A novel medium-throughput biological assay system for HTLV-1 infectivity and drug discovery

Objective(s): Here, a reporter cell line containing two reporter vectors were developed, in order to monitor the Human T-Lymphotropic Virus type1(HTLV-1) infectivity and the cell viability simultaneously. Materials and Methods: The reporter cell line was constructed by stably transfected baby hamster's kidney cell line (BHK-21), with the genomes expressing two different reporters in separate plasmids.The first reporter gene is transactivated by the HTLV-1 tax protein, while the second reporter is continuously expressed when introduced into a mammalian cell. In order to show its functionality, the effect of the drug mix on HTLV-1 was assayed by this system and was compared to the results obtained by other methods. Results: HTLV-1 reporter cell line was found to produce high level of luciferase when co-cultured with MT-2 and Hut-102 cells but not with Jurkat cell. Moreover, the combination therapy against HTLV-1 can reduce luciferase expression of the cell when co-cultured with MT-2 and Hut-102 comparable to the ELISA (R=0.932, P-value =0.002). In addition, the results revealed the superiority of the present system over the molecular methods. Conclusion: The results demonstrated that the biological assay system is a beneficial tool for the medium-throughput anti-HTLV-1 drug screening and inhibitory effect

A novel medium-throughput biological assay system for HTLV-1 infectivity and drug discovery

Objective(s): Here, a reporter cell line containing two reporter vectors were developed, in order to monitor the Human T-Lymphotropic Virus type1(HTLV-1) infectivity and the cell viability simultaneously. Materials and Methods: The reporter cell line was constructed by stably transfected baby hamster's kidney cell line (BHK-21), with the genomes expressing two different reporters in separate plasmids.The first reporter gene is transactivated by the HTLV-1 tax protein, while the second reporter is continuously expressed when introduced into a mammalian cell. In order to show its functionality, the effect of the drug mix on HTLV-1 was assayed by this system and was compared to the results obtained by other methods. Results: HTLV-1 reporter cell line was found to produce high level of luciferase when co-cultured with MT-2 and Hut-102 cells but not with Jurkat cell. Moreover, the combination therapy against HTLV-1 can reduce luciferase expression of the cell when co-cultured with MT-2 and Hut-102 comparable to the ELISA (R=0.932, P-value =0.002). In addition, the results revealed the superiority of the present system over the molecular methods. Conclusion: The results demonstrated that the biological assay system is a beneficial tool for the medium-throughput anti-HTLV-1 drug screening and inhibitory effect

Evaluation of immune response to HBV vaccine in the staff and students of Sabzevar University of Medical Sciences (2014-15)

Evaluation of immune response to HBV vaccine in the staff and students of Sabzevar University of Medical Sciences (2014-15) Background:Hepatitis B is a bloodborne infections and it is predicted that about two billion people in the world have been exposed to the hepatitis B virus. Because of occupational reasons, medical students and staffs are more susceptible to expose to this disease than other members of society. Materials and Methods:This study is a descriptive-analytic study and 238 staffs and students of Sabzevar University of Medical Sciences were randomly selected and sampled. Then, the antibody titer of surface anti-protein of hepatitis B virus (HBs- Ab) was measured using ELISA method and the results were analyzed using the software Stata 12 after recording the demographic results and information. Results:Out of 238, 156 persons were female ( 65.5) and 82 persons ( 34.5) were male. 66 of individuals had antibody higher than 10 mu/ml and 37.4 of individuals showed the appropriate answers higher than 100 u/ml. The relationship between job, sex and marital status with the immune response was significant. 100 of people who received full dose along with the booster vaccine were immune. Over time, the percentage of immune people has been decreased. Conclusion:Considering the reduction of response to vaccines over time and healthcare personnel being at risk, it is recommended that antibody titer was periodically examined in these individuals in 5 to 10 years to administer a booster dose in the case of a decrease in antibody titers

