Gene expression profiling of Mycobacterium avium subsp. paratuberculosis in simulated multi-stress conditions and within THP-1 cells reveals a new kind of interactive intramacrophage behaviour

Recent studies have identified in Mycobacterium avium subsp. paratuberculosis (MAP), already known as a pathogen in ruminants, a potential zoonotic agent of some autoimmune diseases in humans. Therefore, considering the possible risk for public health, it is necessary a thorough understanding of MAP's gene expression during infection of human host as well as the identification of its immunogenic and/or virulence factors for the development of appropriate diagnostic and therapeutic tools.In order to characterize MAP's transcriptome during macrophage infection, we analyzed for the first time the whole gene expression of a human derived strain of MAP in simulated intraphagosomal conditions and after intracellular infection of the human macrophage cell line THP-1 by using the DNA-microarray technology. Results showed that MAP shifts its transcriptome to an adaptive metabolism for an anoxic environment and nutrient starvation. It up-regulates several response factors to oxidative stress or intracellular conditions and allows, in terms of transcription, a passive surface peptidoglycan spoliation within the macrophage along with an intensification of the anabolic activity for lipidic membrane structures.These results indicate a possible interactive system between MAP and its host cell based on the internal mimicry unlike other intracellular pathogens, bringing new hypothesis in the virulence and pathogenicity of MAP and its importance in human health

resolution of rate related left bundle branch block after nitrate therapy

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Insulin Resistance and High Blood Pressure: Mechanistic Insight on the Role of the Kidney

The metabolic effects of insulin predominate in skeletal muscle, fat, and liver where the hormone binds to its receptor, thereby priming a series of cell-specific and biochemically diverse intracellular mechanisms. In the presence of a good secretory reserve in the pancreatic islets, a decrease in insulin sensitivity in the metabolic target tissues leads to compensatory hyperinsulinemia. A large body of evidence obtained in clinical and experimental studies indicates that insulin resistance and the related hyperinsulinemia are causally involved in some forms of arterial hypertension. Much of this involvement can be ascribed to the impact of insulin on renal sodium transport, although additional mechanisms might be involved. Solid evidence indicates that insulin causes sodium and water retention, and both endogenous and exogenous hyperinsulinemia have been correlated to increased blood pressure. Although important information was gathered on the cellular mechanisms that are triggered by insulin in metabolic tissues and on their abnormalities, knowledge of the insulin-related mechanisms possibly involved in blood pressure regulation is limited. In this review, we summarize the current understanding of the cellular mechanisms that are involved in the pro-hypertensive actions of insulin, focusing on the contribution of insulin to the renal regulation of sodium balance and body fluids

Association of Mycobacterium avium subsp. paratuberculosis with Multiple Sclerosis in Sardinian Patients

Mycobacterium avium subsp. paratuberculosis (MAP) infection is highly spread in the ruminant herds of Sardinia, in the Western Mediterranean. The objective of this study was to investigate prevalence of MAP infection in association with Multiple Sclerosis (MS) using clinical specimen from patients and controls. We analyzed samples for the presence of MAP specific DNA and to demonstrate humoral response to a MAP protein (MAP2694), a predicted homologue of the T-cell receptor gamma-chain/complement component 1 of the host. We found presence of MAP DNA in 42% of the MS patients and an extremely significant humoral immune response revealed by the MS patients against the MAP protein. In our opinion, this is the first report that significantly associates MAP infection with MS. Further studies will be required to confirm if MAP could be one of the triggers of MS, according to the molecular mimicry theory, in susceptible (and genetically at risk) individuals

Polyphenols rich diets and risk of type 2 diabetes

Type 2 diabetes is an increasing health concern worldwide. Both genetic and environmental risk factors as improper dietary habits or physical inactivity are known to be crucial in the pathogen-esis of type 2 diabetes. Polyphenols are a group of plant-derived compounds with anti-inflammatory and antioxidant properties that are associated with a low prevalence of metabolic conditions charac-terized by insulin resistance, including obesity, diabetes, and hypertension. Moreover, there is now full awareness that foods that are rich in phytochemicals and polyphenols could play an important role in preserving human cardiovascular health and substantial clinical evidence indicates that regu-lar dietary consumption of such foods affects favorably carbohydrate metabolism. This review briefly summarizes the evidence relating dietary patterns rich in polyphenols with glucose metabolism and highlights the potential benefits of these compounds in the prevention of type 2 diabetes

Association of arterial stiffness with a prothrombotic state in uncomplicated nondiabetic hypertensive patients

