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Background The cardiovascular risk (CVD) in patients with rheumatoid arthritis (RA) is 1.5–2 times higher than that in individuals of the same age and sex. Aims To analyse the degree of endothelial dysfunction, the atherogenic immunoinflammatory serum background and the relationships among some vascular indices, cardiovascular comorbidities, and cognitive performance in subjects with RA. Patients and methods All consecutive patients with a rheumatoid arthritis diagnosis admitted to the Rheumatology Ward of “Policlinico Paolo Giaccone” Hospital of Palermo were enrolled from July 2019 to September 2020. We evaluated our patients’ cognitive functions by administering the Mini-Mental State Examination (MMSE). Reactive Hyperaemia Index (RHI) was evaluated for assessment of endothelial function. Serum levels of angiopoietin 2, osteopontin and pentraxin 3 were assessed by blood collection. Results Fifty-eight consecutive patients with RA and 40 control subjects were analysed. RA patients showed significantly lower mean RHI values, significantly higher mean Augmentation Index (AIX) values and significantly lower mean Mini-Mental State Examination (MMSE) score values than the control group. Patients with rheumatoid arthritis also showed higher mean serum values of pentraxin 3 and angiopoietin 2 than healthy controls. Multivariate logistic regression analysis showed a significant association between pentraxin 3 and angiopoietin 2 and the presence of RA. Discussion Angiopoietin 2 and pentraxin 3 could be considered surrogate biomarkers of endothelial activation and vascular disease, as they could play an essential role in the regulation of endothelial integrity and inflammation.

Background and Aims: No study has examined the relationship between the presence of hypertension and the Mediterranean diet ( MeDi) with regard to other cardiometabolic risk factors A retropective study to evaluate the presence of a lower adherence to the Mediterranean diet in hypertensive subjects, to analyze the correlation between the adherence to Mediterranean Diet and other cardiovascular risk factors . Materials and Methods: We analyzed the records and collected the data of the patients admitted to our Internal Medicine ward from 2010 to 2020 with a discharge diagnosis of metabolic syndrome according to the NCEP ATP-III criteria . The Mediterranean Diet Score was used to evaluate the consumption and frequency of the elements characterizing a Mediterranean-type diet. Results : Hypertensive patients were older and had a higher mean BMI . The degree of adherence to the Mediterranean diet, evaluated by the Mediterranean diet score, was significantly higher in the control group than the hypertensive group. Various comorbidities were more prevalent in hypertensives such as type 2 diabetes mellitus, heart failure, ischemic heart disease, and chronic renal failure .A lower adherence to the Mediterranean diet was significantly associated with an increased prevalence of dyslipidemia, cardiovascular diseases, chronic renal insufficiency and PAD/carotid atherosclerosis and a significantly worse lipid profiles. Conclusion: Our findings show that the in hypertensive patients a lower adherence to a Mediterranean Diet Style is associated with a worse cardiovascular risk factor profile. Thus Mediterrean Diet adherence in hypertensive subjects is associated with a wider cardiometabolic scenario .

Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, predominantly globotriaosylsphingosine (Gb3) in lysosomes, as well as other cellular compartments of several tissues, causing multi-organ manifestations (acroparesthesias, hypohidrosis, angiokeratomas, signs and symptoms of cardiac, renal, cerebrovascular involvement). Pathogenic mutations lead to a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA). In the presence of high clinical suspicion, a careful physical examination and specific laboratory tests are required. Finally, the diagnosis of Fabry’s disease is confirmed by the demonstration of the absence of or reduced alpha-galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females. Measurement of the biomarkers Gb3 and Lyso Gb3 in biological specimens may facilitate diagnosis. The current treatment of Anderson-Fabry disease is represented by enzyme replacement therapy (ERT) and oral pharmacological chaperone. Future treatments are based on new strategic approaches such as stem cell-based therapy, pharmacological approaches chaperones, mRNA therapy, and viral gene therapy. This review outlines the current therapeutic approaches and emerging treatment strategies for Anderson-Fabry disease.

