Tumor necrosis factor-alpha and interleukin-6 gene polymorphisms in Iranian patients with ischemic heart failure

Background: Proinflammatory cytokines have been known to be elevated in patients with Chronic Heart Failure [CHF]. Given the importance of proinflammatory cytokines in the context of the failing heart, the prevalence of Tumor Necrosis Factor-alpha [TNF-alpha], Interleukin [IL]-6 polymorphisms in patients with CHF was studied due to ischemic heart disease

Methods: Forty three patients with ischemic heart failure were enrolled in this study and compared with 140 healthy individuals. The allele and genotype frequency of four Single Nucleotide Polymorphisms [SNPs] within the IL-6 [-174, nt565] and TNF-alpha [-308, -238] genes were determined, using Polymerase Chain Reaction with Sequence-Specific Primers [PCR-SSP] assay

Results: The frequency of the TNF-alpha [-238] A/A genotype was significantly higher in patients comparing to controls [p=0.043], while TNF-alpha G/A genotype at the same position decreased significantly, in comparison with controls [p=0.018]. The most frequent haplotype for TNF-alpha was A/A in the patient group in comparison with controls [p=0.003]. There was no significant difference in allele and genotype frequencies of IL-6 at positions -174 and nt565, and TNF-alpha at position -308

Conclusion: Certain alleles, genotypes, and haplotypes in TNF-alpha, but not IL-6, gene were overrepresented in patients with ischemic heart failure, which may, in turn, predispose individuals to this disease

Association of serotonin transporter gene polymorphism with recurrent aphthous stomatitis

Background: Recurrent Aphthous Stomatitis [RAS] is one of the most common diseases of the oral cavity all over the world [5-66%]. RAS has a multifactorial etiology, while psychological factors such as stress and anger play a role in its manifestation. The serotonergic mechanisms particularly the serotonin-transporter gene [5-HTT] may affect the risk of psychological alterations and stress response. The aim of the present study was to evaluate the polymorphism of the promoter region of 5-HTT [5-HTTLPR] in the patients with RAS, compared to that in the control subjects

Methods: In this case-control study, 100 patients with RAS and 100 healthy subjects were enrolled. PCR was performed on DNA of the samples, using a pair of primers capable of distinguishing S/L alleles and replicating 5-HTTLPR

Results: No statistically significant difference existed between LL and LS genotype frequencies in the case and control groups. However, SS genotype frequency was significantly higher in the case group, as compared to the control group [p=0.001]

Conclusion: The conclusion of the present study demonstrated that S allele could approximately double the risk of RAS

Internationalization of medical education in Iran: a way towards implementation of the plans of development and innovation in medical education

Introduction: academic institutions are the most important organizations for implementation of internationalization policies and practices for integrating an international, intercultural and global dimension in higher education system. Also, a globally increasing demand for higher education has been seen in the past two decades so that the number of students enrolled in higher education institutions in the worldwide nation-states has increased dramatically. The National Plan of International Development of Medical Education was designed with the aim of identifying available potentials in all the universities of medical sciences, encouraging the development of international standards of medical education, and planning for the utilization of the existing capacity in Islamic republic of Iran

Methods: authors have tried to review the several aspects of international activities in higher education in the world and describe national experiences and main policies in globalization of medical education in Iran within implementation of the National Plan for Development and Innovation in Medical Education

Results: the findings of some global experiences provide the policy makers with clear directions in order to develop internationalization of higher education

Conclusion: the Program for International Development of Medical Education was designed by the Deputy of Education in the Ministry of Health and the effective implementation of this Program was so important for promotion of Iranian medical education. But there were some challenges in this regard; addressing them through inter-sectoral collaboration is one of the most important strategies for the development of internationalization of education in the field of medical sciences

Interleukin-2 and interferon-gamma single nucleotide polymorphisms in iranian patients with chronic heart failure

Background: Inflammatory cytokines have been known to be associated with Chronic Heart Failure [CHF]. Given the importance of cytokines in the context of the failing heart, the prevalence of Interleukin-2 [IL-2] and Interferon-gamma [IFN-Gamma] polymorphisms was studied in patients with CHF due to ischemic heart disease in a casecontrol study

Methods: Fifty-six Iranian patients with CHF were enrolled in this study as the case group and compared with 139 healthy subjects, using polymerase chain reaction with sequence-specific primers method, so as to determine the frequency of alleles, genotypes and haplotypes of IFN-Gamma [+874 A/T] and IL-2 [-330 G/T, +166 G/T] SNPs

Results: The GG genotype at IL-2 -330 in patients with CHF was significantly overrepresented in comparison with the control group [p=0.013]. Such a positive genotypic association was also observed for IL-2 +166/TT [p=0.022]. Meanwhile, the GT genotype frequency at IL-2 -330/GT in the patient group was significantly lower than the one in healthy controls [p=0.049]. No significant association was detected between the IFN-Gamma gene polymorphisms and individuals' susceptibility to CHF

