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1

Safe delivery of two parturient women in severe metabolic acidosis.  

PubMed

Care of an acutely ill parturient is particularly difficult when we have to balance the needs of both mother and the fetus to survive. The literature suggests there should be emphasis on stabilising the mother's condition. In dealing with metabolic acidosis, however, we believe delivering the baby early might not only relieve the threat of the acidosis on the mother, it may be the only way to deliver a live baby. We report two parturient women with severe metabolic acidosis which was considerably reduced very soon after the delivery and how our timely delivery resulted in the birth of two neurologically intact babies. PMID:24862427

Shariffuddin, Ina Ismiarti; Rai, Vineya; Chan, Y K; Muniandy, Rajesh Kumar

2014-01-01

2

Extreme ?-butyrolactone overdose with severe metabolic acidosis requiring hemodialysis.  

PubMed

?-Hydroxybutyrate (GHB) and its precursor ?-butyrolactone (GBL) are commonly abused drugs with a narrow therapeutic index. Therefore, overdoses occur readily with recreational use, and severe poisoning can occur after deliberate self-poisoning. We report the sequelae in a patient who ingested a massive dose of GBL, with suicidal intent. Severe metabolic acidosis and an asystolic cardiac arrest were successfully treated with standard resuscitation, supportive care, and continuous venovenous hemodiafiltration. Plasma GHB concentrations were the highest reported to date. The acidosis was attributed to rapid systemic absorption of GBL, followed by rapid metabolism to GHB. PMID:21435738

Roberts, Darren M; Smith, Myles W H; Gopalakrishnan, Manivannan; Whittaker, Geoffrey; Day, Richard O

2011-07-01

3

Metabolic acidosis  

MedlinePLUS

Arterial blood gas Serum electrolytes Urine pH Arterial blood gas analysis and a serum electrolytes test (such as a basic metabolic panel) will confirm acidosis is present and determine whether it is ...

4

Starvation Ketoacidosis: A Cause of Severe Anion Gap Metabolic Acidosis in Pregnancy  

PubMed Central

Pregnancy is a diabetogenic state characterized by relative insulin resistance, enhanced lipolysis, elevated free fatty acids and increased ketogenesis. In this setting, short period of starvation can precipitate ketoacidosis. This sequence of events is recognized as “accelerated starvation.” Metabolic acidosis during pregnancy may have adverse impact on fetal neural development including impaired intelligence and fetal demise. Short periods of starvation during pregnancy may present as severe anion gap metabolic acidosis (AGMA). We present a 41-year-old female in her 32nd week of pregnancy, admitted with severe AGMA with pH 7.16, anion gap 31, and bicarbonate of 5?mg/dL with normal lactate levels. She was intubated and accepted to medical intensive care unit. Urine and serum acetone were positive. Evaluation for all causes of AGMA was negative. The diagnosis of starvation ketoacidosis was established in absence of other causes of AGMA. Intravenous fluids, dextrose, thiamine, and folic acid were administered with resolution of acidosis, early extubation, and subsequent normal delivery of a healthy baby at full term. Rapid reversal of acidosis and favorable outcome are achieved with early administration of dextrose containing fluids. PMID:24963418

Venkatram, Sindhaghatta; Diaz-Fuentes, Gilda

2014-01-01

5

Successful recovery from iatrogenic severe hypernatremia and severe metabolic acidosis resulting from accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment.  

PubMed

Bicarbonate dialysis is the treatment modality of choice for correction of metabolic acidosis in chronic renal failure. However, improper selection of dialysate concentrate can result in life-threatening human errors. We report a case of iatrogenic severe hypernatremia (sodium 207 mEq/L) and severe metabolic acidosis (pH 6.65) that resulted due to accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment. There was successful recovery in this patient with no neurological sequelae. To the best of our knowledge, this is the first case report in adults of severe hypernatremia along with severe metabolic acidosis due to error in the preparation of dialysis fluid. PMID:25579726

Bhosale, Guruprasad P; Shah, Veena R

2015-01-01

6

A patient presenting with metabolic acidosis despite severe vomiting--correct diagnosis by use of the physical-chemical approach.  

PubMed

We describe the case of a 28-year-old otherwise healthy woman who presents to our emergency department with nausea for 2 days and severe vomiting for 1 day. She has no history of travel, and her medical history is unremarkable. The physical examination shows a soft and nontender abdomen. Laboratory examinations reveal the presence of significant metabolic alkalosis despite the severe vomiting of the patient. Hypochloremic alkalosis would be expected to be present in this patient. We explain how to correctly identify the rare cause of metabolic acidosis present in this patient using the physicochemical approach (Stewarts approach) for the analysis of human acid-base disorders. PMID:23478114

Lindner, Gregor; Pfortmüller, Carmen; Exadaktylos, Aristomenis K

2013-06-01

7

Severe metabolic acidosis causes early lethality in NBC1 W516X knock-in mice as a model of human isolated proximal renal tubular acidosis.  

PubMed

We have identified a novel homozygous nonsense mutation (W516X) in the kidney-type electrogenic sodium bicarbonate cotransporter 1 (NBC1) in a patient with isolated proximal renal tubular acidosis (pRTA). To specifically address the pathogenesis of this mutation, we created NBC1 W516X knock-in mice to match the patient's abnormalities. The expression of NBC1 mRNA and protein in the kidneys of NBC1(W516X/W516X) mice were virtually absent, indicating that nonsense-mediated mRNA decay (NMD) is involved in the defective transcription and translation of this mutation. These mice not only recapitulated the phenotypes of this patient with growth retardation, pRTA, and ocular abnormalities, but also showed anemia, volume depletion, prerenal azotemia, and several organ abnormalities, culminating in dehydration and renal failure with early lethality before weaning. In isolated renal proximal tubules, both NBC1 activity and the rate of bicarbonate absorption were markedly reduced. Unexpectedly, there was no compensatory increase in mRNA of distal acid/base transporters. Sodium bicarbonate but not saline administration to these mutant mice markedly prolonged their survival, decreased their protein catabolism and attenuated organ abnormalities. The prolonged survival time uncovered the development of corneal opacities due to corneal edema. Thus, NBC1(W516X/W516X) mice with pRTA represent an animal model for metabolic acidosis and may be useful for testing therapeutic inhibition of NMD in vivo. PMID:21228764

Lo, Yi-Fen; Yang, Sung-Sun; Seki, George; Yamada, Hideomi; Horita, Shoko; Yamazaki, Osamu; Fujita, Toshiro; Usui, Tomohiko; Tsai, Jeng-Daw; Yu, I-Shing; Lin, Shu-Wha; Lin, Shih-Hua

2011-04-01

8

Metabolic acidosis and the progression of chronic kidney disease  

PubMed Central

Metabolic acidosis is a common complication of chronic kidney disease. Accumulating evidence identifies acidosis not only as a consequence of, but as a contributor to, kidney disease progression. Several mechanistic pathways have been identified in this regard. The dietary acid load, even in the absence of overt acidosis, may have deleterious effects. Several small trials now suggest that the treatment of acidosis with oral alkali can slow the progression of kidney disease. PMID:24708763

2014-01-01

9

Metabolic acidosis: neo-considerations for general surgeons  

PubMed Central

Hyperchloraemic metabolic acidosis is a documented complication of neobladder formation. However, it usually improves with time and is mild. Severe and persistent metabolic acidosis may manifest when patients undergo further surgery for other reasons. Neobladder formation following radical cystectomy or cystoprostatectomy is becoming increasingly more common, and surgeons treating patients with neobladders should recognise and treat metabolic acidosis with intravenous fluids and bicarbonate. PMID:23131216

Martin, LCE; Abah, U; Bean, E; Gupta, S

2012-01-01

10

Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress  

PubMed Central

Background A variety of oncogenic and environmental factors alter tumor metabolism to serve the distinct cellular biosynthetic and bioenergetic needs present during oncogenesis. Extracellular acidosis is a common microenvironmental stress in solid tumors, but little is known about its metabolic influence, particularly when present in the absence of hypoxia. In order to characterize the extent of tumor cell metabolic adaptations to acidosis, we employed stable isotope tracers to examine how acidosis impacts glucose, glutamine, and palmitate metabolism in breast cancer cells exposed to extracellular acidosis. Results Acidosis increased both glutaminolysis and fatty acid ?-oxidation, which contribute metabolic intermediates to drive the tricarboxylic acid cycle (TCA cycle) and ATP generation. Acidosis also led to a decoupling of glutaminolysis and novel glutathione (GSH) synthesis by repressing GCLC/GCLM expression. We further found that acidosis redirects glucose away from lactate production and towards the oxidative branch of the pentose phosphate pathway (PPP). These changes all serve to increase nicotinamide adenine dinucleotide phosphate (NADPH) production and counter the increase in reactive oxygen species (ROS) present under acidosis. The reduced novel GSH synthesis under acidosis may explain the increased demand for NADPH to recycle existing pools of GSH. Interestingly, acidosis also disconnected novel ribose synthesis from the oxidative PPP, seemingly to reroute PPP metabolites to the TCA cycle. Finally, we found that acidosis activates p53, which contributes to both the enhanced PPP and increased glutaminolysis, at least in part, through the induction of G6PD and GLS2 genes. Conclusions Acidosis alters the cellular metabolism of several major metabolites, which induces a significant degree of metabolic inflexibility. Cells exposed to acidosis largely rely upon mitochondrial metabolism for energy generation to the extent that metabolic intermediates are redirected away from several other critical metabolic processes, including ribose and glutathione synthesis. These alterations lead to both a decrease in cellular proliferation and increased sensitivity to ROS. Collectively, these data reveal a role for p53 in cellular metabolic reprogramming under acidosis, in order to permit increased bioenergetic capacity and ROS neutralization. Understanding the metabolic adaptations that cancer cells make under acidosis may present opportunities to generate anti-tumor therapeutic agents that are more tumor-specific. PMID:24359630

2013-01-01

11

Metabolic Acidosis of Chronically Hemodialyzed Patients  

Microsoft Academic Search

Metabolic acidosis is a condition that is commonly encountered in both chronic renal failure and in end-stage renal disease. Metabolic acidosis is associated with many adverse effects: negative nitrogen balance, increased protein decomposition, anorexia, fatigue, bone lesions, impaired function of the cardiovascular system, impaired function of the gastrointestinal system, hormonal disturbances, insulin resistance, hyperkalemia, altered gluconeogenesis and triglyceride metabolism, increased

Vedran Kovacic; Luka Roguljic; Vinko Kovacic

2003-01-01

12

Chronic metabolic acidosis destroys pancreas.  

PubMed

One primary reason for the current epidemic of digestive disorders might be chronic metabolic acidosis, which is extremely common in the modern population. Chronic metabolic acidosis primarily affects two alkaline digestive glands, the liver, and the pancreas, which produce alkaline bile and pancreatic juice with a large amount of bicarbonate. Even small acidic alterations in the bile and pancreatic juice pH can lead to serious biochemical/biomechanical changes. The pancreatic digestive enzymes require an alkaline milieu for proper function, and lowering the pH disables their activity. It can be the primary cause of indigestion. Acidification of the pancreatic juice decreases its antimicrobial activity, which can lead to intestinal dysbiosis. Lowering the pH of the pancreatic juice can cause premature activation of the proteases inside the pancreas with the potential development of pancreatitis. The acidification of bile causes precipitation of the bile acids, which irritate the entire biliary system and create bile stone formation. Aggressive mixture of the acidic bile and the pancreatic juice can cause erratic contractions of the duodenum's walls and subsequent bile reflux into the stomach and the esophagus. Normal exocrine pancreatic function is the core of proper digestion. Currently, there is no effective and safe treatment for enhancing the exocrine pancreatic function. Restoring normal acid-base homeostasis can be a useful tool for pathophysiological therapeutic approaches for various gastrointestinal disorders. There is strong research and practical evidence that restoring the HCO3- capacity in the blood can improve digestion. PMID:25435570

Melamed, Peter; Melamed, Felix

2014-01-01

13

Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis  

PubMed Central

Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial regarding clinical outcomes or mortality rate. Patients with advanced chronic kidney disease usually show metabolic acidosis due to increased unmeasured anions and hyperchloremia. It has been suggested that metabolic acidosis might have a negative impact on progression of kidney dysfunction and that sodium bicarbonate administration might attenuate this effect, but further evaluation is required to validate such a renoprotective strategy. Sodium bicarbonate is the predominant buffer used in dialysis fluids and patients on maintenance dialysis are subjected to a load of sodium bicarbonate during the sessions, suffering a transient metabolic alkalosis of variable severity. Side effects associated with sodium bicarbonate therapy include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation. The potential impact of regular sodium bicarbonate therapy on worsening vascular calcifications in patients with chronic kidney disease has been insufficiently investigated. PMID:25405229

Adeva-Andany, María M.; Fernández-Fernández, Carlos; Mouriño-Bayolo, David; Castro-Quintela, Elvira; Domínguez-Montero, Alberto

2014-01-01

14

Sodium bicarbonate therapy in patients with metabolic acidosis.  

PubMed

Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial regarding clinical outcomes or mortality rate. Patients with advanced chronic kidney disease usually show metabolic acidosis due to increased unmeasured anions and hyperchloremia. It has been suggested that metabolic acidosis might have a negative impact on progression of kidney dysfunction and that sodium bicarbonate administration might attenuate this effect, but further evaluation is required to validate such a renoprotective strategy. Sodium bicarbonate is the predominant buffer used in dialysis fluids and patients on maintenance dialysis are subjected to a load of sodium bicarbonate during the sessions, suffering a transient metabolic alkalosis of variable severity. Side effects associated with sodium bicarbonate therapy include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation. The potential impact of regular sodium bicarbonate therapy on worsening vascular calcifications in patients with chronic kidney disease has been insufficiently investigated. PMID:25405229

Adeva-Andany, María M; Fernández-Fernández, Carlos; Mouriño-Bayolo, David; Castro-Quintela, Elvira; Domínguez-Montero, Alberto

2014-01-01

15

Hemolytic Anemia and Metabolic Acidosis: Think about Glutathione Synthetase Deficiency.  

PubMed

Glutathione synthetase deficiency (GSSD) is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with hemolytic anemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low glutathione synthetase activity in erythrocytes or cultured skin fibroblasts. The prognosis seems to depend on early diagnosis and treatment. We report a 4 months old Tunisian male infant who presented with severe metabolic acidosis with high anion gap and hemolytic anemia. High level of 5-oxoproline was detected in her urine and diagnosis of GSSD was made. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. He died of severe metabolic acidosis and sepsis at the age of 15 months. PMID:25166299

Ameur, Salma Ben; Aloulou, Hajer; Nasrallah, Fehmi; Kamoun, Thouraya; Kaabachi, Naziha; Hachicha, Mongia

2015-02-01

16

Molecular and pathophysiologic mechanisms of hyperkalemic metabolic acidosis.  

PubMed Central

In summary, hyperkalemia may have a dramatic impact on ammonium production and excretion. Chronic hyperkalemia decreases ammonium production in the proximal tubule and whole kidney, inhibits absorption of NH4+ in the mTALH, reduces medullary interstitial concentrations of NH4+ and NH3, and decreases entry of NH4+ and NH3 into the medullary collecting duct. The potential for development of a hyperchloremic metabolic acidosis is greatly augmented when renal insufficiency with associated reduction in functional renal mass coexists with the hyperkalemia, or in the presence of aldosterone deficiency or resistance. Such a cascade of events helps to explain, in part, the hyperchloremic metabolic acidosis and reduction in net acid excretion characteristic of several experimental models of hyperkalemic-hyperchloremic metabolic acidosis including: obstructive nephropathy, selective aldosterone deficiency, and chronic amiloride administration (7.9). PMID:10881337

DuBose, T. D.

2000-01-01

17

Profound metabolic acidosis and oxoprolinuria in an adult  

Microsoft Academic Search

Introduction  Profound metabolic acidosis in critically ill adults sometimes remains unexplained despite extensive evaluation.\\u000a \\u000a \\u000a \\u000a Case Report  A 58-year-old female presented in a confused state to the emergency department; she had been confused for several days. Laboratory\\u000a evaluation revealed a high anion gap metabolic acidosis and modestly elevated acetaminophen level. Lactic acid was only modestly\\u000a elevated. There was no evidence of ketoacids, salicylate,

Michael J. Hodgman; James F. Horn; Christine M. Stork; Jeanna M. Marraffa; Michael G. Holland; Richard Cantor; Patti M. Carmel

2007-01-01

18

Clinical Metabolic Acidosis and Alkalosis  

Microsoft Academic Search

\\u000a Acid-base disturbances are common on the intensive care unit (ICU) and should always prompt a search for the underlying cause\\u000a (Tables 15.1–15.3). Recently another, although not all that new (1), way of understanding the mechanism behind acid-base disorders has gained popularity. This chapter starts with just a brief\\u000a discussion of this approach, because there are several excellent overviews in the

Sara Blakeley

19

Acidosis  

MedlinePLUS

... is caused by the loss of too much sodium bicarbonate from the body, which can happen with severe diarrhea. Lactic acidosis is a buildup of lactic acid . This can be caused by: Cancer Drinking too much alcohol Exercising vigorously for a ...

20

Cardiovascular responses to metabolic and respiratory acidosis and anesthesia in larval Ambystoma tigrinum  

Microsoft Academic Search

Larval Ambystoma tigrinum were examined to determine their cardiovascular responses to three types of acidosis: metabolic acidosis via NH4Cl gavage; respiratory acidosis via hypercapnia; and anesthetic-induced acidosis, via triacine methanesulphonate. In addition, another group of (metabolic acidosis) animals were tested to determine the role of ß-mediated catecholamine control on cardiovascular and acid-base regulation. The metabolic and respiratory acidoses produced typical

P. R. Territo; D. F. Stiffler

1994-01-01

21

Metabolic Acidosis in an Infant Associated with Permethrin Toxicity.  

PubMed

Pyrethroids are broad-spectrum insecticides. Permethrin intoxication due to topical application has not been documented in humans. We report a 20-month-old infant who had used 5% permethrin lotion topically for scabies treatment. Approximately 60 mL (20 mL/day) was used and after the third application he developed agitation, nausea, vomiting, respiratory distress, tachycardia, and metabolic acidosis. His clinical symptoms and metabolic acidosis normalized within 20 hours. His follow-up was unremarkable. Toxicity of permethrin is rare, and although permethrin is a widely and safely used topical agent in the treatment of scabies and lice, inappropriate use may rarely cause toxicity. Moreover, in cases of unexplained metabolic acidosis, topically applied medications should be carefully investigated. PMID:25487692

Goksugur, Sevil B; Karatas, Zehra; Goksugur, Nadir; Bekdas, Mervan; Demircioglu, Fatih

2014-12-01

22

Evaluation of acid-base status in brain dead donors and the impact of metabolic acidosis on organ retrieval.  

PubMed

Background: Pathophysiologic changes after brain death can lead to acid-base disturbances. The primary aim of this study was to clarify the acid-base state and its source in brain dead donors using Stewart's approach. Additionally, we investigated whether the presence of metabolic acidosis affected the number of organs retrieved from donors. Methods: A retrospective review of electronic medical records was performed for brain dead donors who had undergone organ harvesting during the past 5 years in a tertiary medical center. The parameters related to acidbase disturbance and the number of organs retrieved from the donors was assessed. Results: Sixty one brain dead donors were evaluated in this study. Twenty three (37.7%) of these patients had metabolic acidosis at the initial diagnosis of brain death. Metabolic acidosis resulted from hyperchloremia and a large strong ion gap. The severity of metabolic acidosis was masked by hypernatremia and hypoalbuminemia. In addition, donors without metabolic acidosis also showed mixed acid-base disturbances in which metabolic acidosis induced by significant hyperchloremia was combined with metabolic alkalosis caused by hypoalbuminemia and hypernatremia. Although more organs were retrieved from the donors without metabolic acidosis than those with metabolic acidosis (P=0.012), serum albumin level (P=0.010) and donor age (P<0.001), rather than metabolic acid-base disturbances, significantly correlated with the number of organs retrieved in multivariate regression analysis. Conclusion: Most brain dead donors exhibited metabolic acid-base disturbances. However, rather than metabolic acidosis, serum albumin level and donor age were well correlated with the number of organs retrieved. PMID:23652168

Lee, J H; Kim, M S; Na, S; Koh, S O; Sim, J; Choi, Y S

2013-05-01

23

Metabolic engineering of lactate dehydrogenase rescues mice from acidosis  

PubMed Central

Acidosis causes millions of deaths each year and strategies for normalizing the blood pH in acidosis patients are greatly needed. The lactate dehydrogenase (LDH) pathway has great potential for treating acidosis due to its ability to convert protons and pyruvate into lactate and thereby raise blood pH, but has been challenging to develop into a therapy because there are no pharmaceutical-based approaches for engineering metabolic pathways in vivo. In this report we demonstrate that the metabolic flux of the LDH pathway can be engineered with the compound 5-amino-2-hydroxymethylphenyl boronic acid (ABA), which binds lactate and accelerates the consumption of protons by converting pyruvate to lactate and increasing the NAD+/NADH ratio. We demonstrate here that ABA can rescue mice from metformin induced acidosis, by binding lactate, and increasing the blood pH from 6.7 to 7.2 and the blood NAD+/NADH ratio by 5 fold. ABA is the first class of molecule that can metabolically engineer the LDH pathway and has the potential to have a significant impact on medicine, given the large number of patients that suffer from acidosis. PMID:24898534

Acharya, Abhinav P.; Rafi, Mohammad; Woods, Elliot C.; Gardner, Austin B.; Murthy, Niren

2014-01-01

24

Effects of metabolic acidosis and alkalosis on sodium and calcium transport in the dog kidney  

Microsoft Academic Search

Effects of metabolic acidosis and alkalosis on sodium and calcium transport in the dog kidney. Clearance and micropuncture studies have been performed in dogs to examine the effects of acute and chronic metabolic acidosis and acute alkalosis on tubular sodium and calcium transport. Acute metabolic acidosis, induced by the infusion of hydrochloric acid, decreased proximal fluid reabsorption and increased the

Roger A L Sutton; Norman L M Wong; John H Dirks

1979-01-01

25

Effects of sodium pyruvate on ameliorating metabolic acidosis.  

PubMed

Objective: To examine the effects of sodium pyruvate (SP) on metabolic acidosis. Methods: For the in vivo experiments, we evaluated effects of SP on an ammonium chloride (NH4Cl)-induced hyperchloremic acidosis rat model. SP was infused at overall doses of 2, 4, and 6 mmol·kg(- 1) for the SP1, SP2, and SP3 groups, respectively. Treatment with sodium bicarbonate (SB) was used as a positive control (2 mmol·kg(- 1)), and treatment with normal saline (NS) was used as a volume control (2 mL·kg(- 1)). Blood was sampled from the ophthalmic venous plexus for pH, blood gases, electrolytes, glucose, creatinine (Cr), and urea analysis after injection. For the in vitro experiment, propionate was applied to induce intracellular acidosis in human endothelial cells. Intracellular pH (pHi) was fluorimetrically measured after the addition of SP. Results: In the in vivo study, the pH of SP1 group showed no significant difference compared with that of the NS group. The SP2 and SP3 groups had a higher pH than the NS group (P < 0.01). The SP3 group had a higher pH than the SB group (P < 0.05) and SP1 group (P < 0.05). Moreover, SP treatment ameliorated the abnormality of calcium and decreased the blood potassium levels. The SP3 group had higher glucose levels than SP1 group (P < 0.05). No significant differences were observed between all the groups in the plasma Cr and urea levels. In the in vitro study, the pHi increased immediately after the addition of SP. Conclusion: The data suggest that intravascular treatment with SP represents a novel therapeutic strategy to ameliorate metabolic acidosis. PMID:24697727

Yang, Jing; Zhao, Jing-Xiang; Wang, Ying; Chen, Gan; Cheng, Wei-Na; Luo, Xin; Pei, Xue-Tao; Zhao, Lian; Su, Qin; Zhou, Hong

2014-04-01

26

Metabolic acidosis and skeletal muscle adaptation to low protein diets in chronic uremia  

Microsoft Academic Search

Metabolic acidosis and skeletal muscle adaptation to low protein diets in chronic uremia. To maintain nitrogen equilibrium when prescribed a low protein diet (LPD), metabolic adaptations occur involving a reduction protein turnover, principally decreased muscle protein degradation. Studies suggest that in patients with chronic renal failure (CRF) uncomplicated by metabolic acidosis (MA), these adaptive responses are intact. Because MA stimulates

Bryan Williams; Jane Hattersley; Ellis Layward; John Walls

1991-01-01

27

High anion gap refractory metabolic acidosis as a critical presentation of endosulfan poisoning  

PubMed Central

Organochloride insecticides are chlorinated cyclic hydrocarbons. One of such insecticides is endosulfan (6,7,8,9,10-10 hexachloro 1,5,5a,6,9,9a-hexahydro-6-methano-2,4,3-hexadithioxanthiep in 3-oxide) and it has been widely used in agriculture since 1960. The uncontrolled use of these compounds in developing countries has resulted in the deaths of animals and humans. Characteristic clinical signs following acute exposure are indicative of CNS disturbances or overstimulation. Mortality and morbidity rates are high and there is no specific antidote. We present an uncommon presentation of endosulfan poisoning in a 32-year-old male with high anion gap severe refractory metabolic acidosis. The patient was treated with continuous renal replacement therapy and was salvaged. Till date, there is no case report from India for endosulfan poisoning with severe metabolic acidosis and hypotension. Through this case report, we emphasize the role of continuous renal replacement therapy as a rescue therapy for endosulfan poisoning with severe refractory metabolic acidosis and hypotension, even though it is a non dialyzable poison. PMID:21845009

Sharma, Raj Kumar; Kaul, Anupama; Gupta, Anurag; Bhadauria, Dharmendra; Prasad, Narayan; Jain, Apoorva; Gurjar, M.; Rao, Bhaskar P.

2011-01-01

28

Uncoventional Views on Certain Aspects of Toxin-Induced Metabolic Acidosis  

PubMed Central

This discussion will highlight the following 9 specific points that related to metabolic acidosis caused by various toxins. The current recommendation suggests that alcohol dehydrogenase inhibitor fomepizole is preferred to ethanol in treatment of methanol and ethylene glycol poisoning, but analysis of the enzyme kinetics indicates that ethanol is a better alternative. In the presence of a modest increase in serum osmolal gap (<30 mOsm/L), the starting dose of ethanol should be far less than the usual recommended dose. One can take advantage of the high vapor pressure of methanol in the treatment of methanol poisoning when hemodialysis is not readily available. Profuse sweating with increased water ingestion can be highly effective in reducing methanol levels. Impaired production of ammonia by the proximal tubule of the kidney plays a major role in the development of metabolic acidosis in pyroglutamic acidosis. Glycine, not oxalate, is the main final end product of ethylene glycol metabolism. Metabolism of ethylene glycol to oxalate, albeit important clinically, represents less than 1% of ethylene glycol disposal. Urine osmolal gap would be useful in the diagnosis of ethylene glycol poisoning, but not in methanol poisoning. Hemodialysis is important in the treatment of methanol poisoning and ethylene glycol poisoning with renal impairment, with or without fomepizole or ethanol treatment. Severe leucocytosis is a highly sensitive indicator of ethylene glycol poisoning. Uncoupling of oxidative phosphorylation by salicylate can explain most of the manifestations of salicylate poisoning. PMID:21468195

2010-01-01

29

Recovery from an activity-induced metabolic acidosis in the American alligator, Alligator mississippiensis  

E-print Network

Recovery from an activity-induced metabolic acidosis in the American alligator, Alligator studied recovery from this pH perturbation in the American alligator. Metabolic rate, minute ventilation in pH. © 2005 Elsevier Inc. All rights reserved. Keywords: Acid-base; Acidosis; Alligator

Bennett, Albert F.

30

Renal adaptation to metabolic acidosis in senescent rats  

SciTech Connect

In this study, the authors compared results obtained in senescent rats with young rats given an equivalent acid load. They examined the renal changes by giving equivalent acid loads for 48 h to both 6- and 24-mo-old rats. The basal excretion of ammonium was the same in both groups, whereas titratable acids, phosphate, and Ca{sup 2+} excretions were increased in the senescent animal. After administration of the acid load, ammonium, phosphate, Ca{sup 2+}, and titratable acid excretions increased in both age groups, but there were greater absolute increases in ammonium and titratable acid excretions in the young rats. The total acid excreted by the 24-mo rats was reduced 50 (day 1) and 25% (day 2) compared with the young rats, which was reflected by the more severe acidosis in those animals. The portion of total acid excreted as titratable acids in senescent animals was also increased during acidosis when compared with the young animals. In isolated proximal tubule brush-border membrane vesicles, acidosis increased Na{sup +}-H{sup +} exchange and decreased Na{sup +}-dependent phosphate transport in both age groups. They also found that the basal activity of the Na{sup +}-H{sup +} exchanger was not changed with age but the Na{sup +} dependent phosphate transporter was less in the 24-mo rat. The results suggest that physiological regulation of these renal processes remains intact in the aged rat but the responses may be reduced or delayed in the senescent animal.

Prasad, R.; Kinsella, J.L.; Sacktor, B. (National Institutes of Health, Baltimore, MD (USA))

1988-12-01

31

Potassium secretion is inhibited by metabolic acidosis in rabbit cortical collecting ducts in vitro.  

PubMed

The role of metabolic acidosis in the regulation of transepithelial potassium transport was examined in rabbit cortical collecting ducts (CCD) using in vitro isolated tubular microperfusion and conventional microelectrode techniques. Basolateral metabolic acidosis, created by reduction of bicarbonate concentration from 25 to 5 meq/l, pH 7.40 to 6.80, depolarized the transepithelial voltage significantly (-6.5 +/- 1.0 to -2.7 +/- 1.3 mV). Basolateral acidosis also suppressed net potassium secretion (-14.3 +/- 2.1 to -9.0 +/- 1.7 pmol.min-1.mm-1). Electrophysiological study in CCD cells demonstrated that basolateral metabolic acidosis depolarized transepithelial voltage and apical and basolateral membrane voltage with an increase of transepithelial and fractional apical resistance. Basolateral acidosis did not affect the 22Na efflux nor 86Rb efflux. The inhibitory action of basolateral acidosis on net potassium secretion remained in the presence of luminal barium and in the absence of bicarbonate. Ouabain could not abolish the effect of basolateral acidosis on transepithelial voltage completely. These data lead us to conclude that basolateral acidosis affects multiple transport pathways, and it inhibits mainly apical barium-sensitive potassium transport. Additionally, it inhibits apical sodium conductance, barium-insensitive potassium transport, and stimulates a ouabain-insensitive electrogenic transport pathway to some degree. PMID:7900849

Tabei, K; Muto, S; Furuya, H; Sakairi, Y; Ando, Y; Asano, Y

1995-03-01

32

Metabolic acidosis mimicking diabetic ketoacidosis after use of calorie-free mineral water.  

PubMed

A previously healthy boy was admitted with fever, tachycardia, dyspnea, and was vomiting. A blood test showed a severe metabolic acidosis with pH 7.08 and an anion gap of 36 mmol/L. His urine had an odor of acetone. The serum glucose was 5.6 mmol/L, and no glucosuria was found. Diabetic ketoacidosis could therefore be eliminated. Lactate level was normal. Tests for the most common metabolic diseases were negative. Because of herpes stomatitis, the boy had lost appetite and only been drinking Diet Coke and water the last days. Diet Coke or Coca-Cola Light is sweetened with a blend containing cyclamates, aspartame, and acesulfame potassium, all free of calories. The etiology of the metabolic acidosis appeared to be a catabolic situation exaggerated by fasting with no intake of calories. The elevated anion gap was due to a severe starvation ketoacidosis, mimicking a diabetic ketoacidosis. Pediatricians should recommend carbohydrate/calorie-containing fluids for rehydration of children with acute fever, diarrhea, or illness. PMID:22457081

Dahl, Gry T; Woldseth, Berit; Lindemann, Rolf

2012-09-01

33

[Acid-base homeostasis: metabolic acidosis and metabolic alkalosis].  

PubMed

Acid-base homeostasis ensured by the kidneys, which maintain the equilibrium between proton generation by cellular metabolism and proton excretion in urine. This requirement is lifesaving because of the protons' ability to bind to anionic proteins in the extracellular space, modifying their structure and functions. The kidneys also regenerate bicarbonates. The kidney is not the sole organ in charge of maintaining blood pH in a very narrow range; lungs are also involved since they allow a large amount of volatile acid generated by cellular respiration to be eliminated. PMID:24993393

Dussol, Bertrand

2014-07-01

34

Proteomic profiling and pathway analysis of the response of rat renal proximal convoluted tubules to metabolic acidosis  

PubMed Central

Metabolic acidosis is a relatively common pathological condition that is defined as a decrease in blood pH and bicarbonate concentration. The renal proximal convoluted tubule responds to this condition by increasing the extraction of plasma glutamine and activating ammoniagenesis and gluconeogenesis. The combined processes increase the excretion of acid and produce bicarbonate ions that are added to the blood to partially restore acid-base homeostasis. Only a few cytosolic proteins, such as phosphoenolpyruvate carboxykinase, have been determined to play a role in the renal response to metabolic acidosis. Therefore, further analysis was performed to better characterize the response of the cytosolic proteome. Proximal convoluted tubule cells were isolated from rat kidney cortex at various times after onset of acidosis and fractionated to separate the soluble cytosolic proteins from the remainder of the cellular components. The cytosolic proteins were analyzed using two-dimensional liquid chromatography and tandem mass spectrometry (MS/MS). Spectral counting along with average MS/MS total ion current were used to quantify temporal changes in relative protein abundance. In all, 461 proteins were confidently identified, of which 24 exhibited statistically significant changes in abundance. To validate these techniques, several of the observed abundance changes were confirmed by Western blotting. Data from the cytosolic fractions were then combined with previous proteomic data, and pathway analyses were performed to identify the primary pathways that are activated or inhibited in the proximal convoluted tubule during the onset of metabolic acidosis. PMID:23804448

Schauer, Kevin L.; Freund, Dana M.; Prenni, Jessica E.

2013-01-01

35

The effects of acidosis and alkalosis on coronary flow and cardiac nucleotide metabolism  

Microsoft Academic Search

Summary The changes of the coronary flows and of the cardiac nucleotide metabolism during acidosis and during alkalosis were studied in 50 perfused guinea pig hearts with and without hypoxia. At pH 7.0 the coronary flows increased, and at pH 7.8 a significant reduction of the flows took place. At 20% O2, acidosis elicited a further flow increase, whereas alkalosis

F. H. Degenring

1976-01-01

36

Effects of acid-base abnormalities on blood capacity of transporting CO 2 : adverse effect of metabolic acidosis  

Microsoft Academic Search

Objective.To investigate the effects of some acid-base abnormalities on blood capacity of transporting CO2. Design. Prospective study. Setting. General and Cardiosurgical ICUs of a University hospital. Patients. Six groups of ten patients characterized by: metabolic alkalosis; respiratory alkalosis; absence of acid-base abnormalities; metabolic acidosis; uncompensated respiratory acidosis; and compensated respiratory acidosis. Measurements and results. The CO2 dissociation curve, Haldane effect,

F. Cavaliere; M. Antonelli; A. Arcangeli; G. Conti; M. Pennisi; R. Proietti

2002-01-01

37

Mild metabolic acidosis impairs the ?-adrenergic response in isolated human failing myocardium  

PubMed Central

Introduction Pronounced extracellular acidosis reduces both cardiac contractility and the ?-adrenergic response. In the past, this was shown in some studies using animal models. However, few data exist regarding how the human end-stage failing myocardium, in which compensatory mechanisms are exhausted, reacts to acute mild metabolic acidosis. The aim of this study was to investigate the effect of mild metabolic acidosis on contractility and the ?-adrenergic response of isolated trabeculae from human end-stage failing hearts. Methods Intact isometrically twitching trabeculae isolated from patients with end-stage heart failure were exposed to mild metabolic acidosis (pH 7.20). Trabeculae were stimulated at increasing frequencies and finally exposed to increasing concentrations of isoproterenol (0 to 1 × 10-6 M). Results A mild metabolic acidosis caused a depression in twitch-force amplitude of 26% (12.1 ± 1.9 to 9.0 ± 1.5 mN/mm2; n = 12; P < 0.01) as compared with pH 7.40. Force-frequency relation measurements yielded no further significant differences of twitch force. At the maximal isoproterenol concentration, the force amplitude was comparable in each of the two groups (pH 7.40 versus pH 7.20). However, the half-maximal effective concentration (EC50) was significantly increased in the acidosis group, with an EC50 of 5.834 × 10-8 M (confidence interval (CI), 3.48 × 10-8 to 9.779 × 10-8; n = 9), compared with the control group, which had an EC50 of 1.056 × 10-8 M (CI, 2.626 × 10-9 to 4.243 × 10-8; n = 10; P < 0.05), indicating an impaired ?-adrenergic force response. Conclusions Our data show that mild metabolic acidosis reduces cardiac contractility and significantly impairs the ?-adrenergic force response in human failing myocardium. Thus, our results could contribute to the still-controversial discussion about the therapy regimen of acidosis in patients with critical heart failure. PMID:22889236

2012-01-01

38

Muscle oxidative metabolism accelerates with mild acidosis during incremental intermittent isometric plantar flexion exercise  

Microsoft Academic Search

BACKGROUND: It has been thought that intramuscular ADP and phosphocreatine (PCr) concentrations are important regulators of mitochondorial respiration. There is a threshold work rate or metabolic rate for cellular acidosis, and the decrease in muscle PCr is accelerated with drop in pH during incremental exercise. We tested the hypothesis that increase in muscle oxygen consumption (o2mus) is accelerated with rapid

Toshiyuki Homma; Takafumi Hamaoka; Takayuki Sako; Motohide Murakami; Kazuki Esaki; Ryotaro Kime; Toshihito Katsumura

2005-01-01

39

Sevelamer hydrochloride dose-dependent increase in prevalence of severe acidosis in hemodialysis patients: analysis of nationwide statistical survey in Japan.  

PubMed

Metabolic acidosis has a negative impact on prognosis of dialysis patients. The aim of this study was to determine the prevalence of severe metabolic acidosis in dialysis patients treated with sevelamer hydrochloride. In 2004, a nationwide survey (101,516 dialysis patients) was conducted by the Japanese Society for Dialysis Therapy. We analyzed 32,686 dialysis patients whose bicarbonate levels were measured in the survey. Sevelamer hydrochloride was prescribed to 9231 dialysis patients while 23,455 dialysis patients were not prescribed sevelamer hydrochloride. In the present study, we defined severe acidosis as bicarbonate <15.8 mmol/L. The mean serum bicarbonate level correlated significantly and negatively with the daily dose of sevelamer hydrochloride (R(2)?= 0.806, P < 0.0001). Logistic regression analysis indicated that the percentage of patients with severe acidosis increased significantly with increased dose of sevelamer hydrochloride (R(2) = 0.885, P < 0.00001). The estimated doses of sevelamer hydrochloride associated with severe acidosis in 10% and 15% of patients were 3.5 g/day (95% confidence interval [95%CI], 2.8-4.4) and 7.7 g/day (95%CI = 5.9-10.9), respectively. Severe acidosis was noted in 4.5% of patients who were not treated with sevelamer hydrochloride and in 16.1% of patients treated with sevelamer hydrochloride at ? 5.25 g/day (P < 0.0001). The results call for careful monitoring of serum bicarbonate level in hemodialysis patients treated with sevelamer hydrochloride. PMID:24499082

Oka, Yoshinari; Miyazaki, Masashi; Matsuda, Hiroaki; Takatsu, Shigeko; Katsube, Ryouichi; Mori, Toshiko; Takehara, Kiyoto; Umeda, Yuzo; Uno, Futoshi

2014-02-01

40

Sympathetic Activation in Exercise Is Not Dependent on Muscle Acidosis Direct Evidence from Studies in Metabolic Myopathies  

Microsoft Academic Search

Muscle acidosis has been implicated as a major determinant of reflex sympathetic activation during exercise. To test this hypothesis we studied sympathetic exercise responses in metabolic myopathies in which muscle acidosis is impaired or augmented during exercise. As an index of reflex sympa- thetic activation to muscle, microneurographic measure- ments of muscle sympathetic nerve activity (MSNA) were obtained from the

John Vissing; Susanne F. Vissing; David A. MacLean; Bengt Saltin; Bjørn Quistorff; Ronald G. Haller

41

Construction and validation of a decision tree for treating metabolic acidosis in calves with neonatal diarrhea  

PubMed Central

Background The aim of the present prospective study was to investigate whether a decision tree based on basic clinical signs could be used to determine the treatment of metabolic acidosis in calves successfully without expensive laboratory equipment. A total of 121 calves with a diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital were included in the study. The dosages of sodium bicarbonate administered followed simple guidelines based on the results of a previous retrospective analysis. Calves that were neither dehydrated nor assumed to be acidemic received an oral electrolyte solution. In cases in which intravenous correction of acidosis and/or dehydration was deemed necessary, the provided amount of sodium bicarbonate ranged from 250 to 750?mmol (depending on alterations in posture) and infusion volumes from 1 to 6.25 liters (depending on the degree of dehydration). Individual body weights of calves were disregarded. During the 24?hour study period the investigator was blinded to all laboratory findings. Results After being lifted, many calves were able to stand despite base excess levels below ?20?mmol/l. Especially in those calves, metabolic acidosis was undercorrected with the provided amount of 500?mmol sodium bicarbonate, which was intended for calves standing insecurely. In 13 calves metabolic acidosis was not treated successfully as defined by an expected treatment failure or a measured base excess value below ?5?mmol/l. By contrast, 24?hours after the initiation of therapy, a metabolic alkalosis was present in 55 calves (base excess levels above +5?mmol/l). However, the clinical status was not affected significantly by the metabolic alkalosis. Conclusions Assuming re-evaluation of the calf after 24?hours, the tested decision tree can be recommended for the use in field practice with minor modifications. Calves that stand insecurely and are not able to correct their position if pushed require higher doses of sodium bicarbonate, if there is clinical evidence of a marked D-lactic acidosis. In those calves, determining the degree of loss of the palpebral reflex was identified as a useful decision criterion to provide an additional amount of 250?mmol sodium bicarbonate. This work demonstrates the clinical relevance of the discovery that D-lactate is responsible for most of the clinical signs expressed in neonatal diarrheic calves suffering from metabolic acidosis. PMID:23216654

2012-01-01

42

The effect of metabolic acidosis and alkalosis on the H +ATPase of rat cerebral microvessels  

Microsoft Academic Search

To determine the role of the proton translocating adenosine triphosphatase (H+-ATPase) of the blood-brain barrier, the density of the 31 Kd subunit of the vacuolar type H+-ATPase was quantitated in isolated rat cerebral microvessels with immunoblotting techniques. To establish the tissue specificity of the findings, synaptosomal membranes were also studied. Metabolic acidosis was induced with 1.5% ammonium chloride in drinking

Arshag D. Mooradian; Bahar Bastani

1997-01-01

43

Rh versus pH: the role of Rhesus glycoproteins in renal ammonia excretion during metabolic acidosis in a freshwater teleost fish.  

PubMed

Increased renal ammonia excretion in response to metabolic acidosis is thought to be a conserved response in vertebrates. We tested the hypothesis that Rhesus (Rh) glycoproteins in the kidney of the freshwater common carp, Cyprinus carpio, play a crucial role in regulating renal ammonia excretion during chronic metabolic acidosis. Exposure to water pH 4.0 (72 h) resulted in a classic metabolic acidosis with reduced plasma arterial pH and [HCO3(-)], no change in PCO2 and large changes in renal function. Urine [NH4(+)] as well as [titratable acidity-HCO3(-)] rose significantly over the acid exposure, but the profound reduction (fivefold) in urine flow rates eliminated the expected elevations in renal ammonia excretion. Low urine flow rates may be a primary strategy to conserve ions, as urinary excretion rates of Na(+), Cl(-) and Ca(2+) were significantly lower during the acid exposure relative to the control period. Interestingly, renal Rhcg1 mRNA and protein levels were elevated in acid-exposed relative to control groups, along with mRNA levels of several ion transporters, including the Na(+)/H(+) exchanger, H(+)-ATPase and Na(+)/K(+)-ATPase. Immunofluorescence microscopy showed a strong apical Rhcg1 signal in distal tubules. Taken together, these data show that renal Rh glycoproteins and associated ion transporters are responsive to metabolic acidosis, but conservation of ions through reduced urine flow rates takes primacy over renal acid-base regulation in the freshwater C. carpio. We propose that an 'acid/base-ion balance' compromise explains the variable renal responses to metabolic acidosis in freshwater teleosts. PMID:24855681

Wright, Patricia A; Wood, Chris M; Wilson, Jonathan M

2014-08-15

44

Sevelamer hydrochloride exacerbates metabolic acidosis in hemodialysis patients, depending on the dosage.  

PubMed

Sevelamer hydrochloride, as a phosphate binder that contains neither aluminum nor calcium, is expected to improve the prognosis of dialysis patients. However, sevelamer hydrochloride has been reported to lower the serum bicarbonate level. In the present study, we performed a retrospective study on the potential influences of sevelamer hydrochloride on metabolic acidosis in hemodialysis patients. The subjects were 72 patients who underwent hemodialysis at our hospital. Thirty-six patients taking sevelamer hydrochloride and 36 patients matched for sex, diabetes mellitus, age and duration of dialysis who were not taking sevelamer hydrochloride were studied. We assigned the 36 patients who had been taking sevelamer hydrochloride to the 'sevelamer group', and the 36 patients not taking sevelamer hydrochloride were the control group. Statistical significance was evaluated by a t-test and Pearson's correlation coefficient. In the sevelamer group, the mean levels of bicarbonate, base excess and pH decreased significantly after administration, compared with the values before administration, but in the control group, aggravation of acidosis was not seen. The levels of bicarbonate, base excess and pH after the medication of sevelamer hydrochloride were found to be significantly and negatively correlated with the daily dose of sevelamer hydrochloride. The levels were also found to be significantly and negatively correlated with the cumulative dose of sevelamer hydrochloride; however, the value of the mean levels of chlorine and the anion gap did not increase with sevelamer hydrochloride. Sevelamer hydrochloride caused metabolic acidosis in a dose-dependent manner in hemodialysis patients without hyperchloremia. PMID:17381531

Oka, Yoshinari; Miyazaki, Masashi; Takatsu, Shigeko; Kunitomo, Kei-ichi; Uno, Futoshi; Maruyama, Masanobu; Matsuda, Hiroaki

2007-04-01

45

Experimentally-Induced Metabolic Acidosis Does not Alter Aortic Fatty Streak Formation in High-Cholesterol Fed Rabbits  

PubMed Central

Objective(s) Cardiovascular disease causes a major clinical problem in patients with end stage renal disease. Since metabolic acidosis is very common in patients with end stage renal disease, we aimed to investigate the effect of experimentally-induced metabolic acidosis on serum lipid profile and aortic fatty streak (FS) formation in normal and high-cholesterol fed rabbits. Materials and Methods Twenty-four male rabbits were divided into four groups (n=6 each): (1) normal diet (ND): (2) hypercholesterolemic diet (HCD) (1%): (3) ND plus acidemic diet: (4) HCD plus acidemic diet. Metabolic acidosis was induced by adding 0.75% NH4Cl in drinking water. After 4 weeks, blood samples were taken and thoracic aortae were dissected for histological examinations. Results Results showed that in the animals who received NH4Cl, metabolic acidosis was successfully induced. Serum total cholesterol and low density lipoprotein (LDL) concentrations in HCD groups were significantly higher than ND groups (P<0.05) and acidosis did not significantly change serum lipid levels neither in ND nor in HCD animals (P>0.05). Histological examination of aortae showed higher mean average grades of pathological evaluation in HCD than ND groups (2.1±0.16 vs. 0±0; P<0.05). Acidosis did not further increase FS formation in HCD groups (P >0.05). Conclusion In this model of experimentally-induced metabolic acidosis, acidosis could not increase FS formation in HCD animals and it seems that it does not interfere in progression of atherosclerosis process. PMID:23653846

Khazaei, Majid; Nematbakhsh, Mehdi

2012-01-01

46

Clinical Predictors and Outcome of Metabolic Acidosis in Under-Five Children Admitted to an Urban Hospital in Bangladesh with Diarrhea and Pneumonia  

Microsoft Academic Search

BackgroundClinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome.MethodsWe prospectively

Mohammod J. Chisti; Tahmeed Ahmed; Hasan Ashraf; A. S. G. Faruque; Pradip K. Bardhan; Sanjoy Kumer Dey; Sayeeda Huq; Sumon Kumar Das; Mohammed A. Salam

2012-01-01

47

The respiratory control system: Analysis of steady state solutions for metabolic and respiratory acidosis-alkalosis and increased metabolism  

Microsoft Academic Search

A system analysis of the respiratory regulator is presented which allows to predict the steady state values of the alveolar ventilation and the pH in the extracellular fluid of the brain in respiratory and metabolic acidosis or alkalosis and during increase or decrease of CO2 production. The brain extracellular fluid pH is considered as the controlled value and the mechanical

H. H. Loeschcke

1973-01-01

48

Enhanced Na(+)-H+ exchanger activity and NHE-1 mRNA levels in human lymphocytes during metabolic acidosis.  

PubMed

It has recently been demonstrated that uremic metabolic acidosis and experimental metabolic acidosis caused by ingestion of ammonium chloride coincide with increased Na(+)-H+ exchanger (NHE-1) activity in human blood cells. In the present study, we investigated whether an increased level of NHE-1 specific mRNA in human lymphocytes during the course of an experimental metabolic acidosis could explain the enhanced transport activity during metabolic acidosis. Six healthy individuals were studied before and after 5 days of taking 15 g of ammonium chloride daily. Plasma pH and bicarbonate decreased significantly, from 7.42 +/- 0.027 to 7.28 +/- 0.05 and from 26.7 +/- 2.0 to 15.6 +/- 2.9 mM, respectively. Basal cytosolic pH (pHi) and Na(+)-H+ exchange activity were measured in lymphocytes loaded with the fluorescent pHi indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Basal pHi remained unchanged during metabolic acidosis (7.03 +/- 0.07 vs. 7.03 +/- 0.06). Ethylisopropylamiloride-sensitive pHi recovery increased from 0.046 +/- 0.007 to 0.076 +/- 0.012 dpHi/min (P < 0.0001). The transcript level of NHE-1 mRNA was measured by reverse-transcription polymerase chain reaction in comparison with a constitutively expressed reference gene (glyceraldehyde-3-phosphate dehydrogenase). NHE-1 mRNA in human lymphocytes increased 1.5-fold in metabolic acidosis. These data suggest that the increased Na(+)-H+ exchange activity in metabolic acidosis may be caused by de novo synthesis of antiport protein. PMID:7511337

Quednau, B; Rosskopf, D; Reusch, H P; Luft, F C; Siffert, W

1994-02-01

49

Na+/H+ exchange in human lymphocytes and platelets in chronic and subacute metabolic acidosis.  

PubMed

The effect of acid-base disturbances on sodium/proton (Na+/H+) exchange has been examined in animal models; however, few data are available from human studies. To test the effect of metabolic acidosis on Na+/H+ exchange in man, as well as to examine the relationship between Na+/H+ exchange and cytosolic calcium ([Ca2+]i), we measured both variables in patients with decreased renal function with mild metabolic acidosis (pH 7.34 +/- 0.06), in normal control subjects (pH 7.41 +/- 0.02), and in subjects before (pH 7.40 +/- 0.01), and after (pH 7.26 +/- 0.04) ammonium chloride (NH4Cl) 15 g for 5 d. Lymphocytes and platelets were loaded with the cytosolic pH (pHi) indicator 2'-7'-bis(carboxyethyl)-5,6-carboxyfluorescein and acidified to pH approximately 6.6 with propionic acid. To quantitate Na+/H+ exchange, dpHi/dt was determined at 1 min. [Ca2+]i was measured with fura-2. Na+/H+ exchange was significantly increased only in lymphocytes of patients with renal insufficiency. Neither intracellular pH (pHi) nor [Ca2+]i was different from controls. NH4Cl resulted in a significant increase in Na+/H+ exchange in lymphocytes, but not in platelets of normal subjects. Values of pHi and [Ca2+]i in either cell type remained unaffected. Since metabolic acidosis influenced Na+/H+ only in lymphocytes, but not in platelets, it is possible that protein synthesis may be involved in increasing Na+/H+ exchange. PMID:8394388

Reusch, H P; Reusch, R; Rosskopf, D; Siffert, W; Mann, J F; Luft, F C

1993-08-01

50

Liquid chromatographic–mass spectrometric method for simultaneous determination of small organic acids potentially contributing to acidosis in severe malaria?  

PubMed Central

Acidosis is an important cause of mortality in severe falciparum malaria. Lactic acid is a major contributor to metabolic acidosis, but accounts for only one-quarter of the strong anion gap. Other unidentified organic acids have an independent strong prognostic significance for a fatal outcome. In this study, a simultaneous bio-analytical method for qualitative and quantitative assessment in plasma and urine of eight small organic acids potentially contributing to acidosis in severe malaria was developed and validated. High-throughput strong anion exchange solid-phase extraction in a 96-well plate format was used for sample preparation. Hydrophilic interaction liquid chromatography (HILIC) coupled to negative mass spectroscopy was utilized for separation and detection. Eight possible small organic acids; l-lactic acid (LA), ?-hydroxybutyric acid (aHBA), ?-hydroxybutyric acid (bHBA), p-hydroxyphenyllactic acid (pHPLA), malonic acid (MA), methylmalonic acid (MMA), ethylmalonic acid (EMA) and ?-ketoglutaric acid (aKGA) were analyzed simultaneously using a ZIC-HILIC column with an isocratic elution containing acetonitrile and ammonium acetate buffer. This method was validated according to U.S. Food and Drug Administration guidelines with additional validation procedures for endogenous substances. Accuracy for all eight acids ranged from 93.1% to 104.0%, and the within-day and between-day precisions (i.e. relative standard deviations) were lower than 5.5% at all tested concentrations. The calibration ranges were: 2.5–2500 ?g/mL for LA, 0.125–125 ?g/mL for aHBA, 7.5–375 ?g/mL for bHBA, 0.1–100 ?g/mL for pHPLA, 1–1000 ?g/mL for MA, 0.25–250 ?g/mL for MMA, 0.25–100 ?g/mL for EMA, and 30–1500 ?g/mL for aKGA. Clinical applicability was demonstrated by analyzing plasma and urine samples from five patients with severe falciparum malaria; five acids had increased concentrations in plasma (range LA = 177–1169 ?g/mL, aHBA = 4.70–38.4 ?g/mL, bHBA = 7.70–38.0 ?g/mL, pHPLA = 0.900–4.30 ?g/mL and aKGA = 30.2–32.0) and seven in urine samples (range LA = 11.2–513 ?g/mL, aHBA = 1.50–69.5 ?g/mL, bHBA = 8.10–111 ?g/mL, pHPLA = 4.30–27.7 ?g/mL, MMA = 0.300–13.3 ?g/mL, EMA = 0.300–48.1 ?g/mL and aKGA = 30.4–107 ?g/mL). In conclusion, a novel bioanalytical method was developed and validated which allows for simultaneous quantification of eight small organic acids in plasma and urine. This new method may be a useful tool for the assessment of acidosis in patients with severe malaria, and other conditions complicated by acidosis. PMID:24200840

Sriboonvorakul, Natthida; Leepipatpiboon, Natchanun; Dondorp, Arjen M.; Pouplin, Thomas; White, Nicholas J.; Tarning, Joel; Lindegardh, Niklas

2013-01-01

51

Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats.  

PubMed

Chronic metabolic acidosis (CMA) might result in a decrease in vivo in bone mass based on its reported in vitro inhibition of bone mineralization, bone formation, or stimulation of bone resorption, but such data, in the absence of other disorders, have not been reported. CMA also results in negative nitrogen balance, which might decrease skeletal muscle mass. This study analyzed the net in vivo effects of CMA's cellular and physicochemical processes on bone turnover, trabecular and cortical bone density, and bone microarchitecture using both peripheral quantitative computed tomography and ?CT. CMA induced by NH4Cl administration (15 mEq/kg body wt/day) in intact and ovariectomized (OVX) rats resulted in stable CMA (mean ?[HCO3(-)]p = 10 mmol/l). CMA decreased plasma osteocalcin and increased TRAP5b in intact and OVX animals. CMA decreased total volumetric bone mineral density (vBMD) after 6 and 10 wk (week 10: intact normal +2.1 ± 0.9% vs. intact acidosis -3.6 ± 1.2%, P < 0.001), an effect attributable to a decrease in cortical thickness and, thus, cortical bone mass (no significant effect on cancellous vBMD, week 10) attributed to an increase in endosteal bone resorption (nominally increased endosteal circumference). Trabecular bone volume (BV/TV) decreased significantly in both CMA groups at 6 and 10 wk, associated with a decrease in trabecular number. CMA significantly decreased muscle cross-sectional area in the proximal hindlimb at 6 and 10 wk. In conclusion, chronic metabolic acidosis induces a large decrease in cortical bone mass (a prime determinant of bone fragility) in intact and OVX rats and impairs bone microarchitecture characterized by a decrease in trabecular number. PMID:24352505

Gasser, Jürg A; Hulter, Henry N; Imboden, Peter; Krapf, Reto

2014-03-01

52

Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate.  

