• La sitostérolémie est une maladie génétique autosomique récessive, rare, due à une mutation inhibitrice des gènes des protéines ABCG5/ABCG8 qui ont pour fonction de rediriger vers la lumière intestinale les stérols végétaux alimentaires absorbés dans l’entérocyte via le transporteur NCP1L1 (pour Niemann-Pick disease C1-like 1). Physiologiquement, l’absorption totale des stérols végétaux est très réduite et leur taux plasmatique extrêmement faible. En cas de sitostérolémie, l’absence de retour des stérols végétaux vers la lumière intestinale, secondaire à la mutation ABCG5/ABCG8, a pour conséquence une absorption importante de ceux-ci dans la circulation plasmatique. Ainsi, les stérols végétaux (principalement sitostérol, campéstérol), dont les taux plasmatiques sont élevés, se déposent dans les parois artérielles, ce qui accroit très significativement le risque d’accidents cardiovasculaires. On observe fréquemment, au cours de la sitostérolémie, des dépôts de stérols végétaux extravasculaires, responsables de xanthélasma et de xanthomes. Il faudra évoquer le diagnostic de sitostérolémie en cas de dépôts lipidiques extravasculaires et/ou d’accidents cardiovasculaires précoces alors que le taux de LDL-cholestérol n’est pas significativement augmenté. Le diagnostic sera porté sur une augmentation des stérols végétaux plasmatiques (sitostérol, campéstérol) dosés par chromatographie, et confirmé d’un point de vue génétique, par la présence d’une mutation d’ABCG5 ou d’ABCG8.• Le traitement repose essentiellement sur l’ézétimibe qui, en inhibant la protéine de transfert NPC1L1, responsable de l’absorption entérocytaire du cholestérol libre et des stérols végétaux, réduit significativement les taux plasmatiques de sitostérol et de campéstérol, chez les patients atteints de sitostérolémie. Par ailleurs, le dépistage (biologique, génétique) des apparentés au 1er degré est essentiel afin de mettre en place une thérapeutique la plus précoce possible.• Sitosterolemia is a rare recessive autosomic disease due to a mutation of the genes of ABCG5/ABCG8 proteins, whose one of the functions is to send back to the intestinal tube plant sterols that have been absorbed in the enterocyte via the NCP1L1 transporter. In normal condition, the total absorption of plant sterols is very weak and their plasma levels are very low. In patients with sitosterolemia, plant sterols that have been absorbed in the enterocyte, are not sent back to the intestinal tube, due to the absence of function of the ABCG5/ABCG8 proteins, and the total absorption of plant sterols in plasma is elevated. As a consequence, plasma levels of plant sterols are elevated (sitosterol, campesterol), leading to plant sterol deposits into the arterial wall that increase significantly the risk for cardiovascular events. In addition, extravascular lipid deposits, such as xanthelasma and xanthomas, are frequent in patients with sitosterolemia. The diagnosis of sitosterolemia has to be considered in patients featuring extravascular lipid deposits and/or premature cardiovascular disease when plasma LDL-cholesterol is not significantly elevated. The diagnosis of sitosterolemia is made by the increase of plasma levels of plant sterol (sitosterol, campesterol), measured by chromatography, and genetically confirmed by a mutation of ABCG5 or ABCG8 genes.• Ezetimibe is the first choice treatment for sitosterolemia. It inhibits the NCP1L1 transporter, responsible for the absorption of free cholesterol and plant sterols in the enterocyte, and decreases significantly plasma levels of sitosterol and campesterol in patients with sitosterolemia. In addition, the screening for sitosterolemia among relatives is important in order to set up a treatment as early as possible.

Padecer un trastorno funcional digestivo (TFD) no es fácil. Muchos pacientes preferirían tener una enfermedad orgánica y un informe médico en el que se describiesen los resultados de alguna prueba concluyendo que se observa una lesión. Por tanto, es fundamental adquirir nuevos conocimientos sobre las causas y tratamientos de estas dolencias. El objetivo de este capítulo es resumir de la manera más fácil y útil posible los trabajos más relevantes sobre TFD y trastornos motores digestivos presentados en el Congreso de la Asociación Americana de Gastroenterología (DDW 2010).Lo más destacable se refiere al estudio de los mecanismos patogénicos y búsqueda de nuevas terapias en trastornos muy prevalentes, como la dispepsia funcional, el síndrome del intestino irritable o el estreñimiento, pero también ha habido estudios interesantes en incontinencia, gastroparesia, síndrome de vómitos cíclicos o acalasia.Cada vez está más claro que los TFD son de origen multifactorial y que tanto los factores genéticos como ambientales, psicológicos, microinflamatorios y neuroinmunoendocrinos forman parte de su complejo puzle. Cada año somos partícipes de los avances que se producen en el ámbito mundial con la esperanza de que repercutan en el bienestar de nuestros pacientes.Functional gastrointestinal (GI) disorders are difficult to live with. Many patients would prefer to have an organic disease and a medical report stating the results of a test providing evidence of a lesion. Therefore, further knowledge of the causes and treatment of these disorders is essential. The present article aims to summarize as simply and usefully as possible the most important studies on functional and motor GI disorders presented at the Congress of the American Gastroenterological Association (Digestive Disease Week 2010).The most notable presentations concerned the pathogenic mechanisms and search for new therapies in highly prevalent disorders such as functional dyspepsia, irritable bowel syndrome and constipation but interesting studies were also presented on incontinence, gastroparesis, cyclic vomiting syndrome and achalasia.It is increasingly clear that functional GI disorders are caused by multiple factors and, therefore, that genetic, environment, psychological, microinflammatory and neuroimmune-endocrine factors form part of this complex puzzle. Each year, advances are made in distinct parts of the world, which will hopefully improve patient well-being.