Stroke is a heterogeneous disease, and within the broad category of brain ischemia and its subtypes vary dramatically in its etiology. : The endothelium can regulate the vascular homeostasis by modulating processes of vascular dilation and constriction by producing and secreting cytokines and chemical mediators, and inflammation represents one of the most important factors that contribute to alteration in vessel structure and function by dysregulation of this fine balance. : Endothelial dysfunction means a basic determinant of the vascular damage, which can be identified in all different clinical subtypes of stroke, and, recently, it has been recognized as an interesting determinant of cerebrovascular risk. The entire spectrum of inflammatory processes is likely to act in concert, and cytokines are important mediators of stroke by inducing immunological/inflammatory reactions, which contribute to brain infarct progression as well as to the disease severity and outcome. : Results from recent studies and ongoing and future researches will allow characterizing these complex mechanisms better and finally leading to innovative therapeutic strategies that may change the natural history of this severe and disabling disease significantly.

There is growing evidence that hypertension is the most important vascular risk factor for the development and progression of cardiovascular and cerebrovascular diseases. The brain is an early target of hypertension-induced organ damage and may manifest as stroke, subclinical cerebrovascular abnormalities and cognitive decline. The pathophysiological mechanisms of these harmful effects remain to be completely clarified. Hypertension is well known to alter the structure and function of cerebral blood vessels not only through its haemodynamics effects but also for its relationships with endothelial dysfunction, oxidative stress and inflammation. In the last several years, new possible mechanisms have been suggested to recognize the molecular basis of these pathological events. Accordingly, this review summarizes the factors involved in hypertension-induced brain complications, such as haemodynamic factors, endothelial dysfunction and oxidative stress, inflammation and intervention of innate immune system, with particular regard to the role of Toll-like receptors that have to be considered dominant components of the innate immune system. The complete definition of their prognostic role in the development and progression of hypertensive brain damage will be of great help in the identification of new markers of vascular damage and the implementation of innovative targeted therapeutic strategies.

Background Recent cardiovascular outcome trials have shown significant reductions in major cardiovascular (CV) events with glucagon-like peptide (GLP)-1 receptor agonists. Additionally, adjunctive surrogates for cardiovascular risk validated by some studies include arterial stiffness and endothelial function indexes. To date, no randomized trial has addressed the possible effects of antidiabetic interventional drugs such as GLP1 agonists on endothelial and arterial stiffness indexes as surrogate markers of vascular damage. Aims We aimed to evaluate metabolic efficacy and surrogate vascular efficacy endpoints of once-weekly dulaglutide (1.5 mg) plus traditional antidiabetic treatment compared with traditional antidiabetic treatment alone in subjects with type 2 diabetes. Methods Men and women (aged ≥ 50 years) with established or newly detected type 2 diabetes whose HbA1c level was 9.5% or less on stable doses of up to two oral glucose­ lowering drugs with or without basal insulin therapy were eligible for randomization. Subcutaneous dulaglutide was initiated at the full dose (1.5 mg/day weekly). Arterial stiffness (PWV: pulse wave velocity and augmentation index) and endothelial function (RHI: reactive hyperaemia index) were evaluated at baseline and at three-month and nine-month examination visits. At each visit (at 3 and 9 months), the subjects were also evaluated for glycaemic variables such as fasting plasma glucose (FPG) and HbA1c and lipid variables such as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels. Results At the three-month follow-up, the subjects treated with dulaglutide showed significantly lower serum levels of FPG and HbA1c than control subjects treated with conventional therapy. At the 9-month follow-up, subjects treated with dulaglutide showed significant lower values of the mean diastolic blood pressure, BMI, total serum cholesterol, LDL cholesterol, FPG, HbA1c and PWV and higher mean RHI values than control subjects treated with conventional therapy. Conclusions Our randomized trial showed that subjects with type 2 diabetes treated with conventional therapy plus 1.5 mg/day of subcutaneous dulaglutide compared with subjects treated with conventional therapy alone showed favourable metabolic effects associated with positive effects on vascular health markers such as arterial stiffness and endothelial function markers. These findings are consistent with previous study findings indicating the strict relationship between cardiovascular risk factors such as systolic blood pressure, total serum cholesterol and LDL levels and cardiovascular events and vascular health surrogate markers.

