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Acidosis
Kinds of Acidosis Selected AbstractsPROTEIN AND AMINO ACID METABOLISM IN UREMIC AND NONUREMIC ACIDOSISNEPHROLOGY, Issue 1 2002Holecek M [source] Calmodulin kinase II initiates arrhythmogenicity during metabolic acidification in murine heartsACTA PHYSIOLOGICA, Issue 1 2009T. H. Pedersen Abstract Aim:, The multifunctional signal molecule calmodulin kinase II (CaMKII) has been associated with cardiac arrhythmogenesis under conditions where its activity is chronically elevated. Recent studies report that its activity is also acutely elevated during acidosis. We test a hypothesis implicating CaMKII in the arrhythmogenesis accompanying metabolic acidification. Methods:, We obtained monophasic action potential recordings from Langendorff-perfused whole heart preparations and single cell action potentials (AP) using whole-cell patch-clamped ventricular myocytes. Spontaneous sarcoplasmic reticular (SR) Ca2+release events during metabolic acidification were investigated using confocal microscope imaging of Fluo-4-loaded ventricular myocytes. Results:, In Langendorff-perfused murine hearts, introduction of lactic acid into the Krebs-Henseleit perfusate resulted in abnormal electrical activity and ventricular tachycardia. The CaMKII inhibitor, KN-93 (2 ,m), reversibly suppressed this spontaneous arrhythmogenesis during intrinsic rhythm and regular 8 Hz pacing. However, it failed to suppress arrhythmia evoked by programmed electrical stimulation. These findings paralleled a CaMKII-independent reduction in the transmural repolarization gradients during acidosis, which previously has been associated with the re-entrant substrate under other conditions. Similar acidification produced spontaneous AP firing and membrane potential oscillations in patch-clamped isolated ventricular myocytes when pipette solutions permitted cytosolic Ca2+ to increase following acidification. However, these were abolished by both KN-93 and use of pipette solutions that held cytosolic Ca2+ constant during acidosis. Acidosis also induced spontaneous Ca2+ waves in isolated intact Fluo-4-loaded myocytes studied using confocal microscopy that were abolished by KN-93. Conclusion:, These findings together implicate CaMKII-dependent SR Ca2+ waves in spontaneous arrhythmic events during metabolic acidification. [source] Evaluation of a bedside blood ketone sensor: the effects of acidosis, hyperglycaemia and acetoacetate on sensor performanceDIABETIC MEDICINE, Issue 7 2004A. S. A. Khan Abstract Aims To assess the performance of a handheld bedside ketone sensor in the face of likely metabolic disturbances in diabetic ketoacidosis, namely: pH, glucose and acetoacetate. Methods The effects of pH (7.44,6.83), glucose (5,50 mmol/l) and acetoacetate (0,5 mmol/l) were examined in venous blood to investigate the accuracy of betahydroxybutyrate measurement (0,5 mmol/l) by a handheld ketone sensor. Sensor results were compared with a reference method. Linear regression models were fitted to the difference between the methods with the concentration of metabolite as the explanatory factor. Results Decreasing pH and increasing glucose had no effect on the accuracy of the handheld ketone sensor; the gradients of the fitted lines were ,0.14 and ,0.003, respectively. The 95% confidence intervals were ,0.7,0.4 and ,0.01,0.004, respectively (P = 0.59 and 0.4, respectively). In the acetoacetate study, a positive relationship between the sensor and reference method results was found, the gradient was 0.09. The 95% confidence interval was 0.05,0.14 (P , 0.001), indicating that high concentrations of acetoacetate interfere with the sensor performance. Conclusions Acidosis and hyperglycaemia have minimal effects on the sensor performance. However, high concentrations of acetoacetate result in some overestimation of betahydroxybutyrate. This bedside ketone sensor provides useful data over a broad range of conditions likely to be encountered during moderate to severe diabetic ketoacidosis. [source] Renal Tubular Acidosis Associated With Zonisamide TherapyEPILEPSIA, Issue 1 2000Article first published online: 19 SEP 200 First page of article [source] Amino Acid Transport Kinetics and Protein Turnover in HemodialysisHEMODIALYSIS INTERNATIONAL, Issue 1 2003Raj Dominic Background: Protein metabolism is abnormal in patients with end-stage renal disease. However, the etiology of abnormal protein turnover is unclear. Also the role of hemodialysis on protein turnover remains controversial. Abnormal protein metabolism could be due to malnutrition or due to abnormal amino acid transport kinetics Hypothesis: 1) Amino acid transport is abnormal in uremia, 2) Hemodialysis increases fractional protein synthesis rate and c) Net protein accretion is negative during hemodialysis because of increased catabolism. Aim: 1) To study the impact of uremia and hemodialysis on intracellular amino acid transport kinetics and 2) Quantify the fractional protein synthesis rate and degradation in a uremic state and during hemodialysis Methods: Protein turnover and amino acid transport kinetics using stable isotopes of phenylalanine in 2 patients and 2 controls. The patients were placed on a standard diet (1.2 gm/Kg protein and 35 Kcal/Kg) for 2 weeks prior to the study. Acidosis as corrected by NaHCO3 supplementation. Amino acid transport and protein turnover were estimated by compartmental model and precursor product approach respectively. Results: Mean protein intake and HCO3 were 1.4 ± 1 gm/day and 26.8 ± 4.1 meq/L respectively. Inward transport (11.2 ± 2.6 vs. 9.8 ± 2.1 nmol/min,1/100 ml leg,1) and outward transport (10.2 ± 1.2 vs.11.0 ± 1.6 l nmol/min,1/100 ml leg,1) were not different before and during HD. Inward and outward transport in controls were 12.6 ± 3.7 and 16.2 ± 3.5 nmol/min,1/100 ml leg,1 respectively. Protein synthesis was higher than catabolism in the pre-dialysis phase (156.8 ± 66.1 vs. 144.3 ± 53.7 nmol/min/ml leg-1, p = NS), but catabolism was higher than synthesis during HD (172.3 ± 20.5 vs. 186.8 ± 25.8 nmol/min/ml leg-1, p = NS). Protein synthesis and catabolism in controls were 110.8 ± 13.5 and 127.4 ± 12.7 nmol/min/ml leg-1. Conclusion: 1. Inward and outward transport of amino acids are not altered by renal failure or hemodialysis. 