Effect of diet on the development of drug metabolism by cytochrome P-450 enzymes in healthy infants

Orally administered caffeine and dextromethorphan (DM) were used as pharmacologic probes to determine the effect of infant diet on acquisition of cytochrome P-450 (CYP) enzyme activity during the first 6 mo of life. The caffeine elimination rate constant (ke) was determined from serum, and concentrations of caffeine, DM, and their respective metabolites were measured in urine by high-performance liquid chromatography (HPLC). Caffeine ke was low at 2 wk and displayed a significant positive linear correlation with age (p < 0.001); increasing faster in formula-fed than in breast-fed infants (p < 0.001). This occurred concomitantly with a significant increase in urinary 1,7-dimethylxanthine (17X) and 1-methylxanthine (1X) (p < 0.001), suggesting faster acquisition of CYP1A2 activity in formula-fed infants. The urinary molar ratio of (17X + 1X)/caffeine and age strongly predicted caffeine ke (r2 = 0.65; p < 0.001) irrespective of feeding type. CYP3A4 activity, assessed as the molar ratio of 3-hydroxymorphinan/dextrorphan showed a similar marked increase with postnatal age (p < 0.001) that was also greater in formula-fed than in breast-fed infants. Formula feeding appears to accelerate maturation of caffeine and DM metabolism by increasing the activity of CYP1A2 and CYP3A4, respectively. Dietary modification of CYP activity may modulate drug biotransformation and thus alter systemic exposure to xenobiotics from a very early age.     

Risk factors and heart disease mortality. A regional perspective

The mortality rates from ischaemic heart disease in the Hunter Region of New South Wales are among the highest in Australia. Within the Region substantial differences occur in death rates from heart disease among the five urban local government areas, the highest being in the coal-mining district of Cessnock and the lowest in the resort and dormitory area of Port Stephens. A recent survey in the Region of risk factors for heart disease has revealed prevalence patterns for high blood pressure, serum cholesterol levels, smoking and overweight and obesity which largely parallel the pattern of heart disease mortality. This suggests that changes in life-style in the communities could reduce the intraregional differences in mortality. In addition, the widespread prevalence of an unhealthy diet and a lack of exercise may explain the Region's high death rates from heart disease and suggests that mortality could be reduced by effective preventive measures.     

Prevention of chronic diseases: a call to action

Chronic (non-communicable) diseases—principally cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes—are leading causes of death and disability but are surprisingly neglected elements of the global-health agenda. They are underappreciated as development issues and underestimated as diseases with profound economic effects. Achievement of the global goal for prevention and control of chronic diseases would avert 36 million deaths by 2015 and would have major economic benefits. The main challenge for achievement of the global goal is to show that it can be reached in a cost-effective manner with existing interventions. This series of papers in The Lancet provides evidence that this goal is not only possible but also realistic with a small set of interventions directed towards whole populations and individuals who are at high risk. The total yearly cost of the interventions in 23 low-income and middle-income countries is about US$5·8 billion (as of 2005). In this final paper in the Series we call for a serious and sustained worldwide effort to prevent and control chronic diseases in the context of a general strengthening of health systems. Urgent action is needed by WHO, the World Bank, regional banks and development agencies, foundations, national governments, civil society, non-governmental organisations, the private sector including the pharmaceutical industry, and academics. We have established the Chronic Disease Action Group to encourage, support, and monitor action on the implementation of evidence-based efforts to promote global, regional, and national action to prevent and control chronic diseases.     

Wallerian degeneration in a patient with Schilder disease: MR imaging demonstration

Wallerian degeneration in the corticospinal tract was demonstrated by magnetic resonance (MR) imaging in a patient with Schilder disease. The histochemical stages of myelin breakdown that allow its demonstration by MR imaging are reviewed.     

用细口径反相柱HPLC分离多种前列腺素

HPLC与放射性同位素联用,可同时分离鉴定多种花生四烯酸代谢产物。目前国外一般是使用普通口径(4.6 mm)的反相柱,以30%左右乙腈为流动相,流速为1～3 ml/min。这种HPLC方法乙腈用量较大,费用太贵,不适合国内实验室常规操作。据报道,细口径