Protective effect of thymoquinone nanoemulsion in reducing the cardiotoxic effect of 5-fluorouracil in rats.

5-Fluorouracil (5-FU), which is one of the most widely used chemotherapy drugs, has various side effects on the heart. Thymoquinone (TMQ), the main bioactive component of Nigella sativa, has antioxidant and protective effects against toxicity. In this study, we investigated the protective effect of thymoquinone against cardiotoxicity caused by 5-FU in vitro and in vivo models. H9C2 cells were exposed to 5-FU and TMQ, and cell viability was evaluated in their presence. Also, 25 male Wistar rats were divided into five control groups, 5-FU, 2.5, and 5 mg TMQ in nanoemulsion form (NTMQ) + 5-FU and 5 mg NTMQ. Cardiotoxicity was assessed through electrocardiography, cardiac enzymes, oxidative stress markers, and histopathology. 5-FU induced cytotoxicity in H9c2 cells, which improved dose-dependently with NTMQ cotreatment. 5-FU caused body weight loss, ECG changes (increased ST segment, prolonged QRS, and QTc), increased cardiac enzymes (aspartate aminotransferase [AST], creatine kinase-myocardial band [CK-MB], and lactate dehydrogenase [LDH]), oxidative stress (increased malondialdehyde, myeloperoxidase, nitric acid; decreased glutathione peroxidase enzyme activity), and histological damage such as necrosis, hyperemia, and tissue hyalinization in rats. NTMQ ameliorated these 5-FU-induced effects. Higher NTMQ dose showed greater protective effects. Thus, the results of our study indicate that NTMQ protects against 5-FU cardiotoxicity likely through antioxidant mechanisms. TMQ warrants further research as an adjuvant to alleviate 5-FU chemotherapy side effects.

Thymoquinone protects against 5-Fluorouracil-induced mucositis by NF-κß and HIF-1 mechanisms in mice.

Mucositis is among the most common side effects of 5-Fluorouracil (5-FU) and other cancer therapeutic drugs. Thymoquinone (TQ), a bioactive constituent extracted from Nigella sativa, has antioxidant and anti-inflammatory properties and can modify acute gastrointestinal injury. To investigate the effects of TQ on mucositis induced by 5-FU, studied animals were divided into four groups: control, 5-FU unit dose (300 mg/kg) to cause oral and intestinal mucositis (OM and IM), TQ (2.5 mg/kg) and TQ (2.5 mg/kg) plus 5-FU. Due to The molecular mechanisms, it was confirmed that the expression of NF-κß and HIF-1 increases in OM. The serum levels of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), as well as pathological parameters, were assessed. Based on our results, the nuclear factor-kappa ß gene expression in the tongue was downregulated significantly in the 5-FU + TQ compared to the 5-FU. TQ treatment can diminish MDA, and a reduction in oxidative stress was shown. TQ could also reduce the severity of tissue destruction and damaging effects induced by 5-FU on the tongue and intestine. We also observed lower villus length and width in the intestine of the 5-FU group compared to the control group. According to our research's pathological, biochemical, and molecular results, treatment with TQ as an anti-inflammatory and antioxidant compound may be the potential to improve and treat 5-FU-induced OM and IM, and TQ could be used against cancer treatment drugs and exhibit fewer adverse effects.

Studying structural and rheological properties of alginate-whey protein isolate cold-set hybrid emulgels at various pH levels.

Effects of different pH values (4-7) and whey protein isolate (WPI) concentrations (0.5-1.5%) were evaluated on physical, mechanical, and rheological properties of cold-set alginate-based soybean oil hybrid emulgels. The pH value changes were more effective than WPI concentration changes on emulgel properties. According to syneresis and texture profile analysis results, 1% WPI was selected as the optimum concentration. The XRD analysis showed that calcium alginate (CA) emulgel at pH 6 had a different peak at 2θ of 14.8°, likely indicating the highest amount of ion-bridging and maximum number of junction zones. The homogeneity of CA and CA + WPI emulgels (determined by image entropy analysis) decreased by pH reduction from 7 to 4, which can be related to acid-induced intermolecular interactions between alginate chains. The rheological properties of CA and CA + WPI emulgels revealed predominant elastic character (G' > G'') at different pH values. Creep test results showed that the relative recovery of emulgel prepared at pH 7 and 5 was 18.10 and 63.83%, respectively, suggesting pH reduction contributed to increase in the elastic component of material. The findings of this study can be applied for developing structured cold-set emulgels as solid fat replacers in meat and dairy products.