2. Protein turnover is increased during hemodialysis, with net balance favoring catabolism [source] Buformin-Induced Lactic Acidosis,A Symptom of Modern Healthcare MaladyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2004Mahesh Krishnamurthy MD No abstract is available for this article. [source] Effect of selected alcohol dehydrogenase inhibitors on human hepatic lactate dehydrogenase activity , an in vitro studyJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2005Jaroslaw Dudka Abstract Metabolic acidosis severely complicates methanol and ethylene glycol intoxications. Acidosis is caused by acid metabolites and can be intensified by lactate elevation. Lactate concentration depends on the NADH2/NAD ratio. Lactate dehydrogenase (LDH, E.C.1.1.1.27.) supplies more lactate when the level of NADH2 is elevated. The aim of the study was to evaluate the effect of alcohol dehydrogenase (ADH) inhibitors and substrates: cimetidine, EDTA, 4-methylpyrazole (4-MP), Ukrain and ethanol on LDH activity. The activity of LDH was determined spectrophotometrically in human liver homogenates incubated with cimetidine, EDTA, 4-MP and Ukrain at concentrations of 2 × 10,6, 10,5 and 5 × 10,5m as well as ethanol at concentrations of 12.50, 25.00, 50.00 mm. The LDH activity was significantly increased by 10,5 and 5 × 10,5m concentrations of cimetidine and 4-MP, and by all concentrations of ethanol. The most effective change of LDH activity of about 26% (P < 0.01) was observed at the highest concentration of ethanol. Ukrain inhibited LDH activity at both concentrations, i.e. 10,5 and 5 × 10,5m (P < 0.05). However, EDTA did not significantly influence LDH activity. The data showed that ethanol and 4-MP, the main antidotes in methanol or ethylene glycol poisoning, may increase liver LDH activity , an undesirable effect during the therapy of patients intoxicated with these alcohols. On the other hand, the decrease of LDH activity in the presence of Ukrain is a promising finding but definitely requires further investigation. Copyright © 2005 John Wiley & Sons, Ltd. [source] Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Response to Acidic pH Through OGR1 in a Human Osteoblastic Cell Line,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2008Hideaki Tomura Abstract Acidosis has been shown to induce depletion of bone calcium from the body. This calcium release process is thought to be partially cell mediated. In an organ culture of bone, acidic pH has been shown to induce cyclooxygenase-2 (COX-2) induction and prostaglandin E2 (PGE2) production, resulting in stimulation of bone calcium release. However, the molecular mechanisms whereby osteoblasts sense acidic circumstances and thereby induce COX-2 induction and PGE2 production remain unknown. In this study, we used a human osteoblastic cell line (NHOst) to characterize cellular activities, including inositol phosphate production, intracellular Ca2+ concentration ([Ca2+]i), PGE2 production, and COX-2 mRNA and protein expression, in response to extracellular acidification. Small interfering RNA (siRNA) specific to the OGR1 receptor and specific inhibitors for intracellular signaling pathways were used to characterize acidification-induced cellular activities. We found that extracellular acidic pH induced a transient increase in [Ca2+]i and inositol phosphate production in the cells. Acidification also induced COX-2 induction, resulting in PGE2 production. These proton-induced actions were markedly inhibited by siRNA targeted for the OGR1 receptor and the inhibitors for Gq/11 protein, phospholipase C, and protein kinase C. We conclude that the OGR1/Gq/11/phospholipase C/protein kinase C pathway regulates osteoblastic COX-2 induction and subsequent PGE2 production in response to acidic circumstances. [source] Regulatory Mechanisms and Physiological Relevance of a Voltage-Gated H+ Channel in Murine Osteoclasts: Phorbol Myristate Acetate Induces Cell Acidosis and the Channel Activation,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2003Hiroyuki Mori Abstract The voltage-gated H+ channel is a powerful H+ extruding mechanism of osteoclasts, but its functional roles and regulatory mechanisms remain unclear. Electrophysiological recordings revealed that the H+ channel operated on activation of protein kinase C together with cell acidosis. Introduction: H+ is a key signaling ion in bone resorption. In addition to H+ pumps and exchangers, osteoclasts are equipped with H+ conductive pathways to compensate rapidly for pH imbalance. The H+ channel is distinct in its strong H+ extrusion ability and voltage-dependent gatings. Methods: To investigate how and when the H+ channel is available in functional osteoclasts, the effects of phorbol 12-myristate 13-acetate (PMA), an activator for protein kinase C, on the H+ channel were examined in murine osteoclasts generated in the presence of soluble RANKL (sRANKL) and macrophage-colony stimulating factor (M-CSF). Results and Conclusions: Whole cell recordings clearly showed that the H+ current was enhanced by increasing the pH gradient across the plasma membrane (,pH), indicating that the H+ channel changed its activity by sensing ,pH. The reversal potential (Vrev) was a valuable tool for the real-time monitoring of ,pH in clamped cells. In the permeabilized patch, PMA (10 nM-1.6 ,M) increased the current density and the activation rate, slowed decay of tail currents, and shifted the threshold toward more negative voltages. In addition, PMA caused a negative shift of Vrev, suggesting that intracellular acidification occurred. The PMA-induced cell acidosis was confirmed using a fluorescent pH indicator (BCECF), which recovered quickly in a K+ -rich alkaline solution, probably through the activated H+ channel. Both cell acidosis and activation of the H+ channel by PMA were inhibited by staurosporine. In ,80% of cells, the PMA-induced augmentation in the current activity remained after compensating for the ,pH changes, implying that both ,pH-dependent and -independent mechanisms mediated