Therapeutic angiogenesis with exosomal microRNAs: an effectual approach for the treatment of myocardial ischemia.

Therapeutic angiogenesis presents a potential approach for treating ischemic heart diseases especially in patients who are not appropriate candidates for traditional approaches of revascularization. This approach acts through inducing the neovascularization or maturation of pre-existing collateral vessels into functional arteries to bypass the blocked arteries and restore perfusion to ischemic myocardium. Successful stimulation of local angiogenesis can be established by the cross talk between stem cells, endothelial cells, and cardiomyocytes, which is mainly mediated by paracrine communication accompanied by secreted exosomes. Exosomes are extracellular vesicles carrying a complex of signaling molecules, such as microRNAs (miRs) that can modulate the function of recipient cells. Such particles have been indicated to exert cardioprotective role through providing signaling cues for angiogenesis, an effect ascribed mainly to their miRs content. Exosomal miRs-mediated therapeutic angiogenesis has been under drastic preclinical and clinical studies. In the current review, it was aimed to summarize pro-angiogenic exosomal miRs released by various cell types mediating angiogenesis, including stem cells, endothelial cells, and cardiomyocytes, which appear to exert a therapeutic effect on the myocardial ischemia. In brief, secreted exosomal miRs including miR-210, miR-23a-3p, miR-424, let-7f, miR-30b, miR-30c, miR-126, miR-21, miR-132, miR-130a-3p, miR-214, miR-378, miR-126, miR-133, and let-7b-5p could protect against myocardial ischemia through inducing cardiac angiogenesis and vascular regeneration resulting in the increase blood flow to ischemic myocardium.

The prevalence of allergic fungal rhinosinusitis in sinonasal polyposis.

Allergic fungal sinusitis (AFS) is a noninvasive form of fungal rhinosinusitis with a prevalence of 6-9 % among all rhinosinusitis cases requiring surgery. The fungi causing AFRS have a great diversity and regional variation in the incidence of AFS has been reported worldwide. The aim of this study was to evaluate the prevalence of AFS among rhinosinusitis patients in the north east of Iran. In a prospective cross-sectional study 127 patients with sinonasal polyposis who were candidates for surgery were recruited. All cases were evaluated by sinonasal CT scan, Prick test for common regional allergens, total serum immunoglobulin E (IgE) level, and allergic mucin culture for fungi in suspected cases. Data analyses were done using SPSS version 13.0. Their mean age was 37.4 ± 11.6 years, the male-to-female ratio was 69/58. Eleven patients (9.45 %) met the AFS criteria. Nine cases had a positive culture for Aspergillus specimen and three for Alternaria. Prick test was positive for at least one allergen in 28 cases (22.05 %). The most common allergen was weed. The total IgE level was significantly higher in AFS patients. This study showed the prevalence of AFS among patients with nasal polyposis to be 9.45 %.

Coronary artery angiographic changes in veterans poisoned by mustard gas.

OBJECTIVES: We aimed to identify coronary artery involvement in mustard gas-poisoned patients. METHODS: We conducted a case-control study on 40 mustard gas-poisoned patients who underwent coronary artery angiography due to cardiac pain. The study was performed during a 3-year interval on patients who were referred to three main hospitals of Mashhad, Iran. The nonexposed control group consisted of 40 normal individuals who had undergone angiography for the same reasons. The primary outcome measurement was coronary artery involvement and its location. Data were collected through studying the angiography films. RESULTS: Among the 40 poisoned patients studied, 15 (37.5%) had coronary artery ectasia, mainly in the left anterior descending artery, but 25 (62.5%) did not. The same values were 2 (5%) and 38 (95%) in the nonexposed group, respectively, which was significantly different compared to the exposed group (p = 0.001). The odds ratio was 11.40. CONCLUSIONS: The prevalence of coronary artery ectasia in mustard gas-poisoned patients was 7.5 times more than in nonexposed controls. Considering the proposed odds ratio, the occurrence of coronary artery ectasia is around 11.4 times greater in mustard gas-poisoned veterans. This is the first study to suggest a strong correlation between mustard gas poisoning and coronary artery ectasia.

