Food avoidance in anorexia nervosa: associated and predicting factors.

PURPOSE: Qualitative food avoidance is a significant issue in patients with anorexia nervosa (AN) and restoring diet diversity is an important part of the treatment process. We aimed to identify clinical factors which drive food avoidance and predict its maintenance in patients with AN. METHODS: In this multicentre longitudinal study, 130 female outpatients with AN were assessed before and after 4 months of care in clinical centres specialized in AN. We assessed levels of avoidance of 16 food items, as well as body mass index (BMI), eating disorder severity, symptoms of depression and anxiety, emotional state, daily-life functioning, and body image perception. RESULTS: We found that qualitative food avoidance was associated with the clinical severity of AN, anxiety and mood dimensions, and BMI- and body image-related factors. A younger age at onset predicted the maintenance of food avoidance after 4 months of treatment. Additional exploratory analyses suggested that anxiety and negative affect caused food avoidance more than the opposite. CONCLUSION: Qualitative food avoidance can be an indicator of illness severity. During treatment, focusing on reducing anxiety and negative affect may be a way to indirectly reduce food avoidance and restore diet diversity. LEVEL OF EVIDENCE: Level III: Evidence obtained from cohort or case-control analytic studies.

Three clinical indicators of borderline personality disorder in anorexia nervosa: A pilot study.

OBJECTIVES: Co-occurrence of Anorexia Nervosa (AN) and borderline personality disorder (BPD) is frequent (8%-40%) and associated with specificities that impact the treatment process. Lifetime history of suicide attempt (HAS), substance use disorder (SUD) and the binge-purging subtype (B-P) might be good markers of such comorbidity. We made the hypothesis that in patients with AN, the presence of HAS, SUD and B-P have sufficient predictive power to efficiently detect an associated BPD comorbidity. METHODS: After a case report analysis on a pilot sample of 119 patients with AN, we performed a cross-sectional analysis on a confirmatory sample of 84 patients with AN in a single center specialized in eating disorders systematically assessing HAS, SUD, B-P and BPD using the Mini International Neuropsychiatric Interview for DSM-5 and the Diagnostic Interview for Borderline (DIB-R). RESULTS: B-P had a 100% negative predictive value, and the combination of SUD plus HAS had a 100% positive predictive value. On a quantitative level, B-P, HAS and SUD were independent explanatory factors of the DIB-R total score. CONCLUSIONS: The main limitations were the low number of patients, the single center analyses, the potential overlapping of assessments and the fact that data were exclusively declarative. In this study, every patient with B-P, SUD and HAS had been diagnosed with BPD.

Methodological considerations for ghrelin isoforms assay in clinical evaluation in anorexia nervosa.

The growing interest concerning the role of metabolic sensors in various eating disorders requires the implementation of a strict methodology to collect, store and process blood samples in clinical studies. In particular, measurement of isoforms of the appetite-stimulating hormone, ghrelin, has been challenging in clinical settings. Indeed the acyl ghrelin (AG) isoform is rapidly degraded into desacyl ghrelin (DAG) by blood esterases, thus optimal conditions for the conservation of AG and accurate determination of AG/DAG ratio should be used. Here, we compared different protease inhibitors (Aprotinin, PHMB, AEBSF) during blood collection, increasing delays (0-180 min) before centrifugation, plasma supplementation with various HCl concentrations, storage durations of frozen plasma (8 and 447 days) and immunoenzyme-assay procedures (one-step versus sequential) in healthy subjects. Optimal conditions were obtained by collecting blood with aprotinin and supplementation of plasma with 0.1 N HCl with subsequent freezing for at least 8 days and using one-step assay. Under such conditions, different patterns of secretion of ghrelin isoforms were characterized in patients with restrictive-type anorexia nervosa (AN-R) before and after nutritional recovery. We illustrate the pulsatile variations of ghrelin isoforms according to the time around a meal and hunger rates in 3 patients with AN-R. This study offers a comprehensive comparison of various conditions using selective and specific immunoassays for both ghrelin isoforms in order to optimize assay sensitivity and consistency among procedures. These assay conditions could therefore be widely used to elucidate precisely the role of ghrelin isoforms on eating behavior in physiological and pathological situations.

Thumb basal joint arthritis: New classification, diagnostic and therapeutic algorithm.

