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Abstract Inadequate blood supply to the expanding adipose tissue (AT) is involved in the unhealthy AT remodeling and cardiometabolic consequences of obesity. Because of the pathophysiological role of upregulated mineralocorticoid receptor (MR) signaling in the complications of obesity, this study tested the vasoactive properties of finerenone, a nonsteroidal MR antagonist, in arteries of human AT. Arteries isolated from the visceral AT of obese subjects were studied in a wire myograph. Finerenone resulted in a concentration‐dependent relaxation of arteries precontracted with either the thromboxane‐A2 analog U46619, ET‐1, or high‐K+ solution; the steroidal MR antagonist potassium canrenoate, by contrast, did not relax arteries contracted with either U46619 or high‐K+ solution. Finerenone‐induced relaxation after precontraction with U46619 was greater in the arteries of obese versus nonobese subjects. Mechanistically, the vasorelaxing response to finerenone was not influenced by preincubation with the nitric oxide synthase inhibitor L‐NAME or by endothelium removal. Interestingly, finerenone, like the dihydropyridine Ca2+‐channel blocker nifedipine, relaxed arteries contracted with the L‐type Ca2+‐channel agonist Bay K8644. In conclusion, finerenone relaxes arteries of human visceral AT, likely through antagonism of L‐type Ca2+ channels. This finding identifies a novel mechanism by which finerenone may improve AT perfusion, hence protecting against the cardiometabolic complications of obesity.

Chronic degenerative non-communicable diseases (CDNCDs) represent the main causes of mortality and morbidity worldwide [...]

Background: Chronic kidney disease (CKD) geriatric patients experience a premature aging process, compared with the general population of the same age and sex. The uremic milieu is capable of enhancing oxidative stress (OS) and microinflammation, leading to a pro-aging mechanism and an increased protein catabolism. Moreover, cognitive disorders are observed. Objectives: The aim of this pilot study was to evaluate the possible beneficial effects on the body composition, cognitive functions, inflammatory state and OS of CKD–geriatric patients induced by the consumption of two different plant-based bars (PBBs). Methods: A total of 20 male (mean age 73 ± 7 years) and 9 female patients (mean age 71 ± 4 years) were enrolled, divided as follows: 19 in the PBBs group (that consumed both bars) and 10 in the control group. They were monitored for 12 weeks. The PBBs presented a moderate caloric value and were enriched with waste and by-products of wine and olive oil supply chains and with organic saffron. Results and Conclusions: At the end of this study, the PBBs group, compared to the control group, showed an improvement in their body composition, detected by bioimpedance analysis and ultrasound examination, and in their cognitive function, revealed by mini-mental state examination. In the PBBs group, we also observed an OS reduction, through the free oxygen radical test.

Cardiogenic pulmonary edema (CPE) is characterized by the development of acute respiratory failure associated with the accumulation of fluid in the lung’s alveolar spaces due to an elevated cardiac filling pressure. All cardiac diseases, characterized by an increasing pressure in the left side of the heart, can cause CPE. High capillary pressure for an extended period can also cause barrier disruption, which implies increased permeability and fluid transfer into the alveoli, leading to edema and atelectasis. The breakdown of the alveolar-epithelial barrier is a consequence of multiple factors that include dysregulated inflammation, intense leukocyte infiltration, activation of procoagulant processes, cell death, and mechanical stretch. Reactive oxygen and nitrogen species (RONS) can modify or damage ion channels, such as epithelial sodium channels, which alters fluid balance. Some studies claim that these patients may have higher levels of surfactant protein B in the bloodstream. The correct approach to patients with CPE should include a detailed medical history and a physical examination to evaluate signs and symptoms of CPE as well as potential causes. Second-level diagnostic tests, such as pulmonary ultrasound, natriuretic peptide level, chest radiograph, and echocardiogram, should occur in the meantime. The identification of the specific CPE phenotype is essential to set the most appropriate therapy for these patients. Non-invasive ventilation (NIV) should be considered early in the treatment of this disease. Diuretics and vasodilators are used for pulmonary congestion. Hypoperfusion requires treatment with inotropes and occasionally vasopressors. Patients with persistent symptoms and diuretic resistance might benefit from additional approaches (i.e., beta-agonists and pentoxifylline). This paper reviews the pathophysiology, clinical presentation, and management of CPE.

