Vitamin D role in hepatitis B: focus on immune system and genetics mechanism.

According to the World Health Organization (WHO) report, viral hepatitis has been a problem in human society. Vitamins play a significant role in preventing the hepatocarcinoma and liver cirrhosis. In this report, we will first focus on the vitamin D function in the immune system reactions, and then investigate its role in the viral infections and the signaling pathway of hepatitis B virus. The existence of the cytochrome P450 (CYP) 27B1 enzyme, which is involved in vitamin D synthesis in immune system cells, has drawn researchers ' attention to the field of immune system. Toll like receptor (TLR) play a significant role in the immune system, and are one of the primary receptors of the innate immune system. In addition, the synthesis of inflammatory cytokines, such as Interferon γ (IFNγ) and Interleukin-2 (IL-2) is one of the key roles of T helper type 1 (Th1) cells; these cells can suppress two cited cytokines via vitamin D. In the chronic phase of hepatitis B, Cytotoxic T lymphocytes (CTLs) cells have weaker performance than the acute phase of the disease. The association between vitamin D physiologies with viral infections is also confirmed by genetic studies, carried out on genetic variations of vitamin D receptor (VDR) R-encoding disease susceptibility gene. Vitamin D affects different phases of the disease. Therefore, further experiments in this area are proposed.

Comparison of fluoxetine and duloxetine hydrochloride therapeutic effects on patients with constipation-predominant irritable bowel syndrome.

Aim: As few randomized clinical trials have verified the efficacy of selective and norepinephrine reuptake inhibitors in IBS, the current study made an inclusive comparison between them, and their effectiveness in IBS-C was proven. Background: Irritable bowel syndrome with constipation (IBS-C) is a functional bowel disorder characterized by changes in bowel movements and abdominal pain in the absence of identifiable structural abnormalities. Despite much progress in the treatment of other types of IBS, limited treatments are available for IBS-C. Methods: The study population comprised 182 IBS-C patients who were randomly divided into 3 groups according to treatment type. One group was given 20 mg of dicyclomine and fluoxetine, the second group received dicyclomine along with duloxetine hydrochloride, and the third group received dicyclomine only for two months. The severity of symptoms was recorded by questionnaire at the beginning and end of the treatment. Results: The average age and BMI of the patients were 28.5 ± 5.2 years and 25.2 ± 2.4 kg/m2, respectively. Duloxetine was more effective than fluoxetine in reducing flatulence (p=0.043), abdominal pain intensity (p≤0.046), and duration (p≤0.003), in increasing the quality of life (p≤0.046), and the frequency of fecal excretion in patients (p≤0.004). Conclusion: Based on the study findings, fluoxetine and duloxetine had greater therapeutic effects on all symptoms of IBD than dicyclomine, with duloxetine, specifically, being more effective than fluoxetine. Further studies on larger groups are suggested to determine the best dosage and identify any potential side effects of these drugs.

Co-Administration of Vitamin E and Atorvastatin Improves Insulin Sensitivity and Peroxisome Proliferator-Activated Receptor-γ Expression in Type 2 Diabetic Patients: A Randomized Double-Blind Clinical Trial.

Background: Negative effects of statins on glucose metabolism have been reported. The present study aimed to investigate the effects of co-administration of vitamin E and atorvastatin on glycemic control in hyperlipidemic patients with type 2 diabetes mellitus (T2DM). Methods: A randomized double-blind clinical trial was conducted at Vali-e-Asr Teaching Hospital (Zanjan, Iran) from July 2017 to March 2018. A total of 30 T2DM female patients were allocated to two groups, namely atorvastatin with placebo (n=15) and atorvastatin with vitamin E (n=15). The patients received daily 20 mg atorvastatin and 400 IU vitamin E or placebo for 12 weeks. Anthropometric and biochemical measures were recorded pre- and post-intervention. Peroxisome proliferator-activated receptor-γ (PPAR-γ) expression was measured in peripheral blood mononuclear cells (PBMCs). Independent sample t test and paired t test were used to analyze between- and within-group variables, respectively. The analysis of covariance (ANCOVA) was used to adjust the effect of baseline variables on the outcomes. P<0.05 was considered statistically significant. Results: After baseline adjustment, there was a significant improvement in homeostatic model assessment for insulin resistance (HOMA-IR) (P=0.04) and serum insulin (P<0.001) in the atorvastatin with vitamin E group compared to the atorvastatin with the placebo group. In addition, co-administration of vitamin E with atorvastatin significantly upregulated PPAR-γ expression (OR=5.4, P=0.04) in the PBMCs of T2DM patients. Conclusion: Co-administration of vitamin E and atorvastatin reduced insulin resistance and improved PPAR-γ mRNA expression. Further studies are required to substantiate our findings. Trial registration number: IRCT 20170918036256N.