The assessment of thumb basal joint arthritis requires a radiographic evaluation and a classification of the lesions to guide the treatment choice. Arthritis of the thumb basal joint is not limited to trapeziometacarpal arthritis. The radiographic assessment must consider the scaphotrapeziotrapezoid joint, the entire carpus and the rest of the thumb column, in particular the metacarpophalangeal joint. There is currently no classification that captures all these items. This article reviews the existing classifications, proposes a new classification system that takes into account the entire thumb column and sets out the therapeutic options.

Jean Talairach (1911-2007). An untold story of the pioneer of stereotactic and functional neurosurgery.

CONTEXT: The Department of neurosurgery of the Sainte-Anne Hospital hosted Jean Talairach who created and developed stereotactic neurosurgery in France. Despite numerous neurosurgical and neuroscientific achievements, little is known about the life of Jean Talairach. METHODS: Systematic screening of Sainte-Anne Hospital Museum, Henry Ey Library, and Bibliothèque Inter-Universitaire de Santé funds, and medical databases using the term "Jean Talairach". RESULTS: Jean Talairach started his medical career at the Sainte-Anne Hospital in 1942 as a psychiatrist and became a neurosurgeon due to his interest in stereotactic neurosurgery. During World War II, Jean Talairach joined the French Resistance in Paris, then the French First Army. Jean Talairach created an original and specific stereotactic methodology with appropriate stereotactic frame and tools and performed one of the first human stereotactic surgeries in 1948. He described the reference lines passing by the anterior and posterior commissures in 1952 and developed a tridimensional co-planar stereotactic atlas of the human brain. With the collaboration of Jean Bancaud, he created stereo-electroencephalography to investigate patients suffering from drug-resistant epilepsy. The "Sainte-Anne school" trained French and foreign stereotactic and functional neurosurgeons ensuring the spread of Jean Talairach's innovative ideas. Jean Talairach retired in 1980. CONCLUSION: Jean Talairach's achievements encapsulate the evolution of neurosurgery in France during the 20th century. He developed an original stereotactic methodology including a tridimensional stereotactic atlas of the human brain and a stereotactic frame. He created stereo-electroencephalography, which remains the gold-standard to investigate patients suffering from drug-resistant epilepsy.

Spatial hand representation in anorexia nervosa: a controlled pilot study.

Body representation distortion (BRD) is a core criterion of Anorexia Nervosa (AN), and is usually assessed subjectively, focusing on body shape. We aimed to develop a new assessment to evaluate body representation independently from socially-mediated body image, on a body part with low emotional salience (hands). In a monocentric open label pilot study, we measured hand representations based on explicit (verbal) and implicit (tactile) instructions. Participants, with eyes closed, had to point targeted locations (knuckles and nails of each finger) based on verbal instructions and tactile stimulations to evaluate body representations respectively. Ratios between hand width and finger length were compared between AN (n = 31) and controls (n = 31) and correlated with current body mass index, AN subtype and disease duration. To control that hand distortion was specific to body representation, we also assessed object representation. Hand representation's width/length ratio was significantly increased in patients with AN, whereas no difference was found in object representation. We found no correlation between hand wideness and clinical traits related to eating disorders. Our results propose that BRD is not limited to body parts with high emotional salience, strengthening the hypothesis that anorexia nervosa is associated with profound unspecific BRD.

Mindfulness-based cognitive therapy added to usual care improves eating behaviors in patients with bulimia nervosa and binge eating disorder by decreasing the cognitive load of words related to body shape, weight, and food.

BACKGROUND: This study aimed to investigate the effectiveness of mindfulness-based cognitive therapy (MBCT) as a complementary approach in patients with bulimia nervosa (BN) or binge eating disorder (BED), and to assess how the reduction of the cognitive load of words related to eating disorders (ED) could constitute an intermediate factor explaining its global efficacy. METHODS: Eighty-eight women and men participated in clinical assessments upon inscription, prior to and following 8-week group MBCT. Mindfulness skills were assessed using the five facet mindfulness questionnaire; eating behaviors were assessed using the Three Factor Eating Questionnaire (TFEQ); comorbid pathologies were assessed using the beck depression index and the state-trait anxiety inventory. The cognitive load of words associated with ED was assessed through a modified version of the Stroop color naming task. RESULTS: Mindfulness skills improved significantly (p < .05) after group MBCT. The improvement of TFEQ scores was accompanied by reduced levels of depressive mood and trait anxiety. The positive impact of MBCT on TFEQ score was directly related to an improvement of the performance in the Stroop task. CONCLUSIONS: MBCT represents an interesting complementary therapy for patients with either BN or BED, at least when cognitive and behavioral domains are concerned. Such efficacy seems to be mediated by the reduction of the cognitive load associated with ED stimuli, which offers a possible explanation of how MBCT could reduce binge-eating behaviors. Other studies are needed, in independent centers, to focus more directly on core symptoms and long-term outcome.