Hearing impairment in pregnancy toxemia.

OBJECTIVE: Preeclampsia, characterized by widespread endothelial damage and dysfunction, systemic toxicity, coagulation defects, and an increased systemic inflammatory response, poses some risk factors for hearing loss. STUDY DESIGN: A case-control study. SUBJECTS AND METHODS: Two groups with 37 preeclamptic and 38 healthy pregnant women were matched by age. Other factors that could possibly influence hearing were ruled out. Transient otoacoustic emission (TEOAE) was carried out for both groups before delivery and was repeated two weeks after delivery in cases of failure. RESULTS: We could not find any abnormality in the healthy pregnant women who underwent the TEOAE test, but five of the preeclamptic women failed the initial test before delivery. This condition was recovered two weeks later. Statistical analysis showed significant difference (TEOAE disturbances) between the two groups (P = 0.025). CONCLUSIONS: This study showed that pregnancy toxemia might have effects on hearing abilities.

Hearing impairment in the neonate of preeclamptic women.

OBJECTIVE: Preeclampsia is a critical condition that puts both pregnant women and their offspring at risk for multiorgan failure, including inner ear, due to systemic toxemia and vascular events. This study was done to determine the probable prevalence of hearing impairment in children whose mothers had pregnancy-induced hypertension, compared to those born to healthy mothers. METHODS AND MATERIALS: A cohort study was performed on two groups; the first group was made up of the offspring of preeclamptic women (n = 36) and the second was made up of offspring born to healthy mothers (n = 114). They were matched for sex and age. Other confounding variables that could have influenced the hearing were excluded. Transient evoked otoacoustic emission (TEOAE) and auditory brain response (ABR) tests were performed to screen hearing loss in each group. RESULTS: Failure rates in the first step for cases and controls were 33.33 percent and 12.76%, respectively, which showed a significant difference statistically (P = 0.001). However, the final results of the second TEOAE and ABR between the two groups were not statistically significant (P > 0.05). CONCLUSION: Although it does not seem that pregnancy toxemia plays a role in permanent hearing loss in neonates of affected mothers, it might have a transient effect on hearing.

Effect of Stem Cell Therapy on Patients' Quality of Life in Heart Failure with Reduced Ejection Fraction.

Introduction: Heart failure with reduced ejection fraction (HFrEF) is a debilitating disease in which Left Ventricular Ejection Fraction (LVEF) is ≤ 40%, and it involves various organs. Regarding the novelty of stem cell therapy in HF, we aimed at studying the effect of stem cell therapy on the QoL of patients with HFrEF. Materials and Methods: In a prospective study, 30 patients diagnosed with HFrEF who had undergone stem cell injection (study group) and 30 patients with HFrEF receiving guideline-directed medical therapy (control group) were recruited by convenience sampling during 2016 in Mashhad, Iran. Patients' quality of life, left ventricular ejection fraction and their disability degree were studied twice with a 3-month interval. For data analysis, paired t-test, chi2 and multivariate linear regression were used. Results: The mean age of study and control groups was 61.3±10.24 and 60.93±7.88 years respectively. Ninety percent of the cases and 56.7% of the controls were male (P=0.003). A significant difference in QoL was observed before and after treatment in each group (P<0.05). However, the QoL score showed no statistical difference between the two groups following treatment (P=0.13). The same result was achieved for LVEF (P=0.18); whereas the NYHA function class showed a significant difference between the two groups following treatment (P=0.017). Conclusions: According to the results, it seems that the treatment of HFrEF patients with stem cells is as effective as conventional therapies in improving the LVEF and QoL and more efficient than conventional treatments in increasing the patients' general satisfaction with life.