PubMed

Alkali therapy of metabolic acidosis in patients with chronic kidney disease (CKD) with plasma total CO2 (TCO2) below 22?mmol/l per KDOQI guidelines appears to preserve estimated glomerular filtration rate (eGFR). Since angiotensin II mediates GFR decline in partial nephrectomy models of CKD and even mild metabolic acidosis increases kidney angiotensin II in animals, alkali treatment of CKD-related metabolic acidosis in patients with plasma TCO2 over 22?mmol/l might preserve GFR through reduced kidney angiotensin II. To test this, we randomized 108 patients with stage 3 CKD and plasma TCO2 22-24?mmol/l to Usual Care or interventions designed to reduce dietary acid by 50% using sodium bicarbonate or base-producing fruits and vegetables. All were treated to achieve a systolic blood pressure below 130?mm?Hg with regimens including angiotensin converting enzyme inhibition and followed for 3 years. Plasma TCO2 decreased in Usual Care but increased with bicarbonate or fruits and vegetables. By contrast, urine excretion of angiotensinogen, an index of kidney angiotensin II, increased in Usual Care but decreased with bicarbonate or fruits and vegetables. Creatinine-calculated and cystatin C-calculated eGFR decreased in all groups, but loss was less at 3 years with bicarbonate or fruits and vegetables than Usual Care. Thus, dietary alkali treatment of metabolic acidosis in CKD that is less severe than that for which KDOQI recommends therapy reduces kidney angiotensin II activity and preserves eGFR. PMID:24694986

Goraya, Nimrit; Simoni, Jan; Jo, Chan-Hee; Wesson, Donald E

2014-11-01

53

Phosphate binders and metabolic acidosis in patients undergoing maintenance hemodialysis-sevelamer hydrochloride, calcium carbonate, and bixalomer.  

PubMed

The serum bicarbonate (HCO3 (-) ) levels are decreased in chronic hemodialysis (HD) patients treated with sevelamer hydrochloride (SH). We assessed the effects of bixalomer on the chronic metabolic acidosis in these patients. We examined 12 of the 122 consecutive Japanese patients with end-stage renal disease on HD, who orally ingested a dose of SH (?2250?mg), and an arterial blood gas analysis and biochemical analysis were performed before HD. Patients whose serum HCO3 (-) levels were under 18?mmol/L were changed from SH to the same dose of bixalomer. A total of 12 patients were treated with a large amount of SH. Metabolic acidosis (a serum HCO3 (-) level under 18?mmol/L) was found in eight patients. These patients were also treated with or without small dose of calcium carbonate (1.2?±?1.1?g). The dose of SH was changed to that of bixalomer. After 1 month, the serum HCO3 (-) levels increased from 16.3?±?1.4 to 19.6?±?1.7?mmol/L (P?Metabolic acidosis was not observed in four patients (serum HCO3 (-) level: 20.3?±?0.7?mmol/L) likely because they were taking 3?g of calcium carbonate with SH. In the present study, the development of chronic metabolic acidosis was induced by HCl containing phosphate binders, such as SH, and partially ameliorated by calcium carbonate, then subsequently improved after changing the treatment to bixalomer. PMID:24980286

Sanai, Toru; Tada, Hideo; Ono, Takashi; Fukumitsu, Toma

2015-01-01

54

Case 76: A Severe Case of Metabolic Acidosis  

Microsoft Academic Search

\\u000a A 48-year-old otherwise healthy female (68 kg and 5 ft 7 in.) with Moyamoya ­disease is scheduled for an extracranial–intracranial\\u000a revascularization (EC–IC bypass). She has a past history of hypertension and hyperlipidemia. Her kidney function is deemed\\u000a normal. She is having this procedure since she has had transient ischemic episodes recently. Five days prior to the surgery,\\u000a she stopped taking

John G. Brock-Utne

55

[A case of metabolic acidosis and tetany after ileal neobladder replacement].  

PubMed

A 64-year-old man visited our hospital with the complaint of macrohematuria and bilateral hydronephrosis. He had undergone total cystectomy and ileal neobladder replacement under the diagnosis of muscle invasive bladder cancer (cT2bN0M0). Tetany due to hyperventilation syndrome appeared on postoperative day 42. Blood gas analysis showed metabolic acidosis (pH 7.260, pO2 148.1 mmHg, pCO2 20.7 mmHg, HCO3 9.1 mmHg, BE -16.0 mmol/l). His condition was immediately improved after a urethral catheter was placed and sodium bicarbonate was administered. After re-removal of the urethral catheter, however, hyperventilation syndrome recurred. He was discharged from the hospital with the urethral catheter placed. PMID:23995533

Nomura, Hironori; Kou, Yohko; Kinjyo, Takanori; Nonomura, Daichi; Yoneda, Suguru; Yamamoto, Yoshiyuki; Tei, Norihide; Takada, Shingo; Matsumiya, Kiyomi

2013-08-01

56

Endothelin and nitric oxide mediate adaptation of the cortical collecting duct to metabolic acidosis.  

PubMed

Endothelin (ET) and nitric oxide (NO) modulate ion transport in the kidney. In this study, we defined the function of ET receptor subtypes and the NO guanylate cyclase signaling pathway in mediating the adaptation of the rabbit cortical collecting duct (CCD) to metabolic acidosis. CCDs were perfused in vitro and incubated for 3 h at pH 6.8, and bicarbonate transport or cell pH was measured before and after acid incubation. Luminal chloride was reversibly removed to isolate H(+) and HCO(3)(-) secretory fluxes and to raise the pH of beta-intercalated cells. Acid incubation caused reversal of polarity of net HCO(3)(-) transport from secretion to absorption, comprised of a 40% increase in H(+) secretion and a 75% decrease in HCO(3)(-) secretion. The ET(B) receptor antagonist BQ-788, as well as the NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME), attenuated the adaptive decrease in HCO(3)(-) secretion by 40%, but only BQ-788 inhibited the adaptive increase in H(+) secretion. There was no effect of inactive d-NAME or the ET(A) receptor antagonist BQ-123. Both BQ-788 and l-NAME inhibited the acid-induced inactivation (endocytosis) of the apical Cl(-)/HCO(3)(-) exchanger. The guanylate cyclase inhibitor LY-83583 and cGMP-dependent protein kinase inhibitor KT-5823 affected HCO(3)(-) transport similarly to l-NAME. These data indicate that signaling via the ET(B) receptor regulates the adaptation of the CCD to metabolic acidosis and that the NO guanylate cyclase component of ET(B) receptor signaling mediates downregulation of Cl(-)/HCO(3)(-) exchange and HCO(3)(-) secretion. PMID:16705153

Tsuruoka, Shuichi; Watanabe, Seiji; Purkerson, Jeffrey M; Fujimura, Akio; Schwartz, George J

2006-10-01

57

The infusion rate dependent influence of acute metabolic acidosis on pulmonary vascular resistance in broilers.  

PubMed

Experiments were conducted to evaluate the pulmonary vascular responses of lightly anesthetized clinically healthy male broilers during acute metabolic acidosis induced by bolus i.v. injections or constant i.v. infusions of HCl. In Experiment 1, broilers received consecutive 1.5 mL i.v. bolus injections of 2.5% mannitol (volume control) and 0.4 N, 0.8 N, and 1.2 N HCl in 2.5% mannitol. Following each injection, equivalent concentrations of mannitol or HCl were infused i.v. at a rate of 0.05 mL/min.kg BW. In Experiment 2, repeated bolus injections of 2.5% mannitol and 1.2 N HCl were administered during ongoing constant infusion of 2.5% mannitol. The following variables were evaluated: pulmonary arterial pressure, pulmonary vascular resistance, mean arterial pressure, total peripheral resistance, cardiac output, stroke volume, heart rate, respiratory rate, hematocrit (HCT), and arterial blood gas (PaO2, PaCO2, pH, HCO3-). Mannitol alone did not alter any of the variables. The HCl loading protocols acidified the arterial blood to sustained (constant infusion) or transient (bolus injection) values averaging between pH 7.2 and 7.3. In both experiments, bolus injections of 1.2 N HCl caused transient increases in pulmonary vascular resistance and pulmonary arterial pressure, coincident with decreases in mean arterial pressure and cardiac output. When HCl was infused at a constant rate in Experiment 1, the arterial blood hydrogen ion concentration, [H+], was positively correlated with pulmonary arterial pressure and cardiac output, negatively correlated with mean arterial pressure and total peripheral resistance, and was not correlated with pulmonary vascular resistance. During constant i.v. infusion of mannitol or HCl in both experiments, pulmonary arterial pressure was positively correlated with pulmonary vascular resistance and cardiac output. Overall, bolus injections of 1.2 N HCl consistently triggered transient pulmonary vasoconstriction (increased pulmonary vascular resistance), leading to a transient increase in pulmonary arterial pressure in spite of opposing changes in cardiac output and mean arterial pressure. In contrast, equivalent or greater increases in [H+] during constant i.v. infusion of HCl caused a substantially lower increment in pulmonary arterial pressure, which, in, turn was primarily attributable to increases in cardiac output rather than pulmonary vascular resistance. Increments in either pulmonary vascular resistance or cardiac output induced by metabolic acidosis would be expected to contribute to the onset of pulmonary hypertension syndrome (PHS, ascites) in broilers. PMID:9495499

Wideman, R F; Kochera Kirby, Y; Forman, M F; Marson, N; McNew, R W; Owen, R L

1998-02-01

58

Regulation of AE1 anion exchanger and H+ATPase in rat cortex by acute metabolic acidosis and alkalosis  

Microsoft Academic Search

Regulation of AE1 anion exchanger and H+-ATPase in rat cortex by acute metabolic acidosis and alkalosis. The cortical collecting duct (CCD) mediates net secretion or reabsorption of protons according to systemic acid\\/base status. Using indirect immunofluorescence, we examined the localization and abundance of the vacuolar H+-ATPase and the AE1 anion exchanger in intercalated cells (IC) of rat kidney connecting segment

Ivan Saboli?; Dennis Brown; Stephen L Gluck; Seth L Alper

1997-01-01

59

Respiratory acidosis  

MedlinePLUS

Ventilatory failure; Respiratory failure; Acidosis - respiratory ... Causes of respiratory acidosis include: Diseases of the airways (such as asthma and chronic obstructive lung disease ) Diseases of the chest ( ...

60

Metabolic Acidosis and Strong Ion Gap in Critically Ill Patients with Acute Kidney Injury  

PubMed Central

Purpose. To determine the influence of physicochemical parameters on survival in metabolic acidosis (MA) and acute kidney injury (AKI) patients. Materials and Methods. Seventy-eight MA patients were collected and assigned to AKI or non-AKI group. We analyzed the physiochemical parameters on survival at 24?h, 72?h, 1 week, 1 month, and 3 months after AKI. Results. Mortality rate was higher in the AKI group. AKI group had higher anion gap (AG), strong ion gap (SIG), and apparent strong ion difference (SIDa) values than non-AKI group. SIG value was higher in the AKI survivors than nonsurvivors and this value was correlated serum creatinine, phosphate, albumin, and chloride levels. SIG and serum albumin are negatively correlated with Acute Physiology and Chronic Health Evaluation IV scores. AG was associated with mortality at 1 and 3 months post-AKI, whereas SIG value was associated with mortality at 24?h, 72?h, 1 week, 1 month, and 3 months post-AKI. Conclusions. Whether high or low SIG values correlate with mortality in MA patients with AKI depends on its correlation with serum creatinine, chloride, albumin, and phosphate (P) levels. AG predicts short-term mortality and SIG value predicts both short- and long-term mortality among MA patients with AKI. PMID:25162029

Zheng, Cai-Mei; Liu, Wen-Chih; Zheng, Jing-Quan; Liao, Min-Tser; Ma, Wen-Ya; Lu, Chien-Lin; Lu, Kuo-Cheng

2014-01-01

61

An Unusual Initial Presentation of Sjögren’s Syndrome: Severe Hypokalemic Paralysis Secondary to Distal Renal Tubular Acidosis  

PubMed Central

Sjögren’s syndrome is mainly affects the exocrine glands. Patients usually complain of persistent dryness of the mouth and eyes. However, nonexocrine organs such as the kidneys are often affected in these patients. Distal renal tubular acidosis (dRTA) and interstitiel nephritis are common in Sjögren’s syndrome. Nonetheless, severe hypokalemia and paralysis secondary to dRTA are unusual initial manifestation of Sjögren’s syndrome. Here, we describe a case of a 48 year old women admitted to the emergency setting with severe hypokalemic paralysis and diagnosed Sjögren’s syndrome.

Sengul, Erkan; Bunul, Fatih; Yazici, Ayten; Sengul, Aysun; Dindar, Sevim; Halhalli, Gökçen Selma Kilic; Binnetoglu, Emine

2013-01-01

62

A Comparison of Treating Metabolic Acidosis in CKD Stage 4 Hypertensive Kidney Disease with Fruits and Vegetables or Sodium Bicarbonate  

PubMed Central

Summary Background and objectives Current guidelines recommend Na+-based alkali for CKD with metabolic acidosis and plasma total CO2 (PTCO2) < 22 mM. Because diets in industrialized societies are typically acid-producing, we compared base-producing fruits and vegetables with oral NaHCO3 (HCO3) regarding the primary outcome of follow-up estimated GFR (eGFR) and secondary outcomes of improved metabolic acidosis and reduced urine indices of kidney injury. Design, setting, participants, & measurements Individuals with stage 4 (eGFR, 15–29 ml/min per 1.73 m2) CKD due to hypertensive nephropathy, had a PTCO2 level < 22 mM, and were receiving angiotensin-converting enzyme inhibition were randomly assigned to 1 year of daily oral NaHCO3 at 1.0 mEq/kg per day (n=35) or fruits and vegetables dosed to reduce dietary acid by half (n=36). Results Plasma cystatin C–calculated eGFR did not differ at baseline and 1 year between groups. One-year PTCO2 was higher than baseline in the HCO3 group (21.2±1.3 versus 19.5±1.5 mM; P<0.01) and the fruits and vegetables group (19.9±1.7 versus 19.3±1.9 mM; P<0.01), consistent with improved metabolic acidosis, and was higher in the HCO3 than the fruits and vegetable group (P<0.001). One-year urine indices of kidney injury were lower than baseline in both groups. Plasma [K+] did not increase in either group. Conclusions One year of fruits and vegetables or NaHCO3 in individuals with stage 4 CKD yielded eGFR that was not different, was associated with higher-than-baseline PTCO2, and was associated with lower-than-baseline urine indices of kidney injury. The data indicate that fruits and vegetables improve metabolic acidosis and reduce kidney injury in stage 4 CKD without producing hyperkalemia. PMID:23393104

Goraya, Nimrit; Simoni, Jan; Jo, Chan-Hee

2013-01-01

63

[Metformin- related lactic acidosis].  

PubMed

Lactic acidosis metformin-related is a potentially fatal complication. Reviews show a stable prevalence of this phenomenon, but nephrological experience is required since it is frequently involved in therapeutic management. Here we report the cases of two old patients with severe lactic acidosis and acute renal failure treated with hemodiafiltration. PMID:25504165

Manes, Massimo; Pellu, Valentina; Caputo, Donatella; Molino, Andrea; Paternoster, Giuseppe; Gabrielli, Danila; Nebiolo, Pier Eugenio

2014-01-01

64

Effects of metabolic acidosis on intracellular pH responses in multiple cell types.  

PubMed

Metabolic acidosis (MAc), a decrease in extracellular pH (pHo) caused by a decrease in [HCO3 (-)]o at a fixed [CO2]o, is a common clinical condition and causes intracellular pH (pHi) to fall. Although previous work has suggested that MAc-induced decreases in pHi (?pHi) differ among cell types, what is not clear is the extent to which these differences are the result of the wide variety of methodologies employed by various investigators. In the present study, we evaluated the effects of two sequential MAc challenges (MAc1 and MAc2) on pHi in 10 cell types/lines: primary-cultured hippocampal (HCN) neurons and astrocytes (HCA), primary-cultured medullary raphé (MRN) neurons, and astrocytes (MRA), CT26 colon cancer, the C2C12 skeletal muscles, primary-cultured bone marrow-derived macrophages (BMDM) and dendritic cells (BMDC), Ink4a/ARF-null melanocytes, and XB-2 keratinocytes. We monitor pHi using ratiometric fluorescence imaging of 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein while imposing MAc: lowering (pHo) from 7.4 to 7.2 by decreasing [HCO3 (-)]o from 22 to 14 mM at 5% CO2 for 7 min. After MAc1, we return cells to the control solution for 10 min and impose MAc2. Using our definition of MAc resistance [(?pHi/?pHo) ? 40%], during MAc1, ?70% of CT26 and ?50% of C2C12 are MAc-resistant, whereas the other cell types are predominantly MAc-sensitive. During MAc2, some cells adapt [(?pHi/?pHo)2 < (?pHi/?pHo)1], particularly HCA, C2C12, and BMDC. Most maintain consistent responses [(?pHi/?pHo)2 ? (?pHi/?pHo)1], and a few decompensate [(?pHi/?pHo)2>(?pHi/?pHo)1], particularly HCN, C2C12, and XB-2. Thus, responses to twin MAc challenges depend both on the individual cell and cell type. PMID:25209413

Salameh, Ahlam Ibrahim; Ruffin, Vernon A; Boron, Walter F

2014-12-15

65

Wilson's disease – A rare cause of renal tubular acidosis with metabolic bone disease  

PubMed Central

We report a 16-year-old boy who presented with weakness of lower limbs. He was diagnosed to have Wilson's disease, renal tubular acidosis and osteoporosis. Screening of siblings showed that his younger sister was also affected by the disease. PMID:25120295

Subrahmanyam, D. K. S.; Vadivelan, M.; Giridharan, S.; Balamurugan, N.

2014-01-01

66

Wilson's disease - A rare cause of renal tubular acidosis with metabolic bone disease.  

PubMed

We report a 16-year-old boy who presented with weakness of lower limbs. He was diagnosed to have Wilson's disease, renal tubular acidosis and osteoporosis. Screening of siblings showed that his younger sister was also affected by the disease. PMID:25120295

Subrahmanyam, D K S; Vadivelan, M; Giridharan, S; Balamurugan, N

2014-05-01

67

Effect of experimentally induced metabolic acidosis on aortic endothelial permeability and serum nitric oxide concentration in normal and high-cholesterol fed rabbits  

PubMed Central

Introduction Metabolic acidosis is present in end stage renal disease. There is a link between enhanced endothelial permeability and accelerated atherosclerosis. In this study, we investigated the effect of experimentally induced metabolic acidosis on aortic endothelial permeability and serum nitric oxide (NO) concentration in normal and high-cholesterol fed rabbits. Material and methods Twenty-four male rabbits were divided into four groups: normal, hypercholesterolemic, acidemic, and hypercholesterolemic plus acidemic. Acidosis and hypercholesterolemia were induced by drinking water containing ammonium chloride (NH4Cl), and cholesterol-rich animal chow (1%), respectively. After 6 weeks, blood samples were taken and endothelial permeability was measured using the Evans blue dye injection method. Results Hypercholesterolemic animals had higher aortic endothelial permeability compared with normal groups (16.18 ±0.91 µg EB/g tissue vs. 12.89 ±0.66 µg EB/g tissue, p < 0.05). Acidosis significantly increased endothelial permeability in the normal group (17.10 ±0.56 µg/g tissue vs. 12.89 ± 0.66 µg/g tissue; p < 0.05) but did not further increase endothelial permeability in hypercholesterolemic animals (16.18 ±0.91 µg EB/g tissue vs. 17.29 ±0.46 µg EB/g tissue; p > 0.05). Serum total cholesterol, low density lipoprotein (LDL) and NO concentrations in hypercholesterolemic animals were significantly higher than the normal group and acidosis could not change them either in the normal or in the high-cholesterol diet group. Conclusions Alterations of serum lipids and NO are not the main mechanism for accelerated atherosclerosis during metabolic acidosis. Acidosis increases aortic endothelial permeability at least in a normal diet which may be a possible mechanism for progression of atherosclerosis processes in end-stage renal disease. PMID:23056086

Nematbakhsh, Mehdi

2012-01-01

68

TASK channels are not required to mount an aldosterone secretory response to metabolic acidosis in mice.  

PubMed

The stimulation of aldosterone production by acidosis enhances proton excretion and serves to limit disturbances in systemic acid-base equilibrium. Yet, the mechanisms by which protons stimulate aldosterone production from cells of the adrenal cortex remain largely unknown. TWIK-related acid sensitive K channels (TASK) are inhibited by extracellular protons within the physiological range and have emerged as important regulators of aldosterone production in the adrenal cortex. Here we show that congenic C57BL/6J mice with genetic deletion of TASK-1 (K(2P)3.1) and TASK-3 (K(2P)9.1) channel subunits overproduce aldosterone and display an enhanced sensitivity to steroidogenic stimuli, including a more pronounced steroidogenic response to chronic NH(4)Cl loading. Thus, we conclude that TASK channels are not required for the stimulation of aldosterone production by protons but their inhibition by physiological acidosis may contribute to full expression of the steroidogenic response. PMID:21111026

Guagliardo, Nick A; Yao, Junlan; Bayliss, Douglas A; Barrett, Paula Q

2011-04-10

69

Veno-venous extracorporeal CO2 removal for the treatment of severe respiratory acidosis: pathophysiological and technical considerations  

PubMed Central

Introduction While non-invasive ventilation aimed at avoiding intubation has become the modality of choice to treat mild to moderate acute respiratory acidosis, many severely acidotic patients (pH <7.20) still need intubation. Extracorporeal veno-venous CO2 removal (ECCO2R) could prove to be an alternative. The present animal study tested in a systematic fashion technical requirements for successful ECCO2R in terms of cannula size, blood and sweep gas flow. Methods ECCO2R with a 0.98 m2 surface oxygenator was performed in six acidotic (pH <7.20) pigs using either a 14.5 French (Fr) or a 19Fr catheter, with sweep gas flow rates of 8 and 16 L/minute, respectively. During each experiment the blood flow was incrementally increased to a maximum of 400 mL/minute (14.5Fr catheter) and 1000 mL/minute (19Fr catheter). Results Amelioration of severe respiratory acidosis was only feasible when blood flow rates of 750 to 1000 mL/minute (19Fr catheter) were used. Maximal CO2-elimination was 146.1?±?22.6 mL/minute, while pH increased from 7.13?±?0.08 to 7.41?±?0.07 (blood flow of 1000 mL/minute; sweep gas flow 16 L/minute). Accordingly, a sweep gas flow of 8 L/minute resulted in a maximal CO2-elimination rate of 138.0?±?16.9 mL/minute. The 14.5Fr catheter allowed a maximum CO2 elimination rate of 77.9 mL/minute, which did not result in the normalization of pH. Conclusions Veno-venous ECCO2R may serve as a treatment option for severe respiratory acidosis. In this porcine model, ECCO2R was most effective when using blood flow rates ranging between 750 and 1000 mL/minute, while an increase in sweep gas flow from 8 to 16 L/minute had less impact on ECCO2R in this setting. PMID:24942014

2014-01-01

70

Metabolic acidosis stimulates H+ secretion in the rabbit outer medullary collecting duct (inner stripe) of the kidney.  

PubMed Central

The outer medullary collecting duct (OMCD) absorbs HCO3- at high rates, but it is not clear if it responds to metabolic acidosis to increase H+ secretion. We measured net HCO3- transport in isolated perfused OMCDs taken from deep in the inner stripes of kidneys from control and acidotic (NH4Cl-fed for 3 d) rabbits. We used specific inhibitors to characterize the mechanisms of HCO3- transport: 10 microM Sch 28080 or luminal K+ removal to inhibit P-type H+,K+-ATPase activity, and 5-10 nM bafilomycin A1 or 1-10 nM concanamycin A to inhibit H+-ATPase activity. The results were comparable using either of each pair of inhibitors, and allowed us to show in control rabbits that 65% of net HCO3- absorption depended on H+-ATPase (H flux), and 35% depended on H+,K+-ATPase (H,K flux). Tubules from acidotic rabbits showed higher rates of HCO3- absorption (16.8+/-0.3 vs. 12.8+/-0.2 pmol/min per mm, P < 0.01). There was no difference in the H,K flux (5.9+/-0.2 vs. 5.8+/-0.2 pmol/min per mm), whereas there was a 61% higher H flux in segments from acidotic rabbits (11.3+/-0.2 vs. 7.0+/-0.2 pmol/min per mm, P < 0.01). Transport was then measured in other OMCDs before and after incubation for 1 h at pH 6.8, followed by 2 h at pH 7.4 (in vitro metabolic acidosis). Acid incubation in vitro stimulated HCO3- absorption (12.3+/-0.3 to 16.2+/-0.3 pmol/min per mm, P < 0.01), while incubation at pH 7.4 for 3 h did not change basal rate (11.8+/-0.4 to 11.7+/-0.4 pmol/min per mm). After acid incubation the H,K flux did not change, (4.7+/-0.4 to 4.6+/-0.4 pmol/min per mm), however, there was a 60% increase in H flux (6.6+/-0.3 to 10.8+/-0.3 pmol/min per mm, P < 0.01). In OMCDs from acidotic animals, and in OMCDs incubated in acid in vitro, there was a higher basal rate and a further increase in HCO3- absorption (16.7+/-0.4 to 21.3+/-0.3 pmol/min per mm, P < 0.01) because of increased H flux (11.5+/-0.3 to 15.7+/-0.2 pmol/min per mm, P < 0.01) without any change in H,K flux (5.4+/-0.3 to 5.6+/-0.3 pmol/min per mm). These data indicate that HCO3- absorption (H+ secretion) in OMCD is stimulated by metabolic acidosis in vivo and in vitro by an increase in H+-ATPase-sensitive HCO3- absorption. The mechanism of adaptation may involve increased synthesis and exocytosis to the apical membrane of proton pumps. This adaptation helps maintain homeostasis during metabolic acidosis. PMID:9077552

Tsuruoka, S; Schwartz, G J

1997-01-01

71

Proteomic profiling of the effect of metabolic acidosis on the apical membrane of the proximal convoluted tubule  

PubMed Central

The physiological response to the onset of metabolic acidosis requires pronounced changes in renal gene expression. Adaptations within the proximal convoluted tubule support the increased extraction of plasma glutamine and the increased synthesis and transport of glucose and of NH4+ and HCO3? ions. Many of these adaptations involve proteins associated with the apical membrane. To quantify the temporal changes in these proteins, proteomic profiling was performed using brush-border membrane vesicles isolated from proximal convoluted tubules (BBMVPCT) that were purified from normal and acidotic rats. This preparation is essentially free of contaminating apical membranes from other renal cortical cells. The analysis identified 298 proteins, 26% of which contained one or more transmembrane domains. Spectral counts were used to assess changes in protein abundance. The onset of acidosis produced a twofold, but transient, increase in the Na+-dependent glucose transporter and a more gradual, but sustained, increase (3-fold) in the Na+-dependent lactate transporter. These changes were associated with the loss of glycolytic and gluconeogenic enzymes that are contained in the BBMVPCT isolated from normal rats. In addition, the levels of ?-glutamyltranspeptidase increased twofold, while transporters that participate in the uptake of neutral amino acids, including glutamine, were decreased. These changes could facilitate the deamidation of glutamine within the tubular lumen. Finally, pronounced increases were also observed in the levels of DAB2 (3-fold) and myosin 9 (7-fold), proteins that may participate in endocytosis of apical membrane proteins. Western blot analysis and accurate mass and time analyses were used to validate the spectral counting. PMID:22357915

Walmsley, Scott J.; Freund, Dana M.

2012-01-01

72

Severe Encephalopathy, Lactic Acidosis, Vegetative Instability and Neuropathy with 5-Fluorouracil Treatment – Pyrimidine Degradation Defect or Beriberi?  

PubMed Central

We present the case of a 19-year-old female with nasopharyngeal carcinoma, who received two courses of chemotherapy with 5-fluorouracil (5-FU) in combination with folic acid and cisplatin. Upon developing esophageal strictures in the course of her radiotherapy, she required total parenteral nutrition. In the course of therapy, the patient developed severe multisystem failure with encephalopathy, lactic acidosis, vegetative instability and neuropathy. The treatment with 5-FU can lead to severe toxicity due to enzyme deficiencies in the degradation of pyrimidines, but it can also lead to thiamine deficiency with the classic symptoms of beriberi. Beriberi is a rare disorder, usually attributed to malnutrition or alcoholism. 5-FU has been shown to induce thiamine depletion. Reduced food intake or total parenteral nutrition devoid of vitamin supplements may aggravate symptoms. We were unable to find a genetic cause for increased 5-FU toxicity in our patient, ruling out deficiencies of dihydropyrimidine dehydrogenase, dihydropyrimidinase or ?-ureidopropionase and double-strand break repair deficits. We come to the conclusion that, even without any definable enzyme deficiency, treatment with 5-FU can lead to high toxicity due to thiamine deficiency if vitamin supplementation is not undertaken. PMID:21941485

Rosen, A.; van Kuilenburg, A.; Assmann, B.; Kuhlen, M.; Borkhardt, A.

2011-01-01

73

Switching hemodialysis patients from sevelamer hydrochloride to bixalomer: a single-center, non-randomized analysis of efficacy and effects on gastrointestinal symptoms and metabolic acidosis  

PubMed Central

Background Bixalomer (BXL) was developed to improve gastrointestinal symptoms and reduce constipation, relative to sevelamer hydrochloride, in hemodialysis patients. We prospectively evaluated the safety and effectiveness of switching maintenance dialysis patients from sevelamer hydrochloride to BXL. Methods Twenty-eight patients were switched from sevelamer hydrochloride to BXL (1:1 dose) from July to October 2012, whereas 84 randomly selected patients not treated with sevelamer hydrochloride were enrolled as a control group. The primary endpoint was improvement of gastrointestinal symptoms; secondary endpoints included improvement in metabolic acidosis, changes in blood biochemistry, and safety 12 weeks after the switch. We also surveyed patient satisfaction with switching to BXL 12 weeks after the switch. Results Before switching, symptoms of epigastric fullness were significantly worse in the switch than in the control group. Twelve weeks after the switch, reflux, epigastric fullness, and constipation had improved significantly in the switch group. Other factors, including stomach ache, diarrhea, and form of stool, did not change significantly. Blood gas analysis showed that metabolic acidosis was significantly improved by switching. Four patients (14%) experienced grade 1 adverse events, all of which improved immediately after stopping BXL. Major adverse events were diarrhea and abdominal discomfort. Mean satisfaction score was 3.1?±?0.7, with 64% of patients reporting they were “neither satisfied nor dissatisfied” after switching. Conclusions A switch from sevelamer hydrochloride to BXL improved symptoms of reflux, epigastric fullness, constipation, and metabolic acidosis in hemodialysis patients. Trial registration The study was registered as Clinical trial: (UMIN000011150). PMID:24119202

2013-01-01

74

Chronic metabolic acidosis augments acidification along the inner medullary collecting duct.  

PubMed

The inner medullary collecting duct (IMCD) of the rat is a major site of acidification. However, previous micropuncture studies have failed to demonstrate acidification along the terminal IMCD during chronic acid feeding. To more completely evaluate this question we used the microcatheterization method in rats fed ammonium chloride for 3-7 days. Arterial pH was 7.30 +/- 0.015, and PCO2 was set at 40 +/- 0.6 mmHg. The IMCD data were analyzed as a function of IMCD length between 40% and the tip. Equilibrium pH decreased from 6.21 +/- 0.11 to 5.47 +/- 0.03, whereas PCO2 was unchanged (28 +/- 1 mmHg between the deep samples and tip). Bicarbonate delivery decreased from 92 +/- 14 to 10 +/- 1 nmol/min, titratable acid increased from 462 +/- 33 to 762 +/- 40 nmol/min, and ammonium delivery increased from 2,235 +/- 121 to 3,528 +/- 140 nmol/min. Thus estimated net acid increased from 2,638 +/- 134 to 4,303 +/- 161 nmol/min. To determine whether increasing delivery of buffer to the IMCD would stimulate acid secretion in acute acidosis, rats were studied during the infusion of HCl and creatinine. Arterial pH was 7.18 +/- 0.02. IMCD acidification was not increased compared with our previously published studies during HCl infusion [Am. J. Physiol. 241 (Renal Fluid Electrolyte Physiol. 10): F669-F676, 1981]. We conclude that chronic ammonium chloride ingestion stimulates IMCD acidification and that this increase may be an intrinsic modification of the acidification mechanism of the IMCD. PMID:3963206

Bengele, H H; Schwartz, J H; McNamara, E R; Alexander, E A

1986-04-01

75

Ability and safety of a heated humidifier to control hypercapnic acidosis in severe ARDS  

Microsoft Academic Search

Objective. To assess the ability of a heated humidifier to improve CO2 clearance in ARDS patients submitted to protective ventilation. Design. Prospective clinical study. Setting. University hospital intensive care unit. Patients. During a 12-month period, we studied 11 ARDS patients under protective mechanical ventilation with severe hypercapnia. Intervention. When PaCO2 was above 55 mmHg, the heat and moisture exchanger (HME)

Sebastian Prin; Karim Chergui; Rock Augarde; Bernard Page; François Jardin; Antoine Vieillard-Baron

2002-01-01

76

Evaluation of the systemic innate immune response and metabolic alterations of nonlactating cows with diet-induced subacute ruminal acidosis.  

PubMed

Subacute ruminal acidosis (SARA) increases lipopolysaccharide endotoxin in the rumen, which might translocate into the systemic circulation, triggering a cascade of clinical and immunological alterations. The objective of this study was to characterize the clinical immune and metabolic responses to ruminal-derived lipopolysaccharide in nonlactating cows induced with SARA using 2 challenges, a grain-based SARA challenge (GBSC) or an alfalfa-pellet SARA challenge (APSC). Six dry, nonlactating Holstein cows were used in a 3 × 3 Latin square arrangement of treatments with 4-wk experimental cycles. All cows received the control diet containing 70% forage and 30% mixed concentrates (dry matter basis) for 3 wk. In wk 4, cows received a control diet, GBSC (38% wheat-barley pellets, 32% other mixed concentrate, and 30% forages), or APSC (45% mixed concentrate, 32% alfalfa pellets, and 23% other forages). Total plasma proteins and immunology-related proteins, acute phase proteins, blood cells, serum chemistry, mRNA gene expression of peripheral blood cell surface markers, and selected proinflammatory cytokines were evaluated. Ruminal pH was lower in both groups with induced SARA compared with a control group. Ruminal endotoxins were higher in GBSC; however, plasma endotoxin was not detected in any study group. No significant differences in feed intake, rectal temperature, white blood cell counts, or differentials were found between control and SARA challenge groups; changes in glucose, urea, Ca, and Mg were observed in SARA groups. Total plasma proteins were lower in both SARA groups, and acute phase proteins were higher in GBSC. The expression of CD14, MD2, and TLR4 mRNA in peripheral blood leukocytes was not affected by SARA induction. The induction of SARA as a result of GBSC or APSC challenge was successful; however, LPS was not detected in plasma. Changes in clinical, metabolic, and inflammatory responses were not observed in the SARA-challenged cows, suggesting that, in this study, SARA was not associated with a systemic response to inflammation. PMID:25459907

Rodríguez-Lecompte, J C; Kroeker, A D; Ceballos-Márquez, A; Li, S; Plaizier, J C; Gomez, D E

2014-10-18

77

Acidosis activates complement system in vitro.  

PubMed

We investigated the in vitro effect of different forms of acidosis (pH 7.0) on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 micromol/ml blood) or lactic acid (5.5 micromol/ml) to heparin blood (N=12) caused significant activation of C3a and C5a compared to control (both p=0.002). Respiratory acidosis activated C3a (p=0.007) and C5a (p=0.003) compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5. PMID:9927235

Emeis, M; Sonntag, J; Willam, C; Strauss, E; Walka, M M; Obladen, M

1998-01-01

78

Protective role of acidic pH-activated chloride channel in severe acidosis-induced contraction from the aorta of spontaneously hypertensive rats.  

PubMed

Severe acidic pH-activated chloride channel (ICl,acid) has been found in various mammalian cells. In the present study, we investigate whether this channel participates in reactions of the thoracic aorta to severe acidosis and whether it plays a role in hypertension. We measured isometric contraction in thoracic aorta rings from spontaneously hypertensive rats (SHRs) and normotensive Wistar rats. Severe acidosis induced contractions of both endothelium-intact and -denuded thoracic aorta rings. In Wistar rats, contractions did not differ at pH 6.4, 5.4 and 4.4. However, in SHRs, contractions were higher at pH 5.4 or 4.4 than pH 6.4, with no difference between contractions at pH 5.4 and 4.4. Nifedipine, ICl,acid blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS) inhibited severe acidosis-induced contraction of aortas at different pH levels. When blocking ICl,acid, the remnant contraction was greater at pH 4.4 than pH 5.4 and 6.4 for both SHRs and Wistar rats. With nifedipine, the remnant contraction was greatly reduced at pH 4.4 as compared with at pH 6.4 and 5.4. With NPPB or DIDS, the ratio of remnant contractions at pH 4.4 and 5.4 (R4.4/5.4) was lower for SHRs than Wistar rats (all <1). However, with nifedipine, the R4.4/5.4 was higher for SHRs than Wistar rats (both >1). Furthermore, patch clamp recordings of ICl,acid and intracellular Ca(2+) measurements in smooth muscle cells confirmed these findings. ICl,acid may protect arteries against excess vasoconstriction under extremely acidic extracellular conditions. This protective effect may be decreased in hypertension. PMID:23580361

Ma, Zhiyong; Qi, Jia; Fu, Zhijie; Ling, Mingying; Li, Li; Zhang, Yun

2013-01-01

79

Further studies on the clinical features and clinicopathological findings of a syndrome of metabolic acidosis with minimal dehydration in neonatal calves.  

PubMed Central

A syndrome of metabolic acidosis of unknown etiology was diagnosed in twelve beef calves 7 to 31 days old. Principal clinical signs were unconsciousness or depression concomitant with weakness and ataxia. Other signs included weak or absent suckle and menace reflexes, succussable nontympanic fluid sounds in the anterior abdomen, and a slow, deep thoracic and abdominal pattern of respiration. The variation in clinical signs between calves was highly correlated (r = 0.87, P less than 0.001) with their acid-base (base deficit) status. Abnormal laboratory findings included reduced venous blood pH, pCO2 and bicarbonate ion concentration as well as hyperchloremia, elevated blood urea nitrogen, increased anion gap and neutrophilic leukocytosis with a left shift. Sodium bicarbonate solution administered intravenously effectively raised blood pH and improved demeanor, ambulation and appetite. All calves did well following a return to a normal acid-base status. PMID:3024795

Kasari, T R; Naylor, J M

1986-01-01

80

Acidosis in a patient with cholera: a need to redefine concepts.  

PubMed

A patient presented with cholera and a severe degree of ECF volume contraction. Despite large losses of bicarbonate (HCO3-)-containing diarrhoeal fluid, laboratory acid-base values were remarkably close to normal. A detailed analysis emphasizing principles of physiology and a quantitative approach provided new insights and eventually better definitions of metabolic and respiratory acidosis. A shift in focus from HCO3- concentration to HCO3- content in the extracellular fluid (ECF) compartment revealed the presence of metabolic acidosis. Central to this analysis was an emphasis on the haematocrit to enable a more accurate estimate of the degree of ECF volume contraction. The latter also revealed 'contraction' metabolic alkalosis, which masked the underlying metabolic acidosis. The presence of a respiratory acidosis of the tissue type was evident from the raised venous PCO2, which was not surprising once the magnitude of the ECF contraction had been appreciated. 'Bad buffering', as defined by Professor McCance, was the immediate danger and prompted swift action to restore an effective circulation. The haematocrit and the venous PCO2 also contribute valuable information to monitor the response to therapy. Nevertheless, there were still dangers to be discovered when an in-depth analysis suggested that the administration of isotonic saline would introduce an unanticipated danger for the patient. PMID:15367740

Zalunardo, N; Lemaire, M; Davids, M R; Halperin, M L

2004-10-01

81

Acidosis and alkalosis impair brain functions through weakening spike encoding at cortical GABAergic neurons  

Microsoft Academic Search

Acidosis and alkalosis, associated with metabolic disorders, lead to the pathological changes of cognition and behaviors in clinical practices of neurology and psychology. Cellular mechanisms for these functional disorders in the central nervous system remain unclear. We have investigated the influences of acidosis and alkalosis on the functions of cortical GABAergic neurons. Both acidosis and alkalosis impair the ability of

Rongrong Song; Liming Zhang; Zichao Yang; Xiaoyan Tian

2011-01-01

82

Liver Pathology and the Metabolic Syndrome X in Severe Obesity  

Microsoft Academic Search

The metabolic syndrome X, characterized by insulin resistance, dyslipidemia, hypertension, and a male, visceral distribution of ad- ipose tissue, is associated with increased morbidity and mortality from several prevalent diseases, such as diabetes, cancers, myocardial infarction, and stroke. Because the liver has a central role in carbo- hydrate, lipid, and steroid metabolism, we investigated the relation- ships between liver pathology

P. Marceau; S. BIRON; F.-S. HOULD; S. MARCEAU; S. SIMARD; S. N. THUNG

1999-01-01

83

Familial renal tubular acidosis.  

PubMed

The kidney maintains systemic acid-base homeostasis through proximal tubular reclamation of filtered bicarbonate, and excretion of the daily mineral acid load by collecting duct type A intercalated cells. Impairment of either process produces renal tubular acidosis (RTA). This article will provide an overview of familial forms of proximal and distal renal tubular acidosis (pRTA and dRTA). Recessive pRTA with ocular and central nervous system abnormalities is caused by loss-of-function mutations in basolateral membrane Na-HCO3- cotransporter NBCe1/ SLC4A4. Recessive dRTA with deafness is caused by loss-of-function mutations in either of 2 subunits of the vacuolar H+-ATPase (V-ATPase) of intercalated cells; the B1 subunit of the V1 cytoplasmic ATPase complex, and the a4 subunit of the V0 transmembrane pore complex. Dominant and recessive forms of dRTA are also caused by loss-of-function mutations in the basolateral membrane AE1 Cl-/HCO3- exchanger of the type A intercalated cell. The dominant AE1 dRTA mutations are accompanied by mild or asymptomatic erythroid changes, while the erythroid dyscrasias accompanying recessive AE1 dRTA mutations can be mild or severe. Recessive mixed proximal-distal RTA is caused by loss-of-function mutations of the cytoplasmic carbonic anhydrase II. Hyperkalemic RTA accompanied by hypertension (pseudohypoaldosteronism type 2 [PHA2]) is caused by dominant gain-of-function mutations in the kinases WNK1 and WNK4. Hyperkalemic RTA accompanied by volume depletion is caused by loss-of-function mutations in genes encoding the mineralocorticoid receptor or the epithelial Na+ channel (ENaC) subunits. Additional RTA genes identified in knockout mice may lead to identification of additional human RTA genes. PMID:21170890

Alper, Seth L

2010-01-01

84

A Review of metabolic staging in severely injured patients  

PubMed Central

An interpretation of the metabolic response to injury in patients with severe accidental or surgical trauma is made. In the last century, various authors attributed a meaning to the post-traumatic inflammatory response by using teleological arguments. Their interpretations of this response, not only facilitates integrating the knowledge, but also the flow from the bench to the bedside, which is the main objective of modern translational research. The goal of the current review is to correlate the metabolic changes with the three phenotypes -ischemia-reperfusion, leukocytic and angiogenic- that the patients express during the evolution of the systemic inflammatory response. The sequence in the expression of multiple metabolic systems that becomes progressively more elaborate and complex in severe injured patients urges for more detailed knowledge in order to establish the most adequate metabolic support according to the evolutive phase. Thus, clinicians must employ different treatment strategies based on the different metabolic phases when caring for this challenging patient population. Perhaps, the best therapeutic option would be to favor early hypometabolism during the ischemia-reperfusion phase, to boost the antienzymatic metabolism and to reduce hypermetabolism during the leukocytic phase through the early administration of enteral nutrition and the modulation of the acute phase response. Lastly, the early epithelial regeneration of the injured organs and tissues by means of an oxidative metabolism would reduce the fibrotic sequelae in these severely injured patients. PMID:20478066

2010-01-01

85

Effect of oral sodium bicarbonate supplementation on progression of chronic kidney disease in patients with chronic metabolic acidosis: study protocol for a randomized controlled trial (SoBic-Study)  

PubMed Central

Background Overt chronic metabolic acidosis in patients with chronic kidney disease develops after a drop of glomerular filtration rate to less than approximately 25 mL/min/1.73 m2. The pathogenic mechanism seems to be a lack of tubular bicarbonate production, which in healthy individuals neutralizes the acid net production. As shown in several animal and human studies the acidotic milieu alters bone and vitamin D metabolism, induces muscle wasting, and impairs albumin synthesis, aside from a direct alteration of renal tissue by increasing angiotensin II, aldosteron and endothelin kidney levels. Subsequent studies testing various therapeutic approaches in very selected study populations showed that oral supplementation of the lacking bicarbonate halts progression of decline of renal function. However, due to methodological limitations of these studies further investigations are of urgent need to ensure the validity of this therapeutic concept. Methods/Design The SoBic-study is a single-center, randomized, controlled, open-label clinical phase IV study performed at the nephrological outpatient service of the Medical University of Vienna. Two-hundred patients classified to CKD stage 3 or 4 with two separate measurements of HCO3- of <21 mmol/L will be 1:1 randomized to either receive a high dose of oral sodium bicarbonate with a serum target HCO3- level of 24?±?1 mmol/L or receive a rescue therapy of sodium bicarbonate with a serum target level of 20?±?1 mmol/L. The follow up will be for two years. The primary outcome is the effect of sodium bicarbonate supplementation on renal function measured by means of estimated glomerular filtration rates (4-variable-MDRD-equation) after two years. Secondary outcomes are change in markers of bone metabolism between groups, death rates between groups, and the number of subjects proceeding to renal replacement therapy across groups. Adverse events, such as worsening of arterial hypertension due to the additional sodium consumption, will be accurately monitored. Discussion We hypothesize that sufficiently balanced acid–base homeostasis leads to a reduction of decline of renal function in patients with chronic kidney disease. The concept of an exogenous bicarbonate supplementation to substitute the lacking endogenous bicarbonate has existed for a long time, but has never been investigated sufficiently to state clear treatment guidelines. Trial registration EUDRACT Number: 2012-001824-36 PMID:23826760

2013-01-01

86

A Review of metabolic staging in severely injured patients  

Microsoft Academic Search

An interpretation of the metabolic response to injury in patients with severe accidental or surgical trauma is made. In the last century, various authors attributed a meaning to the post-traumatic inflammatory response by using teleological arguments. Their interpretations of this response, not only facilitates integrating the knowledge, but also the flow from the bench to the bedside, which is the

Maria-Angeles Aller; Jose-Ignacio Arias; Alfredo Alonso-Poza; Jaime Arias

2010-01-01

87

Distal renal tubular acidosis in a cat with pyelonephritis.  

PubMed

A four-year-old castrated male domestic shorthair cat with recent onset of lethargy and depression was found to have hypokalaemia, low plasma bicarbonate concentration and a urine pH of 7. Subsequent findings of hyperchloraemic metabolic acidosis with failure to produce acid urine led to a diagnosis of distal renal tubular acidosis. Pyelonephritis associated with Escherichia coli infection of the urinary tract was also diagnosed. The urinary tract infection was eliminated by antibiotic treatment. For two years subsequently, the clinical effects of distal renal tubular acidosis have been controlled by oral administration of potassium bicarbonate, although some biochemical abnormalities have persisted. PMID:3529597

Watson, A D; Culvenor, J A; Middleton, D J; Rothwell, T L

1986-07-19

88

[Treatment of metformin-associated lactate acidosis by haemodialysis].  

PubMed

Metformin-associated lactate acidosis is rare but serious and characterized by metabolic acidosis and elevated lactate. We describe a single-institution experience of four cases in one year. Despite pH levels of 6.85 to 7.12 and lactate levels of 11-28 mmol/l three of the patients survived. Two of the patients had normal kidney function previous to hospitalization. Treatment includes fluid replacement, IV sodium bicarbonate and haemodialysis. PMID:22673381

Schousboe, Karin; El Fassi, Daniel; Secher, Erik Lilja; Elming, Hanne; Rasmussen, Knud; Hornum, Mads

2012-06-01

89

The syndrome of irreversible acidosis after prolonged propofol infusion  

Microsoft Academic Search

Introduction: Propofol infusion syndrome is described in the pediatric literature as metabolic acidosis, rhabdomyolysis, and bradycardia\\u000a that results in death. The pathogenesis of this syndrome is thought to be activation of the systemic inflammatory response,\\u000a which culminates in acidosis and muscle necrosis.\\u000a \\u000a \\u000a Materials and Methods: Retrospective chart review of three patients in the Neurological Critical Care Units at Hahnemann and

Monisha A. Kumar; Victor C. Urrutia; Carole E. Thomas; Karine J. Abou-Khaled; Robert J. Schwartzman

2005-01-01

90

Renal tubular acidosis--underrated problem?  

PubMed

Renal tubular acidosis (RTA) is a hyperchloremic metabolic acidosis characterized by a normal anion gap and normal (or near normal) glomerular filtration rate in the absence of diarrhoea. Inherited isolated forms of renal tubular acidosis are not common. However, they can also be a part of a more generalized tubule defect, like in Fanconi syndrome. In recent years more and more gene mutations have been found which are associated with RTA (mutations in the gene SLC4A4, encoding a Na(+)-HCO(3)(-) cotransporter (NBC-1); in the gene SLC4A1, encoding Cl(-)/HCO3(-) exchanger (AE1); in the gene ATP6B1, encoding B1 subunit of H(+)-ATPase; in the gene CA2 encoding carbonic anhydrase II; and others) and allow better understanding of underlying processes of bicarbonate and H(+) transport. Isolated renal tubular acidosis can be frequently acquired due to use of certain drug groups, autoimmune disease or kidney transplantation. As the prevalence of acquired forms of RTA is common, new therapeutic options for the currently used supplementation of oral alkali, are awaited. PMID:22693689

Golembiewska, Edyta; Ciechanowski, Kazimierz

2012-01-01

91

Reversible lactic acidosis associated with repeated intravenous infusions of sorbitol and ethanol.  

PubMed Central

Infusions of fructose or sorbitol are used commonly in parenteral nutrition and may cause lactic acidosis. A case is reported in whom blood lactate concentration was monitored frequently over a 5-day period during intravenous feeding with a sorbitol-ethanol-amino acid mixture. During the first five infusions blood lactate rose only moderately, but with the final infusion lactate rose to 11-1 mmol/l and the patient had a severe metabolic acidosis. In retrospect the patient had shown deterioration in renal and hepatic function tests during the preceding 24 hr. On terminating the infusions the blood lactate concentration fell rapidly. It is suggested that great care should be exercised when using such infusions in ill patients and acid base status and renal and hepatic function should be monitored frequently. PMID:22069

Batstone, G. F.; Alberti, K. G.; Dewar, A. K.

1977-01-01

92

Amlodipine poisoning revisited: Acidosis, acute kidney injury and acute respiratory distress syndrome  

PubMed Central

We report the case of an 18-year-old girl presenting with shock following ingestion of 85 mg of amlodipine and 850 mg of atenolol with suicidal intent. Subsequently, the patient developed severe metabolic acidosis, acute kidney injury, and acute respiratory distress syndrome, which were managed conservatively. The patient ultimately made a full recovery. Given the popularity of amlodipine and atenolol as antihypertensive drugs in this part of the world, it is likely that more such cases will be encountered in the future. Physicians should be aware of the severe complications that can develop with amlodipine overdose. PMID:25097362

Naha, Kushal; Suryanarayana, J.; Aziz, Riffat Abdul; Shastry, Barkur Ananthakrishna

2014-01-01

93

Lactic Acidosis Triggers Starvation Response with Paradoxical Induction of TXNIP through MondoA  

PubMed Central

Although lactic acidosis is a prominent feature of solid tumors, we still have limited understanding of the mechanisms by which lactic acidosis influences metabolic phenotypes of cancer cells. We compared global transcriptional responses of breast cancer cells in response to three distinct tumor microenvironmental stresses: lactic acidosis, glucose deprivation, and hypoxia. We found that lactic acidosis and glucose deprivation trigger highly similar transcriptional responses, each inducing features of starvation response. In contrast to their comparable effects on gene expression, lactic acidosis and glucose deprivation have opposing effects on glucose uptake. This divergence of metabolic responses in the context of highly similar transcriptional responses allows the identification of a small subset of genes that are regulated in opposite directions by these two conditions. Among these selected genes, TXNIP and its paralogue ARRDC4 are both induced under lactic acidosis and repressed with glucose deprivation. This induction of TXNIP under lactic acidosis is caused by the activation of the glucose-sensing helix-loop-helix transcriptional complex MondoA:Mlx, which is usually triggered upon glucose exposure. Therefore, the upregulation of TXNIP significantly contributes to inhibition of tumor glycolytic phenotypes under lactic acidosis. Expression levels of TXNIP and ARRDC4 in human cancers are also highly correlated with predicted lactic acidosis pathway activities and associated with favorable clinical outcomes. Lactic acidosis triggers features of starvation response while activating the glucose-sensing MondoA-TXNIP pathways and contributing to the “anti-Warburg” metabolic effects and anti-tumor properties of cancer cells. These results stem from integrative analysis of transcriptome and metabolic response data under various tumor microenvironmental stresses and open new paths to explore how these stresses influence phenotypic and metabolic adaptations in human cancers. PMID:20844768

Chen, Julia Ling-Yu; Merl, Daniel; Peterson, Christopher W.; Wu, Jianli; Liu, Patrick Yantyng; Yin, Hanwei; Muoio, Deborah M.; Ayer, Don E.; West, Mike; Chi, Jen-Tsan

2010-01-01

94

Examining the relationship between diet-induced acidosis and cancer  

PubMed Central

Increased cancer risk is associated with select dietary factors. Dietary lifestyles can alter systemic acid-base balance over time. Acidogenic diets, which are typically high in animal protein and salt and low in fruits and vegetables, can lead to a sub-clinical or low-grade state of metabolic acidosis. The relationship between diet and cancer risk prompts questions about the role of acidosis in the initiation and progression of cancer. Cancer is triggered by genetic and epigenetic perturbations in the normal cell, but it has become clear that microenvironmental and systemic factors exert modifying effects on cancer cell development. While there are no studies showing a direct link between diet-induced acidosis and cancer, acid-base disequilibrium has been shown to modulate molecular activity including adrenal glucocorticoid, insulin growth factor (IGF-1), and adipocyte cytokine signaling, dysregulated cellular metabolism, and osteoclast activation, which may serve as intermediary or downstream effectors of carcinogenesis or tumor promotion. In short, diet-induced acidosis may influence molecular activities at the cellular level that promote carcinogenesis or tumor progression. This review defines the relationship between dietary lifestyle and acid-base balance and discusses the potential consequences of diet-induced acidosis and cancer occurrence or progression. PMID:22853725

2012-01-01

95

Glue-sniffing and distal renal tubular acidosis: sticking to the facts.  

PubMed

An index case is presented to introduce the subject of the acid-base and electrolyte abnormalities resulting from toluene abuse. These include metabolic acidosis associated with a normal anion gap and excessive loss of sodium and potassium in the urine. The major question addressed is, what is the basis for the metabolic acidosis? Overproduction of hippuric acid resulting from the metabolism of toluene plays a more important role in the genesis of the metabolic acidosis than was previously believed. This conclusion is supported by the observation that the rate of excretion of ammonium was not low during metabolic acidosis in six of eight patients, suggesting that distal renal tubular acidosis was not an important acid-base abnormality in most cases where ammonium was measured. The excretion of hippurate in the urine unmatched by ammonium also mandates an enhanced rate of excretion of the cations, sodium and potassium. The loss of sodium causes extracellular fluid volume contraction and a fall in the glomerular filtration rate, which may transform the normal anion gap type of metabolic acidosis into one with a high anion gap (accumulation of hippurate and other anions). Continuing loss of potassium in the urine leads to hypokalemia. An understanding of the metabolism of toluene provides the basis for the unusual biochemical abnormalities seen with abuse of this solvent. PMID:1912400

Carlisle, E J; Donnelly, S M; Vasuvattakul, S; Kamel, K S; Tobe, S; Halperin, M L

1991-02-01

96

Chronic metabolic acidosis causes an adaptation in the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter in the rat proximal convoluted tubule.  

PubMed

The effect of chronic dietary acid on the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter was examined in the in vivo microperfused rat proximal tubule. Transporter activity was assayed with the epifluorescent measurement of cell pH using the intracellular, pH-sensitive fluorescent dye, (2'7')-bis(carboxyethyl)-(5,6)-carboxy-fluorescein (BCECF). BCECF was calibrated intracellularly, demonstrating similar pH-sensitivity of the dye in control and acidotic animals. In subsequent studies, lumen and peritubular capillaries were perfused to examine Na/H and Na(HCO3)3 transporter activity in the absence of contact with native fluid. The initial rate of change in cell pH (dpHi/dt) was 97, 50, and 44% faster in tubules from acidotic animals when peritubular [HCO3] was changed from 25 to 10 mM in the presence or absence of chloride, or peritubular [Na] was changed from 147 to 50 mM, respectively. dpHi/dt was 57% faster in tubules from acidotic animals when luminal [Na] was changed from 152 to 0 mM. Buffer capacities, measured using NH3/NH+4 addition, were similar in the two groups. The results demonstrate that chronic metabolic acidosis causes an adaptation in the intrinsic properties of both the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter. PMID:2844858

Preisig, P A; Alpern, R J

1988-10-01

97

Acidosis Promotes Bcl-2 Family-mediated Evasion of Apoptosis  

PubMed Central

Acidosis arises in solid and lymphoid malignancies secondary to altered nutrient supply and utilization. Tumor acidosis correlates with therapeutic resistance, although the mechanism behind this effect is not fully understood. Here we show that incubation of lymphoma cell lines in acidic conditions (pH 6.5) blocks apoptosis induced by multiple cytotoxic metabolic stresses, including deprivation of glucose or glutamine and treatment with dexamethasone. We sought to examine the role of the Bcl-2 family of apoptosis regulators in this process. Interestingly, we found that acidic culture causes elevation of both Bcl-2 and Bcl-xL, while also attenuating glutamine starvation-induced elevation of p53-up-regulated modulator of apoptosis (PUMA) and Bim. We confirmed with knockdown studies that these shifts direct survival decisions during starvation and acidosis. Importantly, the promotion of a high anti- to pro-apoptotic Bcl-2 family member ratio by acidosis renders cells exquisitely sensitive to the Bcl-2/Bcl-xL antagonist ABT-737, suggesting that acidosis causes Bcl-2 family dependence. This dependence appears to be mediated, in part, by the acid-sensing G protein-coupled receptor, GPR65, via a MEK/ERK pathway. PMID:22685289

Ryder, Christopher; McColl, Karen; Zhong, Fei; Distelhorst, Clark W.

