts submitted to biomedical journals, randomized controlled trials (RCTs) form the backbone of evidence-based medicine. Hence, their protocol should be designed rigorously and their results should be reported clearly. To improve the quality of RCT reporting, researchers developed the CONSORT Statement in 1996 and updated it in 2010. This study was designed to assess the quality of RCT reporting vis-à-vis adherence to CONSORT among articles published in Iranian medical journals (English, Persian, CONSORT-endorsing, and non-CONSORT-endorsing).
In this cross-sectional study, all RCTs published in all Iranian medical journals from September 2012 to September 2013 were retrieved to evaluate their adherence to CONSORT. The journals’ instructions for authors were also reviewed to find out whether or not they endorsed CONSORT. The CONSORT 2010 Checklist was used. Microsoft Excel 2007 was applied to analyze the data, and MedCalc was employed to compare the groups.
Totally, 492 pharmacological RCTs that met our inclusion criteria were identified. Twenty-five items were reported in fewer than 50% of the articles. The differences between the articles published in Persian and English language journals were statistically significant in 17 items. The differences between the articles published in the CONSORT-endorsing and non-CONSORT-endorsing journals were significant in 8 items.
Our findings showed very weak adherence to CONSORT. Authors, reviewers, and editors should be trained to use standards expressed by the CONSORT Group in reporting RCTs.
PMCID: PMC5684374
Randomized controlled trial; Checklist; Guideline adherence; CONSORT; Journal article; Standards
19.  Cerebral Ischemia-Reperfusion Injuries in Vanadyl-Treated Diabetic Rats 
Ischemic stroke recovery is poor in diabetic mellitus (DM). Vanadium compounds (vanadium) relieve DM signs, but their influences on cerebral ischemia/reperfusion injury (I/RI) are inconclusive. Herein, the intensity of I/RI was inspected in vanadium-treated DM rats.
Rats made diabetic with a single intravenous dose of streptozocin (39 mg/kg). Normal and DM rats used water or vanadyl solution for 45 days. Under isoflurane anesthesia, right middle cerebral artery occlusion was performed for 60 minutes and 12 hours reperfusion. Ischemic rats were divided into untreated-control normal (ICN) and diabetic (ICD), vanadium-treated normal (IVTN) and diabetic (IVTD) groups (n=14 each). After neurological deficit score (NDS) test, the rats were sacrificed and their brain removed and stained with triphenyltetrazolium chloride (TTC) to measure cerebral infarct volume (CIV, mm3) or Evans blue extravasation (EBE, μg/g wet-tissue). Data analysis was performed using one-way ANOVA and Tukey’s test (SPSS software, version 21.0) and P values <0.05 were considered statistically significant.
Blood glucose (BG, mg/dL) was similar in ICN and IVTN, elevated in IVTD and ICD (245±6 vs. 344±2, P<0.001). The increased CIV in ICN and IVTN was similar (48±2 and 34±5), very high in ICD but lower in IVTD (249±37 vs. 110±16, P<0.001). EBE was absent in non-lesioned hemispheres, similarly increased in lesioned hemispheres of ICN and IVTN (14±1 and 13±1). EBE in IVTD was significantly lower than ICD (21±2 vs. 33±5, P=0.01).
I/RI was moderate in normoglycemia and did not change with vanadium. Hyperglycemia robustly intensified I/RI. Vanadium ameliorated hyperglycemia and reduced I/RI. Nonetheless, more investigations are required to link the mechanisms of vanadium on DM and stroke injuries.
PMCID: PMC5684375
Diabetes mellitus; Cerebrum; Ischemia/Reperfusion; Injury; Vanadium; Rat
20.  Antidiabetic and Antidyslipidemic Activities of the Aqueous Extract of Cochlospermum planchonii Leaves in Streptozotocin-Induced Diabetic Rats 
Diabetes mellitus is considered one of the 5 principal causes of death in the world and is recognized as a global public health issue because of its multifactorial facets affecting essential biochemical processes in the body. This study investigated the antidiabetic and antidyslipidemic activities of the aqueous extract of Cochlospermum planchonii (C. planchonii) leaves in streptozotocin (STZ)-induced diabetic rats.
Thirty adult female rats (Rattus norvegicus) weighing 153±3.41g were randomized into 6 groups of 5 animals each. STZ-induced diabetic rats were orally administered 50, 100, and 200 mg/kg body weight of the extract, respectively, once a day, and their blood glucose levels as well as variations of diabetes-associated biomarkers including alpha amylase, glucose-6-phosphate dehydrogenase (G6PDH), and lipid profile by the extract were monitored for 21 days. The results were expressed as means±SEMs and compared with repeated measures using SPSS, Data Editor, version 16.0.
The aqueous extract of C. planchonii leaves significantly reduced the blood glucose level in a dose-dependent manner, with the highest dose producing a 74.52% reduction after 21 days of administration, which compared significantly (P<0.01) with the control and metformin-treated groups. Similarly, STZ-induced diabetic mediated alterations in the serum lipids were significantly (P<0.01) restored by the extract. In addition, the aqueous extract of C. planchonii leaves significantly attenuated the decrease in the activity of G6PDH and the increase in the activity of α-AMY in the liver of the STZ-induced diabetic rats.
