Caffeic Acid Phenethyl Ester With Mesenchymal Stem Cells Improves Behavioral and Histopathological Changes in the Rat Model of Parkinson Disease.

Introduction: Parkinson disease (PD) results from the destruction of dopaminergic neurons in the brain. This study aimed to investigate the protective effects of natural antioxidants such as caffeic acid phenethyl ester (CAPE) to maintain these neurons. Methods: CAPE is one of the main ingredients of propolis. Intranasal administration of 1-methyl-4-phenyl-2;3;4;6-tetrahydropyridine (MPTP) was used to generate a PD model in rats. A total of 2×bone marrow stem cells (BMSCs) were injected from the tail vein. Behavioral tests, immunohistochemistry, DiI, cresyl fast violet, and TUNEL staining were used to evaluate the rats 2 weeks after treatment. Results: In all treatment groups with stem cells, the DiI staining method revealed that the cells migrated to the substantia nigra pars compacta after injection. Treatment with CAPE significantly protects dopaminergic neurons from MPTP. The highest number of tyrosine hydroxylase (TH) positive neurons was seen in the pre-CAPE+PD+stem cell (administration of CAPE, then the creation of PD, finally injection of stem cells) group. The number of TH+cells in all groups that received CAPE was significant compared to groups that received the stem cells only (P<0.001). Intranasal administration of MPTP significantly increases the number of apoptotic cells. The lowest number of apoptotic cells was in the CAPE+PD+stem cell group. Conclusion: The results showed that the use of CAPE and stem cells in Parkinson rats caused a significant reduction in the apoptotic cells.

Chrysin-Enhanced Cytotoxicity of 5-Fluorouracil-Based Chemotherapy for Colorectal Cancer in Mice: Investigating its Effects on Cyclooxygenase-2 Expression

Abstract 5-fluorouracil (5-FU) has been recognized as an effective medication used to treat colorectal cancer (CRC); however, its administration is facing limitations due to some complications reported. It is also generally accepted that combination therapy is among strategies to improve chemotherapy efficiency. Therefore, chrysin, with its anticancer effects, in combination with 5-FU was investigated in the present study. Azoxymethane (AOM) as a carcinogenic substance along with dextran sodium sulfate (DSS) was additionally utilized to induce CRC in mice. The anticancer effects of chrysin were then evaluated using aberrant crypt foci (ACF) counting and percentage of pathologic lesions in epithelial tissues from distal colon. In this study, cyclooxygenase (COX-2) protein expression was correspondingly explored through immunohistochemistry (IHC). The results revealed that chrysin alone or in combination with 5-FU could decrease ACF counting and percentage of pathologic lesions in comparison with AOM (p<0.05). Moreover, the combination of chrysin (at a dose of 50 mg/kg) with 5-FU reduced COX-2 expression compared with 5-FU alone (p<0.001) or 5-FU in combination with chrysin at a dose of 100 mg/kg (p<0.05). Furthermore, the combined chrysin boosted 5-FU efficiency, so it was suggested as an auxiliary therapy for CRC.

Maternal aerobic running during mid or late gestation improves the quality of oogenesis and folliculogenesis in the ovary of neonatal rats: An experimental study.

BACKGROUND: Regular maternal exercise in pregnancy enhances the physiological, metabolic, and psychological health of mother and fetus. OBJECTIVE: To determine the effect of maternal aerobic running during mid or late gestation on plasma levels of estrogen and progesterone and the histological alterations in the ovary of neonatal rats. MATERIALS AND METHODS: Twenty-one female Wistar rats were randomly divided into experimental groups to exercises during the 2 nd or 3 rd wk of pregnancy (n = 14) and a control group (n = 7). After birth, the neonate's blood was obtained and the estrogen and progesterone levels were evaluated. The ovaries were then removed and used for histological investigations and apoptic assessment. RESULTS: Higher concentrations of estrogen and progesterone were found in the neonates of the experimental groups (p = 0.001) compared to the control group. The experimental groups had a large ovarian diameter (2 nd wk: p = 0.044; 3 rd wk: p = 0.005) and angiogenesis (2 nd wk: p = 0.003; 3 rd wk: p = 0.001). In addition, significant enhancements were seen in the the experimental groups in terms of the number (2 nd wk: p = 0.017; p = 0.035) and diameter (2 nd wk: p = 0.046; 3 rd wk: p = 0.004) of primordial follicles, as well as in the diameter of primary oocytes (2 nd wk: p = 0.073; 3 rd wk: p = 0.019) compared to the control group. Moreover, rats that exercised had a lower number of apoptotic primordial follicles than the control group (2 nd wk: p = 0.001; 3 rd wk: p = 0.001). CONCLUSION: It was shown that maternal aerobic running can lead to increased plasma levels of estrogen and progesterone, also improved histological characteristics of the ovary in neonatal rats.