2012-01-01

98

A patient with foot ulcer and severe metabolic alkalosis.  

PubMed

We report a case of triple acid-base disorder with metabolic alkalosis as the primary disorder in a 65-year-old man due to ingestion and application to leg ulcers of baking soda (calcium bicarbonate). The blood pH was 7.65 with hypochloremia, hypokalemia, and prerenal azotemia. He was treated with isotonic saline with K replacement, and the patient improved without any adverse clinical consequences. We discuss the causes, mechanisms, and management of Cl-responsive (depletion) metabolic alkalosis. PMID:21185672

John, Ruby Samuel; Simoes, Sonia; Reddi, Alluru S

2012-01-01

99

Type B Lactic Acidosis Associated With Venlafaxine Overdose.  

PubMed

Lactic acidosis that is not secondary to tissue hypoperfusion or hypoxemia (type B lactic acidosis) is a rare but potentially fatal condition that has been associated with drugs like metformin, linezolid, and nucleoside reverse-transcriptase inhibitors in patients with HIV. We report the first case of type B lactic acidosis caused by overdose of the serotonin-norepinephrine reuptake inhibitor, venlafaxine. A 55-year-old man with no significant medical history was brought to the emergency department after intentional ingestion of around 80 capsules of venlafaxine (a total dose of over 6000 mg) in an attempt to commit suicide. Complete blood count and comprehensive metabolic panel were unremarkable except for a bicarbonate level of 13 mEq/L and an anion gap of 22 mEq/L. An arterial blood gas revealed a pH of 7.39, partial pressure of CO2 of 19 mm Hg, calculated bicarbonate of 11.5 mEq/L, and a lactate level of 8.6 mmol/L. The patient was started on aggressive intravenous hydration with normal saline along with oral activated charcoal with sorbitol. Repeat laboratory work after 4 hours showed an improvement in anion gap (15 mEq/L) and serum lactate (5.6 mmol/L). The patient remained stable throughout the hospital stay and lactic acidosis resolved in 24 hours. In the absence of hypotension, hypoxemia, kidney or liver dysfunction, myopathy, malignancy, or use of other medications, venlafaxine was the most likely cause of lactic acidosis in our case. Rapid improvement of acidosis was probably related to clearance of the drug. PMID:25405896

Iragavarapu, Chaitanya; Gupta, Tanush; Chugh, Savneek S; Aronow, Wilbert S; Frishman, William H

2014-11-17

100

Proximal tubule function and response to acidosis.  

PubMed

The human kidneys produce approximately 160-170 L of ultrafiltrate per day. The proximal tubule contributes to fluid, electrolyte, and nutrient homeostasis by reabsorbing approximately 60%-70% of the water and NaCl, a greater proportion of the NaHCO3, and nearly all of the nutrients in the ultrafiltrate. The proximal tubule is also the site of active solute secretion, hormone production, and many of the metabolic functions of the kidney. This review discusses the transport of NaCl, NaHCO3, glucose, amino acids, and two clinically important anions, citrate and phosphate. NaCl and the accompanying water are reabsorbed in an isotonic fashion. The energy that drives this process is generated largely by the basolateral Na(+)/K(+)-ATPase, which creates an inward negative membrane potential and Na(+)-gradient. Various Na(+)-dependent countertransporters and cotransporters use the energy of this gradient to promote the uptake of HCO3 (-) and various solutes, respectively. A Na(+)-dependent cotransporter mediates the movement of HCO3 (-) across the basolateral membrane, whereas various Na(+)-independent passive transporters accomplish the export of various other solutes. To illustrate its homeostatic feat, the proximal tubule alters its metabolism and transport properties in response to metabolic acidosis. The uptake and catabolism of glutamine and citrate are increased during acidosis, whereas the recovery of phosphate from the ultrafiltrate is decreased. The increased catabolism of glutamine results in increased ammoniagenesis and gluconeogenesis. Excretion of the resulting ammonium ions facilitates the excretion of acid, whereas the combined pathways accomplish the net production of HCO3 (-) ions that are added to the plasma to partially restore acid-base balance. PMID:23908456

Curthoys, Norman P; Moe, Orson W

2014-09-01

101

Proximal Tubule Function and Response to Acidosis  

PubMed Central

Summary The human kidneys produce approximately 160–170 L of ultrafiltrate per day. The proximal tubule contributes to fluid, electrolyte, and nutrient homeostasis by reabsorbing approximately 60%–70% of the water and NaCl, a greater proportion of the NaHCO3, and nearly all of the nutrients in the ultrafiltrate. The proximal tubule is also the site of active solute secretion, hormone production, and many of the metabolic functions of the kidney. This review discusses the transport of NaCl, NaHCO3, glucose, amino acids, and two clinically important anions, citrate and phosphate. NaCl and the accompanying water are reabsorbed in an isotonic fashion. The energy that drives this process is generated largely by the basolateral Na+/K+-ATPase, which creates an inward negative membrane potential and Na+-gradient. Various Na+-dependent countertransporters and cotransporters use the energy of this gradient to promote the uptake of HCO3? and various solutes, respectively. A Na+-dependent cotransporter mediates the movement of HCO3? across the basolateral membrane, whereas various Na+-independent passive transporters accomplish the export of various other solutes. To illustrate its homeostatic feat, the proximal tubule alters its metabolism and transport properties in response to metabolic acidosis. The uptake and catabolism of glutamine and citrate are increased during acidosis, whereas the recovery of phosphate from the ultrafiltrate is decreased. The increased catabolism of glutamine results in increased ammoniagenesis and gluconeogenesis. Excretion of the resulting ammonium ions facilitates the excretion of acid, whereas the combined pathways accomplish the net production of HCO3? ions that are added to the plasma to partially restore acid-base balance. PMID:23908456

2014-01-01

102

Sulfur amino acid metabolism in children with severe childhood undernutrition: methionine kinetics  

Technology Transfer Automated Retrieval System (TEKTRAN)

Children with edematous but not nonedematous severe childhood undernutrition (SCU) have lower plasma and erythrocyte-free concentrations of cysteine and methionine, which suggests a decreased availability of methionine for cysteine synthesis. We propose that methionine production and metabolism will...

103

Therapy of Bicarbonate-losing Renal Tubular Acidosis  

PubMed Central

A 2-year-old-girl with severe bicarbonate-losing renal tubular acidosis was treated successively with bicarbonate, THAM, and two diuretics, hydrochlorothiazide and frusemide. Only with hydrochlorothiazide was adequate correction of the acid-base balance achieved. The relative importance of changes induced by this treatment in the extracellular fluid volume and in chloride depletion was assessed. PMID:5491880

Donckerwolcke, R. A.; Van Stekelenburg, G. J.; Tiddens, H. A.

1970-01-01

104

Low-flow CO2 removal integrated into a renal-replacement circuit can reduce acidosis and decrease vasopressor requirements  

PubMed Central

Introduction Lung-protective ventilation in patients with ARDS and multiorgan failure, including renal failure, is often paralleled with a combined respiratory and metabolic acidosis. We assessed the effectiveness of a hollow-fiber gas exchanger integrated into a conventional renal-replacement circuit on CO2 removal, acidosis, and hemodynamics. Methods In ten ventilated critically ill patients with ARDS and AKI undergoing renal- and respiratory-replacement therapy, effects of low-flow CO2 removal on respiratory acidosis compensation were tested by using a hollow-fiber gas exchanger added to the renal-replacement circuit. This was an observational study on safety, CO2-removal capacity, effects on pH, ventilator settings, and hemodynamics. Results CO2 elimination in the low-flow circuit was safe and was well tolerated by all patients. After 4 hours of treatment, a mean reduction of 17.3 mm Hg (?28.1%) pCO2 was observed, in line with an increase in pH. In hemodynamically instable patients, low-flow CO2 elimination was paralleled by hemodynamic improvement, with an average reduction of vasopressors of 65% in five of six catecholamine-dependent patients during the first 24 hours. Conclusions Because no further catheters are needed, besides those for renal replacement, the implementation of a hollow-fiber gas exchanger in a renal circuit could be an attractive therapeutic tool with only a little additional trauma for patients with mild to moderate ARDS undergoing invasive ventilation with concomitant respiratory acidosis, as long as no severe oxygenation defects indicate ECMO therapy. PMID:23883472

2013-01-01

105

[The role of lactate besides the lactic acidosis].  

PubMed

Lactic acidosis (LA) is the most common form of metabolic acidosis defined by values of lactate greater than 5 mmol / l and by a pH <7.34. The pathogenesis of LA involves hypoxic (type A) and non hypoxic (type B) causes which are often coexisting. Lactic acidosis is usual in hospitalized population especially in subjects in intensive care units, in which lactate levels on admission could be predictors of mortality even in the absence of organ dysfunction or shock. The outcome is mainly dependent on the cardiovascular effects of acidosis. In subjects with cardiogenic shock, the increased lactate/pyruvate ratio, detectable at onset, is correladed with mortality. An early assessment of blood and tissue lactate levels could play a role in the therapeutic management as well as in outcome. LA could be a unfavorable prognostic factor in cancer. The lactate would act also as "signal molecule" and as a promoting factor in angiogenesis and tumor progression. In the presence of risk factors for LA the role of metformin may be overrated. Despite the doctrinal progress to understand the pathogenesis and pathophysiology, there is not univocal consensus on the therapeutic treatment of LA. The identification and the attempt to remove the cause of acidosis are main aims; treatment with sodium bicarbonate is a matter of debate as the data on the cardiovascular effects and mortality are unclear. The therapy with carbicarb, dichloroacetate or THAM has shown no specific advantages in terms of mortality. In experimental models of LA and shock the use of sodium-hydrogen exchanger-1 (NHE1) selective inhibitors reduces cell damage and inflammatory cytokines synthesis; it also improves cardiac performance and decreases mortality. PMID:23868642

Brucculeri, S; Urso, C; Caimi, G

2013-01-01

106

Type B lactic acidosis secondary to thiamine deficiency in a child with malignancy.  

PubMed

Type B lactic acidosis is an underrecognized clinical entity that must be distinguished from type A (hypoxic) lactic acidosis. We present the case of a 4-year-old boy with medulloblastoma who presented with lactic acidosis in the setting of septic shock. His hyperlactatemia persisted to high levels even after his hemodynamic status improved. After administration of intravenous thiamine, his lactate level rapidly normalized and remained stable. It was determined that his total parenteral nutrition was deficient in vitamins due to a national shortage. Because thiamine is an important cofactor for pyruvate dehydrogenase, he was unable to use glucose through aerobic metabolism pathways. We briefly review type A versus type B lactic acidosis in this case report. PMID:25548327

Shah, Sareen; Wald, Eric

2015-01-01

107

Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.  

PubMed

Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis. PMID:10590032

Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

1999-12-01

108

A case of lactic acidosis complicating assessment and management of asthma  

PubMed Central

Introduction Lactic acidosis often occurs in severely unwell patients presenting to Accident and Emergency. It is commonly associated with either hypoxia or decreased tissue perfusion secondary due to cardiovascular collapse or sepsis. Case presentation We present a case of severe lactic acidosis in the presence of normal tissue perfusion and oxygenation in a 31-year-old patient with poorly-controlled asthma. Acidosis promptly reversed on discontinuation of inhaled beta-agonists. Conclusion Lactic acidosis secondary to inhaled beta-agonist administration may be a common scenario which can be misinterpreted very easily and can confuse the clinical picture. Further studies will be needed to establish the exact aetiology of this lactic acid production. PMID:18471314

Veenith, Tonny V; Pearce, Abigail

2008-01-01

109

Management of Moderate to Severe Psoriasis in Patients with Metabolic Comorbidities  

PubMed Central

Psoriasis is a chronic inflammatory skin disease affecting 2–3% of worldwide population. The extent of skin involvement is variable, ranging from a few localized plaques to generalized involvement. Moderate to severe psoriasis (>10% of body surface area) is frequently associated with psoriatic arthritis and metabolic diseases, like abdominal obesity, diabetes, non-alcoholic fatty liver disease, dyslipidemia, metabolic syndrome, and chronic kidney disease. A common genetic background as well as several acquired risk factors links psoriasis to comorbidities. From a clinical prespective, the understanding of the patients in the context of these comorbidities is very important to ensure that treatment is tailored to meet the individual patient needs. Indeed, some pharmacological treatments may negatively affect cardio-metabolic comorbidities, and have important interactions with drugs that are commonly used to treat them. Non-pharmacological intervention such as diet, smoking cessation, and physical exercise could both improve the response to treatments for psoriasis and reduce the cardiovascular risk. PMID:25654080

Gisondi, Paolo; Galvan, Arturo; Idolazzi, Luca; Girolomoni, Giampiero

2015-01-01

110

Lipoamide dehydrogenase deficiency with primary lactic acidosis: favorable response to treatment with oral lipoic acid.  

PubMed

An 8-month-old boy with severe lactic acidosis was found to have lipoamide dehydrogenase deficiency. Treatment with thiamine, biotin, bicarbonate, protein restriction, and ketogenic diet failed to alleviate the lactic acidosis. Oral administration of lipoic acid 25 to 50 mg/kg produced dramatic improvement in lactic and pyruvic acidemia, which has continued for 2 years and which has been accompanied by clinical improvement. PMID:6418873

Matalon, R; Stumpf, D A; Michals, K; Hart, R D; Parks, J K; Goodman, S I

1984-01-01

111

AKI with serious state of acidosis in diabetic patients treated with metformin.  

PubMed

Metformin is a drug increasingly used in the treatment of diabetic patients. In addition to its hypoglycemic effect, it reduces vascular risk and does not determine an increase in body weight. Compared to the older molecule, phenformin, metformin possesses a lower risk of induction of severe lactic acidosis in the general diabetic population. On the other hand, metformin must be used with caution in patients with kidney damage. In patients with a glomerular filtration rate (GFR) below 30 ml/min, the use of metformin is also associated with a high risk of lactic acidosis. The assessment of glomerular filtration rate using MDRD or CKD-EPI formulas allows the clinician to identify patients potentially at risk. All subjects with normal renal function treated with metformin for years are at risk of suddenly developing lactic acidosis during episodes of acute worsening renal function. We report a case of lactic acidosis in association with acute kidney injury (AKI). PMID:24402626

Girasole, Filippo; Piccolo, Giuseppe; Timpanelli, Roberto; Calanna, Massimo; Piazza, Francesca; Vecchio, Sarah

2013-01-01

112

Acidosis and correction of acidosis does not affect rFVIIa function in swine  

PubMed Central

Background: Hemorrhagic shock and trauma are associated with acidosis and altered coagulation. A fall in pH has been reported to attenuate the activity of recombinant activated Factor VII (rFVIIa) in vitro. However, it is not known if acidosis induced by hemorrhagic shock or infusion of HCl attenuates FVIIa activity in vivo. The purpose of this study was to determine if acidosis, induced by two methods, affects recombinant FVIIa (rFVIIa) activity in swine, and if correction of the pH restores rFVIIa activity to normal. Methods: Acidosis was induce in anesthetized swine in two separate models: 1) HCl infusion (n=10) and 2) hemorrhage/hypoventilation (n=8). Three groups per model were used: Control (pH7.4), Acidosis (arterial pH7.1) and Acidosis-Corrected (bicarbonate infusion to return pH from 7.1 to 7.4). Pigs were then injected with rFVIIa (90 ?g/kg) or vehicle (saline) at target pH and arterial blood samples were taken for measurement of coagulation function, including Thromboelastography -TEG, Thrombin Generation, Activated Clotting Time, Prothrombin Time, activated Partial Thromboplastin Time, Fibrinogen Concentration and Platelet count before and 5min after injection of rFVIIa. Results: Acidosis led to a hypocoagulation as measured by almost all coagulation parameters in both models. Furthermore, the change in coagulation function produced after infusion of rFVIIa was not different between control, acidosis and acidosis-corrected groups for all coagulation parameters measured. Conclusion: Acidosis associated with hemorrhagic shock or HCl infusion led to a hypocoagulation that was not corrected with bicarbonate infusion. Furthermore, acidosis did not affect rFVIIa function, and correction of the acidosis with bicarbonate had no effect on rFVIIa function in these models. This suggests that in vivo acidosis did not diminish rFVIIa function. PMID:23272296

Darlington, Daniel N; Kheirabadi, Bijan S; Scherer, Michael R; Martini, Wenjun Z; Cap, Andrew P; Dubick, Michael A

2012-01-01

113

Metabolic Syndrome in Patients with Severe Mental Illness Undergoing Psychiatric Rehabilitation Receiving High Dose Antipsychotic Medication  

PubMed Central

Background: To review evidence of chronic antipsychotic medication and the association with metabolic syndrome in mentally ill patients. This evidence was used to analyse a cohort of patients with severe mental illness and to deduce a correlation between the prevalence of metabolic syndrome and their dose regimens. Materials and Methods: Twenty-four male patients undergoing Psychiatric rehabilitation underwent a review of current medication and assessment of risk factors for metabolic syndrome. Assessment criteria was based upon National Cholesterol Education Programme expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III) (NCEP ATP III) criteria, incorporating waist circumference, raised triglycerides, reduced high density lipoprotein, raised blood pressure and fasting blood glucose. PubMed, Nature and Science Direct databases have been used to compile the medical and scientific background on metabolic syndrome and antipsychotic medication and the effect on patients particularly on high dose. Results: Out of 24 patients, 10 patients (41.7%) were receiving high dose antipsychotics (HDA) and four were on maximum dosage limits of 100%. 8.3% (2/24) patients were receiving only one first generation antipsychotics (FGA), 37.5% (9/24) patients were receiving only one second generation antipsychotic (SGA), 45.8% patients (11/24) were receiving two or more SGA only, and only one patient was receiving two or more FGA. One patient was receiving a combination of FGA and SGA. PRN (“as needed”) therapy was not included in this study as their usage was limited. Clozapine was mostly prescribed in these patients (10/24, 41.6%). Four out of the 24 patients refused blood tests therefore were excluded from the following results. In the patients evaluated, 55% (11/20) had confirmed metabolic syndrome. In these patients with metabolic syndrome, 45.4% (5/11) were on HDA and 27.3% (3/11) were on maximum British National Formulary (BNF) limits of 100% of dosage. Four out of the nine remaining patients not diagnosed with metabolic syndrome were on HDA. Conclusions: Evidence supports the association between antipsychotic medication and metabolic syndrome. The data extrapolated from this cohort of mentally ill patients demonstrates that there is an increase in risk factors for metabolic syndrome and weight gain in the majority of patients on antipsychotic medication. The data however does not support any further predisposition to metabolic syndrome in these patients taking HDA. It also cannot be assumed antipsychotic medication is independently associated with the prevalence of these abnormalities. PMID:23439746

Ravindranath, Bapu V.

2012-01-01

114

Severe metabolic alkalosis due to baking soda ingestion: case reports of two patients with unsuspected antacid overdose.  

PubMed

Oral ingestion of baking soda (sodium bicarbonate) has been used for decades as a home remedy for acid indigestion. Excessive bicarbonate ingestion places patients at risk for a variety of metabolic derangements including metabolic alkalosis, hypokalemia, hypernatremia, and even hypoxia. The clinical presentation is highly variable but can include seizures, dysrhythmias, and cardiopulmonary arrest. We present two cases of severe metabolic alkalosis in patients with unsuspected antacid overdose. The presentation and pathophysiology of antacid-related metabolic alkalosis is reviewed. PMID:9950389

Fitzgibbons, L J; Snoey, E R

1999-01-01

115

Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survival  

PubMed Central

Sustained cellular function and viability of high-energy demanding post-mitotic cells rely on the continuous supply of ATP. The utilization of mitochondrial oxidative phosphorylation for efficient ATP generation is a function of oxygen levels. As such, oxygen deprivation, in physiological or pathological settings, has profound effects on cell metabolism and survival. Here we show that mild extracellular acidosis, a physiological consequence of anaerobic metabolism, can reprogramme the mitochondrial metabolic pathway to preserve efficient ATP production regardless of oxygen levels. Acidosis initiates a rapid and reversible homeostatic programme that restructures mitochondria, by regulating mitochondrial dynamics and cristae architecture, to reconfigure mitochondrial efficiency, maintain mitochondrial function and cell survival. Preventing mitochondrial remodelling results in mitochondrial dysfunction, fragmentation and cell death. Our findings challenge the notion that oxygen availability is a key limiting factor in oxidative metabolism and brings forth the concept that mitochondrial morphology can dictate the bioenergetic status of post-mitotic cells. PMID:24686499

Khacho, Mireille; Tarabay, Michelle; Patten, David; Khacho, Pamela; MacLaurin, Jason G.; Guadagno, Jennifer; Bergeron, Richard; Cregan, Sean P.; Harper, Mary-Ellen; Park, David S.; Slack, Ruth S.

2014-01-01

116

Chronic administration of Eucommia leaf stimulates metabolic function of rats across several organs.  

PubMed

Eucommia bark (Eucommia ulmoides Oliver) has been used as an herbal medicine, and more recently, the plant's leaves have been widely used to prepare tea which may have anti-obesity properties. We used a metabolic syndrome-like rat model, produced by feeding a 35% high-fat diet (HFD), to examine potential anti-obesity and anti-metabolic syndrome effects and mechanisms of chronic administration of Eucommia leaf as an extract or green leaf powder. Eighty rats were studied for 3 months in ten groups. Both forms of Eucommia leaves minimised increases in body weight and visceral fat in a dose-dependent fashion. Increases in plasma levels of TAG and NEFA, and insulin resistance secondary to HFD were lessened by both forms of Eucommia leaf. Concomitantly, an increase in plasma adiponectin levels and suppression of plasma resistin and TNF-? levels were confirmed. Real-time PCR studies showed that both forms of Eucommia leaf enhanced metabolic function across several organs, including diminishing ATP production (white adipose tissue), accelerating ?-oxidation (liver) and increasing the use of ketone bodies/glucose (skeletal muscle), all of which may exert anti-obesity effects under HFD conditions. These findings suggest that chronic administration of either form of Eucommia leaves stimulates the metabolic function in rats across several organs. The anti-obesity and anti-metabolic syndrome activity in this rat model may be maintained through secretion and regulation of adipocytokines that depend on the accumulation of visceral fat to improve insulin resistance or hyperlipaemia. PMID:20691136

Fujikawa, Takahiko; Hirata, Tetsuya; Wada, Atsunori; Kawamura, Naomi; Yamaguchi, Yasuyo; Fujimura, Katsuyuki; Ueda, Taro; Yurugi, Yutaka; Soya, Hideaki; Nishibe, Sansei

2010-12-01

117

Metabolomic profiling reveals severe skeletal muscle group-specific perturbations of metabolism in aged FBN rats.  

PubMed

Mammalian skeletal muscles exhibit age-related adaptive and pathological remodeling. Several muscles in particular undergo progressive atrophy and degeneration beyond median lifespan. To better understand myocellular responses to aging, we used semi-quantitative global metabolomic profiling to characterize trends in metabolic changes between 15-month-old adult and 32-month-old aged Fischer 344 × Brown Norway (FBN) male rats. The FBN rat gastrocnemius muscle exhibits age-dependent atrophy, whereas the soleus muscle, up until 32 months, exhibits markedly fewer signs of atrophy. Both gastrocnemius and soleus muscles were analyzed, as well as plasma and urine. Compared to adult gastrocnemius, aged gastrocnemius showed evidence of reduced glycolytic metabolism, including accumulation of glycolytic, glycogenolytic, and pentose phosphate pathway intermediates. Pyruvate was elevated with age, yet levels of citrate and nicotinamide adenine dinucleotide were reduced, consistent with mitochondrial abnormalities. Indicative of muscle atrophy, 3-methylhistidine and free amino acids were elevated in aged gastrocnemius. The monounsaturated fatty acids oleate, cis-vaccenate, and palmitoleate also increased in aged gastrocnemius, suggesting altered lipid metabolism. Compared to gastrocnemius, aged soleus exhibited far fewer changes in carbohydrate metabolism, but did show reductions in several glycolytic intermediates, fumarate, malate, and flavin adenine dinucleotide. Plasma biochemicals showing the largest age-related increases included glycocholate, heme, 1,5-anhydroglucitol, 1-palmitoleoyl-glycerophosphocholine, palmitoleate, and creatine. These changes suggest reduced insulin sensitivity in aged FBN rats. Altogether, these data highlight skeletal muscle group-specific perturbations of glucose and lipid metabolism consistent with mitochondrial dysfunction in aged FBN rats. PMID:24652515

Garvey, Sean M; Dugle, Janis E; Kennedy, Adam D; McDunn, Jonathan E; Kline, William; Guo, Lining; Guttridge, Denis C; Pereira, Suzette L; Edens, Neile K

2014-06-01

118

Comparisons of normal saline and lactated Ringer’s resuscitation on hemodynamics, metabolic responses, and coagulation in pigs after severe hemorrhagic shock  

PubMed Central

Background Ongoing improvements in trauma care now recommend earlier use of blood products as part of damage control resuscitation, but generally these products are not available at far forward battlefield locations. For the military, questions continue to arise regarding efficacy of normal saline (NS) vs. lactated Ringer’s (LR). Thus, this study compared the effects of LR and NS after severe hemorrhage in pigs. Methods 20 anesthetized pigs were randomized into control (n?=?6), LR (n?=?7), and NS (n?=?7) groups. Hemorrhage of 60% estimated total blood volume was induced in LR and NS groups by removing blood from the left femoral artery using a computer-controlled pump. Afterwards, the pigs were resuscitated with either LR at 3 times the bled volume or the volume of NS to reach the same mean arterial pressure (MAP) as in LR group. Hemodynamics were measured hourly and blood samples were taken at baseline (BL), 15 min, 3 h and 6 h after resuscitation to measure changes in coagulation using thrombelastograph®. Results MAP was decreased by hemorrhage but returned to BL within 1 h after resuscitation with LR (119?±?7 ml/kg) or NS (183?±?9 ml/kg, p?metabolic acidosis and hyperkalemia. PMID:24330733

2013-01-01

119

Obesity and the metabolic response to severe multiple trauma in man.  

PubMed Central

In the obese state profound metabolic disturbances exist and it is not known how this disrupted metabolism in obese subjects (body mass index greater than 30) may change their ability to respond to the superimposed, injury-induced stress. Understanding the mechanisms that modify the metabolic parameters in traumatized obese patients is essential in their nutritional assessment and further treatment. We have investigated in 7 obese and 10 nonobese multiple trauma patients, on a whole-body level, the energy metabolism, protein kinetics, and lipolysis in the early catabolic "flow phase" of severe injury when they were receiving maintenance fluids without calories or nitrogen. Traumatized obese patients mobilized relatively more protein and less fat compared with nonobese subjects. A relative block both in lipolysis and fat oxidation is experienced by injured obese patients that results in a shift to preferential use of proteins and carbohydrates. Reduced endogenous protein synthetic efficiency observed in obese patients implies increased protein recycling. Thus obese patients could not effectively use their most abundant fat fuel sources and have to depend on other fuel sources. The nutritional management of obese trauma victims should therefore be tailored towards provision of enough glucose calories to spare protein. Images PMID:1985100

Jeevanandam, M; Young, D H; Schiller, W R

1991-01-01

120

Renal tubular acidosis in renal transplant patients: the effect of immunosuppressive drugs.  

PubMed

Background Renal tubular acidosis (RTA) is a non-anion gap metabolic acidosis and is generally mild and asymptomatic in kidney recipients. Calcineurine inhibitors (CNIs) increase the frequency of RTA but the frequency of RTA development in kidney transplant recipients receiving mammalian target of rapamycin inhibitors (mTORi) treatment remains unclear. In this study, we aimed to investigate the frequency of RTA in kidney transplant recipients on mTORi and CNI treatment and to compare both groups. Material and Methods We enrolled 137 adult renal transplant patients - 82 patients on mTORi and 55 patients on CNI who had similar age, sex, posttransplant follow-up period, and graft functions. We recorded the parameters of venous blood gas analysis, including serum pH value, serum bicarbonate (HCO3) concentration, presence of metabolic acidosis defined as low HCO3 (<22 mEq/L), and serum pH value (<7.35), as well as base excess and urine pH at last follow-up. RTA was defined to be metabolic acidosis with normal serum anion gap and positive urine anion gap. Results The mean age of our study population was 41.2±11.3 years. RTA frequency was 35% in the mTORi group and 41% in the CNI group. mTORi and CNI groups did not differ significantly in terms of the development of metabolic and renal tubular acidosis. Type I RTA was common in both groups. RTA was affected by duration of time since transplantation and graft functions in both groups. Conclusions The rates of RTA development in patients on long-term CNI and mTORi treatment were similar. PMID:25659354

Tanrisev, Mehmet; Gungor, Ozkan; Kocyigit, Ismail; Kurtulmus, Yusuf; Tugmen, Cem; Colak, Hulya; Altunoren, Orcun; Kebapci, Eyup; Karaca, Cezmi

2015-01-01

121

Comparison of metabolic substrates in alligators and several birds of prey.  

PubMed

On average, avian blood glucose concentrations are 1.5-2 times those of mammals of similar mass and high concentrations of insulin are required to lower blood glucose. Whereas considerable data exist for granivorous species, few data are available for plasma metabolic substrate and glucoregulatory hormone concentrations for carnivorous birds and alligators. Birds and mammals with carnivorous diets have higher metabolic rates than animals consuming diets with less protein whereas alligators have low metabolic rates. Therefore, the present study was designed to compare substrate and glucoregulatory hormone concentrations in several birds of prey and a phylogenetically close relative of birds, the alligator. The hypothesis was that the combination of carnivorous diets and high metabolic rates favored the evolution of greater protein and fatty acid utilization leading to insulin resistance and high plasma glucose concentrations in carnivorous birds. In contrast, it was hypothesized that alligators would have low substrate utilization attributable to a low metabolic rate. Fasting plasma substrate and glucoregulatory hormone concentrations were compared for bald eagles (Haliaeetus leucocephalus), great horned owls (Bubo virginianus), red-tailed hawks (Buteo jamaicensis), and American alligators (Alligator mississippiensis). Avian species had high circulating ?-hydroxybutyrate (10-21 mg/dl) compared to alligators (2.81 ± 0.16 mg/dl). In mammals high concentrations of this byproduct of fatty acid utilization are correlated with insulin resistance. Fasting glucose and insulin concentrations were positively correlated in eagles whereas no relationship was found between these variables for owls, hawks or alligators. Additionally, ?-hydroxybutyrate concentrations were low in alligators. Similar to carnivorous mammals, ingestion of a high protein diet may have favored the utilization of fatty acids and protein for energy thereby promoting the development of insulin resistance and gluconeogenesis-induced high plasma glucose concentrations during periods of fasting in birds of prey. PMID:25043840

Sweazea, Karen L; McMurtry, John P; Elsey, Ruth M; Redig, Patrick; Braun, Eldon J

2014-08-01

122

Metabolic Syndrome Is Associated with Greater Histologic Severity, Higher Carbohydrate, and Lower Fat Diet in Patients with NAFLD  

Microsoft Academic Search

OBJECTIVES:Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome. Insulin resistance (IR) is a key component of metabolic syndrome. The aim was to determine the dietary composition, physical activity, and histologic severity between NAFLD patients with and without metabolic syndrome.METHODS:Ninety-one patients with NAFLD completed the Block Food Frequency Questionnaire and the Paffenbarger Physical Activity Questionnaire.

Hellan Kang; Joel K. Greenson; Jason T. Omo; Cewin Chao; Debra Peterman; Lilian Anderson; Laura Foess-Wood; Mary A. Sherbondy; Hari S. Conjeevaram

2006-01-01

123

Experimentally induced hyperchloremic and DL-lactic acidosis in calves: an attempt to study the effects of oral rehydration on acid-base status.  

PubMed

Many diarrheic calves suffer from metabolic acidosis, which is commonly treated by oral rehydration therapy. Oral rehydration solutions can be prepared in water, milk, or milk replacer. Therefore, the aim of the study was to verify dietary effects of water- or milk replacer-based oral rehydration solutions on parameters of acid-base balance in calves with experimentally induced hyperchloremic and dl-lactate acidosis. In 12 calves, hyperchloremic or dl-lactate acidosis was induced by HCl or dl-lactic acid infusions according to protocols outlined in previous literature. Immediately after induction, the calves were fed with milk replacer or water- or milk replacer-based oral rehydration solutions, or remained fasting, respectively. Blood samples were taken to monitor acid-base status over an experimental period of 4h. Using the protocols, all calves revealed a manifest hyperchloremic or dl-lactate acidosis. Because of high infusion volumes, plasma volume was expanded and effects of feeding regimens on blood parameters were rare. Unexpected clinical aberrations occurred after repeated induction of dl-lactate acidosis: all calves developed a thrombophlebitis of the jugular vein, whereas HCl infusion had no effect on endothelium. Induction of acidosis via infusion is not suitable to study dietary effects. A protocol to induce acidosis and dehydration simultaneously is required to duplicate the metabolic conditions of diarrheic calves. In further investigations, attention should be focused on effects of d-lactate or its metabolites on endothelial tissue. PMID:23415528

Schwedhelm, L; Kirchner, D; Klaus, B; Bachmann, L

2013-04-01

124

Early severe toxicities after capecitabine intake: possible implication of a cytidine deaminase extensive metabolizer profile.  

PubMed

We report here the case of a 19-year-old female patient who suffered from extremely severe toxicities (G4 mucitis, fever, diarrhea, alteration of general state) while undergoing low-dose capecitabine treatment for her metastatic corticosurrenaloma. The severe toxicities stopped as soon as treatment was suspended. Interestingly, this patient was not deficient in DPD, a pharmacogenetic syndrome usually associated with increased risk of developing severe/lethal toxicities in patients undergoing fluoropyrimidine therapy, and she had been treated previously with 5-FU with a good tolerance. We then hypothesized that cytidine deaminase (CDA) extensive phenotype could be responsible for the severe toxicities observed with capecitabine. CDA is affected by genetic polymorphism, with subsequent acquisition of either deficient or extensive metabolizer profile. Phenotypic investigations confirmed that CDA activity in this patient was +180% higher than the ones usually recorded in the general population. This strongly suggests that the extensive activation of triple-prodrug capecitabine could have occurred in this patient, resulting in overexposure to 5-FU and its cytotoxic metabolites eventually. This case report suggest for the first time that severe toxicities with a capecitabine-containing protocol could be, at least in part, linked with an extensive-CDA syndrome. The case reported here suggests therefore that besides DPD, screening for CDA activity could be of interest to ensure a better safety in the handling of oral capecitabine at the bedside. PMID:19107485

Mercier, Cedric; Dupuis, Charlotte; Blesius, Aurore; Fanciullino, Raphaelle; Yang, Chen Guang; Padovani, Laetitia; Giacometti, Sarah; Frances, Nicolas; Iliadis, Athanassios; Duffaud, Florence; Ciccolini, Joseph

2009-05-01

125

Acidosis Activation of the Proton-Sensing GPR4 Receptor Stimulates Vascular Endothelial Cell Inflammatory Responses Revealed by Transcriptome Analysis  

PubMed Central

Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-?B pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2) and stress response genes such as ATF3 and DDIT3 (CHOP). Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-?B pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be suppressed by GPR4 small molecule inhibitors and hold potential therapeutic value. PMID:23613998

Dong, Lixue; Li, Zhigang; Leffler, Nancy R.; Asch, Adam S.; Chi, Jen-Tsan; Yang, Li V.

2013-01-01

126

Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting  

PubMed Central

The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and play a crucial role in maintaining epidermal integrity and barrier function. SAM syndrome-causing mutations resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. The deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect. PMID:23974871

Rapaport, Debora; Ishida-Yamamoto, Akemi; Isakov, Ofer; Koetsier, Jennifer L; Gat, Andrea; Goldberg, Ilan; Bergman, Reuven; Spiegel, Ronen; Eytan, Ori; Geller, Shamir; Peleg, Sarit; Shomron, Noam; Goh, Christabelle S M; Wilson, Neil J; Smith, Frances J D; Pohler, Elizabeth; Simpson, Michael A; McLean, W H Irwin; Irvine, Alan D; Horowitz, Mia; McGrath, John A; Green, Kathleen J; Sprecher, Eli

2013-01-01

127

[A case of mFOLFOX6-induced lactic acidosis in a patient with colon cancer].  

PubMed

Leucovorin calcium, 5-fluorouracil, and oxaliplatin (FOLFOX) therapy is a standard chemotherapy regimen used to treat colorectal cancer. Peripheral nerve disorder and myelosuppression are frequently reported treatment-related adverse events. With modified FOLFOX6 (mFOLFOX6) therapy, adverse events of an altered mental state with reversible posterior leukoencephalopathy and hypoammonemia have been reported, while lactic acidosis is uncommon. We describe a case of mFOLFOX6 - induced lactic acidosis in a 64-year-old man with colorectal cancer who underwent pelvic exenteration following chemotherapy. Postoperative histopathological analysis revealed residual cancer. Following the commencement of mFOLFOX6 therapy, the patient experienced emesis, hiccupping, and an altered mental state. Laboratory testing revealed only severe lactic acidosis, while diagnostic imaging was unrevealing. All symptoms quickly improved upon the administration of intravenous infusion of sodium bicarbonate. PMID:25434453

Ito, Atene; Kawamoto, Kazuyuki; Park, Taebun; Ito, Tadashi

2014-11-01

128

Metformin-induced lactic acidosis with emphasis on the anion gap  

PubMed Central

The presence of an anion gap in a diabetic patient, especially if associated with evidence of compromised renal function, should prompt clinicians to consider metformin as a contributing factor. This consideration is especially important in patients with severe anion gaps associated with lactic acidosis out of proportion to the patient's clinical presentation. PMID:25552792

Blough, Britton; Moreland, Amber

2015-01-01

129

Metformin-induced lactic acidosis with emphasis on the anion gap.  

PubMed

The presence of an anion gap in a diabetic patient, especially if associated with evidence of compromised renal function, should prompt clinicians to consider metformin as a contributing factor. This consideration is especially important in patients with severe anion gaps associated with lactic acidosis out of proportion to the patient's clinical presentation. PMID:25552792

Blough, Britton; Moreland, Amber; Mora, Adan

2015-01-01

130

Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia.  

PubMed

Low serum folate levels previously have been associated with negative symptom risk in schizophrenia, as has the hypofunctional 677C>T variant of the MTHFR gene. This study examined whether other missense polymorphisms in folate-regulating enzymes, in concert with MTHFR, influence negative symptoms in schizophrenia, and whether total risk allele load interacts with serum folate status to further stratify negative symptom risk. Medicated outpatients with schizophrenia (n = 219), all of European origin and some included in a previous report, were rated with the Positive and Negative Syndrome Scale. A subset of 82 patients also underwent nonfasting serum folate testing. Patients were genotyped for the MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTR 2756A>G (rs1805087), MTRR 203A>G (rs1801394), FOLH1 484T>C (rs202676), RFC 80A>G (rs1051266), and COMT 675G>A (rs4680) polymorphisms. All genotypes were entered into a linear regression model to determine significant predictors of negative symptoms, and risk scores were calculated based on total risk allele dose. Four variants, MTHFR 677T, MTR 2756A, FOLH1 484C, and COMT 675A, emerged as significant independent predictors of negative symptom severity, accounting for significantly greater variance in negative symptoms than MTHFR 677C>T alone. Total allele dose across the 4 variants predicted negative symptom severity only among patients with low folate levels. These findings indicate that multiple genetic variants within the folate metabolic pathway contribute to negative symptoms of schizophrenia. A relationship between folate level and negative symptom severity among patients with greater genetic vulnerability is biologically plausible and suggests the utility of folate supplementation in these patients. PMID:22021659

Roffman, Joshua L; Brohawn, David G; Nitenson, Adam Z; Macklin, Eric A; Smoller, Jordan W; Goff, Donald C

2013-03-01

131

Severe Metabolic Bone Disease as a Long-Term Complication of Obesity Surgery  

Microsoft Academic Search

Background: Metabolic bone disease is a well-documented long-term complication of obesity surgery. It is often undiagnosed,\\u000a or misdiagnosed, because of lack of physician and patient awareness. Abnormalities in calcium and vitamin D metabolism begin\\u000a shortly after gastrointestinal bypass operations; however, clinical and biochemical evidence of metabolic bone disease may\\u000a not be detected until many years later. Case Report: A 57-year-old

Whitney S. Goldner; Thomas M. O'Dorisio; Joseph S. Dillon; Edward E. Mason

2002-01-01

132

Immune-related potassium-losing interstitial nephritis: a comparison with distal renal tubular acidosis.  

PubMed

Six patients with immune-related potassium-losing interstitial nephritis (IRPLIN) are described, and compared with 34 patients with immune-related distal renal tubular acidosis (IRdRTA) and 24 with familial distal renal tubular acidosis (FdRTA). Close similarities were found between IRPLIN and IRdRTA. In our experience, both syndromes are confined to postpubertal women, and are characterized by systemic features of autoimmune disease and a chronic interstitial nephritis which is probably immune-mediated and responsible for the functional tubular defects of the two syndromes. In IRPLIN, a renal potassium-losing state is the main consequence (probably mediated at least in part by renin and aldosterone hypersecretion secondary to renal sodium-losing), and urinary acidification is normal or minimally disturbed; consequently there is no systemic acidosis, and the syndrome is not complicated by nephrocalcinosis or renal bone disease. In IRdRTA, the renal tubular lesion also usually causes potassium depletion, but the most prominent tubular fault is a defect in urinary acidification, which commonly causes metabolic acidosis and often leads to nephrocalcinosis and bone disease. Familial dRTA, in contrast, is equally prevalent in the two sexes and presents at an earlier age than IRPLIN and IRdRTA. Patients with FdRTA and IRdRTA have a similar urinary acidification defect and propensity to acidosis, nephrocalcinosis and bone disease. FdRTA is frequently complicated by renal potassium-losing, but hypokalaemia is less common and less profound than in IRdRTA and IRPLIN, suggesting that immune-related interstitial nephritis has a particular tendency to cause renal potassium-losing. PMID:8210309

Wrong, O M; Feest, T G; MacIver, A G

1993-08-01

133

Systemic lupus erythematosus associated with type 4 renal tubular acidosis: a case report and review of the literature  

PubMed Central

Introduction Type 4 renal tubular acidosis is an uncommon clinical manifestation of systemic lupus erythematosus and has been reported to portend a poor prognosis. To the best of our knowledge, this is the first case report which highlights the successful management of a patient with systemic lupus erythematosus complicated by type 4 renal tubular acidosis who did not do poorly. Case presentation A 44-year-old Hispanic woman developed a non-anion gap hyperkalemic metabolic acidosis consistent with type 4 renal tubular acidosis while being treated in the hospital for recently diagnosed systemic lupus erythematosus with multi-organ involvement. She responded well to treatment with corticosteroids, hydroxychloroquine and mycophenolate mofetil. Normal renal function was achieved prior to discharge and remained normal at the patient's one-month follow-up examination. Conclusion This case increases awareness of an uncommon association between systemic lupus erythematosus and type 4 renal tubular acidosis and suggests a positive impact of early diagnosis and appropriate immunosuppressive treatment on the patient's outcome. PMID:21435204

2011-01-01

134

Effects of HIV Infection on the Metabolic and Hormonal Status of Children with Severe Acute Malnutrition  

PubMed Central

Background HIV infection occurs in 30% of children with severe acute malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and recovery from malnutrition are poorly understood. Methods We conducted a prospective cohort study of 75 severely malnourished Ugandan children. HIV status/CD4 counts were assessed at baseline; auxologic data and blood samples were obtained at admission and after 14 days of inpatient treatment. We utilized metabolomic profiling to characterize effects of HIV infection on metabolic status and subsequent responses to nutritional therapy. Findings At admission, patients (mean age 16.3 mo) had growth failure (mean W/H z-score ?4.27 in non-edematous patients) that improved with formula feeding (mean increase 1.00). 24% (18/75) were HIV-infected. Nine children died within the first 14 days of hospitalization; mortality was higher for HIV-infected patients (33% v. 5%, OR?=?8.83). HIV-infected and HIV-negative children presented with elevated NEFA, ketones, and even-numbered acylcarnitines and reductions in albumin and amino acids. Leptin, adiponectin, insulin, and IGF-1 levels were low while growth hormone, cortisol, and ghrelin levels were high. At baseline, HIV-infected patients had higher triglycerides, ketones, and even-chain acylcarnitines and lower leptin and adiponectin levels than HIV-negative patients. Leptin levels rose in all patients following nutritional intervention, but adiponectin levels remained depressed in HIV-infected children. Baseline hypoleptinemia and hypoadiponectinemia were associated with increased mortality. Conclusions Our findings suggest a critical interplay between HIV infection and adipose tissue storage and function in the adaptation to malnutrition. Hypoleptinemia and hypoadiponectinemia may contribute to high mortality rates among malnourished, HIV-infected children. PMID:25050734

Hornik, Christoph P.; Kiyimba, Tonny; Bain, James; Muehlbauer, Michael; Kiboneka, Elizabeth; Stevens, Robert; St. Peter, John V.; Newgard, Christopher B.; Bartlett, John; Freemark, Michael

2014-01-01

135

Lactic Acidosis after Treatment with Linezolid  

Microsoft Academic Search

Linezolid is currently indicated to treat vancomycin-resistant Enterococcus faecium infections, nosocomial pneumonia caused by Staphylococcus aureus or Streptococcus pneumoniae, complicated and uncomplicated skin and skin structure infections, and community-acquired pneumonia. We report a case of\\u000a linezolid-induced lactic acidosis during treatment of vancomycin-resistant enterococcal bacteremia after mitral valve replacement\\u000a and permanent pacemaker implantation. We also review the current literature describing other

M. Wiener; Y. Guo; G. Patel; B. C. Fries

2007-01-01

136

Metabolic crisis in severely head-injured patients: is ischemia just the tip of the iceberg?  

PubMed

Ischemia and metabolic crisis are frequent post-traumatic secondary brain insults that negatively influence outcome. Clinicians commonly mix up these two types of insults, mainly because high lactate/pyruvate ratio (LPR) is the common marker for both ischemia and metabolic crisis. However, LPR elevations during ischemia and metabolic crisis reflect two different energetic imbalances: ischemia (Type 1 LPR elevations with low oxygenation) is characterized by a drastic deprivation of energetic substrates, whereas metabolic crisis (Type 2 LPR elevations with normal or high oxygenation) is associated with profound mitochondrial dysfunction but normal supply of energetic substrates. The discrimination between ischemia and metabolic crisis is crucial because conventional recommendations against ischemia may be detrimental for patients with metabolic crisis. Multimodal monitoring, including microdialysis and brain tissue oxygen monitoring, allows such discrimination, but these techniques are not easily accessible to all head-injured patients. Thus, a new "gold standard" and adapted medical education are required to optimize the management of patients with metabolic crisis. PMID:24130548

Carre, Emilie; Ogier, Michael; Boret, Henry; Montcriol, Ambroise; Bourdon, Lionel; Jean-Jacques, Risso

2013-01-01

137

Metabolic Crisis in Severely Head-Injured Patients: Is Ischemia Just the Tip of the Iceberg?  

PubMed Central

Ischemia and metabolic crisis are frequent post-traumatic secondary brain insults that negatively influence outcome. Clinicians commonly mix up these two types of insults, mainly because high lactate/pyruvate ratio (LPR) is the common marker for both ischemia and metabolic crisis. However, LPR elevations during ischemia and metabolic crisis reflect two different energetic imbalances: ischemia (Type 1 LPR elevations with low oxygenation) is characterized by a drastic deprivation of energetic substrates, whereas metabolic crisis (Type 2 LPR elevations with normal or high oxygenation) is associated with profound mitochondrial dysfunction but normal supply of energetic substrates. The discrimination between ischemia and metabolic crisis is crucial because conventional recommendations against ischemia may be detrimental for patients with metabolic crisis. Multimodal monitoring, including microdialysis and brain tissue oxygen monitoring, allows such discrimination, but these techniques are not easily accessible to all head-injured patients. Thus, a new “gold standard” and adapted medical education are required to optimize the management of patients with metabolic crisis. PMID:24130548

Carre, Emilie; Ogier, Michael; Boret, Henry; Montcriol, Ambroise; Bourdon, Lionel; Jean-Jacques, Risso

2013-01-01

138

[Distal renal tubular acidosis and nephrolithiasis in 3 cases of primary Sjögren syndrome].  

PubMed

Tubulo interstitial nephritis, the main manifestation of renal involvement in Sjögren syndrome, may lead to a tubular dysfunction that is usually subclinical. We report three women, aged 32, 35 and 35 years old, with a primary Sjögren syndrome and symptomatic type I or distal tubular acidosis. Two patients had nephrolithiasis and one a nephrocalcinosis. Two had a basal hyperchloremic metabolic acidosis. The ammonium chloride acidification test was abnormal in all, demonstrating a distal tubular defect. None had proximal tubular dysfunction. All had an urinary pH over 6.5 and hypocitraturia and none had hypercalciuria. Renal calculi were composed of calcium oxalate and calcium phosphate in two patients and calcium phosphate and ammonium phosphate in the other. All women had positive antinuclear antibodies with mottled pattern, two had anti Ro antibodies and positive rheumatoid factor and one had hypergammaglobulinemia. None had anti La antibodies, crioglobulinemia or monoclonal proteins. PMID:9334481

Aguilera, S; López, R; Valdivieso, A

1996-12-01

139

Gingival overgrowth caused by vitamin C deficiency associated with metabolic syndrome and severe periodontal infection: a case report  

PubMed Central

It has been suggested that vitamin C deficiency/scurvy is associated with gingival inflammatory changes; however, the disorder is very infrequently encountered in the modern era. Here, we report a case of extensive gingival overgrowth caused by vitamin C deficiency associated with metabolic syndrome and severe periodontal infection. PMID:25548632

Omori, Kazuhiro; Hanayama, Yoshihisa; Naruishi, Koji; Akiyama, Kentaro; Maeda, Hiroshi; Otsuka, Fumio; Takashiba, Shogo

2014-01-01

140

Anesthetic Management of a Patient with Sustained Severe Metabolic Alkalosis and Electrolyte Abnormalities Caused by Ingestion of Baking Soda  

PubMed Central

The use of alternative medicine is prevalent worldwide. However, its effect on intraoperative anesthetic care is underreported. We report the anesthetic management of a patient who underwent an extensive head and neck cancer surgery and presented with a severe intraoperative metabolic alkalosis from the long term ingestion of baking soda and other herbal remedies. PMID:25180100

Lim, Jeffrey

2014-01-01

141

Anesthetic management of a patient with sustained severe metabolic alkalosis and electrolyte abnormalities caused by ingestion of baking soda.  

PubMed

The use of alternative medicine is prevalent worldwide. However, its effect on intraoperative anesthetic care is underreported. We report the anesthetic management of a patient who underwent an extensive head and neck cancer surgery and presented with a severe intraoperative metabolic alkalosis from the long term ingestion of baking soda and other herbal remedies. PMID:25180100

Soliz, Jose; Lim, Jeffrey; Zheng, Gang

2014-01-01

142

Functional Metabolomics Uncovers Metabolic Alterations Associated to Severe Oxidative Stress in MCF7 Breast Cancer Cells Exposed to Ascididemin  

PubMed Central

Marine natural products are a source of promising agents for cancer treatment. However, there is a need to improve the evaluation of their mechanism of action in tumors. Metabolomics of the response to anti-tumor agents is a tool to reveal candidate biomarkers and metabolic targets. We used two-dimensional high-resolution magic angle spinning proton-NMR spectroscopy-based metabolomics to investigate the response of MCF7 breast cancer cells to ascididemin, a marine alkaloid and lead molecule for anti-cancer treatment. Ascididemin induced severe oxidative stress and apoptosis within 48 h of exposure. Thirty-three metabolites were quantified. Metabolic response involved downregulation of glycolysis and the tricarboxylic acid cycle, and phospholipid metabolism alterations. Candidate metabolic biomarkers of the response of breast cancer cells to ascididemin were proposed including citrate, gluconate, polyunsaturated fatty acids, glycerophospho-choline and -ethanolamine. In addition, candidate metabolic targets were identified. Overall, the response to Asc could be related to severe oxidative stress and anti-inflammatory effects. PMID:24152560

Morvan, Daniel

2013-01-01

143

Distal Renal Tubular Acidosis and Calcium Nephrolithiasis  

NASA Astrophysics Data System (ADS)

Calcium stones are commonly encountered in patients with congenital distal renal tubular acidosis, a disease of renal acidification caused by mutations in either the vacuolar H+-ATPase (B1 or a4 subunit), anion exchanger-1, or carbonic anhydrase II. Based on the existing database, we present two hypotheses. First, heterozygotes with mutations in B1 subunit of H+-ATPase are not normal but may harbor biochemical abnormalities such as renal acidification defects, hypercalciuria, and hypocitraturia which can predispose them to kidney stone formation. Second, we propose at least two mechanisms by which mutant B1 subunit can impair H+-ATPase: defective pump assembly and defective pump activity.

Moe, Orson W.; Fuster, Daniel G.; Xie, Xiao-Song

2008-09-01

144

DIAGNOSING & MANAGING SUBCLINICAL RUMEN ACIDOSIS IN DAIRY CATTLE.  

Technology Transfer Automated Retrieval System (TEKTRAN)

Ruminal acidosis is a major diet-related health disorder of dairy cattle. It appears to present itself as a syndrome that has negative effects on far more than just the rumen. To understand how best to reduce the health problems related to "ruminal acidosis", being able to recognize it and the fac...

145

Near-fatal persistent anion- and osmolal-gap acidosis due to massive gamma-butyrolactone/ethanol intoxication.  

PubMed

We report a case of an ethanol and massive gamma-butyrolactone (GBL) intoxication, the precursor of the recreational drug gamma-hydroxybutyric acid (GHB), resulting in life-threatening metabolic acidosis (pH 6.5) with a highly increased anion- and osmolal gap. Rapid analysis using gas chromatography revealed a GHB plasma concentration of 4400?mg/L, far above the upper limit concentration of 1000?mg/L found in adult fatalities attributed to GBL. Full recovery was established following supportive treatment including haemodialysis. This is the first report of a combined ethanol/GBL intoxication as a cause of high serum anion- and osmolal-gap metabolic acidosis. PMID:25205856

Heytens, Luc; Neels, Hugo; Van Regenmortel, Niels; van den Brink, Wim; Henckes, Manu; Schouwers, Sofie; Dockx, Greet; Crunelle, Cleo L

2014-09-01

146

Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss  

PubMed Central

Autosomal recessive distal renal tubular acidosis (rdRTA) is characterised by severe hyperchloraemic metabolic acidosis in childhood, hypokalaemia, decreased urinary calcium solubility, and impaired bone physiology and growth. Two types of rdRTA have been differentiated by the presence or absence of sensorineural hearing loss, but appear otherwise clinically similar. Recently, we identified mutations in genes encoding two different subunits of the renal ?-intercalated cell's apical H+-ATPase that cause rdRTA. Defects in the B1 subunit gene ATP6V1B1, and the a4 subunit gene ATP6V0A4, cause rdRTA with deafness and with preserved hearing, respectively. We have investigated 26 new rdRTA kindreds, of which 23 are consanguineous. Linkage analysis of seven novel SNPs and five polymorphic markers in, and tightly linked to, ATP6V1B1 and ATP6V0A4 suggested that four families do not link to either locus, providing strong evidence for additional genetic heterogeneity. In ATP6V1B1, one novel and five previously reported mutations were found in 10 kindreds. In 12 ATP6V0A4 kindreds, seven of 10 mutations were novel. A further nine novel ATP6V0A4 mutations were found in "sporadic" cases. The previously reported association between ATP6V1B1 defects and severe hearing loss in childhood was maintained. However, several patients with ATP6V0A4 mutations have developed hearing loss, usually in young adulthood. We show here that ATP6V0A4 is expressed within the human inner ear. These findings provide further evidence for genetic heterogeneity in rdRTA, extend the spectrum of disease causing mutations in ATP6V1B1 and ATP6V0A4, and show ATP6V0A4 expression within the cochlea for the first time. PMID:12414817

Stover, E; Borthwick, K; Bavalia, C; Eady, N; Fritz, D; Rungroj, N; Giersch, A; Morton, C; Axon, P; Akil, I; Al-Sabban, E; Baguley, D; Bianca, S; Bakkaloglu, A; Bircan, Z; Chauveau, D; Clermont, M; Guala, A; Hulton, S; Kroes, H; Li, V; Mir, S; Mocan, H; Nayir, A; Ozen, S; Rodriguez, S; Sanjad, S; Tasic, V; Taylor, C; Topaloglu, R; Smith, A; Karet, F

2002-01-01

147

Metabolism  

MedlinePLUS

Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson BH. Principles of Anatomy and Physiology . 14th ed. Hoboken, NJ: John H Wiley and Sons; 2013: ...

148

[Metabolic side effects of antiretroviral therapy].  