Overall, the aqueous extract of C. planchonii leaves could be used to manage diabetes and other related complications.
PMCID: PMC5684376
Cochlospermum planchonii; Plant Leaves; aqueous extract; Streptozocin; Diabetes Mellitus; Rats
21.  Effects of Subacute Administration of Co-Trimoxazole and Folic Acid on Ovarian Tissue in Adult Female Rats 
Previous studies have reported the antifertility activities of sulfonamides. This study was designed to evaluate the effects of co-trimoxazole and its co-administration with folic acid on ovarian tissue in female rats.
A total of 54 rats were randomly divided into 9 groups (n=6). Group I served as the control and group II (vehicle) received saline. Other groups, III to IX, received co-trimoxazole (30, 60, and 120 mg/kg; i.p.), folic acid (1 mg/kg; i.p.) or their combination for 14 days, respectively. The oocytes were obtained from each group at the end of the 14th days and scored for maturational status as germinal vesicle (GV), metaphase I (MI), or metaphase II (MII). The number of primordial follicle (PrF), primary follicle (PF), and secondary follicle in formalin-fixed ovaries were counted under light microscopy. The data were analyzed by one-way ANOVA followed by post-hoc Dunnet test using SPSS statistical software (version 17.0). Results were considered statistically significant at P<0.05.
Co-trimoxazole (60 and 120 mg/kg) treatment for 14 days caused a significant decrease in the number of GV (P=0.02, P<0.001), MI and MII (P=0.03, P<0.001), a significant increase in structural abnormalities, including PrF, PF and secondary follicle (P<0.001) as well as congestion, inflammation and necrosis of ovarian tissue compared to the vehicle group. Folic acid co-administration with co-trimoxazole reversed partially all these parameters compared to the co-trimoxazole group (P<0.001).
The data showed the adverse effects of co-trimoxazole on the ovarian maturational status and tissue structure which was reversed partially by folic acid co-administration in rats.
PMCID: PMC5684377
Cotrimoxazole; Folic acid; Ovarian maturation status; Ovarian histopathology; Rats
22.  Long-term Low-Intensity Endurance Exercise along with Blood-Flow Restriction Improves Muscle Mass and Neuromuscular Junction Compartments in Old Rats 
During the aging process, muscle atrophy and neuromuscular junction remodeling are inevitable. The present study aimed to clarify whether low-intensity aerobic exercise along with limb blood-flow restriction (BFR) could improve aging-induced muscle atrophy and nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction.
Forty-eight male Wistar rats, aged 23–24 months, were randomly divided into control, sham (Sh: subjected to surgery without BFR), BFR (subjected to BFR), exercise (Ex: subjected to 10 weeks of low-intensity exercise), Sh+Ex, and BFR+Ex groups. Forty-eight hours after the last training session, the animals were sacrificed and their soleus and extensor digitorum longus (EDL) muscles were removed. The hypertrophy index was calculated, and molecular parameters were measured using western blotting. Statistical analysis was done with ANOVA using SPSS (version 20), with a P<0.05 as the level of significance.
The control and Sh groups showed weight gain (P=0.001), whereas the Ex, Sh+Ex, and BFR+Ex groups had significant weight loss (P<0.001). The hypertrophy index of the soleus was significantly higher in the BFR+Ex group than in the control, Sh, and BFR groups (P<0.001). BFR+Ex induced significant hypertrophic effects on the EDL (P<0.001 vs. the control, Sh, Ex, and Sh+Ex groups, and P=0.006 vs. the BFR group). BFR+Ex also increased nAChRs in the soleus (P=0.02 vs. the control and Sh groups) and the EDL (P=0.008 vs. the control and Sh groups).
BFR plus mild exercise is a safe method with potential beneficial effects in protecting and augmenting muscle mass and nAChR clustering at the neuromuscular junction in old rats.
PMCID: PMC5684378
Aging; Blood-flow restriction; Exercise; Nicotinic acetylcholine receptors; Neuromuscular junction
23.  Effects of Saponin from Trigonella Foenum-Graecum Seeds on Dyslipidemia 
Saponins identified from fenugreek (Trigonella foenum-graecum) seeds are reported effective on dyslipidemia. However, the definite mechanism is still not elucidated systematically. In this study, we evaluate the effects of saponin extract on cholesterol absorption, metabolism, synthesis, and reverse cholesterol transport in vivo.