Efficacy of azithromycin versus systemic meglumine antimoniate (Glucantime) in the treatment of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) treatment is painful, and cosmetic results are often unsatisfying. Azithromycin has been reported to be effective in treatment of CL caused by Leishmania viannia braziliensis. The efficacy of azithromycin was compared with Glucantime in treatment of Old World leishmaniasis. Of 49 patients, 22 received 500 mg/day azithromycin for 5 days/month. Treatment cycles were repeated monthly to a maximum of 4 months; 27 patients received 60 mg/kg intramuscular meglumine antimoniate for 20 days. Both groups were followed up for 16 weeks. In the azithromycin group, 2 patients withdrew because of GI symptoms. The response rates of 20 patients (29 lesions) were as follows: full improvement, 10.3%; partial improvement, 27.6%; and 62.1%, no response. In the glucantime group with 27 patients (58 lesions), these rates were 34.4%, 13.8%, and 51.7%, respectively (P = 0.036). Azithromycin was determined to be not as effective as Glucantime in treatment of Old World CL.

Anti-Inflammatory Effect of Crocus sativus on Serum Cytokine Levels in Subjects with Metabolic Syndrome: A Randomized, Double-Blind, Placebo- Controlled Trial.

BACKGROUND/AIMS: A growing body of evidence supports an important role of inflammatory cytokines in the development and progression of the Metabolic Syndrome (MetS), which explains, at least in part, its relationship with an increased cardiovascular-risk. Several studies have reported the therapeutic-impact of crocus-sativus in a preclinical/clinical setting. Here we have explored the effects of crocus-sativus, on the serum concentrations of twelve serum cytokines in subjects with MetS in a randomized control trial. METHODS: Forty four adult volunteers, who met the diagnostic-criteria of MetS, were enrolled and randomly divided into 2 groups, to receive 100 mg/day crocus-sativus for 12 weeks. 12 cytokines, including IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, MCP-1, IFN-γ, EGF, and VEGF were measured using sandwich chemi-luminescence assays before/after therapy. RESULTS: Individuals with MetS who received crocus-sativus had significantly (P<0.05) lower levels of total-cholesterol, low density-lipoprotein-cholesterol and triglyceride (TG), fasting-blood-sugar and hsCRP, however the serum concentration of high density-lipoprotein-cholesterol markedly enhanced after therapy (e.g., TG level reduced from 148.86±71.49 to 101.90±38.19 after therapy, P= 0.003). Moreover, we observed that treatment with Crocus-sativus affected the serumconcentrations of some pro-/anti-inflamatory cytokines. In particular, the level of VEGF was increased from 12.64 pg/mL (95% CI: 9.60-17.67) to 16.59 (95% CI: 11.33-35.98, P= 0.033. Similar results were detected for IL-6 and EGF. CONCLUSION: Our findings provide a novel insight into the therapeutic effects of this therapy in MetS patients via perturbation of serum cytokines and reducing the levels of triglyceride and LDL/TC, but further studies are required in larger populations.

Evaluation of Coronary Arteries in Non-Ischemic Cardiomyopathies: A Case Report.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a congenital cardiac disease with myocardial involvement, most probably right ventricular (RV) dysfunction, accounting for 20% of sudden cardiac deaths. Characterized by the fibro-fatty infiltration of the RV free wall, ARVD/C presents in adolescents with ventricular arrhythmias and heart failure symptoms and as biventricular failure in adults. The coronary risk in these patients is not clear. We present an incidental finding: the left anterior descending artery cut-off in a middle-aged man with ARVD/C. He had been under treatment for heart failure symptoms, which had decompensated frequently commencing 6 months earlier, and therefore he was scheduled for stem cell injection. He had no chest pain or coronary artery disease risk factors. Two-dimensional transthoracic echocardiography demonstrated RV enlargement with moderate to severe dysfunction and left ventricular ejection fraction (LVEF) of 35-40%, which was 45-50% two years before. Selective coronary angiography performed 8 years previously was normal but a new one revealed the cut-off of the left anterior descending artery at the proximal portion, for which percutaneous coronary intervention was performed and showed no significant lesion in the other vessels. One should consider coronary artery disease in uncontrolled heart failure with LVEF reduction, even in the absence of typical chest pain. It may not be the natural course of the underlying disease.

A double-blind, randomized and placebo-controlled trial of Saffron (Crocus sativus L.) in the treatment of anxiety and depression.