PubMed

Antiretroviral therapy for HIV-I-infections is accompanied with the occurrence of several metabolic side effects. An often encountered complication of antiretroviral therapy is the adipose redistribution syndrome characterised by an altered distribution of body fat, and linked with protease inhibitor (PI) and nucleoside-reverse-transcriptase inhibitors (NRTIs). Some NRTIs have lactate acidosis as a side effect in rare cases (0.1%), which is accompanied by a high mortality. The far less serious side effect hyperlactaemia is more frequently observed; this is a symptomatic elevation of the lactate level without acidosis. Insulin resistance is not only ascribed to therapy-induced lipoatrophy and visceral fat accumulation, it is also directly related to the use of some PIs and NRTIs. PIs and abacavir and to a lesser extend didanosine result in a high risk of cardiovascular disease. Moreover, the prevalence of traditional cardiovascular risk factors in HIV-infected subjects is higher than that in HIV-seronegative subjects. Clinically relevant interactions exist between PIs and statins. Pravastatin seems to be accompanied with the lowest chance of interaction and is therefore recommended as cholesterol-lowering therapy. The metabolic side effects are outweighed by the favourable effect of the antiretroviral agents. Counteraction of these side effects may therefore not be at the expense of the antiretroviral therapy. PMID:18590059

van der Valk, M; Reiss, P

2008-05-31

149

Behavioural adaptations of sheep to repeated acidosis challenges and effect of yeast supplementation.  

PubMed

This study aims to determine whether sheep modify their feeding and general behaviour when they undergo acidosis challenge, whether these modifications are maintained when acidosis challenges are repeated and whether yeast supplementation affects these modifications. Twelve rumen-cannulated wethers fed concentrate (wheat) and forage (hay) were exposed to three 28-day periods consisting of a 23-day recovery phase (20% of wheat) followed by a 5-day acidosis challenge (60% of wheat). Both diets limited food intake to 90% of ad libitum intake. Six sheep received a daily supplementation of a live yeast product, six received a placebo. Ruminal pH was recorded continuously. Daily consumption of wheat, hay, water and weekly consumption of salt were monitored. Behavioural observations were performed twice in each period: once under the recovery phase and once under acidosis challenge. These observations included video recordings over 24 h (time budget), social tests (mixing with another sheep for 5 min) and nociception tests (CO2 hot laser). As expected, sheep spent more time with a ruminal pH below 5.6 during challenges than during recovery phases (12.5 v. 4.7 h/day). Sheep drank more water (3.87 v. 3.27 l/day) and ingested more salt (16 v. 11 g/day) during challenges. They also spent more time standing than during recovery phases, adopting more frequent alarm postures and reacting more slowly to the hot stimulus. More severe behavioural modifications were observed during the first challenge than the two other challenges. Significant concentrate refusals were observed during challenge 1: from days 3 to 5 of this challenge, sheep ate only half of the distributed concentrate. Sheep were also more active and more aggressive towards each other in challenge 1. These behavioural modifications disappeared as the challenges were repeated: no behavioural modifications were observed between challenges and recovery phases during periods 2 and 3, and furthermore, sheep rapidly ate all the concentrate distributed during the third challenge. Focusing on the effects of yeast, the only differences registered between the two groups concerned ruminal pH, that is, mean ruminal pH values in the supplemented group were lower during the first challenge (5.11 v. 5.60) but higher during the third challenge (5.84 v. 5.28). In conclusion, our experiment suggests sheep can adapt to acidosis challenges, especially with yeast supplementation. Otherwise, ruminal pH values remained low during challenges, indicating that the modifications of general and feeding behaviour in subacute ruminal acidosis situations are not due exclusively to low ruminal pH values. PMID:23031140

Commun, L; Silberberg, M; Mialon, M M; Martin, C; Veissier, I

2012-12-01

150

Characterization of the interaction between local cerebral metabolic rate for glucose and acid-base index in ischemic rat brain employing a double-isotope methodology  

SciTech Connect

The association between increases in cerebral glucose metabolism and the development of acidosis is largely inferential, based on reports linking hyperglycemia with poor neurological outcome, lactate accumulation, and the severity of acidosis. We measured local cerebral metabolic rate for glucose (lCMRglc) and an index of brain pH-the acid-base index (ABI)-concurrently and characterized their interaction in a model of focal cerebral ischemia in rats in a double-label autoradiographic study, using ({sup 14}C)2-deoxyglucose and ({sup 14}C)dimethyloxazolidinedione. Computer-assisted digitization and analysis permitted the simultaneous quantification of the two variables on a pixel-by-pixel basis in the same brain slices.

Peek, K.E.H.

1988-01-01

151

Stimulation of the plasma membrane Na+/H+ exchanger NHE1 by sustained intracellular acidosis. Evidence for a novel mechanism mediated by the ERK pathway.  

PubMed

Activity of the Na+/H+ exchanger (NHE) isoform 1 (NHE1) is increased by intracellular acidosis through the interaction of intracellular H+ with an allosteric modifier site in the transport domain. Additional regulation is achieved via kinase-mediated modulation of the NHE1 regulatory domain. To determine if intracellular acidosis stimulates NHE1 activity solely by the allosteric mechanism, we subjected cultured neonatal rat ventricular myocytes (NRVM) with native NHE1 expression to intracellular acidosis (pHi approximately 6.6) for up to 6 min by transient exposure to NH4Cl and its washout in the presence of NHE inhibition (by zero [Na+]o or the NHE1 inhibitor cariporide) in HCO3- -free medium. After the desired duration of acidosis, NHE was reactivated (by reintroduction of [Na+]o or removal of cariporide), and the rate of recovery of pHi (dpHi/dt) was measured as the index of NHE activity. Regardless of the method used when intracellular acidosis was sustained for > or =3 min, subsequent NHE activity was significantly increased (>4-fold). Similar NHE stimulatory effects of sustained acidosis were observed in adult rat ventricular myocytes and COS-7 cells. Sustained (3 min) intracellular acidosis activated several NHE1 kinases in NRVM, in an in-gel kinase assay using as substrate a glutathione S-transferase fusion protein of the NHE1 regulatory domain. Detailed investigation of ERK and its downstream effector p90RSK, two putative NHE1 kinases, revealed time-dependent activation of both by intracellular acidosis in NRVM. Furthermore, inhibition of MEK1/2 by pretreatment of NRVM with two structurally distinct inhibitors, PD98059 (30 microM) or UO126 (3 microM), inhibited the activation of ERK and p90RSK and abolished the stimulation of NHE activity by sustained (3 min) intracellular acidosis. Our data show that not only the extent but also the duration of intracellular acidosis regulates NHE1 activity and suggest that the stimulatory effect of sustained intracellular acidosis occurs through a novel mechanism mediated by activation of the ERK pathway. PMID:12791686

Haworth, Robert S; McCann, Caroline; Snabaitis, Andrew K; Roberts, Neil A; Avkiran, Metin

2003-08-22

152

Distal Renal Tubular Acidosis in Infancy: A Bicarbonate Wasting State  

ERIC Educational Resources Information Center

Studied were three unrelated infants with distal renal tubular acidosis (a condition characterized by an inability to acidify the urine to minimal pH levels resulting in the loss of bicarbonates). (DB)

Rodriguez-Soriano, J.; And Others

1975-01-01

153

Putrescine catabolism is a metabolic response to several stresses in Escherichia coli.  

PubMed

Genes whose products degrade arginine and ornithine, precursors of putrescine synthesis, are activated by either regulators of the nitrogen-regulated (Ntr) response or ?(S) -RNA polymerase. To determine if dual control regulates a complete putrescine catabolic pathway, we examined expression of patA and patD, which specify the first two enzymes of one putrescine catabolic pathway. Assays of PatA (putrescine transaminase) activity and ?-galactosidase from cells with patA-lacZ transcriptional and translational fusions indicate dual control of patA transcription and putrescine-stimulated patA translation. Similar assays for PatD indicate that patD transcription required ?(S) -RNA polymerase, and Nac, an Ntr regulator, enhanced the ?(S) -dependent transcription. Since Nac activation via ?(S) -RNA polymerase is without precedent, transcription with purified components was examined and the results confirmed this conclusion. This result indicates that the Ntr regulon can intrude into the ?(S) regulon. Strains lacking both polyamine catabolic pathways have defective responses to oxidative stress, high temperature and a sublethal concentration of an antibiotic. These defects and the ?(S) -dependent expression indicate that polyamine catabolism is a core metabolic response to stress. PMID:23531166

Schneider, Barbara L; Hernandez, V James; Reitzer, Larry

2013-05-01

154

Low-grade inflammation can partly explain the association between the metabolic syndrome and either coronary artery disease or severity of peripheral arterial disease: the CODAM study  

Microsoft Academic Search

Background Low-grade inflammation has been hypothesized to underlie the coronary artery disease (CAD) risk associated with the metabolic syndrome, but the evidence is not conclusive. For peripheral arterial disease (PAD; as measured by the ankle-arm index), this association has not been studied before. The aim was to study whether the association between the metabolic syndrome and CAD or the severity

M. Jacobs; M. M. J. van Greevenbroek; C. J. H. van der Kallen; I. Ferreira; E. E. Blaak; E. J. M. Feskens; E. H. J. M. Jansen; C. G. Schalkwijk; C. D. A. Stehouwer

2009-01-01

155

Unique metabolic characteristics of the major syndromes of severe childhood malnutrition  

Technology Transfer Automated Retrieval System (TEKTRAN)

The major clinical syndromes of severe childhood malnutrition (SCM) are marasmus, kwashiorkor and marasmic-kwashiorkor. Whereas treatment of marasmus is straightforward and the associated mortality is low, kwashiorkor and marasmic-kwashiorkor are difficult to treat and have high morbidity and mortal...

156

Sulfur amino acid metabolism in children with severe childhood undernutrition: cysteine kinetics  

Technology Transfer Automated Retrieval System (TEKTRAN)

Children with edematous but not nonedematous severe childhood undernutrition (SCU) have lower plasma and erythrocyte-free concentrations of cysteine, the rate-limiting precursor of glutathione synthesis. We propose that these lower cysteine concentrations are due to reduced production secondary to s...

157

Severity of neuropsychological impairment in cocaine and alcohol addiction: association with metabolism in the prefrontal cortex  

Microsoft Academic Search

We used exploratory and confirmatory statistical approaches to study the severity of neuropsychological (NP) impairment in 42 crack\\/cocaine addicted subjects and in 112 comparison subjects (40 alcoholics and 72 controls). Twenty neuropsychological test indices most reliably defining predetermined cognitive domains were submitted to exploratory factor analysis. A four-dimensional model of neurocognitive function was derived: Verbal Knowledge, Visual Memory, Verbal Memory,

Rita Z. Goldstein; Andreana C. Leskovjan; Anne L. Hoff; Robert Hitzemann; Francine Bashan; Sahib Singh Khalsa; Gene-Jack Wang; Joanna S. Fowler; Nora D. Volkow

2004-01-01

158

Hearing impairment in association with distal renal tubular acidosis among Saudi children.  

PubMed

A follow-up of seven patients with the autosomal recessive inherited syndrome of distal renal tubular acidosis (RTA) and sensorineural hearing loss is described. Five patients were diagnosed as having primary distal renal tubular acidosis and rickets, four were found to have severe sensorineural hearing loss of over 80 dB: two of which are brothers. Two patients were diagnosed as having secondary distal renal acidosis due to a genetic disorder called osteopetrosis; they are brothers and their audiograms showed a mild conductive hearing loss of an average 35 dB bilaterally. All patients had growth retardation with improvement due to alkaline therapy but their hearing loss was not affected by the medication. The pedigrees of two families with half sibs showed the familial incidence for consanguineous marriage. Consanguinity was found to be positive in five out of the seven patients. The tribal tradition in Saudi Arabia fosters consanguineous marriages for cultural and social reasons and pre-arranged marriages are still seen. PMID:7499943

Zakzouk, S M; Sobki, S H; Mansour, F; al Anazy, F H

1995-10-01

159

Evaluation of the presence and severity of menopausal symptoms among postmenopausal women screened for the metabolic syndrome.  

PubMed

Abstract Background: The prevalence of the metabolic syndrome (METS) increases after the menopause. Reports indicate that the METS and its components, especially obesity, enhance the intensity of menopausal symptoms. Objective: Assess the frequency and severity of menopausal symptoms in postmenopausal women. Factors related to the symptom severity were also analyzed including depressive and metabolic status. Methods: A total of 204 natural postmenopausal women (40-65 years) participating in a METS screening program were asked to fill out the Menopause Rating Scale (MRS), the Hospital Anxiety and Depression Scale (HADS), and a general socio-demographic questionnaire containing personal and partner data. Criteria of the American Heart Association were used to define the METS. Results: Median age of the whole sample was 56 years. A 52.9% presented the METS, with 37.3% presenting hyperglycemia, 51.5% hypertension, 58.3% abdominal obesity, 45.6% high triglyceride and 56.4% low HDL-C levels. Total and subscale MRS scores did not differ in accordance to the presence or not of the METS. The three top prevalent menopausal symptoms were muscle and joint problems (87.2%), physical and mental exhaustion (72%) and depressive mood (64.7%). A 19.6% of women presented total MRS scores above 16 defined as severe. Multivariate linear regression analysis determined that anxiety (higher HADS anxiety subscale scores) was significantly and positively correlated with all components of the MRS (Total and subscale scores). Higher total MRS scores correlated positively with abdominal perimeter and higher parity. Somatic scores correlated inversely with female education and positively with psychotropic drug use; and psychological MRS scores positively correlated depressed mood (higher HADS depressive subscale scores) and abdominal perimeter. Conclusion: In this postmenopausal sample, severity of menopausal symptoms correlated to abdominal obesity, mood and other personal aspects. PMID:25347000

Chedraui, Peter; Pérez-López, Faustino R; Hidalgo, Luis; Villacreses, Diego; Domínguez, Andrea; Escobar, Gustavo S; Genazzani, Andrea R; Simoncini, Tommaso

2014-10-27

160

Sjögren’s, Renal Tubular Acidosis And Osteomalacia - An Asian Indian Series  

PubMed Central

Objective: To study the profile of Renal Tubular Acidosis (RTA) in Asian Indian patients with Primary Sjögren's Syndrome (pSS). Methods: The Electronic medical records of patients with a diagnosis of pSS seen between 2003 and 2010 at our tertiary care teaching hospital were screened for RTA. Clinical features, immunological profile, acid-base balance and electrolyte status, 25-hydroxyvitamin D (25(OH) D3) levels, histopathological changes in minor salivary gland biopsy samples and radiological findings were retrieved. RTA was diagnosed in cases of hyperchloremic metabolic acidosis with urinary pH values higher than 5.5. Those with known features suggestive of RTA including hypokalemic paralysis, hyperchloremia and nephrocalcinosis without acidosis were defined as incomplete RTA. Results: Of the 380 patients with clinically suspected pSS, 25 had RTA. The median age was 32 (18-60) years. Nineteen patients had complete RTA. Six had incomplete RTA. Only 10 patients (40%) had symptoms related to RTA at presentation. Sixteen patients (64%) had present or past history of hypokalemic paralysis. Pseudofractures were seen in 7 patients and an additional 2 had subclinical radiological osteomalacia. Majority of the patients (61.2%) had a normal 25(OH) D3 level. Those with osteomalacia had significantly lower serum phosphate, blood ph and higher alkaline phosphatase. Serum calcium and 25(OH) D3 levels were not significantly different between patients with osteomalacia and those without. Conclusion: Most patients were asymptomatic for RTA inspite of clinically overt and elicitable features. Skeletal manifestation was a common finding in patients with Sjögren and RTA, despite normal levels of 25 (OH) D3 in a majority. PMID:25584094

Sandhya, Pulukool; Danda, Debashish; Rajaratnam, Simon; Thomas, Nihal

2014-01-01

161

Sequential changes in the metabolic response in severely septic patients during the first 23 days after the onset of peritonitis.  

PubMed Central

OBJECTIVE: To quantify the sequential changes in metabolic response occurring in patients with severe sepsis after the onset of peritonitis. SUMMARY BACKGROUND DATA: Understanding the changes in energy expenditure and body composition is essential for the optimal management of severely septic patients; however, they have not been quantified in the context of modern surgical care. METHODS: Twelve patients with severe sepsis secondary to peritonitis (median APACHE II score = 21.5) had measurements of energy expenditure and body composition as soon as they were hemodynamically stable and 5, 10, and 21 days later. Sequential measurements of acute-phase proteins and cytokine responses were also made. RESULTS: Resting energy expenditure rose to 49% above predicted and remained elevated throughout the study period. Total energy expenditure was 1.25 x resting energy expenditure. Body fat was oxidized when energy intake was insufficient to achieve energy balance. There was a positive fluid balance of 12.5 1 over the first 2 days after onset of sepsis; thereafter, body water changes closely paralleled body weight changes and were largely accounted for by changes in extracellular water. During the 21 -day study period, there was a loss of 1.21 kg (13%) of total body protein. During the first 10 days, 67% of the protein lost came from skeletal muscle, but after this time it was predominantly from viscera. Intracellular potassium levels were low but did not deteriorate further after hemodynamic stability had been reached. There was a reprioritization of hepatic protein synthesis that was obligatory and independent of changes in total body protein. The cytokine responses demonstrated the complexity, redundancy, and overlap of mediators. CONCLUSIONS: The period of hypermetabolism in severely septic patients is similar to that previously described, but the fluid changes are larger and the protein loss is greater. Protein loss early on is predominantly from muscle, thereafter from viscera. Fat loss can be prevented and cell function preserved once hemodynamic stability is achieved. PMID:9712558

Plank, L D; Connolly, A B; Hill, G L

1998-01-01

162

Lactic acidosis complicating treatment of ketosis of labour.  

PubMed Central

Hypertonic glucose, fructose, and sorbitol solutions were given intravenously to women in the first stage of labour who had ketonuria and ketonaemia as evidenced by a raised blood acetoacetate and 3-hydrosybutyrate. There was no difference in the antiketogenic action of these, which was rapid and effective, but when compared with a control group who were given normal saline they had a high incidence of hyperlactataemia, and nine out of 28 patients developed lactic acidosis after the infusions. The "lactatogenic" effect was shared by all three substrates, and when they are used in the treatment of ketosis of labour, and the mother develops lactic acidosis, they might exacerbate pre-existing lactic acidosis and precipitate fetal distress. PMID:1203699

Ames, A C; Cobbold, S; Maddock, J

1975-01-01

163

Studies of acidosis in the ischaemic heart by phosphorus nuclear magnetic resonance.  

PubMed Central

1. Phosphorus-nuclear-magnetic-resonance measurements were made on perfused rat hearts at 37 degrees C. 2. With the improved sensitivity obtained by using a wide-bore 4.3 T superconducting magnet, spectra could be recorded in 1 min. 3. The concentrations of ATP, phosphocreatine and Pi and, from the position of the Pi resonance, the intracellular pH (pHi) were measured under a variety of conditions. 4. In a normal perfused heart pHi = 7.05 +/- 0.02 (mean +/- S.E.M. for seven hearts). 5. During global ischaemia pHi drops to 6.2 +/- 0.06 (mean +/- S.E.M.) in 13 min in a pseudoexponential decay with a rate constant of 0.25 min-1. 6. The relation between glycogen content and acidosis in ischaemia is studied in glycogen-depleted hearts. 7. Perfusion of hearts with a buffer containing 100 mM-Hepes before ischaemia gives a significant protective effect on the ischaemic myocardium. Intracellular pH and ATP and phosphocreatine concentrations decline more slowly under these conditions and metabolic recovery is observed on reperfusion after 30min of ischaemia at 37 degrees C. 8. The relation between acidosis and the export of protons is discussed and the significance of glycogenolysis in ischaemic acid production is evaluated. PMID:44193

Garlick, P B; Radda, G K; Seeley, P J

1979-01-01

164

Metabolic Levels in the Corpus Callosum and Their Structural and Behavioral Correlates after Moderate to Severe Pediatric TBI  

PubMed Central

Abstract Diffuse axonal injury (DAI) secondary to traumatic brain injury (TBI) contributes to long-term functional morbidity. The corpus callosum (CC) is particularly vulnerable to this type of injury. Magnetic resonance spectroscopy (MRS) was used to characterize the metabolic status of two CC regions of interest (ROIs) (anterior and posterior), and their structural (diffusion tensor imaging; DTI) and neurobehavioral (neurocognitive functioning, bimanual coordination, and interhemispheric transfer time [IHTT]) correlates. Two groups of moderate/severe TBI patients (ages 12–18 years) were studied: post-acute (5 months post-injury; n?=?10), and chronic (14.7 months post-injury; n?=?8), in addition to 10 age-matched healthy controls. Creatine (energy metabolism) did not differ between groups across both ROIs and time points. In the TBI group, choline (membrane degeneration/inflammation) was elevated for both ROIs at the post-acute but not chronic period. N-acetyl aspartate (NAA) (neuronal/axonal integrity) was reduced initially for both ROIs, with partial normalization at the chronic time point. Posterior, not anterior, NAA was positively correlated with DTI fractional anisotropy (FA) (r?=?0.88), and most domains of neurocognition (r range 0.22–0.65), and negatively correlated with IHTT (r?=??0.89). Inverse corerlations were noted between creatine and posterior FA (r?=??0.76), neurocognition (r range ?0.22 to ?0.71), and IHTT (r?=?0.76). Multimodal studies at distinct time points in specific brain structures are necessary to delineate the course of the degenerative and reparative processes following TBI, which allows for preliminary hypotheses about the nature and course of the neural mechanisms of subsequent functional morbidity. This will help guide the future development of targeted therapeutic agents. PMID:19925210

Marion, Sarah DeBoard; Copeland, Sarah; Alger, Jeffry R.; O'Neill, Joseph; Cazalis, Fabienne; Mink, Richard; Giza, Christopher C.; Vu, Jennifer A.; Hilleary, Suzanne M.; Kernan, Claudia L.; Newman, Nina; Asarnow, Robert F.

2010-01-01

165

Metabolic levels in the corpus callosum and their structural and behavioral correlates after moderate to severe pediatric TBI.  

PubMed

Diffuse axonal injury (DAI) secondary to traumatic brain injury (TBI) contributes to long-term functional morbidity. The corpus callosum (CC) is particularly vulnerable to this type of injury. Magnetic resonance spectroscopy (MRS) was used to characterize the metabolic status of two CC regions of interest (ROIs) (anterior and posterior), and their structural (diffusion tensor imaging; DTI) and neurobehavioral (neurocognitive functioning, bimanual coordination, and interhemispheric transfer time [IHTT]) correlates. Two groups of moderate/severe TBI patients (ages 12-18 years) were studied: post-acute (5 months post-injury; n = 10), and chronic (14.7 months post-injury; n = 8), in addition to 10 age-matched healthy controls. Creatine (energy metabolism) did not differ between groups across both ROIs and time points. In the TBI group, choline (membrane degeneration/inflammation) was elevated for both ROIs at the post-acute but not chronic period. N-acetyl aspartate (NAA) (neuronal/axonal integrity) was reduced initially for both ROIs, with partial normalization at the chronic time point. Posterior, not anterior, NAA was positively correlated with DTI fractional anisotropy (FA) (r = 0.88), and most domains of neurocognition (r range 0.22-0.65), and negatively correlated with IHTT (r = -0.89). Inverse corerlations were noted between creatine and posterior FA (r = -0.76), neurocognition (r range -0.22 to -0.71), and IHTT (r = 0.76). Multimodal studies at distinct time points in specific brain structures are necessary to delineate the course of the degenerative and reparative processes following TBI, which allows for preliminary hypotheses about the nature and course of the neural mechanisms of subsequent functional morbidity. This will help guide the future development of targeted therapeutic agents. PMID:19925210

Babikian, Talin; Marion, Sarah Deboard; Copeland, Sarah; Alger, Jeffry R; O'Neill, Joseph; Cazalis, Fabienne; Mink, Richard; Giza, Christopher C; Vu, Jennifer A; Hilleary, Suzanne M; Kernan, Claudia L; Newman, Nina; Asarnow, Robert F

2010-03-01

166

Changes in the Rumen Epimural Bacterial Diversity of Beef Cattle as Affected by Diet and Induced Ruminal Acidosis  

PubMed Central

Little is known about the nature of the rumen epithelial adherent (epimural) microbiome in cattle fed different diets. Using denaturing gradient gel electrophoresis (DGGE), quantitative real-time PCR (qPCR), and pyrosequencing of the V3 hypervariable coding region of 16S rRNA, epimural bacterial communities of 8 cattle were profiled during the transition from a forage to a high-concentrate diet, during acidosis, and after recovery. A total of 153,621 high-quality gene sequences were obtained, with populations exhibiting less taxonomic variability among individuals than across diets. The bacterial community composition exhibited clustering (P < 0.03) by diet, with only 14 genera, representing >1% of the rumen epimural population, differing (P ? 0.05) among diets. During acidosis, levels of Atopobium, Desulfocurvus, Fervidicola, Lactobacillus, and Olsenella increased, while during the recovery, Desulfocurvus, Lactobacillus, and Olsenella reverted to levels similar to those with the high-grain diet and Sharpea and Succinivibrio reverted to levels similar to those with the forage diet. The relative abundances of bacterial populations changed during diet transition for all qPCR targets except Streptococcus spp. Less than 5% of total operational taxonomic units (OTUs) identified exhibited significant variability across diets. Based on DGGE, the community structures of epithelial populations differed (P ? 0.10); segregation was most prominent for the mixed forage diet versus the grain, acidotic challenge, and recovery diets. Atopobium, cc142, Lactobacillus, Olsenella, RC39, Sharpea, Solobacterium, Succiniclasticum, and Syntrophococcus were particularly prevalent during acidosis. Determining the metabolic roles of these key genera in the rumens of cattle fed high-grain diets could define a clinical microbial profile associated with ruminal acidosis. PMID:23584771

Petri, R. M.; Schwaiger, T.; Penner, G. B.; Beauchemin, K. A.; Forster, R. J.; McKinnon, J. J.

2013-01-01

167

Genetic causes and mechanisms of distal renal tubular acidosis.  

PubMed

The primary or hereditary forms of distal renal tubular acidosis (dRTA) have received increased attention because of advances in the understanding of the molecular mechanism, whereby mutations in the main proteins involved in acid-base transport result in impaired acid excretion. Dysfunction of intercalated cells in the collecting tubules accounts for all the known genetic causes of dRTA. These cells secrete protons into the tubular lumen through H(+)-ATPases functionally coupled to the basolateral anion exchanger 1 (AE1). The substrate for both transporters is provided by the catalytic activity of the cytosolic carbonic anhydrase II (CA II), an enzyme which is also present in the proximal tubular cells and osteoclasts. Mutations in ATP6V1B1, encoding the B-subtype unit of the apical H(+) ATPase, and ATP6V0A4, encoding the a-subtype unit, lead to the loss of function of the apical H(+) ATPase and are usually responsible for patients with autosomal recessive dRTA often associated with early or late sensorineural deafness. Mutations in the gene encoding the cytosolic CA II are associated with the autosomal recessive syndrome of osteopetrosis, mixed distal and proximal RTA and cerebral calcification. Mutations in the AE1, the gene that encodes the Cl(-)/HCO(3)(-) exchanger, usually present as dominant dRTA, but a recessive pattern has been recently described. Several studies have shown trafficking defects in the mutant protein rather than the lack of function as the major mechanism underlying the pathogenesis of dRTA from AE1 mutations. PMID:23114896

Batlle, Daniel; Haque, Syed K

2012-10-01

168

Use of 1H-nuclear magnetic resonance to screen a set of biomarkers for monitoring metabolic disturbances in severe burn patients  

PubMed Central

Introduction To establish a plasma metabolomics fingerprint spectrum for severe burn patients and to use it to identify a set of biomarkers that could be used for clinical monitoring. Methods Twenty-one severe burn patients and three healthy control individuals were enrolled in this study, and the plasma samples from patients and healthy individuals were collected for nuclear magnetic resonance (NMR) measurements. The NMR spectra were analyzed using principal component analysis (PCA) and partial least squares (PLS) in order to establish the metabolomics fingerprint representing the changes in metabolism and to select the major biomarkers. Results NMR spectra of the plasma samples showed significant differences between burn patients and healthy individuals. Using metabolomics techniques, we found an Eigen-metabolome that consists of 12 metabolites, which are regulated by 103 enzymes in a global metabolic network. Among these metabolites, ?-ketoisovaleric acid, 3-methylhistidine, and ?-hydroxybutyric acid were the most important biomarkers that were significantly increased during the early stage of burn injury. These results suggest that the mitochondrial damage and carbohydrate, protein and fatty acid metabolism disturbances occur after burn injury. Our analysis also show that histone deacetylases, which are protein transcription suppressors, were remarkably increased and indicate that protein transcription was inhibited and anabolism was restrained during the early stage of burn injury. Conclusions Metabolomics techniques based on NMR can be used to monitor metabolism in severe burn patients. Our study demonstrates that integrated 1H-NMR metabolome and global metabolic network analysis is useful for visualizing complex metabolic disturbances after severe burn injury and may provide a new quantitative injury severity evaluation for future clinical use. Trial registration Chinese Clinical Trial Registry ChiCTR-OCC-12002145. Registered 25 April 2012. PMID:25059459

2014-01-01

169

Genetics Home Reference: Renal tubular acidosis with deafness  

MedlinePLUS

... a rare disorder; its prevalence is unknown. What genes are related to renal tubular acidosis with deafness? ... caused by mutations in the ATP6V1B1 or ATP6V0A4 gene. These genes provide instructions for making proteins that ...

170

Optogenetic Countering of Glial Acidosis Suppresses Glial Glutamate Release  

E-print Network

Neuron Report Optogenetic Countering of Glial Acidosis Suppresses Glial Glutamate Release through channelrhodopsin-2 (ChR2) is proton, this could be regarded as an optogenetic tool for instant and to release of glutamate. On the other hand, glial alkalization via optogenetic activa- tion of a proton pump

Newman, Eric A.

171

Sodium Bicarbonate for the Treatment of Lactic Acidosis  

Microsoft Academic Search

Lactic acidosis often challenges the intensivist and is associated with a strikingly high mortality. Treatment involves discerning and correcting its underlying cause, ensuring adequate oxygen delivery to tissues, reducing oxygen demand through sedation and mechanical ventilation, and (most controversially) attempting to alkalinize the blood with IV sodium bicarbonate. Here we review the literature to answer the following questions: Is a

Sean M. Forsythe; Gregory A. Schmidt

172

Infantile Renal Tubular Acidosis Due to Mercury Poisoning  

PubMed Central

A 9-month-old infant with renal tubular acidosis is reported. This illness followed the use of ammoniated mercury ointment for a napkin eruption. Raised levels of inorganic mercury were found in the urine. The patient was treated with alkalis, dimercaprol, and penicillamine. After 5 months, all therapy was discontinued and she has remained well. PMID:5419996

Husband, Peter; McKellar, W. J. D.

1970-01-01

173

Acidosis, magnesium and acetylsalicylic acid: Effects on thrombin  

NASA Astrophysics Data System (ADS)

Thrombin, an enzyme from the hydrolase family, is the main component of the blood coagulation system. In ischemic stroke it acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin forming blood clots in the brain. It has been found to phosphoresce at room temperature in the millisecond and microsecond ranges. The phosphorescence of thrombin was studied under physiological conditions, in acidosis (decrease of pH from 8.0 to 5.0) and on the addition of salts (magnesium sulfate and sodium chloride) and of acetylsalicylic acid, and its connection with thrombin function is discussed. Acidosis significantly increased the internal dynamics of thrombin. We propose that lactate-acidosis plays a protective role in stroke, preventing the formation of clots. The addition of NaCl and MgSO4 in different concentrations increased the internal dynamics of thrombin. Also, the addition of MgSO4 decreased thrombin-induced platelet aggregation. However, magnesium sulfate and acetylsalicylic acid in the therapeutic concentrations used for treatment of ischemic stroke had no effect on thrombin internal dynamics. The data obtained will help to elucidate the conformational stability of thrombin under conditions modulating lactate-acidosis and in the presence of magnesium sulfate.

Borisevich, Nikolaj; Loznikova, Svetlana; Sukhodola, Aleksandr; Halets, Inessa; Bryszewska, Maria; Shcharbin, Dzmitry

2013-03-01

174

Bench-to-bedside review: Oxygen debt and its metabolic correlates as quantifiers of the severity of hemorrhagic and post-traumatic shock  

PubMed Central

Evidence is increasing that oxygen debt and its metabolic correlates are important quantifiers of the severity of hemorrhagic and post-traumatic shock and and may serve as useful guides in the treatment of these conditions. The aim of this review is to demonstrate the similarity between experimental oxygen debt in animals and human hemorrhage/post-traumatic conditions, and to examine metabolic oxygen debt correlates, namely base deficit and lactate, as indices of shock severity and adequacy of volume resuscitation. Relevant studies in the medical literature were identified using Medline and Cochrane Library searches. Findings in both experimental animals (dog/pig) and humans suggest that oxygen debt or its metabolic correlates may be more useful quantifiers of hemorrhagic shock than estimates of blood loss, volume replacement, blood pressure, or heart rate. This is evidenced by the oxygen debt/probability of death curves for the animals, and by the consistency of lethal dose (LD)25,50 points for base deficit across all three species. Quantifying human post-traumatic shock based on base deficit and adjusting for Glasgow Coma Scale score, prothrombin time, Injury Severity Score and age is demonstrated to be superior to anatomic injury severity alone or in combination with Trauma and Injury Severity Score. The data examined in this review indicate that estimates of oxygen debt and its metabolic correlates should be included in studies of experimental shock and in the management of patients suffering from hemorrhagic shock. PMID:16277731

Rixen, Dieter; Siegel, John H

2005-01-01

175

Acidosis promotes invasiveness of breast cancer cells through ROS-AKT-NF-?B pathway.  

PubMed

It is well known that acidic microenvironment promotes tumorigenesis, however, the underlying mechanism remains largely unknown. In the present study, we show that acidosis promotes invasiveness of breast cancer cells through a series of signaling events. First, our study indicates that NF-?B is a key factor for acidosis-induced cell invasion. Acidosis activates NF-?B without affecting STAT3 activity; knockdown of NF-?B p65 abrogates the acidosis-induced invasion activity. Next, we show that the activation of NF-?B is mediated through phosphorylation and degradation of I?B?; and phosphorylation and nuclear translocation of p65. Upstream to NF-?B signaling, AKT is activated under acidic conditions. Moreover, acidosis induces generation of reactive oxygen species (ROS) which can be suppressed by ROS scavengers, reversing the acidosis-induced activation of AKT and NF-?B, and invasiveness. As a negative regulator of AKT, PTEN is oxidized and inactivated by the acidosis-induced ROS. Finally, inhibition of NADPH oxidase (NOX) suppresses acidosis-induced ROS production, suggesting involvement of NOX in acidosis-induced signaling cascade. Of considerable interest, acidosis-induced ROS production and activation of AKT and NF-?B can be only detected in cancer cells, but not in non-malignant cells. Together, these results demonstrate a cancer specific acidosis-induced signaling cascade in breast cancer cells, leading to cell invasion. PMID:25504433

Gupta, Subash C; Singh, Ramesh; Pochampally, Radhika; Watabe, Kounosuke; Mo, Yin-Yuan

2014-12-15

176

Acidosis promotes invasiveness of breast cancer cells through ROS-AKT-NF-?B pathway  

PubMed Central

It is well known that acidic microenvironment promotes tumorigenesis, however, the underlying mechanism remains largely unknown. In the present study, we show that acidosis promotes invasiveness of breast cancer cells through a series of signaling events. First, our study indicates that NF-?B is a key factor for acidosis-induced cell invasion. Acidosis activates NF-?B without affecting STAT3 activity; knockdown of NF-?B p65 abrogates the acidosis-induced invasion activity. Next, we show that the activation of NF-?B is mediated through phosphorylation and degradation of I?B?; and phosphorylation and nuclear translocation of p65. Upstream to NF-?B signaling, AKT is activated under acidic conditions. Moreover, acidosis induces generation of reactive oxygen species (ROS) which can be suppressed by ROS scavengers, reversing the acidosis-induced activation of AKT and NF-?B, and invasiveness. As a negative regulator of AKT, PTEN is oxidized and inactivated by the acidosis-induced ROS. Finally, inhibition of NADPH oxidase (NOX) suppresses acidosis-induced ROS production, suggesting involvement of NOX in acidosis-induced signaling cascade. Of considerable interest, acidosis-induced ROS production and activation of AKT and NF-?B can be only detected in cancer cells, but not in non-malignant cells. Together, these results demonstrate a cancer specific acidosis-induced signaling cascade in breast cancer cells, leading to cell invasion. PMID:25504433

Gupta, Subash C.; Singh, Ramesh; Pochampally, Radhika; Watabe, Kounosuke; Mo, Yin-Yuan

2014-01-01

177

An enzymatic bridge between carbohydrate and amino acid metabolism: regulation of glutamate dehydrogenase by reversible phosphorylation in a severe hypoxia-tolerant crayfish.  

PubMed

Glutamate dehydrogenase (GDH) (EC 1.4.1.3) is a crucial enzyme involved in bridging two metabolic pathways, gating the use of glutamate for either amino acid metabolism, or carbohydrate metabolism. The present study investigated GDH from tail muscle of the freshwater crayfish Orconectes virilis exploring changes to kinetic properties, phosphorylation levels and structural stability between two forms of the enzyme (aerobic control and 20-h severe hypoxic). Evidence indicated that GDH was converted to a high phosphate form under oxygen limitation. ProQ Diamond phosphoprotein staining showed a 42% higher bound phosphate content on GDH from muscle of severely hypoxic crayfish compared with the aerobic form, and treatment of this GDH with commercial phosphatase (alkaline phosphatase), and treatments that stimulated the activities of different endogenous protein phosphatases (stimulating PP1 + PP2A, PP2B, and PP2C) yielded significant increases in the fold activation by ADP of GDH from both control and severe hypoxic conditions. By contrast, stimulation of the activities of endogenous protein kinases (AMPK, PKA or CaMK) significantly reduced the ADP fold activation from control animals. The physiological consequence of severe hypoxia-induced GDH phosphorylation may be to suppress GDH activity under low oxygen, shutting off this critical bridge point between two metabolic pathways. PMID:22076534

Dawson, Neal J; Storey, Kenneth B

2012-04-01

178

Metabolic Shifts in Immunity and Inflammation  

PubMed Central

Sites of ongoing inflammation and triggered immune responses are characterized by significant changes in metabolic activity. Recent studies have indicated that such shifts in tissue metabolism result from a combination of profound recruitment of inflammatory cells (neutrophils and monocytes) and high proliferation rates among lymphocyte populations. The resultant shifts in energy supply and demand can result in metabolic acidosis and diminished delivery and/or availability of oxygen, leading to hypoxia extensive enough to trigger transcriptional and translation changes in tissue phenotype. Such phenotypic shifts can imprint fundamental changes to tissue metabolism. Here, we review recent work addressing metabolic changes and metabolic control of inflammation and immunity. PMID:20368286

Kominsky, Douglas J.; Campbell, Eric L.; Colgan, Sean P.

2014-01-01

179

Glucose Metabolism and Pancreatic Defects in Spinal Muscular Atrophy  

PubMed Central

Objective Spinal muscular atrophy (SMA) is the number 1 genetic killer of young children. It is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Although SMA is primarily a motor neuron disease, metabolism abnormalities such as metabolic acidosis, abnormal fatty acid metabolism, hyperlipidemia, and hyperglycemia have been reported in SMA patients. We thus initiated an in-depth analysis of glucose metabolism in SMA. Methods Glucose metabolism and pancreas development were investigated in the Smn2B/? intermediate SMA mouse model and type I SMA patients. Results Here, we demonstrate in an SMA mouse model a dramatic cell fate imbalance within pancreatic islets, with a predominance of glucagon-producing ? cells at the expense of insulin-producing ? cells. These SMA mice display fasting hyperglycemia, hyperglucagonemia, and glucose resistance. We demonstrate similar abnormalities in pancreatic islets from deceased children with the severe infantile form of SMA in association with supportive evidence of glucose intolerance in at least a subset of such children. Interpretation Our results indicate that defects in glucose metabolism may play an important contributory role in SMA pathogenesis. PMID:22926856

Bowerman, Melissa; Swoboda, Kathryn J.; Michalski, John-Paul; Wang, Gen-Sheng; Reeks, Courtney; Beauvais, Ariane; Murphy, Kelley; Woulfe, John; Screaton, Robert A.; Scott, Fraser W.; Kothary, Rashmi

2014-01-01

180

Acute metabolic effects of exercise in bodybuilders using anabolic steroids.  

PubMed Central

Four male bodybuilders who had started taking anabolic steroids were monitored during exercise. Most metabolic indicators were similar to bodybuilders not taking steroids; i.e. metabolic acidosis with little change in glucose. However, there is a marked elevation of creatine kinase. PMID:2620236

McKillop, G; Ballantyne, F C; Borland, W; Ballantyne, D

1989-01-01

181

A distinct mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) phenotype associates with YARS2 mutations  

PubMed Central

Nuclear-encoded disorders of mitochondrial translation are clinically and genetically heterogeneous. Genetic causes include defects of mitochondrial aminoacyl-tRNA synthetases, and factors required for initiation, elongation and termination of protein synthesis as well as ribosome recycling. We report on a new case of myopathy, lactic acidosis and sideroblastic anemia (MLASA) syndrome caused by defective mitochondrial tyrosyl aminoacylation. The patient presented at 1 year with anemia initially attributed to iron deficiency. Bone marrow aspirate at 5 years revealed ringed sideroblasts but transfusion dependency did not occur until 11 years. Other clinical features included lactic acidosis, poor weight gain, hypertrophic cardiomyopathy and severe myopathy leading to respiratory failure necessitating ventilatory support. Long-range PCR excluded mitochondrial DNA rearrangements. Clinical diagnosis of MLASA prompted direct sequence analysis of the YARS2 gene encoding the mitochondrial tyrosyl-tRNA synthetase, which revealed homozygosity for a known pathogenic mutation, c.156C>G;p.F52L. Comparison with four previously reported cases demonstrated remarkable clinical homogeneity. First line investigation of MLASA should include direct sequence analysis of YARS2 and PUS1 (encoding a tRNA modification factor) rather than muscle biopsy. Early genetic diagnosis is essential for counseling and to facilitate appropriate supportive therapy. Reasons for segregation of specific clinical phenotypes with particular mitochondrial aminoacyl tRNA-synthetase defects remain unknown. © 2013 Wiley Periodicals, Inc. PMID:23918765

Shahni, Rojeen; Wedatilake, Yehani; Cleary, Maureen A; Lindley, Keith J; Sibson, Keith R; Rahman, Shamima

2013-01-01

182

A distinct mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) phenotype associates with YARS2 mutations.  

PubMed

Nuclear-encoded disorders of mitochondrial translation are clinically and genetically heterogeneous. Genetic causes include defects of mitochondrial aminoacyl-tRNA synthetases, and factors required for initiation, elongation and termination of protein synthesis as well as ribosome recycling. We report on a new case of myopathy, lactic acidosis and sideroblastic anemia (MLASA) syndrome caused by defective mitochondrial tyrosyl aminoacylation. The patient presented at 1 year with anemia initially attributed to iron deficiency. Bone marrow aspirate at 5 years revealed ringed sideroblasts but transfusion dependency did not occur until 11 years. Other clinical features included lactic acidosis, poor weight gain, hypertrophic cardiomyopathy and severe myopathy leading to respiratory failure necessitating ventilatory support. Long-range PCR excluded mitochondrial DNA rearrangements. Clinical diagnosis of MLASA prompted direct sequence analysis of the YARS2 gene encoding the mitochondrial tyrosyl-tRNA synthetase, which revealed homozygosity for a known pathogenic mutation, c.156C>G;p.F52L. Comparison with four previously reported cases demonstrated remarkable clinical homogeneity. First line investigation of MLASA should include direct sequence analysis of YARS2 and PUS1 (encoding a tRNA modification factor) rather than muscle biopsy. Early genetic diagnosis is essential for counseling and to facilitate appropriate supportive therapy. Reasons for segregation of specific clinical phenotypes with particular mitochondrial aminoacyl tRNA-synthetase defects remain unknown. PMID:23918765

Shahni, Rojeen; Wedatilake, Yehani; Cleary, Maureen A; Lindley, Keith J; Sibson, Keith R; Rahman, Shamima

2013-09-01

183

MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast.  

PubMed

We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial-tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth, respiratory activity, mitochondrial protein synthesis, and complex IV activity. In one case, we also demonstrated that expression of wt MTO1 could rescue the respiratory defect in mutant fibroblasts. The severity of the yeast respiratory phenotypes partly correlated with the different clinical presentations observed in MTO1 mutant patients, although the clinical outcome was highly variable in patients with the same mutation and seemed also to depend on timely start of pharmacological treatment, centered on the control of lactic acidosis by dichloroacetate. Our results indicate that MTO1 mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and MRC deficiency, and that ad hoc recombinant yeast models represent a useful system to test the pathogenic potential of uncommon variants, and provide insight into their effects on the expression of a biochemical phenotype. PMID:23929671

Baruffini, Enrico; Dallabona, Cristina; Invernizzi, Federica; Yarham, John W; Melchionda, Laura; Blakely, Emma L; Lamantea, Eleonora; Donnini, Claudia; Santra, Saikat; Vijayaraghavan, Suresh; Roper, Helen P; Burlina, Alberto; Kopajtich, Robert; Walther, Anett; Strom, Tim M; Haack, Tobias B; Prokisch, Holger; Taylor, Robert W; Ferrero, Ileana; Zeviani, Massimo; Ghezzi, Daniele

2013-11-01

184

MTO1 Mutations are Associated with Hypertrophic Cardiomyopathy and Lactic Acidosis and Cause Respiratory Chain Deficiency in Humans and Yeast  

PubMed Central

We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial-tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth, respiratory activity, mitochondrial protein synthesis, and complex IV activity. In one case, we also demonstrated that expression of wt MTO1 could rescue the respiratory defect in mutant fibroblasts. The severity of the yeast respiratory phenotypes partly correlated with the different clinical presentations observed in MTO1 mutant patients, although the clinical outcome was highly variable in patients with the same mutation and seemed also to depend on timely start of pharmacological treatment, centered on the control of lactic acidosis by dichloroacetate. Our results indicate that MTO1 mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and MRC deficiency, and that ad hoc recombinant yeast models represent a useful system to test the pathogenic potential of uncommon variants, and provide insight into their effects on the expression of a biochemical phenotype. PMID:23929671

Baruffini, Enrico; Dallabona, Cristina; Invernizzi, Federica; Yarham, John W; Melchionda, Laura; Blakely, Emma L; Lamantea, Eleonora; Donnini, Claudia; Santra, Saikat; Vijayaraghavan, Suresh; Roper, Helen P; Burlina, Alberto; Kopajtich, Robert; Walther, Anett; Strom, Tim M; Haack, Tobias B; Prokisch, Holger; Taylor, Robert W; Ferrero, Ileana; Zeviani, Massimo; Ghezzi, Daniele

2013-01-01

185

Ruminal acidosis in a 21-month-old Holstein heifer  

PubMed Central

Rumen and blood biochemical profiles were monitored in 8 Holstein heifers exposed to a carbohydrate feeding challenge. One of the heifers had clinical signs consistent with acute ruminal acidosis on the day of, and subsequent to, the challenge. Within 24 h of challenge, 6 of 7 rumen volatile fatty acids measured were not detectable in this heifer and her rumen total lactate concentration was > 70 mM. PMID:24891639

Golder, Helen M.; Celi, Pietro; Lean, Ian J.

2014-01-01

186

Lactic acidosis during telbivudine treatment for HBV: A case report and literature review  

PubMed Central

All oral nucleoside analogues against hepatitis B virus, with an exception of telbivudine, have been reported causing lactic acidosis (LA). Here we report the first case of chronic hepatitis B developing severe refractory LA during telbivudine monotherapy. A 36-year-old man of Chinese origin received telbivudine antiviral treatment for chronic hepatitis B. After 11 mo of therapy, he developed anorexia, nausea, and vomiting with mild muscle weakness. The patient was found with elevated serum creatine phosphokinase up to 3683 U/L (upper limit of normal 170 U/L) and marked LA. LA did not resolve immediately following discontinuation of telbivudine. His condition began to improve after hemodialysis treatment for 16 times and usage of glucocorticosteroid. The patient fully recovered after 16 wk of treatment. This is the first documented case with severe LA caused by telbivudine monotherapy. Besides serum creatine phosphokinase, blood lactate level should also be closely monitored in patients receiving telbivudine. PMID:24023503

Jin, Jia-Lin; Hu, Piao; Lu, Jia-Hong; Luo, Su-Shan; Huang, Xiao-Yun; Weng, Xin-Hua; Zhang, Ji-Ming

2013-01-01

187

Renal tubular acidosis type II associated with vitamin D deficiency presenting as chronic weakness  

PubMed Central

Chronic vitamin D deficiency, though common in the elderly, is often under diagnosed and when progressing to renal tubular acidosis type II (RTA 2) can cause several simultaneous electrolyte imbalances that may present with weakness and pain as chief symptoms. We present such a case that after months of evaluation and symptomatic treatment did not lead to an effective establishment of the etiology causing chronic weakness and body pain in an elderly female patient. Eventually, after a careful review of the patient’s history, repeat physical examinations, laboratory data evaluation, and diagnostic testing led to the establishment of the diagnosis of proximal RTA 2 associated with vitamin D deficiency, which caused the patient to develop several remarkable secondary electrolyte imbalances such as hypokalemia, hypocalcemia, hypophosphatemia, acidemia, hyperparathyroidism, with weakness and body pain. PMID:25343024

Parekh, Amila; Baig, Mirza; Ali, Taseen; Rafiq, Tazeen

2014-01-01

188

Diisopropylamine Dichloroacetate, a Novel Pyruvate Dehydrogenase Kinase 4 Inhibitor, as a Potential Therapeutic Agent for Metabolic Disorders and Multiorgan Failure in Severe Influenza  

PubMed Central

Severe influenza is characterized by cytokine storm and multiorgan failure with metabolic energy disorders and vascular hyperpermeability. In the regulation of energy homeostasis, the pyruvate dehydrogenase (PDH) complex plays an important role by catalyzing oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid synthesis, and thus its activity is linked to energy homeostasis. The present study tested the effects of diisopropylamine dichloroacetate (DADA), a new PDH kinase 4 (PDK4) inhibitor, in mice with severe influenza. Infection of mice with influenza A PR/8/34(H1N1) virus resulted in marked down-regulation of PDH activity and ATP level, with selective up-regulation of PDK4 in the skeletal muscles, heart, liver and lungs. Oral administration of DADA at 12-h intervals for 14 days starting immediately after infection significantly restored PDH activity and ATP level in various organs, and ameliorated disorders of glucose and lipid metabolism in the blood, together with marked improvement of survival and suppression of cytokine storm, trypsin up-regulation and viral replication. These results indicate that through PDK4 inhibition, DADA effectively suppresses the host metabolic disorder-cytokine cycle, which is closely linked to the influenza virus-cytokine-trypsin cycle, resulting in prevention of multiorgan failure in severe influenza. PMID:24865588

Yamane, Kazuhiko; Indalao, Irene L.; Chida, Junji; Yamamoto, Yoshikazu; Hanawa, Masaaki; Kido, Hiroshi

2014-01-01

189

Diisopropylamine dichloroacetate, a novel pyruvate dehydrogenase kinase 4 inhibitor, as a potential therapeutic agent for metabolic disorders and multiorgan failure in severe influenza.  

PubMed

Severe influenza is characterized by cytokine storm and multiorgan failure with metabolic energy disorders and vascular hyperpermeability. In the regulation of energy homeostasis, the pyruvate dehydrogenase (PDH) complex plays an important role by catalyzing oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid synthesis, and thus its activity is linked to energy homeostasis. The present study tested the effects of diisopropylamine dichloroacetate (DADA), a new PDH kinase 4 (PDK4) inhibitor, in mice with severe influenza. Infection of mice with influenza A PR/8/34(H1N1) virus resulted in marked down-regulation of PDH activity and ATP level, with selective up-regulation of PDK4 in the skeletal muscles, heart, liver and lungs. Oral administration of DADA at 12-h intervals for 14 days starting immediately after infection significantly restored PDH activity and ATP level in various organs, and ameliorated disorders of glucose and lipid metabolism in the blood, together with marked improvement of survival and suppression of cytokine storm, trypsin up-regulation and viral replication. These results indicate that through PDK4 inhibition, DADA effectively suppresses the host metabolic disorder-cytokine cycle, which is closely linked to the influenza virus-cytokine-trypsin cycle, resulting in prevention of multiorgan failure in severe influenza. PMID:24865588

Yamane, Kazuhiko; Indalao, Irene L; Chida, Junji; Yamamoto, Yoshikazu; Hanawa, Masaaki; Kido, Hiroshi

2014-01-01

190

Beyond Warburg effect – dual metabolic nature of cancer cells  

PubMed Central

Warburg effect is a dominant phenotype of most cancer cells. Here we show that this phenotype depends on its environment. When cancer cells are under regular culture condition, they show Warburg effect; whereas under lactic acidosis, they show a nonglycolytic phenotype, characterized by a high ratio of oxygen consumption rate over glycolytic rate, negligible lactate production and efficient incorporation of glucose carbon(s) into cellular mass. These two metabolic modes are intimately interrelated, for Warburg effect generates lactic acidosis that promotes a transition to a nonglycolytic mode. This dual metabolic nature confers growth advantage to cancer cells adapting to ever changing microenvironment. PMID:24820099

Xie, Jiansheng; Wu, Hao; Dai, Chunyan; Pan, Qiangrong; Ding, Zonghui; Hu, Danqing; Ji, Bingyan; Luo, Yan; Hu, Xun

2014-01-01

191

An inherited defect affecting the tricarboxylic acid cycle in a patient with congenital lactic acidosis.  

PubMed

Cultured skin fibroblasts from a 3 yr old girl with severe, diffuse neurologic disease and persistant lactic acidosis, oxidized radioactive citrate, palmitate, and pyruvate at less than one-third the rate of control cells. Her fibroblasts oxidized isocitrate and glutamate at rates comparable with controls. In disrupted cells from this patient, the activity of aconitate hydratase appeared normal. The binding of citrate to aconitate hydratase and the activities of the NAD- and NADP-linked isocitrate dehydrogenases were also normal, while the activity of citrate synthase was slightly below control values. A significant defect was, however, apparent in the activity of the pyruvate dehydrogenase complex although not in the thiamine-dependent first enzyme of that complex. This patient appears to have a partial genetic defect affecting the tricarboxylic acid cycle. PMID:5032527

Blass, J P; Schulman, J D; Young, D S; Hom, E

1972-07-01

192

Genealogy Profiling through Strain Improvement by Using Metabolic Network Analysis: Metabolic Flux Genealogy of Several Generations of Lysine-Producing Corynebacteria  

PubMed Central

A comprehensive approach of metabolite balancing, 13C tracer studies, gas chromatography-mass spectrometry, matrix-assisted laser desorption ionization-time of flight mass spectrometry, and isotopomer modeling was applied for comparative metabolic network analysis of a genealogy of five successive generations of lysine-producing Corynebacterium glutamicum. The five strains examined (C. glutamicum ATCC 13032, 13287, 21253, 21526, and 21543) were previously obtained by random mutagenesis and selection. Throughout the genealogy, the lysine yield in batch cultures increased markedly from 1.2 to 24.9% relative to the glucose uptake flux. Strain optimization was accompanied by significant changes in intracellular flux distributions. The relative pentose phosphate pathway (PPP) flux successively increased, clearly corresponding to the product yield. Moreover, the anaplerotic net flux increased almost twofold as a consequence of concerted regulation of C3 carboxylation and C4 decarboxylation fluxes to cover the increased demand for lysine formation; thus, the overall increase was a consequence of concerted regulation of C3 carboxylation and C4 decarboxylation fluxes. The relative flux through isocitrate dehydrogenase dropped from 82.7% in the wild type to 59.9% in the lysine-producing mutants. In contrast to the NADPH demand, which increased from 109 to 172% due to the increasing lysine yield, the overall NADPH supply remained constant between 185 and 196%, resulting in a decrease in the apparent NADPH excess through strain optimization. Extrapolated to industrial lysine producers, the NADPH supply might become a limiting factor. The relative contributions of PPP and the tricarboxylic acid cycle to NADPH generation changed markedly, indicating that C. glutamicum is able to maintain a constant supply of NADPH under completely different flux conditions. Statistical analysis by a Monte Carlo approach revealed high precision for the estimated fluxes, underlining the fact that the observed differences were clearly strain specific. PMID:12450803

Wittmann, Christoph; Heinzle, Elmar

2002-01-01

193

Intracellular pH during "chemical hypoxia" in cultured rat hepatocytes. Protection by intracellular acidosis against the onset of cell death.  

