Rôles physiologiques des endocannabinoïdes dans le contrôle de l’homéostasie énergétique

Endocannabinoids are endogenous lipids which modulate the release of neurotransmitters and activate different signaling pathways, through the binding to cannabinoïd receptors, CB1 and CB2. Endocannabinoids are involved in the control of a variety of behavioural and neuroendocrine functions, including feeding behaviour. In the central nervous system, they essentially modulate the expression of orexigen or anorexigen neuropeptides thus resulting in the stimulation of food intake. Their peripheral targets are mainly the liver and the white adipose tissue where they stimulate lipogenesis, through the modulation of several enzymes and proteins expressions. Cannabinoïd receptor agonists are nowadays prescribed to improve appetite of people suffering from cancer or AIDS. In the same way, CB1 antagonist, such as Rimonabant, could provide efficient treatment of obesity.     

Effets de l’exposition prolongée au traitement chez des patients tunisiens, évalués par le test génotypique de résistance du VIH-1

Settings

In Tunisia, therapeutic failure profile is detected in 42.22% of treated patients. These patients are still confronted to ethical and socioeconomic problems but also to therapeutic and technical ones. Indeed, the limited number of available antiretroviral (ARV) molecules and the unavailability of resistance genotypic test in routine use is the reason why the same therapeutic combination of ARV molecules is maintained after therapeutic failure in some cases.

Objective and method

The authors studied the evolution, on two consecutive samples, of resistance mutations in patients with prolonged exposure to the same therapeutic combination after therapeutic failure and the resulting effect on management of these patients.

Results

We found a greater number of patients presenting with mutant viral stains after a prolonged exposure to the same ARV molecules. Results also showed that the detected mutation frequency increased and even more on the second sample, compared to the first one. Thus, the early diagnostic of resistance mutations using genotypic resistance test would be of great interest by allowing the physician to take necessary measures to reduce resistance rate and find an optimal treatment for the patient.

Conclusion

The introduction of new ARV molecules in our country was also an important step by improving the therapeutic management of HIV infected patients.     

Métabolisme des nutriments au cours de l'insuffisance rénale chronique

The suppression of renal metabolic function is responsible of metabolic acidosis, uremic toxicity and endocrine disturbances. Subsequent abnormalities of protein metabolism are:

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  an increase in muscle proteolysis related to acidosis and hypercortisolemia;

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  a decrease in hepatosplanchnic amino acid utilization which is responsible for reduced protein synthesis and ureagenesis as well as abnormal amino acid release in the absorptive phase.

Main abnormalities in energy substrate metabolism are: insulin resistance, impaired blood glucose regulation, and reduced triglyceride clearance. Energy metabolism is also characterized by an increase in energy expenditure and an accelerated fasting behaviour. Hypermetabolism together with increased protein turnover are responsible for an increase in nutritional requirements: 35–40 kcal/kg.day and, in dialysis patients, 1,2–1,4 g protein/kg.day.     

Place du diététicien dans l’équipe de soutien nutritionnel : évolution d’une profession

Recognised 30 years ago, hospital nutritional depletion remains a major problem of public health which concerns from 30% to 50% of all patients at admission. The circular DHOS/E 1 n? 2002-186 of the 29 March 2002, recommending the implementation of both the committee for food-nutrition (CLAN: Comité de Liaison Alimentation Nutrition) and the nutrition support team within the hospital, is the result of 10 years effort in regard to food-nutrition and the accreditation process in health care. The dietician, previously accountable for the quality of food and dietary services, has now the opportunity to play a leading role within the nutritional care team for the screening and treatment of nutritional depletion. However, the initial training and the present status of the dietician don’t allow him to follow this evolution effectively. Updating of his training and the redefinition of his missions seem indispensable to respond to today's health care needs. This will help to ensure that above legal recommendation can be applied.     

