Dose-dependent and sequence-dependent cytotoxicity of erlotinib and docetaxel in head and neck squamous cell carcinoma

The purpose of this study was to determine whether the efficacy of taxoid treatment combined with epidermal growth factor receptor (EGFR) inhibition is dose and sequence dependent in head and neck squamous cell carcinoma. Three head and neck squamous cell carcinoma cell lines, chosen on the basis of their diverse EGFR expression levels, were treated with docetaxel, erlotinib, or both. The combination index was calculated using the Chou-Talalay equation. Propidium iodide staining with fluorescence-activated cell sorting analysis was used to evaluate the effects of drugs on cell cycle changes. Western blot analysis was used to determine the effects of agents on cell signaling pathways. Administration of low-dose docetaxel (0.1-3 nmol/l) concurrently or before erlotinib had additive cytotoxic effects in two cell lines but was antagonistic in one line, whereas low-dose docetaxel after erlotinib was synergistic in all cell lines. In contrast, high-dose docetaxel (40 nmol/l) resulted in more apoptosis when given before, rather than after or concurrently with, erlotinib. Low-dose docetaxel induced an accumulation of cells in the sub-G0 phase of the cell cycle with no mitotic arrest or apoptosis, whereas high-dose docetaxel induced mitotic arrest and apoptosis. The low and high doses of docetaxel had opposite effects on EGFR expression: a decrease and an increase, respectively. The dose of docetaxel affects sequence-dependent cytotoxicity when docetaxel is combined with an EGFR inhibitor. The mechanism for this difference is a combination of the dose-dependent effects of docetaxel on the mode of cell death and on EGFR expression.     

Effects and Clinical Significance of GII.4 Sydney Norovirus,United States, 2012–2013

During 2012, global detection of a new norovirus (NoV) strain, GII.4 Sydney, raised concerns about its potential effect in the United States. We analyzed data from NoV outbreaks in 5 states and emergency department visits for gastrointestinal illness in 1 state during the 2012–13 season and compared the data with those of previous seasons. During August 2012–April 2013, a total of 637 NoV outbreaks were reported compared with 536 and 432 in 2011–2012 and 2010–2011 during the same period. The proportion of outbreaks attributed to GII.4 Sydney increased from 8% in September 2012 to 82% in March 2013. The increase in emergency department visits for gastrointestinal illness during the 2012–13 season was similar to that of previous seasons. GII.4 Sydney has become the predominant US NoV outbreak strain during the 2012–13 season, but its emergence did not cause outbreak activity to substantially increase from that of previous seasons.     

Optimization of chitosan film as a substitute for animal and human epidermal sheets for in vitro permeation of polar and non polar drugs

The present investigation is aimed at preparing chitosan films capable of simulating the flux of modal drugs, 5-fluorouracil (5-FU) and indomethacin (INDO), across rat, rabbit and human cadaver epidermal sheets. Application of statistical design revealed that the concentration of chitosan, crosslinking time and concentration of crosslinking agent significantly influenced the in vitro flux of 5-FU and INDO across chitosan films. Multiple linear regression revealed a linear influence of all these active variables on 5-FU and INDO flux. It was deduced from atomic absorption spectroscopic analyses, DSC and IR spectroscopic data that 5% (m/V) sodium tripolyphosphate (NaTPP) produced optimum crosslinking of chitosan films. The in vitro permeation of both 5-FU and INDO across optimized film formulations was found to be comparable to that obtained across rat, rabbit and human epidermal sheets. These results indicate that optimized chitosan films have a potential to be developed as a substitute for animal and human cadaver epidermal sheets for preliminary in vitro permeation studies.     

Reduction of hospitalizations with diarrhea among children aged 0–5 years in Nouakchott,Mauritania, following the introduction of rotavirus vaccine

Introduction

Rotavirus vaccine was introduced in Mauritania in December 2014. We investigated hospitalizations with diarrhea during pre and post-vaccination periods among children aged 0–5?years in Nouakchott, the capital of Mauritania.