The Effects of 8 Weeks of Levothyroxine Replacement Treatment on Metabolic and Anthropometric Indices of Insulin Resistance in Hypothyroid Patients.

BACKGROUND: Insulin resistance (IR) is an independent cardiovascular risk factor. IR predisposes to metabolic syndrome and diabetes. Meanwhile, little evidence exists about the effect of levothyroxine replacement treatment (LRT) on IR in hypothyroid patients. OBJECTIVE: To investigate metabolic and anthropometric indices of IR in hypothyroid patients before and after 8 weeks of LRT. METHODS: This pre-post study evaluated the 8 weeks outcomes of LRT on 66 patients with recently diagnosed hypothyroidism. Outcome measures included body mass index (BMI), waist circumferences (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), body fat percent (BF%), free thyroxin (FT4), triglyceride (TG), low density lipoprotein (LDL), fasting plasma levels of glucose (FPG) and insulin. Sex- specific cut offs of two metabolic indices i.e. the triglyceride-glucose (TyG) and the homeostasis model assessment (HOMA) were used for IR diagnosis. The changes in TyG and HOMA were also compared after LRT. RESULTS: Participants were overt and subclinical hypothyroidism 71% and 29%, respectively. After LRT the mean values of the following anthropometric indices significantly decreased: weight (79.61 vs. 78.64), BMI (29.53 vs. 29.2), WC (98.25 vs. 97.39) and BF% (35.34 vs. 34.95). After LRT the HOMA and TyG had no significant changes relative to their initial values. Also, IR that was determined on the basis of these metabolic indices more commonly observed in participants. CONCLUSION: Despite decreasing some anthropometric indices, the diagnosis of IR based on metabolic indices increased following 8 weeks LRT in hypothyroid cases.

The Role of Bulk and Interface Recombination in High-Efficiency Low-Dimensional Perovskite Solar Cells.

2D Ruddlesden-Popper perovskite (RPP) solar cells have excellent environmental stability. However, the power conversion efficiency (PCE) of RPP cells remains inferior to 3D perovskite-based cells. Herein, 2D (CH3 (CH2 )3 NH3 )2 (CH3 NH3 )n -1 Pbn I3 n +1 perovskite cells with different numbers of [PbI6 ]4- sheets (n = 2-4) are analyzed. Photoluminescence quantum yield (PLQY) measurements show that nonradiative open-circuit voltage (VOC ) losses outweigh radiative losses in materials with n > 2. The n = 3 and n = 4 films exhibit a higher PLQY than the standard 3D methylammonium lead iodide perovskite although this is accompanied by increased interfacial recombination at the top perovskite/C60 interface. This tradeoff results in a similar PLQY in all devices, including the n = 2 system where the perovskite bulk dominates the recombination properties of the cell. In most cases the quasi-Fermi level splitting matches the device VOC within 20 meV, which indicates minimal recombination losses at the metal contacts. The results show that poor charge transport rather than exciton dissociation is the primary reason for the reduction in fill factor of the RPP devices. Optimized n = 4 RPP solar cells had PCEs of 13% with significant potential for further improvements.

Pressure-Gradient Turbulent Boundary Layers Developing Around a Wing Section.