BACKGROUND: Depression and anxiety are prevalent serious psychiatric disorders. Several drugs are used to treat these conditions but these are often associated with serious side effects. For this reason alternative therapies, including herbal medication such as saffron, have been proposed. We aimed to assess the effects of saffron extract for the treatment of anxiety and depression using a 12-week double-blind, placebo-controlled trial design. METHODS: Sixty adult patients with anxiety and depression were randomized to receive a 50 mg saffron capsule (Crocus sativus L. stigma) or a placebo capsule twice daily for 12 weeks. Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) questionnaires were used at baseline, 6 and 12 weeks after initiating medication. 54 subjects completed the trial. RESULTS: Saffron supplements had a significant effect on the BDI and BAI scores of subjects in comparison to placebo at the 12 week time-point (p<0.001). CONCLUSIONS: Saffron appears to have a significant impact in the treatment of anxiety and depression disorder. Side effects were rare.

Systemic Meglumine Antimoniate in Cutaneous Leishmaniasis of Children: Clinical and Laboratory Complications.

Children account for 7%-20% of cutaneous leishmaniasis cases in Iran, but there are few safety data to guide pediatric antiparasitic therapy. We evaluated the clinical and laboratory tolerance of the systemic pentavalent antimonial compound meglumine antimoniate, in 70 Iranian children with cutaneous leishmaniasis. Adverse effects were similar to those seen in adults.

Prenatal and cardiovascular outcome in pregnant patients with dyspnea.

BACKGROUND: Pregnancy is a physiologic phenomenon in women, which leads to significant hemodynamic changes in cardiovascular system. Many patients reach reproductive age due to improvements in diagnosis and treatment of cardiac diseases. Dyspnea is a common complaint in pregnant women and can be a sign to refer patients for an easy and feasible workup such as echocardiography. OBJECTIVES: We aimed to evaluate dyspnea as a common complaint in pregnant women and its prenatal outcome. PATIENTS AND METHODS: Pregnant patients with dyspnea NYHA class > II were included. A thorough physical examination and routine lab tests were performed. Echocardiography was performed to rule out previous cardiac and lung diseases, anemia and thyroid disorders. It was repeated monthly till one month after delivery. Collected data was analyzed after one year. RESULTS: Fifty patients were enrolled with a mean age of 30.49 ± 6.34 years. 58% of them, had NYHA class II, 40% III and 2% IV. Pulmonary rales were diagnosed in 8% and palpitation in 80%, while all had normal lab tests. Mean EF value was 52.26 ± 6.80; 54% had valvular diseases and 12% had pulmonary hypertension. Cesarean section was performed in 26, preeclampsia occurred in 7 and 21 had preterm labor. Three neonates had anomalies and six had an Apgar score below six. Mean birth weight was 2897 ± 540.00 grams. A significant association was found between NYHA Class with valvular disease (P = 0.007) and sys PAP (P = 0.036); however, it had an inverse correlation with LV EF (P = 0.06). CONCLUSIONS: Dyspnea may coincide with cardiac dysfunction and poor prenatal outcome in pregnant patients. In such cases echocardiography is a feasible screening tool.

Bacterial contamination in cutaneous leishmaniasis: its effect on the lesions' healing course.

BACKGROUND: The colonization of aerobic and anaerobic microbial agents on cutaneous leishmaniasis (CL) lesions, especially acute erosive ulcerative ones, has been mentioned in previous studies showing controversial results on the healing course of lesions with the use of antibiotics. AIMS: The purpose of this study was to evaluate the prevalence of secondary bacterial infections in CL lesions and the effect of its elimination on the lesions' improvement rate. MATERIALS AND METHODS: This cross-sectional clinical trial was performed on 84 acute CL patients. The required skin samples were taken. Cultivation for bacteria was conducted. Patients with positive culture results were divided into two groups. Both groups received standard anti-leishmania treatment, whereas only one group was treated with cephalexin 40-50 mg/kg/day for 10 days. The improvement rate was evaluated in the following visits based on changes in the lesions' induration size. RESULTS: Among the 84 studied patients, 22.6% had a negative culture result whereas the result was positive in 77.4%. The most common pathogenic germs were Staphylococcus aureus (52.3%) and Staphylococcus epidermidis (9.5%); 34/5% of the positive lesions received antibiotic treatment. Finally, among the lesions with a 75-100% improvement rate, no significant difference was observed between the antibiotic-treated and -untreated groups (36.1% vs. 63.9%, respectively, P = 0.403). CONCLUSIONS: The most common pathogen was S. aureus and, as a primary outcome, the simultaneous treatment for microbial agents did not have any considerable effect on the improvement rate of CL lesions.