Background Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age. Aims The aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices. Methods We enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection. Results 63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance. Discussion Patients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot.

Aims: We sought to compare the effects of furosemide+hypertonic saline solution (HSS) treatment in patients with acute decompensated heart failure in comparison with furosemide alone and the response in a compensated state after an acute saline load with regard to serum levels of heart failure biomarkers. Methods and results: We enrolled 141 patients with acute decompensated heart failure with reduced ejection fraction admitted to our Internal Medicine ward from March 2017 to November 2019. A total of 73 patients were randomized to treatment with i.v. high-dose furosemide plus HSS, whereas 68 patients were randomized to i.v. high-dose furosemide alone. Patients treated with furosemide plus HSS compared with controls treated with furosemide alone showed a comparable degree of reduction in the serum levels of interleukin (IL)-6, soluble suppression of tumorigenicity 2 (sST2), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the ‘between-group’ analysis. Nevertheless, patients treated with high-dose furosemide+HSS showed significantly higher absolute delta values of IL-6 (2.3±1.2 vs. 1.7±0.9, P&nbsp

Background We report an unusual case of infective colitis by Yersinia enterocolitica complicated by microliver abscesses mimicking multiple liver metastases in a 79 yr old female without any risk factors for bacteriaemia by this pathogen. Case presentation The patient was admitted to the Internal Medicine with Stroke Care ward of University Policlinico “P. Giaccone” in Palermo because of the appearance of diarrhoea. After the antimicrobial treatment for infective colitis, the clinicians observed a persistently increased white blood cells (WBC) count and multiple hepatic lesions; after having excluded any neoplastic disease and inflammatory bowel disease (IBD), blood cultures positive for Y. enterocolitica allowed to establish the final diagnosis was infective micro liver abscesses consequent to infective colitis due to Y. enterocolitica, which were successfully treated with cefixime and doxycycline. Conclusions This case report should make clinicians reflect on how complex the differential diagnosis between microliver abscesses and metastasis could be and the possibility of bacteriaemia by Y. enterocolitica even without iron overload conditions.

Background: Recent cardiovascular outcome trials have shown significant reductions of major cardiovascular (CV) events with glucagon-like peptide (GLP)-1 receptor agonists. Adjunctive surrogates for cardiovascular risk more recently validated by some studies (23,24) are arterial stiffness and endothelial function indexes. No randomized trials have yet addressed the possible effects of antidiabetic interventional drugs such as GLP1 agonists on endothelial and arterial stiffness indexes as surrogate markers of vascular damageAims: A randomized trial to once-weekly dulaglutide (1.5 mg) added to traditional antidiabetic treatment compared to traditional treatment alone to evaluate some metabolic efficacy endpoints and surrogate vascular efficacy endpoints such as endothelial function and arterial stiffness indexes.Methods: Men and women (aged ≥50 years) with established or newly detected type 2 diabetes whose HbA1c was 9.5% or less on stable doses of up to two oral glucose­lowering drugs with or without basal insulin therapy were eligible. Subcutaneous dulaglutide was initiated at the full dose (1.5 mg/day weekly). Arterial stiffness indexes (pulse wave velocity and augmentation index) and endothelial function index (reactive hyperemia index) were evaluated at baseline and at a three-month and nine-month examination visit. At each visit (at 3 and 9 month follow-up) were also evaluated glycemic variables such as fasting plasma glucose (FPG), HbA1c and lipid variables such as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride. Results: at a three month follow up subjects treated with dulaglutide in comparison with subjects treated with conventional therapy showed significantly lower serum levels of FBG and significantly lower percentage of HBa1c. At a 9 month follow up subjects treated with dulaglutide in comparison with control subjects treated with conventional therapy showed a significant lowering of diastolic blood pressure, BMI, mean total serum cholesterol, LDL cholesterol, FPGa significantly lower percentage of HBa1C and PWV and higher mean RHI values.Discussion: These findings are consistent with previous studies indicating the strict relationship between cardiovascular risk factors such as systolic blood pressure, total serum cholesterol and LDL levels and cardiovascular events and vascular health surrogate markers.