Point-of-Care Ultrasound (POCUS) is a rapid and valuable diagnostic tool available in emergency and intensive care units. In the context of cardiac arrest, POCUS application can help assess cardiac activity, identify causes of arrest that could be reversible (such as pericardial effusion or pneumothorax), guide interventions like central line placement or pericardiocentesis, and provide real-time feedback on the effectiveness of resuscitation efforts, among other critical applications. Its use, in addition to cardiovascular life support maneuvers, is advocated by all resuscitation guidelines. The purpose of this narrative review is to summarize the key applications of POCUS in cardiac arrest, highlighting, among others, its prognostic, diagnostic, and forensic potential. We conducted an extensive literature review utilizing PubMed by employing key search terms regarding ultrasound and its use in cardiac arrest. Apart from its numerous advantages, its limitations and challenges such as the potential for interruption of chest compressions during image acquisition and operator proficiency should be considered as well and are discussed herein.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs) representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review, we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

A systematic and narrative literature review was performed, focusing attention on the anatomy of the area located at the junction of the sphenoid and the basal portion of the temporal bone (petrous bone, petrous apex, upper petro-clival region) encircled by the free edge of the tentorium, the insertion of the tentorium itself to the petrous apex and the anterior and posterior clinoid processes that give rise to three distinct dural folds or ligaments: the anterior petroclinoid ligament, the posterior petroclinoid ligament and the interclinoid ligament. These dural folds constitute the posterior portion of the roof of the cavernous sinus denominated “the oculomotor triangle”. The main purpose of this review study was to describe this anatomical region, particularly in the light of the relationships between the anterior margin of the free edge of the tentorium and the above-mentioned components of the sphenoid and petrous bone.

Cancer genomes have been explored from the early 2000s through massive exome sequencing efforts, leading to the publication of The Cancer Genome Atlas in 2013. Sequencing techniques have been developed alongside this project and have allowed scientists to bypass the limitation of costs for whole‐genome sequencing (WGS) of single specimens by developing more accurate and extensive cancer sequencing projects, such as deep sequencing of whole genomes and transcriptomic analysis. The Pan‐Cancer Analysis of Whole Genomes recently published WGS data from more than 2600 human cancers together with almost 1200 related transcriptomes. The application of WGS on a large database allowed, for the first time in history, a global analysis of features such as molecular signatures, large structural variations and noncoding regions of the genome, as well as the evaluation of RNA alterations in the absence of underlying DNA mutations. The vast amount of data generated still needs to be thoroughly deciphered, and the advent of machine‐learning approaches will be the next step towards the generation of personalized approaches for cancer medicine. The present manuscript wants to give a broad perspective on some of the biological evidence derived from the largest sequencing attempts on human cancers so far, discussing advantages and limitations of this approach and its power in the era of machine learning.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spreaded rapidly worldwide, as far as it has become a global pandemic. Therefore, the introduction of serological tests for determination of IgM and IgG antibodies has become the main diagnostic tool, useful for tracking the spread of the virus and for consequently allowing its containment. In our study we compared point of care test (POCT) lateral flow immunoassay (FIA) vs automated chemiluminescent immunoassay (CLIA), in order to assess their specificity and sensibility for COVID-19 antibodies detection. Results We find that different specificities and sensitivities for IgM and IgG tests. Notably IgM POCT FIA method vs CLIA method (gold standard) has a low sensitivity (0.526), while IgG POCT FIA method vs CLIA method (gold standard) test has a much higher sensitivity (0.937); further, with respect of IgG, FIA and CLIA could arguably provide equivalent information. Conclusions FIA method could be helpful in assessing in short time, the possible contagiousness of subjects that for work reasons cannot guarantee “social distancing”.