the channel activation. Activation of the H+ channel shifted the membrane potential toward Vrev. These data suggest that the H+ channel may contribute to regulation of the pH environments and the membrane potential in osteoclasts activated by protein kinase C. [source] Metabolic Acidosis Stimulates RANKL RNA Expression in Bone Through a Cyclo-oxygenase-Dependent Mechanism,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2003Kevin K Frick Abstract Metabolic acidosis inhibits osteoblastic bone formation and stimulates osteoclastic resorption. To determine whether acidosis alters expression of RNA for the osteoclastic differentiation factor RANKL, mouse calvariae were incubated in neutral or physiologically acidic media. Acidosis resulted in a significant cyclo-oxygenase-dependent increase in RANKL RNA levels, which would be expected to induce the associated increase in bone resorption. Introduction: Metabolic acidosis increases net calcium efflux from bone, initially through physicochemical mechanisms and later through predominantly cell-mediated mechanisms. Acidosis decreases osteoblastic bone formation and increases osteoclastic resorption. The growth and maturation of osteoclasts, derived from hematopoietic precursors in the monocyte/macrophage lineage, are dependent on the interplay of a number of factors. Commitment of pre-osteoclasts to osteoclasts is induced by the interaction of the osteoclastic cell-surface receptor RANK with a ligand expressed by osteoblasts, RANKL. The RANK/RANKL interaction not only initiates a differentiation cascade that culminates in mature bone-resorbing osteoclasts but also increases osteoclastic resorptive capacity and survival. Methods: To test the hypothesis that metabolic acidosis increases expression of RANKL, we cultured neonatal mouse calvariae in acidic (initial medium pH ,7.1 and [HCO3,] ,11 mM) or neutral (initial medium pH ,7.5 and [HCO3,] ,25 mM) medium for 24 and 48 h. We determined the relative expression of RANKL RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitated the expression by Northern analysis. Results: In this model of metabolic acidosis, there was significantly increased expression of RANKL RNA at both 24 (2-fold) and 48 h (5-fold) compared with respective controls. Net calcium efflux from bone was also increased in acidic medium compared with control medium. At 48 h, net calcium efflux correlated directly with RANKL expression (r = 0.77, n = 15, p < 0.001). Inhibition of prostaglandin synthesis with indomethacin blocked the acid-induced increase in RANKL RNA as well as the increased calcium efflux. Conclusions: Metabolic acidosis induces osteoblastic prostaglandin synthesis, followed by autocrine or paracrine induction of RANKL. This increase in RANKL would be expected to augment osteoclastic bone resorption and help explain the increase in cell-mediated net calcium efflux. [source] Acidosis Impairs the Protective Role of hERG K+ Channels Against Premature StimulationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2010B.Sc., CHUN YUN DU M.B. Acidosis and the hERG K+ Channel.,Introduction: Potassium channels encoded by human ether-ą-go-go-related gene (hERG) underlie the cardiac rapid delayed rectifier K+ channel current (IKr). Acidosis occurs in a number of pathological situations and modulates a range of ionic currents including IKr. The aim of this study was to characterize effects of extracellular acidosis on hERG current (IhERG), with particular reference to quantifying effects on IhERG elicited by physiological waveforms and upon the protective role afforded by hERG against premature depolarizing stimuli. Methods and Results: IhERG recordings were made from hERG-expressing Chinese Hamster Ovary cells using whole-cell patch-clamp at 37°C. IhERG during action potential (AP) waveforms was rapidly suppressed by reducing external pH from 7.4 to 6.3. Peak repolarizing current and steady state IhERG activation were shifted by ,+6 mV; maximal IhERG conductance was reduced. The voltage-dependence of IhERG inactivation was little-altered. Fast and slow time-constants of IhERG deactivation were smaller across a range of voltages at pH 6.3 than at pH 7.4, and the contribution of fast deactivation increased. A modest acceleration of the time-course of recovery of IhERG from inactivation was observed, but time-course of activation was unaffected. The amplitude of outward IhERG transients elicited by premature stimuli following an AP command was significantly decreased at lower pH. Computer simulations showed that after AP repolarization a subthreshold stimulus at pH 7.4 could evoke an AP at pH 6.3. Conclusion: During acidosis the contribution of IhERG to action potential repolarization is reduced and hERG may be less effective in counteracting proarrhythmogenic depolarizing stimuli. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1160-1169) [source] Extracellular Acidosis Modulates Drug Block of Kv4.3 Currents by Flecainide and QuinidineJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2003Suresh Singarayar M.D. Introduction: As a molecular model of the effect of ischemia on drug block of the transient outward potassium current, the effect of acidosis on the blocking properties of flecainide and quinidine on Kv4.3 currents was studied. Methods and Results: Kv4.3 channels were stably expressed in Chinese hamster ovary cells. Whole-cell, voltage clamp techniques were used to measure the effect of flecainide and quinidine on Kv4.3 currents in solutions of pH 7.4 and 6.0. Extracellular acidosis attenuated flecainide block of Kv4.3 currents, with the IC50 for flecainide (based on current-time integrals) increasing from7.8 ± 1.1 ,Mat pH 7.4 to125.1 ± 1.1 ,Mat pH 6.0. Similar effects were observed for quinidine (IC50 5.2 ± 1.1 ,Mat pH 7.4 and22.1 ± 1.3 ,Mat pH 6.0). Following block by either drug, Kv4.3 channels showed a hyperpolarizing shift in the voltage sensitivity of inactivation and a slowing in the time to recover from inactivation/block that was unaffected by acidosis. In contrast, acidosis attenuated the effects on the time course of inactivation and the degree of tonic- and frequency-dependent block for both drugs. Conclusion: Extracellular acidosis significantly decreases the potency of blockade of Kv4.3 by both flecainide and quinidine. This change in potency may be due to allosteric changes in the channel, changes in the proportion of uncharged drug, and/or changes in the kinetics of drug binding or unbinding. These findings are in contrast to the effects of extracellular acidosis on block of the fast sodium channel by these agents and provide a molecular mechanism for divergent modulation of drug block potentially leading to ischemia-associated proarrhythmia.