One of the most important causes of neurological morbidity and mortality in the world is ischemic stroke. It can be a result of multiple events such as embolism with a cardiac origin, occlusion of small vessels in the brain, and atherosclerosis affecting the cerebral circulation. Increasing evidence shows the intricate function played by the immune system in the pathophysiological variations that take place after cerebral ischemic injury. Following the ischemic cerebral harm, we can observe consequent neuroinflammation that causes additional damage provoking the death of the cells; on the other hand, it also plays a beneficial role in stimulating remedial action. Immune mediators are the origin of signals with a proinflammatory position that can boost the cells in the brain and promote the penetration of numerous inflammatory cytotypes (various subtypes of T cells, monocytes/macrophages, neutrophils, and different inflammatory cells) within the area affected by ischemia; this process is responsible for further ischemic damage of the brain. This inflammatory process seems to involve both the cerebral tissue and the whole organism in cardioembolic stroke, the stroke subtype that is associated with more severe brain damage and a consequent worse outcome (more disability, higher mortality). In this review, the authors want to present an overview of the present learning of the mechanisms of inflammation that takes place in the cerebral tissue and the role of the immune system involved in ischemic stroke, focusing on cardioembolic stroke and its potential treatment strategies.

Among the causes of global death and disability, ischemic stroke (also known as cerebral ischemia) plays a pivotal role, by determining the highest number of worldwide mortality, behind cardiomyopathies, affecting 30 million people. The etiopathogenetic burden of a cerebrovascular accident could be brain ischemia (~80%) or intracranial hemorrhage (~20%). The most common site when ischemia occurs is the one is perfused by middle cerebral arteries. Worse prognosis and disablement consequent to brain damage occur in elderly patients or affected by neurological impairment, hypertension, dyslipidemia, and diabetes. Since, in the coming years, estimates predict an exponential increase of people who have diabetes, the disease mentioned above constitutes together with stroke a severe social and economic burden. In diabetic patients after an ischemic stroke, an exorbitant activation of inflammatory molecular pathways and ongoing inflammation is responsible for more severe brain injury and impairment, promoting the advancement of ischemic stroke and diabetes. Considering that the ominous prognosis of ischemic brain damage could by partially clarified by way of already known risk factors the auspice would be modifying poor outcome in the post-stroke phase detecting novel biomolecules associated with poor prognosis and targeting them for revolutionary therapeutic strategies.

Although each autoimmune disease is associated with specific tissue or organ damage, rheumatic diseases share a pro-inflammatory pattern that might increase cardiovascular risk. Retrospective and prospective studies on patients affected by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) highlighted the concept of “accelerated atherosclerosis”. Therefore, the purpose of this systematic review and meta-analysis is the assessment of symptomatic or asymptomatic cardiovascular events among patients with rheumatic diseases as RA and SLE. The literature research obtained all manuscripts published in the English language between 2015 and 2019 for a total of 2355 manuscripts. After selection through inclusion and exclusion criteria, four articles examined cardiovascular risk in RA patients, 8 in SLE patients, and 2 in RA and SLE patients. Patients with SLE had a RR of 1.98 (95% CI: 1.18–3.31) of symptomatic cardiovascular events compared to the unexposed cohort. The meta-regression analysis showed that younger patient (age per year increase β = −0.12 95%CI: −0.20, −0.4), belonging to studies conducted in continent different from America (β = −0.89; −95% CI: 1.67, −0.10), after 2000 (β = 0.87; 95% CI: 0.09, 1.65) and with a higher quality score 0.80 (95% CI: 0.31, 1.29) had a higher risk of cardiovascular events. In patients with RA, the RR of cardiovascular events was 1.55 (95% CI: 1.18–2.02). These data are helpful to implement cardiovascular preventive strategies among people suffering from rheumatologic diseases to decrease the incidence of cardiovascular events. However, these implementation needs to build a higher network between rheumatologists and primary care healthcare workers to furnish the same information to patients and monitor their preventive practice compliance.

