Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia

AIM： To identify the distribution of hepatitis B virus （HBV） subgenotype and basal core promoter （BCP） mutations among patients with HBV-associated liver disease in Indonesia.
METHODS： Patients with chronic hepatitis （CH, n =61）, liver cirrhosis （LC, n = 62）, and hepatocellular carcinoma （HCC, n = 48） were included in this study. HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing.
RESULTS： HBV genotype B （subgenotypes B2, B3, B4, 85 and B7） the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C （subgenotypes C1, C2 and C3） was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 （84.9%） and C1 （82.2%） were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 （84.9%） and adrq＋ （89.4%） were the most prevalent in HBV genotype B and C, respectively. Double mutation （A1762T/G1764A） in the BCP was significantly higher in LC （59.7%） and HCC （54.2%） than in CH （19.7%）, suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC （46.8%）, but lower in HCC （22.9%） and CH （18.0%）, suggesting that this mutation may be an indicator of cirrhosis.
CONCLUSION： HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease.     

Molecular phylogeography of Culex quinquefasciatus mosquitoes in central Bangladesh

Mosquitoes in the Culex pipiens complex are a major vector of numerous parasitic and arboviral diseases. Here we report the phylogeography of a prevalent Culex mosquito, Cx. quinquefasciatus, from three locations in Bangladesh: Dhaka, Savar and Mymensingh. Sequence analysis of the genes encoding mitochondrial cytochrome oxidase subunit II, nuclear elongation factor-1 alpha, and acetylcholinesterase-2 revealed the lack of a population genetic structure among the three locations. Moreover, the highly divergent ribosomal internal transcribed spacer 2 suggests that this locus has not evolved in concert. The results further show evidence of historical introgression of internal transcribed spacer 2 from Cx. pipiens to Cx. quinquefasciatus of Bangladesh, and that the introgression occurred before Cx. quinquefasciatus had dispersed within this region. The study also reveals historical population expansion in this region, followed by a post-expansion Wolbachia sweep.     

Irritable Bowel Syndrome in a Bangladeshi Urban Community: Prevalence and Health Care Seeking Pattern

Background/Aims:

Although irritable bowel syndrome (IBS) is a common gastrointestinal disorder, its prevalence is unknown, especially in the urban population of Bangladesh. This community-based study aimed to find out the prevalence of IBS and healthcare-seeking patterns using the Rome-II definition.

Materials and Methods:

A population-based cross-sectional survey of 1503 persons aged 15 years and above was carried out in an urban community of Bangladesh. The subjects were interviewed using a valid questionnaire based on Rome-II criteria in a home setting. Statistical analysis was performed with Statistical Package for Social Science (SPSS) Programmers and the level of significance was set at P ≤ 0.05.

Results:

A response rate of 97.2% yielded 1503 questionnaires for analysis. The prevalence of IBS was found to be 7.7% (n = 116) with a male to female ratio of 1:1.36 (49 vs. 67). “Diarrhoea-predominant IBS” (50%, n = 58) was the predominant IBS subgroup. Symptoms of abdominal pain associated with a change in stool frequency (100%) and consistency (88.8%) were quite common. All IBS symptoms were more prevalent among women (P < 0.000). In the past one year, 65.5% (n = 76) IBS subjects had consulted a physician with a slightly higher rate of women consulters (68.6 vs. 61.2%). The main predictor for healthcare-seeking was the presence of multiple dyspeptic symptoms.

Conclusions:

The prevalence of IBS in the urban community was found to be similar to that in rural communities. A higher rate of consultation was found among urban IBS subjects than in the rural subjects, with sex not seen to be a discriminator to seek consultation.     

Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease

Background

IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance.

Objectives

In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined.

Patients and Methods

Frequencies of the protective genotype C/C of SNP, rs12979860 were determined in healthy subjects, spontaneous resolvers, and chronic HCV type 4 patients with low F scores and in patients with end stage liver disease (ESLD). This study included a total of 404 subjects. Patients infected with HCV type 4a (n = 304) were divided into; chronic hepatitis C (CHC) with low F scores (CHC, n = 110), end stage liver disease (n = 110), liver cirrhosis (LC) (n = 35) and hepatocellular carcinoma (HCC) patients (n = 75), spontaneous resolvers of HCV infection (n = 84) were also included. A healthy group representing the Egyptian population (n = 100) was also included in the genotyping of IL28B. The later was typed via a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay analysis on purified genomic DNA extracted from all individuals.

