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At least 793 records · Page 44Linked to original sources
PubMed1991

[Identification of viable myocardium in patients with chronic ischemic disease and left ventricular dysfunction: correlations between blood flow, metabolic activity and regional function].

To identify the presence of viable myocardium in areas of severe systolic dysfunction, we studied 22 patients (age 45 to 78 years) with chronic coronary artery disease and left ventricular dysfunction (mean ejection fraction 29 +/- 9%). All subjects underwent thallium-201 single photon emission computed tomography (SPECT), using the reinjection technique, positron emission tomography (PET) with H2(15)O and 18-fluorodeoxyglucose (FDG) to measure regional blood flow and exogenous glucose uptake, respectively, and nuclear magnetic resonance imaging (MRI). From matched transaxial PET, SPECT and MRI tomograms, a total of 290 left ventricular myocardial regions were analyzed. According to the regional wall thickening, measured from MRI, 3 groups of myocardial regions were identified: akinetic-dyskinetic (n = 60), showing either absence of systolic thickening or systolic thinning; hypokinetic (n = 97), showing an absolute wall thickening less than or equal to 2 mm; normal (n = 133), showing an absolute wall thickening greater than 2 mm. Of the 60 akinetic or dyskinetic regions, 3 were normal by SPECT and 37 corresponded to either a total or partially reversible thallium defect: 34 of these 40 regions also showed presence of FDG uptake by PET. The remaining 20 akinetic or dyskinetic regions showed a thallium defect that remained irreversible after reinjection: in 7 of these 20 regions, however, there was evidence of metabolic activity, as expressed by FDG uptake. Thus, 47 (78%) of the myocardial akinetic or dyskinetic regions showed presence of viable tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2003

Assessment of bone metabolism in cadmium-induced renal tubular dysfunction by measurements of biochemical markers.

Bone metabolism related to the severity of cadmium (Cd)-induced renal tubular dysfunction (RTD) was assessed by measuring several bone biochemical markers. Fifty-three female subjects with RTD aged 65-76 years (mean 70.0+/-3.3 years) and who lived in the Cd-polluted Jinzu River basin in Toyama, Japan were studied. Bone alkaline phosphatase (bone-ALP), intact bone Gla-protein (intact-BGP) and carboxy-terminal propeptide of type I collagen (PICP) in serum as bone formation markers and pyridinoline (Pyr) and deoxypyridinoline (Dpyr) in urine as bone resorption markers were measured. All markers of bone turnover were increased and significantly correlated with each other, suggesting that bone formation and resorption were coupled and increased in Cd-induced RTD. Fractional excretion of beta(2)-microglobulin (beta(2)-m, FE(beta 2-m)) as an index of severity of Cd-induced RTD was extremely varied ranging from 0.45 to 53%. There were no significant correlations between FE(beta 2-m) and each of the five bone biochemical markers. The bone turnover in Cd-induced RTD appeared to be determined by the glomerular filtration rate (GFR): in subjects with GFRs above 50 ml/min, the levels of bone-ALP or intact-BGP tended to be inversely related to the GFRs, whereas in subjects with GFRs below 40 ml/min, those levels tended to decrease. These results suggest that the bone turnover, in particular the bone formation, was influenced by renal tubular function as assessed by the levels of GFR in Cd-induced RTD.

Aged↗
PubMed2000

Metabolic control and ageing.

There appear to be multiple processes that are limiting for longevity and the associated mechanisms of ageing. Among these processes, metabolic control is coming to the forefront, because it has surfaced in studies in several model systems and because of its relevance to mammalian ageing. The genetic and molecular dissection of ageing in yeast points to mechanisms involving three aspects of metabolism. First, dysfunctional mitochondria signal many changes in nuclear gene expression that result in metabolic adjustments that extend life span. Second, manipulation of nutritional status can also increase longevity in a separate caloric-restriction pathway. Finally, protein synthesis is a third aspect, which depends on the transcriptional state of chromatin and the histone deacetylases that modulate it.

Aging↗
PubMed2000

Close relationship of abnormal glucose tolerance with endothelial dysfunction in hypertension.