Non-invasive and invasive brain stimulation in alcohol use disorders: A critical review of selected human evidence and methodological considerations to guide future research.

INTRODUCTION: Alcohol use disorder (AUD) ranks among the leading causes of decrements in disability-adjusted life-years. Long-term exposure to alcohol leads to an imbalance of activity between frontal cortical systems and the striatum, thereby enhancing impulsive behaviours and weakening inhibitory control. Alternative therapeutic approaches such as non-invasive and invasive brain stimulation have gained some momentum in the field of addictology by capitalizing on their ability to target specific anatomical structures and correct abnormalities in dysfunctional brain circuits. MATERIALS AND METHODS: The current review, covers original peer-reviewed published research on the use of brain stimulation methods for the rehabilitation of AUD. A broad and systematic search was carried out on four electronic databases: NCBI PubMed, Web of Science, Handbooks and the Cochrane Library. Any original article in English or French language, without restrictions of patient age or gender, article type and publication outlet, were included in the final pool of selected studies. RESULTS: The outcomes of this systematic review suggest that the dorsolateral prefrontral cortex (DLPFC) is a promising target for treating AUD with high frequency repetitive transcranial magnetic stimulation. Such effect would reduce feelings of craving by enhancing cognitive control and modulating striatal function. Existing literature also supports the notion that changes of DLPFC activity driven by transcranial direct current stimulation, could decrease alcohol craving and consumption. However, to date, no major differences have been found between the efficacy of these two non-invasive brain-stimulation approaches, which require further confirmation. In contrast, beneficial stronger evidence supports an impact of deep brain stimulation reducing craving and improving quality of life in AUD, effects that would be mediated by an impact on the nucleus accumbens, a central structure of the brain's reward circuitry. Overall, neurostimulation shows promise contributing to the treatment of AUD. Nonetheless, progress has been limited by a number of factors such as the low number of controlled randomized trials, small sample sizes, variety of stimulation parameters precluding comparability and incomplete or questionable sham-conditions. Additionally, a lack of data concerning clinical impact on the severity of AUD or craving and the short follow up periods precluding and accurate estimation of effect duration after discontinuing the treatment, has also limited the clinical relevance of final outcomes. CONCLUSION: Brain stimulation remains a promising approach to contribute to AUD therapy, co-adjuvant of more conventional procedures. However, a stronger therapeutic rational based on solid physio-pathological evidence and accurate estimates of efficacy, are still required to achieve further therapeutic success and expand clinical use.

[GABAergic approach of postpartum depression: A translational review of literature]. / Approche GABAergique de la dépression du post-partum : une revue critique translationnelle.

INTRODUCTION: Prevalence of postpartum depression (PPD) ranges from 10 to 15 % of parturients. The impact of the PPD is major on the maternal bond and the health of both mother and child. Its physiopathological mechanisms appear to differ from other types of depression. Today, pharmacotherapy is based on nonspecific treatment, and recent therapeutic advances in this field require a comprehensive approach of the implication of the GABAergic system in the development of PPD. Neurosteroid levels during pregnancy and after parturition and the GABA-A-r modulation are thought to be involved in PPD. OBJECTIVE: To evaluate if the GABAergic approach is relevant in postpartum depression management. METHODS: We conducted a systematic review of literature based on the MEDLINE database with the following Medical Subject Headings (MeSH): "postpartum depression", "GABA", "ganaxolone", "brexanolone", "allopregnanolone", prior to September 2019. We selected articles in English: preclinical and clinical studies, literature review, observational and therapeutic studies. RESULTS: Preclinical models (mouse and rat) show changes in GABAergic inhibition in the peripartum period and correlation between allopregnanolone and GABA-A-r plasticity. This plasticity in the peripartum period maintains levels of inhibition adapted despite increased neurosteroid levels. KO models for the GABA-A-r δ subunit develop depression and anxiety symptoms in the postpartum period, and a change in the expression of the gene coding for the GABA-R alpha-4 subunit was found. Artificial inhibition of progesterone metabolism during post-partum increased depression symptoms. GABAergic fluctuation seems to be interrelated with other systems such as those of oxytocins. A synthetic neurosteroid (SGE-516) was tested on mouse models of PPD, KO for δ-GABA-A-r or KCC2, and showed decreased depressive symptoms and better mothering. Clinical studies confirm neurosteroid fluctuation and changes in the GABAergic system during the peripartum period. Allopregnanolone is the neurosteroid the most studied in PPD, and it is elevated in the brain during the pregnancy. Studies disagree on the presence of significant differences in allopregnanolone plasma levels during pregnancy or postpartum between women with PPD or not. Women with a history of PPD have greater susceptibility to neurosteroid withdrawal. Imagery and genetical data also show a link between allopregnanolone and PPD. The GABA-A-r may not recover in time following a reduced number during pregnancy, and this mismatch between neurosteroid levels and their receptor may trigger PPD. Several randomized controlled trials investigated brexanolone administrated IV, a synthetic formulation of allopregnanolone, and demonstrated a rapid and well tolerated reduction in depressive symptoms. In March 2019 brexanolone obtained FDA approval in PPD indication under the name Zulresso. However, there are differences in the time of beginning of PPD, which could constitute different subgroups of this disease, and which physiopathology could respond to different mechanisms. Prenatal depression does not respond to a GABAergic approach, but women without any risk factor or previous mood disorder developing PPD in the weeks following childbirth could be particularly responsive to this kind of treatment. CONCLUSION: Disability to modulate GABA-A-r expression during pregnancy and restore its previous state after parturition appears to trigger PPD. The GABAergic system is a promising pharmacotherapy target. From preclinical to clinical studies for about twenty years the GABAergic system has been incriminated and targeted in this challenging mental disease.