(J Cardiovasc Electrophysiol, Vol. 14, pp. 641-650, June 2003) [source] Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task ForceJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2005U. MARTINOWITZ Summary.,Background:,Recombinant activated factor VII (rFVIIa) has been approved by the U.S. Food and Drug Administration (FDA) for almost a decade for hemophilic patients with inhibitors. Its off-label use as a hemostatic agent in massive bleeding caused by a wide array of clinical scenarios is rapidly expanding. While evidence-based guidelines exist for rFVIIa treatment in hemophilia, none are available for its off-label use. Objectives:,The aim of this study is to develop expert recommendations for the use of rFVIIa in patients suffering from uncontrolled bleeding (with special emphasis on trauma) until randomized, controlled trials allow for the introduction of more established evidence-based guidelines. Methods:,A multidisciplinary task force comprising representatives of the relevant National Medical Associations, experts from the Medical Corps of the Army, Ministry of Health and the Israel National Trauma Advisory Board was established in Israel. Recommendations were construed based on the analysis of the first 36 multi-trauma patients accumulated in the prospective national registry of the use of rFVIIa in trauma, and an extensive literature search consisting of published and prepublished controlled animal trials, case reports and series. The final consensus guidelines, together with the data of the first 36 trauma patients treated in Israel, are presented in this article. Results:,Results of the first 36 trauma patients: The prolonged clotting assays [prothrombin time (PT) and partial thromboplastin time (PTT)] shortened significantly within minutes following administration of rFVIIa. Cessation of bleeding was achieved in 26 of 36 (72%) patients. Acidosis diminished the hemostatic effect of the drug, while hypothermia did not affect it. The survival rate of 61% (22/36) seems to be favorable compared with published series of similar, or less severe, trauma patients (range 30%,57%). Conclusions:,As a result of the lack of controlled trials, our guidelines should be considered as suggestive rather than conclusive. However, they provide a valuable tool for physicians using rFVIIa for the expanding off-label clinical uses. [source] Lactobacillus GG Does Not Affect D-Lactic Acidosis in Diarrheic Calves, in a Clinical SettingJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2006Julia B. Ewaschuk D-lactate, produced by gastrointestinal fermentation, is a major contributor to metabolic acidosis in diarrheic calves. Lactobacillus rhamnosus GG survives gastrointestinal transit in the neonatal calf and does not produce D-lactate. To determine whether this probiotic reduces gastrointestinal D-lactate production or severity of diarrhea or both, 48 calves (mean, 11 days old; range, 2,30 days) admitted to the clinic for treatment of diarrhea were randomly allocated to 2 groups. The experimental group was given Lactobacillus rhamnosus GG (1×1011 cfu/d) PO, dissolved in milk or oral electrolyte solution, in addition to clinic treatment protocols; the other group served as a control. Serum and fecal samples were obtained at admission and at 24 and 48 hours after initial administration of Lactobacillus rhamnosus GG. All samples were analyzed for D-and L-lactate by using high-pressure liquid chromatography. Feces were also analyzed for pathogens, Lactobacillus rhamnosus GG recovery, and dry matter. D-lactic acidemia (>3 mmol/L) was present in 37/48 calves at admission. Lactobacillus rhamnosus GG was recovered in the feces of 13 experimental calves and 0 control calves 24 hours after administration. No difference in serum or fecal D- or L-lactate between the groups was detected at any time point. After therapy, D-lactic acidosis was absent at 48 hours in all but 1 calf. No relation between fecal pathogen (viral, bacterial, or protozoal) and degree of D-lactic acidosis was observed. The reduction in mortality and greater fecal dry matter in Lactobacillus rhamnosus GG-treated calves was not statistically significant. [source] Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvementNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2006J. Betts Mitochondrial DNA (mtDNA) disease is an important genetic cause of neurological disability. A variety of different clinical features are observed and one of the most common phenotypes is MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes). The majority of patients with MELAS have the 3243A>G mtDNA mutation. The neuropathology is dominated by multifocal infarct-like lesions in the posterior cortex, thought to underlie the stroke-like episodes seen in patients. To investigate the relationship between mtDNA mutation load, mitochondrial dysfunction and neuropathological features in MELAS, we studied individual neurones from several brain regions of two individuals with the 3243A>G mutation using dual cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) histochemistry, and Polymerase Chain Reaction Restriction Fragment Lenght Polymorphism (PCR-RFLP) analysis. We found a low number of COX-deficient neurones in all brain regions. There appeared to be no correlation between the threshold level for the 3243A>G mutation to cause COX deficiency within single neurones and the degree of pathology in affected brain regions. The most severe COX deficiency associated with the highest proportion of mutated mtDNA was present in the walls of the leptomeningeal and cortical blood vessels in all brain