Saffron supplements modulate serum pro-oxidant-antioxidant balance in patients with metabolic syndrome: A randomized, placebo-controlled clinical trial.

OBJECTIVES: We have investigated the effect of a saffron supplement, given at a dose of 100 mg/kg, on prooxidant-antioxidant balance (PAB) in individuals with metabolic syndrome. MATERIALS AND METHODS: A randomized, placebo-controlled trial design was used in 75 subjects with metabolic syndrome who were randomly allocated to one of two study groups: (1) the case group received 100mg/kg saffron and (2) the placebo control group received placebo for 12 weeks. The serum PAB assay was applied to all subjects before (week 0) and after (weeks 6 and 12) the intervention. RESULTS: There was a significant (p=0.035) reduction in serum PAB between week 0 to week 6 and also from week 0 to week 12. CONCLUSION: Saffron supplements can modulate serum PAB in subjects with metabolic syndrome, implying an improvement in some aspects of oxidative stress or antioxidant protection.

Synbiotics in Children with Cow's Milk Allergy: A Randomized Controlled Trial.

OBJECTIVE: Cow`s milk protein allergy usually occurs in infants within the first months of life. It can affect several organs, but gastrointestinal symptoms are the most clinical symptoms observed. The most effective treatment is restricting the cow `s milk protein in mother and infant`s diet. Lactobacillus GG supplementation in infant could be effective through modulation of the immune system and the gut microflora. METHODS: Thirty two breastfed infants with cow`s milk protein allergy were enrolled in a double-blinded randomized controlled trial in which they received Synbiotic (n=16) or placebo (n=16) once a day for one month, simultaneously with cow`s milk protein restriction in mother and infant`s diet. Clinical gastrointestinal symptoms (vomiting, colic, rectal bleeding and diarrhea), head circumference, body length and weight were recorded at the beginning, the end of the first and third month of study. Findings : Percentage of increment in head circumference and weight were statistically more in synbiotic group compared with placebo group at the end of the first and third month of study. There was no significant difference in resolution of clinical gastrointestinal symptoms (vomiting, colic, rectal bleeding or diarrhea) and percentage of increment in body length. CONCLUSION: Synbiotic supplementation in infants may improve increment of head circumference and weight gain, but has no effect on resolution of clinical symptoms.

Saffron in metabolic syndrome: its effects on antibody titers to heat-shock proteins 27, 60, 65 and 70.

BACKGROUND: The metabolic syndrome is the most important risk factor for cardiovascular disease. The heat shock proteins (HSPs) are highly conserved families of proteins expressed by a number of cell types following exposure to stressful environmental conditions include several known risk factors for cardiovascular disease. Recent studies have shown the potential of constituents of saffron in the treatment of atherosclerosis. We aimed on investigating the effect of saffron on antibody titers to HSP in patients with metabolic syndrome. METHODS: This was a randomized, placebo-controlled clinical trial. One-hundred and five subjects with metabolic syndrome were randomly allocated to one of the three groups: the case group received 100 mg/day saffron, the placebo control group received a capsule of placebo and a non-placebo control group received no capsule, for 12 weeks. RESULTS: Antibodies against heat shock proteins 27, 60, 65 and 70 were determined in all patients before (week 0) and after (week 6 and 12) intervention. At 12 weeks, saffron produced a significantly decrease in AntiHSP27, 70 levels. Saffron can decrease AntiHSP27, 70 levels in patients with metabolic syndrome. CONCLUSIONS: The results of this study indicate the efficacy of saffron in the improvement of some markers of autoimmunity HSPs in patients with metabolic syndrome.