[Primary cutaneous CD30+ T-cell lymphoproliferation during treatment with fingolimod: Case report and literature review]. / Lymphoprolifération cutanée primitive CD30+ sous fingolimod : un cas et revue systématique de la littérature.

BACKGROUND: Fingolimod is an oral immunomodulator approved for relapsing-remitting multiple sclerosis. We report a case of a primary cutaneous CD30+ T-cell lymphoproliferation occurring 6 months after initiation of fingolimod. Based on a systematic literature review, the characteristics of these fingolimod-induced lymphoproliferative disorders are described. PATIENTS AND METHODS: A 56-year-old woman developed cutaneous indurated and ulcerated nodular lesions 6 months after starting fingolimod for active relapsing-remitting multiple sclerosis. Histological examination of a punch biopsy sample demonstrated a polymorphous dermal infiltrate containing large atypical CD30+ cells, leading to diagnosis of primary cutaneous CD30+ anaplastic large-cell lymphoma. Chest-abdomen-pelvis CT scans were performed to rule out secondary cutaneous anaplastic large-cell lymphoma. Spontaneous clinical regression was observed and after assessing the benefit/risk ratio, it was decided to continue fingolimod under strict surveillance, with no relapse occurring by month 18. DISCUSSION: A systematic review of PUBMED/Medline and Embase identified seven other cases of lymphoproliferative disorders occurring during fingolimod treatment, including two other cases of primitive cutaneous CD30+ lymphoproliferative disorders. CONCLUSION: Even if cutaneous CD30+ lymphoproliferative disorders occur only rarely during fingolimod treatment, dermatologists should nevertheless be aware of this association for which strict dermatological surveillance is required. We would also stress that these CD30+ lymphoproliferative disorders can disappear spontaneously, as in our case, even if treatment by fingolimod is continued.

Is arthroplasty preferable to internal fixation for the treatment of extracapsular fracture of the upper femur in the elderly?

