Chemical delivery systems and soft drugs: Retrometabolic approaches of drug design

Inclusion of metabolic considerations in the drug design process leads to significant development in the field of chemical drug targeting and the design of safer drugs during past few years which is a part of an approach now designated as Retro metabolic drug design (RMDD). This approach represents systematic methodologies that integrate structure–activity and structure–metabolism relationships and are aimed to design safe, locally active compounds with an improved therapeutic index. It embraces two distinct methods, chemical delivery systems and a soft drug approach. Present review recapitulates an impression of RMDD giving reflections on the chemical delivery system and the soft drug approach and provides a variety of examples to embody its concepts. Successful application of such design principles has already been applied to a number of marketed drugs like esmolol; loteprednol etc., and many other candidates like beta blockers, ACE inhibitors, alkylating agents, antimicrobials etc., are also under investigation.     

Willingness of healthcare workers to accept voluntary stockpiled H5N1 vaccine in advance of pandemic activity

Healthcare workers may be at risk during the next influenza pandemic. Priming with stockpiled vaccine may protect staff and reduce nosocomial transmission. Despite campaigns to increase seasonal influenza vaccine coverage, uptake among healthcare workers is generally low; creating uncertainty whether they would participate in pre-pandemic vaccine programmes. We conducted a cross-sectional questionnaire survey of healthcare workers in a UK hospital during, and 6 months after, a period of media reporting of an H5N1 outbreak at a commercial UK poultry farm. A total of 520 questionnaires were returned, representing 20% of frontline workforce. More respondents indicated willingness to accept stockpiled H5N1 vaccine during the period of media attention than after (166/262, 63.4% vs. 134/258, 51.9%; p = 0.009). Following multivariate analysis, factors associated with willingness to accept H5N1 vaccine included: previous seasonal vaccine (OR 6.2, 95% CI 3.0–12.8, p < 0.0001), awareness of occupational seasonal vaccine campaigns (OR 2.2, 95% CI 1.4–3.5, p = 0.001), belief that seasonal vaccine benefits themselves (OR 2.5, 95% CI 1.6–4.0, p < 0.0001) or the hospital (OR 3.6, 95% CI 2.3–5.8, p < 0.0001), belief that pandemic risk is high/moderate (OR 14.1, 95% CI 7.6–26.1, p < 0.0001) and would threaten healthcare workers (OR 2.9, 95% CI 1.8–4.5, p < 0.0001). Those who would not accept vaccine (220 respondents, 42.7%) if offered before the pandemic do not perceive pandemic influenza as a serious threat, and have concerns regarding vaccine safety. A majority of healthcare workers are amenable to accept stockpiled H5N1 vaccine if offered in advance of pandemic activity.     

Papillon-Lefevre Syndrome

Papillon-Lefevre syndrome in six Saudi children in the same family is described. The parents were unaffected, and parental consanguinity was present. Palmoplantar keratosis started at the age of 1 1/2 years. The loss of deciduous teeth was a consequence of juvenile periodontitis. All essential features of the syndrome were present in this series.     

Biochemical study on the postnatally developing mouse liver after a low level tritiated (HTO) in utero exposure

Pregnant mice were continuously irradiated (0.3 microCi (11.1 kBq)/ml of drinking HTO) from the 16th day post coitum. Biochemical studies were made on liver of mice 1 to 6 weeks post partum. RNA content increased significantly at 1 and 2 weeks while it decreased at later intervals. DNA concentration decreased till 4 weeks but at 5th and 6th week it increased by 3.70% and 22.64%, respectively. Protein content showed biphasic pattern whereas, cholesterol concentration increased after irradiation.     

Prokinetic therapy reduces aspiration pneumonia in tube-fed patients with severe developmental disabilities

To evaluate the clinical benefit of prokinetic therapy in aspiration pneumonia in patients with developmental disabilities, we conducted a retrospective study; records of 22 tube-fed patients were reviewed from December 1990 to October 1998 for a mean of 22.7 months before and 38.9 months during Cisapride therapy. Numbers of hospital admissions per patient-year before and during Cisapride administration were reduced from 2.75 to .61, with a relative risk reduction of 4.5. Days of hospitalization were reduced from 32.3 to 6.4. There were no adverse events noted from the therapy. Appropriately monitored prokinetic therapy may prove to be beneficial in preventing aspiration pneumonia in selected patients with developmental disabilities.     

Metabolic Surgery: Weight Loss,Diabetes, and Beyond

The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity. Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further examines their potential effects on cardiovascular outcomes and mortality and discusses future perspectives.     

The two-dose measles, mumps, and rubella (MMR) immunisation schedule: factors affecting maternal intention to vaccinate.

BACKGROUND: In the light of sub-optimal uptake of the measles, mumps, and rubella (MMR) vaccination, we investigated the factors that influence the intentions of mothers to vaccinate. METHOD: A cross-sectional survey of 300 mothers in Birmingham with children approaching a routine MMR vaccination was conducted using a postal questionnaire to measure: intention to vaccinate, psychological variables, knowledge of the vaccine, and socioeconomic status. The vaccination status of the children was obtained from South Birmingham Child Health Surveillance Unit. RESULTS: The response rate was 59%. Fewer mothers approaching the second MMR vaccination (Group 2) intended to take their children for this vaccination than Group 1 (mothers approaching the first MMR vaccination) (Mann-Whitney U = 2180, P < 0.0001). Group 2 expressed more negative beliefs about the outcome of having the MMR vaccine ('vaccine outcome beliefs') (Mann-Whitney U = 2155, P < 0.0001), were more likely to believe it was 'unsafe' (chi 2 = 9.114, P = 0.004) and that it rarely protected (chi 2 = 6.882, P = 0.014) than Group 1. The commonest side-effect cited was general malaise, but 29.8% cited autism. The most trusted source of information was the general practitioner but the most common source of information on side-effects was television (34.6%). Multiple linear regression revealed that, in Group 1, only 'vaccine outcome beliefs' significantly predicted intention (77.1% of the variance). In Group 2 'vaccine outcome beliefs', attitude to the MMR vaccine, and prior MMR status all predicted intention (93% of the variance). CONCLUSION: A major reason for the low uptake of the MMR vaccination is that it is not perceived to be important for children's health, particularly the second dose. Health education from GPs is likely to have a considerable impact.