Neurological manifestations of coronavirus infections: role of angiotensin-converting enzyme 2 in COVID-19.

AIM OF THE STUDY: In December 2019, a highly pathogenic coronavirus called SARS-CoV-2 (formerly identified as 2019-nCoV) appeared in Wuhan, China, and has since been spreading rapidly around the world. we reviewed the neurological manifestations of this infection and the potential of ACE2 in the nervous system. MATERIALS AND METHODS: Six databases (Medline, Scopus, Embase, Web of Science, WHO, and google scholar) were searched and screened by the authors for having appropriate information about covid-19. Finally, 72 studies were identified, summarized and reviewed. RESULT: The most specific manifestation of SARS-CoV-2 patients is pulmonary distress, and several patients admitted to intensive care units were not able to breathe spontaneously. In addition, the SARS-CoV-2 outbreak has a significant effect on nervous systems and may even lead to serious neurological damage. The neuroinvasive pathobiology is still not fully elucidated and thus the effect of CoV infections on the nervous system needs to be explored. The spike protein of the virus and the angiotensin-converting enzyme 2 (ACE2) lead to the presence of both SARS-CoV and SARS-CoV-2 in the cells and, subsequently, decreased ACE2 expression. CONCLUSION: The therapeutic possibilities of ACE2 antibody, ACE2-derived peptides, and small molecule blockers of ACE2 include a receptor-binding domain blocking approach. Hence, future studies of ACE2 may be very helpful in discovering a therapy for SARS-CoV-2.

Comparison of Gastrointestinal Symptoms between Patients Undergoing Hemodialysis and Healthy Population.

Background: Patients with end-stage renal disease (ESRD) complain of many gastrointestinal (GI) problems. The goal of the current study was to compare the prevalence of GI disorders in a relatively large group of patients with ESRD with healthy participants. Methods: In a matched case-control study, 597 patients undergoing hemodialysis and 740 healthy participants were investigated. All subjects were asked to complete Rome III questionnaire, including five modules to evaluate GI disorders. The Hospital Anxiety and Depression questionnaire, as well as the 12-general health questionnaire for psychological disorders assessment, were used. Results: Our results showed that in patients undergoing hemodialysis, the prevalence of irritable bowel syndrome (IBS) (OR=1.75), gastroesophageal reflux disease (GERD) (OR=1.55), and dyspepsia (OR=3.39) was significantly higher than in healthy control participants, while no significant difference was found in terms of constipation (OR=0.88). The association remained significant for dyspepsia and IBS even after controlling for psychological disorders as important potential confounding variables. On the other hand, adjustment for psychological disorders led to an insignificant association between hemodialysis and GERD. Surprisingly a significant relationship was observed between constipation and hemodialysis after adjustment for mentioned psychological factors. Conclusion: Our results showed that there was a significant relationship between hemodialysis and some GI complaints such as IBS, dyspepsia, GERD, and bloating. Psychological disorders only influence GERD prevalence in patients undergoing hemodialysis.

Diabetes Mellitus, Obesity, and Risk of Pancreatic Ductal Adenocarcinoma: a Large Case-Control Study from Iran.

BACKGROUND Pancreatic cancer (PC) is a deadly, globally increasing cancer. The causes of PC are still insufficiently known, however smoking, diabetes mellitus (DM), and obesity have been identified as risk factors of PC, mostly in the developed countries. We evaluated these risk factors and their contribution to PC among an Iranian population. METHODS Cases and controls were selected from patients who were registered to a tertiary gastrointestinal diseases referral hospital in Tehran, Iran, from Jan 2012 to Jan 2018. Information on risk factors was collected by personal interview using a structured questionnaire. Logistic regression models were used to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS We recruited 470 new patients with histopathological PC diagnosis and 526 sex and age-matched controls. Cigarette-smoking [AOR: 1.65 (1.15-2.38)], opium use [AOR: 1.58 (1.06-2.35)], DM [AOR: 1.99 (1.31-3.02)], and having a history of any cancer in a first-degree family member [AOR: 1.53 (1.14-2.05)] were associated with an increased risk of PC. We did not find an association between obesity [AOR: 0.99 (0.71-1.38)] and PC. Approximately 4.6%, 5.9%, 8.2%, and 10.9% risk of PC were related to cigarette-smoking, opium use, DM, and family history of any cancer, respectively. CONCLUSION This study supports that DM is associated with PC risk; however, similar to many studies in Asia, obesity is not associated with PC in Iranians. DM has the highest impact on PC development in Iranian women.

