Helicobacter pylori in Iran: a systematic review on the association of genotypes and gastroduodenal diseases

Background: Helicobacter pylori (H. pylori) infection is known as a major etiologic factor for a variety of gastroduodenal diseases. In Iran, with a high rate of H. pylori infection close to 90%, numerous studies have revealed many aspects of interaction between the bacterium, mucosal surface and induction of disease outcome. The organism is genetically diverse and several virulence factors are attributed to the more virulent strains. The well-characterized virulence factors of H. pylori are cytotoxin associated gene A and vacuolating cytotoxin gene A. The distribution pattern of H. pylori genotypes and its association with disease status varies geographically. The present review focused on the virulence factors and genotyping of H. pylori in relation to gastroduodenal disorders in different regions of Iran. Methods: In total, 398 studies were reported on different aspects related to H. pylori in our electronic search from 1995-2011. H. pylori infection and its virulence factors in association with disease status were investigated in 159 reports. Looking specifically at the gastrointestinal tract disorders, the most relevant reports including 37 papers were selected. Results: We found no correlation of cagA genotype and disease status in the majority of studies, whereas vacA was demonstrated as a useful marker in predicting the disease outcome. The results of reports on other virulence factors of H. pylori such as blood group antigen-binding adhesion gene A, the induced by contact with epithelium gene A, the outer inflammatory protein A, the duodenal ulcer promoting gene A, and Helicobacter outer membrane gene and their relation with disease status were contradictory. Conclusions: Although different markers of H. pylori were emphasized as useful when predicting disease outcomes in some studies, the inconsistent researches and the scarcity of data made any conclusion or even comparison impossible. Considering the gap of information observed during our search relating to genotyping and other aspects of H. pylori infection, further investigations are suggested

ANALYTICAL METHOD VALIDATION, PHARMACOKINETICS AND BIOEQUIVALENCE STUDY OF DIMETHYL FUMARATE IN HEALTHY IRANIAN VOLUNTEERS

Objective: Pharmacokinetic evaluation of Dimethyl Fumarate (DMF) in the Iranian population wasn’t studied. So, the aim of this research is the validation of the analytical method and evaluation of the pharmacokinetic properties and bioequivalence of the generic form of this drug versus the reference product. Methods: 2 single-dose, test, and reference DMF products were orally administered to 24 healthy volunteers. The washout period was 28 d between the treatments. Monomethyl fumarate as the metabolite of DMF was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the method was validated. Also, the pharmacokinetic parameters were calculated for bioequivalence evaluation. Results: The analytical method was validated and linear over the range of 31.25-4000 ng/ml (R2= 0.997). In addition, the method was precise and accurate in the low, medium, and high concentrations. The results indicated that the 2 products had similar pharmacokinetics. Further, the 90% CI of the mean ratios of the test versus the reference products of the log-transformed area under the concentration-time curve over 10 h (0.99 to 1.02) and peak concentration (0.98 to 1.03) were within the acceptable range of 0.8 to 1.25 and the generic product of DMF could be similar to that of the reference product. Conclusion: The applied analytical method is selective, accurate, precise, and repeatable for the analysis of monomethyl fumarate (MMF) in plasma. Also, the bioequivalence study showed no significant difference between the pharmacokinetic parameters of these 2 products. So, the DMF test product can be claimed to be bioequivalent with the reference product

The Dilemma of TP53 Codon 72 Polymorphism (rs1042522) and Breast Cancer Risk : A Case-Control Study and Meta-Analysis in The Iranian Population

The authors would like to thank all participants in this research. We would also like to thank Mashhad University of Medical Sciences and Omid Hospital (Mashhad, Iran) for their support to the project. This work was financially supported by Mashhad University of Medical Sciences under Grant No. 930891. No potential conflict of interest was reported by the authors.Peer reviewedPublisher PD

Long non-coding RNAs and JAK/STAT signaling pathway regulation in colorectal cancer development

Colorectal cancer (CRC) is one of the main fatal cancers. Cell signaling such as Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling substantially influences the process of gene expression and cell growth. Long non-coding RNAs (lncRNAs) play regulatory roles in cell signaling, cell proliferation, and cancer fate. Hence, lncRNAs can be considered biomarkers in cancers. The inhibitory or activating effects of different lncRNAs on the JAK/STAT pathway regulate cancer cell proliferation or tumor suppression. Additionally, lncRNAs regulate immune responses which play a role in immunotherapy. Mechanisms of lncRNAs in CRC via JAK/STAT regulation mainly include cell proliferation, invasion, metastasis, apoptosis, adhesion, and control of inflammation. More profound findings are warranted to specifically target the lncRNAs in terms of activation or suppression in hindering CRC cell proliferation. Here, to understand the lncRNA cross-talk in CRC through the JAK/STAT signaling pathway, we collected the related in vitro and in vivo data. Future insights may pave the way for the development of novel diagnostic tools, therapeutic interventions, and personalized treatment strategies for CRC patients

D-optimal Design for Preparation and Optimization of Fast Dissolving Bosentan Nanosuspension

Purpose: Bosentan is a drug currently taken orally for the treatment of pulmonary arterialhypertension. However, the water solubility of bosentan is very low, resulting in lowbioavailability. The aim of this study was preparation and optimization of bosentannanosuspension to improve solubility and dissolution rate.Methods: The different formulations designed by Design Expert® software.Nanosuspensions were prepared using precipitation method and the effects of stabilizer typeand content and drug content on the particle size, polydispersity (PDI) and yield ofnanosuspensions were investigated.Results: Particle size, PDI and yield of the optimal nanosuspension formulation were 200.9nm, 0.24 and 99.6%, respectively. Scanning electron microscopy (SEM) results showedspherical morphology for bosentan nanoparticles. Thermal analysis indicated that there wasa partial crystalline structure and change in the pholymorphism of bosentan in thenanoparticles. In addition, reduction of particle size, significantly increased in vitrodissolution rate of the drug.Conclusion: Optimization by design expert software was shown to be a successful methodfor optimization and prediction of responses by less than 10% error and formulation with15.8 mg span 85 as an internal stabilizer and 45 mg drug content were introduced as theoptimum formulation. The solubility of bosentan in the optimal formulation was 6.9 timeshigher than coarse bosentan and could be suggested as promising drug delivery systems forimproving the dissolution rate and possibly the pharmacokinetic of bosentan