Children and cutaneous leishmaniasis: a clinical report and review.

INTRODUCTION: Mashhad, located in north-east Iran, is one of the most important regions for cutaneous leishmaniasis (CL) due to Leishmania tropica. Children account for 7-10% of the infected population in the endemic areas. Despite the high sensitivity and susceptibility of this age group, no comprehensive study has yet investigated the clinical characteristics and demographic data in children in our region. Therefore, we aimed to study the clinical features and demographic information in children visiting the Leishmania clinic of two main teaching hospitals. METHODOLOGY: In a cross-sectional study all the required data were gathered from the children's records available at the cutaneous leishmaniasis clinics of Ghaem and Imam Reza hospitals during October 2008 to September 2011. Data included the patient's age, sex, lesion chronicity and distribution, the clinical features, and the involved body parts. Descriptive statistical tests and SPSS version 11.5 were used for data analyses. RESULTS: Among the 8,801 studied files, 689 (7%) were related to children under the age of 13. Female to male ratio was 0.9 with the highest prevalence in the 6-9 year age group. Regarding disease chronicity, the most common types were acute cases with a 71% prevalence rate. The face was the most involved body part (77.2%) and papules with 37% prevalence were the most common type of lesions seen. CONCLUSION: Childhood cutaneous leishmaniasis accounts for a major portion of CL in north-east Iran, has no apparent sex preference, and its clinical spectrum does not remarkably differ from that of adult CL.

Depression in patients with pemphigus: is it a major concern?

It is suggested that some dermatological diseases due to their chronicity, impact on the body image, unlikelihood of complete recovery and frequent recurrences are one of the major predisposing factors towards depression. Therefore, we aimed to evaluate the rate and level of depression among pemphigus vulgaris and pemphigus foliaceus patients, two of the most common causes of hospitalization in dermatology units. This research was conducted on 55 patients with active pemphigus vulgaris and pemphigus foliaceus referring to pemphigus clinics or admitted as inpatients to the dermatology ward of Qaem and Imam Reza hospitals, Mashhad, Iran, from April 2008 to September 2009. The research tool was the Beck Depression Inventory. Collected data was analyzed by χ(2)-test Student's t-test. Twenty-six (47.3%) patients were female and 29 (52.7%) were male. The mean age was 42.34 ± 18.98 years. The prevalence rate of clinical depression was 28% in pemphigus vulgaris and 20% in pemphigus foliaceus cases. Depression prevalence showed no significant difference between these two groups (P = 0.873). In conclusion, pemphigus patients are at risk for mild depression.

Patient Safety Culture Based on Medical Staff Attitudes in Khorasan Razavi Hospitals, Northeastern Iran.

BACKGROUND: Since establishing a safety culture in an organization is considered as the first step in patient safety improvement, there is always a need for updated field evaluation to better plan future decisions. METHODS: We performed a cross-sectional, analytic-descriptive study in 25 hospitals related to Mashhad University of Medical Sciences (MUMS) during a 3-month period from April to June 2012. A questionnaire, designed by previous patient safety culture studies with confirmed validity and reliability, was used and distributed among a sample of 922 staff, chosen randomly from the mentioned hospitals. Data were analyzed by SPSS software version 16. RESULTS: "Organizational learning - continuous improvement" and "teamwork within unit" had the highest percentage of positive results as 79.85 ± 12.03% and 71.92 ± 17.08%, respectively; whereas "non-punitive response" to errors (21.57 ± 6.42) and "staffing" (26.36 ± 16.84) came out as the least important factors. There were no meaningful statistical relation between general features of the understudy hospitals including the number of beds, educational level or proficiency status with the general safety culture score. CONCLUSION: Most of the safety culture aspects were reported as low to moderate in terms of importance. If something needs to be modified interventionally in this respect, "the approach to confront errors" would be a wise choice. This could be achieved by establishing an atmosphere of open communication and continuous learning through elimination of the fear for reporting errors and installing a more acceptable approach in hospitals.