PubMed Central

The relationships between extracellular pH (pHo), intracellular pH (pHi), and loss of cell viability were evaluated in cultured rat hepatocytes after ATP depletion by metabolic inhibition with KCN and iodoacetate (chemical hypoxia). pHi was measured in single cells by ratio imaging of 2',7'-biscarboxy-ethyl-5,6-carboxyfluorescein (BCECF) fluorescence using multiparameter digitized video microscopy. During chemical hypoxia at pHo of 7.4, pHi decreased from 7.36 to 6.33 within 10 min. pHi remained at 6.1-6.5 for 30-40 min (plateau phase). Thereafter, pHi began to rise and cell death ensued within minutes, as evidenced by nuclear staining with propidium iodide and coincident leakage of BCECF from the cytoplasm. An acidic pHo produced a slightly greater drop in pHi, prolonged the plateau phase of intracellular acidosis, and delayed the onset of cell death. Inhibition of Na+/H+ exchange also prolonged the plateau phase and delayed cell death. In contrast, monensin or substitution of gluconate for Cl- in buffer containing HCO3- abolished the pH gradient across the plasma membrane and shortened cell survival. The results indicate that intracellular acidosis after ATP depletion delays the onset of cell death, whereas reduction of the degree of acidosis accelerates cell killing. We conclude that intracellular acidosis protects against hepatocellular death from ATP depletion, a phenomenon that may represent a protective adaptation against hypoxic and ischemic stress. Images PMID:2536397

Gores, G J; Nieminen, A L; Wray, B E; Herman, B; Lemasters, J J

1989-01-01

194

Sequence and genetic organization of a Zymomonas mobilis gene cluster that encodes several enzymes of glucose metabolism  

SciTech Connect

The Zymomonas mobilis genes that encode glucose-6-phosphate dehydrogenase (zwf), 6-phosphogluconate dehydratase (edd), and glucokinase (glk) were cloned independently by genetic complementation of specific defects in Escherichia coli metabolism. The identify of these cloned genes was confirmed by various biochemical means. Nucleotide sequence analysis established that these three genes are clustered on the genome and revealed an additional open reading frame in this region that has significant amino acid identity to the E.coli xylose-proton symporter and the human glucose transporter. On the basis of this evidence and structural analysis of the deduced primary amino acid sequence, this gene is believed to encode the Z. mobilis glucose-facilitated diffusion protein, glf. The four genes in the 6-kb cluster are organized in the order glf, zwf, edd, glk. The glf and zwf genes are separated by 146 bp. The zwf and edd genes overlap by 8 bp, and their expression may be translationally coupled. The edd and glk genes are separated by 203 bp. The glk gene is followed by tandem transcriptional terminators. The four genes appear to be organized in an operon. Such an arrangement of the genes that govern glucose uptake and the first three steps of the Entner-Doudoroff glycolytic pathway provides the organism with a mechanism for carefully regulating the levels of the enzymes that control carbon flux into the pathway.

Barnell, W.O.; Kyung Cheol Yi; Conway, T. (Univ. of Nebraska, Lincoln (United States))

1990-12-01

195

Effects of increased red cell mass on subclinical tissue acidosis in hyaline membrane disease.  

PubMed Central

AIM: To determine whether there are subclinical deficits in oxygen delivery in ventilated premature neonates. METHOD: Ventilated premature neonates weighing less than 1500 g, who were transfused for anaemia or who were given colloids for clotting abnormalities (or oedema), were haemodynamically monitored during the first week of life. Calf muscle surface pH (pH) was measured in conjunction with peripheral limb blood flow by occlusion plethysmography. RESULTS: Packed red blood cell transfusions corrected a subclinical regional tissue acidosis (low tpH) without affecting arterial pH or limb blood flow. This observation also correlated with an increase in regional oxygen delivery. The data were also suggestive of a pattern of pathological, supply dependent, oxygen delivery and are similar to other observations made in adults with adult respiratory distress syndrome. CONCLUSIONS: Packed red blood cells increase regional oxygen delivery and tissue surface pH. In contrast, colloid infusion provided no substantial cardiovascular or metabolic benefit to these patients and should be avoided when oxygen delivery is at issue and when there may be leaky pulmonary capillaries. PMID:8949689

La Gamma, E F; Krauss, A; Auld, P A

1996-01-01

196

Effects of hypercapnia with and without acidosis on hypoxic pulmonary vasoconstriction.  

PubMed

Acute respiratory disorders and permissive hypercapnic strategy may lead to alveolar hypoxia and hypercapnic acidosis. However, the effects of hypercapnia with or without acidosis on hypoxic pulmonary vasoconstriction (HPV) and oxygen diffusion capacity of the lung are controversial. We investigated the effects of hypercapnic acidosis and hypercapnia with normal pH (pH corrected with sodium bicarbonate) on HPV, capillary permeability, gas exchange, and ventilation-perfusion matching in the isolated ventilated-perfused rabbit lung. No alteration in vascular tone was noted during normoxic hypercapnia with or without acidosis compared with normoxic normocapnia. Hypercapnia with normal pH resulted in a transient increase in HPV during the course of consecutive ventilation maneuvers, whereas hypercapnic acidosis increased HPV over time. Hypercapnic acidosis decreased exhaled NO during hypoxia more than hypercapnia with normal pH and normocapnia, whereas intravascular NO release was unchanged. However, inhibition of NO synthesis by nitro-L-arginine (L-NNA) resulted in a loss of the increased HPV caused by hypercapnic acidosis but not that caused by hypercapnia with normal pH. Furthermore, capillary permeability increased during hypoxic hypercapnia with normal pH but not hypoxic hypercapnic acidosis. This effect was NO-dependent because it disappeared during L-NNA administration. Ventilation-perfusion matching and arterial PO2 were improved according to the strength of HPV in hypercapnia compared with normocapnia during Tween nebulization-induced lung injury. In conclusion, the increased HPV during hypercapnic acidosis is beneficial to lung gas exchange by improving ventilation-perfusion matching and preserving the capillary barrier function. These effects seem to be linked to NO-mediated pathways. PMID:19717554

Ketabchi, Farzaneh; Egemnazarov, Bakytbek; Schermuly, Ralph T; Ghofrani, Hossein A; Seeger, Werner; Grimminger, Friedrich; Shid-Moosavi, Mostafa; Dehghani, Gholam A; Weissmann, Norbert; Sommer, Natascha

2009-11-01

197

Linezolid-induced lactic acidosis corrected with sustained low-efficiency dialysis: a case report.  

PubMed

Linezolid, an oxazolidinone antibiotic, has been reported to increase the risk of lactic acidosis and peripheral neuropathy because it disrupts mitochondrial function. This case report describes the development of lactic acidosis in a 63-year-old man who had received 3 months of treatment with intravenous linezolid for pulmonary nocardiasis, and correction of the acidotic state with sustained low-efficiency dialysis. This case demonstrates that renal replacement therapy can be an alternative to discontinuation alone for rapid reversal of linezolid-induced lactic acidosis. PMID:24961626

Sawyer, Adam J; Haley, Heather L; Baty, Sharon R; McGuffey, Grant E; Eiland, Edward H

2014-09-01

198

Development of Metabolic Indicators of Burn Injury: Very Low Density Lipoprotein (VLDL) and Acetoacetate Are Highly Correlated to Severity of Burn Injury in Rats  

PubMed Central

Hypermetabolism is a significant sequela to severe trauma such as burns, as well as critical illnesses such as cancer. It persists in parallel to, or beyond, the original pathology for many months as an often-fatal comorbidity. Currently, diagnosis is based solely on clinical observations of increased energy expenditure, severe muscle wasting and progressive organ dysfunction. In order to identify the minimum number of necessary variables, and to develop a rat model of burn injury-induced hypermetabolism, we utilized data mining approaches to identify the metabolic variables that strongly correlate to the severity of injury. A clustering-based algorithm was introduced into a regression model of the extent of burn injury. As a result, a neural network model which employs VLDL and acetoacetate levels was demonstrated to predict the extent of burn injury with 88% accuracy in the rat model. The physiological importance of the identified variables in the context of hypermetabolism, and necessary steps in extension of this preliminary model to a clinically utilizable index of severity of burn injury are outlined. PMID:24957642

Izamis, Maria-Louisa; Uygun, Korkut; Sharma, Nripen S.; Uygun, Basak; Yarmush, Martin L.; Berthiaume, Francois

2012-01-01

199

[Morphological analysis of bone dynamics and metabolic bone disease. Does bisphosphonate treatment cause severely suppressed bone turnover (SSBT) ?].  

PubMed

Bisphosphonates are anti-resorptive drug and increase both bone strength and toughness. However, their long term treatment oversuppresses bone turnover and promotes advanced glycation end-products in bone tissue, resulting in low bone quality. These conditions are called "severely suppressed bone turnover (SSBT) " , and can cause "atypical" , low-impact fractures of the femoral subtrochanteric or shaft. It is evident that bisphosphonates prevent fracture risk in vertebral body or femoral neck and improve quality of life in patients with osteoporosis, but clinicians, especially bone specialists, have to keep the associations between bisphosphonate use and SSBT in mind. Rational approach to atypical femoral subtrochanteric÷shaft fractures should be determined in near future. PMID:21447926

Kondo, Naoki; Yoda, Takuya

2011-04-01

200

Successful treatment of severe iron intoxication with gastrointestinal decontamination, deferoxamine, and hemodialysis.  

PubMed

Acute iron poisoning is a common and potentially serious problem in the pediatric population. Early recognition and treatment is crucial for a better outcome and to prevent morbidity and mortality. An 18-year-old female, who had accidental ingestion of 50 tablets of ferrous sulfate (100 mg of elemental iron per 335 mg tablet), 100 mg/kg of elemental iron, developed acute gastrointestinal and neurologic signs of toxicity and severe anion gap metabolic acidosis. The patient had received gastrointestinal decontamination, deferoxamine (DFO) infusion, and hemodialysis (HD) resulting in a decrease in serum iron concentration from 2150 to 160 mcg/dL at 24-h post-ingestion and improved mental status. Our cases demonstrate that HD may assist in decreasing serum iron concentration and improving clinical status in patients with massive overdose and life-threatening toxicity. PMID:23635030

Gumber, Manoj R; Kute, Vivek B; Shah, Pankaj R; Vanikar, Aruna V; Patel, Himanshu V; Balwani, Manish R; Ghuge, Pramod P; Trivedi, Hargovind L

2013-01-01

201

Altered glucose metabolism rather than naive type 2 diabetes mellitus (T2DM) is related to vitamin D status in severe obesity  

PubMed Central

Context The last decades have provided insights into vitamin D physiology linked to glucose homeostasis. Uncertainties remain in obesity due to its intrinsic effects on vitamin D and glucose tolerance. Objectives To assess the relationship between vitamin D and glucose abnormalities in severely obese individuals previously unknown to suffer from abnormal glucose metabolism. Setting Tertiary care centre. Patients 524 obese patients (50.3?±?14.9 yrs; BMI, 47.7?±?7.3 kg/m2) screened by OGTT, HbA1c and the lipid profile. Vitamin D status was assessed by 25(OH)D3, PTH and electrolyte levels. 25(OH)D3 deficiency/insufficiency were set at 20 and 30 ng/ml, respectively. All comparative and regression analyses were controlled for age, BMI and gender. Results The prevalence of vitamin D deficiency/insufficiency and secondary hyperparathyroidism were 95% and 50.8%, respectively. Normal glucose tolerance (NGT), impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) were found in 37.8%, 40.5% and 21.7% of cases, respectively. Large variations in metabolic parameters were seen across categories of vitamin D status, but the only significant differences were found for C-peptide, tryglicerides, LDL- and HDL-cholesterol levels (p?metabolism in a setting of obese patients previously unknown to harbour glucose metabolism abnormalities. PMID:24618074

2014-01-01

202

[Autoradiographic studies on protein metabolism and histochemical demonstration of the brain zinc content in diabetes mellitus. 1. Comparison in experimental streptozotocin-induced diabetes].  

PubMed

By application of streptozotocin diabetes mellitus is induced in rats: 40 mg/kg body weight streptozotocin produce a fairly serious diabetes with minimal ketosis, 125 mg/kg body weight streptozotocin cause a severe diabetic keto-acidosis. After 72 hours these animals and also a group of control animals receive 8.33 mCi/animal 3H-leucine intraperitoneally. By means of stripping film autoradiograms the rates of uptake of 3H-leucine in different areas of the rat brain are measured. The values of the control animals are compared with those of a fairly serious diabetes and those of a severe diabetic keto-acidosis. In the regions of the neocortex parietalis and of the thalamus the 3H-leucine values of the diabetic animals are considerably lower in comparison with the controls, and that irrespective of the degree of severity of the diabetic disease. Compared with the control animals the 3H-leucine values of diabetic animals decrease according to the degree of severity of the disease within the Ammon's horn and the dentate fascia. Within the Ammon's horn and dentate fascia also the zinc contents change very specifically in different areas with the degree of severity of diabetes mellitus. The zinc is identified on H2S-alcohol fixed brains by means of a photographic development. The particular significance of the Ammon's horn and the dentate fascia concerning diabetic metabolic conditions is discussed. PMID:161876

Gatzke, H D; Wildmeister, W

1979-01-01

203

Evaluation of Subcutaneous Tissue Gases and pH during Induction of Acidosis and Alkalosis  

Microsoft Academic Search

Peripheral tissue oxygen utilization was studied during hypoxic-induced acidosis and sodium bicarbonate-induced alkalosis in 8 domestic pigs by measurements of subcutaneous oxygen tension (PscO2), carbon dioxide tension (PscCO2) and pH (pHsc) in relation to central hemodynamic parameters and oxygenation. Hypoxic-induced acidosis resulted in a decrease in PscCO2 and arterial oxygen tension (PaO2) to one third of baseline values (p <

Å. Mellström; Barbara Jedlinska; M. Hartmann; K. Jönsson

2001-01-01

204

Treating Intraoperative Hyperchloremic Acidosis with Sodium Bicarbonate or Tris-Hydroxymethyl Aminomethane: A Randomized Prospective Study  

Microsoft Academic Search

In this study, we evaluated the action of two buffer so- lutions on acid-base equilibrium in cases of hyperchlo- remic acidosis. Twenty-four patients undergoing major gynecological intraabdominal surgery received 40 mL · kg1 ·h 1 of 0.9% saline per protocol. During surgery, in every patient, hyperchloremic acidosis oc- curred. At a standard base excess of 7 mmol\\/L, the patients were

Markus Rehm; Udilo Finsterer

2003-01-01

205

Beetroot juice supplementation speeds O2 uptake kinetics and improves exercise tolerance during severe-intensity exercise initiated from an elevated metabolic rate.  

PubMed

Recent research has suggested that dietary nitrate (NO3(-)) supplementation might alter the physiological responses to exercise via specific effects on type II muscle. Severe-intensity exercise initiated from an elevated metabolic rate would be expected to enhance the proportional activation of higher-order (type II) muscle fibers. The purpose of this study was, therefore, to test the hypothesis that, compared with placebo (PL), NO3(-)-rich beetroot juice (BR) supplementation would speed the phase II VO2 kinetics (?(p)) and enhance exercise tolerance during severe-intensity exercise initiated from a baseline of moderate-intensity exercise. Nine healthy, physically active subjects were assigned in a randomized, double-blind, crossover design to receive BR (140 ml/day, containing ~8 mmol of NO3(-)) and PL (140 ml/day, containing ~0.003 mmol of NO3(-)) for 6 days. On days 4, 5, and 6 of the supplementation periods, subjects completed a double-step exercise protocol that included transitions from unloaded to moderate-intensity exercise (U?M) followed immediately by moderate to severe-intensity exercise (M?S). Compared with PL, BR elevated resting plasma nitrite concentration (PL: 65 ± 32 vs. BR: 348 ± 170 nM, P < 0.01) and reduced the VO2 ?(p) in M?S (PL: 46 ± 13 vs. BR: 36 ± 10 s, P < 0.05) but not U?M (PL: 25 ± 4 vs. BR: 27 ± 6 s, P > 0.05). During M?S exercise, the faster VO2 kinetics coincided with faster near-infrared spectroscopy-derived muscle [deoxyhemoglobin] kinetics (?; PL: 20 ± 9 vs. BR: 10 ± 3 s, P < 0.05) and a 22% greater time-to-task failure (PL: 521 ± 158 vs. BR: 635 ± 258 s, P < 0.05). Dietary supplementation with NO3(-)-rich BR juice speeds VO2 kinetics and enhances exercise tolerance during severe-intensity exercise when initiated from an elevated metabolic rate. PMID:24089377

Breese, Brynmor C; McNarry, Melitta A; Marwood, Simon; Blackwell, Jamie R; Bailey, Stephen J; Jones, Andrew M

2013-12-15

206

Mechanisms of adaptation to chronic respiratory acidosis in the rabbit proximal tubule.  

PubMed

The hyperbicarbonatemia of chronic respiratory acidosis is maintained by enhanced bicarbonate reabsorption in the proximal tubule. To investigate the cellular mechanisms involved in this adaptation, cell and luminal pH were measured microfluorometrically using (2",7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein in isolated, microperfused S2 proximal convoluted tubules from control and acidotic rabbits. Chronic respiratory acidosis was induced by exposure to 10% CO2 for 52-56 h. Tubules from acidotic rabbits had a significantly lower luminal pH after 1-mm perfused length (7.03 +/- 0.09 vs. 7.26 +/- 0.06 in controls, perfusion rate = 10 nl/min). Chronic respiratory acidosis increased the initial rate of cell acidification (dpHi/dt) in response to luminal sodium removal by 63% and in response to lowering luminal pH (7.4-6.8) by 69%. Chronic respiratory acidosis also increased dpHi/dt in response to peritubular sodium removal by 63% and in response to lowering peritubular pH by 73%. In conclusion, chronic respiratory acidosis induces a parallel increase in the rates of the luminal Na/H antiporter and the basolateral Na/(HCO3)3 cotransporter. Therefore, the enhanced proximal tubule reabsorption of bicarbonate in chronic respiratory acidosis may be, at least in part, mediated by a parallel adaptation of these transporters. PMID:2537851

Krapf, R

1989-03-01

207

G418-mediated ribosomal read-through of a nonsense mutation causing autosomal recessive proximal renal tubular acidosis  

PubMed Central

Autosomal recessive proximal renal tubular acidosis is caused by mutations in the SLC4A4 gene encoding the electrogenic sodium bicarbonate cotransporter NBCe1-A. The mutations that have been characterized thus far result in premature truncation, mistargeting, or decreased function of the cotransporter. Despite bicarbonate treatment to correct the metabolic acidosis, extrarenal manifestations persist, including glaucoma, cataracts, corneal opacification, and mental retardation. Currently, there are no known therapeutic approaches that can specifically target mutant NBCe1-A proteins. In the present study, we tested the hypothesis that the NBCe1-A-Q29X mutation can be rescued in vitro by treatment with aminoglycoside antibiotics, which are known for their ability to suppress premature stop codons. As a model system, we cloned the NBCe1-A-Q29X mutant into a vector lacking an aminoglycoside resistance gene and transfected the mutant cotransporter in HEK293-H cells. Cells transfected with the NBCe1-A-Q29X mutant failed to express the cotransporter because of the premature stop codon. Treatment of the cells with G418 significantly increased the expression of the full-length cotransporter, as assessed by immunoblot analysis. Furthermore, immunocytochemical studies demonstrated that G418 treatment induced cotransporter expression on the plasma membrane whereas in the absence of G418, NBCe1-A-Q29X was not expressed. In HEK293-H cells transfected with the NBCe1-A-Q29X mutant not treated with G418, NBCe1-A-mediated flux was not detectable. In contrast, in cells transfected with the NBCe1-A-Q29X mutant, G418 treatment induced Na+- and HCO3?-dependent transport that did not differ from wild-type NBCe1-A function. G418 treatment in mock-transfected cells was without effect. In conclusion, G418 induces ribosomal read-through of the NBCe1-A-Q29X mutation in HEK293-H cells. These findings represent the first evidence that in the presence of the NBCe1-A-Q29X mutation that causes proximal renal tubular acidosis, full-length functional NBCe1-A protein can be produced. Our results provide the first demonstration of a mutation in NBCe1-A that has been treated in a targeted and specific manner. PMID:18614622

Azimov, Rustam; Abuladze, Natalia; Sassani, Pakan; Newman, Debra; Kao, Liyo; Liu, Weixin; Orozco, Nicholas; Ruchala, Piotr; Pushkin, Alexander; Kurtz, Ira

2008-01-01

208

Acidosis environment promotes osteoclast formation by acting on the last phase of preosteoclast differentiation: a study to elucidate the action points of acidosis and search for putative target molecules.  

PubMed

Acidosis promoted tartaric acid-resistant acid phosphatase-positive multinuclear cell (TRAP+MNC) or osteoclast formation. Large osteoclast or TRAP+LMNC formation was observed far more in an acidosis environment than in a physiologically neutral environment. One of the major action points of acidosis was determined to be located in the last phase of preosteoclast differentiation using a co-culture system and a soluble RANKL-dependent bone marrow cell culture system. On-going osteoclast formation in an acidosis environment markedly deteriorated when the medium was replaced with physiologically neutral medium within the first 6h; however, bone marrow cells previously stimulated in an acidosis environment for 9h differentiated into TRAP+LMNC in pH 7.4 medium. Messenger RNA (mRNA) expression levels of DC-STAMP, a key molecule in cell fusion, and NFATc1 did not increase in the acidosis environment compared with those under physiologically neutral conditions. Ruthenium red, a general TRP antagonist, deteriorated acidosis-promoted TRAP+LMNC formation. 4-Alpha-PDD, a TRPV4-specific agonist, added in the last 21 h of preosteoclast differentiation, potentiated TRAP+LMNC formation in a mild acidosis environment, showing synergism between TRPV4 activation and acidosis. RN1734, a TRPV4-specific antagonist, partly inhibited acidosis-promoted TRAP+LMNC formation. We thus narrowed down the major action points of acidosis in osteoclast formation and elucidated the characteristics of this system in detail. Our results show that acidosis effectively uses TRPV4 to drive large-scale cell fusion and also utilizes systems independently of TRPV4. PMID:21575626

Kato, Kohtaro; Morita, Ikuo

2011-08-01

209

Fanconi syndrome and severe polyuria: an uncommon clinicobiological presentation of a Gitelman syndrome  

PubMed Central

Background Gitelman syndrome is an autosomal recessive tubulopathy characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. The majority of patients do not present with symptoms until late childhood or adulthood, and the symptoms are generally mild. We report here the first case of Gitelman syndrome presenting with the biological features of Fanconi syndrome and an early polyuria since the neonatal period. We discuss in this article the atypical electrolytes losses found in our patient, as well as the possible mechanisms of severe polyuria. Case presentation A 6-year-old Caucasian girl was admitted via the Emergency department for vomiting, and initial laboratory investigations found hyponatremia, hypokalemia, metabolic acidosis with normal anion gap, hypophosphatemia, and hypouricemia. Urinalysis revealed Na, K, Ph and uric acid losses. Thus, the initial biological profile was in favor of a proximal tubular defect. However, etiological investigations were inconclusive and the patient was discharged with potassium chloride and phosphorus supplementation. Three weeks later, further laboratory analysis indicated persistent hypokalemia, a metabolic alkalosis, hypomagnesemia, and hypocalciuria. We therefore sequenced the SLC12A3 gene and found a compound heterozygosity for 2 known missense mutations. Conclusions Gitelman syndrome can have varying and sometimes atypical presentations, and should be suspected in case of hypokalemic tubular disorders that do not belong to any obvious syndromic entity. In this case, the proximal tubular dysfunction could be secondary to the severe hypokalemia. This report emphasizes the need for clinicians to repeat laboratory tests in undiagnosed tubular disorders, especially not during decompensation episodes. PMID:25112827

2014-01-01

210

Analysis of Metabolic Flux Phenotypes for Two Arabidopsis Mutants with Severe Impairment in Seed Storage Lipid Synthesis1[W][OA  

PubMed Central

Major storage reserves of Arabidopsis (Arabidopsis thaliana) seeds are triacylglycerols (seed oils) and proteins. Seed oil content is severely reduced for the regulatory mutant wrinkled1 (wri1-1; At3g54320) and for a double mutant in two isoforms of plastidic pyruvate kinase (pkp?1pkp?; At5g52920 and At3g22960). Both already biochemically well-characterized mutants were now studied by 13C metabolic flux analysis of cultured developing embryos based on comparison with their respective genetic wild-type backgrounds. For both mutations, in seeds as well as in cultured embryos, the oil fraction was strongly reduced while the fractions of proteins and free metabolites increased. Flux analysis in cultured embryos revealed changes in nutrient uptakes and fluxes into biomass as well as an increase in tricarboxylic acid cycle activity for both mutations. While in both wild types plastidic pyruvate kinase (PKp) provides most of the pyruvate for plastidic fatty acid synthesis, the flux through PKp is reduced in pkp?1pkp? by 43% of the wild-type value. In wri1-1, PKp flux is even more reduced (by 82%), although the genes PKp?1 and PKp? are still expressed. Along a common paradigm of metabolic control theory, it is hypothesized that a large reduction in PKp enzyme activity in pkp?1pkp? has less effect on PKp flux than multiple smaller reductions in glycolytic enzymes in wri1-1. In addition, only in the wri1-1 mutant is the large reduction in PKp flux compensated in part by an increased import of cytosolic pyruvate and by plastidic malic enzyme. No such limited compensatory bypass could be observed in pkp?1pkp?. PMID:19755540

Lonien, Joachim; Schwender, Jörg

2009-01-01

211

Early Cerebral Hemodynamic, Metabolic, and Histological Changes in Hypoxic–Ischemic Fetal Lambs during Postnatal Life  

PubMed Central

The hemodynamic, metabolic, and biochemical changes produced during the transition from fetal to neonatal life may be aggravated if an episode of asphyxia occurs during fetal life. The aim of the study was to examine regional cerebral blood flow (RCBF), histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress in the first hours of postnatal life following severe fetal asphyxia. Eighteen chronically instrumented newborn lambs were randomly assigned to either a control group or the hypoxic–ischemic (HI) group, in which case fetal asphyxia was induced just before delivery. All the animals were maintained on intermittent positive pressure ventilation for 3?h after delivery. During the HI insult, the injured group developed acidosis, hypoxia, hypercapnia, lactic acidosis, and tachycardia (relative to the control group), without hypotension. The intermittent positive pressure ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilatory support, there continued to be an increased RCBF in inner regions among the HI group, but no significant differences were detected in cortical flow compared to the control group. Also, the magnitude of the increase in TUNEL positive cells (apoptosis) and antioxidant enzymes, and decrease of ATP reserves was significantly greater in the brain regions where the RCBF was not higher. In conclusion, our findings identify early metabolic, histological, and hemodynamic changes involved in brain damage in premature asphyxiated lambs. Such changes have been described in human neonates, so our model could be useful to test the safety and the effectiveness of different neuroprotective or ventilation strategies applied in the first hours after fetal HI injury. PMID:21960958

Rey-Santano, Carmen; Mielgo, Victoria E.; Gastiasoro, Elena; Murgia, Xabier; Lafuente, Hector; Ruiz-del-Yerro, Estibaliz; Valls-i-Soler, Adolf; Hilario, Enrique; Alvarez, Francisco J.

2011-01-01

212

Usefulness of metabolic syndrome score in the prediction of angiographic coronary artery disease severity according to the presence of diabetes mellitus: relation with inflammatory markers and adipokines  

PubMed Central

Background It is a matter of debate whether metabolic syndrome (MS) improves cardiovascular risk prediction beyond the risk associated with its individual components. The present study examined the association of MS score with high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), resistin, adiponectin, and angiographic coronary artery disease (CAD) severity according to the presence of DM. In addition, the predictive value of various clinical and biochemical parameters were analyzed, including the MS score for angiographic CAD. Methods The study enrolled 363 consecutive patients (196 men, 62?±?11 years of age) who underwent coronary angiography for evaluation of chest pain. Blood samples were taken prior to elective coronary angiography. MS was defined by the National Cholesterol Education Program criteria, with MS score defined as the numbers of MS components. CAD was defined as?>?50% luminal diameter stenosis of at least one major epicardial coronary artery. CAD severity was assessed using the Gensini score. Results Of the 363 patients studied, 174 (48%) had CAD and 178 (49%) were diagnosed with MS. When the patients were divided into 4 subgroups according to MS score (0–1, 2, 3, 4–5), IL-6 levels and the CAD severity as assessed by the Gensini score increased as MS scores increased. In contrast, adiponectin levels decreased significantly as MS scores increased. When subjects were divided into two groups according to the presence of DM, the relationships between MS score and IL-6, adiponectin, and Gensini score were maintained only in patients without DM. Age, smoking, DM, MS score, and adiponectin independently predicted angiographic CAD in the whole population. However, age is the only predictor for angiographic CAD in patients with DM. Conclusions In the presence of DM, neither adipokines nor MS score predicted angiographic CAD. However, in non-diabetic patients, IL-6 and adiponectin showed progressive changes according to MS score, and MS score was an independent predictor of CAD in patients without DM. PMID:24088407

2013-01-01

213

Long-term safety of dichloroacetate in congenital lactic acidosis.  

PubMed

We followed 8 patients (4 males) with biochemically and/or molecular genetically proven deficiencies of the E1? subunit of the pyruvate dehydrogenase complex (PDC; 3 patients) or respiratory chain complexes I (1 patient), IV (3 patients) or I+IV (1 patient) who received oral dichloroacetate (DCA; 12.5 mg/kg/12 h) for 9.7 to 16.5 years. All subjects originally participated in randomized controlled trials of DCA and were continued on an open-label chronic safety study. Patients (1 adult) ranged in age from 3.5 to 40.2 years at the start of DCA administration and are currently aged 16.9 to 49.9 years (mean ± SD: 23.5 ± 10.9 years). Subjects were either normal or below normal body weight for age and gender. The 3 PDC deficient patients did not consume high fat (ketogenic) diets. DCA maintained normal blood lactate concentrations, even in PDC deficient children on essentially unrestricted diets. Hematological, electrolyte, renal and hepatic status remained stable. Nerve conduction either did not change or decreased modestly and led to reduction or temporary discontinuation of DCA in 3 patients, although symptomatic worsening of peripheral neuropathy did not occur. We conclude that chronic DCA administration is generally well-tolerated in patients with congenital causes of lactic acidosis and is effective in maintaining normal blood lactate levels, even in PDC-deficient children not consuming strict ketogenic diets. PMID:23611579

Abdelmalak, Monica; Lew, Alicia; Ramezani, Ryan; Shroads, Albert L; Coats, Bonnie S; Langaee, Taimour; Shankar, Meena N; Neiberger, Richard E; Subramony, S H; Stacpoole, Peter W

2013-06-01

214

Ammonium metabolism in humans.  

PubMed

Free ammonium ions are produced and consumed during cell metabolism. Glutamine synthetase utilizes free ammonium ions to produce glutamine in the cytosol whereas glutaminase and glutamate dehydrogenase generate free ammonium ions in the mitochondria from glutamine and glutamate, respectively. Ammonia and bicarbonate are condensed in the liver mitochondria to yield carbamoylphosphate initiating the urea cycle, the major mechanism of ammonium removal in humans. Healthy kidney produces ammonium which may be released into the systemic circulation or excreted into the urine depending predominantly on acid-base status, so that metabolic acidosis increases urinary ammonium excretion while metabolic alkalosis induces the opposite effect. Brain and skeletal muscle neither remove nor produce ammonium in normal conditions, but they are able to seize ammonium during hyperammonemia, releasing glutamine. Ammonia in gas phase has been detected in exhaled breath and skin, denoting that these organs may participate in nitrogen elimination. Ammonium homeostasis is profoundly altered in liver failure resulting in hyperammonemia due to the deficient ammonium clearance by the diseased liver and to the development of portal collateral circulation that diverts portal blood with high ammonium content to the systemic blood stream. Although blood ammonium concentration is usually elevated in liver disease, a substantial role of ammonium causing hepatic encephalopathy has not been demonstrated in human clinical studies. Hyperammonemia is also produced in urea cycle disorders and other situations leading to either defective ammonium removal or overproduction of ammonium that overcomes liver clearance capacity. Most diseases resulting in hyperammonemia and cerebral edema are preceded by hyperventilation and respiratory alkalosis of unclear origin that may be caused by the intracellular acidosis occurring in these conditions. PMID:22921946

Adeva, Maria M; Souto, Gema; Blanco, Natalia; Donapetry, Cristóbal

2012-11-01

215

Diets enriched with N-3 fatty acids ameliorate lactic acidosis by improving endotoxin-induced tissue hypoperfusion in guinea pigs.  

PubMed Central

The effect of 6 weeks dietary lipid manipulation on the acute physiologic response to 7-hour continuous endotoxin infusion in guinea pigs was examined. One diet was enriched with N-3 fatty acids, whereas the other contained N-6 fatty acids, primarily linoleic acid. Animals fed N-6 fatty acids developed significant lactic acidemia, microvascular muscle hypoperfusion, and pulmonary infiltrates in response to endotoxin infusion. N-3 fatty acid-fed animals demonstrated improved lactate levels, microvascular muscle perfusion, and lung morphology compared to N-6 fatty acid-fed animals after endotoxin infusion. There was no significant change in cardiac output, PaO2, or mean arterial blood pressure at the end of the endotoxin infusion in either group. Pretreatment with indomethacin, or BM 13505, a specific thromboxane A2 receptor blocker, ameliorated the development of metabolic acidosis in N-6 fatty acid-fed animals, demonstrating a role for prostanoids in the sequelae of endotoxemia. The ability of dietary pretreatment with N-3 fatty acids to influence favorably the physiologic response to endotoxin represents a novel nutrient-metabolic interaction with potential therapeutic implications. Images Fig. 6. Fig. 7. PMID:1992944

Pomposelli, J J; Flores, E A; Blackburn, G L; Zeisel, S H; Bistrian, B R

1991-01-01

216

Carotid body, insulin, and metabolic diseases: unraveling the links.  

PubMed

The carotid bodies (CB) are peripheral chemoreceptors that sense changes in arterial blood O2, CO2, and pH levels. Hypoxia, hypercapnia, and acidosis activate the CB, which respond by increasing the action potential frequency in their sensory nerve, the carotid sinus nerve (CSN). CSN activity is integrated in the brain stem to induce a panoply of cardiorespiratory reflexes aimed, primarily, to normalize the altered blood gases, via hyperventilation, and to regulate blood pressure and cardiac performance, via sympathetic nervous system (SNS) activation. Besides its role in the cardiorespiratory control the CB has been proposed as a metabolic sensor implicated in the control of energy homeostasis and, more recently, in the regulation of whole body insulin sensitivity. Hypercaloric diets cause CB overactivation in rats, which seems to be at the origin of the development of insulin resistance and hypertension, core features of metabolic syndrome and type 2 diabetes. Consistent with this notion, CB sensory denervation prevents metabolic and hemodynamic alterations in hypercaloric feed animal. Obstructive sleep apnea (OSA) is another chronic disorder characterized by increased CB activity and intimately related with several metabolic and cardiovascular abnormalities. In this manuscript we review in a concise manner the putative pathways linking CB chemoreceptors deregulation with the pathogenesis of insulin resistance and arterial hypertension. Also, the link between chronic intermittent hypoxia (CIH) and insulin resistance is discussed. Then, a final section is devoted to debate strategies to reduce CB activity and its use for prevention and therapeutics of metabolic diseases with an emphasis on new exciting research in the modulation of bioelectronic signals, likely to be central in the future. PMID:25400585

Conde, Sílvia V; Sacramento, Joana F; Guarino, Maria P; Gonzalez, Constancio; Obeso, Ana; Diogo, Lucilia N; Monteiro, Emilia C; Ribeiro, Maria J

2014-01-01

217

31P-NMR study of normoxic and anoxic perfused turtle heart during graded CO2 and lactic acidosis.  

PubMed

We studied the effects of graded acidosis (both CO2 and lactic acid) and anoxia on intracellular pH (pHi) regulation, high-energy phosphates, and mechanical function of isolated perfused hearts of the turtle (Chrysemys picta bellii) at 20 degrees C using 31P-nuclear magnetic resonance (NMR) spectroscopy. During CO2 acidosis, anoxia had no effect on apparent nonbicarbonate buffer value (d[HCO3-]/dpHi = 71 and 89 mM/pH in normoxia and anoxia, respectively) or on pHi regulation (dpHi/dpHe = 0.52 and 0.43 in normoxia and anoxia, respectively, where pHe is extracellular pH). During normoxic lactic acidosis, dpHi/dpHe was similar to the values observed in CO2 acidosis and averaged 0.55 overall. During anoxic lactic acidosis, however, similar regulation occurred over only a narrow range of pHe, and then dpHi/dpHe increased to greater than 1.0 at pHe less than 7.1. Creatine phosphate (CP), calculated as the area of the NMR peak, fell more in response to normoxic CO2 acidosis than to normoxic lactic acidosis; in anoxia, the fall in CP was further increased but to similar extreme levels (10-20% of control) in both acid perfusions. Cardiac output and maximum rate of pressure development each fell during acidosis in similar fashion in all protocols, and the responses were similar in normoxic and anoxic hearts. Heart rate, in contrast, decreased during acidosis, but this effect was more pronounced when hearts were anoxic. We conclude that the effect of acidosis on cardiac function can depend on the type of acidosis imposed. Based on the heart's insensitivity to anoxia alone, we suggest that anoxia may normally depress function indirectly via its effect on intracellular acid-base state. PMID:1905494

Jackson, D C; Arendt, E A; Inman, K C; Lawler, R G; Panol, G; Wasser, J S

1991-06-01

218

Expression of acidosis-dependent genes in human cancer nests.  

PubMed

Previous studies investigating cancer cells cultured at acidic pH have shown that the expression level of ~700 genes were more than two-fold higher than those of the cells cultured in alkaline medium at pH 7.5. The aim of the present study was to confirm whether these acidosis-induced genes are expressed in human cancer tissues. Therefore, 7 genes were selected from our previous study, which encoded interleukin 32 (IL-32), lysosomal H(+) transporting ATPase, V0 subunit d2 (ATP6V0D2), tumor necrosis factor receptor superfamily, member 9 (TNFRSF9), amphiregulin, schwannoma-derived growth factor (AREG), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ErbB3), PRR5-ARHGAP8 (LOC553158) and dimethylglycine dehydrogenase (DMGDH), and their expression was examined in human clinical specimens from patients with cancer. In addition, the expression of the gene encoding manganese superoxide dismutase (MnSOD) was examined. The specimens from patients with colon, stomach and renal cancer showed increased MnSOD, IL-32, and TNFRSF9 transcripts compared to those from non-tumorous regions of the same patients. Notably, an elevated expression of ATP6V0D2 was found in the specimens from patients with stomach cancer, whereas the expression was decreased in those from patients with colon and renal cancer. The expression of LOC553158 was upregulated in colon and stomach cancer specimens. These results indicate that the investigation of gene expression under acidic conditions is useful for the development of novel cancer markers and/or chemotherapeutic targets. PMID:25279216

Fukamachi, Toshihiko; Ikeda, Shunsuke; Saito, Hiromi; Tagawa, Masatoshi; Kobayashi, Hiroshi

2014-11-01

219

Expression of acidosis-dependent genes in human cancer nests  

PubMed Central

Previous studies investigating cancer cells cultured at acidic pH have shown that the expression level of ~700 genes were more than two-fold higher than those of the cells cultured in alkaline medium at pH 7.5. The aim of the present study was to confirm whether these acidosis-induced genes are expressed in human cancer tissues. Therefore, 7 genes were selected from our previous study, which encoded interleukin 32 (IL-32), lysosomal H+ transporting ATPase, V0 subunit d2 (ATP6V0D2), tumor necrosis factor receptor superfamily, member 9 (TNFRSF9), amphiregulin, schwannoma-derived growth factor (AREG), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ErbB3), PRR5-ARHGAP8 (LOC553158) and dimethylglycine dehydrogenase (DMGDH), and their expression was examined in human clinical specimens from patients with cancer. In addition, the expression of the gene encoding manganese superoxide dismutase (MnSOD) was examined. The specimens from patients with colon, stomach and renal cancer showed increased MnSOD, IL-32, and TNFRSF9 transcripts compared to those from non-tumorous regions of the same patients. Notably, an elevated expression of ATP6V0D2 was found in the specimens from patients with stomach cancer, whereas the expression was decreased in those from patients with colon and renal cancer. The expression of LOC553158 was upregulated in colon and stomach cancer specimens. These results indicate that the investigation of gene expression under acidic conditions is useful for the development of novel cancer markers and/or chemotherapeutic targets. PMID:25279216

FUKAMACHI, TOSHIHIKO; IKEDA, SHUNSUKE; SAITO, HIROMI; TAGAWA, MASATOSHI; KOBAYASHI, HIROSHI

2014-01-01

220

In vitro activation of complement and contact system by lactic acidosis.  

PubMed

The activation of complement and contact systems occurs in reperfusion injuries with initial tissue hypoxia, and lactic acidosis such as mycardial infarction and birth asphyxia. The aim of our experiment was the formal proof of activation by sole lactic acidosis. Lactic acid was added to blood and plasma samples from 10 healthy volunteers. C5a and factor XIIa were measured by EIA after incubation at 37 degrees C for 1 h. Both concentrations increased (P < 0.0001 by Friedman analysis) in blood and plasma samples with increasing amount of added lactic acid. Lactic acidosis can activate C5 from the complement system and factor XII from the contact system directly, even in the absence of cellular components. PMID:9839699

Sonntag, J; Emeis, M; Strauss, E; Obladen, M

1998-01-01

221

Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy.  

PubMed

OBJECTIVE. The relationship between metformin accumulation and lactate increase is still debated. This observational case series aims to evaluate the correlation of metformin plasma levels with the pH, lactate and creatinine levels, and with the mortality rate in selected patients with metformin accumulation confirmed through metformin plasma concentration detection at hospital admission. MATERIAL AND METHODS. All cases of lactic acidosis (pH, ? 7.35; arterial lactate, ? 5 mmol/L) related to metformin accumulation (plasma level ? 4 mcg/mL) from 2007 to 2011 were retrospectively reviewed. Erroneous ingestion and voluntary overdoses were excluded. Epidemiological, medical history, clinical and laboratory data were evaluated in all cases. RESULTS. Sixty-six patients were included. Thirty-one patients (47%) had contraindication to therapy with metformin. All patients showed severe lactic acidosis (pH, 6.91 ± 0.18; lactate, 14.36 ± 4.90 mmol/L) and acute renal failure (creatinine, 7.24 ± 3.29 mg/dL). The mean metformin plasma concentration was 40.68 ± 27.70 mcg/mL. Metformin plasma concentrations showed a correlation, statistically significant even if not strong, with creatinine (p = 0.002, R = 0.37), pH (p < 0.0001, R = - 0.43) and plasma lactate levels (p = 0.001, R = 0.41). Sixty-two (94%) underwent dialysis. Early mortality (before discharge from ICU) was 26% (17 cases). Lactate and metformin concentrations had mean levels not statistically different in surviving and deceased patients. CONCLUSIONS. Patients on chronic therapy with metformin may develop a mitochondrial-related toxicity that should be considered when patients present with lactic acidosis, renal failure, and frequently, a medical history of gastrointestinal manifestations during the days preceding the hospital admission. The correlation between metformin plasma concentrations and creatinine, pH, and lactate levels seems to be related to the mechanism of action (inhibition of complex I of the mitochondrial respiratory chain) and to the kinetic properties (high distribution volume and low protein binding) of the drug. The relevant early mortality seems not correlated with the levels of metformin or lactates: this could be due to the possible role of concurrent illness even if, such as for the relationships with lactate and creatinine, a more proper toxicological evaluation could be obtained by assessing metformin erythrocyte concentrations instead of the plasmatic ones. PMID:24283301

Vecchio, S; Giampreti, A; Petrolini, V M; Lonati, D; Protti, A; Papa, P; Rognoni, C; Valli, A; Rocchi, L; Rolandi, L; Manzo, L; Locatelli, C A

2014-02-01

222

p53 and metabolism  

Microsoft Academic Search

Although metabolic alterations have been observed in cancer for almost a century, only recently have the mechanisms underlying these changes been identified and the importance of metabolic transformation realized. p53 has been shown to respond to metabolic changes and to influence metabolic pathways through several mechanisms. The contributions of these activities to tumour suppression are complex and potentially rather surprising:

Karen H. Vousden; Kevin M. Ryan

2009-01-01

223

The Effects of Bupivacaine and Ropivacaine on Baroreflex Sensitivity With or Without Respiratory Acidosis and Alkalosis in Rats  

Microsoft Academic Search

Systemic toxicity of local anesthetics causes cardiac and central nervous system (CNS) depression that could be enhanced in the presence of respiratory acidosis. We examined a potential suppression of baroreflex func- tion with bupivacaine and ropivacaine during hyper- capnic acidosis or hypocapnic alkalosis. Baroreflex sen- sitivity (BRS) was randomly tested in rats with one of 13 conditions during intravenous administration

Yukinaga Watanabe; Shuji Dohi; Hiroki Iida; Tadahiko Ishiyama

1997-01-01

224

Pharmacokinetics, bioavailability, metabolism and acute and chronic antihypertensive effects of nitrendipine in patients with chronic renal failure and moderate to severe hypertension.  

PubMed Central

1. The pharmacokinetics, bioavailability, metabolism and antihypertensive effects of nitrendipine have been studied in 12 patients with impaired renal function and moderate to severe hypertension. The drug was administered simultaneously by the i.v. [13C4] and oral (commercial tablet 20 mg) routes. 2. No differences in the pharmacokinetic parameters were observed between the two routes of administration. The systemic clearance after i.v. administration in patients with renal impairment (18.2 +/- 6.1 ml min-1 kg-1) was similar to that observed in healthy volunteers. Despite complete absorption of drug from the tablet the bioavailability of the parent compound was 21.2 +/- 12.5%. Cumulative urinary excretion of nitrendipine metabolites was correlated with the creatinine clearance (r = 0.946). 3. Significant reductions in mean arterial blood pressure (mean: 23.6%) at the end of the nitrendipine infusion and after oral administration of 20 mg (mean: 17.5%) were observed. The blood pressure lowering effect of nitrendipine could be correlated within individuals with serum nitrendipine concentrations using a log linear model. 4. Following 4 weeks of therapy an average dose of 77 mg nitrendipine day-1 was required to achieve a systolic blood pressure below 160 mm Hg or a diastolic blood pressure below 90 mm Hg. The reduction in blood pressure during multiple dosing was related to the nitrendipine steady-state concentration. There was a significant relationship between the nitrendipine bioavailability and the dose required for sufficient blood pressure control. 5. No accumulation of nitrendipine caused by impaired renal function was observed during multiple dosing. Thus, no reduction of the nitrendipine dose in patients with renal impairment is necessary. PMID:2054271

Mikus, G; Mast, V; Fischer, C; Machleidt, C; Kuhlmann, U; Eichelbaum, M

1991-01-01

225

Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies  

PubMed Central

Proximal renal tubular acidosis (RTA) (Type II RTA) is characterized by a defect in the ability to reabsorb HCO3 in the proximal tubule. This is usually manifested as bicarbonate wastage in the urine reflecting that the defect in proximal tubular transport is severe enough that the capacity for bicarbonate reabsorption in the thick ascending limb of Henle's loop and more distal nephron segments is overwhelmed. More subtle defects in proximal bicarbonate transport likely go clinically unrecognized owing to compensatory reabsorption of bicarbonate distally. Inherited proximal RTA is more commonly autosomal recessive and has been associated with mutations in the basolateral sodium-bicarbonate cotransporter (NBCe1). Mutations in this transporter lead to reduced activity and/or trafficking, thus disrupting the normal bicarbonate reabsorption process of the proximal tubules. As an isolated defect for bicarbonate transport, proximal RTA is rare and is more often associated with the Fanconi syndrome characterized by urinary wastage of solutes like phosphate, uric acid, glucose, amino acids, low-molecular-weight proteins as well as bicarbonate. A vast array of rare tubular disorders may cause proximal RTA but most commonly it is induced by drugs. With the exception of carbonic anhydrase inhibitors which cause isolated proximal RTA, drug-induced proximal RTA is associated with Fanconi syndrome. Drugs that have been recently recognized to cause severe proximal RTA with Fanconi syndrome include ifosfamide, valproic acid and various antiretrovirals such as Tenofovir particularly when given to human immunodeficiency virus patients receiving concomitantly protease inhibitors such as ritonavir or reverse transcriptase inhibitors such as didanosine. PMID:23235953

Haque, Syed K.; Ariceta, Gema; Batlle, Daniel

2012-01-01

226

Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension.  

PubMed

Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O(2)) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH(4)Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH(4)Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening, and enhances pulmonary vascular responsiveness to vasoconstrictor and vasodilator stimuli. Together with our finding that acidosis decreases VSMC proliferation, the results are consistent with the possibility that nonhypercapnic acidosis promotes differentiation of pulmonary VSMCs to a more contractile phenotype, which may enhance the effectiveness of vasodilator therapies in PH. PMID:22287610

Christou, Helen; Reslan, Ossama M; Mam, Virak; Tanbe, Alain F; Vitali, Sally H; Touma, Marlin; Arons, Elena; Mitsialis, S Alex; Kourembanas, Stella; Khalil, Raouf A

2012-05-01

227

Everything you need to know about distal renal tubular acidosis in autoimmune disease.  

PubMed

Renal acid-base homeostasis is a complex process, effectuated by bicarbonate reabsorption and acid secretion. Impairment of urinary acidification is called renal tubular acidosis (RTA). Distal renal tubular acidosis (dRTA) is the most common form of the RTA syndromes. Multiple pathophysiologic mechanisms, each associated with various etiologies, can lead to dRTA. The most important consequence of dRTA is (recurrent) nephrolithiasis. The diagnosis is based on a urinary acidification test. Potassium citrate is the treatment of choice. PMID:24682397

Both, Tim; Zietse, Robert; Hoorn, Ewout J; van Hagen, P Martin; Dalm, Virgil A S H; van Laar, Jan A M; van Daele, Paul L A

2014-08-01

228

THE CORRELATION OF SERUM BICARBONATE AND METABOLIC ACIDOSIS TO ALBUMIN IN HEMODIALYSIS PATIENTS  

E-print Network

based on a patient’s dialysis schedule. The blood tests listed below were collected monthly at the dialysis center according to the doctor’s orders (35). Blood samples were collected through the patients’ dialysis accesses (e.g. AV fistula, graft...

Vyduna, Jennifer Lynn

2012-12-31

229

Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports  

Microsoft Academic Search

OBJECTIVE--To examine the possible contribution of sedation with propofol in the deaths of children who were intubated and required intensive care. DESIGN--Case note review. SETTING--Three intensive care units. SUBJECTS--Five children with upper respiratory tract infections aged between 4 weeks and 6 years. RESULTS--Four patients had laryngotracheo-bronchitis and one had bronchiolitis. All were sedated with propofol. The clinical course in all

T. J. Parke; J. E. Stevens; A. S. Rice; C. L. Greenaway; R. J. Bray; P. J. Smith; C. S. Waldmann; C. Verghese

1992-01-01

230

Activation of GPR4 by Acidosis Increases Endothelial Cell Adhesion through the cAMP/Epac Pathway  

PubMed Central

Endothelium-leukocyte interaction is critical for inflammatory responses. Whereas the tissue microenvironments are often acidic at inflammatory sites, the mechanisms by which cells respond to acidosis are not well understood. Using molecular, cellular and biochemical approaches, we demonstrate that activation of GPR4, a proton-sensing G protein-coupled receptor, by isocapnic acidosis increases the adhesiveness of human umbilical vein endothelial cells (HUVECs) that express GPR4 endogenously. Acidosis in combination with GPR4 overexpression further augments HUVEC adhesion with U937 monocytes. In contrast, overexpression of a G protein signaling-defective DRY motif mutant (R115A) of GPR4 does not elicit any increase of HUVEC adhesion, indicating the requirement of G protein signaling. Downregulation of GPR4 expression by RNA interference reduces the acidosis-induced HUVEC adhesion. To delineate downstream pathways, we show that inhibition of adenylate cyclase by inhibitors, 2?,5?-dideoxyadenosine (DDA) or SQ 22536, attenuates acidosis/GPR4-induced HUVEC adhesion. Consistently, treatment with a cAMP analog or a Gi signaling inhibitor increases HUVEC adhesiveness, suggesting a role of the Gs/cAMP signaling in this process. We further show that the cAMP downstream effector Epac is important for acidosis/GPR4-induced cell adhesion. Moreover, activation of GPR4 by acidosis increases the expression of vascular adhesion molecules E-selectin, VCAM-1 and ICAM-1, which are functionally involved in acidosis/GPR4-mediated HUVEC adhesion. Similarly, hypercapnic acidosis can also activate GPR4 to stimulate HUVEC adhesion molecule expression and adhesiveness. These results suggest that acidosis/GPR4 signaling regulates endothelial cell adhesion mainly through the Gs/cAMP/Epac pathway and may play a role in the inflammatory response of vascular endothelial cells. PMID:22110680

Leffler, Nancy R.; Asch, Adam S.; Witte, Owen N.; Yang, Li V.

2011-01-01

231

Paying Attention to Dietary Cation-Anion Balance Can Mean More Milk and Fewer Metabolic Problems  

Microsoft Academic Search

Charles C. Stallings, Professor and Extension Dairy Scientist, Virginia Tech Dietary cation-anion difference (DCAD) or balance can be used to alter the metabolic status of both dry and lactating cows. Research demonstrates that dry cows can benefit from a mild systemic acidosis at calv - ing, resulting in improved bone calcium mobilization. Lactating cows benefit from a mild systemic alkalosis

Mark A. McCann; Alma C. Hobbs

232

Diffuse large B-cell lymphoma: A metabolic disorder?  

PubMed Central

Patient Male, 81 Final Diagnosis: Non-Hodgkin lymphoma Symptoms: General weakness • hypoglycemia • metabolic acidosis Medication: — Clinical Procedure: — Specialty: Hematology Objective: Challenging differential diagnosis Background: B cell lymphoma constitutes 80–85% of cases of Non Hodgkin’s lymphoma in the Untied States. Metabolic complications may arise from the disease itself or through its end organ involvement. Case Report: We describe a case of a diffuse large B cell lymphoma diagnosed by abdominal computed tomography after it initially presented as hypoglycemia not correctable by dextrose infusion that instead resulted in increased anion gap metabolic acidosis with elevated lactate levels. Conclusions: The case illustrates how lymphomas can present unusually with hypoglycemia and lactic acidosis, the latter being an ominous sign that can occur without liver involvement. In this regard, the case demonstrates the metabolic sequelae of lymphoma that should raise suspicion for an underlying process. This has implications for diagnosis, treatment, and patient survival. Attention should be paid especially in the primary care setting in order to minimize delays in diagnosis. PMID:24349605

Tanios, Georges; Aranguren, Ines M.; Goldstein, Jack S.; Patel, Chirag B.

2013-01-01

233

Missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis.  

PubMed

Mutations in SLC4A4, the gene encoding the electrogenic Na(+)-HCO3(-) cotransporter NBCe1, cause severe proximal renal tubular acidosis (pRTA), growth retardation, decreased IQ, and eye and teeth abnormalities. Among the known NBCe1 mutations, the disease-causing mechanism of the T485S (NBCe1-A numbering) mutation is intriguing because the substituted amino acid, serine, is structurally and chemically similar to threonine. In this study, we performed intracellular pH and whole cell patch-clamp measurements to investigate the base transport and electrogenic properties of NBCe1-A-T485S in mammalian HEK 293 cells. Our results demonstrated that Ser substitution of Thr485 decreased base transport by ~50%, and importantly, converted NBCe1-A from an electrogenic to an electroneutral transporter. Aqueous accessibility analysis using sulfhydryl reactive reagents indicated that Thr485 likely resides in an NBCe1-A ion interaction site. This critical location is also supported by the finding that G486R (a pRTA causing mutation) alters the position of Thr485 in NBCe1-A thereby impairing its transport function. By using NO3(-) as a surrogate ion for CO3(2-), our result indicated that NBCe1-A mediates electrogenic Na(+)-CO3(2-) cotransport when functioning with a 1:2 charge transport stoichiometry. In contrast, electroneutral NBCe1-T485S is unable to transport NO3(-), compatible with the hypothesis that it mediates Na(+)-HCO3(-) cotransport. In patients, NBCe1-A-T485S is predicted to transport Na(+)-HCO3(-) in the reverse direction from blood into proximal tubule cells thereby impairing transepithelial HCO3(-) absorption, possibly representing a new pathogenic mechanism for generating human pRTA. PMID:23636456

Zhu, Quansheng; Shao, Xuesi M; Kao, Liyo; Azimov, Rustam; Weinstein, Alan M; Newman, Debra; Liu, Weixin; Kurtz, Ira

2013-08-15

234

Missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis  

PubMed Central

Mutations in SLC4A4, the gene encoding the electrogenic Na+-HCO3? cotransporter NBCe1, cause severe proximal renal tubular acidosis (pRTA), growth retardation, decreased IQ, and eye and teeth abnormalities. Among the known NBCe1 mutations, the disease-causing mechanism of the T485S (NBCe1-A numbering) mutation is intriguing because the substituted amino acid, serine, is structurally and chemically similar to threonine. In this study, we performed intracellular pH and whole cell patch-clamp measurements to investigate the base transport and electrogenic properties of NBCe1-A-T485S in mammalian HEK 293 cells. Our results demonstrated that Ser substitution of Thr485 decreased base transport by ?50%, and importantly, converted NBCe1-A from an electrogenic to an electroneutral transporter. Aqueous accessibility analysis using sulfhydryl reactive reagents indicated that Thr485 likely resides in an NBCe1-A ion interaction site. This critical location is also supported by the finding that G486R (a pRTA causing mutation) alters the position of Thr485 in NBCe1-A thereby impairing its transport function. By using NO3? as a surrogate ion for CO32?, our result indicated that NBCe1-A mediates electrogenic Na+-CO32? cotransport when functioning with a 1:2 charge transport stoichiometry. In contrast, electroneutral NBCe1-T485S is unable to transport NO3?, compatible with the hypothesis that it mediates Na+-HCO3? cotransport. In patients, NBCe1-A-T485S is predicted to transport Na+-HCO3? in the reverse direction from blood into proximal tubule cells thereby impairing transepithelial HCO3? absorption, possibly representing a new pathogenic mechanism for generating human pRTA. PMID:23636456

Shao, Xuesi M.; Kao, Liyo; Azimov, Rustam; Weinstein, Alan M.; Newman, Debra; Liu, Weixin; Kurtz, Ira

2013-01-01

235

Dilution acidosis and contraction alkalosis: Review of a concept  

Microsoft Academic Search

In the clinical evaluation of disorders of hydrogen ion homeostasis, it is customary to classify those conditions associated with a primary change in carbon dioxide tension as “respiratory”, and those associated with a primary change in the concentration of plasma bicarbonate as “metabolic” [1, 2]. Under most circumstances changes in plasma bicarbonate concentration reflect a discrepancy between the rate of

Serafino Garella; Bruce S Chang; Sewell I Kahn

1975-01-01

236

Identification of Differentially Expressed Proteins in Liver in Response to Subacute Ruminal Acidosis (SARA) Induced by High-concentrate Diet.  