Hypertension is frequently accompanied by left ventricular hypertrophy, endothelial dysfunction, and abnormal glucose metabolism. However, no study has examined the relative pathological significance of left ventricular hypertrophy and abnormal glucose metabolism on endothelial dysfunction in hypertension. This study was conducted to evaluate whether abnormal glucose tolerance assessed by 75-g oral glucose tolerance test or left ventricular hypertrophy is more closely associated with endothelial dysfunction in never-treated hypertensive patients without elevated fasting blood glucose. We studied 107 unmedicated hypertensive patients (mean age, 54+/-10 years) whose fasting blood glucose was <7.0 mmol/L. Endothelial function was assessed by change in brachial artery diameter in response to reactive hyperemia, and left ventricular mass index was determined by ultrasonography. Simple linear regression analysis demonstrated that endothelial function significantly correlated with left ventricular mass index and 2-hour blood glucose in 75-g oral glucose tolerance test, but not with fasting blood glucose. Multiple linear regression analysis revealed that endothelial function significantly correlated with 2-hour blood glucose (beta=-2.68, P<0.05) after we controlled for other clinical variables. Patients were divided into 3 groups according to 2-hour blood glucose levels. Endothelial function was more impaired in patients with diabetes (n=12; 4.7+/-1.8%) and in those with impaired glucose tolerance (n=31; 6.3+/-2.9%) than in those with normal glucose tolerance (n=64; 8.4+/-4.5%) (P<0.05), but left ventricular mass index was similar in these 3 groups. Abnormal glucose tolerance assessed by 75-g oral glucose tolerance test, rather than left ventricular hypertrophy, may have direct pathophysiological relevance to endothelial dysfunction in borderline to moderate hypertensive patients.

Adult↗
PubMed1976

[Nutrition problems in kidney diseases].

The practice of dietetic therapy is unusual today for patients suffering from renal failure without hypertension and reduction of glomerular filtration rate. Specific treatment is needed, however, for arterial hypertension, uremia, calculus and uralith disease. Experiments in rats showed, that a lot of uremic symptoms following poorly functioning kidneys are partly at least caused by disturbances in amino acid metabolism. Uremia patients with dysfunctioning plasma protein metabolism (transferrin, complement, cholinesterase, prealbumin and retinolbinding protein) need oral, respectively parenteral substitution of essential amino acids. This substitution is very important under catabolic stress conditions in uremic syndrome with and without vividialysis treatment.

Amino Acids↗
PubMed2002

Influence of severe renal dysfunction on the pharmacokinetics and metabolism of bosentan, a dual endothelin receptor antagonist.

BACKGROUND: One of the potential indications of bosentan, a dual endothelin receptor antagonist, is chronic heart failure. Patients with chronic heart failure frequently also suffer from impaired renal function. OBJECTIVE: To explore the influence of severe renal dysfunction on the pharmacokinetics and metabolism of bosentan in a monocenter, open label, parallel group study. METHODS: Eight renal patients with creatinine clearance 17 - 27 ml/min and 8 healthy subjects (creatinine clearance 99 - 135 ml/min) received a single oral dose of 125 mg bosentan and plasma samples drawn for up to 36 hours after administration were analyzed for bosentan and 3 metabolites. RESULTS: The pharmacokinetic parameters of bosentan did not differ significantly between the study groups: geometric means (95% confidence interval) for Cmax were 1.8 (1.2 - 2.8) and 1.1 microg/ml (0.74 - 1.7), and for AUC0-infinity 7.2 (5.1 - 10.4) and 6.4 (3.4 - 11.2) microg x h/ml in healthy subjects and renal patients, respectively. Levels of the 3 CYP2C9- and CYP3A4-derived metabolites increased approximately 2-fold in renal patients, both in absolute terms and in relation to the parent compound. In renal patients, the exposure to Ro 48-5033, the only pharmacologically active metabolite, was 13% of that to bosentan. CONCLUSION: Severe renal dysfunction did not affect the pharmacokinetics of bosentan to a clinically relevant extent and, therefore, no dose adjustments are deemed necessary in patients with any grade of renal insufficiency.

Adult↗
PubMed2005

Obesity, insulin resistance, and the metabolic syndrome: determinants of endothelial dysfunction in whites and blacks.