Conclusion: Certain genotypes in IL-2 gene were overrepresented in patients with CHF, which could render individuals more vulnerable to this disease

Introducing a new experimental islet transplantation model using biomimetic hydrogel and a simple high yield islet isolation technique

Background: Islet transplantation could be an ideal alternative treatment to insulin therapy for type 1 diabetes Mellitus [T1DM]. This clinical and experimental field requires a model that covers problems such as requiring a large number of functional and viable islets, the optimal transplantation site, and the prevention of islet dispersion. Hence, the methods of choice for isolation of functional islets and transplantation are crucial

Methods: The present study has introduced an experimental model that overcomes some critical issues in islet transplantation, including in situ pancreas perfusion by digestive enzymes through common bile duct. In comparison with conventional methods, we inflated the pancreas in Petri dishes with only 1 ml collagenase type XI solution, which was followed by hand-picking isolation or Ficoll gradient separation to purify the islets. Then we used a hydrogel composite in which the islets were embedded and transplanted into the peritoneal cavity of the streptozotocin-induced diabetic C57BL/6 mice

Results: As compared to the yield of the classical methods, in our modified technique, the mean yield of isolation was about 130-200 viable islets/mouse pancreas. In vitro glucosemediated insulin secretion assay indicated an appropriate response in isolated islets. In addition, data from in vivo experiments revealed that the allograft remarkably maintained blood glucose levels under 400 mg/dl and hydrogel composite prevents the passage of immune cells

Conclusion: In the model presented here, the rapid islet isolation technique and the application of biomimetic hydrogel wrapping of islets could facilitate islet transplantation procedures

Role of the immune cells, mediators and cytokines in pathogenesis of asthma: a review article

Asthma is a chronic inflammatory disorder of the airways, associated with airway re-modeling and hyperresponsiveness. It is expressed that asthma influences about 300 million people around the world, which is estimated to increase to about 400 million by 2025. The prevalence rate is 15 to 20 percent in children and 5 to 10 percent in adults, while its trend is still increasing. Inflammation plays an important role in the patho-physiology of asthma, which involves an interaction of different types of the immune cells and mediators. It leads to a number of pathophysiology changes, including bron-chial inflammation, airway obstruction, and clinical episodes such as cough, wheeze and shortness of breath. Asthma is now greatly being introduced as a heterogeneous disorder and it is pointed out to the role of T cells, including Th1, Th2, Th17, and regu-latory T cells. Other immune cells, especially neutrophils, macrophages and dendritic cells, as well structural cells such as epithelial and airway smooth muscle cells also produce disease-associated cytokines in asthma. Increased levels of these immune cells and cytokines have been recognized in clinical samples and mouse models of asthma. Different cytokines, including pro-inflammatory cytokines [such as TNF[alpha], IL-1, and IL-6], T helper 2 cytokines [such as IL-4, IL-5, IL-9, IL-13], and growth factors [such as GM-CSF, PDGF] play a role in the pathogenesis of asthma. Indeed chemokines [such as MPC-1, RANTES, MIP-1] and the chemokine receptors [such as CCR3, CCR4, CCL11, CCL24, and CCL26] play an important role in the recruitment of circu-lating inflammatory cells into the airways in asthmatic patients and also is related with increased T helper 2 cytokines after inhaled allergens. Among new approaches, treat-ment of asthma with anti-cytokine drugs such as antibodies blocking IL-4, IL-5, IL-9 could reduce recruitment inflammatory cells into the airways and remodeling. The final perspective of asthma treatments would be to alter from the symptomatic treatments to disease modifying

Autonomy of children and adolescents in consent to treatment: ethical, jurisprudential and legal considerations

Autonomy is usually considered as a main principle in making decisions about individuals' health. Children and particularly adolescents have the capacity to take part in medical decision-making to some extent For the most part the parent-doctor-child/adolescent triangle sides are essentially in agreement, but this may not be true in some cases, causing physicians to face problems attempting to determine their professional duties. According to Islamic jurisprudent upon reaching the age of Taklif [15 full lunar years for boys and 9 full lunar years for girls] no one can be treated as incompetent based on mental immaturity unless his or her insanity or mental immaturity is provend Moreover the Islamic Sharia, decrees that parents should lose their authority to make medical decisions for their children, if their bad faith or imprudence is proven, in which case a fit and proper person or an institution will be appointed to make decisions in this respect based on the child's best interests

randomized clinical trial of insulin Glargine and Aspart, compared to NPH and regular insulin in children with type 1 diabetes mellitus

