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Cocaine not only is an arterial vasoconstrictor but also may contribute to arterial thrombosis by activating platelets and increasing their aggregability diabete oms generic actoplus met 500 mg on line, enhancing thromboxane production diabetes type 1 normal blood sugar discount actoplus met 500mg amex, and inducing endothelial cell injury diabetes diet handout spanish purchase actoplus met line. Isolated case reports have attributed a wide variety of glomerular and tubulointerstitial renal diseases to cocaine use diabetes type 2 jewelry order 500 mg actoplus met. Cocaine use has been associated with antiglomerular basement membrane disease diabetic diet using exchanges proven actoplus met 500mg, acute interstitial nephritis epilepsy and diabetes in dogs purchase genuine actoplus met on-line, hyponatremia, and systemic necrotizing vasculitis (Alfaro et al. However, a causal relationship between cocaine use and many of these disorders remains to be established. Chronic administration of cocaine to rats induces glomerulosclerosis and chronic tubulointerstitial injury including tubular dilation and necrosis of tubular cells (Barroso-Moguel et al. In vitro studies of renal tissue indicate that cocaine enhances mesangial cell uptake of macromolecules, increases the release of macrophage secretory products and cytokines that stimulate mesangial cell proliferation, and is cytotoxic to proximal tubular epithelial cells (Mattana et al. Cocaine also increases cellular oxidative stress and decreases intracellular glutathione levels in renal epithelial cells (Palamara et al. However, the relationship of these experimental observations to human disease remains to be established. However, this relationship has not always been supported by epidemiological studies. These investigators concluded that cocaine use may cause an acute elevation in blood pressure but was not associated with chronic hypertension. There was no significant difference in age-adjusted blood pressure in the population of cocaine users as compared to a control group. In addition, microalbuminuria was not detected in patients who had used cocaine for a mean of 12 years. Accelerated atherosclerosis of the renal vasculature has been attributed to cocaine use even in the absence of hypertension (Di Paolo et al. Cocaine addicts not only showed extensive atherosclerosis with medial thickening, luminal narrowing, and vessel obstruction but also showed more glomerular hyalinosis, periglomerular fibrosis, and interstitial cellular infiltration as compared to controls. The pathogenesis of accelerated hyperplastic atherosclerotic damage in cocaine addicts is unclear. Cocaine use may also accelerate atherosclerosis by inducing mononuclear cell infiltration of atherosclerotic plaques and by increasing the permeability of the vascular endothelium to diffusion of atherogenic lipoproteins. Numerous congenital renal abnormalities have been associated with maternal cocaine use including hydronephrosis, horseshoe kidney, prune belly syndrome, renal agenesis, prominent renal pelvis, nephromegaly, unilateral small kidney, and genital abnormalities (Battin et al. Urine output is frequently reduced in fetuses exposed to cocaine (Mitra, 1999; Mitra et al. Prenatal cocaine exposure has also been associated with an increased incidence of urinary tract infections (Gottbrath-Flaherty et al. Stillborn fetuses exposed to cocaine in utero may show thickening of the renal interlobular artery walls with luminal narrowing and multivessel intimal-type fibromuscular dysplasia (Mitra et al. Vascular abnormalities are associated with elevated renal artery resistive indices (Mizutani et al. Prenatal exposure to cocaine has also been associated with persistent postnatal hypertension and, in particular, severe hypertension secondary to renal artery stenosis (Ho et al. Renovascular disease and congenital urinary tract abnormalities are also seen in experimental models of in utero cocaine exposure (Finnell et al. Proposed mechanisms for these developmental abnormalities include cocaine-induced vasoconstriction of uterine and fetal blood vessels and cocaine-induced alterations in calcium metabolism. Persistent postnatal hypertension in the absence of renal developmental abnormalities has been attributed to cocaine-induced sympathetic nervous system dysfunction (Horn, 1992). Although a wide variety of drugs were involved, methamphetamine was used in nearly all reported cases and was used exclusively in one case. However, in recent years, the existence of a distinct clinical syndrome of systemic necrotizing vasculitis in amphetamine users has been questioned. Vasculitis may have been due to unrecognized infection with hepatitis B or hepatitis C virus. Levamisole not only is used as a cutting and bulking agent but also potentiates the psychotropic effects of cocaine. It also possesses immunomodulatory properties that induce the loss of tolerance to numerous autoantigens. Detection of levamisole in the urine may be problematic due to its short half-life of 5. Pauci-immune complex necrotizing and crescentic glomerulonephritis and leukocytoclastic angiitis involving the skin were documented. Antimyeloperoxidase antibodies were present in the serum of all cases, and 50% also showed antiprotease 3 antibodies. To circumvent Federal regulation, these agents are sold as plant food, fertilizer, incense, bath additives or insect repellent and labeled as not intended for human consumption. Many of these compounds are not detected by routine urine drug screening and have been associated with a broad spectrum of renal complications (Luciano and Perazella, 2014; Pendergraft et al. The compound may be administered by various routes and can be ingested, smoked, injected, or inhaled. This occurs predominantly in young women in an idiosyncratic, nondose-dependent manner, often in first-time users. In addition, increased thirst and dry mouth lead to excessive free water ingestion and contribute to the development of dilutional hyponatremia. Synthetic cannabinoids