Perception gustative des lipides alimentaires

The profound technical and economic changes of the 20^th Century had a deep effect on our way of life and, consequently, on our eating behaviour. For the first time in its history, much of the world's population no longer has to “run after calories”. An abundance of food has obvious consequences: it promotes our specific appetites. Lipids account for about 40% of the calories ingested in Western countries, whereas nutritional recommendations are 5 to 10% lower. This excessive lipid intake, associated with a qualitative imbalance (excess of saturated fatty acids and cholesterol, too high ω6/ω3 ratio) strongly favours the development of obesity and associated diseases (atherosclerosis, non insulin-dependent diabetes, hypertension, cancer). This attraction to fatty foods is not specific to humans. Rats and mice spontaneously prefer lipid-rich foods if provided with a free choice. Until recently, it was thought that oral lipid detection involved only somesthesic and olfactory cues. This restrictive view has been challenged by recent observations suggesting that sense of taste is also involved in spontaneous fat preference underlying that the “fatty” taste might constitute a sixth gustatory modality. This mini-review highlights recent findings in this new field of investigations in both rodents and humans.     

Les acides gras : molécules informatives du contrôle nerveux de l’homéostasie énergétique

Free fatty acids (FFA) are not fuel for neurons and do not cross “easily” blood brain barrier. However, it is know well established that FFA could act as informative molecules and any change in plasma FFA concentration are detected at the level of central nervous system (CNS) structure such as hypothalamus and brainstem, where FFA sensitive neurons are located. These neurons control in turn energy homeostasis including food behaviour, hepatic glucose production or insulin secretion. Sub-populations of FFA sensitive neurons (either excited or inhibited) are now described in hypothalamus. Regarding, cell signaling, both acyl-CoA and malonyl-CoA could be major factor to mediate FFA effect. Indeed, increased intracellular concentration of malonyl-CoA in hypothalamus induce food intake inhibition. Such effects are partly related to decrease in NPY gene expression, as well as increase in alpha-MSH expression. Finally, dysregulation of FFA sensing in CNS could lead to development of metabolic diseases such as obesity or type 2 diabetes, in predisposed subject.     

Détection centrale des acides gras et contrôle du bilan d’énergie

Nutrient sensitive neurons (glucose and fatty acids (FA) are present in many sites throughout the brain, including the hypothalamus and brainstem, and play a key role in the neural control of energy and glucose homeostasis. Through neuronal output, FA may modulate feeding behaviour as well as both insulin secretion and action. For example, central administration of oleate inhibits food intake and glucose production in rats. This suggests that daily variations in plasma FA concentrations might be detected by the central nervous system as a signal, which contributes to the regulation of energy balance. At the cellular level, subpopulations of neurons in the ventromedial and arcuate hypothalamic nuclei are selectively either inhibited or activated by FA. Possible molecular effectors of these FA effects likely 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 signaling effects of FA, at least half of the FA responses in ventromedial hypothalamic neurons are mediated by interaction with FAT/CD36, a FA transporter/receptor that does not require intracellular metabolism to activate downstream signaling. 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. Besides these physiological effects, FA overload or metabolic dysfunction might impair neural control of energy homeostasis and contribute to obesity and/or type 2 diabetes in predisposed subjects.     

Évaluation de l’antibiothérapie des bactériémies et place d’une équipe mobile pour l’amélioration de la prescription antibiotique

Introduction

Antibiotic management teams (AMTs) are recommended, but they are rarely implemented in France and their activity seldom evaluated.

Objective

The study was made to evaluate the appropriateness of antibiotic therapy (AT) for bloodstream infections (BSI) and to assess the role of an AMT for improving AT in a 950-bed teaching hospital.

Methods

A prospective analysis was made of all significant BSIs outside ICU in 2008. AT was assessed by the AMT and change was suggested if deemed necessary: effective if at least one prescribed antibiotic was effective in vitro, and appropriate if consistent with local recommendations.