Coronary microcirculation is impaired in idiopathic dilated cardiomyopathy (IDC), possibly because of endothelial dysfunction. High-density lipoproteins (HDLs) have the potential to regulate endothelial function and modulate inflammation and the innate immune response. This study investigated whether reduced HDLs, concomitantly with the activation of inflammation, are associated with IDC. Fifty-five patients with IDC, without evidence of other organ or systemic, chronic, or recurrent diseases, were compared with 55 healthy controls for HDLs and complete lipid profiles, C-reactive protein, C3 and C4 complement fractions, soluble intercellular adhesion molecule-1 and soluble endothelial leukocyte adhesion molecule-1, haptoglobin, and ceruloplasmin. Patients with IDC differed from controls, with lower HDL levels, lower apolipoprotein A-I and A-II levels, and higher triglyceride levels, but not on total and low-density lipoprotein cholesterol, apolipoprotein B, or lipoprotein(a). In addition, all measured inflammation markers were significantly greater in patients with IDC than in controls and were negatively correlated with HDLs. A strong and independent association with IDC was found for age, soluble intercellular adhesion molecule-1, and HDLs that, when categorized as <40 or >40 mg/dl, showed the strongest association (prevalence odds ratio 0.10, p <0.0005) with the disease. In conclusion, the data here reported on reduced HDLs and increased endothelial inflammatory activation and the linear negative correlation between HDLs and inflammation markers, particularly soluble intercellular adhesion molecule-1, could suggest a role for HDLs in the endothelial-microvascular dysfunction seen in IDC.

Extrafetal tissues are a noncontroversial and inexhaustible source of mesenchymal stem cells that can be harvested noninvasively at low cost. In the veterinary field, as in man, stem cells derived from extrafetal tissues express plasticity, reduced immunogenicity, and have high anti-inflammatory potential making them promising candidates for treatment of many diseases. Umbilical cord mesenchymal cells have been isolated and characterized in different species and have recently been investigated as potential candidates in regenerative medicine. In this study, cells derived from bovine Wharton jelly (WJ) were isolated for the first time by enzymatic methods, frozen/thawed, cultivated for at least 10 passages, and characterized. Wharton jelly–derived cells readily attached to plastic culture dishes displaying typical fibroblast-like morphology and, although their proliferative capacity decreased to the seventh passage, these cells showed a mean doubling time of 34.55 ± 6.33 hours and a mean frequency of one colony-forming unit fibroblast like for every 221.68 plated cells. The results of molecular biology studies and flow cytometry analyses revealed that WJ-derived cells showed the typical antigen profile of mesenchymal stem cells and were positive for CD29, CD44, CD105, CD166, Oct-4, and c-Myc. They were negative for CD34 and CD14. Remarkably, WJ-derived cells showed differentiation ability. After culture in induced media, WJ-derived cells were able to differentiate into osteogenic, adipogenic, chondrogenic, and neurogenic lines as shown by positive staining and expression of specific markers. On polymerase chain reaction analysis, these cells were negative for MHC-II and positive for MHC-I, thus reinforcing the role of extrafetal tissue as an allogenic source for bovine cell–based therapies. These results provide evidence that bovine WJ-derived cells may have the potential to differentiate to repair damaged tissues and reinforce the importance of extrafetal tissues as stem cell sources in veterinary regenerative medicine. A more detailed evaluation of their immunologic properties is necessary to better understand their potential role in cellular therapy.

Objectives. High levels of plasma high sensitivity C-reactive protein (CRP), sensitive to therapy with statins, have been described in hyperchole sterolaemia. In vitro evidence shows that CRP activates the complement system, which, in turn, leads to an increased expression of ICAM-1. Our objectives were to verify whether primary hypercholesterolaemia (PHC) is associated with an upregulation of the inflammatory/immune response, and whether this is sensitive to atorvastatin.Methods and results. We examined the levels of sICAM-1, C3, C4 complement fractions in 48 patients with PHC, with (CAD group) or without (No-CAD group) coronary artery disease (CAD) in comparison with a group of 48 healthy controls. The two patient groups were studied before and after atorvastatin therapy. Both hypercholesterolaemic groups showed higher mean values of sICAM-1, C3 and C4 (P < 0.0001) when compared with the controls. The two groups of patients responded differently to atorvastatin therapy. After 3 months, the C3 levels normalized in both groups of patients (P < 0.02 compared with basal values); C4 was greatly reduced only in the CAD group (P < 0.01). After 12 months of therapy, in CAD group C3 mean levels were still significantly lower than baseline values (P < 0.01); a further decrease in the C4 values (P < 0.05 with respect to levels after 3 months of therapy) and also a substantial reduction in sICAM-1 values (P < 0.001 with respect to basal values) were observed.Conclusions. High plasma values of C3 and C4 in PHC cluster with high values of sICAM-1, distinguish subjects with CAD and could be used to monitor the anti-inflammatory effect of statin therapy in these patients.