bind to the cannabis receptors and exert cannabis-like psychoactive effects. They are marketed as "Spice," "K2," "Spice Gold," or "Kronic," combined with herbal mixtures in the form of incense, bath additives, or air fresheners. Although prerenal azotemia due to volume depletion may occur, most cases show no hemodynamic compromise and only modest elevations of creatine phosphokinase enzyme levels, suggesting a direct nephrotoxic effect. Biopsy of the kidney has demonstrated acute tubular necrosis or less commonly acute interstitial nephritis. The primary mechanism of action of mephedrone is stimulation of dopamine release and inhibition of reuptake through interactions with the dopamine transporter. These compounds are marketed in capsule, pill, or powder form as plant food, fertilizer, bath salts, or insect repellents not suitable for human consumption and are commonly referred to as "bath salts. A number of renal complications have been associated with the use of these agents (Alansari and Hamilton, 2006; Berney-Meyer et al. Their use has been linked to acute tubular necrosis in the presence or absence of rhabdomyolysis associated with hyperthermia and seizures. Isolated case reports describe immune complex-mediated glomerulonephritis, interstitial nephritis, urinary retention, and hyponatremia associated with their use. These compounds are marketed as "Solaris," "Smiles," "N bomb," and "Cimbi-5" in the form of capsules, powder, or liquid preparations. Chronic abuse of ketamine has been associated with a wide variety of urological disorders including decreased bladder capacity, bladder wall thickening, papillary necrosis, renal infarction, ureteral strictures, hydronephrosis, dysuria, urinary frequency, suprapubic pain, microscopic or gross hematuria, and renal functional impairment (Chen et al. Death") increases release of serotonin and, to a lesser degree dopamine, from presynaptic neurons. Clinical manifestations include renal functional impairment, proteinuria, and nephrotic syndrome. Renal biopsies haves demonstrated focal and segmental glomerulosclerosis with perihilar lesions suggestive of hyperfiltration injury or, less commonly, collapsing glomerular lesions. Nonanion gap hyperchloremic metabolic acidosis attributed to toluene sniffing was first described by Taher et al. A distal renal tubular acidosis was suggested by the finding of a high urinary pH and urinary bicarbonate wasting. Renal tubular acidosis rapidly resolved after discontinuation of toluene abuse but recurred with repeated episodes of toluene exposure. Hypokalemia, resulting from renal potassium wasting due to secondary hyperaldosteronism, was a characteristic feature, which in turn led to generalized muscle weakness or even flaccid quadriparesis. Numerous additional cases of hyperchloremic metabolic acidosis due to toluene abuse have subsequently been reported. Maternal toluene abuse has been reported to give rise to transient Nephrotoxicity of Lithium and Drugs of Abuse 327 congenital renal tubular dysfunction with hyperchloremic metabolic acidosis (Erramouspe et al. Patients frequently presented with muscle weakness, which in some cases progressed to quadriparesis. Muscle symptoms were attributed in most cases to nontraumatic rhabdomyolysis due to hypokalemia and/or hypophosphatemia. However, rhabdomyolysis also occurred in the absence of these electrolyte disturbances, suggesting that toluene may have direct toxic effects on skeletal muscle. Although serum calcium levels were normal on presentation, calcium levels frequently declined during fluid repletion and led to symptomatic hypocalcemia in some patients. Tolueneabusers were unable to acidify the urine despite normal urinary bicarbonate reabsorption. Hydrogen ion back diffusion was excluded as a factor in the genesis of the acidification defect. Toluene reduced the rate of proton secretion in a turtle urinary bladder preparation. These data led the investigators to conclude that impaired active hydrogen ion transport was responsible for the defect in distal acidification observed in toluene abusers. The anion gap is elevated in one-third of the cases of metabolic acidosis associated with toluene abuse (Carlisle et al. Accumulation of products of toluene metabolism, including benzoic acid and hippuric acid, is responsible for the elevated anion gap. Impaired renal function contributes to the accumulation of these anions and the development of high anion gap metabolic acidosis. In the presence of normal renal function, overproduction and urinary excretion of the anions of these organic acids contribute to the development of nonanion gap hyperchloremic metabolic acidosis (Carlisle et al. Pyuria, microscopic hematuria, and proteinuria are frequently observed after toluene exposure (Hayden et al. Nephrolithiasis due to toluene-induced distal renal tubular acidosis with hypercalciuria has also been reported (Kaneko et al. Isolated case reports have associated toluene abuse with antiglomerular basement membrane-mediated glomerulonephritis, focal glomerulosclerosis, and membranoproliferative glomerulonephritis (Beirne, 1972; Bonzel et al. However, a causal relationship between these disorders and toluene abuse remains to be established. Isolated case reports of antiglomerular basement membrane-mediated glomerulonephritis and hemolytic-uremic syndrome have also been reported in solvent abusers (Locatelli and Pozzi, 1983; Nathan and Toseland, 1979); however, a causal relationship is yet to be established. Heroin-associated focal and segmental glomerulosclerosis and secondary amyloidosis have been supplanted by human immunodeficiency virusassociated focal and segmental glomerulosclerosis and hepatitis C-related membranoproliferative glomerulonephritis. Concurrently, there has been an increase in the incidence and spectrum of nephrotoxicity associated with the use of cocaine and designer recreational drugs. Trade-off between the benefits of lithium treatment and the risk of chronic kidney disease. Toxicological and histopathological analysis of a patient who died nine days after a