Objective: Appropriate treatment of patients with Type 1 diabetes mellitus [T1DM] is necessary to avoid further complications. This study was performed to compare the efficacy of insulin Glargine and Aspart with NPH insulin and regular insulin regimen in a group of children with T1DM

Methods: Forty patients with T1DM were enrolled in this study. During run-in, all subjects were treated with conventional therapy consisting of twice-daily NPH and thrice-daily regular. Following randomization, 20 subjects received Glargine and Aspart and 20 subjects received NPH and Regular insulin

Findings: Mean HbA1c was 8.8% and 8.6% at first and 8.4% and 8.2% at the end of study for subjects randomized initially to Glargine and Aspart and for those randomized to NPH and Regular, respectively [P>0.05]. Mean fasting blood glucose [FBS] of the subjects randomized initially to Glargine and Aspart was 217+/-101 mg/dL, with no significant difference to 196+/-75 mg/dL for those randomized to NPH and Regular [P=0.48]. This was also true at the end of the study. The difference in total cholesterol and triglyceride between the two groups in the beginning of study and at the end did not show any significance

Conclusion: The current study showed no significant difference in glycemic control [Glycated hemoglobin [HbA1c] and FBS] and lipid profile [total cholesterol and triglyceride] between two regimes

Evaluation of physicians' awareness of pediatric diseases in Iran

Physicians' awareness about pediatric health problems is very important in health system. This has not been investigated in Iran as yet. Therefore this study was conducted to characterize the knowledge of the Iranian physicians which has direct association with health status of children. One hundred and four physicians, mainly pediatric specialists [58.6%] working in the state hospitals [45.1%] were enrolled. They filled a valid and reliable questionnaire, containing 26 questions about basic and important pediatric issues before and after an educational pediatric program [EPP]. Thirty nine [37.5%] physicians answered correctly more than 2/3 of all questions [passed the examination] before EPP, which increased to 42.3% after EEP. Subgroup analysis showed that the total scores of general practitioners [P=0.007] was significantly increased after the EPP. Moreover, physicians with shorter practicing time [P=0.006] and those with shorter time past graduation [P=0.01] had a significant improvement in their total scores after the program. The best scores of educational issues were documented in growth and development [16.0%; P=0.04], followed by dermatology [9.2%, P=0.04], urology [9.1%; P=0.04], and asthma and allergy [9.0%, P=0.04]. This study revealed that there are gaps in the knowledge of professionals about the pediatric issues

Efficacy of pregabalin in childhood refractory partial seizure

About one third of partial seizures are refractory to treatment. Several anticonvulsant drugs have entered the market in recent decades but concerns about intolerance, drug interactions, and the safety of the drug are notable. One of these new anticonvulsants is pregabalin, a safe drug with almost no interaction with other antiepileptic drugs. In this open label clinical trial study, pregabalin was used for evaluation of its efficacy on reducing seizure frequency in 29 children suffering from refractory partial seizures. Average daily and weekly seizure frequency of the patients was recorded during a 6-week period [baseline period]. Then, during a period of 2 weeks [titration period], pregabalin was started with a dose of 25-75 mg/d, using method of flexible dose, and was brought to maximum dose of drug that was intended in this study [450 mg/d] based on clinical response of the patients and seizure frequency. Then the patients were given the drug for 12 weeks and the average frequency of daily and weekly seizures were recorded again [treatment period]. Reduction in seizure frequency in this study was 36% and the responder rate or number of patients who gained more than 50% reduction in seizure frequency was 51.7%. This study showed that pregabalin can be used with safety and an acceptable efficacy in treatment of childhood refractory partial seizures

Evaluation of haptoglobin phenotypes in association with clinical features of patients suffered from preterm labor disease

Preterm birth means the birth before thirty seven week of pregnancy that causes a lot of complications for the baby. Variety factors are suggested to be involved in disease. In this study, we decided to evaluate haptoglobin [Hp] phenotypes association with clinical features of patients suffered from premature delivery to understand better the possible correlation of genetic and clinical features in this disease. This cross-sectional analytic descriptive study has been carried out in two groups of 120 women, 60 with preterm and 60 with term labor. Patients were selected with previously diagnosed by gynecologist with preterm birth in the labor during the study period. After performing diagnostic tests, the frequency of each haptoglobin phenotype in the two groups was analyzed using the Chi-square test [X2] test and SPSS software. The maximum serum haptoglobin phenotype frequency in patients with Hp2-2, was 43 [71.7%] whereas in healthy individuals, 35 [58.3%]. No, statistically significant differences between the two groups were found [p=0.310]. But based on some patients clinical features such as their history of preterm delivery, previous history of recurrent abortions and history of preterm delivery in their family, significant association was found with Hp2-2 compared with healthy control [p<0.003]. This study showed that Hp2-2 phenotypes levels in the case group was higher than in control but the factors influencing the presence or absence of preterm labor is clinically various

Evaluation of Antibody Response to Polysaccharide Vaccine and Switched Memory B Cells in Pediatric Patients with Inflammatory Bowel Disease

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients. METHODS: Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated. RESULTS: Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9+/-32.5 microg/mL vs 219.8+/-59.0 microg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed. CONCLUSIONS: A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.

