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The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project. [ABSTRACT FROM AUTHOR]

Cancer cachexia is one of the leading causes of mortality for late-stage cancer patients. One of its key characteristics is abnormal metabolism and loss of metabolic flexibility, i.e., loss of ability to switch between use of fats and carbohydrates as needed. Here, it is hypothesized that late-stage systemic cancer creates a chronic resource drain on the body that may result in the same metabolic adaptations that occur during intense endurance exercise, activating some of the same mechanisms of nutrient consumption that are supposed to be transient during strenuous physical activity. This hypothesis is evaluated by creating a mathematical model that characterizes the relationships between increased exercise intensity and carbohydrate and fat oxidation. The model is parametrized using published data on these characteristics for a group of professional athletes, moderately active individuals, and individuals with metabolic syndrome. Transitions between different zones of relative nutrient consumption as a function of increased effort are captured through explicitly modeling ventilatory thresholds, particularly VT1 and VT2, where fat is primarily used below VT1, both carbohydrates and fats are used between VT1 and VT2, and where carbohydrates become the primary source of fuel above VT2. A simulation is conducted of projected patterns of nutrient consumption when simulated "effort" remains between VT1 and VT2, or above VT2, and it is proposed that it is the scenario when the simulated effort is maintained primarily above VT2 that most closely resembles metabolic patterns characteristic of cachexia. A discussion of a broader framework for understanding cachectic metabolism using insights from exercise physiology, including potential intervention strategies, concludes this paper. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes Mellitus (DM) is the most challenging health problem in the world. Understanding the pathogenesis, maintaining sugar levels and preventing its long term complications are still the major goals of research in diabetic patients. Emerging scientific evidences has disclosed relationship between serum magnesium concentration in patients of Type 2 DM (T2DM), its complications and poor glycaemic control. Hypomagnesemia may be a factor implicated in pathogenesis of poor glycaemic control and diabetic complications. Aim: The present study was undertaken to assess level of serum magnesium concentration in T2DM patients with and without complications and find out correlation between serum magnesium concentrations with glycaemic control. Materials and Methods: A cross-sectional study was conducted which included 150 cases divided into 3 groups. In group I, there were 50 normal healthy controls. In group II, 50 patients having DM type 2 without any complications and with good glycaemic control were included. In group III, 50 patients with DM type 2 with one or more chronic complications and having poor glycaemic control were selected. The significance of difference in serum magnesium concentration between all three groups was tested by One-way ANOVA test. Results: Statistically significant decrease was observed in magnesium concentration (with p-value

Objective: To develop a Metabolic Derangement Score (MDS) based on parameters available after initial testing and assess the score's ability to predict survival after out-of hospital cardiac arrest (OHCA) and the likely usefulness of extracorporeal life support (ECLS)., Methods: A total of 5100 cases in the Korean Cardiac Arrest Research Consortium registry were included. Patients' mean age was 67 years, and 69% were men. Findings from initial tests (pH; PaCO2; PaO2; and potassium, hemoglobin, lactate, and creatinine levels) were extracted from the registry. The primary composite outcome was death or poor neurologic outcome (Cerebral Performance Category Scale, $ 3) at 30 days. We developed the model for the MDS using automated machine learning algorithms in a development cohort (60% of the patients) and tested it in a validation cohort (40%)., Results: Risk for the primary outcome increased by 34% as the MDS rose from 0 to 7 in the test cohort. Patients with scores of 2 or lower had no increased risk for the outcome according to whether ECLS had been used or not. However, ECLS patients with a score of 3 or more did have lower risk for the outcome, based on a restricted mean survival time of 6.5 days and a ratio of restricted mean time lost of 0.76; P .001, both comparisons). Registered test results were consistent between patients who did or did not receive ECLS. The MDS predicted the composite outcome better than the OHCA, Cardiac Arrest Hospital Prognosis, and NULL-PLEASE scores (P .05)., Conclusions: The MDS we developed predicts prognosis in patients with OHCA and identifies patients who could benefit from ECLS.