Abstract The identification of individual or clusters of predictive genetic alterations might help in defining the outcome of cancer treatment, allowing for the stratification of patients into distinct cohorts for selective therapeutic protocols. Neuroblastoma (NB) is the most common extracranial childhood tumour, clinically defined in five distinct stages (1–4 & 4S), where stages 3–4 define chemotherapy-resistant, highly aggressive disease phases. NB is a model for geneticists and molecular biologists to classify genetic abnormalities and identify causative disease genes. Despite highly intensive basic research, improvements on clinical outcome have been predominantly observed for less aggressive cancers, that is stages 1,2 and 4S. Therefore, stages 3–4 NB are still complicated at the therapeutic level and require more intense fundamental research. Using neuroblastoma as a model system, here we herein outline how cancer prediction studies can help at steering preclinical and clinical research toward the identification and exploitation of specific genetic landscape. This might result in maximising the therapeutic success and minimizing harmful effects in cancer patients.

Background: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5+) to counteract white adipogenesis by promoting WAT browning. Methods: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5+, or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines. Results: A5+ administration significantly reduced lipids’ accumulation in adipocytes when compared to control cells (p < 0.005). Similarly, A5+ inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (p < 0.0001). We also found that A5+ significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (p < 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (p < 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation. Conclusion: Overall, these results demonstrated that the synergistic effect of compounds contained in A5+ may be able to counteract adipogenesis and then obesity by inducing fat browning.

Chronic non-communicable diseases (CNCDs) are one of the major causes of mortality and morbidity worldwide [...]

Over the past 2 to 3 decades, research has focused on the changes in the vascular effects of insulin occurring in insulin resistant states like obesity. Consistent evidence indicates that obesity results in reduced endothelial release of nitric oxide in response to insulin, associated with concomitant enhancement in the production of endothelin-1. More recent work has pointed toward reduced vascular permeability and changes in the physical-chemical characteristics of the perivascular extracellular matrix as additional mechanisms of impaired insulin sensitivity in obesity. All these perturbations are important, because they contribute to impaired delivery of insulin itself and metabolic substrates to the target tissues and may play a role in the development of both diabetes and vascular damage. This review will describe the physiological vascular actions of insulin and their changes in obesity, focusing on some established pathophysiological determinants of the derangement of vascular insulin signaling, such as the lipid overflow from expanded fat depots and signals originating from inflamed obese adipose tissue (both distant and perivascular). Also, it will outline novel evidence underscoring the contribution of dysregulated adipokine secretion and changes in intestinal permeability and gut microbiome. Finally, it will touch upon some unresolved issues, such as the potential role of vascular insulin resistance in obesity-driven adipose tissue remodeling, and will discuss perspectives for future studies, regarding in particular possible therapeutic strategies with translational implications for the patients care.

Individuals suffering from severe obesity but not presenting the typical metabolic alterations, are included in a subclass of obesity defined Metabolically Healthy Obesity (MHO). The physiological factors underlying what seems a protective and favourable metabolic profile remain unclear. MHO individuals are more insulin-sensitive, have relatively lower visceral/ectopic fat accumulation and reduced levels of chronic low-grade inflammation, compared to obese subjects with co-morbidities. The study of MHO subjects represents a great opportunity for the recognition of the mechanisms that lead to the vascular and metabolic complications in obesity. Finding the differences among the metabolic profile of visceral adipose tissue between metabolically healthy and unhealthy obesity may lead to future personalized and stratified therapies.This review article summarizes the pathomechanisms and metabolic changes in MHO and metabolically unhealthy obesity (MUO), reviews clinical studies on the subject, and discusses preventive and therapeutic options.

Adrenocortical oncocytomas are rare and mostly nonfunctioning neoplasms. We report the case of a 27-year-old woman diagnosed with an ACTH-independent Cushing’s syndrome due to left adrenal oncocytoma. She underwent laparoscopic adrenalectomy. Histopathological examination revealed an oncocytoma of uncertain malignant potential with a low Ki-67 proliferation index, inhibin A positivity, and chromogranin A negativity. Electron micrographs confirmed adrenal oncocytoma cells, characterized by the presence of a large amount of mitochondria. The postoperative course was uneventful, and the patient experienced a progressive regression of Cushing-related symptoms. Periodical follow-ups with MRI and cortisol dosage are required due to the neoplasm’s uncertain malignant potential. Considerations on the diagnosis, pathology findings, clinical remarks, and interventions are made.