H. pylori effects on ghrelin axis: Preliminary change in gastric pathogenesis.

Ghrelin and its receptors are present in the stomach, suggesting that the ghrelin axis plays an essential role in gastrointestinal complications. This investigation aimed to explore the effects of H. pylori infection and gastritis on serum ghrelin and ghrelin axis gene expression. In this study, we enrolled 68 adult ambulatory people referred for upper gastrointestinal endoscopy. The individuals were classified into three groups based on H. pylori infection and gastritis. Total serum ghrelin and tissue gene expression were tested with ELISA and quantitative RT-PCR, respectively. Serum ghrelin and mRNA expression were significantly lower in H. pylori-positive with gastritis subjects compared with both H. pylori-negative with and without gastritis. Growth hormone secretagogue receptor1a mRNA expression was not different between groups while GHSR1b expression was significantly higher in patients with H. pylori infection and gastritis. We propose the ghrelin axis intermediaries, such as GHSR1b, as a potential clinical target for gastric disorders.

Co-administration of 5FU and propolis on AOM/DSS induced colorectal cancer in BALB-c mice.

AIMS: Currently, the main problems with chemotherapy are its side effects, toxicity, and drug resistance. Propolis has biological activities, such as anti-inflammatory and anti-cancer properties. This study aims to examine the combined effects of 5-fluorouracil (5FU) and propolis on colorectal cancer (CRC) in mouse models. MATERIALS AND METHODS: The chemical composition of ethanolic extract of propolis was determined by gas chromatography-mass spectrometry (GC-MS). In this study, 49 male Balb/c mice (16-20 g) were divided in seven groups as a control group and experimental groups (treated and untreated CRC model [azoxymethane + dextran sodium sulfate]). This study was conducted in 8 weeks. To examine the anti-cancer effects of propolis, the number of aberrant crypt foci (ACF) was counted and the pathological lesions in the distal colonic epithelial tissue were diagnosed. In this study, the expression of beta-catenin (ß-catenin), induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) proteins, which play a major role in the incidence and progression of cancer, were determined. KEY FINDINGS: GC-MS analysis of propolis showed the presence of hydrocarbons, alcohols, ketones, terpenes, phenols, and flavonoids. Administering propolis in combination with 5FU reduced the number of ACFs and pathological lesions in comparison with cancer control groups (p < 0.0001) and 5FU-alone treatment (p < 0.05). The propolis combined with 5FU reduced the expression of Cox-2, iNOS, and ß-catenin proteins. SIGNIFICANCE: The results showed that propolis increased the efficiency of 5FU and could be taken into account as the adjunct therapy for colorectal cancer.

Co-administration of Aluminum Sulfate and Propolis Regulates Matrix Metalloproteinases-2/9 Expression and Improves the Uterine Leiomyoma in Adult Rat Model.

The aim of this study was to evaluate the effects of aluminum sulfate (alum) with propolis (PR) on uterine leiomyoma (UL) in rat model. One hundred and four female Wistar rats (180-200 g) were allocated into two main groups of control (Co, n = 8) and experiment (UL model [estradiol benzoate 200 µg/kg/IM twice/week/8 weeks] with/without treatment) defined in 13 subgroups with/without treatment with coil oil (UL + COi), PR (100 or 200 mg/kg) as UL + PR100 or 200, alum (35, 75 or 150 mg/Kg) as UL + AL 35, 75, or 150, and PR (100 mg/kg or 200) with alum (35, 75, or 150 mg/Kg) as UL + PR100 or 200 + AL35, 75, or 150. Subgroups received doses of therapeutics for 14 days (IP). In the end, rats were sacrificed, and the uteri were isolated for molecular and histopathological investigations. The myometrium thickness, collagen contents, and gene expression of MMP-2 and 9 increased significantly in experimental groups with/without treatment (P Ë‚ 0.05). PR administration (100 and 200 mg/kg) alone or with alum (35 and 75 mg/kg) significantly decreased myometrium collagen contents and the gene expression and protein concentration of MMP-2 and 9 compared with UL and UL + Coi subgroups (P Ë‚ 0.05). Alum (75 mg/kg) with PR (200 mg/kg) could improve UL features and reduce MMP-2 and 9 gene expression.

Evaluation of Interleukin 25 and Interleukin 25 Receptor Expression in Peripheral Blood Mononuclear Cells of Breast Cancer Patients and Normal Subjects.