single intravenous dose of methamphetamine: A case report. Lithium induced toxicity in rats: Blood serum chemistry, antioxidative enzymes in red blood cells and histopathological studies. The impact of modern treatment principles may have eliminated lithium-induced renal failure. Severe hyponatremia and inappropriate antidiuretic hormone secretion following ecstasy use. Cocaine-induced acute interstitial nephritis: A case report and review of the literature. Long-term, low-dose lithium treatment does not impair renal function in the elderly: A 2-year randomized, placebo-controlled trial followed by singleblind extension. On the mechanism of lithium-induced renal tubular acidosis: Studies in the turtle bladder. Liver and kidney toxicity in chronic use of opioids: An experimental long term treatment model. Hyperosmolar nonketotic coma precipitated by lithium-induced nephrogenic diabetes insipidus. Mechanisms of renal lithium handling and their relationship to mineralocorticoids: A dissociation between sodium and lithium ions. Journal of Investigative Medicine High Impact Case Reports, 2(3), 2324709614551557. Comparison of intermittent haemodialysis, prolonged intermittent renal replacement therapy and continuous renal replacement haemofiltration for lithium toxicity: A case report. Rhabdomyolysis and acute renal failure associated with phencyclidine intoxication. Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy. Amiloride restores renal medullary osmolytes in lithium-induced nephrogenic diabetes insipidus. Kidney damage in long-term lithium patients: A cross-sectional study of patients with 15 years or more on lithium. Renal function on and off lithium in patients treated with lithium for 15 years or more. Hyperparathyroidism and long-term lithium therapydA cross-sectional study and the effect of lithium withdrawal. A historical cohort study of kidney damage in long-term lithium patients: Continued surveillance needed. The effects of lithium on the permeability of an epithelial membrane, the toad urinary bladder.

Exacerbated inflammatory response induced by insulin-like growth factor i treatment in rats with ischemic acute renal failure diabetes in dogs clinical signs order genuine actoplus met. Prevalence and clinical outcome associated with preexisting malnutrition in acute renal failure: A prospective cohort study different kinds of diabetes in dogs order actoplus met 500mg with mastercard. Uncomplicated acute renal failure and hospital resource utilization: A retrospective multicenter analysis diabetes symptoms type 1 vs type 2 buy actoplus met with a visa. Ischemic acute renal failure: Long-term histology of cell and matrix changes in the rat diabetes symptoms early signs order actoplus met 500mg on line. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus diabetes mellitus nih order 500 mg actoplus met with visa. The prognostic importance of different definitions of worsening renal function in congestive heart failure diabetic diet guidelines pdf purchase genuine actoplus met on line. The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency. Effect of dialysis membrane in the treatment of patients with acute renal failure. Antisense oligonucleotides for icam-1 attenuate reperfusion injury and renal failure in the rat. The effects of fenoldopam on renal function in patients undergoing elective aortic surgery. Outcomes and cost-effectiveness of initiating dialysis and continuing aggressive care in seriously ill hospitalized adults. Study to understand prognoses and preferences for outcomes and risks of treatments. Nephrologist follow-up improves all-cause mortality of severe acute kidney injury survivors. Cellular and molecular predictors of chronic renal dysfunction after initial ischemia/reperfusion injury of a single kidney. Genome-wide gene-expression patterns of donor kidney biopsies distinguish primary allograft function. Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure. The contribution of tumour necrosis factor-alpha and endothelin-1 to the increase of coronary resistance in hearts from rats treated with endotoxin. Rifle criteria for acute kidney injury are associated with hospital mortality in critically ill patients: A cohort analysis. Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in post-ischemic acute renal failure. Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome. Continuous renal replacement therapy improves renal recovery from acute renal failure. Continuous venovenous high-flux dialysis in multiorgan failure: A 5year single-center experience. Haemodialysismembrane biocompatibility and mortality of patients with dialysis-dependent acute renal failure: A prospective randomised multicentre trial. Development of a clinical research agenda for acute kidney injury using an international, interdisciplinary, three-step modified Delphi process. Antibody to intercellular adhesion molecule-1 protects the kidney against ischemic injury. Intercellular adhesion molecule-1 deficient mice are protected against ischemic renal injury. Protection from toxicant-mediated renal injury in the rat with anti-cd54 antibody. Induction of stress response proteins and experimental renal ischemia/reperfusion. Guanosine supplementation reduces apoptosis and protects renal function in the setting of ischemic injury. P53 mediates the apoptotic response to gtp depletion after renal ischemia-reperfusion: Protective role of a p53 inhibitor. Minocycline inhibits apoptosis and inflammation in a rat model of ischemic renal injury. Intravenous cell therapy for acute renal failure with serum amyloid A protein reprogrammed cells. Hypoxic renal tissue damage by endothelin-mediated arterial vasoconstriction during radioangiography in man. Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Prognosis of patients who develop acute renal failure during the first 24 h of cardiogenic shock after myocardial infarction. Costs of care, long-term prognosis and quality of life in patients requiring renal replacement therapy during intensive care. Serum and urinary insulin-like growth factor-1 and tumor necrosis factor in neonates with and without acute renal failure. Renal ischemia/reperfusion leads to macrophage-mediated increase in pulmonary vascular permeability. Lack of renoprotective effect of theophylline during aortocoronary bypass surgery. P38 map kinases: Key signalling molecules as therapeutic targets for inflammatory diseases. Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy. The rise of prevalence and the fall of mortality of patients with acute renal failure: What the analysis of two databases does and does not tell us. Beneficial impact of fenoldopam in critically ill patients with or at risk for acute renal failure: A meta-analysis of randomized clinical trials. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: A prospective cohort study. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: Do we have to revise current definitions of acute renal failure A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Epidemiology and outcomes of acute renal failure in hospitalized patients: A national survey. The spectrum of acute renal failure in the intensive care unit compared with that seen in other settings. Protective effect of atrial natriuretic factor and mannitol following renal ischemia. Ischemia increases neutrophil retention and worsens acute renal failure: Role of oxygen metabolites and icam1. Rip1 (receptor-interacting protein kinase 1) mediates necroptosis and contributes to renal ischemia/reperfusion injury. Immediate post-operative renal function deterioration in cardiac surgical patients predicts in-hospital mortality and long-term survival. A clinical index to predict survival in acute renal failure patients requiring dialysis. Improved long-term survival and renal recovery after acute kidney injury in hospitalized patients, a 20 years experience. Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: A multiple-center epidemiological study. Cost of acute renal failure requiring dialysis in the intensive care unit: Clinical and resource implications of renal recovery. Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction. A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure. Spectrum of acute renal failure in the intensive care unit: the Picard experience. Acute kidney injury network: Report of an initiative to improve outcomes in acute kidney injury. Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease. Prevention of contrast-induced nephropathy with sodium bicarbonate: A randomized controlled trial. Rat models for clinical use of insulin-like growth factor I in acute renal failure. Measuring glomerular filtration rate in the intensive care unit: No substitutes please. Technology insight: Biomarker development in acute kidney injury: What can we anticipate Long-term outcomes in acute renal failure patients treated with continuous renal replacement therapies. Transgenic sickle mice are markedly sensitive to renal ischemia-reperfusion injury. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. In vivo targeting of inducible no synthase with oligodeoxynucleotides protects rat kidney against ischemia. Apoptosis of tubular epithelial cells in donor kidney biopsies predicts early renal allograft function. Selective A2A adenosine receptor activation reduces ischemia-reperfusion injury in rat kidney. A(2A) adenosine receptor-mediated inhibition of renal injury and neutrophil adhesion. A randomized trial of pulsatile perfusion using an intra-aortic balloon pump versus nonpulsatile perfusion on short-term changes in kidney function during cardiopulmonary bypass during myocardial reperfusion. Renal replacement therapy in patients with acute renal failure: A systematic review. Survival of hemodialysis patients in the United States is improved with a greater quantity of dialysis. Impact of prealbumin levels on mortality in patients with acute kidney injury: An observational cohort study. Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: A prospective randomized double-blind placebo-controlled trial. Changes in renal medullary po2 during water diuresis as evaluated by blood oxygenation level-dependent magnetic resonance imaging: Effects of aging and cyclooxygenase inhibition. Glomerular and tubular factors in urine flow rates of acute renal failure patients. Fenoldopam prophylaxis of postoperative acute renal failure in high-risk cardiac surgery patients. Dose and efficiency of renal replacement therapy: Continuous renal replacement therapy versus intermittent hemodialysis versus slow extended daily dialysis. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: A prospective randomised trial. Cardiac surgery as a cause of acute kidney injury: Pathogenesis and potential therapies. Incidence, risk factors, and prognosis of a moderate increase in plasma creatinine early after cardiac surgery. Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure. Morphologic, biochemical, and molecular evidence of apoptosis during the reperfusion phase after brief periods of renal ischemia. Epidemiology of acute renal failure and outcome of haemodiafiltration in intensive care. Mechanisms of disease: Cell death in acute renal failure and emerging evidence for a protective role of erythropoietin. Calcium channel blockers for preventing acute tubular necrosis in kidney transplant recipients. The pathology of acute renal failure (arf): Leukocyte accumulation in the vasa recta. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Variation in risk and mortality of acute kidney injury in critically ill patients: A multicenter study. Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. Increased mortality associated with growth hormone treatment in critically ill adults. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. Influence of renal dysfunction on mortality after cardiac surgery: Modifying effect of preoperative renal function. Acute renal failure in critically ill patients: A multinational, multicenter study. An assessment of the rifle criteria for acute renal failure in hospitalized patients.