Results

Of 875 +BCs, 560 were significant, 383 were outside ICU and 344 could be evaluated (170 community-acquired, 124 nosocomial, and 50 healthcare-associated [HCA]). The clinical ward has already initiated an effective and appropriate AT in 128 (37%), inappropriate but effective in 104 (30%), and ineffective or absent in 112 (33%) BSIs. The only independent variable associated with ineffective/absent AT was nosocomial and/or HCA BSI (aOR: 2.71; 95%CI: 1.72–4.27; p < 0.001). A recommendation was given and followed in 177/190 (93%) BSIs requiring an intervention. The AMT intervened on the day of the +BC in 256 (84%) cases, the day before the +BC in 12 (4%) cases, and one day later or more in 37 (12%) BSI cases.

Conclusion

Two third of BSIs were not initially treated by appropriate AT, more often in nosocomial BSI. Recommendation provided by the AMT was followed in 93% of cases.     

La dictature de la minceur

The contemporary medical message insists on the individual's responsibility in managing his own health. The messages relayed by the various media are often confusing and contradictory, to which are added all the publicities for “healthy foods” because they are “light” and will insure weight loss. The equation slimness or even thinness is a particularly strong representation, especially among young and very young women and has great influence on the food behaviour of adolescents. These lead to “small anorexia” as defined by J.-P. Corbeau. Obsession with diet leads to nutritional pathologies, negation of pleasure and conviviality that the moral condemnation of fatness will only increase.     

Rôle de l’alimentation dans la prévention des caries

Over the last three decades the condition of the teeth of children has improved tremendously. This has generally been attributed to the increased use of fluoride toothpaste. During this period the total amount of sugars disappearing into the population per capita has hardly changed. This suggests that the relationship between diet and caries has to be reassessed, which provokes different opinions among dental experts.Some suggest a maximum threshold level for the daily amount of sugars to prevent caries. Others propose that in general the amount of sugars eaten is not an important determinant of caries experience. The scientific evidence for the various opinions on the role of diet in caries development will be discussed. It is concluded that the role of diet is not so much related to the diet itself, but to the individual behaviour of people. Where oral hygiene and fluoride supplementation are adequate, the diet has become a lesser factor in caries prevention. However, those diets may cause caries when there is too little fluoride. It is a mistake to classify a diet as cariogenic it may be potentially cariogenic. When one wants to decrease this potency, one should modify those factors that are actually controlling it, which is, in most cases, the topical presence of fluoride and not the composition of the diet.     

Eau du robinet : une exigence de qualité…

French regulation of tap water relies on strict standards warranting its quality. It is presently one of the most controlled alimentary products, from natural resources up to the tap including factory and distribution network. Worm out water is treated before returned to natural milieu in order to protect environment. In France, regulations are edited by Minister of Health accounting for EU and WHO recommendations establishing maximal doses of some substances that one can ingest daily and lifelong without any harm; the maximum tolerable doses are then calculated, usually with a safety margin. Current Public Health regulations include 56 quality parameters: chemical, physical or microbiological. The treatment of water includes mostly physical or biological processes, efficacy of which is severely controlled. In addition of supervision of the different steps of the production by the development companies, steady health controls are performed by the departmental directions of health and social affairs (DDASS). During year 2006, more than 31,000 samples have been performed allowing more than eight millions analysis. Information on the quality of water is mandatory and local details are sticked in city hall or joined clearly to the water invoice by DDASS; it is also possible to contact the web sites of most of the companies distributing water. Tap water is a source of minerals and trace elements: calcium, magnesium, fluor… which are naturally present in soils and rocks that water flows through. Mineral thresholds are determined by norms in order to ensure a good mineral balance.     

De l’épizootie à l’épidémie : perception et gestion d’un risque dans l’ancien régime

Recent events, from mad cow disease to bird flu, suggest that modern societies are exposed to novel food-associated risks. This impression of novelty is illusory. History has been marked by several alimentary crises, among which critical situations associated with meat intake during times of epizooties. The first of such crises that was well documented, thanks to physicians’ reports, was the cattle plague that spread over Europe in the years 1711-1714. In France and Italy, it thus becomes possible to analyze reactions to animal disease, in particular among consumers and public authorities. In all cases, a hyper-responsiveness is noted to potential dangers associated with meat, in line with the intellectual context of the time: limited scientific knowledge, and also popular representations of nutrition. While concerns are shared, prevention policies vary in different places. Individual behaviors as well as public policies are rational, aiming to establish a favorable risk to benefit ratio, given that a “no risk” situation cannot be obtained.     