[Figure: see text] Interleukin 25 (IL-25) is a ligand for IL-25 receptor (IL-25R) with apoptotic effect on breast cancer epithelial cells that are produced by peripheral blood mononuclear cells (PBMCs). In this study, we aimed to evaluate IL-25/IL-25R mRNA expression in PBMCs, and also investigate correlation of IL-25/IL-25R with tumor stages/grades in patients with breast cancer. PBMCs and serum were isolated from 30 patients with breast cancer and 18 normal subjects. ELISA test was conducted for IL-25 cytokine. Total RNA was isolated from 2 × 106 PBMCs and reverse transcribed to cDNA. Quantitative PCRs were performed for IL-25, IL-25R, and GAPDH genes. IL-25 mRNA expression in PBMCs of breast cancer patients (malignant and benign) was significantly lower than that in normal subjects, Also IL-25 expression in breast cancer patients with malignant tumor was significantly lower than that in nonmalignant patients. IL-25R expression in malignant patients was significantly higher than that of benign and normal subjects (P < 0.05). IL-25 in serum of normal subjects was higher than that of benign and malignant patients. There was a direct association between IL-25R expression and tumor grade/stage of cancer. In conclusion, IL-25 seems as a potential prognostic factor in the serum of breast cancer patients and reduction of IL-25 is associated with a higher grade/stage of cancer.

Effects of cigarette smoking on morphological features of platelets in healthy men.

OBJECTIVES: To assess the effects of cigarette smoking on thrombocytopoiesis and some platelet morphological parameters in healthy male smokers. METHODS: In this cross-sectional study, 542 consecutive healthy men (aged 20 to 88 years), referred to the laboratory of Fatemieh Hospital, Semnan, Iran, between November 2011 and November 2012 for checking up were enrolled. The subjects were divided into 2 groups of smokers (n=258 with frequency of 10 or more cigarette per day with more than 12 months duration of smoking) and non-smokers (n=284). The blood samples were extracted to examine values of platelet indices using an ABX Micros 60 cell counter. RESULTS: Comparing platelet indices across smokers and non-smokers showed that the mean platelet count was statistically significantly higher in adult smokers than in nonsmokers (264.1 ± 81.2/µl versus 247.7 ± 83.9/µl, p=0.021), while the mean plateletcrit value was contrarily lower in the adult smokers (18.0 ± 12.0% versus 25.0 ± 10.0%, p less than 0.001). Other platelet indicators were not discrepant between the smokers and non-smokers. CONCLUSION: Cigarette smoking in healthy individuals results in significant and considerable effects on platelet morphological indices. The mean platelet count is significantly increased, and plateletcrit values are reduced, compared with non-smoking status.

Designing and conducting in silico analysis for identifying of Echinococcus spp. with discrimination of novel haplotypes: an approach to better understanding of parasite taxonomic.

The definitive identification of Echinococcus species is currently carried out by sequencing and phylogenetic strategies. However, the application of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) patterns is not broadly used as a result of heterogeneity traits of Echinococcus genome in different regions of the world. Therefore, designing and conducting a standardized pattern should indigenously be considered in under-studied areas. In this investigation, an in silico mapping was designed and developed for eight Echinococcus spp. on the basis of regional sequences in Iran and the world. The numbers of 60 Echinococcus isolates were collected from the liver and lungs of 15 human, 15 sheep, 15 cattle, and 15 camel cases in Semnan province, Central Iran. DNA samples were extracted and examined by polymerase chain reaction of ribosomal DNA (rDNA) internal transcribed spacer 1 (ITS1) and PCR-RFLP via Rsa1 endonuclease enzyme. Moreover, 15 amplicons of cytochrome oxidase 1 (Cox1) were directly sequenced in order to identify the strains/haplotypes. PCR-RFLP and phylogenetic analyses revealed firmly the presence of the G1 and G6 genotypes with heterogeneity (three novel haplotypes) of Cox1 gene although no other expected genotypes were found in the region. Finding shows that the identification of novel haplotypes along with discrimination of Echinococcus spp. through regional patterns can unambiguously illustrate the real taxonomic status of parasite in Central Iran.

Evaluation of noninvasive tests for diagnosis of Helicobacter pylori infection in hemodialysis patients.