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Systematic review and metaanalysis of air pollution exposure and risk of diabetes metabolic disorder vomiting generic 500mg actoplus met free shipping. Chronic fine particulate matter exposure induces systemic vascular dysfunction via nadph oxidase and tlr4 pathways diabetic diet percentages discount 500mg actoplus met overnight delivery. Elevation of serum endothelins and cardiotoxicity induced by particulate matter (pm2 diabetes in dogs diagnosis buy actoplus met 500 mg online. Particulate matter induces translocation of il-6 from the lung to the systemic circulation diabetes grapes purchase actoplus met without prescription. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction metabolic disease syndrome order generic actoplus met from india. Air pollution particulate matter collected from an appalachian mountaintop mining site induces microvascular dysfunction diabetes type 2 weight loss buy cheap actoplus met online. The spontaneously hypertensive rat as a model of human cardiovascular disease: Evidence of exacerbated cardiopulmonary injury and oxidative stress from inhaled emission particulate matter. Vascular and cardiac impairments in rats inhaling ozone and diesel exhaust particles. Vascular responses to long- and short-term exposure to fine particulate matter: Mesa air (multi-ethnic study of atherosclerosis and air pollution). Ozone co-exposure modifies cardiac responses to fine and ultrafine ambient particulate matter in mice: Concordance of electrocardiogram and mechanical responses. Contribution of endothelin 1 to the vascular effects of diesel exhaust inhalation in humans. Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man. The impact of decreases in air temperature and increases in ozone on markers of endothelial function in individuals having type-2 diabetes. Nanoparticle inhalation impairs endothelium-dependent vasodilation in subepicardial arterioles. Nanoparticle inhalation impairs coronary microvascular reactivity via a local reactive oxygen species-dependent mechanism. Effect of exposure to atmospheric ultrafine particles on production of free fatty acids and lipid metabolites in the mouse small intestine. Exposure to inhaled nickel nanoparticles causes a reduction in number and function of bone marrow endothelial progenitor cells. Inhalation of diesel exhaust does not exacerbate cardiac hypertrophy or heart failure in two mouse models of cardiac hypertrophy. Exaggerated effects of particulate matter air pollution in genetic type ii diabetes mellitus. Retinal microvascular responses to short-term changes in particulate air pollution in healthy adults. Blood pressure changes in association with black carbon exposure in a panel of healthy adults are independent of retinal microcirculation. Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men. Gasoline exhaust emissions induce vascular remodeling pathways involved in atherosclerosis. The oxidized low-density lipoprotein receptor mediates vascular effects of inhaled vehicle emissions. Stroke mortality associated with living near main roads in England and wales: A geographical study. Impaired cardiac mitochondrial function and contractile reserve following an acute exposure to environmental particulate matter. The time course of vasoconstriction and endothelin receptor a expression in pulmonary arterioles of mice continuously exposed to ambient urban levels of air pollution. Design, characterization, and evaluation of a small-scale diesel exhaust exposure system. Generation and characterization of gasoline engine exhaust inhalation exposure atmospheres. Engine-operating load influences diesel exhaust composition and cardiopulmonary and immune responses. Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized tio(2). Diesel exhaust particulate increases the size and complexity of lesions in atherosclerotic mice. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Exposure to concentrated ambient particles does not affect vascular function in patients with coronary heart disease. Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation. Hazard identification of particulate matter on vasomotor dysfunction and progression of atherosclerosis. Exacerbation of thrombotic events by diesel exhaust particle in mouse model of hypertension. Pancreatic effects of diesel exhaust particles in mice with type 1 diabetes mellitus. Type 2 diabetes across generations: From pathophysiology to prevention and management. Systemic microvascular dysfunction and inflammation after pulmonary particulate matter exposure. Effects of maternal exposure to ultrafine carbon black on brain perivascular macrophages and surrounding astrocytes in offspring mice. Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice. Episodic exposure to fine particulate air pollution decreases circulating levels of endothelial progenitor cells. Ozone inhalation impairs coronary artery dilation via intracellular oxidative stress: Evidence for serum-borne factors as drivers of systemic toxicity. Ambient air pollution and cardiovascular emergency department visits in potentially sensitive groups. Air pollution, personal activities, and onset of myocardial infarction in a case-crossover study. An epidemiological appraisal of the association between heart rate variability and particulate air pollution: A meta-analysis. Particulate air pollution as a predictor of mortality in a prospective study of U. Cardiovascular mortality and long-term exposure to particulate air pollution: Epidemiological evidence of general pathophysiological pathways of disease. Relationships between fine particulate air pollution, cardiometabolic disorders, and cardiovascular mortality. Diesel exhaust particles impair endothelial progenitor cells, compromise endothelial integrity, reduce neoangiogenesis, and increase atherogenesis in mice. Comparative effects of inhaled diesel exhaust and ambient fine particles on inflammation, atherosclerosis, and vascular dysfunction. A comparison of ground-level air quality data with New York State Department of Environmental Conservation monitoring stations data in South Bronx, New York. Particulate matter exposure in cars is associated with cardiovascular effects in healthy young men. Diesel exhaust particulate induces pulmonary and systemic inflammation in rats without impairing endothelial function ex vivo or in vivo. Inhalation of ultrafine and fine particulate matter disrupts systemic vascular function. Montelukast prevents vascular endothelial dysfunction from internal combustion exhaust inhalation during exercise. Identification of chemical components of combustion emissions that affect pro-atherosclerotic vascular responses in mice. Production of arrhythmias by elevated carboxyhemoglobin in patients with coronary artery disease. Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. Nitrogen dioxide air pollution near ambient levels is an atherogenic risk primarily in obese subjects: A brief communication. Exposure to inhaled particulate matter impairs cardiac function in senescent mice. Effects of ozone and particulate matter on cardiac mechanics: Role of the atrial natriuretic peptide gene. C(6)(0) exposure augments cardiac ischemia/reperfusion injury and coronary artery contraction in Sprague Dawley rats. Differential regulation of the lung endothelin system by urban particulate matter and ozone. Differential cardiopulmonary effects of size-fractionated ambient particulate matter in mice. Evidence for an association between air pollution and daily stroke admissions in Kaohsiung, Taiwan. Surface area-dependence of gas-particle interactions influences pulmonary and neuroinflammatory outcomes. Effects of acute exposure to ozone on heart rate and blood pressure of the conscious rat. Ultrafine carbon particle mediated cardiovascular impairment of aged spontaneously hypertensive rats. Atherosclerotic plaque rupturedPathologic basis of plaque stability and instability. Associations between outdoor air pollution and emergency department visits for stroke in Edmonton, Canada. Autism spectrum disorder: Interaction of air pollution with the met receptor tyrosine kinase gene. Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities. Specific phospholipid oxidation products inhibit ligand activation of Toll-like receptors 4 and 2. Effect of changes in ambient temperature on extrapulmonary physiological parameters. Cardiac arrhythmia induction after exposure to residual oil fly ash particles in a rodent model of pulmonary hypertension. Acute exposure to diesel exhaust impairs nitric oxide-mediated endothelial vasomotor function by increasing endothelial oxidative stress. Air pollution and hospital admissions for ischemic and hemorrhagic stroke among medicare beneficiaries. Particulate air pollution and hospital admissions for congestive heart failure in seven United States cities. Relation of long-term exposure to air pollution to brachial artery flow-mediated dilation and reactive hyperemia. Cardiovascular remodeling in response to long-term exposure to fine particulate matter air pollution. Retinal microvascular abnormalities and blood pressure in older people: the cardiovascular health study. Retinal microvascular abnormalities and 10-year cardiovascular mortality: A populationbased case-control study. Effect of early particulate air pollution exposure on obesity in mice: Role of p47phox. Association of systemic inflammation with marked changes in particulate air pollution in Beijing in 2008. Inflammatory response to fine particulate air pollution exposure: Neutrophil versus monocyte. Effects of diesel exhaust particles on left ventricular function in isoproterenol-induced myocardial injury and healthy rats. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model. Ambient particulates alter vascular function through induction of reactive oxygen and nitrogen species. Exposure to concentrated ambient particulate matter induces reversible increase of heart weight in spontaneously hypertensive rats. Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models. Conklin made all editorial changes, which were not substantial, and no changes to sections/figures/tables were made. This structural difference has great significance for chemical reactivity as unsaturated aldehydes are two to three orders of magnitude more reactive than saturated aldehydes of similar carbon length. Nonetheless, aldehydes, in general, are ubiquitous components of the environment and their increased abundance is associated with increased risk of cardiovascular disease in humans. However, aldehyde abundance in the environment does not always spell doom because many familiar foods contain a variety of non-toxic aldehydes that in addition to providing flavor to foods. Some of these aldehydes are difficult to measure accurately and can change in chemical structure over time 516 Aldehydes and Cardiovascular Disease due to chemical interactions in the air. Although environmental aldehydes are inhaled by all members of the population, a shorter list of aldehydes through their direct use in industrial processes can lead to potentially dangerous occupational exposures associated with the generation/use of these aldehydes in these industries, such as in embalming and perfumery practices. This scenario has led to more than one illustrative example of the potentially harmful effects of aldehyde exposure.