Aims: This study aims to assess glycemic and lipid derangement in acute and chronic liver disorders. Materials and Methods: A cross-sectional study was conducted on 104 patients diagnosed with acute or chronic liver disorder. Acute liver disease (ALD) patients were 40 and chronic liver disease (CLD) patients were 64. Results: The mean value of fasting plasma glucose (FPG) in patients with ALD was 91.8 ± 5.4 mg/dl and in CLD was 115.7 ± 17.9 mg/dl, the difference was significant. The mean value of A1c was 4.3 ± 0.6 in ALD and 6.1 ± 0.8 in CLD, the difference was significant. In patients with CLD mean cholesterol was higher 177.4 ± 28.8 mg/dl when compared to ALD 140 ± 35.1 mg/dl, but the difference was not significant. ALD patients' high-density lipoprotein (HDL) was 50.4 ± 5.1 mg/dl, and in CLD patients, HDL was 44.4 ± 6.1 mg/dl. In CLD mean triglyceride (T) was 148.9 ± 6.4 mg/dl while in ALD T was 134.8 ± 14.2 mg/dl, the difference was significant. Conclusions: CLD is associated with glycemic derangement demonstrated by deranged FPG and A1c. In patients of ALD, no metabolic derangement was observed.

Glioblastoma (GBM, Grade IV astrocytoma) is the most common and most aggressive of the primary malignant brain tumors in adults. Hypoxia is a distinct feature in GBM and plays a significant role in tumor progression, resistance to treatment and poor outcomes. This review considers the effects of hypoxia on astrocytic tumors and the mechanisms that contribute to tumor progression and therapeutic resistance, with a focus on the vascular changes, chemotaxic signaling pathways and metabolic alterations involved.

Non-alcoholic fatty liver disease is a globally prevalent disorder that can rapidly progress if not detected early. Currently, no accepted markers exist for early diagnosis and prognosis of NAFLD. This review describes derangement in major metabolic pathways of lipid, carbohydrate, and amino acids in NAFLD. It suggests that measuring levels of thrombospondin, TyG index, asymmetric dimethylarginine, LAL-A, GLP-1, FGF-21, and GSG index are potential markers for early diagnosis of NAFLD. A single marker may not indicate early NAFLD, and further large-scale studies on correlating levels of Thrombospondin-2, triglyceride-glucose index, and FGF-21 with NAFLD are warranted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We previously demonstrated that uridine adenosine tetraphosphate (UpA) induces potent and partially endothelium-dependent relaxation in the healthy porcine coronary microvasculature. We subsequently showed that UpA-induced porcine coronary relaxation was impaired via downregulation of P1 receptors after myocardial infarction. In view of the deleterious effect of metabolic derangement on vascular function, we hypothesized that the coronary vasodilator response to UpA is impaired in metabolic derangement, and that the involvement of purinergic receptor subtypes and endothelium-derived vasoactive factors (EDVFs) is altered. Coronary small arteries, dissected from the apex of healthy swine and swine 6 months after induction of diabetes with streptozotocin and fed a high-fat diet, were mounted on wire myographs. UpA (10-10 M)-induced coronary relaxation was maintained in swine with metabolic derangement compared to normal swine, despite impaired endothelium-dependent relaxation to bradykinin and despite blunted P2X receptor and NO-mediated vasodilator influences of UpA. Moreover, a thromboxane-mediated vasoconstrictor influence was unmasked. In contrast, an increased UpA-mediated vasodilator influence via P2Y receptors was observed, while, in response to UpA, cytochrome P 2C9 switched from producing vasoconstrictor to vasodilator metabolites in swine with metabolic derangement. Coronary vascular expression of A and P2X receptors as well as eNOS, as assessed with real-time PCR, was reduced in swine with metabolic derangement. In conclusion, although the overall coronary vasodilator response to UpA was maintained in swine with metabolic derangement, the involvement of purinergic receptor subtypes and EDVF was markedly altered, revealing compensatory mechanisms among signaling pathways in UpA-mediated coronary vasomotor influence in the early phase of metabolic derangement. Future studies are warranted to investigate the effects of severe metabolic derangement on coronary responses to UpA. [ABSTRACT FROM AUTHOR]

Aims: This study aims to assess glycemic and lipid derangement in acute and chronic liver disorders. Materials and Methods: A cross-sectional study was conducted on 104 patients diagnosed with acute or chronic liver disorder. Acute liver disease (ALD) patients were 40 and chronic liver disease (CLD) patients were 64. Results: The mean value of fasting plasma glucose (FPG) in patients with ALD was 91.8 ± 5.4 mg/dl and in CLD was 115.7 ± 17.9 mg/dl, the difference was significant. The mean value of A1c was 4.3 ± 0.6 in ALD and 6.1 ± 0.8 in CLD, the difference was significant. In patients with CLD mean cholesterol was higher 177.4 ± 28.8 mg/dl when compared to ALD 140 ± 35.1 mg/dl, but the difference was not significant. ALD patients' high-density lipoprotein (HDL) was 50.4 ± 5.1 mg/dl, and in CLD patients, HDL was 44.4 ± 6.1 mg/dl. In CLD mean triglyceride (T) was 148.9 ± 6.4 mg/dl while in ALD T was 134.8 ± 14.2 mg/dl, the difference was significant. Conclusions: CLD is associated with glycemic derangement demonstrated by deranged FPG and A1c. In patients of ALD, no metabolic derangement was observed. [ABSTRACT FROM AUTHOR]

