Modular alpha-helical mimetics with antiviral activity against respiratory syncitial virus

A 13-residue peptide sequence from a respiratory syncitial virus fusion protein was constrained in an alpha-helical conformation by fusing two back-to-back cyclic alpha-turn mimetics. The resulting peptide, Ac-(3 -> 7; 8 -> 12)-bicyclo-FP[KDEFD][KSIRD]V-NH2, was highly alpha-helical in water by CD and NMR spectroscopy, correctly positioning crucial binding residues (F488, I491, V493) on one face of the helix and side chain-side chain linkers on a noninteracting face of the helix. This compound displayed potent activity in both a recombinant fusion assay and an RSV antiviral assay (IC50 = 36 nM) and demonstrates for the first time that back-to-back modular alpha-helix mimetics can produce functional antagonists of important protein-protein interactions.

Temperature and the respiratory properties of whole blood in two reptiles, Pogona barbata and Emydura signata

We investigated the capacity of two reptiles, an agamid lizard Pogona barbata and a chelid turtle Emydura signata, to compensate for the effects of temperature by making changes in their whole blood respiratory properties. This was accomplished by measuring the P-50 (at 10, 20 and 30 degrees C), hematocrit (Hct), haemoglobin concentration ([Hb]) and mean cell haemoglobin concentration (MCHC) in field acclimatised and laboratory acclimated individuals. The acute effect of temperature on P50 in P barbata, expressed as heat of oxygenation (Delta H), ranged from -16.8 +/- 1.84 to -28.5 +/- 2.73 kJ/mole. P-50 of field acclimatised P barbata increased significantly from early spring to summer at the test temperatures of 20 degrees C (43.1 +/- 1.2 to 48.8 +/- 2.1 mmHg) and 30 degrees C (54.7 +/- 1.2 to 65.2 +/- 2.3 mmHg), but showed no acclimation under laboratory conditions. For E. signata, Delta H ranged from -31.1 +/- 6.32 to -48.2 +/- 3.59 kJ/mole. Field acclimatisation and laboratory acclimation of P-50 did not occur. However, in E. signata, there was a significant increase in [Hb] and MCHC from early spring to summer in turtles collected from the wild (1.0 +/- 0.1 to 1.7 +/- 0.2 mmol/L and 4.0 +/- 0.3 to 6.7 +/- 0.7 mmol/L, respectively). (C) 2005 Published by Elsevier Inc.

Zinc and vitamin A supplementation in Indigenous Australian children hospitalised with lower respiratory tract infection: a randomised controlled trial

Objective: To evaluate the efficacy of supplementation with zinc and vitamin A in Indigenous children hospitalised with acute lower respiratory infection (ALRI). Design: Randomised controlled, 2-by-2 factorial trial of supplementation with zinc and vitamin A. Setting and participants: 187 Indigenous children aged < 11 years hospitalised with 215 ALRI episodes at Alice Springs Hospital (April 2001 to July 2002). Interventions: Vitamin A was administered on Days 1 and 5 of admission at a dose of 50 000 IU (infants under 12 months), or 100 000 IU; and zinc sulfate was administered daily for 5 days at a daily dose of 20 mg (infants under 12 months) or 40 mg. Main outcome measure: Time to clinical recovery from fever and tachypnoea, duration of hospitalisation, and readmission for ALRI within 120 days. Results: There was no clinical benefit of supplementation with vitamin A, zinc or the two combined, with no significant difference between zinc and no-zinc, vitamin A and no-vitamin A or zinc + vitamin A and placebo groups in time to resolution of fever or tachypnoea, or duration of hospitalisation. Instead, we found increased morbidity; children given zinc had increased risk of readmission for ALRI within 120 days (relative risk, 2.4; 95% CI, 1.003–6.1). Conclusion: This study does not support the use of vitamin A or zinc supplementation in the management of ALRI requiring hospitalisation in Indigenous children living in remote areas. Even in populations with high rates of ALRI and poor living conditions, vitamin A and zinc therapy may not be useful. The effect of supplementation may depend on the prevalence of deficiency of these micronutrients in the population.

Perspective on the host response to human metapneumovirus infection: what can we learn from respiratory syncytial virus infections?

Human metapneumovirus (HMPV) is a recently discovered pathogen first identified in respiratory specimens from young children suffering from clinical respiratory syndromes ranging from mild to severe lower respiratory tract illness. HMPV has worldwide prevalence, and is a leading cause of respiratory tract infection in the first years of life, with a spectrum of disease similar to respiratory syncytial virus (RSV). The disease burden associated with HMPV infection has not been fully elucidated; however, studies indicate that HMPV may cause upper or lower respiratory tract illness in patients between ages 2 months and 87 years, may co-circulate with RSV, and HMPV infection may be associated with asthma exacerbation. The mechanisms and effector pathways contributing to immunity or disease pathogenesis following infection are not fully understood; however, given the clinical significance of HMPV, there is a need for a fundamental understanding of the immune and pathophysiological processes that occur following infection to provide the foundation necessary for the development of effective vaccine or therapeutic intervention strategies. This review provides a current perspective on the processes associated with HMPV infection, immunity, and disease pathogenesis. (c) 2005 Elsevier SAS. All rights reserved.

Predictors of an antibiotic prescription by GPs for respiratory tract infections: a pilot

Background. Antibiotics are over-prescribed for respiratory tract infections in Australia. Objectives. The aim of this study was to describe the clinical predictors of GPs' prescribing of antibiotics. Methods. We used Clinical Judgment Analysis to study the responses of GPs to hypothetical paper-based vignettes of a 20-year-old with a respiratory tract infection. The nature of four symptoms and signs (colour of nasal mucous discharge; soreness of the throat; presence of fever; and whether any cough was productive of sputum) was varied and their effect on prescribing measured using logistic regression. Results. Twenty GPs participated. The nature of each symptom and sign significantly predicted prescribing of an antibiotic. Cough productive of yellow sputum; presence of sore throat; fever; and coloured nasal mucus increased the probability of an antibiotic being prescribed. Conclusions. GPs are influenced by clinical signs and symptoms to use antibiotics for respiratory infections for which there is poor evidence of efficacy from the literature.