Background and aims: Past studies reported a significant contribution of a prothrombotic state to the development and progression of target organ damage in hypertensive patients. Stiffening of arterial vessels is associated with aging and hypertension, and additional factors could contribute to this process. This study was designed to examine the relationships between arterial stiffening and the hemostatic and fibrinolytic system. Methods: In 128 middle-aged, nondiabetic, essential hypertensive patients without major cardiovascular and renal complications, we measured coagulation markers that express the spontaneous activation of the hemostatic and fibrinolytic system and assessed stiffness of the arterial tree by measurement of the carotid/femoral pulse wave velocity (cfPWV) and pulse wave analysis with calculation of the brachial augmentation index (AIx). Results: Levels of fibrinogen (FBG), D-dimer (D-d), and plasminogen activator-inhibitor 1 (PAI-1) were significantly higher in patients with PWV and AIx above the median of the distribution. FBG, D-d, and PAI-1 were significantly and directly related with both cfPWV and AIx, and multivariate regression analysis indicated that the relationships of D-d and PAI-1 with both cfPWV and AIx and of FBG with AIx, were independent of age, body mass index, severity and duration of hypertension, use of antihypertensive drugs, blood glucose, and plasma lipids. Conclusion: In middle-aged, uncomplicated, nondiabetic patients with essential hypertension, spontaneous activation of plasma hemostatic cascade and impaired fibrinolysis is significantly and independently associated with stiffening of the arterial tree

Association of non-alcoholic fatty liver disease with left ventricular changes in treatment-naive patients with uncomplicated hypertension

Background and aims: Cardiac structural and functional changes have been demonstrated in patients with non-alcoholic fatty liver disease (NAFLD). Because of the frequent association of NAFLD with hypertension, we aimed to examine the relationship of liver steatosis with left ventricular (LV) changes in patients with hypertension. Materials and methods: In a cross-sectional study, we included 360 untreated, essential hypertensive patients who were free of major cardiovascular and renal complications. Liver steatosis was assessed by three different biochemical scores (NAFLD Liver Fat Score, LFS; Fatty Liver Index, FLI; Hepatic Steatosis Index, HSI). Echocardiography was performed with standard B-mode and tissue-Doppler imaging. Results: LV hypertrophy was present in 19.4% and LV diastolic dysfunction in 49.2% of patients who had significantly higher body mass index (BMI), blood pressure (BP), and homeostatic model assessment (HOMA) index and higher frequency of the metabolic syndrome and liver steatosis that was defined by presence of 2 or more positive scores. LV mass index increased progressively across patients who had none, 1, or 2 or more liver steatosis scores, with associated progressive worsening of LV diastolic function. LV mass index was significantly and positively correlated with age, BMI, BP, HOMA-index, LFS, and HSI. Logistic regression analysis showed that age, BP, and liver steatosis scores independently predicted LV hypertrophy and diastolic dysfunction. Liver steatosis independently predicted LV dysfunction but not LV hypertrophy even after inclusion in analysis of the HOMA-index. Conclusion: NAFLD is associated with LV hypertrophy and diastolic dysfunction in untreated patients with hypertension. In hypertension, NAFLD could contribute to LV diastolic dysfunction with mechanisms unrelated to insulin resistance

Alcohol Intake and Arterial Hypertension: Retelling of a Multifaceted Story

Alcoholic beverages are common components of diets worldwide and understanding their effects on humans’ health is crucial. Because hypertension is the leading risk factor for cardiovascular diseases and all-cause mortality, the relationship of alcohol consumption with blood pressure (BP) has been the subject of extensive investigation. For the purpose of this review, we searched the terms “alcohol”, “ethanol”, and “arterial hypertension” on Pubmed MeSH and selected the most relevant studies. Short-term studies showed a biphasic BP response after ingestion of high doses of alcohol, and sustained alcohol consumption above 30 g/day, significantly, and dose-dependently, increased the risk for hypertension. These untoward effects of alcoholic beverages on BP can be mediated by a multiplicity of neurohormonal mechanisms. In addition to the effects on BP, excess alcohol intake might contribute to cardiac and renal hypertensive organ damage, although some studies suggest possible benefits of moderate alcohol consumption on additional cardiovascular risk factors, such as diabetes and lipoprotein(a). Some intervention studies and cumulative analyses support the evidence of a benefit of the reduction/withdrawal of alcohol consumption on BP and cardiovascular outcomes. This is why guidelines of scientific societies recommend avoidance or limitation of alcohol intake below one unit/day for women and two units/day for men. This narrative article overviews all these topics, providing an update of the current knowledge on the relationship between alcohol and BP

Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study

Direct-acting antiviral agents (DAAs) are extremely effective in eradicating hepatitis C virus (HCV) in chronically infected patients. However, the protective role of the sustained virologic response (SVR) achieved by second- and third-generation DAAs against the onset of hepatocellular carcinoma (HCC) and mortality is less well established