Alpha 1 antitrypsin deficiency in infants with neonatal cholestasis

Alpha 1-antitrypsin deficiency [A1ATD] is the most important indication for liver transplantation in children. The gene frequencies vary in different ethnic groups. In the present study, we attempt to determine the frequencies of the most common defective alleles, Z and S, in Iranian children suffering from idiopathic neonatal cholestasis. Eighty-seven infants were typed for Z and S alleles. In a single center study, 87 consecutive liver biopsies from infants with cholestasis were reviewed and patients with neonatal cholestasis enrolled in the study and cases with confirmed biliary tract atresia excluded. Formalin fixed paraffin embedded blocks were used for DNA extraction. AAT genotype was determined by polymerase chain reaction [PCR] assay and amplification of the two most common deficiency variants, S and Z alleles, and then sequencing of PCR products. There were 48 [55.2%] males and 39 [44.8%] females, with a median age of 60 days. Out of 87 of the study subject, 2 [2.2%] were heterozygous for the S allele, and no ZZ, SS or MZ individual was found in the patients. No other polymorphism was found in the sequencing results. In comparison to other populations, AAT deficiency seems not to be an important etiologic factor for neonatal cholestatic liver disease in Iran; however, further studies are recommended to estimate the true mutant gene frequencies

GCK mutation in a child with maturity onset diabetes of the young, type 2

Maturity onset diabetes of the young type 2 [MODY] is an inherited disorder due to mutations in glucokinase [GCK] gene, which lead to mild fasting hyperglycemia. Herein an otherwise healthy 9-year old boy with hyperglycemia is presented in whom the diagnosis of MODY2 was suspected. Genetic studies showed heterozygous inactivating GCK gene mutation in exon 8 [c.1010delA] in this patient. The same mutation was found in his father as well. The patient received some dietary advices without any medication. The identification of GCK mutation and diagnosis of MODY2 helps the clinicians to predict the disease course, prognosis and to exclude other types of diabetes

Acanthosis nigricans. abnormal facial appearance and dentition in an insulin resistance syndrome

Insulin resistance syndromes are a heterogeneous group of disorders with variable clinical phenotypes, associated with increased blood glucose and insulin levels. Herein, a 10-year old girl with abnormal face and dentition is presented. She has suffered from diabetes mellitus type 1 since she was 6 years old. Hyperglycemia did not respond to age appropriate insulin dosage; therefore, insulin dosage was increased, but did not lead to appropriate glycemic control. Twenty two exons of insulin receptor gene [INSR], on short arm of chromosome 19, were sequenced, but no identifiable disease causing mutation was detected. Although a rare mutation within the intronic or promoter region has not been exduded in this case, further molecular studies on patients with insulin resistance syndromes associated with certain features are needed

[ effect of purslane in the treatment of recurrent aphthous stomatitis]

Recurrent aphthous stomatitis [RAS] is a common disease with unknown etiology. There is no curative treatment. Purslane is considered as a rich source of antioxidants with anti-inflammatory effects. The purpose of this study is to evaluate the effect of Purslane in the treatment of RAS. A total of 50 patients were selected for this randomized triple-blind placebocontrolled clinical trial from School of Dentistry of Tehran University of Medical Sciences in 2011. All subjects were randomly divided into two groups. Groups A and B received placebo and Purslane, respectively, for three months. Pain intensity based on the visual analogue scale [VAS], the mean intervals of lesions occurrence, number of lesions and the mean duration of complete healing at baseline and at months 1, 2 and 3 were recorded. While no patient complained from increased severity of pain, decreased severity of pain for 4, 3, 2, and 1 grades were recorded in%16,%20, 20%, and 40%, respectively, which were much higher than 4%, 8%, 8%, and 28%, respectively, in the control group. A significant decrease in pain intensity in VAS scores were seen after treatment in group B [P<0.001]. The mean duration of complete healing showed significant differences [P<0.001] between groups A [-1.52 +/- 4.07 days] and group B [-6.56 +/- 4.50 days]. The mean intervals between lesions also showed significant differences [P<0.001] between group A [17.88 days] and group B [33.12 days]. No significant differences were found between group A and group B regarding to number of lesions. No serious side-effects occurred in either group. According to our study, Purslane is clinically effective in treatment of RAS and considering the lack of side-effects during the study period, this medicine may be a favorable alternative treatment for recurrent aphthous stomatitis.