BACKGROUND: Hemodialysis is the most common method of renal replacement therapy for treatment of acute and chronic kidney failure. Helicobacter pylori (H. pylori) plays a major role in development of peptic ulcer, gastric neoplasms, and lymphoma as well as increased risk of cardiovascular disorders in hemodialysis patients. OBJECTIVES: In this study the diagnostic values of noninvasive tests [i.e. urea breath test (UBT), helicobacter pylori stool antigen test (HPSA) and serology] in diagnosis of H. pylori infection in hemodialysis patients have been studied. PATIENTS AND METHODS: All patients undergoing hemodialysis in Fatemieh Hospital, Semnan, Iran, were enrolled in the study, and their H. pylori status were assessed by using non-invasive tests including UBT, HPSA and serology. Patients with at least two out of 3 positive tests were considered infected with H. pylori. RESULTS: The sensitivity, specificity, and positive and negative predictive values of the tests used in diagnosing H. pylori infection were 62.5%, 65.4%, 62.5% and 65.4% for UBT, 100%, 72.2%, 58.3% and 100% for serology, and 100%, 75%, 60.9% and 100% for fecal antigen test, respectively. CONCLUSIONS: This study showed that H. pylori serology and stool antigen tests have higher diagnostic values than UBT, and they are more reliable than UBT in diagnosis of H. pylori infection in hemodialysis patients.

Percutaneous transvenous mitral commissurotomy: significance of echocardiographic assessment in prediction of immediate result.

BACKGROUND: The current study aims to identify demographic, clinical characteristics, echocardiographic and/or mitral valve morphological parameters that may predict the successful result of percutaneous transvenous mitral commissurotomy (PTMC).  METHODS: The medical records of 196 patients (48 males, mean age: 42.7 ± 11.5 years) who underwent PTMC were reviewed. Prior to PTMC, a combination of transthoracic and transesophageal echocardiography were used to investigate substantial mitral valve morphological subcomponents (thickening, mobility, calcification, and subvalvular thickness) and suitability for PTMC. The second transthoracic echocardiographic assessment was performed within six weeks after PTMC. Patients were divided into two categories of successful or unsuccessful according to PTMC results. Successful PTMC was defined as: final mitral valve area (MVA) ≥1.5 cm2 without a post-procedure mitral regurgitation (MR) grade >2. The significant predictor of the result was identified by comparing demographic data, initial echocardiographic assessments and mitral valve morphological scores within both groups.  RESULTS: The mean MVA increased from 1.0 ± 0.2 cm2 to 1.7 ± 0.4 cm2, and mitral valve mean gradient (MVMG) decreased from 11.5 ± 5.2 to 5.2 ± 3.3 mmHg (P < 0.001 for both). Successful results were obtained in 139 (70.9%) patients compared to unsuccessful results in 57 (29.1%). Unsuccessful results were due to suboptimal secondary MVA < 1.5 cm2 in 50 (25.5%) patients and post-procedure MR grade >2 in 7 (3.6%). Multiple logistic regression analysis indicated that young age, lower size of the left atrium (LA), and smaller degree of mitral valve thickness were the predictors of successful result.  CONCLUSION: Pre-procedure echocardiographic assessment appears to be helpful in predicting PTMC results. Successful PTMC is influenced by the patients' age, LA size, and mitral valve thickness.

The use of low-dose etanercept as an alternative therapy for treatment of ankylosing spondylitis: a case series.

During recent decades, biological medications play a crucial role for treating rheumatologic disorders and thus are strongly recommended for initial treatment of ankylosing spondylitis. However, because of high cost of biological drugs, the use of these drugs has been limited. In current series, we tried to assess safety of low-dose etanercept as a common usable biological drug in patients with ankylosing spondylitis. In a case-series study, 4 men with ankylosing spondylitis were treated with low-dose etanercept (25 mg/2 weeks) plus methotrexate (10 mg/week). Safety was assessed by measuring rate of differences in severity of clinical manifestations and level of C-reactive protein (CRP). After the completion of treatment with low-dose etanercept, inflammatory low back pain and morning stiffness was reduced lower than 30 min in all patients. Only one patient had baseline high serum ESR and positive CRP that was changed to negative following treatment protocol. At one-year follow-up, all participants continued their regular treatment regimen with the etanercept survival rate 100%. Neither side effects related to drug nor clinical complications were observed within the follow-up period. Our findings suggest that low-dose etanercept (25 mg/2 weeks) has an acceptable safety and effectiveness profile in individuals with ankylosing spondylitis and can be good alternative instead of conventional therapy with etanercept (25 mg two times per week).

Gabapentin Effect on Pain Associated with Heroin Withdrawal in Iranian Crack: a Randomized Double-blind Clinical Trial.