A direct numerical simulation database of the flow around a NACA4412 wing section at Rec = 400,000 and 5∘ angle of attack (Hosseini et al. Int. J. Heat Fluid Flow 61, 117-128, 2016), obtained with the spectral-element code Nek5000, is analyzed. The Clauser pressure-gradient parameter ß ranges from ≃ 0 and 85 on the suction side, and from 0 to - 0.25 on the pressure side of the wing. The maximum Re𝜃 and Reτ values are around 2,800 and 373 on the suction side, respectively, whereas on the pressure side these values are 818 and 346. Comparisons between the suction side with zero-pressure-gradient turbulent boundary layer data show larger values of the shape factor and a lower skin friction, both connected with the fact that the adverse pressure gradient present on the suction side of the wing increases the wall-normal convection. The adverse-pressure-gradient boundary layer also exhibits a more prominent wake region, the development of an outer peak in the Reynolds-stress tensor components, and increased production and dissipation across the boundary layer. All these effects are connected with the fact that the large-scale motions of the flow become relatively more intense due to the adverse pressure gradient, as apparent from spanwise premultiplied power-spectral density maps. The emergence of an outer spectral peak is observed at ß values of around 4 for λz ≃ 0.65δ99, closer to the wall than the spectral outer peak observed in zero-pressure-gradient turbulent boundary layers at higher Re𝜃 . The effect of the slight favorable pressure gradient present on the pressure side of the wing is opposite the one of the adverse pressure gradient, leading to less energetic outer-layer structures.

Prevalence of Enterotoxin Genes and Antibacterial Susceptibility Pattern of Staphylococcus aureus Strains Isolated from Animal Originated Foods in West of Iran.

OBJECTIVES: The aims of our study were to evaluate the prevalence of Staphylococcus aureus (S. aureus) strains in food samples of animal origin, examine their antibacterial susceptibility pattern, and to detect staphylococcal enterotoxin (SEs) genes and the mecA gene in isolated S. aureus strains using the polymerase chain reaction (PCR). . METHODS: A total of 1050 food samples including 671 raw milk and dairy products and 379 raw meats were collected between September 2013 and June 2014 in Hamadan, Iran. Food samples were analyzed for S. aureus identification. The antibiotic susceptibility pattern of all isolates was determined using the disk agar diffusion method followed by detecting mecA resistance gene using PCR. In addition, harboring of SE genes were determined using a multiplex PCR assay targeting nine genes. . RESULTS: A total of 98 (9.3%) S. aureus strains were isolated from 1050 food samples. Of the 98 isolates examined, the most frequent resistance was observed to erythromycin (30.6%), followed by tetracycline (29.6%), gentamicin (27.6%), clindamycin (26.5%), ciprofloxacin and rifampin (24.5%), trimethoprim-sulfamethoxazole (14.3%), and cefoxitin (5.1%). All cefoxitin resistant isolates were positive for mecA. The prevalence of SEs was 77.6% (n=76). Among the genes that code classic enterotoxins, sea was the most frequent and was carried by 25.5% of isolates, followed by see in 18.4%, sed in 11.2%, sec in 5.1%, and seb in 4.1% of isolates. Among the detected enterotoxins, seg was the predominantly identified enterotoxin gene in isolates with prevalence of 35.7%. The seh gene with prevalence of 1% and sei gene with 3.1% were other detected enterotoxins with low frequencies. . CONCLUSION: The high prevalence of SE genes detected indicates a potential risk for causing animal-originated food poisoning. The increasing prevalence of community-acquired MRSA and its emerging antibiotic resistance in foods is a serious problem for public health.

Ondansetron or placebo in the augmentation of fluvoxamine response over 8 weeks in obsessive-compulsive disorder.

The aim of this study was to investigate the efficacy and safety of ondansetron as an augmentative agent to fluvoxamine in the treatment of patients with obsessive-compulsive disorder (OCD). Forty-six men and women, aged 18-60 years, who fulfilled the diagnostic criteria of OCD on the basis of the DSM-IV-TR and had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of at least 21 were recruited into the study. The patients randomly received either ondansetron (8 mg/day) or placebo for 8 weeks. All patients received fluvoxamine (100 mg/day) for the first 4 weeks, followed by 200 mg/day for the rest of the trial. The patients were assessed using the Y-BOCS and the adverse event checklists at baseline, and the second, fourth, sixth, and eighth week. Forty-four patients completed the study. The Y-BOCS total score as well as the Y-BOCS obsession subscale score and compulsion subscale score showed significantly greater reduction in the ondansetron group than in the placebo group. There was no significant difference in adverse events between the two groups. In this 8-week double-blind randomized-controlled trial, ondansetron showed significant beneficial effect as an augmentative agent with fluvoxamine in patients with moderate to severe OCD and it was generally well tolerated.