BACKGROUND: Insulin resistance is strongly associated with obesity and other components of the metabolic syndrome (MS). The relative importance of these components in the determination of endothelial function is unknown. Furthermore, there is conflicting evidence about whether ethnic differences exist in the relative importance of these components in regard to other cardiovascular outcomes. We evaluated the contributions of insulin resistance, obesity, and the other components of the MS to impaired endothelial function. METHODS AND RESULTS: The relationships of the MS components (as defined according the National Cholesterol Education Program) and insulin resistance (estimated using the homeostasis model) with endothelium-dependent vasodilation were examined in 42 white and 55 black subjects. Endothelium-dependent vasodilation was assessed as the increment in leg blood flow (measured by thermodilution) after exposure to methacholine chloride. Waist circumference, glucose, blood pressure, and insulin resistance distributions did not differ between ethnic groups; blacks in our sample had higher HDL cholesterol (1.31 versus 1.09 mmol/L; P<0.001) and lower triglyceride levels (1.01 versus 1.37 mmol/L; P=0.005) than white subjects. In the absence of the MS, black subjects exhibited reduced endothelium-dependent vasodilation compared with white subjects (P=0.005), and both groups demonstrated significantly worse endothelial function when the MS was present (maximal increase in leg blood flow: blacks: 107+/-9% MS absent, 53+/-16% MS present; whites: 163+/-16% MS absent, 54+/-18% MS absent; P=0.007, MS absent versus present; P=NS for interaction of ethnicity and MS). Multivariable regression analysis examining relationships of endothelial function with the 5 MS components (analyzed as continuous variables) revealed independent relationships only with waist circumference (P=0.01) and systolic blood pressure (P=0.02). Waist circumference was no longer independently associated after adding insulin resistance to the modeling (P=0.02 for log of homeostasis model index of insulin resistance, P=0.02 for systolic blood pressure). Ethnicity still exerted an independent effect on endothelial function after accounting for the above components (P=0.04 for an additional effect of ethnic status on endothelial function), with an ethnic difference in the effect of insulin resistance on endothelial function (P=0.046 for interaction of ethnicity and log of homeostasis model index of insulin resistance). CONCLUSIONS: These findings suggest that insulin resistance and systolic blood pressure are the principal determinants of endothelial dysfunction in the MS and that there are ethnic differences in the relative importance of these factors. These differences may imply different benefits from treatments targeting blood pressure or insulin resistance in different ethnic groups.

Adult↗
PubMed2005

Endothelial and erectile dysfunction, diabetes mellitus, and the metabolic syndrome: common pathways and treatments?

The past decade has witnessed a dramatic increase in the prevalence of obesity. Comorbidities of obesity include type 2 diabetes mellitus, hypertension, and lipid abnormalities, all of which contribute to cardiovascular disease (CVD) and are associated with endothelial dysfunction. These abnormalities frequently cluster in individuals, and the term metabolic syndrome is now widely used to define this cluster. The syndrome is frequently (although not invariably) associated with insulin resistance and CVD. Diabetes is associated with CVD, which may be asymptomatic in some cases, particularly when associated with autonomic neuropathy. This has implications for guidelines on the evaluation of patients with erectile dysfunction (ED) and CVD. Treatment of ED in men with diabetes has been revolutionized by the introduction of phosphodiesterase 5 inhibitors. However, men with diabetes tend to respond less positively to these agents, at least as currently prescribed. This decreased responsiveness may be related to the severity of endothelial function in patients with diabetes. Additional therapeutic strategies may be needed to overcome this problem.

Diabetes Mellitus↗
PubMed1997

Evaluation of patterns of perfusion and metabolism in dobutamine-responsive myocardium.

OBJECTIVES: We investigated the patterns of perfusion and metabolism in dysfunctional myocardium whose contractility improved with dobutamine. BACKGROUND: Clinical studies have suggested that dobutamine echocardiography can identify hibernating myocardium, but laboratory studies suggest that reduced perfusion limits the response to dobutamine. METHODS: Twenty-five patients with coronary disease and ventricular dysfunction underwent low (5 and 10 micrograms/kg body weight per min) and high dose (maximum of 50 micrograms/kg per min) dobutamine echocardiography and positron emission tomography (PET) using nitrogen-13 (N-13) ammonia and fluorine-18 fluorodeoxyglucose (FDG) for imaging of perfusion and metabolism. Wall motion and tracer uptake were scored in 16 left ventricular segments. RESULTS: Perfusion and metabolism were normal in 56.4%, mildly reduced in 29.1% and mismatched (reduced perfusion, preserved FDG uptake) in 14.5% of dysfunctional segments viable on PET. Wall motion improved with dobutamine in 89 dysfunctional segments (62 at low dose, 27 only at peak dose), and 86 of these (97%) were viable on PET. Improvement in wall motion with dobutamine was more common in segments with normal perfusion and metabolism (56.5%) than in those with mildly reduced tracer uptake (28.5%, p < 0.001) and those with mismatch (32%, p = 0.03). All the segments with a biphasic response were supplied by vessels with > or = 70% stenosis, and 88% had normal perfusion and metabolism. CONCLUSIONS: The majority of viable segments with rest dysfunction had normal perfusion and metabolism, suggesting that myocardial stunning was common. Improvement of wall motion at low and high doses of dobutamine was highly correlated with myocardial viability on PET and was more common in myocardium with normal perfusion. A biphasic response to dobutamine identified segments with normal perfusion and metabolism supplied by severely diseased vessels.