Nutrition des traumatisés crâniens graves

Traumatic injury and severe brain injuries in particular, have systemic consequences affecting all major functions. As energy expenditure increases, energy needs are covered by gluconeogenesis from muscle protein even if they are modulated by the use of different drugs. A gradual erosion of protein reserves results in an acute state of malnutrition exacerbating the immunosuppression induced by trauma, and facilitates infection. Artificial nutrition may limit this process. Gastric feeding route should be initiated early and guided by a written protocol. Gastroparesis being one of the main causes of failure of this route, it must be quickly identified, before calorie deficit harms patients. Nasojejunal tube or parenteral nutrition must be then considered in order to cover nutritional requirements which correspond to about 20–25 kcal/kg per day during the initial phase, and up to 30 kcal/kg per day during the recovery period. Sepsis, agitation or autonomic dysfunction syndromes may increase nutritional requirements. Their evaluation can be improved by mathematical formulas or calorimetry in complex situations (obesity…). Despite the intensity of muscle catabolism, protein intake should be approximately 1.5 g/kg per day. Furthermore, trauma is associated with depletion of glutamine, some vitamins and trace elements including selenium. Supplementation of glutamine reduces infectious morbidity. It must be given at a sufficient dosage and may be associated with selenium. Finally, an adequate glycemic control is essential to avoid brain damage.     

Défaillance multiviscérale et infection disséminée à adénovirus

Background

Peripheral blood stem cell transplantation is a frequent option, especially for patients with hematological malignancies.

Case reports

A first patient received this treatment for acute myeloblastic leukemia, the second for Richter's syndrome (follicular lymphoma). In both cases, allograft (unrelated donor, non myeloablative conditioning) was followed by graft versus host disease (GVH) requiring an immunosuppressive treatment. Respectively 15 and three months after graft, these two patients presented with multiple organ failure including very severe hepatic dysfunction. The diagnosis was made according to positive blood PCR, positive BAL, and hepatic histological findings.

Discussion

Adenoviruses, frequent in pediatrics, can be responsible for extremely severe infections among immunocompromised adults. T lymphocyte depletion plays a key role.

Conclusion

Adenoviral infections can be fatal among immunocompromised patients. Diagnostic improvement should lead to early treatment, which however, remains to be clearly defined.     

Les eaux embouteillées

Bottled waters, natural mineral water and spring water, meet the specific criteria defined by the regulation. Natural mineral water is characterized by its underground origin, the stability of its composition and its “original purity”. Water is an essential nutrient whose primary function is to hydrate. However, some natural mineral water can contribute to meet the recommended daily allowances (RDA) of minerals such as calcium and magnesium. These minerals from water are well absorbed and as consequence can contribute to meeting until 64 and 44% of daily intake in calcium and magnesium respectively. This recommendation is particularly relevant for children and adolescents, pregnant and lactating women, menopausal women and the elderly whom daily needs are increased. Concerning sulphates, the studies conducted to date do not allow establishing an upper limit of consumption via drinking water as they do not conclude on adverse effects in human being. In conclusion, as part of a balanced diet, natural mineral waters represent a natural source of minerals not negligible all the more they may have beneficial effects on health.     

Évaluation nutritionnelle chez le dialysé

Malnutrition is common among patients with end stage renal disease treated by hemodialysis or peritoneal dialysis. It is a major cause of morbidity and mortality. Nutritional status may be assessed by several clinical markers including dietary records, anthropometric measurements and subjective global assessment. Among biochemical parameters, albumin is the most commonly examined nutritional index and transthyretin the most useful. Protein catabolic rate reflects dietary protein intake. Body composition analysis by bioelectrical impedance analysis or better by dual energy X-ray absorptiometry offers a reasonable estimation of body compartments such as total body water, fat mass and lean body mass. Periodic assessment of nutritional status must take into account the limitations of all the criteria used.     