Dental pulp polyps contain stem cells comparable to the normal dental pulps.

OBJECTIVES: Few studies investigated the isolation of stem cells from pathologically injured dental tissues. The aim of this study was to assess the possibility of isolation of stem cells from pulp polyps (chronic hyperplastic pulpitis), a pathological tissue produced in an inflammatory proliferative response within a tooth. STUDY DESIGN: Pulp polyp tissues were enzymatically digested and the harvested single cells were cultured. Cultured cells underwent differentiation to adipocytes and osteoblasts as well as flowcytometric analysis for markers such as: CD90, CD73, CD105, CD45, and CD14. In addition we tried to compare other characteristics (including colonigenic efficacy, population doubling time and the cell surface antigen panels) of these cells to that of healthy dental pulp stem cells (DPSCs). RESULTS: Cells isolated from pulp polyps displayed spindle shape morphology and differentiated into adipocytes and osteoblasts successfully. These cells expressed CD90, CD73, and CD105 while were negative for CD45, CD14. Number of colonies among 104 tissue cells was higher in the normal pulp tissue derived cells than the pulp polyps (P=0.016); but as polyp tissues are larger and contain more cells (P=0.004), the total number of the stem cell in a sample tissue was higher in polyps but not significantly (P=0.073). CONCLUSIONS: The cells isolated from pulp polyps fulfill minimal criteria needed for MSC definition; hence, it can be concluded that pulp polyps contain stem cells. Although pulp polyps are rare tissues in daily practice but when they are present, may serve as a possible new non-invasively acquired tissue resource of stem cells for affected patients. List of abbreviations: APC = allophycocyanin, BM = Bone Marrow, CFU-F = Colony Forming Unit Fibroblast, DPSC = Dental Pulp Stem Cell, FITC = fluorescein isothiocyanate, MNC = mononuclear cells, MSC = Multipotent Mesenchymal Stromal Cell, PE = Phycoerythrin, PerCP = Peridinin chlorophyll protein, PPSC = Pulp Polyp Stem Cell. Key words:Adult stem cell, chronic hyperplastic pulpitis, dental pulp stem cell, pulp polyp.

Serological surveillance of bluetongue virus in cattle in central Iran.

The aim of this study was to evaluate the seroprevalence and distribution of antibodies to the bluetongue virus (BTV) among dairy Holstein cattle of central Iran. From September 2010 to August 2011, 892 blood samples from Holstein dairy cattle were collected from healthy animals. Blood samples were divided according to type of farm (industrial and non-industrial), season (warm and cold), location (North, South, East, and West), cattle production groups (calf, heifer, dairy and dry) and age groups (under 6 months, 6 months-2 years and over 2 years). The sera were screened using a commercially competitive enzyme-linked immunosorbent assay (c-ELISA) kit. Twenty-four sera (2.69 %) were found to be positive for BTV. Bluetongue virus seroprevalence was significantly higher (χ(2)=8.29, df=3, p < 0.05) in cattle in southern locations as compared to those in other locations. Older animals (>2 years) showed a relatively higher seroprevalence, but the difference was not statistically significant (p=0.06). No statistically significant difference in BTV seroprevalence was noted between farming systems, seasons and cattle production groups (p > 0.05). The results demonstrate that the seroprevalence of BTV is low in cattle from the Isfahan province, central Iran. Further studies are needed to determine the serotypes and vectors of BTV in the central region of Iran.

Determination of square equivalent field for rectangular field in electron therapy.

Equivalent field for electron beams is considered by using pencil beam theory. According to the Fermi-Eyges model the dose distribution of an electron pencil beam has a Gaussian profile. For this function determination of mean square radial displacement scattering of electrons is important. In this study the contribution of back scatter electron has been taken into account by using the multiple scattering theories for calculating mean square radial displacement scattering. The dimension of standard equivalent field depends on depth and shape of treatment field. Here the depth under study is the depth that mean square radial displacement scattering is extremum and the shape of treatment field is rectangular. In this study four energies were used 6, 9,12 and 15 MeV electron beams of 2100C/D Varian Linac. Findings of this study are based on analytical calculations, which are in good agreement with other experimental data. The findings of this study that were resulted from formula, shows, for all circular fields of radius ≥LSE (lateral scattering equilibrium) were considered broad field and equivalent. For validating the findings, Percentage Depth Dose (PDD) and Output factors were measured in 15 MeV electron beams for 7 × 3-cm, 6 × 4-cm and 4 × 2-cm and their equivalent squares and equivalent circular fields and compared.