Ammonia↗
PubMed2026

Metabolic ketosis attenuates NLRP3 inflammasome activation and is associated with improvements in hepatic steatosis and liver stiffness in MASLD: a pilot randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic-inflammatory disorder in which metabolic stress and innate immune activation, particularly through the NLRP3 inflammasome, contribute to disease progression. Metabolic ketosis, characterized by increased levels of circulating ketone bodies, especially &#x3b2;-hydroxybutyrate, has emerged as a promising strategy to modulate substrate utilization, inflammatory signaling, and hepatic injury. However, clinical evidence integrating molecular, metabolic, and hepatic outcomes remains limited. METHODS: In this pilot randomized controlled trial, 20 participants with newly diagnosed MASLD were randomly assigned to either a 3-month intervention with a daily C8-enriched medium-chain fatty acid formulation (m-CAP; meta-Capridin, providing approximately 20 g/day of C8) or a standardized low-carbohydrate dietary protocol. Metabolic indices, inflammatory mediators, adipokines, and hepatic enzymes were assessed. The expression of key inflammasome components (NLRP3, caspase-1, and ASC) was evaluated in peripheral blood mononuclear cells, and hepatic steatosis and liver stiffness were measured via transient elastography. RESULTS: The C8-enriched intervention was associated with increased circulating &#x3b2;-hydroxybutyrate levels, indicating the achievement of nutritional ketosis. Changes over time were observed in metabolic parameters, including fasting serum glucose (p < 0.05), HOMA-IR (p < 0.05), body fat percentage (p < 0.05), and BMI (p < 0.05). Alterations in inflammatory mediators and adipokine-related outcomes were also observed following the intervention. At the molecular level, changes in inflammasome-related markers were detected, including caspase-1 mRNA expression (p < 0.05) and NLRP3 expression at the transcriptional (p < 0.05) and protein levels (p < 0.01), whereas ASC expression remained unchanged. Changes in hepatic steatosis (p < 0.01) and liver stiffness measurements were observed following the intervention. Given the absence of significant Group &#xd7; Time interactions for several secondary outcomes, these findings should be interpreted as exploratory and hypothesis-generating. CONCLUSIONS: Induction of metabolic ketosis was associated with changes in metabolic, inflammatory, and hepatic parameters in patients with MASLD. The observed associations between ketosis, inflammasome-related markers, and noninvasive liver outcomes warrant further investigation of ketosis-based interventions as adjunctive approaches in MASLD. Larger and longer-term clinical trials are needed to confirm these findings and to determine whether short-term changes in liver stiffness reflect sustained alterations in hepatic status rather than structural fibrosis regression. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); Unique identifier: IRCT20170315033086N12; Registration date: 19 September 2024; Registry URL: https://www.irct.ir. IRCT is a primary registry in the WHO Registry Network (https://www.who.int/tools/clinical-trials-registry-platform/network/primary-registries).

Humans↗
PubMed2003

Characterization of dysfunctional myocardium by positron emission tomography and magnetic resonance: relation to functional outcome after revascularization.

