siRNA drug development against hepatitis B virus infection

Introduction: Hepatitis B virus (HBV) infection is the worldwide leading cause of liver cirrhosis and hepatocellular carcinoma. Currently available medication can suppress viral replication in the majority of patients, but clearance of the viral antigens can be achieved in only about 10%.

Areas covered: RNA interference is a very attractive therapeutic option since a well-designed compound could possibly inhibit all HBV mRNA and thus synthesis of all its antigens, which could combine antiviral and immunomodulatory modes of action. The aim of the article is to provide current knowledge on possible use of small interfering RNA (siRNA) molecules in the treatment of chronic HBV infection.

Expert opinion: Based on the current status of clinical trials, we should expect that within the coming five years at least one siRNA molecule will be registered for clinical use. However, most important at this stage of development will be the safety profile, improving the route of administration, selection of the optimal combination with other anti-HBV drugs (nucleoside analogues, interferons) and finally selection of the optimal system introducing siRNA molecules into infected cells. Current therapeutic options for HBV, the siRNA mechanism of action, as well as preclinical and clinical studies with siRNA molecules are presented in this article.     

Neurodegenerative Genes Polymorphisms of the -491A/T APOE,the -877T/C APP and the Risk of Primary Open-angle Glaucoma in the Polish Population

Background: Glaucoma is characterized by optic neuropathy of the retinal ganglion cell. It may be possible that β-amyloid (Aβ) and apolipoprotein E (APOE), the main proteins of the pathogenesis of AD, play a role in glaucoma development. The aim of this study was to evaluate a relationship between the APP and APOE gene polymorphisms and the risk of primary open-angle glaucoma (POAG) occurrence.

Materials and methods: The study consisted of 183 patients with POAG and 209 healthy subjects. Genomic DNA was extracted from peripheral blood. Analysis of the gene polymorphisms was performed using PCR-RFLP.

Results: We found a statistically significant increase of the -491?T allele frequency (p?=?0.02; OR?=?1.48; 95% CI?=?1.06–2.08) of APOE in POAG compared to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the APP polymorphism between patients and controls group. We also found an association between APOE polymorphic variant and retinal nerve fiber layer (RNFL). There was a statistically significant difference in the APOE gene A/T genotype frequency in the early POAG stage and middle-advanced POAG stage in comparison to the advanced POAG stage (p?=?0.04; OR?=?3.38; 95% CI?=?1.04–10.97).

Conclusions: The -491?T allele of APOE polymorphism may be associated with a risk of POAG occurrence in the Polish population.     

Evaluation of a risk of a cross-reactivity with Echinococcus multilocularis-specific Em2plus antigen in patients with liver cancer

The incidence of non-specific reactions with E. multilocularis antigen in patients with liver malignancies, and the risk of a supradiagnosis of alveolar echinococcosis (AE) in space-occupying lesions in the liver due to neoplastic proliferative diseases were studied. Analysis of specific IgG serum antibody against Em2plus antigenic complex was performed in 11 AE patients in comparison to 76 individuals with malignant neoplasms of abdominal or extra-hepatic location, including some patients with primary hepatocellular cancer or distant metastases to liver, and 42 patients with benign hepatic lesions. Only one false borderline result was reported in a case with colorectal cancer, and dissemination to liver. Low risk of false positive results with E. multilocularis-specific Em2plus antigen in patients with liver malignancies makes the test valuable for practical reasons in a differential diagnosis of irregular tumor masses visualized by imaging techniques.     

Inhibition by secretin of the gastric acid responses to meals and to pentagastrin in duodenal ulcer patients

The inhibitory effects of intravenous secretion on the gastric acid responses to a meal and to pentagastrin were studied in seven duodenal ulcer patients.

A test meal of 10% peptone adjusted to pH 5·0 was introduced into the stomach and the Fordtran and Walsh method was used to measure the gastric acid output by monitoring the rate at which a solution of 0·3 M sodium bicarbonate had to be added to keep the pH of the gastric content constant at the value of 5·0. A constant dose of secretin (1 U/kg-hr) significantly depressed the serum gastrin response to a meal and produced an inhibition of acid secretion by about 70% of the control level. Secretin inhibited the acid response induced by pentagastrin by about 60% and simultaneously provoked a pancreatic bicarbonate output sufficient to neutralize about 60% of the gastric acid output to pentagastrin. We conclude that secretin is a strong inhibitor of gastric secretion in duodenal ulcer patients induced by a meal and by pentagastrin.

     

A rare coexistence of primary hyperparathyroidism and hyperthyroidism due to toxic nodular goiter--a case report

The frequent association of thyroid and parathyroid disorders has been reported. Most commonly, hyperthyroidism may coexist with hypercalcemia, but the latter is successfully treated when euthyroidism is achieved. However, the concomitant hyperthyroidism with primary hyperparathyroidism is of a rare occurrence. Moreover, it may frequently go unrecognized. In this paper we report a case of a patient with hypercalcemia due to PTH--secreting parathyroid adenoma associated with hyperthyroidism due to toxic nodular goiter. This case demonstrates the dramatic outcome of those two coexisting disorders. We point out that in patients with primary hyperparathyroidism thyroid function test should always be carried out. A proper, first-line treatment of hyperthyroidism will prevent the deterioration of primary hyperparathyroidism course, and thus surgical parathyroid treatment may safely be introduced.     

Effects of adolescent online gaming time and motives on depressive,musculoskeletal, and psychosomatic symptoms

Aim. To investigate whether adolescent online gaming time and the additive effect of gaming motives were associated with depressive, musculoskeletal, and psychosomatic symptoms. The hypothesis was that adolescents who engage in online gaming with escape motives and increased online gaming time have higher probability for depressive, musculoskeletal, and psychosomatic symptoms compared to adolescents with other online gaming motives and/or less online gaming time.Method. An anonymous and voluntary questionnaire was completed during class hours by 7,757 Swedish adolescents aged 13–18 years. The questionnaire included demographic background, gaming habits, and depressive, musculoskeletal, and psychosomatic symptoms.Results. It was found that increased online gaming time during weekdays increased the probability of having depressive, musculoskeletal, and psychosomatic symptoms. However, these relations with time spent gaming were further explained by online gaming motives. Weekday online gaming for more than five hours a day, in combination with escape motives, was associated with an increased probability of depressive symptoms (odds ratio (OR) 4.614, 95% CI 3.230–6.590), musculoskeletal symptoms (OR 2.494, 95% CI 1.598–3.892), and psychosomatic symptoms (OR 4.437, 95% CI 2.966–6.637). The probability of ill health decreased when gaming was for fun or had social motives.Conclusion. Excessive gaming time and escape motives were found to be associated with increased probability of ill health among adolescents. Gaming motives may identify gamers in need of support to reduce unhealthy gaming behaviour as well as identify individuals at risk for ill health.