regions. We conclude that vascular mitochondrial dysfunction is important in the pathogenesis of the stroke-like episodes in MELAS patients. As migraine is a commonly encountered feature in MELAS, we propose that coupling of the vascular mitochondrial dysfunction with cortical spreading depression (CSD) might underlie the selective distribution of ischaemic lesions in the posterior cortex in these patients. [source] Effects of desmopressin on platelet function under conditions of hypothermia and acidosis: an in vitro study using multiple electrode aggregometry,ANAESTHESIA, Issue 7 2010A. A. Hanke Summary Hypothermia and acidosis lead to an impairment of coagulation. It has been demonstrated that desmopressin improves platelet function under hypothermia. We tested platelet function ex vivo during hypothermia and acidosis. Blood samples were taken from 12 healthy subjects and assigned as follows: normal pH, pH 7.2, and pH 7.0, each with and without incubation with desmopressin. Platelet aggregation was assessed by multiple electrode aggregometry. Baseline was normal pH and 36 °C. The other samples were incubated for 30 min and measured at 32 °C. Acidosis significantly impaired aggregation. Desmopressin significantly increased aggregability during hypothermia and acidosis regardless of pH, but did not return it to normal values at low pH. During acidosis and hypothermia, acidosis should be corrected first; desmopressin can then be administered to improve platelet function as a bridge until normothermia can be achieved. [source] Better Correction of Metabolic Acidosis, Blood Pressure Control, and Phagocytosis with Bicarbonate Compared to Lactate Solution in Acute Peritoneal DialysisARTIFICIAL ORGANS, Issue 2 2001Visith Thongboonkerd Abstract: Lactate solution has been the standard dialysate fluid for a long time. However, it tends to convert back into lactic acid in poor tissue-perfusion states. The aim of this study was to evaluate the efficacy of magnesium (Mg)- and calcium (Ca)-free bicarbonate solution compared with lactate solution in acute peritoneal dialysis (PD). Renal failure patients who were indicated for dialysis and needed acute PD were classified as shock and nonshock groups, and then were randomized to receive either bicarbonate or lactate solution. Twenty patients were enrolled in this study (5 in each subgroup). In the shock group, there were more rapid improvements and significantly higher levels of blood pH (7.40 ± 0.04 versus 7.28 ± 0.05, p < 0.05), serum bicarbonate (23.30 ± 1.46 versus 18.37 ± 1.25 mmol/L, p < 0.05), systolic pressure (106.80 ± 3.68 versus 97.44 ± 3.94 mm Hg, p < 0.05), mean arterial pressure (80.72 ± 2.01 versus 73.28 ± 2.41 mm Hg, p < 0.05), percentages of phagocytosis of circulating leukocytes (65.85%± 2.22 versus 52.12%± 2.71, p < 0.05), and percentages of positive nitroblue tetrazolium (NBT) reduction test without and with stimulation (14.43 ± 1.93 versus 9.43 ± 2.12, p < 0.05 and 65.08 ± 6.80 versus 50.23 ± 4.21, p < 0.05, respectively) in the bicarbonate subgroup compared with the lactate subgroup. In the nonshock group, blood pH, serum bicarbonate, and phagocytosis assays in both subgroups were comparable. Lactic acidosis was more rapidly recovered and was significantly lower with bicarbonate solution for both shock and nonshock groups (3.63 ± 0.37 versus 5.21 ± 0.30 mmol/L, p < 0.05 and 2.92 ± 0.40 versus 3.44 ± 0.34 mmol/L, p < 0.05, respectively). Peritoneal urea and creatinine clearances in both subgroups were comparable for both shock and nonshock groups. There was no peritonitis observed during the study. Serum Mg and Ca levels in the bicarbonate subgroup were significantly lower, but no clinical and electrocardiographic abnormality were observed. We concluded that Mg- and Ca-free bicarbonate solution could be safely used and had better outcomes in correction of metabolic acidosis, blood pressure control, and nonspecific systemic host defense with comparable efficacy when compared to lactate solution. It should be the dialysate of choice for acute PD especially in the poor tissue-perfusion states such as shock, lactic acidosis, and multiple organ failure. [source] Elevation of anions in exercise-induced acidosis: a study by ion-exchange chromatography/mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 3 2008William McKinnon Abstract Acidosis is a major factor that determines the upper limit of exercise endurance. We have previously shown that anions usually associated with intermediary metabolism are elevated in critically ill patients with metabolic acidosis and contribute significantly to acidosis generation. This study was to determine whether volunteers with normal metabolism would exhibit similar elevations in anions associated with intermediate metabolism when exposed to a short-term physiological stress leading to a brief lactic acidosis. Physiological stress was induced on five healthy male subjects by means of a ramped exercise protocol. Blood was obtained immediately prior to and post-exercise, plasma ultrafiltrate was prepared and analysed immediately both by enzyme assay and liquid chromatography coupled to electrospray,mass spectrometry (LC/ESI-MS). Metabolic acidosis concomitant with a significant increase in blood lactate occurred in each subject, but in addition, anions normally associated with intermediate metabolism were significantly elevated after exercise. The contribution of these anions to generating an acidosis, and thus potentially limiting the extent of exercise, has never been acknowledged. Copyright © 2007 John Wiley & Sons, Ltd. [source] Acidosis and Catecholamine Evaluation Following Simulated Law Enforcement "Use of Force" EncountersACADEMIC EMERGENCY MEDICINE, Issue 7 2010Jeffrey D. Ho MD ACADEMIC EMERGENCY MEDICINE 2010; 17:E60,E68 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives:, Law enforcement authorities are often charged with controlling resisting suspects. These encounters sometimes result in the sudden and unexpected death of the suspect. Drug intoxication, excited delirium syndrome, or excessive uses of force are factors that are often blamed, but sometimes the mechanism of these deaths