ANALYTICAL METHOD VALIDATION AND BIOEQUIVALENCE STUDY OF ERLOTINIB 150 MG TABLETS IN IRANIAN HEALTHY VOLUNTEERS UNDER FASTING CONDITION

Objective: This study aims to compare a generic formulation of the drug erlotinib 150 mg tablet to the brand-name version to validate the analytical method and bioequivalence studies. Methods: Erlotinib hydrochloride tablets (test versus reference formulation) were compared in a randomized, two-period crossover study to determine their pharmacokinetic properties and bioequivalence in healthy Iranian volunteers. 14 days passed between each treatment during the washout period. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze erlotinib, and the method validation is presented. Results: Over the range of 6.25- 3200 ng/ ml, the analytical method was verified as linear (R2= 0.998). The technique was also accurate and precise at various concentrations. The results showed that the pharmacokinetics of the two products were comparable. Following administration of the test and reference products, the geometric averages for (Area under the curve) AUC0-72, AUCinf, and maximum plasma concentration (Cmax) were 104.71 (90% CI, 93.39-117.40), 104.68 (90% CI, 93.47-117.23), and 104.85 (90% CI, 94.61-116.21), respectively. The outcomes fell within the permitted tolerance of 0.8 to 1.25. Conclusion: For the determination of erlotinib in plasma, the used analytical approach is accurate, precise, repeatable, and selective. Additionally, the bioequivalence research revealed no appreciable differences in pharmacokinetic characteristics between the reference and test products. Therefore, it is possible to assert that the generic erlotinib product and the reference product are bioequivalent

Responses of Endothelin-1 and Arterial Blood Pressure of Postmenopausal Women to Aerobic Exercise Training

Objectives:&nbsp;Endothelin-1 is a strong constrictor of blood vessels that is secreted by endothelial cells and identified as the strongest vascular constrictor. The aim of the present study was to investigate the effect of eight week aerobic exercise on the endothelin-1 concentration of plasma and its relationship with blood pressure in elderly postmenopausal women. Methods & Materials: A total of 20 menopausal women (with the average age of 67.85&plusmn;5.67 years , height 153.50&plusmn;7.7 cm, weight 66.16&plusmn;11.96 kg, BMI of 28.15&plusmn;4.98, fat percentage of 18.41&plusmn;3.65, and WHR of 0.92&plusmn;0.04) were selected and randomly assigned into two groups of ten each. The experimental group underwent eight weeks of aerobic training spanning across three sessions in a week with the intensity of 60 to 70% of maximum heart rate. The resting level of endothelin-1 concentration along with the systolic and diastolic blood pressure for each participant were measured and recorded before and after eight weeks of exercise .Paired t-test was used for investigating the changes within the group while the independent t-test was used for investigating the differences between the groups. Pearson correlation coefficient was used for investigating the relationship between endothelin-1 and blood pressure. A significance level less than 0.05 were considered to be significant. Results:&nbsp;The result of this study showed that one duration of aerobic exercise had a significant effect on endothelin-1 plasma density (P<0.01) and decreasing systolic (P<0.01) as well as diastolic(P=0.002) blood pressure in older women. A direct correlation was established between endothelin-1 and systolic blood pressure (P=0.59). Nevertheless, no correlation was noted between endothelin-1 and diastolic blood pressure (r=0.39). Conclusion: It was concluded that single duration of aerobic exercise with the agreed intensity and volume could decrease the systolic and diastolic blood pressure and the endothelin-1 concentration of plasma

Helicobacter pylori in Iran: A systematic review on the antibiotic resistance

Objective(s):Helicobacter pylori (H. pylori) is a pathogenic bacterium that colonizes the stomachs of approximately 50% of the world’s population. Resistance of H. pylori to antibiotics is considered as the main reason for the failure to eradicate this bacterium. The aim of this study was to determine the rate of resistant H. pylori strains to various antimicrobial agents in different areas of Iran.   Materials and Methods: A systematic review of literatures on H. pylori antibiotic resistance in Iran was performed within the time span of 1997 to 2013. Data obtained from various studies were tabulated as following, 1) year of research and number strains tested, 2) number of H. pylori positive patients, 3) study place, 4) resistance of H. pylori to various antibiotics as percentage, and 5) methods used for evaluation of antibiotic resistance. Results: Over the period, a total of 21 studies on H. pylori antibiotic resistance have been conducted in different parts of Iran. In these studies, H. pylori resistance to various antibiotics, including metronidazole, clarithromycin, amoxicillin, tetracycline, ciprofloxacin, levofloxacin and furazolidone were 61.6%, 22.4% ,16.0%, 12.2%, 21.0%, 5.3% and 21.6%, respectively. We found no study on                 H. pylori resistance to rifabutin in Iran. Conclusion: Compared to the global average, we noted that the prevalence of H. pylori resistance to metronidazole, clarithromycin, amoxicillin, and tetracycline has been rapidly growing in Iran. This study showed that in order to determine an appropriate drug regimen against H. pylori, information on antibiotic susceptibility of the bacterium within different geographical areas of Iran is required