Obesity associates with premature atherosclerosis and an increased burden of cardiovascular disease, especially when accompanied by abnormalities of lipid and glucose metabolism. Angiopoietin-like (ANGPTL)3 and ANGPTL4 are metabolic regulators, whose upregulation is associated with dyslipidemia, insulin resistance and atherosclerosis. We analyzed, therefore, changes in circulating ANGPTL3 and ANGPTL4 in obese patients with different metabolic phenotypes and their relation with impaired vasodilator reactivity, an early abnormality in atherosclerosis. Compared to the lean subjects (n = 42), circulating ANGPTL3 was elevated (both p > 0.001) in the patients with metabolically unhealthy obesity (MUO; n = 87) and type 2 diabetes (T2D; n = 31), but not in those with metabolically healthy obesity (MHO; n = 48, p > 0.05). Circulating ANGPTL4, by contrast, was increased in all obese subgroups (all p < 0.001 vs. lean subjects). Vasodilator responses to both acetylcholine and sodium nitroprusside were reduced in the three obese subgroups vs. lean subjects (all p < 0.001), with greater impairment in the patients with T2D than in those with MHO and MUO (all p < 0.05). In the whole population, an inverse relationship (r = 0.27; p = 0.003) was observed between circulating ANGPTL4 and endothelium-dependent vasorelaxation. Circulating ANGPTL3 and ANGPTL4 undergo variable changes in obese patients with different metabolic phenotypes; changes in ANGPTL4 relate to endothelial dysfunction, making this protein a possible target for vascular prevention in these patients.

Chronic kidney disease (CKD) represents a world-wide public health problem. Inflammation, endothelial dysfunction (ED) and vascular calcifications are clinical features of CKD patients that increase cardiovascular (CV) mortality. CKD-related CV disease pathogenic mechanisms are not only associated with traditional factors such as arterial hypertension and dyslipidemia, but also with ED, oxidative stress and low-grade inflammation. The typical comorbidities of CKD contribute to reduce the performance and the levels of the physical activity in nephropathic patients compared to healthy subjects. Currently, the effective role of physical activity on ED is still debated, but the available few literature data suggest its positive contribution. Another possible adjuvant treatment of ED in CKD patients is represented by natural bioactive compounds (NBCs). Among these, minor polar compounds of extra virgin olive oil (hydroxytyrosol, tyrosol and oleocanthal), polyphenols, and vitamin D seem to exert a beneficial role on ED in CKD patients. The objective of the review is to evaluate the effectiveness of physical exercise protocols and/or NBCs on ED in CKD patients.

Background: CV risk exponentially increases as the number of damaged organs increases The Systemic Hemodynamic Atherosclerotic Syndrome (SHATS) represents a novel conceptualization of the CV continuum focusing on simultaneous multi-organ alteration. This is the first study operationally defining SHATS and aimed at identifying its determinants. Methods: Left Ventricular Hypertrophy (echocardiography), Common Carotid Artery plaque and increased thickness (ultrasound), and Chronic Kidney Disease (estimated Glomerular Filtration Rate) indexed selective target organ damage. SHATS was operationally defined as their simultaneous presence in a patient. PWV was measured by Sphygmocor® and BP variability by 24 h ABPM. Results: SHATS affected 19.9% of the 367 studied subjects. Subjects with SHATS had a similar prevalence in diabetes mellitus, but a greater prevalence of very stiff artery (84.9 vs 64.3 %, p < 0.01) and use of antihypertensive medications. In the presence of similar office BP, SHATS was associated with higher 24 h SBP and lower 24 h DBP (a greater pulsatile pressure!), reduced nighttime SBP fall, and a twofold greater prevalence of reverse dipper status (48.2 vs 20.2 %, p < 0.001). BMI (positive correlation) and DBP (negative correlation) were the only traditional CV risk factors significantly associated with the odds of having SHATS. Very stiff artery and BP variability were significant independent determinants of SHATS, with highly predictive accuracy. Conclusion: SHATS, the simultaneous damage of multiple target organs, may easily operationally defined. Very stiff artery and BP variability represent key factors for SHATS. The present results support the hypothesis of SHATS as a systemic condition, needing further characterization.