Intranasal oxytocin as an adjunct to risperidone in patients with schizophrenia : an 8-week, randomized, double-blind, placebo-controlled study.

BACKGROUND: Impairment of oxytocinergic function and/or oxytocin receptor genetic abnormalities has been demonstrated in patients with schizophrenia. Oxytocin reverses emotional recognition deficit and might restore sense of trust in patients with schizophrenia. Some short-term studies have shown efficacy and tolerability of oxytocin in patients with schizophrenia. However, there is a lack of evidence on the efficacy and tolerability of oxytocin in patients with schizophrenia beyond 3 weeks. OBJECTIVE: The objective of this study was to assess the efficacy and tolerability of oxytocin intranasal spray (given as an adjuvant to risperidone) in patients with schizophrenia. STUDY DESIGN: This was an 8-week, randomized, double-blind, placebo-controlled study. STUDY SETTING: Inpatients of two large referral psychiatric hospitals in Iran were recruited for the study. PATIENTS: Forty patients (male and female gender) aged 18-50 years with a diagnosis of schizophrenia (DSM-IV-TR) who were on a stable dose of risperidone for a minimum of 1 month and who were chronically partially responsive to antipsychotic monotherapy were included in the study. INTERVENTIONS: The patients were randomly assigned to oxytocin intranasal spray (Syntocinon(®); Novartis, Basel, Switzerland) or placebo intranasal spray containing normal saline (ACER, Tehran, Iran) for 8 weeks. Oxytocin spray was administered as 20 IU (five sprays) twice a day for the first week followed by 40 IU (ten sprays) twice a day for the following 7 weeks. Placebo spray was administered at the same dose as the oxytocin spray. In addition, participants were on a stable dose of risperidone (5 or 6 mg/day). OUTCOMES: The patients were assessed using Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 0, 2, 4, 6 and 8. Primary outcomes were the differences in the PANSS scores between the two groups at the end of the trial. Adverse effects were recorded using a checklist and the Extrapyramidal Symptom Rating Scale (ESRS) at baseline and at weeks 1, 2, 4, 6 and 8. RESULTS: All patients had at least one post-baseline measurement and 37 patients (19 in the oxytocin and 18 in the placebo group) completed the study. Repeated measure analysis of variance showed significant effect for time X treatment interaction on the PANSS total [F(2.291,87.065) = 22.124, p < 0.001], positive [F(1.285,48.825) = 11.655, p = 0.001], negative [F(2.754,104.649) = 11.818, p < 0.001] and general psychopathology [F(1.627,61.839) = 4.022, p = 0.03] subscale scores. By week 8, patients in the oxytocin group showed significantly greater improvement on the positive (Cohen's d = 1.2, 20 % vs. 4 % reduction in score, p < 0.001), negative (Cohen's d = 1.4, 7 % vs. 2 % reduction in score, p < 0.001) and general psychopathology (Cohen's d = 0.8, 8 % vs. 2 % reduction in score, p = 0.021) subscales and total (Cohen's d = 1.9, 11 % vs. 2 % reduction in score, p < 0.001) PANSS scores than the placebo group. Adverse effects including the sodium concentration change were similar between the two groups. CONCLUSION: Oxytocin as an adjunct to risperidone tolerably and efficaciously improves positive symptoms of schizophrenia. In addition, effects on negative and total psychopathology scores were statistically significant, but likely to be clinically insignificant. The interesting findings from the present pilot study need further replication in a larger population of patients.

Third-Degree Heart Block in Thalassemia major: A Case Report.