PubMed

The aim of this study was to evaluate protein expression patterns of liver in response to subacute ruminal acidosis (SARA) induced by high-concentrate diet. Sixteen healthy mid-lactating goats were randomly divided into 2 groups and fed either a high-forage (HF) diet or a high-concentrate (HC) diet. The HC diet was expected to induce SARA. After ensuring the occurrence of SARA, liver samples were collected. Proteome analysis with differential in gel electrophoresis technology revealed that, 15 proteins were significantly modulated in liver in a comparison between HF and HC-fed goats. These proteins were found mainly associated with metabolism and energy transfer after identified by matrix-assisted laser desorption ionization/time of flight. The results indicated that glucose, lipid and protein catabolism could be enhanced when SARA occurred. It prompted that glucose, lipid and amine acid in the liver mainly participated in oxidation and energy supply when SARA occurred, which possibly consumed more precursors involved in milk protein and milk fat synthesis. These results suggest new candidate proteins that may contribute to a better understanding of the mechanisms that mediate liver adaptation to SARA. PMID:25083113

Jiang, X Y; Ni, Y D; Zhang, S K; Zhang, Y S; Shen, X Z

2014-08-01

237

Identification of Differentially Expressed Proteins in Liver in Response to Subacute Ruminal Acidosis (SARA) Induced by High-concentrate Diet  

PubMed Central

The aim of this study was to evaluate protein expression patterns of liver in response to subacute ruminal acidosis (SARA) induced by high-concentrate diet. Sixteen healthy mid-lactating goats were randomly divided into 2 groups and fed either a high-forage (HF) diet or a high-concentrate (HC) diet. The HC diet was expected to induce SARA. After ensuring the occurrence of SARA, liver samples were collected. Proteome analysis with differential in gel electrophoresis technology revealed that, 15 proteins were significantly modulated in liver in a comparison between HF and HC-fed goats. These proteins were found mainly associated with metabolism and energy transfer after identified by matrix-assisted laser desorption ionization/time of flight. The results indicated that glucose, lipid and protein catabolism could be enhanced when SARA occurred. It prompted that glucose, lipid and amine acid in the liver mainly participated in oxidation and energy supply when SARA occurred, which possibly consumed more precursors involved in milk protein and milk fat synthesis. These results suggest new candidate proteins that may contribute to a better understanding of the mechanisms that mediate liver adaptation to SARA. PMID:25083113

Jiang, X. Y.; Ni, Y. D.; Zhang, S. K.; Zhang, Y. S.; Shen, X. Z.

2014-01-01

238

Biochemical study in 28 children with lactic acidosis, in relation to Leigh's encephalomyelopathy  

Microsoft Academic Search

An enzymatic study of cultured skin fibroblasts was made in 28 patients with lactic acidosis. In three of these patients a diagnosis of Leigh's encephalomyelopathy was established from autopsy findings. Pyruvate decarboxylase (PDC) deficiency was found in four patients. In two of them, in whom Leigh's encephalomyelopathy was proved by autopsy, PDC activity was lower than 10% of the normal.

S. Miyabayashi; T. Ito; K. Narisawa; K. Iinuma; K. Tada

1985-01-01

239

Effects of Respiratory Acidosis and Alkalosis on the Distribution of Cyanide into the Rat Brain  

Microsoft Academic Search

The aim of this study was to determine whether respiratory acidosis favors the cerebral distribution of cyanide, and con- versely, if respiratory alkalosis limits its distribution. The phar- macokinetics of a nontoxic dose of cyanide were first studied in a group of 7 rats in order to determine the distribution phase. The pharmacokinetics were found to best fit a 3-compartment

Amina Djerad; Claire Monier; Pascal Houze; Stephen W. Borron; Jeanne-Marie Lefauconnier; Frederic J. Baud

2001-01-01

240

Lactic acidosis treatment by nanomole level of spermidine in an animal model.  

PubMed

Lactic acidosis occurs in a number of clinical conditions, e.g. in surgeries, orthotopic liver transplant, and anesthetic agent administration, which has deleterious effects on the patient's survival. The most rational therapy for these patients, the sodium bicarbonate administration, cannot prevent those accompanying deficiencies and may actually be harmful. In addition, tromethamine adjusts the blood pH, it does not affect the lactate accumulation. Therefore, discovery of a therapeutic agent is still a major unsolved problem. In this study, the rats were divided into different groups and lactic acidosis type B was induced in them. Then, the effect of different injection doses of spermidine (0-20nmol) on lactic acidosis was analyzed by measuring the lactate level and pH in the rat blood samples. The results showed that spermidine effectively and simultaneously inhibited the lactate and pyruvate accumulations, and also adjusted the pH of bloodstream. On the other hand, it has been shown (Damuni et al., 1984; Rahmatullah and Roche, 1988) that spermidine increases the activity of phosphatase, leading to prevention of lactate accumulation. The results indicate that administration of only nanomole level of spermidine may be the best treatment in the liver transplant and other patients suffering from lactic acidosis type B. PMID:25201010

Sedigh-Ardekani, Mozhgan; Sahmeddini, Mohammad Ali; Sattarahmady, Naghmeh; Mirkhani, Hossein

2014-11-01

241

Outcomes of Extremely Low Birth Weight Infants with Acidosis at Birth  

PubMed Central

OBJECTIVES To test the hypothesis that acidosis at birth is associated with the combined primary outcome of death or neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants, and to develop a predictive model of death/NDI exploring perinatal acidosis as a predictor variable. STUDY DESIGN The study population consisted of ELBW infants born between 2002-2007 at NICHD Neonatal Research Network hospitals. Infants with cord blood gas data and documentation of either mortality prior to discharge or 18-22 month neurodevelopmental outcomes were included. Multiple logistic regression analysis was used to determine the contribution of perinatal acidosis, defined as a cord blood gas with a pH<7 or base excess (BE)<-12, to death/NDI in ELBW infants. In addition, a multivariable model predicting death/NDI was developed. RESULTS 3979 patients were identified of whom 249 had a cord gas pH<7 or BE<-12 mEq/L. 2124 patients (53%) had the primary outcome of death/NDI. After adjustment for confounding variables, pH<7 and BE<-12 mEq/L were each significantly associated with death/NDI (OR=2.5[1.6,4.2]; and OR=1.5[1.1,2.0], respectively). However, inclusion of pH or BE did not improve the ability of the multivariable model to predict death/NDI. CONCLUSIONS Perinatal acidosis is significantly associated with death/NDI in ELBW infants. Perinatal acidosis is infrequent in ELBW infants, however, and other factors are more important in predicting death/NDI. PMID:24554564

Randolph, David A.; Nolen, Tracy L.; Ambalavanan, Namasivayam; Carlo, Waldemar A.; Peralta-Carcelen, Myriam; Das, Abhik; Bell, Edward F.; Davis, Alexis S.; Laptook, Abbot R.; Stoll, Barbara J.; Shankaran, Seetha; Higgins, Rosemary D.

2014-01-01

242

Metabolism and Hormonal Regulation Collagen Production in Fasted and Food-Restricted Rats: Response to Duration and Severity of Food Deprivation1'2  

Microsoft Academic Search

Malnutritionis associated with defects in connective tissue metabolism such as altered growth and wound healing. Because collagen is the major protein in most tissues, we determined the threshold for induction of altered collagen production by partial food restriction in rats. Groups of animals were fasted 2 or 4 d or were fed 20-100% of a predetermined food intake for 4

ROBERT SPANHEIMER; NKO ZLATEV; GUILLERMO ÃœMPIERREZ; MARIO DiGIROLAMO

243

The central role of BMP signaling in the regulation of iron metabolism Iron is an essential nutrient that is regulated by several complex intracellular and  

E-print Network

the body. Dysregulation of iron metabolism leads to common diseases such as hemochromatosis and anemia in early onset Juvenile Hemochromatosis, is a bone morphogenetic protein (BMP) co-receptor whose BMP hemochromatosis similar to HJV null mice. Our data show that 1) HJV selectively binds BMP ligands, 2) HJV

Miyashita, Yasushi

244

A role for adenosine in metabolic depression in the marine invertebrate Sipunculus nudus.  

PubMed

Involvement of neurotransmitters in metabolic depression under hypoxia and hypercapnia was examined in Sipunculus nudus. Concentration changes of several putative neurotransmitters in nervous tissue during anoxic or hypercapnic exposure or during combined anoxia and hypercapnia were determined. Among amino acids (gamma-aminobutyric acid, glutamate, glycine, taurine, serine, and aspartate) and monoamines (serotonin, dopamine, and norepinephrine), some changes were significant, but none were consistent with metabolic depression under all experimental conditions applied. Only the neuromodulator adenosine displayed concentration changes in accordance with metabolic depression under all experimental conditions. Levels increased during anoxia, during hypercapnia, and to an even greater extent during anoxic hypercapnia. Adenosine infusions into coelomic fluid via an indwelling catheter induced a significant depression of the normocapnic rate of O2 consumption from 0.36 +/- 0.04 to a minimum of 0.24 +/- 0.02 (SE) mumol.g-1.h-1 after 90 min (n = 6). Application of the adenosine antagonist theophylline caused a transient rise in O2 consumption 30 min after infusion during hypercapnia but not during normocapnia. Effects of adenosine and theophylline were observed in intact individuals but not in isolated body wall musculature. The results provide evidence for a role of adenosine in inducing metabolic depression in S. nudus, probably through the established effects of decreasing neuronal excitability and neurotransmitter release. In consideration of our previous finding that metabolic depression in isolated body wall musculature was elicited by extracellular acidosis, it is concluded that central and cellular mechanisms combine to contribute to the overall reduction in metabolic rate in S. nudus. PMID:9039028

Reipschläger, A; Nilsson, G E; Pörtner, H O

1997-01-01

245

Metabolic bone disease  

Microsoft Academic Search

Bone is a complex organ that is highly metabolically active, particularly in children. Normal metabolism is dependent upon the three main elements, matrix, mineral and cells that are integral components of bone. In addition, there are several humoral factors that also influence bone. Abnormalities in any of these components can give rise to metabolic bone disease. Abnormalities of mineralisation are

Jeremy Allgrove

2011-01-01

246

A patient with Graves' disease who survived despite developing thyroid storm and lactic acidosis  

PubMed Central

A 56-year-old woman with Graves' disease presented with the complaints of diarrhea and palpitations. Physical examination and laboratory data revealed hypothermia and signs of mild hyperthyroidism, heart failure, hepatic dysfunction with jaundice, hypoglycemia, and lactic acidosis. The patient was diagnosed as having developed the complication of thyroid storm in the absence of marked elevation of the thyroid hormone levels, because of the potential hepatic and cardiac dysfunctions caused by heavy alcohol drinking. A year later, after successful treatment, the patient remains well without any clinical evidence of heart failure or hepatic dysfunction. Thyroid storm associated with lactic acidosis and hypothermia is a serious condition and has rarely been reported. Prompt treatment is essential even if the serum thyroid hormone levels are not markedly elevated. We present a report about this patient, as her life could eventually be saved. PMID:20731531

2010-01-01

247

Grain-based versus alfalfa-based subacute ruminal acidosis induction experiments: Similarities and differences between changes in milk fatty acids.  

PubMed

Subacute ruminal acidosis (SARA) is one of the most important metabolic disorders, traditionally characterized by low rumen pH, which might be induced by an increase in the dietary proportion of grains as well as by a reduction of structural fiber. Both approaches were used in earlier published experiments in which SARA was induced by replacing part of the ration by a grain mixture or alfalfa hay by alfalfa pellets. The main differences between both experiments were the presence of blood lipopolysaccharide and Escherichia coli and associated effects on the rumen microbial population in the rumen of grain-based induced SARA animals as well as a great amount of quickly fermentable carbohydrates in the grain-based SARA induction experiment. Both induction approaches changed rumen pH although the pH decrease was more substantial in the alfalfa-based SARA induction protocol. The goal of the current analysis was to assess whether both acidosis induction approaches provoked similar shifts in the milk fatty acid (FA) profile. Similar changes of the odd- and branched-chain FA and the C18 biohydrogenation intermediates were observed in the alfalfa-based SARA induction experiment and the grain-based SARA induction experiment, although they were more pronounced in the former. The proportion of trans-10 C18:1 in the last week of the alfalfa-based induction experiment was 6 times higher than the proportion measured during the control week. The main difference between both induction experiments under similar rumen pH changes was the decreasing sum of iso FA during the grain-based SARA induction experiment whereas the sum of iso FA remained stable during the alfalfa-based SARA induction experiment. The cellulolytic bacterial community seemed to be negatively affected by either the presence of E. coli and the associated lipopolysaccharide accumulation in the rumen or by the amount of starch and quickly fermentable carbohydrates in the diet. In general, changes in the milk FA profile were related to changes in rumen pH. Nevertheless, feed characteristics (low in structural fiber vs. high in starch) also affected the milk FA profile and, as such, both effects should be taken into account when subacute acidosis occurs. PMID:23628250

Colman, E; Khafipour, E; Vlaeminck, B; De Baets, B; Plaizier, J C; Fievez, V

2013-07-01

248

Effect of acidosis on urine supersaturation and stone formation in genetic hypercalciuric stone-forming rats  

Microsoft Academic Search

Effect of acidosis on urine supersaturation and stone formation in genetic hypercalciuric stone-forming rats.BackgroundWe have successively inbred over 45 generations a strain of rats to maximize urine calcium excretion. The rats now consistently excrete 8 to 10 times as much calcium as controls and uniformly form poorly crystalline calcium phosphate kidney stones. In humans with calcium nephrolithiasis, consumption of a

David A. Bushinsky; Marc D. Grynpas; John R. Asplin

2001-01-01

249

Respiratory acidosis prolongs, while alkalosis shortens, the duration and recovery time of vecuronium in humans  

Microsoft Academic Search

Study Objective: To determine the effects of respiratory acidosis and alkalosis by mechanical ventilation on the onset, duration, and recovery times of vecuronium.Design: Randomized, prospective study.Setting: Operating rooms in the Sapporo Medical University Hospital and Kitami Red Cross Hospital.Patients: 90 ASA physical status I and II patients undergoing lower abdominal surgery.Interventions: Patients were randomly allocated to one of three groups

Masanori Yamauchi; Hiromi Takahashi; Hiroshi Iwasaki; Akiyoshi Namiki

2002-01-01

250

Prevalence of acidosis and inflammation and their association with low serum albumin in chronic kidney disease  

Microsoft Academic Search

Prevalence of acidosis and inflammation and their association with low serum albumin in chronic kidney disease.BackgroundLow serum albumin is a strong risk factor for mortality, but its association with low serum bicarbonate and inflammation in the setting of mild to moderately decreased kidney function is uncertain.MethodsWe analyzed data from 15,594 subjects over the age of 20 who participated in the

Joseph A. Eustace; BRAD ASTOR; Paul M. Muntner; T. Alp Ikizler; JOSEF CORESH

2004-01-01

251

Hypokalaemic paralysis precipitated by distal renal tubular acidosis secondary to Sjögren's syndrome.  

PubMed

A 43-year-old woman presented with a sudden onset of hypokalaemic paralysis requiring intubation and ventilatory support. Subsequent biochemical and clinical assessments established a diagnosis of distal renal tubular acidosis (RTA) in association with underlying Sjögren's syndrome as the aetiology of her profound hypokalaemia. Distal RTA is rare, but Sjögren's syndrome is one of the more common causes in adults and should be considered in the differential diagnosis of patients who present with hypokalaemic muscular paralysis. PMID:18325192

Comer, D M; Droogan, A G; Young, I S; Maxwell, A P

2008-03-01

252

Recessive distal renal tubular acidosis in Sarawak caused by AE1 mutations  

Microsoft Academic Search

Mutations of the AE1 (SLC4A1, Anion-Exchanger 1) gene that codes for band 3, the renal and red cell anion exchanger, are responsible for many cases of familial distal renal tubular acidosis (dRTA). In Southeast Asia this disease is usually recessive, caused either by homozygosity of a single AE1 mutation or by compound heterozygosity of two different AE1 mutations. We describe

Keng E. Choo; Taija K. Nicoli; Lesley J. Bruce; Michael J. A. Tanner; Andres Ruiz-Linares; Oliver M. Wrong

2006-01-01

253

Effect of respiratory acidosis and activity on airway smooth muscle intracellular pH.  

PubMed

Previous work in our laboratory has shown that respiratory acidosis (RA) impaired mechanical function in canine tracheal smooth muscle (TSM). Since an intracellular acidosis could be brought on by the increased CO2 content of the bathing medium and alter the Km's of rate-limiting glycolytic enzymes in the pathway of energy production for contractile function, we have investigated the effects of RA on the intracellular pH (pHi) of TSM. Using the DMO method, paired unstimulated or resting TSM strips were incubated under normocapnic conditions (PO2 600 Torr, PCO2 40 Torr, pH 7.40) and RA (PO2 550 Torr, PCO2 110 Torr, pH 6.95) with 14C-labeled DMO and 3H-labeled inulin or PEG-4000. In another set of paired experiments, TSM strips were tetanized electrically every 5 min or pharmacologically throughout the incubation period ("active" muscle strips). The tissue and an aliquot of bathing medium were counted for 3H and 14C content and the values entered into the Wadell and Butler equation. The pHi's of "resting" normocapnic and acidotic strips were 7.041 +/- 0.017 (SE) and 6.752 +/- 0.012, respectively. However, the pHi's of "active" normocapnic and acidotic strips were 7.275 +/- 0.017 and 7.017 +/- 0.015, respectively. We conclude that respiratory acidosis lowers intracellular pH in both resting and mechanically active TSM's; however, "active" preparations whether exposed to normocapnia or acidosis were unexpectedly more alkaline than their "resting" counterparts. PMID:14103

Stephens, N L; Mitchell, R W

1977-03-01

254

Edaravone alleviates hypoxia-acidosis/reoxygenation-induced neuronal injury by activating ERK1/2.  

PubMed

Edaravone, a free radical scavenger, is the first clinical drug of neuroprotection for ischemic stroke patients in the world, and has been shown to be an effective agent to alleviate cerebral ischemic injury. It has been established that acidosis is a common feature of cerebral ischemia and underlies the pathogenesis of ischemic stroke. In the present study, we investigated the role of edaravone in hypoxia-acidosis/reoxygenation (H-A/R)-induced neuronal injury that is partially mediated by the activation of acid-sensing ion channels (ASICs). Here, we observed that pretreatment of cultured neurons with edaravone largely reduced LDH release induced by acidosis or H-A/R. We also found that edaravone exhibited its neuroprotective roles by enhancing brain-derived neurotrophic factor (BDNF) and Bcl-2 expression, suppressing caspase-3 activity and promoting extracellular signal-regulated kinase1/2 (ERK1/2) activation. Furthermore, the addition of MEK (mitogen-activated protein kinase/ERK kinase) antagonists PD98059 and U0126 nearly abolished the beneficial effects of edaravone. Similarly, ASICs blockade produced the protective effects comparable to edaravone administration. These results indicate that edaravone is capable of attenuating H-A/R-mediated neurotoxicity at least partially through activating ERK1/2. PMID:23562504

Wang, Guibin; Su, Jingjing; Li, Lingjuan; Feng, Jie; Shi, Lei; He, Wei; Liu, Yunhai

2013-05-24

255

QTL for several metabolic traits map to loci controlling growth and body composition in an F2 intercross between high- and low-growth chicken lines.  

PubMed

Quantitative trait loci (QTL) for metabolic and body composition traits were mapped at 7 and 9 wk, respectively, in an F(2) intercross between high-growth and low-growth chicken lines. These lines also diverged for abdominal fat percentage (AFP) and plasma insulin-like growth factor-I (IGF-I), insulin, and glucose levels. Genotypings were performed with 129 microsatellite markers covering 21 chromosomes. A total of 21 QTL with genomewide level of significance were detected by single-trait analyses for body weight (BW), breast muscle weight (BMW) and percentage (BMP), AF weight (AFW) and percentage (AFP), shank length (ShL) and diameter (ShD), fasting plasma glucose level (Gluc), and body temperature (T(b)). Other suggestive QTL were identified for these parameters and for plasma IGF-I and nonesterified fatty acid levels. QTL controlling adiposity and Gluc were colocalized on GGA3 and GGA5 and QTL for BW, ShL and ShD, adiposity, and T(b) on GGA4. Multitrait analyses revealed two QTL controlling Gluc and AFP on GGA5 and Gluc and T(b) on GGA26. Significant effects of the reciprocal cross were observed on BW, ShD, BMW, and Gluc, which may result from mtDNA and/or maternal effects. Most QTL regions for Gluc and adiposity harbor genes for which alleles have been associated with increased susceptibility to diabetes and/or obesity in humans. Identification of genes responsible for these metabolic QTL will increase our understanding of the constitutive "hyperglycemia" found in chickens. Furthermore, a comparative approach could provide new information on the genetic causes of diabetes and obesity in humans. PMID:19531576

Nadaf, Javad; Pitel, Frédérique; Gilbert, Hélène; Duclos, Michel J; Vignoles, Florence; Beaumont, Catherine; Vignal, Alain; Porter, Tom E; Cogburn, Larry A; Aggrey, Samuel E; Simon, Jean; Le Bihan-Duval, Elisabeth

2009-08-01

256

Neurologic presentation, diagnostics, and therapeutic insights in a severe case of adenylosuccinate lyase deficiency.  

PubMed

Epilepsy in adenylosuccinate lyase deficiency may be difficult to treat, and there is no standardized therapy. The authors describe a case of severe adenylosuccinate lyase deficiency resulting from a heterozygous mutation of the ADSL gene (p.D215H/p.I351T). The patient presented with tonic-clonic seizures, opisthotonus, tremor, and myoclonus in the 4th day of life. The seizures were refractory on various combinations of antiepileptic treatment. A ketogenic diet was introduced at the age of 2 resulting in a seizure-free period. The patient, however, developed a metabolic hyperchloremic acidosis with Fanconi syndrome, which disappeared a month after cessation of the diet at the age of 5. Since the withdrawal of the ketogenic diet, seizures have returned to a frequency of several times a day. In conclusion, a ketogenic diet could be considered a valid therapeutic option in patients with intractable seizures in a course of adenylosuccinate lyase deficiency; however, it requires a formal study. PMID:22140128

Jurecka, Agnieszka; Opoka-Winiarska, Violetta; Rokicki, Dariusz; Tylki-Szyma?ska, Anna

2012-05-01

257

The effects of subacute ruminal acidosis on sodium bicarbonate-supplemented water intake for lactating dairy cows.  

PubMed

Four multiparous ruminally fistulated Holstein dairy cows were used in an 8-wk experiment utilizing a repeated measures block design to determine the effects of subacute ruminal acidosis (SARA) on supplemented water intake. Animals were subjected to SARA, which was induced by replacing 25% of the ad libitum intake of the total mixed ration (dry matter basis) with 50:50 wheat:barley pellets utilizing a grain challenge model. Cows had free choice from 2 water bowls. One bowl contained water with sodium bicarbonate (SB) supplemented at 2.5 g/L. The other bowl contained unsupplemented water. Ruminal pH was monitored continuously during the trial using indwelling pH probes. The induction of SARA reduced daily mean ruminal pH and increased the duration when ruminal pH was below 6. The total mixed ration intake by the cows decreased during the SARA periods. The overall preference for SB-supplemented water did not change, as the preference ratio was similar during the control and SARA periods. During the period of greatest ruminal pH depression, total water intake was higher during the SARA periods than during the control periods. During SARA, there was no difference in the preference of a SB water source to unsupplemented water. During the period of day with the most severe ruminal pH depression, the lactating dairy cows subjected to SARA increased their total water intake. PMID:15328239

Cottee, G; Kyriazakis, I; Widowski, T M; Lindinger, M I; Cant, J P; Duffield, T F; Osborne, V R; McBride, B W

2004-07-01

258

The central role of chloride in the metabolic acid-base changes in canine parvoviral enteritis.  

PubMed

The acid-base disturbances in canine parvoviral (CPV) enteritis are not well described. In addition, the mechanisms causing these perturbations have not been fully elucidated. The purpose of the present study was to assess acid-base changes in puppies suffering from CPV enteritis, using a modified strong ion model (SIM). The hypothesis of the study was that severe acid-base disturbances would be present and that the SIM would provide insights into pathological mechanisms, which have not been fully appreciated by the Henderson-Hasselbalch model. The study analysed retrospective data, obtained from 42 puppies with confirmed CPV enteritis and 10 healthy control dogs. The CPV-enteritis group had been allocated a clinical score, to allow classification of the data according to clinical severity. The effects of changes in free water, chloride, l-lactate, albumin and phosphate were calculated, using a modification of the base excess algorithm. When the data were summated for each patient, and correlated to each individual component, the most important contributor to the metabolic acid-base changes, according to the SIM, was chloride (P<0.001). Severely-affected animals tended to demonstrate hypochloraemic alkalosis, whereas mildly-affected puppies had a hyperchloraemic acidosis (P=0.007). In conclusion, the acid-base disturbances in CPV enteritis are multifactorial and complex, with the SIM providing information in terms of the origin of these changes. PMID:24613416

Burchell, Richard K; Schoeman, Johan P; Leisewitz, Andrew L

2014-04-01

259

Comprehensive review on lactate metabolism in human health.  

PubMed

Metabolic pathways involved in lactate metabolism are important to understand the physiological response to exercise and the pathogenesis of prevalent diseases such as diabetes and cancer. Monocarboxylate transporters are being investigated as potential targets for diagnosis and therapy of these and other disorders. Glucose and alanine produce pyruvate which is reduced to lactate by lactate dehydrogenase in the cytoplasm without oxygen consumption. Lactate removal takes place via its oxidation to pyruvate by lactate dehydrogenase. Pyruvate may be either oxidized to carbon dioxide producing energy or transformed into glucose. Pyruvate oxidation requires oxygen supply and the cooperation of pyruvate dehydrogenase, the tricarboxylic acid cycle, and the mitochondrial respiratory chain. Enzymes of the gluconeogenesis pathway sequentially convert pyruvate into glucose. Congenital or acquired deficiency on gluconeogenesis or pyruvate oxidation, including tissue hypoxia, may induce lactate accumulation. Both obese individuals and patients with diabetes show elevated plasma lactate concentration compared to healthy subjects, but there is no conclusive evidence of hyperlactatemia causing insulin resistance. Available evidence suggests an association between defective mitochondrial oxidative capacity in the pancreatic ?-cells and diminished insulin secretion that may trigger the development of diabetes in patients already affected with insulin resistance. Several mutations in the mitochondrial DNA are associated with diabetes mellitus, although the pathogenesis remains unsettled. Mitochondrial DNA mutations have been detected in a number of human cancers. d-lactate is a lactate enantiomer normally formed during glycolysis. Excess d-lactate is generated in diabetes, particularly during diabetic ketoacidosis. d-lactic acidosis is typically associated with small bowel resection. PMID:24929216

Adeva-Andany, M; López-Ojén, M; Funcasta-Calderón, R; Ameneiros-Rodríguez, E; Donapetry-García, C; Vila-Altesor, M; Rodríguez-Seijas, J

2014-07-01

260

Treatment of severe malaria.  

PubMed Central

In the treatment of severe Plasmodium falciparum infection antimalarial drugs should, ideally, be given by controlled rate intravenous infusion until the patient is able to swallow tablets. In cases where infection has been acquired in a chloroquine resistant area, and where it has broken through chloroquine prophylaxis or where the geographical origin or species are uncertain, quinine is the treatment of choice. When access to parenteral quinine is likely to be delayed, parenteral quinidine is an effective alternative. A loading dose of quinine is recommended in order to achieve therapeutic plasma concentrations as quickly as possible. In the case of chloroquine sensitive P. falciparum infection, chloroquine, which can be given safely by slow intravenous infusion, may be more rapidly effective and has fewer toxic effects than quinine. There is limited experience with parenteral administration of pyrimethamine sulphonamide combinations such as Fansidar, and resistance to these drugs has developed in South East Asia and elsewhere. Mefloquine and halofantrine cannot be given parenterally. Qinghaosu derivatives are not readily available and have not been adequately tested outside China. Supportive treatment includes the prevention or early detection and treatment of complications, strict attention to fluid balance, provision of adequate nursing for unconscious patients and avoidance of harmful ancillary treatments. Anaemia is inevitable and out of proportion to detectable parasitaemia. Hypotension and shock ('algid malaria') are often attributable to secondary gram-negative septicaemia requiring appropriate antimicrobial therapy and haemodynamic resuscitation. Many patients with severe falciparum malaria are hypovolaemic on admission to hospital and require cautious fluid replacement. Failure to rehydrate these patients may lead to circulatory collapse, lactic acidosis, renal failure and severe hyponatraemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2693726

Warrell, D A

1989-01-01

261

Acidosis dilates brain parenchymal arterioles by conversion of calcium waves to sparks to activate BK channels  

PubMed Central

Rationale Acidosis is a powerful vasodilator signal in the brain circulation. However, the mechanisms by which this response occurs are not well understood, particularly in the cerebral microcirculation. One important mechanism to dilate cerebral (pial) arteries is by activation of large-conductance, calcium-sensitive potassium (BKCa) channels by local Ca2+ signals (Ca2+ sparks) through ryanodine receptors (RyRs). However, the role of this pathway in the brain microcirculation is not known. Objective The objectives of this study were to determine the mechanism by which acidosis dilates brain parenchymal arterioles (PAs) and to elucidate the roles of RyRs and BKCa channels in this response. Methods and Results Internal diameter and vascular smooth muscle cell (VSMC) Ca2+ signals were measured in isolated pressurized murine PAs, using imaging techniques. In physiological pH (7.4), VSMCs exhibited primarily RyR-dependent Ca2+ waves. Reducing external pH from 7.4 to 7.0 in both normocapnic and hypercapnic conditions decreased Ca2+ wave activity, and dramatically increased Ca2+ spark activity. Acidic pH caused a dilation of PAs which was inhibited by about 60% by BKCa channel or RyR blockers, in a non-additive manner. Similarly, dilator responses to acidosis were reduced by nearly 60% in arterioles from BKCa channel knockout mice. Dilations induced by acidic pH were unaltered by inhibitors of KATP channels or nitric oxide synthase. Conclusions These results support the novel concept that acidification, by converting Ca2+ waves to sparks, leads to the activation of BKCa channels to induce dilation of cerebral parenchymal arterioles. PMID:22095728

Dabertrand, Fabrice; Nelson, Mark T.; Brayden, Joseph E.

2012-01-01

262

Genetic Variation in Iron Metabolism Is Associated with Neuropathic Pain and Pain Severity in HIV-Infected Patients on Antiretroviral Therapy  

PubMed Central

HIV sensory neuropathy and distal neuropathic pain (DNP) are common, disabling complications associated with combination antiretroviral therapy (cART). We previously associated iron-regulatory genetic polymorphisms with a reduced risk of HIV sensory neuropathy during more neurotoxic types of cART. We here evaluated the impact of polymorphisms in 19 iron-regulatory genes on DNP in 560 HIV-infected subjects from a prospective, observational study, who underwent neurological examinations to ascertain peripheral neuropathy and structured interviews to ascertain DNP. Genotype-DNP associations were explored by logistic regression and permutation-based analytical methods. Among 559 evaluable subjects, 331 (59%) developed HIV-SN, and 168 (30%) reported DNP. Fifteen polymorphisms in 8 genes (p<0.05) and 5 variants in 4 genes (p<0.01) were nominally associated with DNP: polymorphisms in TF, TFRC, BMP6, ACO1, SLC11A2, and FXN conferred reduced risk (adjusted odds ratios [ORs] ranging from 0.2 to 0.7, all p<0.05); other variants in TF, CP, ACO1, BMP6, and B2M conferred increased risk (ORs ranging from 1.3 to 3.1, all p<0.05). Risks associated with some variants were statistically significant either in black or white subgroups but were consistent in direction. ACO1 rs2026739 remained significantly associated with DNP in whites (permutation p<0.0001) after correction for multiple tests. Several of the same iron-regulatory-gene polymorphisms, including ACO1 rs2026739, were also associated with severity of DNP (all p<0.05). Common polymorphisms in iron-management genes are associated with DNP and with DNP severity in HIV-infected persons receiving cART. Consistent risk estimates across population subgroups and persistence of the ACO1 rs2026739 association after adjustment for multiple testing suggest that genetic variation in iron-regulation and transport modulates susceptibility to DNP. PMID:25144566

Kallianpur, Asha R.; Jia, Peilin; Ellis, Ronald J.; Zhao, Zhongming; Bloss, Cinnamon; Wen, Wanqing; Marra, Christina M.; Hulgan, Todd; Simpson, David M.; Morgello, Susan; McArthur, Justin C.; Clifford, David B.; Collier, Ann C.; Gelman, Benjamin B.; McCutchan, J. Allen; Franklin, Donald; Samuels, David C.; Rosario, Debralee; Holzinger, Emily; Murdock, Deborah G.; Letendre, Scott; Grant, Igor

2014-01-01

263

Physiological changes in rumen fermentation during acidosis induction and its control using a multivalent polyclonal antibody preparation in heifers.  

PubMed

Physiological changes in rumen fermentation during acidosis induction and its control using a multivalent polyclonal antibody preparation (PAP) were studied in a completely randomized experiment using 12 crossbred heifers (452 +/- 20 kg of BW). Treatments were control (CTR) or PAP. The acidosis induction protocol consisted of 3 periods: 3 mo of 100% fescue hay fed for ad libitum intake, 10 d (from d 1 to 10 of the experiment) of adaptation to the treatment (100% forage feeding + 10 mL/d of PAP top-dressed to the treatment group), and 5 d (from d 11 to 15 of the experiment) of transition, which consisted of increasing the concentrate (16.5% CP) 2.5 kg/d up to 12.5 kg/d while maintaining ad libitum intake of fescue and providing 10 mL/d of PAP to the treated heifers. Concentrate feeding of 12.5 kg/d was maintained until heifers developed acidosis (from d 16 to 22 of the experiment). When an animal was considered acidotic, it was changed to a 50:50 forage:concentrate diet, monitored for 4 d, and removed from the experiment. Samples of ruminal fluid were collected before and 6 h after feeding to determine pH, VFA, lactate, protozoa counts, and DNA extraction for quantitative real-time PCR and denaturing gradient gel electrophoresis analyses. Only samples collected during adaptation to the treatment, at 3 and 1 d before acidosis, on the acidosis day, and at 1 and 4 d after acidosis were analyzed. Differences were declared at P < 0.05. Heifers (83% for CTR, and 50% for PAP) entered into acidosis 5.25 +/- 0.17 d after the beginning of the transition. The fermentation profile of animals with acidosis was similar between treatments. From 3 d before acidosis to acidosis day, decreases in pH and in acetate-to-propionate ratio and increases in total VFA, butyrate, and entodiniomorph counts were observed. However, the greatest concentrations of Streptococcus bovis and Megasphaera elsdenii (79 +/- 54 and 104 +/- 73 ng of DNA/mL of ruminal fluid, respectively) and a decrease in DMI (10.6 vs. 6.46 kg, respectively) were recorded 1 d after acidosis. Compared with CTR heifers, heifers fed PAP had greater pH before feeding on d 6 (6.70 vs. 6.11), 8 (6.54 vs. 5.95), and 9 (7.26 vs. 6.59) after the beginning of the feeding challenge. Heifers fed PAP tended to have greater total VFA concentrations than CTR (124 and 114 +/- 4.0 mM, respectively). These results indicate that PAP may be effective in controlling acidosis of heifers during a rapid transition to a high-concentrate diet. PMID:19213715

Blanch, M; Calsamiglia, S; DiLorenzo, N; DiCostanzo, A; Muetzel, S; Wallace, R J

2009-05-01

264

Modulation of ventricular transient outward K? current by acidosis and its effects on excitation-contraction coupling.  

PubMed

The contribution of transient outward current (Ito) to changes in ventricular action potential (AP) repolarization induced by acidosis is unresolved, as is the indirect effect of these changes on calcium handling. To address this issue we measured intracellular pH (pHi), Ito, L-type calcium current (ICa,L), and calcium transients (CaTs) in rabbit ventricular myocytes. Intracellular acidosis [pHi 6.75 with extracellular pH (pHo) 7.4] reduced Ito by ~50% in myocytes with both high (epicardial) and low (papillary muscle) Ito densities, with little effect on steady-state inactivation and activation. Of the two candidate ?-subunits underlying Ito, human (h)Kv4.3 and hKv1.4, only hKv4.3 current was reduced by intracellular acidosis. Extracellular acidosis (pHo 6.5) shifted Ito inactivation toward less negative potentials but had negligible effect on peak current at +60 mV when initiated from -80 mV. The effects of low pHi-induced inhibition of Ito on AP repolarization were much greater in epicardial than papillary muscle myocytes and included slowing of phase 1, attenuation of the notch, and elevation of the plateau. Low pHi increased AP duration in both cell types, with the greatest lengthening occurring in epicardial myocytes. The changes in epicardial AP repolarization induced by intracellular acidosis reduced peak ICa,L, increased net calcium influx via ICa,L, and increased CaT amplitude. In summary, in contrast to low pHo, intracellular acidosis has a marked inhibitory effect on ventricular Ito, perhaps mediated by Kv4.3. By altering the trajectory of the AP repolarization, low pHi has a significant indirect effect on calcium handling, especially evident in epicardial cells. PMID:23585132

Saegusa, Noriko; Garg, Vivek; Spitzer, Kenneth W

2013-06-15

265

Correlation analysis of hypothalamic mRNA levels of appetite regulatory neuropeptides and several metabolic parameters in 28-day-old layer chickens.  

PubMed

Various lines of evidence suggest that appetite-related neuropeptides in the hypothalamus are regulated by adiposity signals such as leptin and insulin in mammals. In the present study, we examined age-dependent changes in the weight of abdominal fat and hypothalamic mRNA levels of neuropeptide Y (NPY, an orexigenic neuropeptide) and proopiomelanocortin (POMC, a precursor of anorexigenic neuropeptides) in growing chickens at 7, 14, 21 and 28 days of age. Hypothalamic NPY mRNA levels were significantly (P?several parameters at 28 days of age. There were no significant correlations between hypothalamic mRNA levels of NPY or POMC and the percentage of abdominal fat. These findings suggest that the gene expressions of NPY and POMC do not depend on adiposity in chickens, at least in 28-day-old layer chickens. PMID:25441031

Honda, Kazuhisa; Saneyasu, Takaoki; Aoki, Koji; Shimatani, Tomohiko; Yamaguchi, Takuya; Kamisoyama, Hiroshi

2014-11-30

266

Severe renal failure and hyperammonemia in a newborn with propionic acidemia: effects of treatment on the clinical course.  

PubMed

Neonatal-onset propionic acidemia (PA), the most common form, is characterized by poor feeding, vomiting, and somnolence in the first days of life in a previously healthy infant, followed by lethargy, seizures, and can progress to coma if not identified and treated appropriately. It is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. PA is caused by deficiency of propionyl-CoA carboxylase (PCC), the enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA. Herein, we report a case of 3-day-old neonate with PA presented with acute renal failure and metabolic acidosis was effectively treated by peritoneal dialysis and conventional methods. PMID:24329397

Kasapkara, Ci?dem Seher; Akar, Melek; Yürük Y?ld?r?m, Zeynep Nagehan; Tüzün, Heybet; Kanar, Berat; Ozbek, Mehmet Nuri

2014-04-01

267

Sustained metabolic scope.  

PubMed Central

Sustained metabolic rates (SusMR) are time-averaged metabolic rates that are measured in free-ranging animals maintaining constant body mass over periods long enough that metabolism is fueled by food intake rather than by transient depletion of energy reserves. Many authors have suggested that SusMR of various wild animal species are only a few times resting (basal or standard) metabolic rates (RMR). We test this conclusion by analyzing all 37 species (humans, 31 other endothermic vertebrates, and 5 ectothermic vertebrates) for which SusMR and RMR had both been measured. For all species, the ratio of SusMR to RMR, which we term sustained metabolic scope, is less than 7; most values fall between 1.5 and 5. Some of these values, such as those for Tour de France cyclists and breeding birds, are surely close to sustainable metabolic ceilings for the species studied. That is, metabolic rates higher than 7 times RMR apparently cannot be sustained indefinitely. These observations pose several questions: whether the proximate physiological causes of metabolic ceilings reside in the digestive tract's ability to process food or in each tissue's metabolic capacity; whether ceiling values are independent of the mode of energy expenditure; whether ceilings are set by single limiting physiological capacities or by coadjusted clusters of capacities (symmorphosis); what the ultimate evolutionary causes of metabolic ceilings are; and how metabolic ceilings may limit animals' reproductive effort, foraging behavior, and geographic distribution. PMID:2315323

Peterson, C C; Nagy, K A; Diamond, J

1990-01-01

268

Rare mutation in the SLC26A3 transporter causes life-long diarrhoea with metabolic alkalosis.  

PubMed

SLC26A3, a chloride/bicarbonate transporter mainly expressed in the intestines, plays a pivotal role in chloride absorption. We present a 23-year-old woman with a history of congenital chloride diarrhoea (CCD) and renal transplant who was admitted for rehydration and treatment of acute kidney injury after she presented with an acute diarrhoeal episode. Laboratory investigations confirmed metabolic alkalosis and severe hypochloraemia, consistent with her underlying CCD. This contrasts with most other forms of diarrhoea, which are normally associated with metabolic acidosis. Genetic testing was offered and revealed a homozygous non-sense mutation in SLC26A3 (Gly-187-Stop). This loss-of-function mutation results in bicarbonate retention in the blood and chloride loss into the intestinal lumen. Symptomatic management with daily NaCl and KCl oral syrups was supplemented with omeprazole therapy. The loss of her own kidneys is most likely due to crystal-induced nephropathy secondary to chronic volume contraction and chloride depletion. This case summarises the pathophysiology and management of CCD. PMID:25568271

Abou Ziki, Maen D; Verjee, Mohamud A

2015-01-01

269

Topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis.  

PubMed

NBCe1-A electrogenically cotransports Na(+) and HCO(3)(-) across the basolateral membrane of renal proximal tubule cells. Eight missense mutations and 3 nonsense mutations in NBCe1-A cause severe proximal renal tubular acidosis (pRTA). In this study, the topologic properties and structural importance of the 8 endogenous residues mutated in pRTA and the in situ topology of NBCe1-A were examined by the substituted cysteine accessibility method. Of the 55 analyzed individually introduced cysteines, 8 were labeled with both membrane permeant (biotin maleimide (BM)) and impermeant (2-((5(6)-tetramethylrhodamine)carboxylamino)ethyl methanethiosulfonate (MTS-TAMRA)) sulfhydryl reagents, 4 with only BM, and 3 with only MTS-TAMRA. The location of the labeled and unlabeled introduced cysteines clearly indicates that the transmembrane region of NBCe1-A contains 14 transmembrane segments (TMs). In this in situ based NBCe1-A topology, residues mutated in pRTA (pRTA residues) are assigned as: Ser(427), TM1; Thr(485) and Gly(486), TM3; Arg(510) and Leu(522), TM4; Ala(799), TM10; and Arg(881), TM12. Substitution of pRTA residues with cysteines impaired the membrane trafficking of R510C and R881C, the remaining membrane-processed constructs had various impaired transport function. Surprisingly, none of the membrane-processed constructs was accessible to labeling with BM and MTS-TAMRA, nor were they functionally sensitive to the inhibition by (2-aminoethyl)methanethiosulfonate. Functional analysis of Thr(485) with different amino acid substitutions indicated it resides in a unique region important for NBCe1-A function. Our findings demonstrate that the pRTA residues in NBCe1-A are buried in the protein complex/lipid bilayer where they perform important structural roles. PMID:20197274

Zhu, Quansheng; Kao, Liyo; Azimov, Rustam; Newman, Debra; Liu, Weixin; Pushkin, Alexander; Abuladze, Natalia; Kurtz, Ira

2010-04-30

270

Metabolic Syndrome  

MedlinePLUS

... is a signal that someone could be on the road to serious health problems. Diagnosing metabolic syndrome helps ... like heart disease or type 2 diabetes down the road. What Exactly Is Metabolic Syndrome? Metabolic syndrome is ...

271

Individual animal variability in ruminal bacterial communities and ruminal acidosis in primiparous Holstein cows during the periparturient period  

Technology Transfer Automated Retrieval System (TEKTRAN)

The purpose of this study was to investigate variability among individual cows for their susceptibility to ruminal acidosis (RA) pre- and postpartum, and determine whether this variability was related to differences in their ruminal bacterial community composition (BCC). Variability in susceptibilit...

272

Effects of acute hypercapnia with and without acidosis on lung inflammation and apoptosis in experimental acute lung injury.  

PubMed

We investigated the effects of acute hypercapnic acidosis and buffered hypercapnia on lung inflammation and apoptosis in experimental acute lung injury (ALI). Twenty-four hours after paraquat injection, 28 Wistar rats were randomized into four groups (n=7/group): (1) normocapnia (NC, PaCO2=35-45mmHg), ventilated with 0.03%CO2+21%O2+balancedN2; (2) hypercapnic acidosis (HC, PaCO2=60-70mmHg), ventilated with 5%CO2+21%O2+balancedN2; and (3) buffered hypercapnic acidosis (BHC), ventilated with 5%CO2+21%O2+balancedN2 and treated with sodium bicarbonate (8.4%). The remaining seven animals were not mechanically ventilated (NV). The mRNA expression of interleukin (IL)-6 (p=0.003), IL-1? (p<0.001), and type III procollagen (PCIII) (p=0.001) in lung tissue was more reduced in the HC group in comparison with NC, with no significant differences between HC and BHC. Lung and kidney cell apoptosis was reduced in HC and BHC in comparison with NC and NV. In conclusion, in this experimental ALI model, hypercapnia, regardless of acidosis, reduced lung inflammation and lung and kidney cell apoptosis. PMID:25246186

Nardelli, L M; Rzezinski, A; Silva, J D; Maron-Gutierrez, T; Ornellas, D S; Henriques, I; Capelozzi, V L; Teodoro, W; Morales, M M; Silva, P L; Pelosi, P; Garcia, C S N B; Rocco, P R M

2015-01-01

273

A reliable, practical, and economical protocol for inducing diarrhea and severe dehydration in the neonatal calf.  

PubMed Central

Fifteen healthy, colostrum-fed, male dairy calves, aged 2 to 7 d were used in a study to develop a diarrhea protocol for neonatal calves that is reliable, practical, and economical. After instrumentation and recording baseline data, diarrhea and dehydration were induced by administering milk replacer [16.5 mL/kg of body weight (BW), PO], sucrose (2 g/kg in a 20% aqueous solution, p.o.), spironolactone and hydrochlorothiazide (1 mg/kg, PO) every 8 h, and furosemide (2 mg/kg, i.m., q6h). Calves were administered sucrose and diuretic agents for 48 h to induce diarrhea and severe dehydration. Clinical changes after 48 h were severe watery diarrhea, severe depression, and marked dehydration (mean, 14% BW loss). Cardiac output, stroke volume, mean central venous pressure, plasma volume, thiocyanate space, blood pH and bicarbonate concentration, base excess, serum chloride concentration, and fetlock temperature were decreased. Plasma lactate concentration, hematocrit, and serum potassium, creatinine, phosphorus, total protein and albumin concentrations were increased. This non-infectious calf diarrhea protocol has a 100% response rate, while providing a consistent and predictable hypovolemic state with diarrhea that reflects most of the clinicopathologic changes observed in osmotic/maldigestive diarrhea caused by infection with rotavirus, coronavirus or cryptosporidia. Limitations of the protocol, when compared to infectious diarrhea models, include failure to induce a severe metabolic acidosis, absence of hyponatremia, renal instead of enteric loss of chloride, renal as well as enteric loss of free water, absence of profound clinical depression and suspected differences in the morphologic and functional effect on intestinal epithelium. Despite these differences, the sucrose/diuretic protocol should be useful in the initial screening of new treatment modalities for calf diarrhea. To confirm their efficacy, the most effective treatment methods should then be examined in calves with naturally-acquired diarrhea. PMID:9684050

Walker, P G; Constable, P D; Morin, D E; Drackley, J K; Foreman, J H; Thurmon, J C

1998-01-01

274

Impact of hard vs. soft wheat and monensin level on rumen acidosis in feedlot heifers.  

PubMed

Many feedlot finishing diets include wheat when the relative wheat prices are low. This study was conducted to examine the responses in ruminal pH and fermentation as well as site and extent of digestion from substituting soft or hard wheat for barley grain and to determine whether an elevated monensin concentration might decrease indicators of ruminal acidosis in feedlot heifers. Five ruminally cannulated beef heifers were used in a 5 × 5 Latin square with 2 × 2 + 1 factorial arrangement. Treatments included barley (10% barley silage, 86% barley, 4% supplement, with 28 mg monensin/kg DM) and diets where barley was substituted by either soft or hard wheat with either 28 or 44 mg monensin/kg diet DM. Intake of DM was not affected by grain source, whereas increasing monensin with wheat diets reduced (P < 0.02) DMI. Mean ruminal pH was lower (P < 0.04) and durations of pH < 5.8 and pH < 5.5 greater (P < 0.03) for wheat than for barley diets. However, ruminal pH was not affected by wheat type or monensin level. Total VFA concentrations were greater (P < 0.03) for wheat than barley diets with no effect of wheat type. The molar proportion of propionate was greater (P < 0.04), whereas butyrate (P < 0.01) and ratio of acetate to propionate tended to be lower (P < 0.09), with the high as compared to low level of monensin. Replacing barley with wheat in finishing diets did not affect the duodenal flow or the digestibility of OM, likely as a result of greater (P < 0.01) NDF digestion from barley offsetting the increased (P < 0.03) supply of digested starch from wheat. Feeding soft vs. hard wheat delivered a greater (P < 0.03) duodenal supply of OM and nonammonia N with no differences in total tract nutrient digestion. The increased monensin concentration decreased the flow of OM (P < 0.01), total N (P < 0.05), and microbial protein (P < 0.05) to the small intestine due to decreased DMI. These results indicated that hard and soft wheat exhibited digestive characteristics similar to barley, but ruminal pH measurements indicate that compared with barley, wheat increased the risk of ruminal acidosis. Although an increased level of monensin had limited impact on ruminal indicators of acidosis, an increase in propionate would be expected to improve efficiency of feed use by heifers fed wheat-based finishing diets. PMID:25253812

Yang, W Z; Xu, L; Zhao, Y L; Chen, L Y; McAllister, T A

2014-11-01

275

Targeting the Metabolic Microenvironment of Tumors  

PubMed Central

The observation of aerobic glycolysis by tumor cells in 1924 by Otto Warburg, and subsequent innovation of imaging glucose uptake by tumors in patients with PET-CT has incited a renewed interest in the altered metabolism of tumors. As tumors grow in situ, a fraction of it is further away from their blood supply, leading to decreased oxygen concentrations (hypoxia), which induces the hypoxia response pathways of HIF1?, mTOR and UPR. In normal tissues, these responses mitigate hypoxic stress and induce neo-angiogenesis. In tumors, these pathways are dysregulated and lead to decreased perfusion and exacerbation of hypoxia as a result of immature and chaotic blood vessels. Hypoxia selects for a glycolytic phenotype and resultant acidification of the tumor microenvironment, facilitated by upregulation of proton transporters. Acidification selects for enhanced metastatic potential and reduced drug efficacy through ion trapping. In this review, we provide a comprehensive summary of pre-clinical and clinical drugs under development for targeting aerobic glycolysis, acidosis, hypoxia and hypoxia-response pathways. Hypoxia and acidosis can be manipulated, providing further therapeutic benefit for cancers that feature these common phenotypes. PMID:22959024

Bailey, Kate M.; Wojtkowiak, Jonathan W.; Hashim, Arig Ibrahim; Gillies, Robert J.

2013-01-01

276

Dermal bone in early tetrapods: a palaeophysiological hypothesis of adaptation for terrestrial acidosis.  

PubMed

The dermal bone sculpture of early, basal tetrapods of the Permo-Carboniferous is unlike the bone surface of any living vertebrate, and its function has long been obscure. Drawing from physiological studies of extant tetrapods, where dermal bone or other calcified tissues aid in regulating acid-base balance relating to hypercapnia (excess blood carbon dioxide) and/or lactate acidosis, we propose a similar function for these sculptured dermal bones in early tetrapods. Unlike the condition in modern reptiles, which experience hypercapnia when submerged in water, these animals would have experienced hypercapnia on land, owing to likely inefficient means of eliminating carbon dioxide. The different patterns of dermal bone sculpture in these tetrapods largely correlates with levels of terrestriality: sculpture is reduced or lost in stem amniotes that likely had the more efficient lung ventilation mode of costal aspiration, and in small-sized stem amphibians that would have been able to use the skin for gas exchange. PMID:22535781

Janis, Christine M; Devlin, Kelly; Warren, Daniel E; Witzmann, Florian

2012-08-01

277

Acidosis prevents and alkalosis augments endothelium-dependent contractions in mouse arteries.  

PubMed

Changes in pH modulate the responsiveness of vascular smooth muscle cells to vasoconstrictor stimuli, but their effect on endothelium-dependent responses is unknown. Therefore, the influence of moderate changes in pH on responses to endothelium-dependent and -independent agonists was determined in aortae and carotid arteries of 15- to 26-week-old male C57BL/6N mice. Isolated rings were suspended in Halpern-Mulvany myographs for isometric tension recording. The preparations were exposed to either acidic (pH 7), control (pH 7.4) or alkaline (pH 7.8) modified Krebs-Ringer bicarbonate buffer solutions and their contractions and relaxations compared. Endothelium-dependent relaxations to acetylcholine (in the presence of meclofenamate or of the thromboxane-prostanoid (TP) receptor antagonist S18886) were comparable at the three pH values tested in contracted aortic or carotid arterial rings. Endothelium-dependent contractions of quiescent carotid arteries were reduced in acidosis and potentiated in alkalosis compared to control; these effects were reversible. The carotid arteries produced equal amounts of 6-keto prostaglandin F1? and thromboxane B2 at the different pH values tested. Contractions to the full TP receptor agonist U46619 were similar in the three milieus, but after inducing partial TP receptor blockade (with low concentrations of the TP receptor antagonist S18886) they were depressed in acidosis compared to alkalosis. Prostacyclin as a partial TP receptor activator also induced weaker contractions at low than at high pH, whereas its vasodilator effect was not affected. These findings demonstrate that changes in pH modulate endothelium-dependent contractions in mouse arteries primarily by altering the sensitivity of TP receptors of vascular smooth muscle to endothelium-derived contracting factors. PMID:23873352

Baretella, Oliver; Xu, Aimin; Vanhoutte, Paul M

2014-02-01

278

Extracorporeal membrane oxygenation in adults for severe acute respiratory failure.  