is not fully understood. It is possible that worsening acidosis or excessive catecholamine release play a part. The objective of this study was to determine the effect on markers of acidosis and catecholamines of various tasks intended to simulate common arrest-related situations. Methods:, Subjects were assigned to one of five task groups: 1) a 150-meter sprint and wall hurdle (simulated flight from arrest); 2) 45 seconds of striking a heavy bag (simulated physical resistance); 3) a 10-second TASER X26 electronic control device exposure; 4) a fleeing and resistance exercise involving a law enforcement dog (K-9); or 5) an oleoresin capsicum (OC) exposure to the face and neck. Baseline serum pH, lactate, potassium, troponin I, catecholamines, and creatine kinase (CK) were evaluated. Serum catecholamines, pH, lactate, and potassium were sampled immediately after the task and every 2 minutes for 10 minutes posttask. Vital signs were repeated immediately after the task. Serum CK and troponin I were evaluated again at 24 hours posttask. Results:, Sixty-six subjects were enrolled; four did not complete their assigned task. One subject lost the intravenous (IV) access after completing the task and did not have data collected, and one subject only received a 5-second TASER device exposure and was excluded from the study, leaving 12 subjects in each task group. The greatest changes in acidosis markers occurred in the sprint and heavy bag groups. Catecholamines increased the most in the heavy bag group and the sprint group and increased to a lesser degree in the TASER, OC, and K-9 groups. Only the sprint group showed an increase in CK at 24 hours. There were no elevations in troponin I in any group, nor any clinically important changes in potassium. Conclusions:, The simulations of physical resistance and fleeing on foot led to the greatest changes in markers of acidosis and catecholamines. These changes may be contributing or causal mechanisms in sudden custodial arrest-related deaths (ARDs). This initial work may have implications in guiding applications of force for law enforcement authorities (LEAs) when apprehending resisting subjects. [source] Bedside Detection of Urine ,-Hydroxybutyrate in Diagnosing Metabolic AcidosisACADEMIC EMERGENCY MEDICINE, Issue 8 2008Silas W. Smith MD Abstract Objectives:, While critically important, the rapid identification of the etiology of metabolic acidosis (MA) may be labor-intensive and time-consuming. Alcoholic, starvation, and severe diabetic ketoacidosis (AKA, SKA, and DKA, respectively) may produce ,-hydroxybutyrate (BOHB) in marked excess of acetone (ACET) and acetoacetate (AcAc). Unfortunately, current urine dipstick technology poorly detects ACET and cannot measure BOHB. The inability to detect BOHB might delay therapy for ketoacidoses or provoke unnecessary evaluation or empiric treatment of other causes of MA, such as toxic alcohol poisoning. The authors tested the previous assertion that commonly available hydrogen peroxide (H2O2) would improve BOHB detection. The effectiveness of alkalinization and use of a silver nitrate (AgNO3) catalyst was also assessed. Methods:, Control and urine test specimens containing from 0.5 to 800 mmol/L ACET, AcAc, and BOHB were prepared. Urine specimens were oxidized with H2O2 (3%) 1:9 (H2O2:urine), alkalinized with potassium hydroxide (KOH; 10%), exposed to AgNO3 sticks, or altered with a combination of these methods in a random fashion. Three emergency physicians (EPs) blinded to the preparation technique evaluated urine dipsticks (Multistix, Bayer Corp.) placed in the specimens for "ketones." Results:, Multistix detected AcAc appropriately; ACET was detected only at high concentrations of ,600 mmol/L. Multistix failed to measure BOHB at all concentrations tested. H2O2 improved urinary BOHB detection, although not to clinically relevant levels (40 mmol/L). Alkalinization and AgNO3 sticks did not improve BOHB detection beyond this threshold. Conclusions:, Addition of H2O2 (3%), alkalinization, or AgNO3 sticks did not improve clinically meaningful urine BOHB detection. Clinicians should use direct methods to detect BOHB when suspected. [source] Evaluation of Protein S-100 serum concentrations in healthy newborns and seven newborns with perinatal acidosisACTA PAEDIATRICA, Issue 5 2000J Maschmann We measured Protein S-100 serum levels in 66 healthy newborns during the first week of life and in 7 newborns with perinatal acidosis. Normal values (n= 66) constantly ranged between 0.66 and 3.33 ug/1 (2.5 and 97.5 percentiles) during the evaluation period. Conclusions: Newborns with signs of hypoxic-ischaemic encephalopathy (HIE) after perinatal acidosis showed elevated Protein S-100 serum levels, whereas newborns without these signs had normal concentrations. S-100 might thus be a marker of central nervous system damage in newborns. [source] Effect of Normal Saline Infusion on the Diagnostic Utility of Base Deficit in Identifying Major Injury in Trauma PatientsACADEMIC EMERGENCY MEDICINE, Issue 12 2006Richard Sinert DO Abstract Background Base deficit (BD) is a reliable marker of metabolic acidosis and is useful in gauging hemorrhage after trauma. Resuscitation with chloride-rich solutions such as normal saline (NS) can cause a dilutional acidosis, possibly confounding the interpretation of BD. Objectives To test the diagnostic utility of BD in distinguishing minor from major injury after administration of NS. Methods This was a prospective observational study at a Level 1 trauma center. The authors enrolled patients with significant mechanism of injury and measured BD at triage (BD-0) and at four hours after triage (BD-4). Major injury was defined by any of the following: injury severity score of ,15, drop in hematocrit of ,10 points, or the patient requiring a blood transfusion. Patients were divided into a low-volume (NS < 2L) and a high-volume (NS , 2L) group. Data were reported as mean (±SD). Student's t- and Wilcoxon tests were used to compare data. Receiver operating characteristic (ROC) curves tested the utility of BD-4 in differentiating minor from major injury in the study groups. Results Four hundred eighty-nine