Gabapentin seems to be a safe and well tolerated medication for treating heroine dependence. This study examined the efficacy of gabapentin for relieving withdrawal-related pain due to heroin use. Sixty men were recruited from an inpatient psychiatric ward of Fatemieh hospital in Semnan and randomized to receive either placebo (n = 30) or gabapentin (1800 mg/day) (n = 30) for 7 days. Subjective Opioid Withdrawal Scale (SOWS) was measured as a self-administered scale for grading body pain at baseline, and on days 1, 2, 3, 4, 6, and 7. Mean of pain score had a significant decrease trend in both gabapentin and placebo groups. Pain severity during the most of detoxification duration was significantly lower in gabapentin group compared with the placebo group. It is suggested that gabapentin may have an effective role in removing heroin withdrawal-related pain.

Renal tubular dysfunction measured by N-acetyl-beta glucosaminidase/Creatinine activity index in children receiving antiepileptic drugs: a randomized controlled trial.

To evaluate renal side-effects of anti-epileptic medication by valproate (VPA) and carbamazepine (CBZ), we performed a prospective study to assess renal tubular function by measuring N-acetyl-ß glucosaminidase (NAG)/Cr activity index in epileptic children. The study was conducted on 112 children who were diagnosed with epilepsy (28 patients were observed before treatment with anti-epileptics, 28 children were administered VPA, 28 children were treated with CBZ, and 28 healthy children were selected age &sex matched for). An especial NAG assay kit was used for quantitative measuring of NAG in patient urine samples. The patients receiving VPA exhibited higher rate of NAG activity compared with the two groups which not receiving anti-epileptic drugs. Measurement of urinary NAG/Cr index in the children who received CBZ also, was significantly higher than those who were not administered anti-epileptic drugs. The measurement of NAG/Cr index in the VPA group was significantly higher than that in the CBZ group (NAG index: 2.75 versus 1.71). Children on anti-epileptic treatment with VPA or CBZ might demonstrate signs of renal tubular dysfunction, reflected by NAG/Cr activity index. This side effect can be potentially more occurred following VPA administration.

Prospective evaluation of a new "paper urease test" for ultra-rapid detection of Helicobacter pylori.

BACKGROUND: The purpose of this study was to determine the sensitivity, specificity, and positive and negative predictive values of a newly developed paper urease test (PUT) for ultra-rapid detection of helicobacter pylori (HP) in gastric mucosa. MATERIAL/METHODS: 100 patients (43 men) with a mean age of 57+/-6.8 years participated. Patients presenting for upper endoscopy with no recent exposure to HP-altering drugs were enrolled. Gastric biopsy specimens were tested by the PUT and histology methods, and then the patients underwent [13C] urea breath tests (UBT). HP was considered positive when either UBT or histology demonstrated it, and negative if HP was not detected in either UBT or histology. The PUT was reported at 15 minutes. RESULTS: 87 of 100 patients tested positive for HP. The PUT correctly identified 74 of 87 HP-positive and 13 of 13 HP-negative patients, yielding sensitivity, specificity, and positive and negative predictive values of 87%, 100%, 100% and 53.5%, respectively, in this population. CONCLUSIONS: Rapidly available and reliable results from the PUT can facilitate clinical decision prior to patient discharge from the endoscopy suite. We recommend PUT for screening of HP in endoscopy candidates, due to high specificity, rapid reaction, simplicity and low cost. A positive result shows a definite diagnosis, although a negative result needs further diagnostic methods.

Clinicopathological features of primary central nervous system lymphoma.

OBJECTIVE: To investigate the anatomic location, immunologic, and clinicopathological features of patients with primary central nervous system lymphoma (PCNSL). METHODS: From May 1993 to December 2004, at Shohada Hospital, Tehran, Iran, the clinical data of 110 PCNSL patients, including the age, sex, duration of symptoms, radiological findings, site of tumors, immune status, and history of immunocompromised state (such as organ transplantation, radiotherapy, steroid therapy or AIDS) were assessed. RESULTS: The mean age of the patients with PCNSL was 47.02 +/- 15.8 years. There were 42 female and 68 male patients. One hundred and six cases (96.3%) were diagnosed as B-cell lymphoma. Most of the PCNSL in our study are unifocal. More than 70% of tumors were in a cerebral hemisphere and periventricular location, usually involving the corpus callosum or basal ganglia. No patients had been in immunocompromised states. Symptoms of increased intracranial pressure or changes in personality, vision, or motor function are most common. Seizures are seen in approximately 10% of patients. The number of PCNSL cases showed a gradual rise in incidence. CONCLUSION: The results of this single hospital 12-year survey of PCNSL are in agreement with data from other single institutions and regional surveys concerning clinical features. However, in contrast with the literature, most of our patients were immunocompetent. The age at diagnosis is also lower than in most reports.