PubMed

The purpose of this review is to examine the indications of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). This technique of oxygenation has significantly increased worldwide with the H1N1 flu pandemic. The goal of ECMO is to maintain a safe level of oxygenation and controlled respiratory acidosis under protective ventilation. The enthusiasm for ECMO should not obscure the consideration for potential associated complications. Before widespread diffusion of ECMO, new trials should test the efficacy of early initiation or CO2 removal in addition to, or even as an alternative to mechanical ventilation for severe ARDS. PMID:25128980

Rozé, H; Repusseau, B; Ouattara, A

2014-01-01

279

Lactate metabolism: a new paradigm for the third millennium  

PubMed Central

For much of the 20th century, lactate was largely considered a dead-end waste product of glycolysis due to hypoxia, the primary cause of the O2 debt following exercise, a major cause of muscle fatigue, and a key factor in acidosis-induced tissue damage. Since the 1970s, a ‘lactate revolution’ has occurred. At present, we are in the midst of a lactate shuttle era; the lactate paradigm has shifted. It now appears that increased lactate production and concentration as a result of anoxia or dysoxia are often the exception rather than the rule. Lactic acidosis is being re-evaluated as a factor in muscle fatigue. Lactate is an important intermediate in the process of wound repair and regeneration. The origin of elevated [lactate] in injury and sepsis is being re-investigated. There is essentially unanimous experimental support for a cell-to-cell lactate shuttle, along with mounting evidence for astrocyte–neuron, lactate–alanine, peroxisomal and spermatogenic lactate shuttles. The bulk of the evidence suggests that lactate is an important intermediary in numerous metabolic processes, a particularly mobile fuel for aerobic metabolism, and perhaps a mediator of redox state among various compartments both within and between cells. Lactate can no longer be considered the usual suspect for metabolic ‘crimes’, but is instead a central player in cellular, regional and whole body metabolism. Overall, the cell-to-cell lactate shuttle has expanded far beyond its initial conception as an explanation for lactate metabolism during muscle contractions and exercise to now subsume all of the other shuttles as a grand description of the role(s) of lactate in numerous metabolic processes and pathways. PMID:15131240

Gladden, L B

2004-01-01

280

Phenotypic variability and identification of novel YARS2 mutations in YARS2 mitochondrial myopathy, lactic acidosis and sideroblastic anaemia  

PubMed Central

Background Mutations in the mitochondrial tyrosyl-tRNA synthetase (YARS2) gene have previously been identified as a cause of the tissue specific mitochondrial respiratory chain (RC) disorder, Myopathy, Lactic Acidosis, Sideroblastic Anaemia (MLASA). In this study, a cohort of patients with a mitochondrial RC disorder for who anaemia was a feature, were screened for mutations in YARS2. Methods Twelve patients were screened for YARS2 mutations by Sanger sequencing. Clinical data were compared. Functional assays were performed to confirm the pathogenicity of the novel mutations and to investigate tissue specific effects. Results PathogenicYARS2 mutations were identified in three of twelve patients screened. Two patients were found to be homozygous for the previously reported p.Phe52Leu mutation, one severely and one mildly affected. These patients had different mtDNA haplogroups which may contribute to the observed phenotypic variability. A mildly affected patient was a compound heterozygote for two novel YARS2 mutations, p.Gly191Asp and p.Arg360X. The p.Gly191Asp mutation resulted in a 38-fold loss in YARS2 catalytic efficiency and the p.Arg360X mutation did not produce a stable protein. The p.Phe52Leu and p.Gly191Asp/p.Arg360X mutations resulted in more severe RC deficiency of complexes I, III and IV in muscle cells compared to fibroblasts, but had relatively normal YARS2 protein levels. The muscle-specific RC deficiency can be related to the increased requirement for RC complexes in muscle. There was also a failure of mtDNA proliferation upon myogenesis in patient cells which may compound the RC defect. Patient muscle had increased levels of PGC1-? and TFAM suggesting mitochondrial biogenesis was activated as a potential compensatory mechanism. Conclusion In this study we have identified novel YARS2 mutations and noted marked phenotypic variability among YARS2 MLASA patients, with phenotypes ranging from mild to lethal, and we suggest that the background mtDNA haplotype may be contributing to the phenotypic variability. These findings have implications for diagnosis and prognostication of the MLASA and related phenotypes. PMID:24344687

2013-01-01

281

Features and Prognosis of Severe Malaria Caused by Plasmodium falciparum, Plasmodium vivax and Mixed Plasmodium Species in Papua New Guinean Children  

PubMed Central

Background Mortality from severe pediatric falciparum malaria appears low in Oceania but Plasmodium vivax is increasingly recognized as a cause of complications and death. The features and prognosis of mixed Plasmodium species infections are poorly characterized. Detailed prospective studies that include accurate malaria diagnosis and detection of co-morbidities are lacking. Methods and Findings We followed 340 Papua New Guinean (PNG) children with PCR-confirmed severe malaria (77.1% P. falciparum, 7.9% P. vivax, 14.7% P. falciparum/vivax) hospitalized over a 3-year period. Bacterial cultures were performed to identify co-incident sepsis. Clinical management was under national guidelines. Of 262 children with severe falciparum malaria, 30.9%, 24.8% and 23.2% had impaired consciousness, severe anemia, and metabolic acidosis/hyperlactatemia, respectively. Two (0.8%) presented with hypoglycemia, seven (2.7%) were discharged with neurologic impairment, and one child died (0.4%). The 27 severe vivax malaria cases presented with similar phenotypic features to the falciparum malaria cases but respiratory distress was five times more common (P?=?0.001); one child died (3.7%). The 50 children with P. falciparum/vivax infections shared phenotypic features of mono-species infections, but were more likely to present in deep coma and had the highest mortality (8.0%; P?=?0.003 vs falciparum malaria). Overall, bacterial cultures were positive in only two non-fatal cases. 83.6% of the children had alpha-thalassemia trait and seven with coma/impaired consciousness had South Asian ovalocytosis (SAO). Conclusions The low mortality from severe falciparum malaria in PNG children may reflect protective genetic factors other than alpha-thalassemia trait/SAO, good nutrition, and/or infrequent co-incident sepsis. Severe vivax malaria had similar features but severe P. falciparum/vivax infections were associated with the most severe phenotype and worst prognosis. PMID:22216212

Manning, Laurens; Laman, Moses; Law, Irwin; Bona, Cathy; Aipit, Susan; Teine, David; Warrell, Jonathan; Rosanas-Urgell, Anna; Lin, Enmoore; Kiniboro, Benson; Vince, John; Hwaiwhanje, Ilomo; Karunajeewa, Harin; Michon, Pascal; Siba, Peter

2011-01-01

282

Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8  

PubMed Central

Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65) is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs). Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression. PMID:24152439

Li, Zhigang; Dong, Lixue; Dean, Eric; Yang, Li V.

2013-01-01

283

Inhibition of the K+ channel Kv1.4 by acidosis: protonation of an extracellular histidine slows the recovery from N-type inactivation  

PubMed Central

Acidosis alters the transient outward current, ito, in the heart. We have studied the mechanism underlying the effect of acidosis on one of the K+ channels, Kv1.4 (heterologously expressed in Xenopus laevis oocytes), known to underlie ito.At pH 6.5, wild-type Kv1.4 current was inhibited during repetitive pulsing, in part as a result of a slowing of recovery from N-type inactivation.Acidosis still caused slowing of recovery after deletion of just one (either the first or second) of the N-terminal inactivation ball domains. However, deletion of both the N-terminal inactivation ball domains greatly reduced the inhibition.As well as the N-terminus, other parts of the channel are also required for the effect of acidosis, because, whereas the transfer of the N-terminus of Kv1.4 to Kv1.2 conferred N-type inactivation, it did not confer acidosis sensitivity.Replacement of an extracellular histidine with a glutamine residue (H508Q) abolished the slowing of recovery by acidosis. Reduction of C-type inactivation by raising the bathing K+ concentration or by the mutation K532Y also abolished the slowing.It is concluded that binding of protons to H508 enhances C-type inactivation and this causes a slowing of recovery from N-type inactivation and, thus, an inhibition of current during repetitive pulsing. PMID:10896716

Claydon, T W; Boyett, M R; Sivaprasadarao, A; Ishii, K; Owen, J M; O'Beirne, H A; Leach, R; Komukai, K; Orchard, C H

2000-01-01

284

Effect of induction of subacute ruminal acidosis on milk fat profile and rumen parameters.  

PubMed

High-concentrate diets can lead to subacute ruminal acidosis and are known to result in changes of the ruminal fermentation pattern and mammary secretion of fatty acids. The objective of this paper is to describe modifications in milk fatty acid proportions, particularly odd- and branched-chain fatty acids and rumen biohydrogenation intermediates, associated with rumen parameters during a 6-wk subacute ruminal acidosis induction protocol with 12 ruminally fistulated multiparous cows. The protocol involved a weekly gradual replacement of a standard dairy concentrate with a wheat-based concentrate (610 g of wheat/kg of concentrate) during the first 5 wk and an increase in the total amount of concentrate in wk 6. Before the end of induction wk 6, cows were switched to a control diet because 7 cows showed signs of sickness. The pH was measured continuously by an indwelling pH probe. Milk and rumen samples were taken on d 2 and 7 of each week. Data were analyzed using a linear mixed model and by principal component analysis. A pH decrease occurred after the first concentrate switch but rumen parameters returned to the original values and remained stable until wk 5. In wk 5 and 6, rumen pH values were indicative of increasing acidotic conditions. After switching to the control diet in wk 6, rumen pH values rapidly achieved normal values. Odd- and branched-chain fatty acids and C18:1 trans-10 increased with increasing amount of concentrate in the diet, whereas C18:1 trans-11 decreased. Four fatty acids [C18:1 trans-10, C15:0 and C17:0+C17:1 cis-9 (negative loadings), and iso C14:0 (positive loading)] largely correlated with the first principal component (PC1), with cows spread along the PC1 axis. The first 4 wk of the induction experiment showed variation across the second principal component (PC2) only, with high loadings of anteiso C13:0 (negative loading) and C18:2 cis-9,trans-11 and C18:1 trans-11 (positive loadings). Weeks 5 and 6 deviated from PC2 and tended toward the negative PC1 axis. A discriminant analysis using a stepwise approach indicated the main fatty acids discriminating between the control and acidotic samples as iso C13:0, iso C16:0, and C18:2 cis-9,trans-11 rather than milk fat content or C18:1 trans-10, which have been used before as indicators of acidosis. This shows that specific milk fatty acids have potential in discriminating acidotic cases. PMID:20855010

Colman, E; Fokkink, W B; Craninx, M; Newbold, J R; De Baets, B; Fievez, V

2010-10-01

285

Reduction of hypoxic pulmonary vasoconstriction by diethyl ether in the isolated perfused cat lung: The effect of acidosis and alkalosis  

Microsoft Academic Search

Summary  Hypoxic pulmonary vasoconstriction is a protective mechanism diverting pulmonary blood flow away from hypoxic areas toward\\u000a more optimally oxygenated lung units. Venous admixture is reduced and arterial oxygenation improved. Hypoxic pulmonary vasoconstriction\\u000a was demonstrated during acidosis, alkalosis and normal pH in the isolated perfused cat lung under conditions of constant flow\\u000a and constant left atrial and airway pressures. Two per

J. B. Hurtig; A. R. Tait; M. K. Sykes

1977-01-01

286

Influence of respiratory acidosis or alkalosis on pressor responses mediated by ? 1 - and ? 2 -adrenoceptors in pithed normotensive rats  

Microsoft Academic Search

The effect of respiratory acidosis and alkalosis on the vasoconstriction toa1- anda2-adrenoceptor stimulation was studied in pithed normotensive rats. The selectivea1-adrenoceptor agonists (-)amidephrine, cirazoline, (±)erythro methoxamine (-)phenylephrine, Sgd 101\\/75 and St 587 were used, as well as the selectivea2-adrenoceptor agonists B-HT 920, B-HT 933, DP-6,7-ADTN, M-7 and UK 14,304. The non-selectivea-adrenoceptor agonists xylazine, noradrenaline and adrenaline were included as well.

C. Korstanje; M. J. Mathy; K. Charldorp; A. Jonge; P. A. Zwieten

1985-01-01

287

Effect of Acidosis and Alkalosis on Divalent Ion Transport across the Proximal Straight Tubule of the Rabbit  

Microsoft Academic Search

In vitro microperfusion experiments were performed on the cortical proximal straight tubule of the rabbit to examine the effect of acid base disturbances on calcium and magnesium transport by this segment of the nephron. During acidosis (pH 7.22 ± 0.01) net calcium reabsorption was reduced, whereas during alkalosis (pH 7.82 ± 0.02) net calcium reabsorption was increased. Our flux experiments

Norman L. M. Wong; John H. Dirks

1987-01-01

288

The endothelin receptor antagonist bosentan restores gut oxygen delivery and reverses intestinal mucosal acidosis in porcine endotoxin shock  

Microsoft Academic Search

Background—Endothelin-1, the most potent vasoconstrictor known, is produced in septic states and may be involved in the pathophysiology of the deteriorated splanchnic circulation seen in septic shock.Aims—To elucidate the capability of bosentan, a non-peptide mixed endothelin receptor antagonist, to attenuate splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in endotoxic shock.Methods—In 16 anaesthetised pigs, central and regional haemodynamics were

A Oldner; M Wanecek; M Goiny; E Weitzberg; A Rudehill; K Alving; A Sollevi

1998-01-01

289

Alzheimer-type pathology in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS)  

Microsoft Academic Search

A 53-year-old Japanese woman with a point mutation in mitochondrial DNA (tRNALeu(UUR), nt3243) consistent with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and Alzheimer-type\\u000a brain pathology is reported. This woman had suffered myopathy and psychosis without any clinical evidence of, stroke-like\\u000a episodes during the last 10 years of her life, and had died after an accident. At autopsy

M. Kaido; H. Fujimura; F. Soga; K. Toyooka; H. Yoshikawa; T. Nishimura; T. Higashi; K. Inui; H. Imanishi; S. Yorifuji; T. Yanagihara

1996-01-01

290

Non-Hodgkins lymphoma with lactic acidosis at presentation: A case report of a rare oncologic emergency.  

PubMed

Lactic acidosis (LA) has been reported to be associated with high grade lymphoma as a terminal event. Its causes are multi-factorial. It can either occur due to overproduction of lactic acid by rapidly dividing tumor or due to its underutilization due to involvement of liver by lymphomatous deposits. The prognosis of lymphoma associated with LA is dismal. We present a patient of non-Hodgkins lymphoma (NHL) who presented with LA, after an initial response succumbed. PMID:25006291

Kumar, Arvind; Raina, Vinod

2014-01-01

291

Non-Hodgkins lymphoma with lactic acidosis at presentation: A case report of a rare oncologic emergency  

PubMed Central

Lactic acidosis (LA) has been reported to be associated with high grade lymphoma as a terminal event. Its causes are multi-factorial. It can either occur due to overproduction of lactic acid by rapidly dividing tumor or due to its underutilization due to involvement of liver by lymphomatous deposits. The prognosis of lymphoma associated with LA is dismal. We present a patient of non-Hodgkins lymphoma (NHL) who presented with LA, after an initial response succumbed. PMID:25006291

Kumar, Arvind; Raina, Vinod

2014-01-01

292

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers  

PubMed Central

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response. PMID:25013355

Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica

2014-01-01

293

Ischemia/Reperfusion-Induced CHOP Expression Promotes Apoptosis and Impairs Renal Function Recovery: The Role of Acidosis and GPR4  

PubMed Central

Endoplasmic reticulum (ER) stress-induced apoptosis is implicated in a wide range of diseases, including ischemia/reperfusion injury (IRI). As a common feature of ER stress, the role of CCAT/enhancer-binding protein homologous protein (CHOP) in renal IRI has not been thoroughly investigated. We found that IR led to renal CHOP expression, accompanied by apoptosis induction. Renal IRI was markedly alleviated in CHOP?/? mice. Observations from bone marrow chimeras showed that this was based on CHOP inactivation in renal parenchymal cells rather than inflammatory cells. In vivo and in vitro studies demonstrated that IRI induced CHOP expression in both endothelial and epithelial cells, which was responsible for apoptosis induction. These results were reinforced by the observation that CHOP knockout led to improvement of the postischemic microcirculatory recovery. In vitro studies revealed hypoxia-induced acidosis to be a major inducer of CHOP in endothelial cells, and neutralizing acidosis not only diminished CHOP protein, but also reduced apoptosis. Finally, knockdown of a proton-sensing G protein-coupled receptor GPR4 markedly reduced CHOP expression and endothelial cell apoptosis after hypoxia exposure. These results highlight the importance of hypoxia-acidosis in ER stress signaling regulation in ischemic kidneys and suggest that GPR4 inhibitors or agents targeting CHOP expression may be promising in the treatment of renal IRI. PMID:25343248

Xu, Longmei; Zhang, Ming; Fu, Yaowen; Xia, Qiang

2014-01-01

294

Metabolic Syndrome  

MedlinePLUS

... to occur together. You must have at least three metabolic risk factors to be diagnosed with metabolic syndrome. A large ... syndrome may overtake smoking as the leading risk factor for heart disease. It is possible to prevent or ... Metabolic Syndrome Clinical Trials Clinical trials are ...

295

Standardized treatment of severe methanol poisoning with ethanol and hemodialysis  

SciTech Connect

Seven patients with methanol poisoning were treated with ethanol, hemodialysis and supportive measures. The interval between ingestion and initiation of ethanol therapy varied from 3 to 67 hours and from ingestion to dialysis from 9 to 93 hours. All patients survived, but one had permanent visual impairment. A 10% ethanol solution administered intravenously is a safe and effective antidote for severe methanol poisoning. Ethanol therapy is recommended when plasma methanol concentrations are higher than 20 mg per dl, when ingested doses are greater than 30 ml and when there is evidence of acidosis or visual abnormalities in cases of suspected methanol poisoning. 13 references, 1 figure, 2 table.

Ekins, B.R.; Rollins, D.E.; Duffy, D.P.; Gregory, M.C.

1985-03-01

296

Use of intravenous immunoglobulin therapy in the treatment of septic shock, in particular severe invasive group A streptococcal disease  

PubMed Central

Group A streptococcus (GAS) is a ?-hemolytic bacterium often found in the throat and skin. The two most severe clinical manifestations of GAS are streptococcal toxic shock syndrome and necrotizing fasciitis. Intravenous immunoglobulin (IVIg) is a gamma globulin made from purified pooled plasma of thousands of donors, consisting mainly of IgG. We report the case of a 40-year-old man admitted after 2 days of vomiting and severe right-sided chest pain. He was hypotensive with a sinus tachycardia, pyrexial, and vasodilated. The only other positive finding was a swollen and erythematous chest wall. Muscle layer biopsies and blood cultures soon grew extensive GAS, and an initial diagnosis of necrotizing fasciitis was made. The clinical syndrome was of severe septic shock secondary to invasive GAS. The patient quickly deteriorated with a worsening metabolic acidosis. Despite maximal intensive care therapy including fluids, vasoactive agents, and also activated protein C, the patient continued to remain profoundly hypotensive. A decision was made to commence IVIg, with the aim of immunomodulation of the inflammatory cascade seen in sepsis. Over the next 24 hours the patient improved, was extubated 3 days later, and subsequently discharged from hospital after 2 weeks. Although the evidence for the use of IVIg in severe invasive GAS disease is limited, we feel that on reviewing the available literature its use in this case was justified. The limited worldwide supply and high costs, together with a limited evidence base, warrant restricting its use to cases in which conventional therapy has failed. The literature for use of intravenous immunoglobulin in invasive GAS infection will be reviewed in this article. PMID:22557832

Raithatha, Ajay H.; Bryden, Daniele C.

2012-01-01

297

Epidemiologic characteristics of mortality from diabetes with acidosis or coma, United States, 1970-78.  

PubMed Central

Deaths due to diabetes with acidosis or coma (DAC) in the United States from 1970 through 1978 were analyzed to determine epidemiologic characteristics associated with mortality likely to be due to diabetic ketoacidosis (DKA), a complication of diabetes mellitus considered largely preventable. Annual age-adjusted rates for DAC deaths decreased during the study period, and the secular trend was significant in all regional, race, and sex groups examined. General population-based mortality rates increased linearly with age, were higher in non-Whites than in Whites among persons aged greater than 14, were higher in females, and increased significantly with age in both races and both sexes. By region, rates were lowest in the West. DAC mortality rates specific to estimated diabetic populations decreased annually from 1970 to 1978 in all race and sex groups, and were highest at age greater than or equal to 65, but did not show significant linear increases with age, except in non-Whites. These results indicate declining secular trends, as well as age, race, sex, and regional differences in the risk of such deaths. Further studies are warranted to determine factors contributing to these differences. PMID:6412575

Holman, R C; Herron, C A; Sinnock, P

1983-01-01

298

A novel mutation in YARS2 causes myopathy with lactic acidosis and sideroblastic anemia.  

PubMed

Mutations in the mitochondrial aminoacyl-tRNA synthetases (ARSs) are associated with a strikingly broad range of clinical phenotypes, the molecular basis for which remains obscure. Here, we report a novel missense mutation (c.137G>A, p.Gly46Asp) in the catalytic domain of YARS2, which codes for the mitochondrial tyrosyl-tRNA synthetase, in a subject with myopathy, lactic acidosis, and sideroblastic anemia (MLASA). YARS2 was undetectable by immunoblot analysis in subject myoblasts, resulting in a generalized mitochondrial translation defect. Retroviral expression of a wild-type YARS2 complementary DNA completely rescued the translation defect. We previously demonstrated that the respiratory chain defect in this subject was only present in fully differentiated muscle, and we show here that this likely reflects an increased requirement for YARS2 as muscle cells differentiate. An additional, heterozygous mutation was detected in TRMU/MTU1, a gene encoding the mitochondrial 2-thiouridylase. Although subject myoblasts and myotubes contained half the normal levels of TRMU, thiolation of mitochondrial tRNAs was normal. YARS2 eluted as part of high-molecular-weight complexes of ?250 kDa and 1 MDa by gel filtration. This study confirms mutations in YARS2 as a cause of MLASA and shows that, like some of the cytoplasmic ARSs, mitochondrial ARSs occur in high-molecular-weight complexes. PMID:22504945

Sasarman, Florin; Nishimura, Tamiko; Thiffault, Isabelle; Shoubridge, Eric A

2012-08-01

299

Anaerobic Metabolism 1 ANAEROBIC METABOLISM  

E-print Network

to aerobic metabolsm. This said, it is not uncommon to hear microbiologists talk about anaerobic respiration it for respiration. However, in many animals anaerobic metabolism may occur even when there are large amounts of O2Anaerobic Metabolism 1 ANAEROBIC METABOLISM 1 Introduction About the Next Three Sets of Class Notes

Prestwich, Ken

300

Imaging acute ischemic tissue acidosis with pH-sensitive endogenous amide proton transfer (APT) MRI - Correction of tissue relaxation and concomitant RF irradiation effects toward mapping quantitative cerebral tissue pH  

PubMed Central

Amide proton transfer (APT) MRI is sensitive to ischemic tissue acidosis and has been increasingly used as a research tool to investigate disrupted tissue metabolism during acute stroke. However, magnetization transfer asymmetry (MTRasym) analysis is often used for calculating APT contrast, which only provides pH-weighted images. In addition to pH- dependent APT contrast, in vivo MTRasym is subject to a baseline shift (?MTR?asym) attributable to the slightly asymmetric magnetization transfer (MT) effect. Additionally, APT contrast approximately scales with T1 relaxation time. Tissue relaxation time may also affect the experimentally obtainable APT contrast via saturation efficiency and RF spillover effects. In this study, we acquired perfusion, diffusion, relaxation and pH-weighted APT MRI data, and spectroscopy (MRS) in an animal model of acute ischemic stroke. We modeled in vivo MTRasym as a superposition of pH-dependent APT contrast and a baseline shift ?MTR?asym (i.e., MTRasym=APTR(pH) + ?MTR?asym), and quantified tissue pH. We found pH of the contralateral normal tissue to be 7.03 ± 0.05 and the ipsilateral ischemic tissue pH was 6.44 ± 0.24, which correlated with tissue perfusion and diffusion rates. In summary, our study established an endogenous and quantitative pH imaging technique for improved characterization of ischemic tissue acidification and metabolism disruption. PMID:22178815

Sun, Phillip Zhe; Wang, Enfeng; Cheung, Jerry S

2011-01-01

301

Niche metabolism in parasitic protozoa  

PubMed Central

Complete or partial genome sequences have recently become available for several medically and evolutionarily important parasitic protozoa. Through the application of bioinformatics complete metabolic repertoires for these parasites can be predicted. For experimentally intractable parasites insight provided by metabolic maps generated in silico has been startling. At its more extreme end, such bioinformatics reckoning facilitated the discovery in some parasites of mitochondria remodelled beyond previous recognition, and the identification of a non-photosynthetic chloroplast relic in malarial parasites. However, for experimentally tractable parasites, mapping of the general metabolic terrain is only a first step in understanding how the parasite modulates its streamlined, yet still often puzzlingly complex, metabolism in order to complete life cycles within host, vector, or environment. This review provides a comparative overview and discussion of metabolic strategies used by several different parasitic protozoa in order to subvert and survive host defences, and illustrates how genomic data contribute to the elucidation of parasite metabolism. PMID:16553311

Ginger, Michael L

2005-01-01

302

Non-Specific Inhibition of Ischemia- and Acidosis-Induced Intracellular Calcium Elevations and Membrane Currents by ?-Phenyl-N-tert-butylnitrone, Butylated Hydroxytoluene and Trolox  

PubMed Central

Ischemia, and subsequent acidosis, induces neuronal death following brain injury. Oxidative stress is believed to be a key component of this neuronal degeneration. Acute chemical ischemia (azide in the absence of external glucose) and acidosis (external media buffered to pH 6.0) produce increases in intracellular calcium concentration ([Ca2+]i) and inward membrane currents in cultured rat cortical neurons. Two ?-tocopherol analogues, trolox and butylated hydroxytoluene (BHT), and the spin trapping molecule ?-Phenyl-N-tert-butylnitrone (PBN) were used to determine the role of free radicals in these responses. PBN and BHT inhibited the initial transient increases in [Ca2+]i, produced by ischemia, acidosis and acidic ischemia and increased steady state levels in response to acidosis and the acidic ischemia. BHT and PBN also potentiated the rate at which [Ca2+]i increased after the initial transients during acidic ischemia. Trolox inhibited peak and sustained increases in [Ca2+]i during ischemia. BHT inhibited ischemia induced initial inward currents and trolox inhibited initial inward currents activated by acidosis and acidic ischemia. Given the inconsistent results obtained using these antioxidants, it is unlikely their effects were due to elimination of free radicals. Instead, it appears these compounds have non-specific effects on the ion channels and exchangers responsible for these responses. PMID:24583849

Katnik, Christopher; Cuevas, Javier

2014-01-01

303

Metabolic myopathies  

NASA Technical Reports Server (NTRS)

Metabolic myopathies are disorders of muscle energy production that result in skeletal muscle dysfunction. Cardiac and systemic metabolic dysfunction may coexist. Symptoms are often intermittent and provoked by exercise or changes in supply of lipid and carbohydrate fuels. Specific disorders of lipid and carbohydrate metabolism in muscle are reviewed. Evaluation often requires provocative exercise testing. These tests may include ischemic forearm exercise, aerobic cycle exercise, and 31P magnetic resonance spectroscopy with exercise.

Martin, A.; Haller, R. G.; Barohn, R.; Blomqvist, C. G. (Principal Investigator)

1994-01-01

304

Metabolic ecology.  

PubMed

Ecological theory that is grounded in metabolic currencies and constraints offers the potential to link ecological outcomes to biophysical processes across multiple scales of organization. The metabolic theory of ecology (MTE) has emphasized the potential for metabolism to serve as a unified theory of ecology, while focusing primarily on the size and temperature dependence of whole-organism metabolic rates. Generalizing metabolic ecology requires extending beyond prediction and application of standardized metabolic rates to theory focused on how energy moves through ecological systems. A bibliometric and network analysis of recent metabolic ecology literature reveals a research network characterized by major clusters focused on MTE, foraging theory, bioenergetics, trophic status, and generalized patterns and predictions. This generalized research network, which we refer to as metabolic ecology, can be considered to include the scaling, temperature and stoichiometric models forming the core of MTE, as well as bioenergetic equations, foraging theory, life-history allocation models, consumer-resource equations, food web theory and energy-based macroecology models that are frequently employed in ecological literature. We conclude with six points we believe to be important to the advancement and integration of metabolic ecology, including nomination of a second fundamental equation, complementary to the first fundamental equation offered by the MTE. PMID:24028511

Humphries, Murray M; McCann, Kevin S

2014-01-01

305

Subacute ruminal acidosis and total mixed ration preference in lactating dairy cows.  

PubMed

Subacute ruminal acidosis (SARA) is a condition where the pH of the rumen becomes abnormally acidic because of increased and altered production of volatile fatty acids. The objective of this experiment was to determine how a SARA challenge affects total mixed ration selection in dairy cows. In this study, 8 multiparous, lactating, ruminally cannulated Holstein cows were given a choice between a long-forage-particle-size diet with slow-fermenting starch (LC) and a short-forage-particle-size diet with fast-fermenting starch in a crossover design. Cows were allowed to adapt to this feeding scheme and were then subjected to a rumen challenge to induce a bout of SARA. The rumen challenge successfully decreased rumen pH and altered rumen volatile fatty acid profiles. Daily average rumen pH decreased from 6.02 to 5.77, and average minimum rumen pH decreased from 5.59 to 5.28. In addition, following the rumen challenge, concentrations of acetate, butyrate, and valerate, and acetate-to-propionate ratio increased. In response to the rumen challenge, intake of LC increased from the baseline level of 18.1% of total daily dry matter intake to 38.3% for that day. During the first recovery day after the rumen challenge, LC intake moderated to 28.0% of total daily dry matter intake. On the second recovery day, LC intake returned to baseline levels at 18.6%. These results indicate that cows are able to alter their diet preference for higher physically effective fiber and slower starch fermentability during a bout of SARA and that they can effectively fully recover from this type of SARA within 72 h when appropriate diets are available. PMID:23932130

Maulfair, D D; McIntyre, K K; Heinrichs, A J

2013-10-01

306

Severe Storms  

NSDL National Science Digital Library

Part of the University of Illinois Weather World 2010 project, this guide uses multimedia technology and the dynamic capabilities of the web to incorporate text, colorful diagrams, animations, computer simulations, audio, and video to introduce topics and concepts in the atmospheric sciences. This module is a combination of two elements. The first is the National Oceanic and Atmospheric Administration (NOAA) Severe Storms Spotters Guide. The second is a section discussing the efforts and results of modeling severe storms. The Spotters Guide contains supplemental instructional resources and a program designed to familiarize meteorologists and advanced severe storm spotters with the building blocks of convective storm structure. The focus of the training series is the development of a thunderstorm spectrum and a discussion of the physical characteristics and severe weather potential of the various storm types in the spectrum.

2010-01-01

307

Electrochemical potentials of potassium in skeletal muscle under different metabolic states.  

PubMed

Intracellular potassium and membrane potential were measured simultaneously by means of double-barrelled liquid ion-exchange microelectrodes in single fibers of rat thigh muscle in vivo in rats maintained in seven different metabolic states. The K+ equilibrium potential (EK) was more negative than the simultaneously measured membrane potential (Em) in the normal state by 18.4 mV. K+ loading, acute and chronic, resulted in depolarization of Em due to increased serum K+ (hyperkalemia) with no increase in intracellular K+. K+ depletion resulted in hyperpolarization of Em as plasma K+ decreased proportionately more than intracellular K+. Low Na+ diet had no effect. Intracellular K+ was decreased in acute acidosis but not in the chronic state. Thus K+ depletion and acute acidosis are associated with intracellular K+ decrease. The fact that hyperpolarization exists in the former and not the latter is a reflection that hypokalemia accompanies the former condition. The hyperpolarizing states of K+ depletion and chronic acidosis are accompanied by decreased excitability and muscle weakness. PMID:1447314

Khuri, R N; Agulian, S K; Abdulnour-Nakhoul, S; Nakhoul, N L

1992-12-01

308

Structural control of metabolic flux.  

PubMed

Organisms have to continuously adapt to changing environmental conditions or undergo developmental transitions. To meet the accompanying change in metabolic demands, the molecular mechanisms of adaptation involve concerted interactions which ultimately induce a modification of the metabolic state, which is characterized by reaction fluxes and metabolite concentrations. These state transitions are the effect of simultaneously manipulating fluxes through several reactions. While metabolic control analysis has provided a powerful framework for elucidating the principles governing this orchestrated action to understand metabolic control, its applications are restricted by the limited availability of kinetic information. Here, we introduce structural metabolic control as a framework to examine individual reactions' potential to control metabolic functions, such as biomass production, based on structural modeling. The capability to carry out a metabolic function is determined using flux balance analysis (FBA). We examine structural metabolic control on the example of the central carbon metabolism of Escherichia coli by the recently introduced framework of functional centrality (FC). This framework is based on the Shapley value from cooperative game theory and FBA, and we demonstrate its superior ability to assign "share of control" to individual reactions with respect to metabolic functions and environmental conditions. A comparative analysis of various scenarios illustrates the usefulness of FC and its relations to other structural approaches pertaining to metabolic control. We propose a Monte Carlo algorithm to estimate FCs for large networks, based on the enumeration of elementary flux modes. We further give detailed biological interpretation of FCs for production of lactate and ATP under various respiratory conditions. PMID:24367246

Sajitz-Hermstein, Max; Nikoloski, Zoran

2013-01-01

309

Structural Control of Metabolic Flux  

PubMed Central

Organisms have to continuously adapt to changing environmental conditions or undergo developmental transitions. To meet the accompanying change in metabolic demands, the molecular mechanisms of adaptation involve concerted interactions which ultimately induce a modification of the metabolic state, which is characterized by reaction fluxes and metabolite concentrations. These state transitions are the effect of simultaneously manipulating fluxes through several reactions. While metabolic control analysis has provided a powerful framework for elucidating the principles governing this orchestrated action to understand metabolic control, its applications are restricted by the limited availability of kinetic information. Here, we introduce structural metabolic control as a framework to examine individual reactions' potential to control metabolic functions, such as biomass production, based on structural modeling. The capability to carry out a metabolic function is determined using flux balance analysis (FBA). We examine structural metabolic control on the example of the central carbon metabolism of Escherichia coli by the recently introduced framework of functional centrality (FC). This framework is based on the Shapley value from cooperative game theory and FBA, and we demonstrate its superior ability to assign “share of control” to individual reactions with respect to metabolic functions and environmental conditions. A comparative analysis of various scenarios illustrates the usefulness of FC and its relations to other structural approaches pertaining to metabolic control. We propose a Monte Carlo algorithm to estimate FCs for large networks, based on the enumeration of elementary flux modes. We further give detailed biological interpretation of FCs for production of lactate and ATP under various respiratory conditions. PMID:24367246

Sajitz-Hermstein, Max; Nikoloski, Zoran

2013-01-01

310

Metabolic arthropathies.  

PubMed

In this article, recent advances in the understanding of some of the metabolic arthropathies are reviewed. Among hemoglobinopathies, sickle-cell disease is frequently the source of rheumatic syndromes, as emphasized in recent epidemiologic studies. Avascular necrosis is one of the most common features and may be disabling, leading to total joint replacement of the hip or knee. Joint effusions more rarely are observed and have been associated with subchondral bone infarctions. The clinical and radiologic presentations of the arthropathy of hemochromatosis have been extensively reviewed. Screening for the disease appears important, because it is the only way to prevent progressive worsening of organ involvement and arthropathy in particular. The rheumatic involvement in type IIa and type III hyperlipoproteinemias recently was confirmed in a case-control study. Magnetic resonance imaging appears to be useful in assessing the extent and activity of bone marrow involvement in Gaucher's disease. Replacement therapy is developing. Dialysis-associated amyloidosis remains the target of active research, which recently led to the identification of several newly recognized components, including alpha 2-macroglobulin and hyaluronan. The main component of this amyloid, beta 2-microglobulin, has been shown to be modified by advanced glycosylation products, and these changes appear to confer inflammatory properties on the molecule. PMID:8068518

Timsit, M A; Bardin, T

1994-07-01

311

Surgical management and outcomes of severe gastrointestinal injuries due to corrosive ingestion  

PubMed Central

AIM: To report our experience in the surgical management of severe injuries of the gastrointestinal tract due to corrosive ingestion. METHODS: A retrospective review of patients who underwent emergency surgery for severe gastrointestinal injuries following corrosive ingestion between 1983 and 2010 was carried out. Data was extracted from a prospectively maintained esophageal disease database. Severe corrosive injuries were defined as full thickness necrosis with perforation of the esophagus or the stomach (with or without involvement of the adjacent viscera) with resultant mediastinitis or peritonitis. RESULTS: Between 1983 and 2010, 209 patients with corrosive injury of the esophagus were managed. Of these, 13 (6.2%) patients underwent emergency surgery for severe corrosive injury. The median age of the patients was 22 years and the median interval between ingestion of the corrosive substance and surgery was 24 h. The surgical procedures done included esophagogastrectomy alone (n = 6), esophagogastrectomy with duodenectomy (n = 4), esophagogastrectomy with pancreaticoduodenectomy (n = 1), esophagogastrectomy with splenectomy (n = 1) and distal gastrectomy with duodenectomy (n = 1). Two patients died in the postoperative period and one after discharge awaiting the second surgery. The factors significantly predictive of mortality following such an injury included renal failure at the time of initial presentation, presence of metabolic acidosis, delay of more than 24 h between corrosive ingestion and surgery, and corrosive induced adjacent organ injury (pancreatic) (P < 0.001, 0.02, 0.005 and 0.015 respectively). Ten patients underwent subsequent surgery for restoration of the alimentary tract continuity with a colonic pull-up (n = 8) and gastrojejunostomy (n = 1). In one patient, the attempted colon pull-up failed due to extensive scarring of the mesocolon. The median follow up (following restoration of continuity of the gastrointestinal tract) was 36.5 mo. One patient developed dysphagia due to a stricture at the anastomotic site, which was successfully managed by dilatation. Another patient developed severe aspiration, necessitating laryngeal inlet closure and permanent tracheostomy, and 3 patients complained of occasional regurgitation. CONCLUSION: Management of severe corrosive injury involves prompt resuscitation and urgent surgical debridement. Although the subsequent restoration of continuity may be complicated and may not always be possible, long term outcomes are acceptable in the majority. PMID:22655126

Javed, Amit; Pal, Sujoy; Krishnan, Elan Kumaran; Sahni, Peush; Chattopadhyay, Tushar Kanti

2012-01-01

312

Oxygen-deficient metabolism and corneal edema  

PubMed Central

Wear of low-oxygen-transmissible soft contact lenses swells the cornea significantly, even during open eye. Although oxygen-deficient corneal edema is well-documented, a self-consistent quantitative prediction based on the underlying metabolic reactions is not available. We present a biochemical description of the human cornea that quantifies hypoxic swelling through the coupled transport of water, salt, and respiratory metabolites. Aerobic and anaerobic consumption of glucose, as well as acidosis and pH buffering, are incorporated in a seven-layer corneal model (anterior chamber, endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film). Corneal swelling is predicted from coupled transport of water, dissolved salts, and especially metabolites, along with membrane-transport resistances at the endothelium and epithelium. At the endothelium, the Na+/K+ - ATPase electrogenic channel actively transports bicarbonate ion from the stroma into the anterior chamber. As captured by the Kedem–Katchalsky membrane-transport formalism, the active bicarbonate-ion flux provides the driving force for corneal fluid pump-out needed to match the leak-in tendency of the stroma. Increased lactate-ion production during hypoxia osmotically lowers the pump-out rate requiring the stroma to swell to higher water content. Concentration profiles are predicted for glucose, water, oxygen, carbon dioxide, and hydronium, lactate, bicarbonate, sodium, and chloride ions, along with electrostatic potential and pressure profiles. Although the active bicarbonate-ion pump at the endothelium drives bicarbonate into the aqueous humor, we find a net flux of bicarbonate ion into the cornea that safeguards against acidosis. For the first time, we predict corneal swelling upon soft-contact-lens wear from fundamental biophysico-chemical principles. We also successfully predict that hypertonic tear alleviates contact-lens-induced edema. PMID:21820076

Leung, B.K.; Bonanno, J.A.; Radke, C.J.

2014-01-01

313

Intoxication with over-the-counter antitussive medication containing dihydrocodeine and chlorpheniramine causes generalized convulsion and mixed acidosis.  

PubMed

We report a 35-year-old man who was referred to our hospital with generalized convulsion and mixed acidosis presumably caused by abuse of SS-BRON tablets, an over-the-counter (OTC) antitussive medication sold in Japan. These tablets contain dihydrocodeine phosphate, methylephedrine, chlorpheniramine, and caffeine. Although it is difficult to discern which component caused these symptoms, it seems that dihydrocodeine phosphate or methylephedrine was involved in the addiction to SS-BRON and chlorpheniramine may have caused the generalized convulsion. It should be recognized that an OTC antitussive, which is quite easy to obtain, can be abused and subsequently induce serious intoxication. PMID:18520112

Murao, Satoshi; Manabe, Hiroaki; Yamashita, Tetsuji; Sekikawa, Takashi

2008-01-01

314

Metabolic Syndrome  

MedlinePLUS

Having three or more risk factors is a sign that the body is resistant to insulin, an important hormone produced by the pancreas. ... diagnosed with the metabolic syndrome if you have three or more risk factors (see table below). FAcT SHeeT the metabolic syndrome ...

315

Metabolic and Cardiovascular Implications of a Metabolically Healthy Obesity Phenotype  

PubMed Central

Metabolically healthy obesity (MHO) is a new concept in which an individual may exhibit an obese phenotype in the absence of any metabolic abnormalities. There are a number of definitions of MHO that utilize a variety of components. The findings of clinical and basic studies indicate that subjects with MHO do not exhibit an increased mortality, an increased risk of cardiovascular disease, or an increased risk of type 2 diabetes mellitus, as compared to normal-weight controls. Although these findings imply that metabolic health is a more important factor than obesity, several studies have shown that subjects with MHO have a similar risk of metabolic or cardiovascular diseases as those with metabolically unhealthy obesity. Thus, there is still debate regarding not only the implications of the MHO phenotype but its very existence. Accordingly, future studies should focus on developing a unified definition of MHO and distinguishing subjects who will be at a high risk for metabolic and cardiovascular diseases. PMID:25559571

Seo, Mi Hae

2014-01-01

316

The Bed Nucleus of the Stria Terminalis Is Critical for Anxiety-Related Behavior Evoked by CO2 and Acidosis  

PubMed Central

Carbon dioxide (CO2) inhalation lowers brain pH and induces anxiety, fear, and panic responses in humans. In mice, CO2 produces freezing and avoidance behavior that has been suggested to depend on the amygdala. However, a recent study in humans with bilateral amygdala lesions revealed that CO2 can trigger fear and panic even in the absence of amygdalae, suggesting the importance of extra-amygdalar brain structures. Because the bed nucleus of the stria terminalis (BNST) contributes to fear- and anxiety-related behaviors and expresses acid-sensing ion channel-1A (ASIC1A), we hypothesized that the BNST plays an important role in CO2-evoked fear-related behaviors in mice. We found that BNST lesions decreased both CO2-evoked freezing and CO2-conditioned place avoidance. In addition, we found that CO2 inhalation caused BNST acidosis and that acidosis was sufficient to depolarize BNST neurons and induce freezing behavior; both responses depended on ASIC1A. Finally, disrupting Asic1a specifically in the BNST reduced CO2-evoked freezing, whereas virus-vector-mediated expression of ASIC1A in the BNST of Asic1a?/? and Asic1a+/+ mice increased CO2-evoked freezing. Together, these findings identify the BNST as an extra-amygdalar fear circuit structure important in CO2-evoked fear-related behavior. PMID:25080586

Taugher, Rebecca J.; Lu, Yuan; Wang, Yimo; Kreple, Collin J.; Ghobbeh, Ali; Fan, Rong; Sowers, Levi P.

2014-01-01

317

The bed nucleus of the stria terminalis is critical for anxiety-related behavior evoked by CO2 and acidosis.  

PubMed

Carbon dioxide (CO2) inhalation lowers brain pH and induces anxiety, fear, and panic responses in humans. In mice, CO2 produces freezing and avoidance behavior that has been suggested to depend on the amygdala. However, a recent study in humans with bilateral amygdala lesions revealed that CO2 can trigger fear and panic even in the absence of amygdalae, suggesting the importance of extra-amygdalar brain structures. Because the bed nucleus of the stria terminalis (BNST) contributes to fear- and anxiety-related behaviors and expresses acid-sensing ion channel-1A (ASIC1A), we hypothesized that the BNST plays an important role in CO2-evoked fear-related behaviors in mice. We found that BNST lesions decreased both CO2-evoked freezing and CO2-conditioned place avoidance. In addition, we found that CO2 inhalation caused BNST acidosis and that acidosis was sufficient to depolarize BNST neurons and induce freezing behavior; both responses depended on ASIC1A. Finally, disrupting Asic1a specifically in the BNST reduced CO2-evoked freezing, whereas virus-vector-mediated expression of ASIC1A in the BNST of Asic1a(-/-) and Asic1a(+/+) mice increased CO2-evoked freezing. Together, these findings identify the BNST as an extra-amygdalar fear circuit structure important in CO2-evoked fear-related behavior. PMID:25080586

Taugher, Rebecca J; Lu, Yuan; Wang, Yimo; Kreple, Collin J; Ghobbeh, Ali; Fan, Rong; Sowers, Levi P; Wemmie, John A

2014-07-30

318

Fatal Lactic Acidosis in a Kidney Transplant Recipient on Combination Antiretroviral Therapy after Initiation of Tacrolimus Therapy  

PubMed Central

In general, kidney transplantation is safe and efficacious in patients receiving treatment for HIV. Although multiple drug interactions between antiviral and immunosuppressive treatments exist, few patients experience serious adverse reactions. We report a case of fatal lactic acidosis in a healthy kidney transplant recipient with stable HIV infection who had previously received treatment for and cleared hepatitis C virus infection. Death occurred less than one month following the initiation of tacrolimus therapy. Based on predicted drug interactions, appropriate tacrolimus dosing was calculated prior to its commencement, yet plasma tacrolimus levels were initially unexpectedly high. The patient subsequently developed lactic acidosis and hepatic steatosis, presumably due to mitochondrial toxicity from the antiretroviral regimen on which he had previously been stable. We suspect CYP2C19*2 (poor metaboliser) genotype status and concomitant treatment with lansoprazole, tacrolimus, and antiretroviral (ARV) medications resulted in hepatic decompensation. This highlights the importance of careful interaction screening for all new drugs administered to patients with HIV who have complex treatment regimens as well as heightened clinical vigilance for unexpected toxicities. PMID:23213600

Holmes, Michael V.; Kulasegaram, Ranjababu; Lucas, Sebastian B.; Wong, Terry; Hilton, Rachel

2011-01-01

319

A Case of Chronic Ethylene Glycol Intoxication Presenting without Classic Metabolic Derangements  

PubMed Central

Acute ethylene glycol ingestion classically presents with high anion gap acidosis, elevated osmolar gap, altered mental status, and acute renal failure. However, chronic ingestion of ethylene glycol is a challenging diagnosis that can present as acute kidney injury with subtle physical findings and without the classic metabolic derangements. We present a case of chronic ethylene glycol ingestion in a patient who presented with acute kidney injury and repeated denials of an exposure history. Kidney biopsy was critical to the elucidation of the cause of his worsening renal function. PMID:25215251

Toth-Manikowski, Stephanie M.; Menn-Josephy, Hanni

2014-01-01

320

Computational Approaches for Understanding Energy Metabolism  

PubMed Central

There has been a surge of interest in understanding the regulation of metabolic networks involved in disease in recent years. Quantitative models are increasingly being used to i nterrogate the metabolic pathways that are contained within this complex disease biology. At the core of this effort is the mathematical modeling of central carbon metabolism involving glycolysis and the citric acid cycle (referred to as energy metabolism). Here we discuss several approaches used to quantitatively model metabolic pathways relating to energy metabolism and discuss their formalisms, successes, and limitations. PMID:23897661

Shestov, Alexander A; Barker, Brandon; Gu, Zhenglong; Locasale, Jason W

2013-01-01

321

Oxidative Metabolism in Muscle  

NASA Astrophysics Data System (ADS)

Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantages and problems of near-infrared spectroscopy measurements, in resting and exercising skeletal muscles studies, are discussed through some representative examples.

Ferrari, M.; Binzoni, T.; Quaresima, V.

1997-06-01

322

Oxidative metabolism in muscle.  

PubMed Central

Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantages and problems of near-infrared spectroscopy measurements, in resting and exercising skeletal muscles studies, are discussed through some representative examples. PMID:9232855

Ferrari, M; Binzoni, T; Quaresima, V

1997-01-01

323

Interleukin1? Targeted Therapy in Severe Persistent Asthma (SPA) and Chronic Obstructive Pulmonary Disease (COPD): Proposed Similarities between Biphasic Pathobiology of SPA\\/COPD and Ischemia-Reperfusion Injury  

Microsoft Academic Search

The histopathology of severe persistent asthma and chronic obstructive pulmonary disease is predominantly characterized by neutrophilic inflammation. It is posited that chronic hypoxia from hypoventilation in combination with hypoperfusion and hypercapnia are associated with induction of pulmonary tissue acidosis in SPA and COPD, which in turn provide ideal conditions to induce danger-associated molecular patterns, i.e., crystallized and calcium pyrophosphate. These

Alan A. Wanderer

324

Metabolism Roundup  

NSDL National Science Digital Library

Laboratory rats with large amounts of type II muscle fiber, maintained health for a longer period of time. In addition, those fed artificial sweetener tended to slow down their metabolism and show weight gain.

Science Update (AAAS; )

2008-02-29

325

Metabolic Syndrome  

MedlinePLUS

... to manage your condition. Medications can also treat risk factors such as high blood pressure or high blood glucose. If you think you have risk factors for the metabolic syndrome, talk with your doctor. ...

326

Metabolic Engineering  

Microsoft Academic Search

\\u000a \\u000a The metabolic engineering of primary metabolism provides an enormous potential to improve the value of plant-based raw materials\\u000a for food and industrial applications. This chapter focuses on the current progress in the manipulation of carbohydrate and\\u000a lipid biosynthesis in transgenic starch and oilseed crops, respectively. In most approaches, the manipulation of the biosynthetic\\u000a routes revealed limitations and bottlenecks in the

Lars M. Voll; Frederik Börnke

327

Congenital metabolic diseases: Diagnosis and treatment  

SciTech Connect

This book contains eight parts, each consisting of several papers. The part titles are: The Heritage of Sir Archibald Garrod; New Approaches to the Diagnosis and Treatment of Genetic Disease; Achievements, New Trends, and Policies in the Detection of Inborn Errors of Metabolism; Disorders of Amino Acid Metabolism; Diseases of Energy Metabolism; Problems of Abnormal Storage Diseases; Inherited Diseases of Membrane Transport and Receptors; and Inborn Errors of Purine Metabolism and Urea Synthesis.

Wapnir, R.A.

1985-01-01

328

Metabolic myopathies: update 2009.  

PubMed

Metabolic myopathies are inborn errors of metabolism that result in impaired energy production due to defects in glycogen, lipid, mitochondrial, and possibly adenine nucleotide metabolism. Fatty acid oxidation defects (FAOD), glycogen storage disease, and mitochondrial myopathies represent the 3 main groups of disorders, and some consider myoadenylate deaminase (AMPD1 deficiency) to be a metabolic myopathy. Clinically, a variety of neuromuscular presentations are seen at different ages of life. Newborns and infants commonly present with hypotonia and multisystem involvement (liver and brain), whereas onset later in life usually presents with exercise intolerance with or without progressive muscle weakness and myoglobinuria. In general, the glycogen storage diseases result in high-intensity exercise intolerance, whereas the FAODs and the mitochondrial myopathies manifest predominately during endurance-type activity or under fasted or other metabolically stressful conditions. The clinical examination is often normal, and testing requires various combinations of exercise stress testing, serum creatine kinase activity and lactate concentration determination, urine organic acids, muscle biopsy, neuroimaging, and specific genetic testing for the diagnosis of a specific metabolic myopathy. Prenatal screening is available in many countries for several of the FAODs through liquid chromatography-tandem mass spectrometry. Early identification of these conditions with lifestyle measures, nutritional intervention, and cofactor treatment is important to prevent or delay the onset of muscle weakness and to avoid potential life-threatening complications such as rhabdomyolysis with resultant renal failure or hepatic failure. This article will review the key clinical features, diagnostic tests, and treatment recommendations for the more common metabolic myopathies, with an emphasis on mitochondrial myopathies. PMID:19258857

van Adel, Brian A; Tarnopolsky, Mark A

2009-03-01

329

Ibuprofen-Induced Hypokalemia and Distal Renal Tubular Acidosis: A Patient's Perceptions of Over-the-Counter Medications and Their Adverse Effects.  

PubMed

We highlight a case of distal renal tubular acidosis secondary to ibuprofen and codeine use. Of particular interest in this case are the patient's perception of over-the-counter (OTC) medication use, her own OTC use prior to admission, and her knowledge of adverse reactions or side effects of these medications prior to taking them. PMID:24829833

Salter, Mark D

2013-01-01

330

ER Stress Modulates Cellular Metabolism  

PubMed Central

Synopsis Changes in metabolic processes play a critical role in the survival or death of cells subjected to various stresses. Here, we have investigated the effects of endoplasmic reticulum (ER) stress on cellular metabolism. A major difficulty in studying metabolic responses to ER stress is that ER stress normally leads to apoptosis and metabolic changes observed in dying cells may be misleading. Therefore, we have used IL-3-dependent Bak?/? Bax?/? hematopoietic cells which do not die in the presence of the ER stress-inducing drug, tunicamycin. Tunicamycin-treated Bak?/?Bax?/? cells remain viable but cease growth, arresting in G1 and undergoing autophagy in the absence of apoptosis. In these cells we used NMR-based stable isotope resolved metabolomics (SIRM) to determine the metabolic effects of tunicamycin. Glucose was found to be the major carbon source for energy production and anabolic metabolism. Following tunicamycin exposure, glucose uptake and lactate production are greatly reduced. Decreased 13C labeling in several cellular metabolites suggests that mitochondrial function in cells undergoing ER stress is compromised. Consistent with this, mitochondrial membrane potential, oxygen consumption, and cellular ATP level are much lower compared with untreated cells. Importantly, the effects of tunicamycin on cellular metabolic processes may be related to a reduction of cell surface Glut-1 levels which, in turn, may reflect decreased Akt signaling. These results suggest that ER stress exerts profound effects on several central metabolic processes which may help explain cell death arising from ER stress in normal cells. PMID:21241252

Wang, Xiaoli; Eno, Colins O.; Altman, Brian J.; Zhu, Yanglong; Zhao, Guoping; Olberding, Kristen E.; Rathmell, Jeffrey C.; Li, Chi

2011-01-01

331

Abnormalities of colonic mucin secretion and metabolic changes after internal urinary diversion for bladder exstrophy. A prospective study.  

PubMed

Ten patients with different types of internal urinary diversion for bladder exstrophy were studied prospectively in order to assess metabolic abnormalities and morphological, histochemical and lectin binding changes in the colorectal mucosa. The histochemical and/or lectin binding changes which were found in the majority of patients were identical to those observed in premalignant and malignant conditions of the colon. In some cases they were detectable 3 years after the initial examination but were completely absent from the colorectal mucosa of normal subjects. Metabolic disturbances (metabolic acidosis, increased anion gap, hyperchloraemia) were observed in a substantial number of asymptomatic patients. These findings stress the need for regular endoscopic, histological and metabolic follow-up in these patients and for life-long treatment with bicarbonate or citrate. PMID:2039917

Marcheggiano, A; Iannoni, C; Latella, G; Frieri, G; Diosi, D; De Dominicis, C; Laurenti, C; Caprilli, R

1991-05-01

332

Plasma pH does not influence the cerebral metabolic ratio during maximal whole body exercise  

PubMed Central

Exercise lowers the cerebral metabolic ratio of O2 to carbohydrate (glucose + 1/2 lactate) and metabolic acidosis appears to promote cerebral lactate uptake. However, the influence of pH on cerebral lactate uptake and, in turn, on the cerebral metabolic ratio during exercise is not known. Sodium bicarbonate (Bicarb, 1 m; 350–500 ml) or an equal volume of normal saline (Sal) was infused intravenously at a constant rate during a ‘2000 m’ maximal ergometer row in six male oarsmen (23 ± 2 years; mean ± s.d.). During the Sal trial, pH decreased from 7.41 ± 0.01 at rest to 7.02 ± 0.02 but only to 7.36 ± 0.02 (P < 0.05) during the Bicarb trial. Arterial lactate increased to 21.4 ± 0.8 and 32.7 ± 2.3 mm during the Sal and Bicarb trials, respectively (P < 0.05). Also, the arterial–jugular venous lactate difference increased from –0.03 ± 0.01 mm at rest to 3.2 ± 0.9 mm (P < 0.05) and 3.4 ± 1.4 mm (P < 0.05) following the Sal and Bicarb trials, respectively. Accordingly, the cerebral metabolic ratio decreased equally during the Sal and Bicarb trials: from 5.8 ± 0.6 at rest to 1.7 ± 0.1 and 1.8 ± 0.2, respectively. The enlarged blood-buffering capacity after infusion of Bicarb eliminated metabolic acidosis during maximal exercise but that did not affect the cerebral lactate uptake and, therefore, the decrease in the cerebral metabolic ratio. PMID:21098003

Volianitis, S; Rasmussen, P; Seifert, T; Nielsen, H B; Secher, N H

2011-01-01

333

Dynamics of metabolic compensation and hematological changes in chicken (Gallus gallus) embryos exposed to hypercapnia with varying oxygen.  

PubMed

In day 15 chicken embryos, we determined the time course responses of acid-base balance and hematological respiratory variables during 24h exposure to 15, 20, 40 or 90% O(2), in the presence of 5% CO(2). Hypercapnic respiratory acidosis was initially (2h) only slightly (?20%) compensated by metabolic alkalosis in normoxic/hyperoxic embryos. After 6h, respiratory acidosis was partially (?40-50%) compensated not only in normoxic/hyperoxic embryos, but also in hypoxic embryos. However, partial metabolic compensation in 15% O(2) could not be preserved after 24h. Preservation of metabolic compensation required oxygen concentration ([O(2)]) above 20%, but the magnitude of partial metabolic compensation was unrelated to [O(2)]. Hematocrit (Hct), together with mean corpuscular volume (MCV), markedly increased in hypercapnic hypoxia, and was maintained at 24h due to a subsequent increase in red blood cell concentration ([RBC]). In contrast, Hct, together with MCV, decreased in hypercapnic normoxia/hyperoxia accompanied by a subsequent decrease in [RBC] at 24h. Regulation of variables takes place similarly irrespective of environmental [O(2)] above 20%, matching acid-base regulation. PMID:23063740

Mueller, Casey A; Tazawa, Hiroshi; Burggren, Warren W

2013-01-15

334

[Hypovitaminosis D and metabolic syndrome].  