BACKGROUND: Metabolic assessment of dysfunctional myocardium by PET allows prediction of functional recovery after revascularization. Contrast-enhanced MR (ce-MR) discriminates transmural distribution of viable and scar tissue with excellent spatial resolution. Both techniques were applied in ischemic chronic left ventricular dysfunction to relate metabolism and tissue composition to changes of contractile function after revascularization. METHODS AND RESULTS: Nineteen patients with myocardial infarctions (>3 months) were studied by MR and PET, and 10 patients were followed by MR 11+/-2 months after revascularization. In 56 to 64 segments/heart, systolic wall thickening, viable mass, and thickness of viable rim tissue were determined by MR (inversion-recovery MR with 0.25 mmol/kg Gd-chelate). [18F]Fluorodeoxyglucose (FDG) uptake and resting perfusion (13N-ammonia) were determined by PET. Viable tissue per segment on ce-MR correlated with FDG uptake per segment (r=0.62 and 0.82 for segments with and without flow metabolism mismatch, P<0.0001). FDG uptake > or =50% (a predictor of functional recovery) corresponded to a viable rim thickness of 4.5 mm on ce-MR. Thick (>4.5 mm) and metabolically viable segments (> or =50% FDG uptake) showed functional recovery in 85%, whereas thin metabolically nonviable segments improved function in 13% (P<0.0005). Metabolically viable segments with a thin viable rim and thick segments with reduced FDG uptake improved function in only 36% and 23% of segments, respectively (NS versus thin metabolically nonviable). In these 2 classes of segments, scar per segment was higher than in thick viable segments (P<0.0001). CONCLUSIONS: Metabolism and tissue composition discriminate various classes of dysfunctional myocardium. Most metabolically viable segments with a thick viable rim on ce-MR recover function after revascularization, whereas all other classes showed low recovery rates of contractile function.

Female↗
PubMed1999

Elevated carboxy terminal cross linked telopeptide of type I collagen in alcoholic cirrhosis: relation to liver and kidney function and bone metabolism.

BACKGROUND: The carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy. AIMS: To assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis. METHODS: In 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured. RESULTS: Circulating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism. CONCLUSIONS: ICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis.

Adult↗
PubMed2005

[Microvascular dysfunction as an explanation for the metabolic syndrome].

The metabolic syndrome is a cluster of mutually related risk factors that confers an increased risk for both type 2 diabetes mellitus and cardiovascular disease. Although the metabolic syndrome seems to have multiple aetiological factors, microvascular dysfunction is a potential explanation for the above-mentioned cluster of multiple metabolic risk factors such as hypertension, insulin resistance and glucose intolerance. Microvascular dysfunction leads not only to increased peripheral vascular resistance and blood pressure, but may also decrease the insulin-mediated glucose uptake in muscles. The different effect on the microcirculation may explain why some antihypertensive drugs (beta-blockers) lead to an increased incidence of type 2 diabetes, whereas others (angiotensin-converting enzyme (ACE) inhibitors) are associated with a decrease of that risk.

Antihypertensive Agents↗
PubMed2002

New factors in the regulation of adipose differentiation and metabolism.

Obesity and lipoatrophy are major risks for insulin resistance, type 2 diabetes and cardiovascular diseases. The molecular links between adipocyte dysfunction and metabolic disorders were elusive until the discovery that adipose tissue operates as an endocrine organ and releases factors targeting a wide range of organs. This article attempts to review the more recent advances from research on the transcriptional control of adipogenesis and on new adipocyte-secreted proteins that have been proposed as molecular links between adipose tissue and insulin resistance.

Adiponectin↗
PubMed2000

Abnormal cytokine and adrenocortical hormone regulation in myotonic dystrophy.

Metabolic-endocrine dysfunctions, including hyperinsulinemia, hypertriglyceridemia, increased fat mass, and dysregulation of the hypothalamic-pituitary-adrenal axis, are common in myotonic dystrophy (MD). We hypothesized that increased production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) may be important underlying mechanisms. We studied the diurnal rhythmicity of cytokines and cortisol, ACTH, and dehydroepiandrosterone in 18 men with adult onset MD and 18 controls. Morning levels of androstenedione, 17-hydroxyprogesterone, testosterone, and insulin were also determined. Genetic analyses were performed, including calculation of allele sizes. Median circulating 24-h levels of IL-6 (P < 0.001), TNF-alpha (P = 0.05), ACTH (P < 0.05), and cortisol (P < 0.05) were all significantly increased in MD, whereas dehydroepiandrosterone levels were decreased (P < 0.001). The diurnal rhythms of these cytokines/ hormones were disturbed in patients. Morning testosterone levels were decreased and insulin levels increased (P < 0.01 for both). Patients with high body fat mass had significantly increased insulin levels and decreased morning levels of cortisol, ACTH, and testosterone. IL-6 and TNF-alpha levels are increased and adrenocortical hormone regulation is disturbed in MD. Adiposity may contribute to these disturbances, which may be of importance for decreased adrenal androgen hormone production and metabolic, muscular, and neuropsychiatric dysfunction in MD.

Adipose Tissue↗