trauma patients (mean age, 36 [± 18] yr) were enrolled; 82% were male, and 34% had penetrating injury. Major-(20%) compared with minor-(80%) injury patients were significantly (p = 0.0001) more acidotic (BD-0 mean difference: ,3.3 mmol/L; 95% confidence interval [CI] =,2.5 to ,4.2). The high-volume group (n = 174) received 3,342 (±1,821) mL, and the low-volume group (n = 315) received 621 (±509) mL of NS. Areas under the ROC curves for the high-volume (0.63; 95% CI = 0.52 to 0.74) and low-volume (0.73; 95% CI = 0.60 to 0.86) groups were not significantly different from each other. Conclusions Base deficit was able to distinguish minor from major injury after four hours of resuscitation, irrespective of the volume of NS infused. [source] Calmodulin kinase II initiates arrhythmogenicity during metabolic acidification in murine heartsACTA PHYSIOLOGICA, Issue 1 2009T. H. Pedersen Abstract Aim:, The multifunctional signal molecule calmodulin kinase II (CaMKII) has been associated with cardiac arrhythmogenesis under conditions where its activity is chronically elevated. Recent studies report that its activity is also acutely elevated during acidosis. We test a hypothesis implicating CaMKII in the arrhythmogenesis accompanying metabolic acidification. Methods:, We obtained monophasic action potential recordings from Langendorff-perfused whole heart preparations and single cell action potentials (AP) using whole-cell patch-clamped ventricular myocytes. Spontaneous sarcoplasmic reticular (SR) Ca2+release events during metabolic acidification were investigated using confocal microscope imaging of Fluo-4-loaded ventricular myocytes. Results:, In Langendorff-perfused murine hearts, introduction of lactic acid into the Krebs-Henseleit perfusate resulted in abnormal electrical activity and ventricular tachycardia. The CaMKII inhibitor, KN-93 (2 ,m), reversibly suppressed this spontaneous arrhythmogenesis during intrinsic rhythm and regular 8 Hz pacing. However, it failed to suppress arrhythmia evoked by programmed electrical stimulation. These findings paralleled a CaMKII-independent reduction in the transmural repolarization gradients during acidosis, which previously has been associated with the re-entrant substrate under other conditions. Similar acidification produced spontaneous AP firing and membrane potential oscillations in patch-clamped isolated ventricular myocytes when pipette solutions permitted cytosolic Ca2+ to increase following acidification. However, these were abolished by both KN-93 and use of pipette solutions that held cytosolic Ca2+ constant during acidosis. Acidosis also induced spontaneous Ca2+ waves in isolated intact Fluo-4-loaded myocytes studied using confocal microscopy that were abolished by KN-93. Conclusion:, These findings together implicate CaMKII-dependent SR Ca2+ waves in spontaneous arrhythmic events during metabolic acidification. [source] The use of neuroimaging in the diagnosis of mitochondrial diseaseDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2010Seth D. Friedman Abstract Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. Magnetic resonance imaging changes may be nonspecific, such as atrophy (both general and involving specific structures, such as cerebellum), more suggestive of particular disorders such as focal and often bilateral lesions confined to deep brain nuclei, or clearly characteristic of a given disorder such as stroke-like lesions that do not respect vascular boundaries in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS). White matter hyperintensities with or without associated gray matter involvement may also be observed. Across patients and discrete disease subtypes (e.g., MELAS, Leigh syndrome, etc.), patterns of these features are helpful for diagnosis. However, it is also true that marked variability in expression occurs in all mitochondrial disease subtypes, illustrative of the complexity of the disease process. The present review summarizes the role of neuroimaging in the diagnosis and characterization of patients with suspected mitochondrial disease. © 2010 Wiley-Liss, Inc. Dev Disabil Res Rev 2010;16:129,135. [source] Topiramate-induced metabolic acidosis: report of two casesDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 10 2001Chun-hung Ko MRCP FHKAM Medical Officer Two children who presented with symptomatic metabolic acidosis after being put on topiramate (TPM) are reported. The first patient was an 11-year-old male with refractory complex partial epilepsy who was put on TPM for 13 months. He developed hyperventilation 1 week after increasing the dose to 300mg/day. Arterial blood gas revealed hyperchloraemic metabolic acidosis with partial respiratory compensation: pH 7.36, PCO2 27.2 mmHg, bicarbonate 14.9 mEq/L, base excess -8.9 mmol/L. Hyperventilation and acidosis resolved after administration of sodium bicarbonate and reduction of the dose of TPM. The second patient was a female who developed increasing irritability at age 16 months and 21 months, each time associated with introduction of TPM and resolved promptly upon withdrawal of the drug. Venous blood gas taken during the second episode revealed pH 7.34, PCO2 37.4 mmHg, bicarbonate 20.4 mEq/L, base excess -4.2 mmol/L. The predominant mechanism of TPM-induced hyperventilation involves inhibition of carbonic anhydrase at the proximal renal tubule, resulting in impaired proximal bicarbonate reabsorption. The occurrence of hyperpnoea or mental status change in any patient who is on TPM should prompt an urgent blood gas sampling, with correction of the acid-base disturbances accordingly. [source] Cytochrome oxidase deficiency presenting as birth asphyxiaDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 6 2000Tracey A Willis MRCPI Hypoxic-ischaemic encephalopathy (HIE) was diagnosed in an infant with acidosis. At 7 weeks of age further investigations revealed abnormal neuroimaging (CT and MRI scans) and a raised plasma and CSF lactate. A skeletal-muscle biopsy at 2 months of age confirmed the diagnosis of cytochrome oxidase deficiency. The course of the patient's disorder has taken that of a static encephalopathy (cerebral palsy). Inborn disorders