Physiological and pathophysiological implications of lipid sensing in the brain.

Fatty acid (FA)-sensitive neurons are present in the brain, especially the hypothalamus, and play a key role in the neural control of energy homeostasis. Through neuronal output, FA may modulate feeding behaviour as well as insulin secretion and action. Subpopulations of neurons in the ventromedial and arcuate hypothalamic nuclei are selectively either inhibited or activated by FA. Molecular effectors of these FA effects probably include chloride or potassium ion channels. While intracellular metabolism and activation of the ATP-sensitive K⁺ channel appear to be necessary for some of the signalling effects of FA, at least half of the FA responses in ventromedial hypothalamic neurons are mediated by interaction with FAT/CD36, an FA transporter/receptor that does not require intracellular metabolism to activate downstream signalling. Thus, FA or their metabolites can modulate neuronal activity as a means of directly monitoring ongoing fuel availability by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. Recently, the role of lipoprotein lipase in FA sensing has also been shown in animal models not only in hypothalamus, but also in hippocampus and striatum. Finally, FA overload might impair neural control of energy homeostasis through enhanced ceramide synthesis and may contribute to obesity and/or type 2 diabetes pathogenesis in predisposed subjects.

Involvement of general practitioners in mass screening. Experience of a colorectal cancer mass screening programme in the Calvados region (France).

Good compliance with screening programmes is essential and experience from ongoing studies points to the importance of involving general practitioners (GPs). The aim of this study was to evaluate factors influencing the participation of GPs in a screening programme, as well as acceptance of the test by the population. Fifty GPs were randomly chosen among the 117 practices of three districts in Calvados (France) where haemoccult test-based mass screening for colorectal cancer was underway. Each GP was asked to fill in a personal questionnaire as well as a detailed record for each patient between 45 and 74 years seen in the practice during a 1-week period. The GPs offered the test to 95% of the patients. The overall refusal rate was 7.8%, and was higher in women than in men (9.9% vs 5.9%; P < 0.05). Manual workers had a lower refusal rate than other occupational groups (2.5% vs 8.5%; P < 0.05). The GP's motivation was an important factor in patient compliance: the refusal rate was 5.4% in the case of highly motivated GPs, against 20.0% when the GP was poorly motivated (P < 0.01). GP motivation was higher in urban than in rural areas (P < 0.05) but did not depend on sex, age or the duration or type of practice. According to the GPs, motivating factors were the perceived need for screening, involvement in planning the campaign, and regular feedback. Conversely, a lack of time and the possibility of false-negative results were the most important impediments. This study demonstrates that patient compliance is closely linked to practitioner motivation.(ABSTRACT TRUNCATED AT 250 WORDS)