Measurement of benzene oxide in the blood of rats following administration of benzene

Although it is generally assumed that metabolism of benzene proceeds through an initial step involving oxidation to benzene oxide (BO) by CYP450 in the liver, the production of BO has never been unambiguously confirmed in animals dosed with benzene. Furthermore, prevailing hypotheses of the mechanism by which benzene causes cancer have ignored the possibility that BO might play a direct role, despite the fact that BO is electrophilic, binds covalently to cell macromolecules and is presumably genotoxic. A likely reason for this lack of attention to the role of BO in the carcinogenesis of benzene is the presumption that this epoxide is too reactive to escape the hepatocyte after it is formed. We employed gas chromatography-mass spectrometry to measure BO in the blood of F344 rats, both in vitro and up to 24 h following oral administration of benzene. Surprisingly, BO was relatively stable in rat blood at 37 degrees C (estimated half-life = 7.9 min) and, after administering a single dosage of 400 mg benzene/kg body wt, a blood concentration of 90 nM BO (8.5 ng/ml) was measured for approximately 9 h. Using a published PBPK model we estimate that approximately 4.3% of the metabolized dose of benzene was released as BO from the liver into blood. This confirms that BO is, indeed, formed from metabolism of benzene and is sufficiently stable to be distributed throughout the body at levels which are likely to be greater than those of the other electrophilic benzene metabolites.      

A randomised, placebo controlled trial of inhaled salbutamol and beclomethasone for recurrent cough

AIMS: To test the hypothesis that inhaled salbutamol or beclomethasone will reduce the frequency of cough in children with recurrent cough. A secondary aim was to determine if the presence of airway hyperresponsiveness (AHR) can predict the response. DESIGN: Randomised, double blind, placebo controlled trial. METHODS: During a coughing phase, 43 children (age 6-17 years) with recurrent cough were randomised to receive inhaled salbutamol or placebo (phase I) for 5-7 days and then beclomethasone or placebo (phase II) for 4-5 weeks, and in a subgroup of children for 8-9 weeks. The children used an ambulatory cough meter, kept cough diaries, and performed the capsaicin cough sensitivity, hypertonic saline bronchoprovocation, and skin prick tests. RESULTS: Salbutamol or beclomethasone had no effect on cough frequency or score, irrespective of the presence of AHR. CONCLUSIONS: Most children with recurrent cough without other evidence of airway obstruction, do not have asthma and neither inhaled salbutamol nor beclomethasone is beneficial.     

Gastric tonometry in septic shock

OBJECTIVES: To investigate the prognostic value of intramucosal pH (pHi) and the relation among pHi, arterial pH, base excess, and lactate in children with septic shock. DESIGN: Children admitted to the paediatric intensive care unit with a diagnosis of septic shock were prospectively enrolled. A gastrointestinal tonometer (Tonometrics Division, Instrumentarium Corporation, Helsinki, Finland) was placed into the stomach and intramucosal pH, arterial pH, base deficit, and lactate were measured on admission and six hours later. Sequential data were analysed on 24 patients (17 survivors, seven non-survivors), median age 46 months (range: 2.8-168 months). RESULTS: Median pHi on admission was 7.39 (interquartile range 7.36-7.51) in survivors compared with 7.2 (interquartile range 7.18-7.35) in non-survivors (p = 0.01). There was no significant difference in arterial pH, base excess, or lactate among survivors and non-survivors. Admission pHi < 7.32 predicted mortality with sensitivity (57%), specificity (94%), and positive predictive value (80%). Patients with admission pHi < 7.32 who failed to improve > or = 7.32 within six hours (n = 3) had 100% mortality. CONCLUSION: In children with septic shock the admission pHi is significantly lower in non-survivors. pHi is a better prognostic indicator of mortality than either standard acid-base values or lactate. pHi < 7.32 that does not improve within six hours is associated with a poor prognosis.     

Impact of zinc supplementation on persistent diarrhoea in malnourished Bangladeshi children

To evaluate the impact of zinc supplementation on the clinical recovery and body weight of children with persistent diarrhoea, a randomized, double-blind, controlled trial was conducted in 190 children with persistent diarrhoea aged between 3 and 24 months. Children were randomly allocated to receive either zinc (20 mg d⁻¹) syrup with multivitamin (2 × RDA) or multivitamin alone in three divided daily doses for 2 weeks. The trial was conducted in a diarrhoeal disease hospital in Dhaka, Bangladesh. Duration until clinical recovery (d), impact on body weight and serum zinc level after 2 weeks of zinc supplementation were recorded. The duration of illness was significantly reduced (33%) with zinc supplementation among children who were underweight (≤70% wt/age, p = 0:03). Supplemented male children also had a significant reduction (27%) in duration for recovery compared with unsupplemented children ( p = 0:05). From baseline to convalescence, zinc-supplemented children maintained their serum zinc concentration (13.4 vs 13.6/ μ mol l⁻¹), whereas unsupplemented children had a decrease in serum zinc after the 2 weeks of diarrhoea (13.6 vs 11.8 μ mol l⁻¹, p < 0:03). The mean body weight of the children in the supplemented group was maintained (5.72 vs 5.70 kg, p = 0:62) during hospitalization, unlike that of the control group, in which there was a reduction in body weight (5.75 vs 5.67 kg, p = 0:05). Five children in the unsupplemented group and one child in the zinc-supplemented group died during the 2 weeks of supplementation ( p = 0:06). Zinc supplementation in persistent diarrhoea significantly reduced the length of the recovery period in malnourished children and prevented a fall in body weight and serum zinc concentration, indicating that zinc is a beneficial therapeutic strategy in this high-risk childhood illness.     

Effects of alendronate on bone healing after tooth extraction in rats

Oral Diseases (2010) 16 , 674–685 Objectives: Tooth extraction has been identified as an important risk factor for bisphosphonate‐induced osteonecrosis of the jaw. Therefore, the main goal of this study was to determine the effects of alendronate on healing of the extraction socket and on interdental alveolar bone after tooth extraction in rats. Materials and methods: Animals were injected subcutaneously with vehicle or alendronate for 3–4 weeks before the first mandibular molar was extracted and these treatments were continued during post‐extraction periods of 10, 21, 35 and 70 days. Mandibles were processed to evaluate healing of the extraction socket and adjacent alveolar bone by assessing bone formation, bone resorption and vascularity by histomorphometric techniques. Results: Alendronate decreased new woven bone formation, blood vessel area, perimeter and number in the extraction socket at 10 days postextraction, but not at later time points. Furthermore, alendronate‐treated rats had increased interdental alveolar bone volume and height only at 10 days postextraction. In addition, a 2.5‐fold increase in the percentage of empty osteocyte lacunae was found in alveolar bone of alendronate‐treated rats only at 10 days postextraction. Conclusions: Alendronate transiently decreases bone formation and vascularity in the extraction socket and delays the removal of interdental alveolar bone after tooth extraction in rats.     

Intervention,recruitment and evaluation challenges in the Bangladeshi community: Experience from a peer lead educational course

Background  

The incidence of Type 2 diabetes is increasing worldwide and diabetes is four times more common among ethnic minority groups than among the general Caucasian population. This study reflects on the specific issues of engaging people and evaluating interventions through written questionnaires within older ethnic minority groups.