Background:Dyslipidaemias is a recognized risk factor for atherosclerosis, however, new evidence brought to light by trials investigating therapies to enhance HDLcholesterol have suggested an increased atherosclerotic risk when HDL-C is high.Results:Several studies highlight the central role in atherosclerotic disease of dysfunctional lipoproteins; oxidised LDL-cholesterol is an important feature, according to “oxidation hypothesis”, of atherosclerotic lesion, however, there is today a growing interest for dysfunctional HDL-cholesterol. The target of our paper is to review the functions of modified and dysfunctional lipoproteins in atherogenesis.Conclusion:Taking into account the central role recognized to dysfunctional lipoproteins, measurements of functional features of lipoproteins, instead of conventional routine serum evaluation of lipoproteins, could offer a valid contribution in experimental studies as in clinical practice to stratify atherosclerotic risk

Fabry disease is a rare lysosomal storage disorder caused by a deficiency of α-galactosidase A, resulting in multisystemic involvement. Lyso-Gb3 (globotriaosylsphingosine), the deacylated form of Gb3, is currently measured in plasma as a biomarker of classic Fabry disease. Intensive research of biomarkers has been conducted over the years, in order to detect novel markers that may potentially be used in clinical practice as a screening tool, in the context of the diagnostic process and as an indicator of response to treatment. An interesting field of application of such biomarkers is the management of female heterozygotes who present difficulty in predictable clinical progression. This review aims to summarise the current evidence and knowledge about general and specific markers that are actually measured in subjects with confirmed or suspected Fabry disease; moreover, we report potential novel markers such as microRNAs. Recent proteomic or metabolomic studies are in progress bringing out plasma proteome profiles in Fabry patients: this assessment may be useful to characterize molecular pathology of the disease, to improve diagnostic process, and to monitor response to treatment. The management of Fabry disease may be improved by the identification of biomarkers that reflect clinical course, severity, and the progression of the disease.

BACKGROUND: No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. AIM OF THE STUDY: We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. MATERIALS AND METHODS: The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (RHI). The mini-mental state examination (MMSE) was administered to test cognitive performance. RESULTS: 80 consecutive patients with biopsy-proven NAFLD and 83 controls without fatty liver disease. NAFLD subjects showed significantly lower mean RHI, higher mean arterial stiffness indexes and lower mean MMSE score. Multivariable analysis after correction for BMI, dyslipidaemia, hypertension, sex, diabetes, age and cardiovascular disease showed that BMI, diastolic blood pressure and RHI are significantly associated to NAFLD. Simple linear regression analysis showed among non-alcoholic steatohepatitis (NASH) subjects a significant negative relationship between ballooning grade and MMSE and a significant positive association between Kleiner steatosis grade and augmentation index. CONCLUSIONS: Future research will be addressed to evaluate the relationship between inflammatory markers and arterial stiffness and endothelial function indexes in NAFLD subjects. These study will evaluate association between cardiovascular event incidence and arterial stiffness, endothelial and cognitive markers, and they will address the beneficial effects of cardiovascular drugs such as statins and ACE inhibitors on these surrogate markers in NAFLD subjects.