of the respiratory chain should be considered in the differential diagnosis of HIE. [source] Combination therapy using metformin or thiazolidinediones and insulin in the treatment of diabetes mellitusDIABETES OBESITY & METABOLISM, Issue 6 2005Suzanne M. Strowig The biguanide, metformin, sensitizes the liver to the effect of insulin, suppressing hepatic glucose output. Thiazolidinediones such as rosiglitazone and pioglitazone enhance insulin-mediated glucose disposal, leading to reduced plasma insulin concentrations. These classes of drugs may also have varying beneficial effects on features of insulin resistance such as lipid levels, blood pressure and body weight. Metformin in combination with insulin has been shown to significantly improve blood glucose levels while lowering total daily insulin dose and body weight. The thiazolidinediones in combination with insulin have also been effective in lowering blood glucose levels and total daily insulin dose. Triple combination therapy using insulin, metformin and a thiazolidinedione improves glycaemic control to a greater degree than dual therapy using insulin and metformin or insulin and a thiazolidinedione. There is insufficient evidence to recommend the use of metformin or thiazolidinediones in type 1 diabetic patients. Although these agents are largely well tolerated, some subjects experience significant gastrointestinal problems while using metformin. Metformin is associated with a low risk of lactic acidosis, but should not be used in patients with elevated serum creatinine or those being treated for congestive heart failure. The thiazolidinediones are associated with an increase in body weight, although this can be avoided with careful lifestyle management. Thiazolidinediones may also lead to oedema and are associated with a low incidence of hepatocellular injury. Thiazolidinediones are contraindicated in patients with underlying heart disease who are at risk of congestive heart failure and in patients who have abnormal hepatic function. The desired blood glucose-lowering effect and adverse event profiles of these agents should be considered when recommending these agents to diabetic patients. The potential for metformin or the thiazolidinediones to impact long-term cardiovascular outcomes remains under investigation. [source] Type 1 (distal) renal tubular acidosis in a patient with Type 1 diabetes mellitus,not all cases of metabolic acidosis in Type 1 diabetes mellitus are due to diabetic ketoacidosisDIABETIC MEDICINE, Issue 1 2008J. A. Dymot No abstract is available for this article. [source] Establishing pragmatic estimated GFR thresholds to guide metformin prescribingDIABETIC MEDICINE, Issue 10 2007J. S. Shaw Abstract Aims, Renal impairment is a contraindication to metformin treatment because of the perceived increased risk of lactic acidosis. Current guidelines define renal impairment according to the serum creatinine of the individual, but this measure is being supplanted by the use of estimated glomerular filtration rate (eGFR) as it gives a closer estimate to true GFR. This study aimed to establish pragmatic eGFR limits for use in patients being considered for metformin treatment. Methods, Estimated GFR measurements corresponding to currently used metformin creatinine limits of 130 and 150 µmol/l were derived and then applied to 12 482 patients with diabetes in Hull and East Yorkshire. Results, Few patients with a serum creatinine of 130 or 150 µmol/l have an eGFR of < 30 ml/min/1.73 m2[chronic kidney disease (CKD) stage 4 or greater], while most are between 30 and 59 ml/min/1.73 m2 (CKD stage 3). When applied to the 12 482 patients (median age 67 years, interquartile range 56,75), males predominated when using creatinine cut-offs (13.6% of males and 8.3% of females had creatinine > 130 µmol/l; 8.2% males and 5.2% females > 150 µmol/l), but not using eGFR CKD thresholds (3.3% males and 4.7% females < 30 ml/min/1.73 m2; 20.8% males and 28.1% females eGFR 30,59 ml/min/1.73 m2). Similar proportions of patients as currently would have metformin withheld if using eGFR cut-offs between 30 and 49 ml/min/1.73 m2. Conclusions, We have proposed pragmatic eGFR limits to guide metformin prescribing in patients with renal impairment. CKD stage 4 or greater should be an absolute contraindication to metformin, while CKD stage 3 should alert clinicians to consider other risk factors before initiating or continuing treatment. [source] Evaluation of a bedside blood ketone sensor: the effects of acidosis, hyperglycaemia and acetoacetate on sensor performanceDIABETIC MEDICINE, Issue 7 2004A. S. A. Khan Abstract Aims To assess the performance of a handheld bedside ketone sensor in the face of likely metabolic disturbances in diabetic ketoacidosis, namely: pH, glucose and acetoacetate. Methods The effects of pH (7.44,6.83), glucose (5,50 mmol/l) and acetoacetate (0,5 mmol/l) were examined in venous blood to investigate the accuracy of betahydroxybutyrate measurement (0,5 mmol/l) by a handheld ketone sensor. Sensor results were compared with a reference method. Linear regression models were fitted to the difference between the methods with the concentration of metabolite as the explanatory factor. Results Decreasing pH and increasing glucose had no effect on the accuracy of the handheld ketone sensor; the gradients of the fitted lines were ,0.14 and ,0.003, respectively. The 95% confidence intervals were ,0.7,0.4 and ,0.01,0.004, respectively (P = 0.59 and 0.4, respectively). In the acetoacetate study, a positive relationship between the sensor and reference method results was found, the gradient was 0.09. The 95% confidence interval was 0.05,0.14 (P , 0.001), indicating that high concentrations of acetoacetate interfere with the sensor performance. Conclusions Acidosis and hyperglycaemia have minimal effects on the sensor performance. However, high concentrations of acetoacetate result in some overestimation of betahydroxybutyrate. This bedside ketone sensor provides useful data over a broad range of conditions likely to be encountered during moderate to severe diabetic ketoacidosis. [source] | ||||||||||||||||||||||||||||||||||||||||||||||