Long-term Efficacy of Combined Treatment in Patients with Idiopathic Achalasia.

BACKGROUND Several treatment strategies are available to treat achalasia. Although combined therapy has been used for several years, there are limited data on long-term outcomes. We aimed to determine its long-term efficacy in patients who were resistant or those with rapid relapse. METHODS In this prospective study, we reviewed the records of 1100 patients with achalasia, who were candidates for pneumatic balloon dilatation (PBD) in our center from 1996 to 2018. We enrolled 197 patients resistant to initial treatment or with rapid relapse of symptoms after three sessions of PBD. Clinical evaluation and time barium esophagogram (TBE) were done before treatment, a month afterward, and when clinical symptoms increased in order to confirm relapse, and at the end of follow-up. RESULTS A total of 168 patients accepted combined therapy. The mean duration of follow-up was 9.04 years. Achalasia symptom score (ASS) dropped from 10.82 to 3.62 a month after treatment and was 3.09 at the end of the follow-up (p = 0.0001 and 0.001). TBE had a decrease in mean height of barium one month after treatment (9.23 vs. 5.10, p = 0.001), and this reduction persisted until the end of follow-up (3.39, p = 0.001). Vantrappen score at the end of the follow-up showed 56 patients in excellent, 51 in good, 33 in moderate, and 14 in poor condition (89% acceptable response rate). CONCLUSION Our results showed the long-term efficacy of combined treatment in patients with achalasia who otherwise had to undergo a high-risk and costly procedure, which makes it a safe and effective alternative for myotomy.

Efficacy and Safety of Tofacitinib for Treatment of Moderate to Severe Active Ulcerative Colitis: First Report from Iran.

BACKGROUND: Tofacitinib, a selective inhibitor of JAK/STAT pathway, has recently become available in our region. Here, we examined the safety and efficacy of tofacitinib in active ulcerative colitis (UC). METHODS: In a prospective, non-randomized, placebo-free, 52-week clinical trial defined in two phases of induction and maintenance, adult patients with active UC and no response or loss of response to previous conventional treatments, or anti-TNF were recruited (IRCT20181217042020N2). Patients received 10 mg/BID of tofacitinib for 8 weeks. Clinically responding patients were entered into the maintenance phase and received tofacitinib 5 mg/BID for 44 weeks. Clinical evaluation, biochemical tests and endoscopy at time points of baseline, 8, 24 and 52 weeks were performed. The primary outcome was clinical remission at 8 and 52 weeks. RESULTS: Fifty out of 53 enrolled patients completed the induction phase. Clinical response and clinical remission at 8 weeks occurred in 84% and 9.5%, respectively. Forty-two patients who had clinical response entered the maintenance phase. Clinical remission based on the total Mayo score and the partial Mayo score occurred in 38.9% and 55.3% at 24 weeks and in 61.1% and 72.2% at 52 weeks, respectively. There was significant correlation between the total and partial Mayo score with regard to clinical remission in both 24 and 52 weeks. No serious adverse events, no case of herpes zoster, but two cases of deep vein thrombosis were seen. CONCLUSIONS: Our study showed acceptable efficacy and safety for tofacitinib and suggested a correlation between the total Mayo score with partial Mayo score with regard to clinical remission.

The prevalence of metabolic syndrome parameters and their association with headache characteristics among migraineurs.