BACKGROUND: Stroke represent one of the most devastating of all neurological diseases, affecting about 15 million people per year and is an important cause of morbidity and mortality worldwide and currently the leading cause of adult disability in developed countries. Blood pressure and heart rate may undergo several modifications in patients with both ischemic and hemorrhagic stroke in fact raised blood pressure levels may lead to cerebral edema, hematoma expansion or hemorrhagic transformation and in contrast low blood pressure can lead to increased cerebral infarction or perihematomal ischemia. In addition, ECG abnormalities and cardiac arrhythmias, especially atrial fibrillation, are relatively frequent after stroke, and other well known complications such as heart failure, miocardial infarction and sudden death have been reported. The acute phase of brain infarction requires a careful management of both blood pressure levels and heart rate but despite the large amount of information, blood pressure and heart rate management are still under debate. OBJECTIVE: Provide clear indications about the optimal blood pressure and heart rate management of both ischemic and hemorrhagic stroke, in view of the main available evidence. METHOD: In this review, we discuss the evidence for blood pressure and heart rate management in acute stroke, the challenges and issues raised, and look to on-going and future trials that may provide some clarity in this controversial area.

// Antonino Tuttolomondo 1 , Irene Simonetta 1 , Giovanni Duro 2 , Rosaria Pecoraro 1 , Salvatore Miceli 1 , Paolo Colomba 2 , Carmela Zizzo 2 , Antonia Nucera 3, 4 , Mario Daidone 1 , Tiziana Di Chiara 1 , Rosario Scaglione 1 , Vittoriano Della Corte 1 , Francesca Corpora 1 , Danai Vogiatzis 1 and Antonio Pinto 1 1 U.O.C di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S), University of Palermo, Palermo, Italy 2 CNR-IBIM: Institute of Biomedicine and Molecular Immunology “A. Monroy” Palermo, Palermo, Italy 3 Stroke Unit, Neurology, Saint Andrea Hospital, La Spezia, Italy 4 Department of Clinical Neurological Sciences, Western University, London, Ontario, Canada Correspondence to: Antonino Tuttolomondo, email: bruno.tuttolomondo@unipa.it Keywords: Anderson-Fabry disease (AFD), family, variability Received: March 20, 2017 Accepted: April 11, 2017 Published: May 29, 2017 ABSTRACT Background: Anderson-Fabry disease (AFD) is an inborn lysosomal enzymopathy resulting from the deficient or absent activity of the lysosomal exogalactohydrolase, α-galactosidase A. This deficiency, results in the altered metabolism of glycosphingolipids which leads to their accumulation in lysosomes, thus to cellular and vascular dysfunction. To date, numerous mutations (according to recent data more than 1000 mutations) have been reported in the GLA intronic and exonic mutations. Traditionally, clinical manifestations are more severe in affected hemizygous males than in females. Nevertheless, recent studies have described severe organ dysfunction in women. The aim of the study: This study reports clinical, biochemical, and molecular findings of the members of three Sicilian families. The clinical history of these patients highlights a remarkable interfamilial and intrafamilial phenotypic variability which characterizes Fabry disease relative to target organs and severity of clinical manifestations. Discussion: Our findings, in agreement with previous data, report a little genotype-phenotype correlation for the disease, suggesting that the wide phenotypic variability of Anderson-Fabry disease is not completely ascribable to different gene mutations but other factors and mechanisms seem to be involved in the pathogenesis and clinical expression of the disease. Moreover, this study emphasies the importance of pedigree analysis in the family of each proband for identifying other possibly affected relatives.