Consommation alimentaire et durée d’hémodialyse chez l’insuffisant rénal chronique : corrélation aux paramètres nutritionnels

The aim of this study was to describe food consumption of CRF patients after different hemodialysis duration and to correlate them with some nutritional parameters. Fifty-eight patients divided into three groups: GI: <1 year, GII: 1 to 5 years, GIII: 5 to 13 years of hemodialysis were compared with 22 controls. Reduction of total energy intake by 47% and 30% and protein intake by 49% and 38% was noted in GIII vs GI and GII, respectively. Patients had a dialysis dose (Kt/V) of 0.83±0.35 and a low body mass index. Seventy-seven per cent of patients had hypoalbuminemia (<37g/L). Decreased food consumption involves protein-energy malnutrition and represents a mortality risk.     

Ertapénem intraveineux ou sous-cutané pour le traitement des infections urinaires à entérobactérie sécrétrice de BLSE

Introduction

Ertapenem could be used to treat urinary tract infections (UTI) caused by ESBL producing enterobacteriacae (ESBL-E) and administered subcutaneously.

Method

The authors made a retrospective study on adult patients treated with ertapenem administered intravenously or subcutaneously for UTI caused by ESBL-E, between May 2009 and August 2011 at the Chambery hospital, France.

Results

Twenty-five patients were treated (13 cases of prostatitis, ten of pyelonephritis, two of cystitis) mostly caused by Escherichia coli (24 cases). Subcutaneous injections were administered to 20 patients and 23 were treated through outpatient parenteral antibiotic therapy (OPAT). All patients were cured at the end of the ertapenem therapy. Urine samples collected during treatment for 12 patients were sterile. Three months after the end of the treatment, five patients had relapsed, and six had developed a UTI caused by another bacteria.

Conclusion

Ertapenem administered intravenously or subcutaneously could be an effective treatment for UTI caused by ESBL-E, especially using OPAT.     

Immunosénescence et infections,mythe ou réalité ?

The susceptibility of elderly people to infectious diseases is usually associated to increasing risk factors found in young adults. However, the role of immune function ageing is associated with the decline of immune function but this decline is not homogenous. Some functions such as the cellular immune system are altered but others are enhanced such as innate immunity. The important events of immune ageing are modifications of lymphocyte subsets with accumulation of memory cells, decrease in proliferative response, and a chronic inflammatory state. The chronic antigenic load throughout life is responsible for gaps in the antigenic system with a greater sensitivity to new antigens. These immune system changes are all the more important that diseases are severe and that denutrition is associated. These diseases will speed up the ageing process. The interaction between immunosenescence and pathology is an important phenomenon to consider. This review outlines the immune system changes due to ageing, their relationship with diseases of the aged patient, and the consequences of these modifications on vaccination effectiveness.     

Connaissances et attentes d’une communauté d’internautes hypercholestérolémiques sur leur prise en charge nutritionnelle

Hygienodietetic recommendations are poorly followed by hypercholesterolemic subjects despite general practitioners’ advices. We aimed at determining the reasons for this failure. We studied an Internet community made of hypercholesterolemic subjects in order to assess their level of knowledge, their wish to learn and to take care of themselves. The nutritional solution of hypercholesterolemia is perceived as a daily effort. In that context, doctor's advices are crucial. However, mainly due to lack of time and tools, these advices are not adequately delivered to the subjects. Patients are therefore ready to look for information on Internet. The dietary changes are therefore limited rather because of a lack of knowledge than a lack of will. Internet became a daily and essential reference for searching information, which should be considered as complementary to the doctor. Our study showed that patients are ready to use the Internet in order to learn how to better manage their cholesterol and to be better informed.