سال:1391 | دوره: | شماره: |تعداد مقالات:9

Background: In spite of dozens of clinical trials to establish effective therapeutic and/or preventive vaccine to resolve HCV infection, no real vaccine has been proved to date. Genetic vaccines based on replication-defective adenoviruses have proved to elicit strong and long lasting T-cell responses against a number of viral antigens and are even currently being used for vaccine trials in humans. According to the controversy in the immune modulatory effects of both core and NS3 full length genes, it seemed more practical to employ some parts of these HCV proteins for vaccine design.Objectives: To generate recombinant Adenoviral vectors containing new overlapping-truncated region of NS3 gene or both the N- and C-terminal deleted parts of core gene, as well as a fusion fragment derived from both of them.Materials and Methods: The corresponding transfer vectors expressing truncated fragments of core, NS3 or a fusion fragment of both genes were prepared. The integrity and sequence of the transfer vectors were confirmed, and followed by experiments involving homologous recombination between them and the adenovirus backbone plasmid in the bacterial host.Recombinant Ad-pNS3, Ad-pCore and Ad-pNS3pCore viruses were prepared by transfection of these new recombined constructs into 293 packaging cell lines. The virus titer was then calculated by an immunohistochemistry based method. The RT-PCR, Real-Time PCR and western blotting were used to evaluate gene expression by all recombinant constructs. The production of complete virion particles was evaluated by detailed electron microscopy in addition to the appearance of typical cytopathic effects (CPE) and GFP expression patterns in 293 cells.The RT-PCR and GFP detection were employed to monitor the integrity as well as infectivity potency of the viral particles in Hep-G2 cells.Results: RT-PCR, Real-Time PCR or western blotting confirmed expression of truncated fragment of NS3, core or a fusion fragment of theirs by newly constructed Ad-pNS3, Ad-pCore AdpNS3pCore particles. Electron microscopy, which revealed many adenovirus-like particles and characteristics of CPE in infected cells in addition to GFP detection, confirmed the infectivity, potency and integrity of recombinant adenoviral particles.Conclusions: These adenoviruses expressing novel fragments of NS3 and core genes may be suitable tools to overcome shortcomings associated with full gene expression in the setting of HCV vaccine therapy.

Context: Occult hepatitis B (OHB), or persistent HBV DNA in patients who are hepatitis B surface antigen (HBsAg) negative, is a recently recognized entity. In an attempt to sum- marize the issues, this review presents an overview of the current proposed hypothesis on the clinical relevance and also updates the knowledge on the classification of OHB in different clinical settings. Evidence Acquisition: OHB could be found in different population and clinical back-grounds including: viral co-infections (with either human immunodeficiency or hepatitis C viruses), HBV chronic carriers, dialysis patients, transplantation settings and certain clinical situations (named in here: special clinical settings) with no apparent distinguishable clinical parameters.Results: The exact magnitude, pathogenesis, and clinical relevance of OHB are unclear. Even the possible role exerted by this cryptic infection on liver disease outcome, and he- patocellular carcinoma development remains unknown. Conclusions: monitoring of Individuals with positive anti-HBc, mass immunization programs and improvement in diagnostic tools seem to be important to control the probability of transmission of HBV through cryptic HBV infection.

Background: Although liver transplantation is the last resort for treating end stage liver diseases, this medical procedure is not available for all needful patients because of inadequate organ supply. Therefore, guidelines have been developed by medical experts to regulate the process. Some professionals believe that medical criteria are inadequate for organ allocation in all situations and may not secure fairness of organ allocation.Objectives: The current study has been designed to identify decision criteria about allocation of donated liver to potential recipients from public points of view.Patients and Methods: This is a qualitative study that was conducted through individual interviews and Focus Group Discussions. Individual interviews were conducted among patients’ companions and nurses in one of the two liver transplant centers in Iran. Group discussions were conducted among groups of ordinary people who had not dealt previously with the subject. Data was analyzed by Thematic Analysis method.Results: Most of the participants in this study believe that in equal medical conditions, some individual and societal criteria could be used to prioritize patients for receiving donated livers. The criteria include psychological acceptance, ability to pay post-operative care costs, being breadwinner of the family, family support, being socially valued, ability to be instructed, lack of mental disorders, young age of the recipient, being on waiting list for a long time, lack of patient’s role in causing the illness, first time transplant recipient, critical medical condition, high success rate of transplantation, lack of concurrent medical illnesses, not being an inmate at the time of receiving transplant, and bearing Iranian nationality.Conclusions: Taking public opinion into consideration may smooth the process of organ allocation to needful patients with equal medical conditions. It seems that considering these viewpoints in drafting organ allocation guidelines may increase confidence of the society to the equity of organ allocation in the country. This strategy may also persuade people to donate organs particularly after death.

Background: Single nucleotide polymorphism in the interleukin28B (IL28B) gene was recently shown to be associated with a significant increase in response to interferon-α and ribavirin treatment in patients with chronic hepatitis C. Similarly, thyroid disease (TD) occurring during treatment confer an improved sustained virologic response (SVR).Objectives: To determine the role of IL28B genotypes in a cohort of hepatitis C patients who develop TD during treatment and its relationship to SVR.Patients and Methods: IL28B gene profiles including rs12979860, rs12980275 and rs 8099917 and their genotypes were determined in a cohort of 23 hepatitis C patients who developed TD during treatment and their relationship to SVR.Results: Out of 23 studies cases, 19 has one or more favorable genotypes, of which 15 (78.9%) achieved SVR. Eleven has all three unfavorable genotypes and yet achieved 72.7% SVR. The presence of more than one favorable genotype only correctly predicts SVR vs. non- SVR in ~50% of cases, i.e. by chance.Conclusions: Despite the small number of subjects, the presence of one or more unfavorable IL28B genotype does not portend a poor SVR prognostic outcome. This suggests that TD in this clinical context may be a critical factor in the achievement of SVR, probably above that of the genetic predisposition.