Heart failure: A cardiovascular outcome in diabetes that can no longer be ignored blood sugar glucose level generic actoplus met 500 mg amex. Dipeptidyl peptidase-4 inhibitors and heart failure: A meta-analysis of randomized clinical trials diabetic diet plan lose weight order 500 mg actoplus met visa. Effects on lipid profile of dipeptidyl peptidase 4 inhibitors diabetes mellitus type 2 and dka discount actoplus met 500mg online, pioglitazone diabetes mellitus type 2 en espanol purchase 500 mg actoplus met visa, acarbose diabetes medications for nurses order actoplus met 500mg mastercard, and sulfonlyureas: Meta-analysis of placebocontrolled trials diabetes mellitus type 2 in the philippines generic 500mg actoplus met mastercard. Thiazolidinedione use, fluid retention, and congestive heart failure: A consensus statement from the American Heart Association and American Diabetes Association. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. Effects of ingestion of triglyceride or galactose on secretion of gastric inhibitory polypeptide and on responses to intravenous glucose in normal and diabetic subjects. Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: A population study of 3. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. Heart failure, saxagliptin, and diabetes mellitus: Observations from the savor-timi 53 randomized trial. Effects of individual fatty acids on glucose uptake and glycogen synthesis in soleus muscle in vitro. Insulin, insulin resistance and platelet function: Similarities with insulin effects on cultured vascular smooth muscle cells. Drug usage patterns and treatment costs in newly-diagnosed type 2 diabetes mellitus cases 2007 vs. Hypoadiponectinemia in obesity and type 2diabetes: Close association with insulin resistance and hyperinsulinemia. Angiotensin-converting enzyme inhibitor use and major cardiovascular outcomes in type 2 diabetes mellitus treated with the dipeptidyl peptidase 4 inhibitor alogliptin. Dipeptidyl peptidase-4 inhibitors and cardiovascular outcomes: Meta-analysis of randomized clinical trials with 55,141 participants. In vivo myocardial protection from ischemia/reperfusion injury by the peroxisome proliferator-activated receptor-g agonist rosiglitazone. Mechanisms of Drug-Induced Cardiovascular Toxicity: Cardiotoxicity Associated With Diabetes Medications 431 Zhang, X. Effects of dipeptidyl peptidase-4 inhibitors on blood pressure in patients with type 2 diabetes: A systematic review and meta-analysis. Long term exposure to fatty acids and ketones inhibits b-cell functions in human pancreatic islets of Langerhans. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus (May, 2012). Management of hyperglycemia in type 2 diabetes, 2015: A patient-centered approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase inhibitors. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. When measured in serum, subtypes of cardiac troponin, such as cTnT and cTnI, are sensitive indicators of cardiac damage. Dexrazoxane An iron chelator approved for use in Europe and the United States to reduce anthracycline cardiotoxicity. Trastuzumab A monoclonal antibody specific to the human epidermal growth factor receptor type 2. Thomas R Cochran, Vivian I Franco, Rebecca Scully, and Steven E Lipshultz have updated the text throughout the article. Fortunately, earlier detection and improved treatment have increased the number of survivors. Limiting the efficacy of chemotherapy are pervasive late effects, particularly in children, where treatment can lead to lifelong morbidity (Oeffinger et al. Dysfunction translates to increased morbidity and mortality among long-term survivors. Self-reported health is significantly lower among long-term survivors, even in the absence of clinical cardiac dysfunction (Cox et al. Clinical cardiomyopathy, particularly when associated with anthracycline chemotherapy, is often refractory to treatment and carries a particularly poor prognosis (Felker et al. The Childhood Cancer Survivor Study reported a standardized mortality ratio for cardiac causes that was 8. Increased understanding of the molecular pathways of tumorigenesis has led to the development of targeted therapies. However, as with anthracyclines and radiation, trastuzumab has been associated with marked cardiotoxicity (Slamon et al. Although both trastuzumab and anthracyclines are associated with treatment-induced cardiotoxicity, the mechanisms are distinct. Type I chemotherapy-induced cardiotoxicity, that of anthracyclines, is progressive, nonreversible, and associated with cellular apoptosis. Trastuzumab, particularly when administered in combination with anthracyclines, has a toxicity that not only highlights the complexity of cell signaling pathways, but also offers greater insight into the mechanisms of toxicity and acute adaptation to stress in the heart muscle, neither of which is yet fully characterized. However, when the cardioprotectant dexrazoxane is administered before every dose of anthracycline, the additive cardiotoxicity of trastuzumab and anthracycline is mitigated (Ebb et al. In the early 1960s, daunorubicin was the first anthracycline to show effectiveness as an antitumor agent against acute leukemia in humans. Liposomal doxorubicin is efficacious in treating recurrent epithelial ovarian carcinoma and metastatic breast cancer (Harris et al. Epirubicin and idarubicin, anthracycline derivatives, are also widely used, particularly to treat advanced breast cancer and myelogenous leukemias (Robert et al. Pirarubicin, an anthracycline analogue, has been used to treat several malignancies, most recently acute myelogenous leukemia related to Down syndrome, in which rates of complete remission were high and rates of cardiotoxicity were extremely low (Kudo et al. Mitoxantrone, an anthraquinone, has antiviral, antibacterial, immunomodulator, and antitumor properties. Doxorubicin and daunorubicin each act as an electron acceptor and are reduced to semiquinone radical species (Davies and Doroshow, 1986). Mitochondria catalyze reduction, which is followed by rapid oxidation, spurring the generation of superoxides. At elevated concentrations, doxorubicin inhibits succinate dehydrogenase, succinate oxidase, and cytochrome c oxidase activities, which interrupts the electron transport chain (Marcillat et al. Genomic analysis in spontaneously hypertensive male rats provided further evidence that mitochondria are the primary target of the doxorubicininduced oxidative damage that causes cardiomyopathy and are also the site of its cardioprotective actions (Thompson et al. Other proposed theories for anthracycline-related cardiac damage include elevated concentrations of proinflammatory markers and progressive myocardial injury in the absence of repair. Several additional anthracycline-induced subcellular changes have been identified. Cardiomyocyte loss is likely the result of accumulated insults rather than the end result of a single