Archives of Gynecology and Obstetrics / Prospective cohort study of pregnancy complications and birth outcomes in women with asthma

Background Asthma is the most common potentially serious medical complication in pregnancy. The purpose of this study was to determine the association between maternal asthma and a spectrum of adverse neonatal and maternal outcomes. Methods Events during pregnancy and birth outcome were evaluated in 34 asthmatic as well as 1569 non-asthmatic pregnant women who were enrolled in a prospective cohort study undertaken at the antenatal clinics of Mobini Hospital in Iran. The women were interviewed and classified according to clinical severity and asthma control as per GINA guidelines. Information on asthma symptoms was collected by a questionnaire as well as by spirometry and physical examination. All subjects were followed until delivery, and postpartum charts were reviewed to assess neonatal and maternal outcomes. Eosinophil cells counts were obtained and total IgE was measured by ELISA. Results were assessed by multivariate logistic regression adjusting for maternal age and parity, and for birth outcomes, for gestational diabetes, and hypertension/pre-eclampsia. Results The well-known relationship between family history of asthma and asthma in pregnancy was again supported (p < 0.001). Women with asthma had more bleeding events 3 weeks or more before delivery (OR 3.30, 95% CI 1.417.26), more often placenta problems (OR 6.86, 95% CI 1.4233.02), and gestational diabetes mellitus (OR 3.82, 95% CI 1.0613.75). No significant differences between asthmatic and non-asthmatic mothers regarding duration of gestation, birthweight, low Apgar scores, or neonatal respiratory difficulties were found. Total IgE antibody levels and eosinophil counts did not differ by asthma control and severity. Conclusions Asthma in pregnancy poses some risk for pregnancy complications and adverse perinatal outcomes. Managing asthma effectively throughout pregnancy could benefit women and their babies and help to reduce the health burden associated with asthma during pregnancy.(VLID)359028

SD1000: High Sustained Viral Response Rate in 1361 Patients With Hepatitis C Genotypes 1, 2, 3, and 4 Using a Low-cost, Fixed-dose Combination Tablet of Generic Sofosbuvir and Daclatasvir: A Multicenter, Phase III Clinical Trial

Background. The combination of sofosbuvir and daclatasvir is a potent, pangenotypic regimen suitable for mass-scale hepatitis C treatment, especially in resource-limited countries where newer, expensive combinations are not available. This combination has been widely tested on genotype 4. However, Phase III trials of this combination in other genotypes have been cost prohibitive. With the introduction of generic, low-cost sofosbuvir and daclatasvir, large-scale studies in resource-limited countries are now possible. Methods. Sofosbuvir at 400 mg and daclatasvir at 60 mg were coformulated into a fixed-dose combination (FDC) tablet (Sovodak, Rojan Pharma, Tehran, Iran). Patients from 46 centers were dosed for 12 or 24 weeks with or without ribavirin, in line with existing guidelines. Responses to treatment were evaluated 12 weeks after the end of treatment (for a sustained virological response at Week 12; SVR12). Results. There were 1361 patients recruited. Overall, the patients were 21% female, with a mean age of 50 years; 39% were cirrhotic; 22% were treatment-experienced; 47% were genotype 1, 41% were genotype 3, and 2% were other genotypes. The genotype was not known in 10% of the patients. The intention-to-treat and per-protocol SVR12 rates were 94.7% and 98.8%, respectively. The safety profile was unremarkable, treatment was well tolerated, and compliance with the single-tablet regimen was excellent. Conclusions. The treatment with FDC of sofosbuvir and daclatasvir achieved high SVR12 rates, equivalent to those seen in Phase III trials of other pangenotypic options, and has been conducted at a similar scale in a representative, real-world population at a cost of under $100 per patient, which makes this combination suitable for elimination protocols in resource-limited countries. Keywords:sofosbuvir; daclatasvir; Hepatitis C; sustained virological response; generic drug