Vaccine induced serum cytokines not only serves as a biomarker of immunity but also serves as a reliable measure of inflammation. Long term persistence of inflammation can lead to metabolic derangement. Towards this end, in the present study, we measured levels of cytokines along with hormones (insulin, leptin and adiponectin) in children who have been vaccinated with Salmonella typhi Vi conjugate vaccine, 30 months after vaccination. Vaccinated children showed a unique cytokine profile with suppressed Th1-Th2 and increased Th9-Th17 cytokines indicating immune polarization which was associated with decreased serum adiponectin (but not insulin or leptin) levels. The study gains major importance since it is a longitudinal study which reports vaccine induced long term persistence of inflammation for the first time in the high risk ethnic population. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that high fructose consumption may be a potentially important factor responsible for the rising incidence of insulin resistance and diabetes worldwide. The present study investigated the preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high fructose fed male Wistar rats at the molecular level. Fructose feeding for 10 weeks caused oxidative stress, inflammation and insulin resistance. Curcumin treatment attenuated the insulin resistance by decreasing IRS-1 serine phosphorylation and increasing IRS-1 tyrosine phosphorylation in the skeletal muscle of high fructose fed rats. It also attenuated hyperinsulinemia, glucose intolerance and HOMA-IR level. Curcumin administration lowered tumor necrosis factor alpha (TNF-α), C reactive protein (CRP) levels and downregulated the protein expression of cyclo-oxygenase 2 (COX-2), protein kinase theta (PKCθ). In addition, inhibitor κB alpha (IκBα) degradation was prevented by curcumin supplementation. Treatment with curcumin inhibited the rise of malondialdehyde (MDA), total oxidant status (TOS) and suppressed the protein expression of extracellular kinase ½ (ERK ½), p38 in the skeletal muscle of fructose fed rats. Further, it enhanced Glutathione Peroxidase (GPx) activity in the muscle of fructose fed rats. At the molecular level, curcumin inhibited the activation of stress sensitive kinases and inflammatory cascades. Our findings conclude that curcumin attenuated glucose intolerance and insulin resistance through its antioxidant and anti-inflammatory effects. Thus, we suggest the use of curcumin as a therapeutic adjuvant in the management of diabetes, obesity and their associated complications. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is associated with cardiovascular risks like obesity, insulin resistance, dyslipidemia that can lead to sympathovagal imbalance (SVI). The study was designed to assess the cardiovascular risk in PCOS and link of metabolic derangements to SVI. Thirty-five newly diagnosed PCOS patients and 32 age-matched controls were recruited. Waist-hip ratio, body mass index (BMI), basal cardiovascular parameters such as basal heart rate (BHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and rate pressure product (RPP) were recorded. Autonomic functions were assessed using short-term heart rate variability (HRV) analysis, heart rate and blood pressure response to standing (30:15 ratio), deep breathing (E:I ratio) and isometric handgrip (ΔDBPihg). Fasting plasma glucose, insulin, lipid profile and testosterone were assayed. Insulin resistance (HOMA-IR) and lipid risk factors were calculated. The cases had increased BHR, BMI, SBP, DBP, MAP and RPP. The ratio of low-frequency to high-frequency (LF-HF) of HRV, the marker of SVI was significantly increased in cases. 30:15 ratio and ΔDBPihg were increased and E:I ratio was decreased in the cases. HOMA-IR, lipid risk factors and testosterone were significantly elevated in cases. There was a significant correlation of LF-HF with BMI, BHR, RPP, insulin resistance and lipid risk factors. On regression analysis, insulin resistance and lipid risk factors had independent association with LF-HF. PCOS patients have SVI, decreased HRV and increased RPP and the potential cardiovascular risks. The insulin resistance and dyslipidemia contribute to SVI and cardiovascular risks in PCOS patients. [ABSTRACT FROM AUTHOR]