pathway (Table 1) (Minotti et al. Anthracycline, Trastuzumab, and Cardiovascular Toxicity 435 Topoisomerase 2b has been found to be involved in anthracycline-induced cardiotoxicity (Zhang et al. Reduction in antioxidant enzyme gene transcription is also dependent on topoisomerase 2b (Zhang et al. Additionally, Topoisomerase 2b and anthracycline significantly reduce peroxisome proliferator-activated receptor-g coactivator 1-a and peroxisome proliferator-activated receptor-g coactivator 1-b, which are both critical to mitochondrial biogenesis (Zhang et al. Animal studies have found that topoisomerase 2b deletion protects mice from anthracycline induced cardiotoxicity (Veipongsa and Yeh, 2014a, 2014b). Pathologic findings related to this widespread degenerative chronic anthracycline cardiotoxicity include loss of myofibrils within cardiomyocytes, vascular degeneration, impaired mitochondrial generation, and interstitial fibrosis (Billingham et al. On a gross scale, as cardiomyocytes undergo apoptosis, the ventricular walls become thinner, and the remaining cells compensate through hypertrophy to maintain cardiac output (Lipshultz et al. Onset can be acute, occurring during therapy; early, occurring within months of treatment; or late, presenting a year or more after completing treatment. Risk factors and high-risk populations for ventricular dysfunction are highlighted where preventive or early therapeutic strategies may be effective. The circled numbers 1 through 5 indicate points of preventive or therapeutic interventions and in which biomarker measurements may be helpful. Toxicity is generally reversible and resolves when treatment is discontinued (Shankar et al. Although adults typically experience chronic dilated cardiomyopathy, children often present initially with dilated cardiomyopathy, which then progresses to a restrictive form. In a study of all Pediatric Oncology Group patients receiving anthracyclines between 1974 and 1990, 1. Of these 106 patients, cardiotoxicity was diagnosed in 95, either during therapy or during the first year after therapy. The incidence of late-onset cardiotoxicity increases with time and typically manifests as cardiomyopathy, which is often refractory to standard treatment (Lipshultz et al. However, at 15 years of follow-up, mean values were a full standard deviation below normal. Dashed lines are the upper and lower 95% confidence limits from the predicted mean. Stressors include pregnancy, surgery, weight-bearing exercise, weight lifting, and acute viral infection. Of 547 long-term survivors of childhood acute myelogenous leukemia, cardiotoxicity developed in 16 at a median follow-up of 5. Few data exist about late-onset anthracycline cardiotoxicity in long-term survivors of adults with cancer, although it is unlikely that adults are free from cardiac effects. Women with breast cancer often receive high doses of chemotherapy as well as mediastinal radiation, both of which can cause substantial cardiac damage (Rowlings et al. Congestive heart failure was particularly prevalent (standardized incidence ratio, 5. Among the breast cancer survivors in the United States over the age of 65, doxorubicin is associated with increased rates of cardiomyopathy (hazard ratio, 2. Cumulative dose is widely accepted as a risk factor, but peak delivery dose, age at diagnosis, concomitant radiation, female sex, genetic factors, and cardiac health before treatment also mediate cardiovascular risk (Lipshultz et al. A relationship between cumulative lifetime dose and cardiotoxicity is clear (Lipshultz et al. Several studies have found a significant incidence of late cardiotoxicity 10 or more years after treatment (Lipshultz et al. Anthracycline-induced cardiotoxicity is increased with current as well as previous exposure to certain other treatments. Radiation to the chest before anthracycline exposure increases the risk of toxicity, and previous treatment with anthracyclines increases the cardiotoxic effects of trastuzumab. It appears that early insults make the heart more susceptible to future adverse events (Adams and Lipshultz, 2005). Adults > 70 years old and children younger than 5 years old are at the greatest risk for cardiotoxicity (Von Hoff et al. Further, cardiac mortality is lower in children who are diagnosed after the age of 7 years (Lipshultz et al. Furthermore, the effect of sex increased at higher cumulative doses (Lipshultz et al. Excess mortality is also significantly higher in long-term female survivors of childhood cancer and in their male counterparts (Mertens et al. Trisomy 21 is also a risk factor for both myeloproliferative disorders and anthracycline-related cardiotoxicity (Krischer et al. Patients with preexisting cardiac disease are presumably at an increased risk of cardiac effects, though these patients are often excluded from long-term studies of treatment-related cardiotoxicity, making post hoc evaluation of this group difficult. One study that did include women with breast cancer and preexisting heart disease found it to be a significant risk factor for cardiomyopathy after anthracycline chemotherapy (Doyle et al. Mutations in the hemochromatosis gene interfere with iron metabolism, leading to iron overload, which increases the susceptibility of anthracycline-induced cardiotoxicity (Lipshultz et al. Obesity is common in cancer survivors, with women who received cranial radiation before the age of 5 years being 3. The risk of obesity after cranial radiation is increased in those receiving radiation doses of 20 Gy or higher, leaving men 1. The association between obesity and cranial radiation is thought to be the result of radiation-induced changes in growth hormone production and leptin sensitivity. Reduced peak delivery dose may help to limit the concentration of doxorubicin within the cardiomyocyte, reducing the potential for toxicity. However, the risk of subclinical cardiac dysfunction did not differ significantly groups (Van Dalen et al. Dexrazoxane is an iron chelator approved for use in Europe and the United States to reduce anthracycline cardiotoxicity.