BACKGROUND: First and second-degree heart blocks are partly common rhythm disorders in thalassemic patients but complete heart block is a very rare complication of iron overload cardiomyopathy. CASE PRESENTATION: This 15-year-old boy, a known case of major ß-thalassemia was admitted to our emergency unit with dyspnea and cough because of decompensated heart failure. The electrocardiogram showed complete heart block with junctional escape rhythm. Interestingly, his previous electrocardiogram taken 2 months earlier, had some PVC and second degree, Mobitz type 1 (Wenckebach) heart block. After improvement of dyspnea and control of blood pressure in normal range, the patient was referred to ER. A dual-chamber permanent pacemaker was implanted and his symptoms improved, but he died 24 days after discharge from hospital. CONCLUSION: We present a rare case of complete heart block after a second-degree (Mobitz 1) heart block that was due to severe iron overload cardiomyopathy.

Prevention and management of dysphonia during anterior cervical spine surgery.

OBJECTIVES/HYPOTHESIS: Dysphonia is a common postoperative complaint following anterior cervical spine surgery (ACSS). The purpose of this study was to analyze voice outcomes following ACSS, to identify risk factors predicting vocal cord impairment, and to develop an algorithm for postoperative management of dysphonic patients. STUDY DESIGN: Retrospective cohort study. METHODS: This was a retrospective review of 815 consecutive patients undergoing ACSS from January 2000 to January 2009. All cases were performed using a team approach with a neurosurgeon and head and neck surgeon. Factors associated with voice change and vocal cord motion impairment were analyzed. RESULTS: The mean age of the cohort was 53 years (range, 13-88 years), with a male-to-female ratio of 1.2. There were 32 of 815 available patients (3.9%) who developed dysphonia following ACSS. Fiberoptic laryngoscopy demonstrated that only nine (1.1%) of these patients had ipsilateral vocal fold motion impairment. Of these nine patients, only one (0.1%) was found to have permanent vocal fold paralysis at 1-year follow-up. Factors that correlated significantly with voice change included kyphosis, revision surgery, and level C6-C7 surgery. Kyphosis was the only independent factor correlating with voice change. CONCLUSIONS: ACSS is a safe surgical procedure with a low incidence of postoperative dysphonia when exposure is provided by a head and neck surgeon. Team performance of ACSS appears to reduce laryngeal complications and optimize the management of temporary or permanent postoperative dysphonia.

Our experience with caustic oesophageal burn in south of Iran.

CONTEXT: The alkaline oesophageal burn (EB) is a very debilitating injury and common in the southern rural area of Iran, where the air conditioning systems are cleaned with an alkaline liquid, which is accidentally ingested by children. AIMS: The aim is to share our experiences with caustic injury in children. SETTINGS AND DESIGN: A 'before' and 'after' clinical trial. MATERIALS AND METHODS: From November 2006-2009, 35 cases of alkaline burns were referred to our center. All underwent flexible endoscopy and thereafter received steroid, antibiotic and H2 blocker. They subsequently underwent rigid oesophagoscopy, with grade IIb or higher burns, for inserting the two different kinds of stents. RESULTS: Four out of 10 (GIIa <) underwent dilatation occasionally. Fifteen (GIIb) with early large stent (eight weeks) developed complications (three antral contractures, one oesophagotracheal fistula, one tracheobronchial fistula, three perforations, three deaths, and the remaining cases had not undergone dilatation yet. Four out of 10 with (GIIb), who had small stents (Six months) and early gastrostomy needed dilatation every four to six weeks and all recovered, with no significant complications. CONCLUSIONS: Early use of gastrostomy prevents malnutrition in patients. Small size stents are much more tolerable for a prolonged time are not obstructed by saliva that washes the wall of the damaged oesophagus continuously and promotes healing.

Bowel perforation by crumpled paper in a patient presenting with acute abdominal pain.

Many of the abdominal foreign bodies are due to accidental ingestion. Our objective in this case report is to emphasize the importance of the enquiry about the foreign body in the differential diagnosis of acute abdominal pain. According to our knowledge, this is the first report of bowel perforation caused by paper ingestion. A 14-year-old boy with abdominal pain underwent exploratory laparotomy and was found to have abdominal pus and ileal perforation. A crumpled paper was found at the site of perforation. Postoperative enquiry revealed that the patient had ingested 10 crumpled papers. We highlight that recording the history is an important aspect in the management of patients with acute abdominal pain and that foreign bodies should be included in its differential diagnosis.