The circulating microRNAs (miRNAs) associated with type 2 diabetes (T2D) in elderly patients are still being defined. To identify novel miRNA biomarker candidates for monitoring responses to sitagliptin in such patients, we prospectively studied 40 T2D patients (age > 65) with HbA1c levels of 7.5–9.0% on metformin. After collection of baseline blood samples (t0), the dipeptidyl peptidase-IV (DPP-IV) inhibitor (DPP-IVi) sitagliptin was added to the metformin regimen, and patients were followed for 15 months. Patients with HbA1c 0.5% after 3 and 15 months of therapy were classified as “responders” (group R, n=34); all others were classified as “nonresponders” (group NR, n=6). Circulating miRNA profiling was performed on plasma collected in each group before and after 15 months of therapy (t0 and t15). Intra- and intergroup comparison of miRNA profiles pinpointed three miRNAs that correlated with responses to sitagliptin: miR-378, which is a candidate biomarker of resistance to this DPP-IVi, and miR-126-3p and miR-223, which are associated with positive responses to the drug. The translational implications are as immediate as evident, with the possibility to develop noninvasive diagnostic tools to predict drug response and development of chronic complications.

Healthy middle-aged postmenopausal women have higher endothelium-dependent dilation and lower vasoconstrictor activity of endothelin-1 than men. Whether these sex-specific differences extend to patients with cardiovascular risk factors has not been investigated. The current study aimed to determine whether, in patients with cardiovascular risk factors, sex-specific differences exist in endothelium-dependent dilation and endothelin-1 activity.Forearm blood flow responses were measured by strain-gauge plethysmography during the intra-arterial infusion of acetylcholine, sodium nitroprusside, and the selective endothelin type A receptor blocker BQ-123 in 50 women and 64 men with cardiovascular risk factors.Acetylcholine and sodium nitroprusside induced a significant vasodilation in women and men alike (p < 0.01 for both). Also BQ-123 caused a significant vasodilation (p < 0.001) in both groups. The vasodilator response to acetylcholine was greater in women compared to men; however there were no differences in the response to sodium nitroprusside and BQ-123 (p = NS for both) between the two sex groups.Middle-aged women with cardiovascular risk factors have significantly higher endothelium-dependent dilation than middle-aged men; however, vascular endothelin 1 activity is similar in the two groups. These findings suggest that the presence of cardiovascular risk factors is associated with sex-specific effects on endothelium-dependent dilation but not on endothelin 1 activity. Further study is needed to confirm our findings and to characterize the mechanisms underlying this sex-specific regulation of endothelial function.

ObjectiveTo investigate the effects of TLR4 antagonism on human endothelial cells activation and cytokine expression, and whether the Asp299Gly TLR4 polymorphism is associated with better endothelial function in patients with rheumatoid arthritis (RA).MethodsHuman aortic endothelial cells (HAECs) were treated with lipopolysaccharide (LPS), OxPAPC, and free fatty acids (FFA) at baseline and after incubation with the TLR4 antagonist eritoran (E5564). Cytokine expression was assessed by quantitative real-time PCR. In vivo endothelial function was assessed as brachial artery flow-mediated dilation (FMD) in RA patients with the wild type gene (aa) and with the Asp299Gly TLR4 polymorphic variant (ag).ResultsIn HAEC, TLR4 antagonism with eritoran inhibited LPS-induced mRNA expression of IL-6, IL-8, TNFα, CCL-2, VCAM and ICAM (P0.05). In 30 patients with RA (15 with the ag allele) undergoing measurement of FMD, no differences in FMD and plasma levels of IL-6, IL-8, VCAM, and ICAM were found between the aa and the ag phenotype (P>0.05 for all).ConclusionsTLR4 signaling in endothelial cells may be triggered by LPS and oxidized phospholipids, leading to endothelial activation and inflammation, which are inhibited by eritoran. Our in vivo investigation, however, does not support an association between the Asp299Gly TLR4 polymorphism and improved endothelium-dependent vasodilator function in patients with RA. Further study is needed to better understand the potential role of TLR4 on endothelial dysfunction in this and other patient populations.