Background: Migraine is associated with metabolic syndrome (MetS). There are evidences that components of MetS are more prevalent among migraine patients than non-migraineurs. Since both migraine and MetS are associated with a high risk of cardiovascular events, it is likely that the parameters of MetS increase the occurrence of cardiovascular disease (CVD) in migraineurs. The present research project was conducted for the purpose of investigating the relationship between MetS parameters and different items of migraine headaches. Methods: This descriptive-analytical, cross-sectional study was performed on 240 migraineurs [according to International Headache Society (HIS) II criteria] within the 17+ age range. The participants were selected via consecutive and convenience sampling method. The evaluated parameters for each subject included 2 arms: migraine characteristics (intensity, frequency of attacks, subtype, duration, and treatment regimen) and indices of MetS according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP-III) report criteria [high-density lipoprotein-cholesterol ( HDL-C), triglyceride (TG), fasting plasma glucose (FPG), height, waist circumference (WC), systolic and diastolic blood pressure (BP), and body mass index (BMI)]. All data were analyzed in SPSS software. Results: Total prevalence of MetS was 16.25% (39 patients). There was a statistically meaningful relationship between hypertriglyceridemia and gender (P = 0.021), hypertriglyceridemia and prophylactic antimigraine regimen (P = 0.022), hyperglycemia and age group (P = 0.010), hyperglycemia and the intensity of headache (P = 0.048), hyperglycemia and prophylactic treatment (P = 0.001), systolic hypertension and migraine subtype (P = 0.004), systolic hypertension and the duration of migraine disease (P = 0.005), diastolic hypertension and migraine subtype (P = 0.002), WC and gender (P = 0.001), WC and the intensity of headache (P = 0.028), WC and prophylactic medication (P = 0.017), HDL and gender (P = 0.001), HDL and the prophylactic regimen (P = 0.023), and MetS and gender (P = 0.005). The prevalence of MetS was increased with increase in the severity of migraine headache. Conclusion: Due to the relative increase in the prevalence of MetS in patients with more severe migraine, an evaluation of the mechanisms of MetS is recommended in this population.

Celiac Crisis in a Young Woman: Raising Awareness of a Life-Threatening Condition.

Celiac crisis is a rare, acute, and life-threatening presentation of celiac disease. Its clinical presentations consist of severe watery non-bloody diarrhea, electrolyte disturbances (i.e. hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, and metabolic acidosis), hypoproteinemia, and dehydration. Here we present a 33-year-old woman who referred with profuse diarrhea, weight loss, hemodynamic instability, hypokalemia, hypoproteinemia, ascites, pancytopenia, and iron deficiency anemia. She used herbal medicines for constipation and had severe weakness after her childbirth. The patient was diagnosed as having celiac disease through pathological and serological evaluations 10 months earlier. Diagnosis of celiac crisis after ruling out the other causes of resistant celiac was made and she was treated with steroids.

Combined effects of synbiotic and sitagliptin versus sitagliptin alone in patients with nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases in recent years. The aim of this study was to evaluate the effects of sitagliptin with and without a synbiotic supplement in the treatment of patients with NAFLD. METHODS: In total, 138 NAFLD patients aged 18-60 years were enrolled in the study. Patients were randomized to one of the following treatments for 16 weeks: Group I (n=68), sitagliptin 50 mg daily plus placebo (one capsule per day) or group II (n=70) sitagliptin 50 mg daily plus synbiotic (one capsule per day). Changes in fasting blood glucose (FBS), liver enzymes, lipid profile, and body mass index were compared between the groups. RESULTS: The mean change in FBS with sitagliptin-placebo from baseline was -10.47±5.77 mg/dL, and that with sitagliptin-synbiotic was -13.52±4.16 mg/dL. There was a significant difference between the groups (P<0.001). The mean change in cholesterol (Chol) was -8.34±28.83 mg/dL with sitagliptin-placebo and -21.25±15.50 mg/dL with sitagliptinsynbiotic. There was a significant difference between the two groups (P=0.029). The administration of sitagliptin-placebo induced an increase of 6.13±27.04 mg/dL in low density lipoprotein (LDL), whereas sitagliptin-synbiotic induced a decrease of 14.92±15.85 mg/dL in LDL. A significant difference was observed between the two groups (P<0.001). On the other hand, in the sitagliptin-synbiotic group, there was significant improvement in aspartate aminotransferase (AST) level compared to the sitagliptin-placebo group (P=0.018). CONCLUSION: Sitagliptin-synbiotic produced greater improvement in FBS, AST, Chol, and LDL compared to sitagliptin alone in patients with NAFLD.

A High Serum-Ascites Albumin Gradient and Mediastinal Fibrosarcoma: A Case Report.