Broadening the age restriction for initiating rotavirus vaccination in regions with high rotavirus mortality: Benefits of mortality reduction versus risk of fatal intussusception

Introduction

Recently developed rotavirus vaccines have the potential to reduce diarrhea mortality in children in developing countries. Available data to date do not indicate risk of intussusception with these new vaccines. To avoid a potential unanticipated risk post-licensure, it is recommended that rotavirus immunization be initiated before 12 weeks of age when background intussusception rates are low. This policy could exclude a substantial number of children from vaccination, especially in developing countries where delays in vaccination are common.

Methods

We conducted a scenario analysis to assess the potential benefits of mortality reduction from rotavirus versus the risk of fatal intussusception when the first dose of the vaccine is strictly administered by 12 weeks of age compared with a free strategy with vaccine administered before 1 year of age using data on rotavirus disease, vaccine safety and efficacy, and current diphtheria–tetanus–pertussis vaccination rates, and by incorporating hypothetical risks of intussusception.

Results

In developing countries, assuming vaccine efficacy of 50% and 75% for doses 1 and 2, respectively, and a hypothetical sixfold and threefold increased relative risk of intussusception within 7 days of doses 1 and 2, respectively, initiating rotavirus immunization before 12 weeks of age would prevent 194,564 of the 517,959 annual rotavirus-associated deaths among children <5 years, while potentially resulting in 1106 fatal intussusception events. Administration of the first dose to infants up to 1 year of age would prevent an additional 54,087 rotavirus-associated deaths (total = 248,651) while potentially resulting in an additional 1226 intussusception deaths (total = 2332).

Conclusion

In developing countries, the additional lives saved by broadening the age restrictions for initiation of rotavirus vaccination would far outnumber the hypothetical excess intussusception deaths that would accompany such an approach.     

Determining the effectiveness of the pentavalent rotavirus vaccine against rotavirus hospitalizations and emergency department visits using two study designs

The objective of this study is to determine the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) for preventing rotavirus-related hospitalizations and emergency department (ED) visits during the 2006–07 and 2007–08 rotavirus seasons using two study designs. Active, prospective population-based surveillance was conducted to identify cases of laboratory-confirmed rotavirus-related hospitalizations and ED visits to be used in case-cohort and case-control designs. VE was calculated using one comparison group for the case-cohort method and two comparison groups for the case-control method. The VE estimates produced by the three analyses were similar. Three doses of RV5 were effective for preventing rotavirus-related hospitalizations and ED visits in each analysis, with VE estimated as 92% in all three analyses. Two doses of RV5 were also effective, with VE ranging from 79% to 83%. A single dose was effective in the case-cohort analysis, but was not significant in either of the case-control analyses. The case-cohort and the case-control study designs produced the same VE point estimates for completion of the three dose series. Two and three doses of RV5 were effective in preventing rotavirus-related hospitalizations and ED visits.     

Effect of Community-based Behavior Change Communication on Delivery and Newborn Health Care Practices in a Resettlement Colony of Delhi

Background:

Neonatal morbidity and mortality in India continue to be high. Among other reasons, newborn care practices are major contributors for such high rates.

Objective:

To assess the effect of behavior change communication (BCC) package among pregnant women regarding neonatal care.

Materials and Methods:

Semistructured and pretested schedule was used to interview 200 multigravidas on various aspects of neonatal care. Based on the preliminary data, BCC package was designed and implemented in intervention block in the community. Follow-up was done to find out change in their behavior.

Statistical Analysis:

Data were analyzed using Epi info and Fischer exact test and chi-square test were applied in the baseline data. A P value of less than 0.05 was considered significant. Effect of the BCC package is given in terms of relative risk.

Results:

BCC package increased 1.76 times higher number of deliveries conducted by trained dais in intervention group. There was significant improvement in using sterile cord tie (P = 0.01), applied nothing to the cord (P < 0.0001) and giving bath to their baby within 6 h of birth (P = 0.02) in intervention group as compared to nonintervention group. Significant difference was found between the two groups with regard to breastfeeding practices of baby. Harmful practices were reduced in the intervention group. Significant improvement was found in intervention group as compared to nonintervention group with regard to knowledge of danger signals, physiological variants, management of breastfeeding-related problems, and awareness of skin-to-skin technique for the management of hypothermic baby.