OBJECTIVE:To test the working hypothesis that inflammation underlying precocious and severe coronary atherosclerotic disease in familial hypoalphalipoproteinaemia (FH) can be mediated by up regulation of the innate immune response.METHODS AND RESULTS:52 patients with FH were compared with 52 healthy controls with regard to immune system markers such as C reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), C3c, and C4. Patients differed from controls in their significantly lower concentrations of high density lipoprotein cholesterol (30.2 (4.0) v 50.5 (13.6) mg/dl, p < 0.0001) and apolipoprotein A I (113.2 (19.9) v 148.7 (25.1) mg/dl, p < 0.0001) and their higher triglyceride (139.3 (63.2) v 81.4 (41.7) mg/dl, p < 0.0001) and CRP plasma concentrations (median 0.33 mg/dl, range 0.02-4.66 mg/dl v median 0.07 mg/dl, range 0.02-0.85 mg/dl, p < 0.0001), but not in their total cholesterol and low density lipoprotein cholesterol concentrations. Concentrations of protein complement were higher in patients (C3: 150.8 (42.3) v 101.9 (17.4) mg/dl, p < 0.0001; C4: 35.5 (13.6) v 22.8 (6.4) mg/dl, p < 0.0001) and sICAM-1 concentrations were more than double those found in the controls (335.1 (107.5) v 159.5 (78.2) mg/dl, p < 0.0001).CONCLUSIONS:Increased concentrations of sICAM-1, C3c, and C4 co-express with high concentrations of CRP in FH. The lack of signs and symptoms of inflammation in these patients may suggest that the immune response is up regulated as part of the pro-inflammatory mechanisms that are activated in this atherogenic condition.

Background-HDL molecules have an established role in the regression processes of atherosclerosis as well as a putative role as antiinflammatory agents. Our study investigated whether familial hypoalphalipoproteinemia, a genetic form of dyslipidemia characterized by very low HDL levels, might be associated with increased inflammation markers such as C-reactive protein.Methods and Results-A total of 50 subjects with hypoalphalipoproteinemia (age, 53.1 +/- 16.7 years) were compared with 64 healthy controls (age, 51.9 +/- 12.4 years). Apart from significantly lower values of HDL cholesterol (30.2 +/- 4.0 versus 52.5 +/- 12.7 mg/dL, P<0.0001) and apolipoprotein AI (113.3 +/- 20.0 versus 155.4 +/- 24.9 mg/dL, P<0.0001) and higher levels of triglycerides (141.3 +/- 62.9 versus 73.5 +/- 39.9 mg/dL, P<0.0001), patients did not show different plasma values of total cholesterol and LDL cholesterol when compared with healthy controls (181.5 +/- 36.6 versus 186.3 +/- 32.6 mg/dL; 123.0 +/- 31.5 versus 119.1 +/- 30.3 mg/dL). CRP plasma values were significantly higher in patients than in controls (median 0.34 [range 0.02 to 4.66] versus 0.07 [0.02 to 0.85] mg/dL, P<0.0001). In the patient group, CRP values were significantly higher in subjects with angiographically documented coronary atherosclerotic disease than in those without. Moreover, CRP concentrations were inversely correlated with both HDL cholesterol (r= -0.44, P=0.0006) and apolipoprotein AI (r= -0.45, P=0.0006) values.Conclusions-Elevation of C-reactive protein values in familial hypoalphalipoproteinemia, in the absence of signs and symptoms of local or systemic inflammation or systemic or recurrent disease, may suggest an upregulation of proinflammatory mechanisms, which is further exacerbated by the presence of coronary atherosclerotic disease.

To the Editor: The article by Sampietro et al1 in the January 8, 2002, issue of Circulation is important because it points out that low levels of high-density lipoprotein (HDL) are associated with elevations of C-reactive protein (CRP), and that those patients with atherothrombotic disease (ATD) have higher CRP levels than do those without ATD. CRP levels correlate with the severity of ATD, and hence, the finding of lower CRP levels in controls (average HDL=52.1 mg/dL) than in patients (average HDL=30.2 mg/dL) at the same low-density lipoprotein (LDL) level (average 181.5 versus 186.3 mg/dL) provides direct evidence of the protective effect of HDL against ATD. It also provides direct proof that it is the ratio between LDL and HDL, rather than simple LDL or HDL levels, that is the best predictor of atherosclerosis. The conclusions of Sampietro et al1 and the accompanying editorial by Ridker,2 however, divert attention from this important finding to the general subject of inflammation of the arterial wall. This, I believe, is an error, because it diverts attention away from causal …