Results

A significant increase (P < 0.0005) was observed in frequencies of IL-28B rs12979860 C/C genotypes in the healthy population, than in the CHC, LC and HCC groups (C/C = 48%, 13%, 0%.and 0% respectively). On the other hand the C/C genotype was significantly higher (P < 0.0005) in spontaneous resolvers than in healthy subjects. A comparable significant increase in the frequency of C/T allele accompanied by mild elevation of T/T allele frequency, were detected along the progression towards ESLD.

Conclusions

Genotype C/C is associated with viral clearance during acute infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in ESLD suggests a central role of this genotype against HCV disease progression.     

The effects of Pilates on metabolic control and physical performance in adolescents with Type 1 diabetes mellitus

Physical activity is a substantial method in the management of children and adolescents with Type 1 diabetes mellitus but it is not considered as a treatment for diabetes. The aim of this study was to investigate the effects of Pilates exercises on metabolic control and physical performance in patients with type 1 diabetes mellitus. Thirty one sedentary patients with type 1 diabetes mellitus, ranging in age from 12 to 17 (experimental group, n=17 and control group, n=14) were submitted to 12 weeks of Pilates training. Participants underwent tests to determine the physical performance and metabolic control before and after 12 weeks of Pilates session. At the end of study, there were significant alterations in physical performance of the study group. Peak power, mean power, vertical jump and flexibility of study group increased. There were no alterations for this parameters in the control group. There was no significant difference for glycated hemoglobin (HbA1c) in both groups. Conclusions: Physical performance increased via Pilates exercises in the patients with type 1 DM. However there were no changes in metabolic control. In the present study, the positive effects of exercise on metabolic control could not be shown in patients with Type 1 DM.     

Adjustment of sweep gas flow during cardiopulmonary bypass

Cardiopulmonary bypass (CPB) is one of the major tools of cardiac surgery. However, no clear data are available for the ideal value of sweep gas flow to oxygenator during CPB. The aim of this study was to determine the best value for sweep gas flow during CPB. Thirty patients undergoing isolated CABG were randomly and equally allocated into three groups. Sweep gas flow to oxygenator was kept at 1.35 l/min/m2 in group 1, 1.60 l/min/m2 in group 2, and 2.0 l/min/m2 in group 3. All patients were operated on under the same anaesthetic regime and surgical techniques. Samples for blood gas analysis were collected at T1: before CPB; T2: 5 min after the initiation of CPB; T3: just before rewarning; and T4: at the end of rewarming. Five minutes after the initiation of CPB (T2), pCO2 decreased significantly in groups 2 and 3 compared to group 1 (p < 0.02). With the addition of hypothermia (T3), the changes in the pH and pCO2 became more profound and, in this period, the levels in group 3 patients outranged the physiologic limits, with pCO2 and pH values being 28 +/- 3 mmHg and 7.50 +/- 0.04, respectively. At the end of the rewarming period (T4), in spite of increased carbon dioxide production, pCO2 values were below the physiologic limits in groups 2 and 3. We conclude that sweep gas flow to the oxygenator should be kept between 1.35 and 1.60 l/min/m2 during CPB to avoid hypocapnia, which results in alkalosis and has hazardous effects on lung mechanics, cerebral blood flow, and the cardiovascular system.     