Accumulation of free fluid in the peritoneal cavity is called ascites. The first step in identifying its etiology is to determine the serum-ascites albumin gradient (SAAG). According to this parameter, a high SAAG is regarded as a gradient greater than 1.1 g/dL. This condition has some differential diagnoses such as liver cirrhosis, Budd-Chiari syndrome, heart failure, and idiopathic portal fibrosis. In the present article, we present a young man with abdominal distention due to a high SAAG. Further evaluation of the abdominal and thoracic cavity revealed a mass in the posterior mediastinum, which had compressed the inferior vena cava and left atrium and led to Budd-Chiari syndrome. Evaluation of the biopsy sample showed fibrosarcoma. Mediastinal fibrosarcomas, though rare, should be considered in the differential diagnosis of mediastinal masses.

The Best Cut-Off Value for HbA1c as a Screening Tool in Iranian Women With Gestational Diabetes Mellitus.

Objective: Gestational diabetes mellitus (GDM) is a prevalent disorder which increases maternal and fetal complications. The oral glucose tolerance test (OGTT) is a traditional, time -consuming and intensive test which is poorly tolerated by pregnant women. To date, increasing evidence considered HbA1c as a screening tool and reported various cut-off values in different populations. In alignment with existing literature, we determined for the first time, the optimal cut-off value for HbA1c in Iranian women with GDM. Materials and methods: This case-control study was conducted in Valie-Asr hospital between June 2015 and March 2016. A total of 200 pregnant women who were diagnosed with GDM were selected as study cases. For the control group, 200 healthy women were randomly selected. Fasting blood samples were taken for biochemical analysis, and OGTT was done in all participants. Demographic and anthropometric indexes were measured. Performance of the HbA1c test was analyzed by the Receiver Operating Characteristic (ROC) curve, and the sensitivity and specificity for different HbA1c cut-off points were calculated subsequently. Results: Analysis showed that the mean age (p < 0.001) and BMI (p < 0.001) were significantly higher in the GDM group compared to those in non-GDM pregnant women. GDM participants reported positive family- and previous history of GDM more than healthy pregnant women (p = 0.04 and p < 0.001, respectively). All the markers for Lipid profile were significantly different between the two groups (p = <0.001) except for total cholesterol. The rate of Caesarean section and neonate's Apgar score were not significantly different between the two groups. The best equilibrium between sensitivity (80%) and specificity (76%) for HbA1c was 5.05%. Conclusion: Our results suggest that pregnant women with HbA1c of ≥ 5.05% should proceed with an OGTT. Further investigations with larger sample size are needed to provide more robust evidence for the diagnostic and screening value of HbA1c in identifying pregnant women with GDM.

Comparative Study on Adding Pioglitazone or Sitagliptin to Patients with Type 2 Diabetes Mellitus Insufficiently Controlled With Metformin.

BACKGROUND: Diabetes mellitus is a progressive disorder that often requires combination therapy. AIM: This study aimed to compare and study of add-on sitagliptin versus pioglitazone in patients with type 2 diabetes inadequately controlled with metformin. METHODS: This 12-week, randomised, open-label and single centre study compared sitagliptin (100 mg daily, n = 80) and pioglitazone (30 mg daily, n = 80) in type 2 diabetic patients whose disease was not adequately controlled with metformin. RESULTS: The mean change in HbA1c from baseline was -1.001 ± 0.83 with sitagliptin and -0.75 ± 1.20 with pioglitazone, and there were no significant difference between groups (P = 0.132). The mean change in fasting blood sugar (FBS) was -18.48 ± 33.32 mg/dl with sitagliptin and -20.53 ± 53.97 mg/dl with pioglitazone, and there were no significant difference between groups (P = 0.773). Sitagliptin caused 1.08 ± 2.39 kg decrease in weight, whereas pioglitazone caused 0.27 ± 2.42 kg increase in weight, with a between-group difference of 0.81 kg (P < 0.001). On the other hand, in sitagliptin group, there was greater improvement in lipid profile than pioglitazone group. CONCLUSION: Sitagliptin and Pioglitazone demonstrated similar improvements in glycemic control in type 2 diabetes mellitus patients whose diabetes had been inadequately controlled with metformin. Nevertheless, sitagliptin was more effective than pioglitazone regarding lipid and body weight change.