Background: The crucial role of endothelium is due to the ability of endothelial cells to receive and concurrently respond to humoral and hemodynamic stimuli. The mechanisms that mediate these reactions are: the production of endothelium-derived factors and metabolizing enzymes; the expression of binding proteins and adhesive molecules; and the consequential shape changes. In fact, a wide range of anti-atherosclerotic action substances is produced by the endothelial cells with the objective of maintaining the balance between vasoconstriction and vasodilation, and inhibit or stimulate the proliferation and migration of smooth muscle cells, thrombogenesis and fibrinolysis. Smoke, age, hypercholesterolemia, hypertension, hyperglycemia, and a family history of atherosclerotic disease may induce functional and structural changes in the endothelium that imply the progressive loss of its protective role and the development of a proatherosclerotic state called endothelial dysfunction. Methods: The evaluation of the function of endothelial cells is based on the measurement of endothelial cell response to the stimulation by vasoactive substances. The endothelial response can be assessed in the coronary arteries and peripheral circulations. On our opinion, among the techniques, the most advantageous, reproducible, minimally invasive and statistically valid, as shown in many trials, is the Endo-PAT. This technique assesses endothelial function on peripheral arteries evaluating, at the level of the distal phalanx of the index finger, the vascular response to a period of ischemia in the arm induced through occlusion of the brachial artery (for five minutes) and subsequent restoration of blood flow. An additional method that is used to evaluate the state of wellness of large arteries is arterial stiffness. Arterial stiffness can be described as a reduced capability of a vessel to dilate or contract in response to pressure changes; it is defined using two parameters: compliance and distensibility. Result and Conclusion: The present review intends to clarify the mechanisms behind the development of endothelial dysfunction, and aims to show how widely proven is the correlation between endothelial dysfunction (assessed both by Endo-PAT and sphigmoCOR) and cardiovascular diseases, such as atherosclerosis, hypertension, diabetes mellitus, stroke, coronary artery disease and heart failure. Moreover, the assessment of endothelial dysfunction may represent an integral adjuvant test to identify the predisposed patients at risk for future cardiovascular accidents, as we suggest.

Several studies indicated how dietary patterns that were obtained from nutritional cluster analysis can predict disease risk or mortality. Low-grade chronic inflammation represents a background pathogenetic mechanism linking metabolic risk factors to increased risk of chronic degenerative diseases. A Mediterranean diet (MeDi) style has been reported as associated with a lower degree of inflammation biomarkers and with a protective role on cardiovascular and cerebrovascular events. There is heterogeneity in defining the MedDiet, and it can, owing to its complexity, be considered as an exposome with thousands of nutrients and phytochemicals. Recently, it has been reported a novel positive association between baseline plasma ceramide concentrations and cardiovascular events and how adherence to a Mediterranean Diet-style may influence the potential negative relationship between elevated plasma ceramide concentrations and cardiovascular diseases (CVD). Several randomized controlled trials (RCTs) showed the positive effects of the MeDi diet style on several cardiovascular risk factors, such as body mass index, waist circumference, blood lipids, blood pressure, inflammatory markers and adhesion molecules, and diabetes and how these advantages of the MeDi are maintained in comparison of a low-fat diet. Some studies reported a positive effect of adherence to a Mediterranean Diet and heart failure incidence, whereas some recent studies, such as the PREDIMED study, showed that the incidence of major cardiovascular events was lower among those assigned to MeDi supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. New studies are needed to better understand the molecular mechanisms, whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases, but also discussing other related diseases. We review MedDiet composition and assessment as well as the latest advances in the genomic, epigenomic (DNA methylation, histone modifications, microRNAs, and other emerging regulators), transcriptomic (selected genes and whole transcriptome), and metabolomic and metagenomic aspects of the MedDiet effects (as a whole and for its most typical food components). We also present a review of the clinical effects of this dietary style underlying the biochemical and molecular effects of the Mediterranean diet. Our purpose is to review the main features of the Mediterranean diet in particular its benefits on human health, underling the anti-inflammatory, anti-oxidant and anti-atherosclerotic effects to which new knowledge about epigenetic and gut-microbiota relationship is recently added.

Focal atrial tachycardia is a relatively uncommon paroxysmal supraventricular tachycardia. Although atrioventricular conduction is regularly 1:1 and the PR interval is often in the normal range, occasionally a 1:1 atrial tachycardia may have a short RP interval, especially when the heart rate is particularly high or the atrioventricular conduction is markedly increased. In these cases, it is necessary to differentiate focal atrial tachycardia from common atrioventricular nodal reentrant tachycardia , which is the most frequent form of paroxysmal supraventricular tachycardia. We describe a case of unusual focal atrial tachycardia with a short RP interval (< 90 ms) in a patient with a marked AV first-degree block which simulates a typical atrioventricular nodal reentrant tachycardia.