Increased inflammatory markers are associated with obesity and not with target organ damage in newly diagnosed untreated essential hypertensive patients

The aim of this study was to investigate whether inflammatory markers are associated with hypertensive end organ damage or obesity in patients with hypertension. Seventy newly diagnosed essential hypertensive patients (29 men and 41 women aged 49.6 ± 9.5 y) and 25 age-sex-matched normotensive subjects (12 men and 13 women aged 45.8 ± 7.3 y) were asked about their family history of hypertension and smoking habits, and body mass index (BMI) was recorded and blood samples were taken to measure fibrinogen, C-reactive protein (CRP), and homocysteine levels. In hypertensive patients, creatinine clearance, urinary albumin extraction, and left ventricular mass index were determined. Hypertensive patients had significantly higher BMIs and inflammatory markers when compared with normotensive healthy controls. The CRP was positively associated with BMI (P < .05), diastolic blood pressure (P < .05), fibrinogen (P < .01), urinary albumin extraction (P < .01), and left ventricular mass index (P < .05). The BMI and serum fibrinogen level were independently associated with CRP. The effect of inflammation on the development of hypertensive end organ damage may be associated with obesity, so that control of obesity may eliminate the inflammatory state in hypertensive patients and also hypertensive end organ damage.     

Single-stranded DNA oligonucleotides inhibit TLR3-mediated responses in human monocyte-derived dendritic cells and in vivo in cynomolgus macaques

TLR3 is a key receptor for recognition of double-stranded RNA and initiation of immune responses against viral infections. However, hyperactive responses can have adverse effects, such as virus-induced asthma. Strategies to prevent TLR3-mediated pathology are therefore desired. We investigated the effect of single-stranded DNA oligonucleotides (ssDNA-ODNs) on TLR3 activation. Human monocyte-derived dendritic cells up-regulate maturation markers and secrete proinflammatory cytokines on treatment with the synthetic TLR3 ligand polyinosine-polycytidylic acid (poly I:C). These events were inhibited in cultures with ssDNA-ODNs. Poly I:C activation of nonhematopoietic cells was also inhibited by ssDNA-ODNs. The uptake of poly I:C into cells was reduced in the presence of ssDNA-ODNs, preventing TLR3 engagement from occurring. To confirm this inhibition in vivo, we administered ssDNA-ODNs and poly I:C, alone or in combination, via the intranasal route in cynomolgus macaques. Proinflammatory cytokines were detected in nasal secretions in the poly I:C group, while the levels were reduced in the groups receiving ssDNA-ODNs or both substances. Our results demonstrate that TLR3-triggered immune activation can be modulated by ssDNA-ODNs and provide evidence of dampening proinflammatory cytokine release in the airways of cynomolgus macaques. These findings may open novel perspectives for clinical strategies to prevent or treat inflammatory conditions exacerbated by TLR3 signaling.     

Evaluation of rabbit antibody response against 8 and 16 kDa recombinant subunits of antigen B from Echinococcus granulosus

ObjectiveTo immunize rabbits with 12 and 16 kDa recombinant subunits of antigen B from Echinococcus granulosus (E. granulosus) and measuring polyclonal antibody and humoral immune response using ELISA and gel diffusion.MethodsTwo mentioned antigens were cloned and expressed in expression vector and purified by affinity chromatography. Four young rabbits were selected and challenged intradermally with yielded recombinant antigens. Rabbits' sera were collected post infection and were tested using ELISA and gel diffusion for polyclonal antibody detection 10 days after last injection.ResultsThe specific antibody against the recombinant peptides was efficiently produced within 4 weeks post infection.ConclusionsProduced recombinants proteins could induce the immune response of the rabbits successfully. This process might improve the clarification of diagnosis and vaccination as regards hydatidosis.     

Fibrodysplasia ossificans progressiva without characteristic skeletal anomalies

Fibrodysplasia ossificans progressiva (FOP) is a rare but extremely disabling genetic disease of the skeletal system. This disease is characterized by progression of heterotopic ossification within skeletal muscles, ligaments and tendons. Most patients with FOP are misdiagnosed early in life before the appearance of heterotopic ossification and undergo diagnostic procedures such as biopsy that can cause lifelong disability. Almost all of the patients have some peculiar congenital anomalies, including short great toes, hallux valgus, short thumbs and hypoplasia of digital phalanges. These congenital defects support the diagnosis of FOP, but are not constantly observed in the totality of patients. If necessary, genetic studies can be performed to confirm the diagnosis. Once diagnosed, patients should be advised in order to avoid unnecessary traumas, surgical procedures, biopsies, intramuscular injections and vaccinations. Here, we describe a patient with FOP without characteristic congenital skeletal anomalies.