Conclusion:

Inadequate knowledge and adverse practices regarding neonatal care among mothers in study areas were found. BCC package had favorable impact on behavior of mothers for neonatal care in intervention group.     

Diarrhoea-related hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico

Objective

To assess, by socioeconomic setting, the effect of nationwide vaccination against species A rotavirus (RVA) on childhood diarrhoea-related hospitalizations in Mexico.

Methods

Data on children younger than 5 years who were hospitalized for diarrhoea in health ministry hospitals between 1 January 2003 and 31 December 2011 were collected from monthly discharge reports. Human development indexes were used to categorize the states where hospitals were located as having generally high, intermediate or low socioeconomic status. Annual rates of hospitalization for diarrhoea – per 10 000 hospitalizations for any cause – were calculated. Administrative data were used to estimate vaccine coverage.

Findings

In the states with high, intermediate and low socioeconomic status, coverage with a two-dose monovalent RVA vaccine – among children younger than 5 years – had reached 93%, 86% and 71%, respectively, by 2010. The corresponding median annual rates of hospitalization for diarrhoea – per 10 000 admissions – fell from 1001, 834 and 1033 in the “prevaccine” period of 2003–2006, to 597, 497 and 705 in the “postvaccine” period from 2008 to 2011, respectively. These decreases correspond to rate reductions of 40% (95% confidence interval, CI: 38–43), 41% (95% CI: 38–43) and 32% (95% CI: 29–34), respectively. Nationwide, RVA vaccination appeared to have averted approximately 16 500 hospitalizations for childhood diarrhoea in each year of the postvaccine period.

Conclusion

Monovalent RVA vaccination has substantially reduced childhood diarrhoea-related hospitalizations for four continuous years in discretely different socioeconomic populations across Mexico.     

Effect of breastfeeding on immunogenicity of oral live-attenuated human rotavirus vaccine: a randomized trial in HIV-uninfected infants in Soweto,South Africa

Objective

To investigate the effect of abstention from breastfeeding, for an hour before and after each vaccination, on the immune responses of infants to two doses of rotavirus vaccine.

Methods

In Soweto, South Africa, mother–infant pairs who were uninfected with human immunodeficiency virus (HIV) were enrolled as they presented for the “6-week” immunizations of the infants. Each infant was randomly assigned to Group 1 – in which breastfeeding was deferred for at least 1 h before and after each dose of rotavirus vaccine – or Group 2 – in which unrestricted breastfeeding was encouraged. Enzyme-linked immunosorbent assays were used to evaluate the titres of rotavirus-specific IgA in samples of serum collected from each infant immediately before each vaccine dose and 1 month after the second dose. Among the infants, a fourfold or greater increase in titres of rotavirus-specific IgA following vaccination was considered indicative of seroconversion.

Findings

The evaluable infants in Group 1 (n = 98) were similar to those in Group 2 (n = 106) in their baseline demographic characteristics and their pre-vaccination titres of anti-rotavirus IgA. After the second vaccine doses, geometric mean titres of anti-rotavirus IgA in the sera of Group-1 infants were similar to those in the sera of Group-2 infants (P = 0.685) and the frequency of seroconversion in the Group-1 infants was similar to that in the Group-2 infants (P = 0.485).

Conclusion

Among HIV-uninfected South African infants, abstention from breastfeeding for at least 1 h before and after each vaccination dose had no significant effect on the infants’ immune response to a rotavirus vaccine.     

Microwave-assisted synthesis of some novel and potent antibacterial and antifungal compounds with biological screening

Hydantoins have widely been used as antiarrythmic, anticonvulsant and antitumor agents but recent research has shown a different and novel cytotoxic activity of hydantoins and its derivatives, i.e. anti HIV, antibacterial and antifungal. The following research article deals with the synthesis of hydantoins and their derivatives by Mannich reaction viz., 3-(substituted)-5,5-diphenylimidazolidine-2,4-dione and 1-(substituted)-3,5,5-triphenylimidazolidine-2,4-dione. The synthesised compounds are novel and some of the compounds showed good antibacterial and antifungal activity equivalent to the standards used. All synthetic procedures were carried out in a microwave and not by conventional methods, which led to speedy process and high yield for the same.