Relationship between Crohn’s disease, infection with Mycobacterium avium subspecies paratuberculosis and SLC11A1 gene polymorphisms in Sardinian patients

AIM: To study the association between Crohn’s disease (CD), Mycobacterium avium subspecies paratubercu- losis (MAP), and genetic factors by examining the role of natural resistance-associated macrophage protein 1 (NRAMP1) gene polymorphisms (now SLC11A1) in Sar dinian patients with CD and controls. METHODS: Thirty-seven CD patients and 34 controls with no inflammatory bowel disease (IBD) were recruited at the University of Sassari after giving written con sent. Six SCL11A1 polymorphisms previously reported to be the most significantly associated with IBD were searched. M. paratuberculosis was identified by IS900 PCR and sequencing. Logistic regression was used to cal culate odds ratios (OR) for the associations among CD presence of MAP, and 6 loci described above. RESULTS: For the first time, a strong association was observed between polymorphisms at NRAMP1 locus 823C/T and CD. While CD was strongly associated withboth NRAMP1 and MAP, NRAMP1 polymorphisms and MAP themselves were not correlated. CONCLUSION: Combined with previous work on the NOD2/CARD15 gene, it is clear that the interplay of ge- netic, infectious, and immunologic factors in the etiology of CD is complex.

Early renal failure as a cardiovascular disease:Focus on lipoprotein(a) and prothrombotic state

Patients with renal failure are at increased risk of cardiovascular events even at the earliest stages of disease.In addition to many classic cardiovascular risk factors,many conditions that are commonly identified as emerging risk factors might contribute to occurrence of cardiovascular disease.Changes in circulating levels of many of these emerging risk factors have been demonstrated in patients with early stages of renal failure caused by different types of renal disease and have been associated with detection of cardiovascular complications.However,for most of these factors evidence of benefits of correction on cardiovascular outcome is missing.In this article,we comment on the role of lipoprotein(a) and prothrombotic factors as potential contributors to cardiovascular events in patients with early renal failure.

Mycobacterium avium subspecies paratuberculosis infects and multiplies in enteric glial cells

AIM: To establish the role of enteric glial cells during infection with Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn's disease. METHODS: In order to establish the role of enteric glial cells during infection with M. avium subspecies paratuberculosis (MAP) in Crohn's disease, Map adhesion experiments on enteric glial cells were performed as well as expression analysis of Map sigma factors during infection. RESULTS: In this study, for the first time, we found a high affinity of MAP to enteric glial cells and we analyzed the expression of MAP sigma factors under different conditions of growth. CONCLUSION: The fact that Map showed a high affinity to the glial cells raises concerns about the complicated etiology of the Crohn's disease. Elucidation of the mechanisms whereby inflammation alters enteric neural control of gut functions may lead to novel treatments for Crohn's disease.

Kidney in primary aldosteronism: A key determinant of treatment outcome

Recently, it has been suggested that primary aldosteronism(PA) is associated with a variety of cardiac,vascular, metabolic, and renal sequelae that reflect the capability of elevated aldosterone to induce organ damage beyond that induced by hypertension itself. The evidence supporting of these views has been obtained from experiments conducted in rodents and clinica studies conducted in patients with this endocrine disorder. It has been suggested that untoward effects of high-salt intake are dependent on activation of mineralocorticoid receptors that might result from increased oxidative stress and changes in the intracellular redox potential. Unilateral adrenalectomy or treatment with mineralocorticoid receptor antagonists are the current options for treating an aldosterone-producing adrena adenoma or idiopathic adrenal hyperplasia. Treatments are largely effective in correcting hypertension and hypokalemia, and currently available information on their capability to prevent deterioration of renal function indicates that surgery and medical treatment are equallybeneficial in the long term. This editorial review will focus on the renal aspects of PA and highlights the role of the kidney as a key determinant of both adaptation to aldosterone-induced volume retention and response of blood pressure to treatment.

Diabetes, diabetic complications, and blood pressure targets

Association of diabetes with hypertension is frequent and it well known that high blood pressure potentiates the probability of diabetic patients to develop macrovascularand microvascular complications. Strong evidence obtained in a number of large scale prospective studies indicates that adequate blood pressure control in diabetic patients is highly beneficial for prevention of cardiovascular events. Nonetheless, only a limited proportion of hypertensive-diabetic individuals included in studies on anti-hypertensive treatment has met the predefined blood pressure goal. The optimal blood pressure goal to be pursued in diabetic patients with hypertension to guarantee effective protection from cardiovascular outcomes is still under intense debate and recommendations of current guidelines on hypertension treatment are still inconsistent. We comment here on the most important studies and conclude that current evidence does not conclusively support the need to reach a blood pressure target in hypertensive patients with diabetes different from nondiabetic hypertensive individuals.