INTRODUCTION: Although internal fixation is the reference treatment for extracapsular fracture of the upper femur, indications for arthroplasty are broadening, especially in unstable comminutive fracture in fragile bone. The present study hypothesis was that arthroplasty reduces early mortality and morbidity and provides better recovery of autonomy in over-80 year-old patients than does internal fixation. MATERIAL AND METHODS: A prospective multicenter study was conducted on 8 sites. Internal fixation was systematically used in 5 centers; arthroplasty was used systematically in 1 center, and reserved for unstable fracture in 2 centers. A total of 697 patients aged over 80 years (mean age, 85±5 years), presenting with extracapsular fracture, were included; 521 were treated by internal fixation and 176 by arthroplasty. Results were studied on multivariate analysis of ASA score, blood loss, transfusion, and also of treatment modality as an independent factor for early (first 6 months) mortality and morbidity (mechanical, general and nutritional complications) and functional outcome (autonomy and dependence). RESULTS: Overall mortality was 19.2%. Autonomy deteriorated in 56% of patients alive at 6 months and dependence worsened in 44%. Two percent of those managed by internal fixation underwent revision for disassembly (n=8) or infection (n=1). Eight percent of those managed by arthroplasty underwent revision for dislocation (n=4), implant loosening (n=3) or infection (n=7). On univariate analysis, mortality was higher in the arthroplasty group (25%) than with internal fixation (17%; P=0.002), as were blood loss (425±286mL versus 333±223mL; P<0.0001), transfusion rate (61% versus 32%; P<0.0001) and infection (4% versus 0.2%; P<0.001). On multivariate analysis, however, treatment modality no longer showed impact on mortality or on morbidity and autonomy at 6 months. Nutritional status was better conserved at 6 months following arthroplasty, but dependence worsened. Poor preoperative autonomy, ASA score, and nutritional status and time to treatment were independent factors for mortality. Transfusion, associated with onset of mechanical complications, significantly increased dependence. CONCLUSION: Type of treatment had little impact on mortality, morbidity or functional outcome. Differences seemed more related to preoperative functional and nutritional status. LEVEL OF EVIDENCE: III, prospective case-control study.

[Breastfeeding: opinion and knowledge of pharmacists. A study in a semi-urban territory]. / Allaitement maternel : opinions et connaissances des pharmaciens dans la métropole lilloise.

BACKGROUND: Because of the French delay regarding breastfeeding compared to other Europeans countries, its promotion was one of the 9 specific nutritional goals of the 2001, 2006, and 2011 National Nutritional Health Program. The objective of this study was to establish the opinion and knowledge of pharmacists from a selected semi-urban territory of the Lille metropolitan area on breastfeeding. METHOD: The 33 pharmacies around the city of Villeneuve-d'Ascq were contacted. First, the goal and the principles of the study were presented to the pharmacists and they were invited to participate in a survey. This survey was divided into 6 topics with 26 questions. The topics were: advice on breastfeeding, pain and inflammation during breastfeeding, use of a breast pump, preservation and reheating of breast milk, breastfeeding and medication, breastfeeding and contraception, and breastfeeding promotion. The survey also evaluated their willingness to promote breastfeeding and the assistance needed for undertaking this promotion. By counting the right answers from 13 of the 26 questions, a global grade was calculated reflecting the knowledge of the participants. The maximum grade was 20 because many questions had several correct answers. RESULTS: Twenty-nine pharmacies agreed to participate (participation rate, 88%). The mean grade was 13.4 (95% CI: 12.7-14.0). Professional and personal experience had no influence on the grades. In the opinion of the pharmacists, the 3 topics most frequently raised by women were cracked nipples, mastitis, and painful breast (quoted by 83% of the pharmacists), the infant formula to use as a complete or partial substitute for breastfeeding (66%), and breastfeeding and medication (59%). Fifty-five percent of the participants were aware of the WHO recommendations on exclusive breastfeeding up to 6 months of age. The desire to promote breastfeeding was strong (68%). Thus, all pharmacists favored the distribution of a leaflet giving information on breastfeeding. CONCLUSION: This study shows a strong desire to promote breastfeeding among the pharmacists surveyed. It allows focusing on the themes that could be the target for continuing education, based on mothers' needs.

[Erythema elevatum diutinum associated with pyoderma gangrenosum in an HIV-positive patient]. / Association d'un erythema elevatum diutinum et d'un pyoderma gangrenosum chez un patient infecté par le VIH.

BACKGROUND: Erythema elevatum diutinum (EED) is a very rare form of chronic dermatosis clinically characterised by reddish-violet papular nodules extending to the surfaces of the limbs and extremities. Histologically, there are classically two phases of progression initially involving associated neutrophilic dermatosis and leucocytoclastic vasculitis, which is later followed by fibrosis of characteristic appearance. We report the association of EED and pyoderma gangrenosum in a patient infected with HIV. PATIENTS AND METHODS: A 53-year-old male seen since 1989 for HIV infection had been presenting firm bilateral and symmetrical nodules on the feet for 6 months. Histological analysis of one of these nodules resulted in diagnosis of chronic erythema elevatum diutinum and treatment with dapsone was initiated. Three months later, despite regression of the EED lesions under dapsone, two large pustules appeared on the outer aspect of the right leg; they were confluent and progressed towards a superficial ulcer with rounded edges with a clinical appearance evocative of pyoderma gangrenosum (PG). Histopathological analysis demonstrated a massive dermal infiltrate beneath the ulcer comprising neutrophils with evidence of leucocytoclasia, all of which militated in favour of the diagnosis of pyoderma gangrenosum. DISCUSSION: We report for the first time the association of two forms of neutrophilic dermatosis, EED and PG, in an HIV-positive patient. This case report and certain data in the literature suggest that the various forms of neutrophilic dermatosis tend to result in a range of lesions rather than in clearly distinct entities.