Saponin extract was prepared according to a craft established in our previous study. After the establishment of dyslipidemia model, 40 male Sprague-Dawley rats were divided into five groups, namely the control group (normal diet plus normal saline), HFD group (high fat diet plus normal saline), Lipitor group (high fat diet plus Lipitor (2 mg/kg)), and L, M, and H-saponin groups (high fat diet plus saponin in dosages of 6, 12, and 24 mg/kg, respectively). Rats were sacrificed at the end of the 9th week after treatment. Biochemical characteristics of rats were tested, histopathological sections of liver tissue were observed, and the protein and mRNA expression of related factors of cholesterol in the intestine and liver were determined. One-way ANOVA test (SPSS software version 11.5, Chicago, IL, USA) was used to determine statistically significant differences between the HFD and other groups.
In saponin groups, the serum lipid, bile acid efflux, anti-peroxide activities, and lipid area of liver tissue improved. Cholesterol 7alpha-hydroxylase and scavenger receptor class B type I elevated in the liver. 3-hydroxy-3-methylglutaryl coenzyme A reductase levels were suppressed in both the serum and liver. However, significant cholesterol efflux was not found and Niemann-Pick C1-Like 1 levels elevated in the intestine.
The mechanisms of saponin in Fenugreek effect on ameliorating dyslipidemia are probably related to accelerated cholesterol metabolism, inhibited cholesterol synthesis, and facilitated reverse cholesterol transport, but not cholesterol absorption.
PMCID: PMC5684379
Fenugreek; Saponins; Dyslipidemias; Cholesterol
24.  Deltamethrin-Induced Hepatotoxicity and Virgin Olive Oil Consumption: An Experimental Study 
Deltamethrin (DM) is a synthetic pyrethroid insecticide which can lead to pathological effects in mammals through oxidative stress. On the other hand, virgin olive oil (VOO) is a rich source of phenolic compounds with antioxidants. The aim of the present study was to determine the protective effects of VOO against DM-induced hepatotoxicity.
Thirty-six mice were randomly separated into 4 groups: vehicle group, VOO group, DM group, and DM plus VOO group. Immunohistochemistry of PARP, COX-2, and caspase-3 with the biochemical analysis of malondialdehyde and total antioxidant capacity levels were performed in the liver samples 5 weeks after gavaging. Statistical analysis was performed using SPSS, version 15. The data were compared between the groups using the Tukey multiple comparison tests and the analysis of the variance. A P value <0.05 was considered significant.
The malondialdehyde level in the liver was increased in the DM group (71.18±0.01), whereas it was significantly (P=0.001) decreased after VOO administration in the DM plus VOO group (39.59±2.43). While the total antioxidant capacity level in the liver was decreased in the DM group (3.05±0.05), it was significantly increased (P=0.03) after VOO administration in the DM plus VOO group (3.95±0.04). A greater expression of caspase-3 (P=0.008), COX-2 (P =0.004), and PARP (P 0.006) could be detected in the DM group, while it was significantly (P=0.009) attenuated in the DM plus VOO group. Also, the degeneration of hepatocytes, which was detected in the DM group, was attenuated after VOO consumption.
VOO exerted protective effects against DM-induced hepatotoxicity, which might be associated with its anti-apoptotic, anti-inflammatory, and antioxidative properties.
PMCID: PMC5684380
Decamethrin; Olive oil; Antioxidants; Inflammation; Apoptosis; Hepatotoxicity
25.  Impacts of Bone Marrow Stem Cells on Caspase-3 Levels after Spinal Cord Injury in Mice 
Spinal cord injury (SCI) is a drastic disability that leads to spinal cord impairment. This study sought to determine the effects of bone marrow stem cells (BMSCs) on caspase-3 levels after acute SCI in mice. Forty-two mice were randomly divided into 3 groups: control (2 subcategories), subjected to no intervention; sham (3 subcategories), subjected to acute SCI; and experimental (2 subcategories), subjected to SCI and cell transplantation. In the experimental group, 2×105 BMSCs were injected intravenously 1 day after SCI. The mesenchymal property of the cells was assessed. The animals in the 3 groups were sacrificed 1, 21, and 35 days after the induction of injury and caspase-3 levels were evaluated using a caspase-3 assay kit. The obtained values were analyzed with ANOVA and Tukey tests using GraphPad and SPSS. Based on the assessments, the transplanted cells were spindle-shaped and were negative for the hematopoietic markers of CD34 and CD45 and positive for the expression of the mesenchymal marker of CD90 and osteogenic induction. The caspase-3 levels showed a significant increase in the sham and experimental groups in comparison to the control group. One day after SCI, the caspase-3 level was significantly higher in the sham group (1.157±0.117) than in the other groups (P<0.000). Twenty-one days after SCI, the caspase-3 level was significantly lower in the experimental group than in the sham group (0.4±0.095 vs. 0.793±0.076; P˂0.000). Thirty-five days following SCI, the caspase-3 level was lower in the experimental group than in the sham group (0.223±0.027 vs. 0.643±0.058; P˂0.000). We conclude that BMSC transplantation was able to downregulate the caspase-3 level after acute SCI, underscoring the role of caspase-3 as a marker for the assessment of treatment efficacy in acute SCI.
PMCID: PMC5684381
Bone marrow transplantation; Mesenchymal stromal cells; Caspase-3; Spinal cord injuries; Mice

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