Acute pancreatitis (AP) is a serious medical condition usually associated with severe upper abdominal pain. The purpose of our study is to assess the therapeutic consequences of contrast-enhanced computed tomography (CE-CT) and the predictive value of CRP for severe pancreatitis. We included patients with a threefold increase of plasma lipase who had received a CE-CT or had a CRP of =150 mg/dl. A total of 74 out of 283 patients got a contrast-enhanced CT scan; in 11 cases the CT was followed by endoscopic or surgical interventions as therapeutic consequences compared with 19 out of 50 control cases. 69 out of 283 patients (24,3%) had CRP >150 mg/dl within 48 hours after admission. 32 of them had SAP. The CRP cutoff of 150 mg/L had a sensitivity of 80% and a specificity of 65%. The positive predictive value for SAP in patients beyond the cutoff is 46.4%. The negative predictive value for SAP in patients below the cutoff was 89.5%. Our results support the opinion that an early CE-CT is usually not indicated. CRP helps to assess the course of AP; levels below 150 mg/dl between the first 48 h indicate a mild course in most of the cases.

A 30-year-old woman with severe hypertension was admitted to the hospital with a history of headache, palpitations, and diaphoresis following sexual intercourse. Twenty-four hour urinary excretion of free catecholamines and metabolites was markedly increased as was serum chromogranin A. Computed tomography scan revealed a large mass in the left adnex site and magnetic resonance imaging confirmed the computer tomography finding, suggesting the presence of extra-adrenal sympathetic paraganglioma. I-metaiodobenzyl guanidine scintigram revealed an increased uptake in the same area. Transcatheter arterial embolization of the mass resulted in marked decreases in blood pressure and urinary excretion of free catecholamines and metabolites. Surgical excision of the mass was then accomplished without complication. Preoperative embolization is a useful and safe procedure which may reduce the risk of catecholamines release at the time of surgical excision in large pelvic extra-adrenal sympathetic paraganglioma.

BACKGROUND: The efficacy of Phosphodiesterase 5 (PDE5) inhibitors to re-establish endothelial function is reduced in diabetic patients. Recent evidences suggest that therapy with PDE5 inhibitors, i.e. sildenafil, may increase the expression of nitric oxide synthase (NOS) proteins in the heart and cardiomyocytes. In this study we analyzed the effect of sildenafil on endothelial cells in insulin resistance conditions in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Human umbilical vein endothelial cells (HUVECs) were treated with insulin in presence of glucose 30 mM (HG) and glucosamine 10 mM (Gluc-N) with or without sildenafil. Insulin increased the expression of PDE5 and eNOS mRNA assayed by Real time-PCR. Cytofluorimetric analysis showed that sildenafil significantly increased NO production in basal condition. This effect was partially inhibited by the PI3K inhibitor LY 294002 and completely inhibited by the NOS inhibitor L-NAME. Akt-1 and eNOS activation was reduced in conditions mimicking insulin resistance and completely restored by sildenafil treatment. Conversely sildenafil treatment can counteract this noxious effect by increasing NO production through eNOS activation and reducing oxidative stress induced by hyperglycaemia and glucosamine. CONCLUSIONS/SIGNIFICANCE: These data indicate that sildenafil might improve NOS activity of endothelial cells in insulin resistance conditions and suggest the potential therapeutic use of sildenafil for improving vascular function in diabetic patients.

Obesity is a chronic disease, whose incidence is alarmingly growing. It is associated with metabolic abnormalities and cardiovascular complications. These complications are clustered in the metabolic syndrome (MetS) leading to high cardiovascular morbidity and mortality. Obesity predisposes to diabetic nephropathy, hypertensive nephrosclerosis, and focal and segmental glomerular sclerosis and represents an independent risk factor for the development and progression of chronic kidney disease (CKD). Albuminuria is a major risk factor for cardiovascular diseases (CVDs). Microalbuminuria has been described as early manifestation of MetS-associated kidney damage and diabetic nephropathy. Obesity and MetS affect renal physiology and metabolism through mechanisms which include altered levels of adipokines such as leptin and adiponectin, oxidative stress, and inflammation. Secretory products of adipose tissue also deeply and negatively influence endothelial function. A better understanding of these interactions will help in designing more effective treatments aimed to protect both renal and cardiovascular systems.