Livestock waste treatment systems for reducing environmental exposure to hazardous enteric pathogens: some considerations.

Intensive livestock production systems produce significant quantities of excreted material that must be managed to protect water, air, and crop quality. Many jurisdictions mandate how livestock wastes are managed to protect adjacent water quality from microbial and chemical contaminants that pose an environmental and human health challenge. Here, we consider innovative livestock waste treatment systems in the context of multi-barrier strategies for protecting water quality from agricultural contamination. Specifically, we consider some aspects of how enteric bacterial populations can evolve during manure storage, how their fate following land application of manure can vary according to manure composition, and finally the challenge of distinguishing enteric pathogens of agricultural provenance from those of other sources of fecal pollution at a policy-relevant watershed scale. The beneficial impacts of livestock waste treatment on risk to humans via exposure to manured land are illustrated using quantitative microbial risk assessment (QMRA) scenarios. Overall, innovative livestock treatment systems offer a crucially important strategy for making livestock wastes more benign before they are released into the broader environment.

PPAR: a new pharmacological target for neuroprotection in stroke and neurodegenerative diseases.

PPARs (peroxisome-proliferator-activated receptors) are ligand-activated transcriptional factor receptors belonging to the so-called nuclear receptor family. The three isoforms of PPAR (alpha, beta/delta and gamma) are involved in regulation of lipid or glucose metabolism. Beyond metabolic effects, PPARalpha and PPARgamma activation also induces anti-inflammatory and antioxidant effects in different organs. These pleiotropic effects explain why PPARalpha or PPARgamma activation has been tested as a neuroprotective agent in cerebral ischaemia. Fibrates and other non-fibrate PPARalpha activators as well as thiazolidinediones and other non-thiazolidinedione PPARgamma agonists have been demonstrated to induce both preventive and acute neuroprotection. This neuroprotective effect involves both cerebral and vascular mechanisms. PPAR activation induces a decrease in neuronal death by prevention of oxidative or inflammatory mechanisms implicated in cerebral injury. PPARalpha activation induces also a vascular protection as demonstrated by prevention of post-ischaemic endothelial dysfunction. These vascular effects result from a decrease in oxidative stress and prevention of adhesion proteins, such as vascular cell adhesion molecule 1 or intercellular cell-adhesion molecule 1. Moreover, PPAR activation might be able to induce neurorepair and endothelium regeneration. Beyond neuroprotection in cerebral ischaemia, PPARs are also pertinent pharmacological targets to induce neuroprotection in chronic neurodegenerative diseases.

[Anti-cholesterol agents, new therapeutic approaches]. / Les anticholestérolémiants, nouvelles approches thérapeutiques.

Statins and fibrates constitute the two major families of lipid-lowering agents. Statins are widely used for the treatment of pure hypercholesterolaemia while fibrates are used for the treatment of hypertriglyceridemia. Both drugs are also used for the treatment of mixed dyslipidemia. Some fibrates efficiently lower serum LDL-cholesterol. Statins inhibit HMG-CoA reductase and decrease cellular cholesterol synthesis. The resulting lower intracellular cholesterol concentration induces the activation of SREBP thus inducing the over expression and transcription of the LDL receptor gene. This over expression of the LDL receptor in the liver increases the clearance of circulating LDL thus decreasing the LDL-cholesterol plasma levels. The effects of fibrates on lipid metabolism are entirely due to their capacity to activate PPAR-alpha and to induce the over expression of genes containing a PPRE in their promoter. Fibrates decrease triglyceride concentrations by increasing the beta-oxidation of fatty acids in the liver and by decreasing triglyceride-VLDL synthesis. Fibrates also decrease triglycerides by increasing the hydolysys of triglycerides in chylomicron and VLDL through their capacity to increase and to decrease the lipoprotein lipase and the apo C-III transcription, respectively. Fibrates could decrease triglycerides partly by inducing apo A-V over-expression. These molecules increase HDL-cholesterol by increasing apo A-I and apo A-II transcription. Therefore the mechanisms of action of statins and fibrates depend on their capacity to modulate the expression of genes controlling lipoprotein metabolism.