Sometimes some members of multicellular organisms need to sacrifice for the good of the whole. Perhaps with the exception of immunomodulatory processes (1, 2), it is the intrinsic death pathway, often triggered by p53 (3-5), modulated by Bcl2-family members, and executed primarily by caspases that is most commonly employed to trigger cell death (6-8). Apoptotic or autophagic cell death is triggered by physical insults such as cold (9), natural compounds and their derivatives (10-12), viruses (13), or even disturbances within the cell cycle (14, 15). Apoptotic cell death is preceded by mitochondrial release of cytochrome c, which leads to increases in cytochrome c in serum (16).

Background: Wilson’s disease (WD) is a rare autosomal-recessive disorder characterized by a mutation in the ATP7B gene, located on chromosome 13, which encodes a protein involved in the metabolism of copper.Case Presentation: We described the case of an Indian male with a history of polydipsia and polyuria, related to hypercalciuria and consequent nephrocalcinosis. The symptoms began at the age of five years old, but he was not diagnosed with WD until he reached an adolescent age. We started therapy with D-Penicillamine, B-vitamin complex and recommended a low copper diet. Renal involvement in Wilson’s disease, characterizing by hypercalciuria, was firstly reported by Litin in 1959.Conclusion: Our case was different and peculiar from the previously described cases because the patient presented a very long history (10 years) of permanent hypercalciuria without any acute episode of nephrolithiasis.

Dear Editor: We read with interest the paper entitled "Prevalence of Hepatitis D Virus Infection among Hepatitis B Virus Infected Patients in Qom Province, Center of Iran" by Ghadiret al. (1) which was performed to determine the prevalence of hepatitis D in the general population of Qom province and the potential risk factors for acquiring HDV. They found 48 subjects (1.3%) suffered from hepatitis B and only one HBsAg-positive case with HDV infection (0.03%) and concluded that the prevalence of hepatitis D in Qom is the lowest in Iran. Despite this fact that the only person who was positive for hepatitis D was a 31-years-old woman, living in Qom but originated from Afghanistan (opposite of study’s method which claimed that those who were not Iranian were excluded from the study) (1), there are some skeptical concerns regarding the comparison with hepatitis B positive and hepatitis D positive for potential risk factors.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common reasons of enzyme increase in liver. In About 10 percent of patients with NAFLD, the disease progresses toward Non Alcoholic Steatohepatitis (NASH) and about one third of them may progress toward cirrhosis, liver dysfunction, and even hepatocellular carcinoma.Objectives: According to high prevalence of NAFLD and the fact that there is no consensus on treatment of this disease, the aim of this study was to assess the effects of metformin, pioglitazone, and silymarin on treatment of NAFLD.Patients and Methods: Sixty-six patients with NAFLD who were presented in the Endocrinology and Metabolism clinic of Boo’ali Hospital, Qazvin, Iran, were assigned randomly into three groups (n=22). First group was treated by pioglitazone 15 mg/d, second group by metformin 500 mg/d, and third group by silymarin 140 mg/d. All patients underwent clinical and biochemical evaluations including weight, fasting blood sugar (FBS), lipid profiles, body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum insulin levels in pre- and post-intervention after eight-week follow up.Results: Before the treatment there was no significant difference between three groups with respect to average age, BMI and gender, FBS, lipid profile, AST, ALT, serum insulin level, and Homeostasis Model Assessment (HOMA) index for insulin resistance. After the intervention, a significant reduction was observed in average amount of FBS, lipid profile, ALT, AST, serum insulin level and HOMA index in three groups (P<0.01). The most reduction in average FBS, TG, serum insulin level, and HOMA index was observed in pioglitazone group, the most reduction in average amount of cholesterol was seen in metformin group, and the most decrease in average amount of AST and ALT occurred in silymarin group.Conclusions: These results suggest that all drugs are beneficial in improving biochemical indices in patients with NAFLD. Changes in AST and ALT in silymarin group were demonstrated more than that in other groups and the average difference between changes was significant between silymarin and metformin groups.

Background: Many types of cardiovascular complications such as; cardiac arrhythmias, impaired cardiac function, myocardial ischemia and decreased left ventricular function, have been attributed to interferon therapy.Objectives: The aim of this study was to evaluate the effects of combination therapy pegylated interferon and ribavirin on left ventricular systolic and diastolic functions in patients with a chronic hepatitis C infection.Patients and Methods: A total of 120 patients, eligible for hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin, were included in this study. All patients underwent a full cardiovascular baseline examination including; detailed medical history, thorough clinical examination, 12 lead electrocardiogram (ECG), and echocardiography.A cardiac evaluation was performed at the beginning and six months after starting combination therapy.Results: No significant changes regarding cardiac symptoms including; shortness of breath, cough, palpitations, chest pain and hypertension, were found during or six months after starting the combined therapy. ECG findings showed statistically nonsignificant decreases in the QT interval, while corrected QT showed statistically nonsignificant increases six months after beginning combined therapy, when compared to their values before treatment. Also with regard to the echocardiography findings, there was no statistically significant difference found between any of the echocardiography parameters six months after starting combined therapy compared to their values before treatment.Conclusions: The results of our study suggest that, combination therapy does not cause a significant deterioration in cardiac function in patients with a chronic hepatitis C infection, and it may be used safely in patients without cardiac disease.