PubMed

Metabolic syndrome and hypovitaminosis D are 2 diseases with high prevalence that share several risk factors, while epidemiological evidence shows they are associated. Although the mechanisms involved in this association are not well established, hypovitaminosis D is associated with insulin resistance, decreased insulin secretion and activation of the renin-angiotensin system, mechanisms involved in the pathophysiology of metabolic syndrome. However, the apparent ineffectiveness of vitamin D supplementation on metabolic syndrome components, as well as the limited information about the effect of improving metabolic syndrome components on vitamin D concentrations, does not clarify the direction and the mechanisms involved in the causal relationship between these 2 pathologies. Overall, because of the high prevalence and the epidemiological association between both diseases, hypovitaminosis D could be considered a component of the metabolic syndrome. PMID:24529881

Miñambres, Inka; de Leiva, Alberto; Pérez, Antonio

2014-12-23

335

The effect of acidosis on systolic Ca2+ and sarcoplasmic reticulum calcium content in isolated rat ventricular myocytes  

PubMed Central

We have investigated the mechanisms responsible for the changes of systolic Ca2+ that occur in voltage-clamped rat ventricular myocytes during acidosis produced by application of the weak acid butyrate (30 mM). Intracellular pH regulation was inhibited with dimethylamiloride (bicarbonate-free solution). The application of butyrate produced an intracellular acidification of 0.33 pH units. This was accompanied by a decrease in systolic Ca2+ to about 50 % of control. However, within 2 min, systolic Ca2+ returned to control levels. The decrease in systolic Ca2+ was accompanied by a decrease in the Na+-Ca2+ exchange current observed on repolarisation so that the calculated Ca2+ efflux on Na+-Ca2+ exchange was less than the entry on the L-type Ca2+ current. The magnitude of the Na+-Ca2+ exchange current recovered along with systolic Ca2+ until it equalled the Ca2+ entry on the L-type Ca2+ current. From the measurement of Ca2+ fluxes, it was calculated that, during acidosis, the cell gains 121.6 ± 16.2 ?mol l?1 of Ca2+. This is equal to the measured increase of sarcoplasmic reticulum (SR) calcium content obtained by applying caffeine (20 mM) and integrating the resulting Na+-Ca2+ exchange current. We conclude that the recovery of the amplitude of the systolic Ca2+ transient is due to decreased SR calcium release, resulting in reduced Ca2+ efflux from the cell leading to increased SR calcium content. PMID:11118496

Choi, H S; Trafford, A W; Orchard, C H; Eisner, D A

2000-01-01

336

Repeated acidosis challenges and live yeast supplementation shape rumen microbiota and fermentations and modulate inflammatory status in sheep.  

PubMed

This study aimed to investigate the impact of repeated acidosis challenges (ACs) and the effect of live yeast supplementation (Saccharomyces cerevisiae I-1077, SC) on rumen fermentation, microbial ecosystem and inflammatory response. The experimental design involved two groups (SC, n=6; Control, n=6) of rumen fistulated wethers that were successively exposed to three ACs of 5 days each, preceded and followed by resting periods (RPs) of 23 days. AC diets consisted of 60% wheat-based concentrate and 40% hay, whereas RPs diets consisted of 20% concentrate and 80% hay. ACs induced changes in rumen fermentative parameters (pH, lactate and volatile fatty-acid concentrations and proportions) as well as in microbiota composition and diversity. The first challenge drove the fermentation pattern towards propionate. During successive challenges, rumen pH measures worsened in the control group and the fermentation profile was characterised by a higher butyrate proportion and changes in the microbiota. The first AC induced a strong release of rumen histamine and lipopolysaccharide that triggered the increase of acute-phase proteins in the plasma. This inflammatory status was maintained during all AC repetitions. Our study suggests that the response of sheep to an acidosis diet is greatly influenced by the feeding history of individuals. In live yeast-supplemented animals, the first AC was as drastic as in control sheep. However, during subsequent challenges, yeast supplementation contributed to stabilise fermentative parameters, promoted protozoal numbers and decreased lactate producing bacteria. At the systemic level, yeast helped normalising the inflammatory status of the animals. PMID:24128750

Silberberg, M; Chaucheyras-Durand, F; Commun, L; Mialon, M M; Monteils, V; Mosoni, P; Morgavi, D P; Martin, C

2013-12-01

337

Modeling of Zymomonas mobilis central metabolism for novel metabolic engineering strategies  

PubMed Central

Mathematical modeling of metabolism is essential for rational metabolic engineering. The present work focuses on several types of modeling approach to quantitative understanding of central metabolic network and energetics in the bioethanol-producing bacterium Zymomonas mobilis. Combined use of Flux Balance, Elementary Flux Mode, and thermodynamic analysis of its central metabolism, together with dynamic modeling of the core catabolic pathways, can help to design novel substrate and product pathways by systematically analyzing the solution space for metabolic engineering, and yields insights into the function of metabolic network, hardly achievable without applying modeling tools. PMID:24550906

Kalnenieks, Uldis; Pentjuss, Agris; Rutkis, Reinis; Stalidzans, Egils; Fell, David A.

2014-01-01

338

Metabolic Bone Disease  

Microsoft Academic Search

\\u000a Metabolic bone disease encompasses a number of disorders that typically show involvement of the entire skeleton. They are\\u000a mostly associated with increased bone turnover and increased uptake of radiolabeled diphosphonate. The increased uptake produces\\u000a heightened contrast on bone scan between bone and soft tissues, deceptively giving the appearance of excellent image quality.\\u000a In more severe cases, there may be characteristic

Paul J. Ryan

339

Metabolic analysis.  

PubMed

Analysis of the metabolome with coverage of all of the possibly detectable components in the sample, rather than analysis of each individual metabolite at a given time, can be accomplished by metabolic analysis. Targeted and/or nontargeted approaches are applied as needed for particular experiments. Monitoring hundreds or more metabolites at a given time requires high-throughput and high-end techniques that enable screening for relative changes in, rather than absolute concentrations of, compounds within a wide dynamic range. Most of the analytical techniques useful for these purposes use GC or HPLC/UPLC separation modules coupled to a fast and accurate mass spectrometer. GC separations require chemical modification (derivatization) before analysis, and work efficiently for the small molecules. HPLC separations are better suited for the analysis of labile and nonvolatile polar and nonpolar compounds in their native form. Direct infusion and NMR-based techniques are mostly used for fingerprinting and snap phenotyping, where applicable. Discovery and validation of metabolic biomarkers are exciting and promising opportunities offered by metabolic analysis applied to biological and biomedical experiments. We have demonstrated that GC-TOF-MS, HPLC/UPLC-RP-MS and HILIC-LC-MS techniques used for metabolic analysis offer sufficient metabolome mapping providing researchers with confident data for subsequent multivariate analysis and data mining. PMID:19488710

Tolstikov, Vladimir V

2009-01-01

340

Metabolic Syndrome  

MedlinePLUS

... Web version Metabolic Syndrome Overview What is insulin resistance? Your body changes most of the food you eat into glucose (a form of sugar). Insulin is a hormone produced by the pancreas that allows ... as insulin resistance. If you have insulin resistance, your body will ...

341

Effect of a low-moisture buffer block on ruminal pH in lactating dairy cattle induced with subacute ruminal acidosis.  

PubMed

The objective of this study was to evaluate the effect of a low-moisture buffer block on ruminal pH and milk production in cows induced with subacute ruminal acidosis (SARA). Sixteen ruminally cannulated cows were randomly assigned to treatment (access to buffer blocks) or control (no buffer blocks). Ruminal pH was recorded each minute; dry matter intake (DMI), milk yield, and milk composition were measured daily. The experiment lasted 12 d and consisted of a 3-d pre-SARA period (without access to buffer blocks; d 1 to 3), after which 8 cows were given access to buffer blocks and 8 cows continued without access to buffer blocks. The next 4 d (d 4 to 7) were for evaluating the response to buffer blocks. On d 8, cows were restricted to 50% of previous DMI, and on d 9 SARA was induced (addition of 4 kg of wheat/barley pellet to pre-SARA total mixed ration (TMR). Cows were then monitored for a 3-d recovery period (d 10 to 12). The SARA challenge was successful in decreasing mean ruminal pH and time and area below pH 5.6. Intake of buffer blocks averaged 0.33 kg of DM/cow per day and was greatest on d 4 and d 8. Total DMI (TMR plus buffer block) and yields of milk and milk components were not affected by treatment. Although there was no overall effect of treatment on any of the ruminal pH variables measured, there were significant treatment by period interactions for several ruminal pH variables. Cows on the control treatment tended to experience a greater decrease in mean ruminal pH when induced with SARA than cows with access to buffer blocks (-0.55 vs. -0.20 pH units). Cows on the control treatment also experienced a greater increase in time (9.7 vs. 4.1 h/d) and area (249 vs. 83 min x pH units/d) below pH 5.6 compared with cows with access to buffer blocks. Ruminal volatile fatty acids, lactate, ethanol, and succinate concentrations during the SARA challenge did not differ between treatments. Eating behavior was not affected by treatment. Size of the first meal of the day was greater on the SARA challenge day than during the pre-SARA period (11.0 vs. 5.7 kg, as fed). Giving cows access to a buffer-containing molasses block may reduce the duration and the severity of a 1-d SARA challenge. PMID:19109292

Krause, K M; Dhuyvetter, D V; Oetzel, G R

2009-01-01

342

Tumor Macroenvironment and Metabolism  

PubMed Central

In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%–20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient’s outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. PMID:24787299

Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

2014-01-01

343

Tumor macroenvironment and metabolism.  

PubMed

In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. PMID:24787299

Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

2014-04-01

344

[Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period].  

PubMed

Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug. PMID:24791334

Makarova, L M; Prikhod'ko, M A; Pogorely?, V E; Skachilova, S Ia; Mirzoian, R S

2014-01-01

345

Cellular Metabolism  

NSDL National Science Digital Library

This is a lesson about the evidence for life on other planets. Learners will play a game to examine processes in cellular metabolism and explore both direct and indirect evidence for fingerprints of life. Includes teacher notes, learning objectives, and assessment of prior knowledge and preconceptions. This is Lesson 2 in Exploring Deep-Subsurface Life. Earth Analogues for Possible Life on Mars: Lessons and Activities.

2012-12-06

346

Metabolic Downregulation  

PubMed Central

Background and Purpose The search for effective neuroprotectants remains frustrating, particularly with regard to specific pharmaceuticals. However, laboratory studies have consistently shown remarkable neuroprotection with 2 nonpharmacological strategies—therapeutic hypothermia and ischemic preconditioning. Recent studies have shown that the mechanism of protection underlying both of these treatments is correlated to downregulation of cellular and tissue metabolism. Thus, understanding the mechanisms underlying such robust protective effects could lead to appropriate translation at the clinical level. In fact, hypothermia is already being used at many centers to improve neurological outcome from cardiac arrest. Methods A systematic review of both topics is presented in terms of underlying pathophysiological mechanisms and application at the clinical level. Results Although the mechanisms of protection for both therapeutic strategies are multifold, both share features of downregulating metabolism. Both therapeutic strategies are robust neuroprotectants, but translating them to the clinical arena is challenging, though not impossible, and clinical studies have shown or suggest benefits of both treatments. Conclusions The strategy of metabolic downregulation should be further explored to identify effective neuroprotectants that can be easily applied clinically. PMID:18658035

Yenari, Midori; Kitagawa, Kazuo; Lyden, Patrick; Perez-Pinzon, Miguel

2008-01-01

347

Type IV renal tubular acidosis following resolution of acute kidney injury and disseminated intravascular coagulation due to hump-nosed viper bite  

PubMed Central

Hump-nosed viper bite can cause acute kidney injury (AKI) and disseminated intravascular coagulation. In some patients, it can cause chronic kidney disease necessitating life-long renal replacement therapy. Lack of effective antivenom makes the management of these patients difficult. A 51-year-old Sri Lankan male was admitted with AKI and disseminated intravascular coagulation following a hump-nosed viper bite. He made a complete recovery with blood product support and hemodialysis. Renal biopsy was performed as his renal recovery was prolonged which revealed patchy tubular atrophy and interstitial inflammation suggestive of subacute interstitial nephritis. Later, he presented with hyperkalemic paralysis and acidosis. A diagnosis of late onset type 4 renal tubular acidosis was made and he responded well to a course of fludrocortisone. PMID:23960348

Karunarathne, S.; Udayakumara, Y.; Govindapala, D.; Fernando, H.

2013-01-01

348

Complete Heart Block and Persistent Lactic Acidosis as an Initial Presentation of Non-Hodgkin Lymphoma in a Critically Ill Newly Diagnosed AIDS Patient  

PubMed Central

A 66-year-old male with newly diagnosed untreated acquired immunodeficiency syndrome (AIDS) presented with chronic nonspecific complaints of weakness, fatigue, myalgia, and weight loss. His initial EKG showed complete heart block necessitating temporary pacemaker placement. He had no previous history of cardiac disease. He was also found to have a persistent lactic acidosis and imaging studies showed abdominal lymphadenopathy. The patient underwent biopsy of these lymph nodes and was found to have diffuse large B-cell lymphoma. The hospital course was complicated by respiratory failure requiring mechanical ventilator support and cardiac arrest. Patient remained critically ill; he was not a candidate for chemotherapy and, after a month of hospitalization, he died. Lactic acidosis and heart block as an initial presentation of non-Hodgkin lymphoma in an AIDS patient are an unusual and unique presentation. PMID:25431684

Niazi, Masooma

2014-01-01

349

Cell Metabolism Postprandial Hepatic Lipid Metabolism  

E-print Network

Cell Metabolism Article Postprandial Hepatic Lipid Metabolism Requires Signaling through Akt2 in the absence of Akt2. These data show that insulin signaling through Akt2 promotes anabolic lipid metabolism. Sabatini,2,3,4,5 and Morris J. Birnbaum1,* 1The Institute of Diabetes, Obesity, and Metabolism, University

Sabatini, David M.

350

OXYGEN DEFICIENCY AND ROOT METABOLISM: Injury and Acclimation Under Hypoxia and Anoxia.  

PubMed

Oxygen deficiency in the rooting zone occurs with poor drainage after rain or irrigation, causing depressed growth and yield of dryland species, in contrast with native wetland vegetation that tolerates such conditions. This review examines how roots are injured by O2 deficiency and how metabolism changes during acclimation to low concentrations of O2. In the root apical meristem, cell survival is important for the future development; metabolic changes under anoxia help maintain cell survival by generating ATP anaerobically and minimizing the cytoplasmic acidosis associated with cell death. Behind the apex, where cells are fully expanded, ethylene-dependent death and lysis occurs under hypoxia to form continuous, gas-filled channels (aerenchyma) conveying O2 from the leaves. This selective sacrifice of cells may resemble programmed cell death and is distinct from cell death caused by anoxia. Evidence concerning alternative possible mechanisms of anoxia tolerance and avoidance is presented. PMID:15012263

Drew, Malcolm C.

1997-06-01

351

Effects of partial mixed rations and supplement amounts on milk production and composition, ruminal fermentation, bacterial communities, and ruminal acidosis.  

PubMed

Late-lactation Holstein cows (n=144) that were offered 15kg dry matter (DM)/cow per day of perennial ryegrass to graze were randomized into 24 groups of 6. Each group contained a fistulated cow and groups were allocated to 1 of 3 feeding strategies: (1) control (10 groups): cows were fed crushed wheat grain twice daily in the milking parlor and ryegrass silage at pasture; (2) partial mixed ration (PMR; 10 groups): PMR that was isoenergetic to the control diet and fed twice daily on a feed pad; (3) PMR+canola (4 groups): a proportion of wheat in the PMR was replaced with canola meal to produce more estimated metabolizable protein than other groups. Supplements were fed to the control and PMR cows at 8, 10, 12, 14, or 16kg of DM/d, and to the PMR+canola cows at 14 or 16kg of DM/d. The PMR-fed cows had a lower incidence of ruminal acidosis compared with controls, and ruminal acidosis increased linearly and quadratically with supplement fed. Yield of milk fat was highest in the PMR+canola cows fed 14 or 16kg of total supplement DM/d, followed by the PMR-fed cows, and was lowest in controls fed at these amounts; a similar trend was observed for milk fat percentage. Milk protein yield was higher in the PMR+canola cows fed 14 or 16kg of total supplement DM/d. Milk yield and milk protein percentage were not affected by feeding strategy. Milk, energy-corrected milk, and milk protein yields increased linearly with supplement fed, whereas milk fat percentage decreased. Ruminal butyrate and d-lactate concentrations, acetate-to-propionate ratio, (acetate + butyrate)/propionate, and pH increased in PMR-fed cows compared with controls for all supplement amounts, whereas propionate and valerate concentrations decreased. Ruminal acetate, butyrate, and ammonia concentrations, acetate-to-propionate ratio, (acetate + butyrate)/propionate, and pH linearly decreased with amounts of supplement fed. Ruminal propionate concentration linearly increased and valerate concentration linearly and quadratically increased with supplement feeding amount. The Bacteroidetes and Firmicutes were the dominant bacterial phyla identified. The Prevotellaceae, Ruminococcaceae, and Lachnospiraceae were the dominant bacterial families, regardless of feeding group, and were influenced by feeding strategy, supplement feeding amount, or both. The Veillonellaceae family decreased in relative abundance in PMR-fed cows compared with controls, and the Streptococcaeae and Lactobacillaceae families were present in only minor relative abundances, regardless of feeding group. Despite large among- and within-group variation in bacterial community composition, distinct bacterial communities occurred among feeding strategies, supplement amounts, and sample times and were associated with ruminal fermentation measures. Control cows fed 16kg of DM of total supplement per day had the most distinct ruminal bacterial community composition. Bacterial community composition was most significantly associated with supplement feeding amount and ammonia, butyrate, valerate, and propionate concentrations. Feeding supplements in a PMR reduced the incidence of ruminal acidosis and altered ruminal bacterial communities, regardless of supplement feeding amount, but did not result in increased milk measures compared with isoenergetic control diets component-fed to late-lactation cows. PMID:24997657

Golder, H M; Denman, S E; McSweeney, C; Wales, W J; Auldist, M J; Wright, M M; Marett, L C; Greenwood, J S; Hannah, M C; Celi, P; Bramley, E; Lean, I J

2014-09-01

352

The metabolism of fungicides.  

PubMed

Of the three main groups of pesticides (insecticides, fungicides and herbicides), fungicides have probably the longest history, dating back to the accidental discovery in 1882 of Bordeaux mixture and the value of copper-based preparations for the control of vine downy mildew disease. In more recent times a wide range of fungicides have become available, including compounds with not only protectant but systemic activity, and total world-wide sales in 1983 were estimated at 2.8 billion dollars. This review attempts to summarize the current state of knowledge as it relates to the metabolism in animals and plants of examples of several of the major fungicide groups. Specifically the metabolism of maneb, mancozeb, zineb, captan, chlorothalonil, benomyl, triadimefon, triadimenol and cymoxanil are discussed. PMID:3541392

Somerville, L

1986-01-01

353

Targeting Energetic Metabolism  

PubMed Central

This perspective highlights advances in the understanding of the role of cellular metabolism in the pathogenesis of pulmonary hypertension. Insights gained in the past 20 years have revealed several similarities between the cellular processes underlying the pulmonary vascular remodeling in pulmonary hypertension and those seen in cancer processes. In line with these insights, there is increasing recognition that abnormal cellular metabolism, notably of aerobic glycolysis (the “Warburg effect”), the potential involvement of hypoxia-inducible factor in this process, and alterations in mitochondrial function, are key elements in the pathogenesis of this disease. The glycolytic shift may underlie the resistance to apoptosis and increased vascular cell proliferation, which are hallmarks of pulmonary hypertension. These investigations have led to novel approaches in the diagnosis and therapy of pulmonary hypertension. PMID:22077069

Davis, Laura A.; Graham, Brian B.

2012-01-01

354

Effects of regional hypoxia and acidosis on Rb(+) uptake and energetics in isolated pig hearts: (87)Rb MRI and (31)P MR spectroscopic study.  

PubMed

The study compared the effects of regional hypoxia and acidosis on Rb(+) uptake and energetics in isolated pig hearts perfused by the Langendorff method. The left anterior descending artery (LAD) was cannulated and the LAD bed was perfused with the same specific flow as the whole heart. Following equilibration with normal Krebs-Henseleit buffer (KHB, pO(2) 568 mm Hg, pH 7.42) the perfusate was switched to one that contained Rb(+) (Rb-KHB). Simultaneously, perfusion through the LAD was carried out with hypoxic (pO(2)=31 mm Hg), an acidemic (pH 7.12) or normal (pO(2)=550 mm Hg) Rb-KHB for 120 min. (87)Rb images of the entire heart or localized (31)P spectra from the left ventricular anterior wall were acquired. Hypoxia decreased the maximal (87)Rb image intensity and Rb(+) flux in the anterior wall to 79+/-9% and 85+/-7%, respectively, of that in the posterior wall. Extracellular acidosis did not affect (87)Rb image intensity and reduced Rb(+) flux (83+/-10%). During hypoxia phosphocreatine and ATP decreased to 36+/-10 and 50+/-15% of baseline, respectively and intracellular pH (pHi) decreased to 6.90+/-0.05. Extracellular acidosis did not affect the phosphocreatine or ATP levels but reduced pHi (7.06+/-0.18 vs. 7.26+/-0.06 in control). We suggest that intracellular acidosis plays a role in the inhibition of Rb(+) uptake during hypoxia. PMID:11781150

Kupriyanov, V V; Xiang, B; Sun, J; Jilkina, O; Deslauriers, R

2002-01-01

355

Characterization of a highly polymorphic marker adjacent to the SLC4A1 gene and of kidney immunostaining in a family with distal renal tubular acidosis  

Microsoft Academic Search

Background. Mutations in the human SLC4A1 (AE1\\/ band 3) gene are associated with hereditary spherocytic anaemia and with distal renal tubular acidosis (dRTA). The molecular diagnosis of AE1 mutations has been complicated by the absence of highly polymorphic genetic markers, and the pathogenic mechanisms of some dRTA-associated AE1 mutations remain un- clear. Here, we characterized a polymorphic dinucleo- tide repeat

Chairat Shayakul; Petr Jarolim; Marie Zachlederova; Daniel Prabakaran; Dionisio Cortez-Campeao; Dana Kalabova; Alan K. Stuart-Tilley; Hiroshi Ideguchi; Christlieb Haller; Seth L. Alper

356

Metabolic regulation of antibiotic resistance.  

PubMed

It is generally assumed that antibiotics and resistance determinants are the task forces of a biological warfare in which each resistance determinant counteracts the activity of a specific antibiotic. According to this view, antibiotic resistance might be considered as a specific response to an injury, not necessarily linked to bacterial metabolism, except for the burden that the acquisition of resistance might impose on the bacteria (fitness costs). Nevertheless, it is known that changes in bacterial metabolism, such as those associated with dormancy or biofilm formation, modulate bacterial susceptibility to antibiotics (phenotypic resistance), indicating that there exists a linkage between bacterial metabolism and antibiotic resistance. The analyses of the intrinsic resistomes of bacterial pathogens also demonstrate that the building up of intrinsic resistance requires the concerted action of many elements, several of which play a relevant role in the bacterial metabolism. In this article, we will review the current knowledge on the linkage between bacterial metabolism and antibiotic resistance and will discuss the role of global metabolic regulators such as Crc in bacterial susceptibility to antibiotics. Given that growing into the human host requires a metabolic adaptation, we will discuss whether this adaptation might trigger resistance even in the absence of selective pressure by antibiotics. PMID:21645016

Martínez, José L; Rojo, Fernando

2011-09-01

357

Lipid metabolism in prostate cancer  

PubMed Central

The malignant transformation of cells requires adaptations across multiple metabolic processes to satisfy the energy required for their increased rate of proliferation. Dysregulation of lipid metabolism has been a hallmark of the malignant phenotype; increased lipid accumulation secondary to changes in the levels of a variety of lipid metabolic enzymes has been documented in a variety of tumors, including prostate. Alterations in prostate lipid metabolism include upregulation of several lipogenic enzymes as well as of enzymes that function to oxidize fatty acids as an energy source. Cholesterol metabolism and phospholipid metabolism are also affected. With respect to lipogenesis, most studies have concentrated on increased expression and activity ofthe de novo fatty acid synthesis enzyme, fatty acid synthase (FASN), with suggestions that FASN might function as an oncogene. A central role for fatty acid oxidation in supplying energy to the prostate cancer cell is supported by the observation that the peroxisomal enzyme, ?-methylacyl-CoA racemase (AMACR), which facilitates the transformation of branched chain fatty acids to a form suitable for ?-oxidation, is highly overexpressed in prostate cancer compared with normal prostate. Exploitation of the alterations in lipid metabolic pathways in prostate cancer could result in the development of new therapeutic modalities as well as provide candidates for new prognostic and predictive biomarkers. AMACR has already proven to be a valuable biomarker in distinguishing normal from malignant prostate tissue, and is used routinely in clinical practice. PMID:25374912

Wu, Xinyu; Daniels, Garrett; Lee, Peng; Monaco, Marie E

2014-01-01

358

Acidosis decreases low Ca2+ -induced neuronal excitation by inhibiting the activity of calcium-sensing cation channels in cultured mouse hippocampal neurons  

PubMed Central

The effects of extracellular pH (pHo) on calcium-sensing non-selective cation (csNSC) channels in cultured mouse hippocampal neurons were investigated using whole-cell voltage-clamp and current-clamp recordings. Decreasing extracellular Ca2+ concentrations ([Ca2+]o) activated slow and sustained inward currents through the csNSC channels. Decreasing pHo activated amiloride-sensitive transient proton-gated currents which decayed to baseline in several seconds. With proton-gated channels inactivated by pre-perfusion with low pH solution or blocked by amiloride, decreasing pHo to 6.5 inhibited the csNSC currents with a leftward shift of the Ca2+ dose–inhibition curve. Increasing pH to 8.5, on the other hand, caused a rightward shift of the Ca2+ dose–inhibition curve and potentiated the csNSC currents. Intracellular alkalinization following bath perfusion of quinine mimicked the potentiation of the csNSC currents by increasing pHo, while intracellular acidification by addition and subsequent withdrawal of NH4Cl mimicked the inhibition of the csNSC currents by decreasing pHo. Intracellular pH (pHi) imaging demonstrated that decreasing pHo induced a corresponding decrease in pHi. Including 30 mM Hepes in the pipette solution eliminated the effects of quinine and NH4Cl on the csNSC currents, but only partially reduced the effect of lowering pHo. In current-clamp recordings, decreasing [Ca2+]o induced sustained membrane depolarization and excitation of hippocampal neurons. Decreasing pHo to 6.5 inhibited the low [Ca2+]o-induced csNSC channel-mediated membrane depolarization and the excitation of neurons. Our results indicate that acidosis may inhibit low [Ca2+]o-induced neuronal excitation by inhibiting the activity of the csNSC channels. Both the extracellular and the intracellular sites are involved in the proton modulation of the csNSC channels. PMID:12777448

Chu, Xiang-Ping; Zhu, Xiao-Man; Wei, Wen-Li; Li, Guo-Hua; Simon, Roger P; MacDonald, John F; Xiong, Zhi-Gang

2003-01-01

359

HCO(3)(-)-independent conductance with a mutant Na(+)/HCO(3)(-) cotransporter (SLC4A4) in a case of proximal renal tubular acidosis with hypokalaemic paralysis.  

PubMed

The renal electrogenic Na(+)/HCO(3)(?) cotransporter (NBCe1-A) contributes to the basolateral step of transepithelial HCO(3)(?) reabsorption in proximal tubule epithelia, contributing to the buffering of blood pH. Elsewhere in the body (e.g. muscle cells) NBCe1 variants contribute to, amongst other processes, maintenance of intracellular pH. Others have described a homozygous mutation in NBCe1 (NBCe1-A p.Ala799Val) in an individual with severe proximal renal tubular acidosis (pRTA; usually associated with defective HCO(3)(?) reabsorption in proximal tubule cells) and hypokalaemic periodic paralysis (hypoPP; usually associated with leaky cation channels in muscle cells). Using biotinylation and two-electrode voltage-clamp on Xenopus oocytes expressing NBCe1, we demonstrate that the mutant NBCe1-A (A(A799V)) exhibits a per-molecule transport defect that probably contributes towards the observed pRTA. Furthermore, we find that A(A799V) expression is associated with an unusual HCO(3)(?)-independent conductance that, if associated with mutant NBCe1 in muscle cells, could contribute towards the appearance of hypokalaemic paralysis in the affected individual. We also study three novel lab mutants of NBCe1-A: p.Ala799Ile, p.Ala799Gly and p.Ala799Ser. All three exhibit a per-molecule transport defect, but only A(A799I) exhibits an A(A799V)-like ion conductance. A(A799G) and A(A799S) exhibit unusual outward rectification in their HCO(3)(?)-dependent conductance and A(A799G) exhibits reduced sensitivity to both DIDS and tenidap. A799G is the first mutation shown to affect the apparent tenidap affinity of NBCe1. Finally we show that A(A799V) and A(A799I), which accumulate poorly in the plasma membrane of oocytes, exhibit signs of abnormal intracellular accumulation in a non-polarized renal cell-line. PMID:22331414

Parker, Mark D; Qin, Xue; Williamson, Rosalind C; Toye, Ashley M; Boron, Walter F

2012-04-15

360

Acidosis decreases low Ca(2+)-induced neuronal excitation by inhibiting the activity of calcium-sensing cation channels in cultured mouse hippocampal neurons.  

PubMed

The effects of extracellular pH (pHo) on calcium-sensing non-selective cation (csNSC) channels in cultured mouse hippocampal neurons were investigated using whole-cell voltage-clamp and current-clamp recordings. Decreasing extracellular Ca2+ concentrations ([Ca2+]o) activated slow and sustained inward currents through the csNSC channels. Decreasing pHo activated amiloride-sensitive transient proton-gated currents which decayed to baseline in several seconds. With proton-gated channels inactivated by pre-perfusion with low pH solution or blocked by amiloride, decreasing pHo to 6.5 inhibited the csNSC currents with a leftward shift of the Ca2+ dose-inhibition curve. Increasing pH to 8.5, on the other hand, caused a rightward shift of the Ca2+ dose-inhibition curve and potentiated the csNSC currents. Intracellular alkalinization following bath perfusion of quinine mimicked the potentiation of the csNSC currents by increasing pHo, while intracellular acidification by addition and subsequent withdrawal of NH4Cl mimicked the inhibition of the csNSC currents by decreasing pHo. Intracellular pH (pHi) imaging demonstrated that decreasing pHo induced a corresponding decrease in pHi. Including 30 mM Hepes in the pipette solution eliminated the effects of quinine and NH4Cl on the csNSC currents, but only partially reduced the effect of lowering pHo. In current-clamp recordings, decreasing [Ca2+]o induced sustained membrane depolarization and excitation of hippocampal neurons. Decreasing pHo to 6.5 inhibited the low [Ca2+]o-induced csNSC channel-mediated membrane depolarization and the excitation of neurons. Our results indicate that acidosis may inhibit low [Ca2+]o-induced neuronal excitation by inhibiting the activity of the csNSC channels. Both the extracellular and the intracellular sites are involved in the proton modulation of the csNSC channels. PMID:12777448

Chu, Xiang-Ping; Zhu, Xiao-Man; Wei, Wen-Li; Li, Guo-Hua; Simon, Roger P; MacDonald, John F; Xiong, Zhi-Gang

2003-07-15

361

Metabolic depression during environmental stress: the role of extracellular versus intracellular pH in Sipunculus nudus  

PubMed

Environmental stresses such as hypoxia or hypercapnia are known to cause acid-base disturbances and in several organisms they lead to metabolic depression. The present study was undertaken to quantify the influence of these changes in acid­p;base parameters on metabolic rate. We determined the rate of oxygen consumption in a non-perfused preparation of the body wall musculature of the marine worm Sipunculus nudus at various levels of extra- and intracellular pH (pHe and pHi, respectively), PCO2 and [HCO3-]. The acid­p;base status of the tissue was modified and clamped by long-term exposure to media set to specific values of extracellular pH, PCO2 and [HCO3-]. At a pHe of 7.90, which is equivalent to the normoxic normocapnic in vivo extracellular pH, and an ambient PCO2 of 0.03 kPa (control conditions), pHi was 7.26±0.02 (mean ± s.d., N=5). A reduction of extracellular pH from 7.90 to 7.20 resulted in a significant decrease of pHi to 7.17±0.05 at 0.03 kPa PCO2 (normocapnia) and to 7.20±0.02 at 1.01 kPa PCO2 (hypercapnia). At the same time, the rate of oxygen consumption of the tissue was significantly depressed by 18.7±4.7 % and 17.7±3.0 %, respectively. A significant depression of oxygen consumption by 13.7±4.7 % also occurred under hypercapnia at pHe 7.55 when pHi was elevated above control values (7.32±0.01). No significant changes in oxygen consumption were observed when pHe was either drastically elevated to 8.70 under normocapnia (pHi 7.36±0.05) or maintained at 7.90 during hypercapnia (pHi 7.37±0.03). ATP and phospho-l-arginine concentrations, as well as the Gibbs free energy change of ATP hydrolysis (dG/dATP), were maintained at high levels during all treatments, indicating an equilibrium between energy supply and demand. We conclude that the depression of aerobic energy turnover in isolated body wall musculature of S. nudus is induced by low extracellular pH. A model is proposed which could explain a reduced ATP cost of pHi regulation during extracellular acidosis, thus contributing to metabolic depression. PMID:9319709

ReipschlÄGer; PÖRtner

1996-01-01

362

A Simple Score to Predict the Outcome of Severe Malaria in Adults  

PubMed Central

Background World Health Organization treatment guidelines recommend that adults with severe malaria be admitted to an intensive care unit (ICU). However, ICU facilities are limited in the resource-poor settings where most malaria occurs. Identification of patients at greater risk of complications may facilitate their triage and resource allocation. Methods With use of data from a trial conducted in Southeast Asia (n = 868), a logistic regression model was built to identify independent predictors of mortality among adults with severe malaria. A scoring system based on this model was tested in the original dataset and then validated in 2 series from Bangladesh (n = 188) and Vietnam (n = 292). Results Acidosis (base deficit) and cerebral malaria (measured as Glasgow Coma Score) were the main independent predictors of outcome. The 5-point Coma Acidosis Malaria (CAM) score was simply derived from these 2 variables. Mortality increased steadily with increasing score. A CAM score <2 predicted survival with a positive predictive value (PPV) of 95.8% (95% confidence interval [CI], 93%–97.7%). Of the 14 of 331 patients who died with a CAM score <2, 11 (79%) had renal failure and death occurred late after hospital admission (median, 108 h; range, 40–360 h). Substitution of plasma bicarbonate as the measure of acidosis only slightly reduced the prognostic value of the model. Use of respiratory rate was inferior, but a score <2 still predicted survival with a PPV of 92.2% (95% CI, 89.1%–94.7%). Conclusions Patients with a CAM score <2 at hospital admission may be safely treated in a general ward, provided that renal function can be monitored. PMID:20105074

Hanson, Josh; Lee, Sue J.; Mohanty, Sanjib; Faiz, M. A.; Anstey, Nicholas M.; Charunwatthana, Prakaykaew; Yunus, Emran Bin; Mishra, Saroj K.; Tjitra, Emiliana; Price, Ric N.; Rahman, Ridwanur; Nosten, Francois; Htut, Ye; Hoque, Gofranul; Chau, Tran Thi Hong; Phu, Nguyen Hoan; Hien, Tran Tinh; White, Nicholas J.; Day, Nicholas P. J.; Dondorp, Arjen M.

2015-01-01

363

Metabolism and biochemistry in hypogravity  

NASA Technical Reports Server (NTRS)

The headward shift of body fluid and increase in stress-related hormones that occur in hypogravity bring about a number of changes in metabolism and biochemistry of the human body. Such alterations may have important effects on health during flight and during a recovery period after return to earth. Body fluid and electrolytes are lost, and blood levels of several hormones that control metabolism are altered during space flight. Increased serum calcium may lead to an increased risk of renal stone formation during flight, and altered drug metabolism could influence the efficacy of therapeutic agents. Orthostatic intolerance and an increased risk of fracturing weakened bones are concerns at landing. It is important to understand biochemistry and metabolism in hypogravity so that clinically important developments can be anticipated and prevented or ameliorated.

Leach, Carolyn S.

1991-01-01

364

Metabolic pancreatitis: Etiopathogenesis and management  

PubMed Central

Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis. PMID:24083160

Kota, Sunil Kumar; Krishna, S.V.S.; Lakhtakia, Sandeep; Modi, Kirtikumar D.

2013-01-01

365

[Metabolic surgery].  

PubMed

The prevalence of obesity and diabetes mellitus type 2 is constantly rising worldwide and is one of the most threatening global health and health economic problems. Whereas bariatric surgery is well established in the treatment of morbid obesity, the surgical treatment options for type 2 diabetes mellitus alone are still under discussion (metabolic surgery). Bariatric procedures differ considering weight loss and influencing associated comorbidities. Detailed knowledge of available surgical treatment options for morbid obesity, the risks and requirements of laparoscopic skills, effectiveness and, as far as already known, mechanisms of action are crucial for appropriate implementation. PMID:22695815

Jurowich, C; Germer, C T; Seyfried, F; Thalheimer, A

2012-06-01

366

Application of research findings and summary of research needs: Bud Britton Memorial Symposium on Metabolic Disorders of Feedlot Cattle.  

PubMed

Updated research findings with acidosis, feedlot bloat, liver abscesses, and sudden death syndromes were presented at the Bud Britton Memorial Symposium on Metabolic Disorders of Feedlot Cattle. Possible industry applications include the need to establish guidelines for use of clostridial vaccines in feedlot cattle, further assessment of the relationship between acidosis and polioencephalomalacia, examination of the effects of various ionophores on the incidence of metabolic disorders, and evaluation of the effects of feed bunk management and limit- and restricted-feeding programs on the incidence of metabolic disorders. A multidisciplinary approach among researchers, consulting nutritionists and veterinarians, and feedlot managers will be required for effective progress in research and in the application of research findings. Areas suggested for further research include 1) assessment of feed consumption patterns and social behavior of cattle in large-pen, feedlot settings; 2) evaluation of the relationship between feed intake management systems (feed bunk management programs, limit- and programmed-feeding) and the incidence of metabolic disorders, including delineation of the role of variability in feed intake in the etiology of such disorders; 3) efforts to improve antemortem and postmortem diagnosis, and to establish standardized regional or national epidemiological databases for various metabolic disorders; 4) ascertaining the accuracy of diagnosis of metabolic disorders and determining the relationship of previous health history of animals to the incidence of metabolic disorders; 5) further defining ruminal and intestinal microbiology as it relates to metabolic disorders and deeper evaluation of metabolic changes that occur with such disorders; 6) continued appraisal of the effects of grain processing and specific feed ingredients and nutrients on metabolic disorders, and development of new feed additives to control or prevent these disorders; and 7) application of biotechnology to develop grain varieties with altered nutrient degradation profiles that decrease the propensity for disastrous acid loads in the rumen, feed-grade enzymes and probiotics that modify nutrient digestion or microbial profiles in the rumen and intestine, and specific strains of ruminal bacteria and protozoa that alter ruminal and metabolic conditions that may precipitate metabolic disorders. PMID:9464915

Galyean, M L; Eng, K S

1998-01-01

367

Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4.  

PubMed

Hearing depends on a high K(+) concentration bathing the apical membranes of sensory hair cells. K(+) that has entered hair cells through apical mechanosensitive channels is transported to the stria vascularis for re-secretion into the scala media(). K(+) probably exits outer hair cells by KCNQ4 K(+) channels(), and is then transported by means of a gap junction system connecting supporting Deiters' cells and fibrocytes() back to the stria vascularis. We show here that mice lacking the K(+)/Cl(-) (K-Cl) co-transporter Kcc4 (coded for by Slc12a7) are deaf because their hair cells degenerate rapidly after the beginning of hearing. In the mature organ of Corti, Kcc4 is restricted to supporting cells of outer and inner hair cells. Our data suggest that Kcc4 is important for K(+) recycling() by siphoning K(+) ions after their exit from outer hair cells into supporting Deiters' cells, where K(+) enters the gap junction pathway. Similar to some human genetic syndromes(), deafness in Kcc4-deficient mice is associated with renal tubular acidosis. It probably results from an impairment of Cl(-) recycling across the basolateral membrane of acid-secreting alpha-intercalated cells of the distal nephron. PMID:11976689

Boettger, Thomas; Hübner, Christian A; Maier, Hannes; Rust, Marco B; Beck, Franz X; Jentsch, Thomas J

2002-04-25

368

An in vitro rat diaphragmatic fatigue model induced by combined hypoxic and hypercapnic acidosis and the effect of salmeterol.  

PubMed

Hypoxia or hypercapnia impairs diaphragmatic contractility and induces fatigue. However, little is known about the combined effect of hypoxic and hypercapnic acidosis (HHA) on diaphragmatic fatigue. In this study, a gas mixture (21% O2, 12% CO2 and 67% N2) was used to produce HHA-induced rat diaphragmatic fatigue. Force-frequency relationships and twitch characteristics including peak twitch tension (PTT), time to peak tension (TPT), half relaxation time (1/2RT), maintaining tension (MT) and direct-muscle-stimulation tension (MST) were measured in diaphragm preparations from male SD rats. The HHA gas mixture attenuated force at all frequencies (5-120 Hz) and decreased PTT, MT and MST significantly. Aminophylline, a positive control drug, blocked the negative inotropic effect of HHA in a dose-dependent manner. Moreover, salmeterol, a long-acting beta2-adrenoceptor agonist, inhibited the harmful effect of HHA at high frequencies (40-120 Hz), but without effect on MT and MST. These results suggest that an in vitro HHA-induced rat diaphragmatic fatigue model could be established by aerating with the gas mixture, which may be an optimal model to screen effective drugs for diaphragmatic fatigue. Furthermore, salmeterol may play a protective role in HHA-induced impairment. PMID:16310375

Xu, Xuanli; Zhou, Jianying; Yang, Qiuhuo; Fang, Liben; Xie, Qiangmin; Shen, Yueliang

2006-02-01

369

Structure, Function, and Regulation of the SLC4 NBCe1 Transporter and its Role in Causing Proximal Renal Tubular Acidosis  

PubMed Central

Purpose of review There has been significant progress in our understanding of the structural and functional properties and regulation of NBCe1, a membrane transporter that plays a key role in renal acid-base physiology. NBCe1-A mediates basolateral electrogenic sodium-base transport in the proximal tubule and is critically required for transepithelial bicarbonate absorption. Mutations in NBCe1 cause autosomal recessive proximal renal tubular acidosis (pRTA). The review summarizes recent advances in this area. Recent findings A topological model of NBCe1 has been established that provides a foundation for future structure-functional studies of the transporter. Critical residues and regions have been identified in NBCe1 that play key roles in its structure, function (substrate transport, electrogenicity) and regulation. The mechanisms of how NBC1 mutations cause pRTA have also recently been elucidated. Summary Given the important role of proximal tubule transepithelial bicarbonate absorption in systemic acid-base balance, a clear understanding of the structure-functional properties of the NBCe1-A is a prerequisite for elucidating the mechanisms of defective transepithelial bicarbonate transport in pRTA. PMID:23917030

Kurtz, Ira; Zhu, Quansheng

2014-01-01

370

Proximal renal tubular acidosis mediated by mutations in NBCe1-A: unraveling the transporter's structure-functional properties.  

PubMed

NBCe1 belongs to the SLC4 family of base transporting membrane proteins that plays a significant role in renal, extrarenal, and systemic acid-base homeostasis. Recent progress has been made in characterizing the structure-function properties of NBCe1 (encoded by the SLC4A4 gene), and those factors that regulate its function. In the kidney, the NBCe1-A variant that is expressed on the basolateral membrane of proximal tubule is the key transporter responsible for overall transepithelial bicarbonate absorption in this nephron segment. NBCe1 mutations impair transepithelial bicarbonate absorption causing the syndrome of proximal renal tubular acidosis (pRTA). Studies of naturally occurring NBCe1 mutant proteins in heterologous expression systems have been very helpful in elucidation the structure-functional properties of the transporter. NBCe1 mutations are now known to cause pRTA by various mechanisms including the alteration of the transporter function (substrate ion interaction, electrogenicity), abnormal processing to the plasma membrane, and a perturbation in its structural properties. The elucidation of how NBCe1 mutations cause pRTA in addition to the recent studies which have provided further insight into the topology of the transporter have played an important role in uncovering its critically important structural-function properties. PMID:24391589

Kurtz, Ira; Zhu, Quansheng

2013-01-01

371

Phthalate Exposure Changes the Metabolic Profile of Cardiac Muscle Cells  

PubMed Central

Background: Phthalates are common plasticizers present in medical-grade plastics and other everyday products. They can also act as endocrine-disrupting chemicals and have been linked to the rise in metabolic disorders. However, the effect of phthalates on cardiac metabolism remains largely unknown. Objectives: We examined the effect of di(2-ethylhexyl)phthalate (DEHP) on the metabolic profile of cardiomyocytes because alterations in metabolic processes can lead to cell dysfunction. Methods: Neonatal rat cardiomyocytes were treated with DEHP at a concentration and duration comparable to clinical exposure (50–100 ?g/mL, 72 hr). We assessed the effect of DEHP on gene expression using microarray analysis. Physiological responses were examined via fatty acid utilization, oxygen consumption, mitochondrial mass, and Western blot analysis. Results: Exposure to DEHP led to up-regulation of genes associated with fatty acid transport, esterification, mitochondrial import, and ?-oxidation. The functional outcome was an increase in myocyte fatty acid–substrate utilization, oxygen consumption, mitochondrial mass, PPAR? (peroxisome proliferator-activated receptor ?) protein expression, and extracellular acidosis. Treatment with a PPAR? agonist (Wy-14643) only partially mimicked the effects observed in DEHP-treated cells. Conclusions: Data suggest that DEHP exposure results in metabolic remodeling of cardiomyocytes, whereby cardiac cells increase their dependence on fatty acids for energy production. This fuel switch may be regulated at both the gene expression and posttranscription levels. Our findings have important clinical implications because chronic dependence on fatty acids is associated with an accumulation in lipid intermediates, lactate, protons, and reactive oxygen species. This dependence can sensitize the heart to ischemic injury and ventricular dysfunction. PMID:22672789

Swift, Luther M.; Kay, Matthew W.; Lee, Norman H.; Sarvazyan, Narine

2012-01-01

372

An Advance Organizer for Teaching Bacterial Metabolism  

ERIC Educational Resources Information Center

The metabolic versatility of bacteria is a source of learning difficulty for students in classical microbiology courses. To facilitate the learning process, the authors developed an advance organizer. It consists of a set of six diagrams of metabolic pathways describing the basic living requirements of several types of bacteria: energy, carbon…

Barbosa, Heloiza R.; Marques, Marilis V.; Torres, Bayardo B.

2005-01-01

373

Metabolic zonation in teleost gastrointestinal tract  

Microsoft Academic Search

Activities of several metabolic enzymes show distinct patterns of zonation along the intestinal tract of tilapia ( Oreochromis niloticus), rainbow trout ( Oncorhynchus mykiss) and copper rockfish ( Sebastes caurinus). Zonation is species and enzyme specific, with different metabolic activities concentrated in specific areas, and few generalizations can be made. The rockfish show the smallest degree of zonation, with highest

T. P. Mommsen; H. L. Osachoff; M. E. Elliott

2003-01-01

374

Candidate human genetic polymorphisms and severe malaria in a Tanzanian population.  

PubMed

Human genetic background strongly influences susceptibility to malaria infection and progression to severe disease and death. Classical genetic studies identified haemoglobinopathies and erythrocyte-associated polymorphisms, as protective against severe disease. High throughput genotyping by mass spectrometry allows multiple single nucleotide polymorphisms (SNPs) to be examined simultaneously. We compared the prevalence of 65 human SNP's, previously associated with altered risk of malaria, between Tanzanian children with and without severe malaria. Five hundred children, aged 1-10 years, with severe malaria were recruited from those admitted to hospital in Muheza, Tanzania and compared with matched controls. Genotyping was performed by Sequenom MassArray, and conventional PCR was used to detect deletions in the alpha-thalassaemia gene. SNPs in two X-linked genes were associated with altered risk of severe malaria in females but not in males: heterozygosity for one or other of two SNPs in the G6PD gene was associated with protection from all forms of severe disease whilst two SNPs in the gene encoding CD40L were associated with respiratory distress. A SNP in the adenyl cyclase 9 (ADCY9) gene was associated with protection from acidosis whilst a polymorphism in the IL-1? gene (IL1A) was associated with an increased risk of acidosis. SNPs in the genes encoding IL-13 and reticulon-3 (RTN3) were associated with increased risk of cerebral malaria. This study confirms previously known genetic associations with protection from severe malaria (HbS, G6PD). It identifies two X-linked genes associated with altered risk of severe malaria in females, identifies mutations in ADCY9, IL1A and CD40L as being associated with altered risk of severe respiratory distress and acidosis, both of which are characterised by high serum lactate levels, and also identifies novel genetic associations with severe malaria (TRIM5) and cerebral malaria(IL-13 and RTN3). Further studies are required to test the generality of these associations and to understand their functional consequences. PMID:23144702

Manjurano, Alphaxard; Clark, Taane G; Nadjm, Behzad; Mtove, George; Wangai, Hannah; Sepulveda, Nuno; Campino, Susana G; Maxwell, Caroline; Olomi, Raimos; Rockett, Kirk R; Jeffreys, Anna; Riley, Eleanor M; Reyburn, Hugh; Drakeley, Christopher

2012-01-01

375

Metabolic Response of Pediatric Traumatic Brain Injury.  

PubMed

Traumatic brain injury (TBI) in the pediatric brain presents unique challenges as the complex cascades of metabolic and biochemical responses to TBI are further complicated ongoing maturational changes of the developing brain. TBIs of all severities have been shown to significantly alter metabolism and hormones which impair the ability of the brain to process glucose for cellular energy. Under these conditions, the brain's primary fuel (glucose) becomes a less favorable fuel and the ability of the younger brain to revert to ketone metabolism can an advantage. This review addresses the potential of alternative substrate metabolic intervention as a logical pediatric TBI neuroprotective strategy. PMID:25336427

Prins, Mayumi L; Matsumoto, Joyce

2014-10-21

376

Predicting the Clinical Outcome of Severe Falciparum Malaria in African Children: Findings From a Large Randomized Trial  

PubMed Central

Background.?Data from the largest randomized, controlled trial for the treatment of children hospitalized with severe malaria were used to identify such predictors of a poor outcome from severe malaria. Methods.?African children (<15 years) with severe malaria participated in a randomized comparison of parenteral artesunate and parenteral quinine in 9 African countries. Detailed clinical assessment was performed on admission. Parasite densities were assessed in a reference laboratory. Predictors of death were examined using a multivariate logistic regression model. Results.?Twenty indicators of disease severity were assessed, out of which 5 (base deficit, impaired consciousness, convulsions, elevated blood urea, and underlying chronic illness) were associated independently with death. Tachypnea, respiratory distress, deep breathing, shock, prostration, low pH, hyperparasitemia, severe anemia, and jaundice were statistically significant indicators of death in the univariate analysis but not in the multivariate model. Age, glucose levels, axillary temperature, parasite density, heart rate, blood pressure, and blackwater fever were not related to death in univariate models. Conclusions.?Acidosis, cerebral involvement, renal impairment, and chronic illness are key independent predictors for a poor outcome in African children with severe malaria. Mortality is markedly increased in cerebral malaria combined with acidosis. Clinical Trial Registration.?ISRCTN50258054. PMID:22412067

Olaosebikan, Rasaq; Hendriksen, Ilse C. E.; Lee, Sue J.; Adedoyin, Olanrewaju Timothy; Agbenyega, Tsiri; Nguah, Samuel Blay; Bojang, Kalifa; Deen, Jacqueline L.; Evans, Jennifer; Fanello, Caterina I.; Gomes, Ermelinda; Pedro, Alínia José; Kahabuka, Catherine; Karema, Corine; Kivaya, Esther; Maitland, Kathryn; Mokuolu, Olugbenga A.; Mtove, George; Mwanga-Amumpaire, Juliet; Nadjm, Behzad; Nansumba, Margaret; Ngum, Wirichada Pan; Onyamboko, Marie A.; Reyburn, Hugh; Sakulthaew, Tharisara; Silamut, Kamolrat; Tshefu, Antoinette K.; Umulisa, Noella; Gesase, Samwel; Day, Nicholas P. J.; White, Nicholas J.; Dondorp, Arjen M.

2012-01-01

377

Protein metabolism and liver disease.  

PubMed

In health, the liver orchestrates the metabolism of proteins and amino acids. When the liver is diseased, the regulation of protein metabolism is frequently disturbed. The manifestations of disturbed protein metabolism in liver disease are varied and change with disease aetiology and severity. The hallmarks of protein and amino acid metabolism in liver disease are lowered concentrations of circulating branched-chain and increased concentrations of circulating aromatic amino acids with concomitantly altered amino acid kinetics. The changes in amino acid kinetics in liver disease are characterized by increased endogenous leucine flux, an indicator of protein breakdown, and leucine oxidation in the post-absorptive state (when calculated using a reciprocal-pool model and normalized for body cell mass). In addition, the increase in whole-body protein synthesis in response to an amino acid infusion may be attenuated in patients with cirrhosis. These changes are often accompanied by clinically apparent muscle wasting, manifest as protein-calorie malnutrition, and associated low levels of hepatically synthesized plasma proteins. While the pathogenesis of these changes in protein and amino acid metabolism has not been elucidated, altered levels of circulating hormones, known to affect protein metabolism, are probably important. Lowered levels of micronutrients and trace metals and elevated levels of cytokines may also play a role. PMID:9022955

Charlton, M R

1996-10-01

378

Metabolic distance estimation based on principle component analysis of metabolic turnover.  

PubMed

Visualization of metabolic dynamism is important for various types of metabolic studies including studies on optimization of bio-production processes and studies of metabolism-related diseases. Many methodologies have been developed for metabolic studies. Among these, metabolic turnover analysis (MTA) is often used to analyze metabolic dynamics. MTA involves observation of changes in the isotopomer ratio of metabolites over time following introduction of isotope-labeled substrates. MTA has several advantages compared with (13)C-metabolic flux analysis, including the diversity of applicable samples, the variety of isotope tracers, and the wide range of target pathways. However, MTA produces highly complex data from which mining useful information becomes difficult. For easy understanding of MTA data, a new approach was developed using principal component analysis (PCA). The resulting PCA score plot visualizes the metabolic distance, which is defined as distance between metabolites on the real metabolic map. And the score plot gives us some hints of interesting metabolism for further study. We used this method to analyze the central metabolism of Saccharomyces cerevisiae under moderated aerobic conditions, and time course data for 77 isotopomers of 14 metabolites were obtained. The PCA score plot for this dataset represented a metabolic map and indicated interesting phenomena such as activity of fumarate reductase under aerated condition. These findings show the importance of a multivariate analysis to MTA. In addition, because the approach is not biased, this method has potential application for analysis of less-studied pathways and organisms. PMID:24680283

Nakayama, Yasumune; Putri, Sastia P; Bamba, Takeshi; Fukusaki, Eiichiro

2014-09-01

379

Metabolic effects of hypergravity on experimental animals  

NASA Technical Reports Server (NTRS)

Several experiments concerned with the exposure of animals to acute or chronic centrifugation are described. The effects of hypergravity particularly discussed include the decreased growth rate and body weight, increased metabolic rate, skeletal deformation, and loss of body fat.

Oyama, J.

1982-01-01

380

Fatty acid metabolism and vascular disease.  

PubMed

Fatty acid metabolism is abnormal in insulin-resistant states that increase the risk of atherosclerosis such as type 2 diabetes and the metabolic syndrome. How fatty acids promote vascular disease is poorly understood, but lipoprotein lipase and peroxisome proliferator-activated receptor alpha (PPARalpha)-physiologically related proteins involved in fatty acid metabolism-may be involved. Glucocorticoid metabolism is also abnormal in insulin-resistant states and may promote several components of the metabolic syndrome. Recent studies have shown that hepatic fatty acid metabolism is required for the development of insulin resistance and hypertension caused by glucocorticoid excess, suggesting that crosstalk between glucocorticoid receptor-and PPARalpha-dependent pathways may contribute to vascular disease. PMID:15030793

Semenkovich, Clay F

2004-02-01

381

Towards reconstructing a metabolic tree of life  

PubMed Central

Using information from several metabolic databases, we have built our own metabolic database containing 434 pathways and 1157 different enzymes. We have used this information to construct a dendrogram that demonstrates the metabolic similarities between 282 species. The resulting species distribution and the clusters defined in the tree show a certain taxonomic congruence, especially in recent relationships between species. This dendrogram is another representation of the tree of life, based on metabolism that may complement the trees constructed by other methods. For example, the metabolic dissimilarity we demonstrate between Symbiobacterium thermophilum (previously defined as Actinobacteria) and the other Actinobacteria species, and the metabolic similarity between S. thermophilum and Clostridia, combined with other evidence, suggest that S. thermophilum may be re-classified as Firmicutes, Clostridia. PMID:21670791

Marcet-Houben, Marina; Puigbò, Pere; Romeu, Antoni; Garcia-Vallve, Santiago

2007-01-01

382

Aquatic Toxicology 54 (2001) 261275 Sensitivity of the spiny dogfish (Squalus acanthias) to  

E-print Network

. Arterial PaO2 rapidly declined below 20 Torr, and blood acidosis (both respiratory and metabolic) occurred less severe, although slight mortality (12.5%) still occurred. Respiratory alkalosis occurred, together

Grosell, Martin

383

Metabolic regulation in mammalian hibernation: Enzyme and protein adaptations  

Microsoft Academic Search

Mammalian hibernation requires specific regulatory controls on metabolism to coordinate entry, maintenance, and arousal stages, as well as adjustments to many metabolic functions to support long-term dormancy. Several mechanisms of metabolic regulation are involved in potentiating survival. One of these is the reversible phosphorylation of regulatory enzymes, including glycogen phosphorylase, phosphofructokinase, pyruvate kinase, and pyruvate dehydrogenase. In particular, the sharp

Kenneth B. Storey

1997-01-01

384

Establishment of Quantitative Severity Evaluation Model for Spinal Cord Injury by Metabolomic Fingerprinting  

PubMed Central

Spinal cord injury (SCI) is a devastating event with a limited hope for recovery and represents an enormous public health issue. It is crucial to understand the disturbances in the metabolic network after SCI to identify injury mechanisms and opportunities for treatment intervention. Through plasma 1H-nuclear magnetic resonance (NMR) screening, we identified 15 metabolites that made up an “Eigen-metabolome” capable of distinguishing rats with severe SCI from healthy control rats. Forty enzymes regulated these 15 metabolites in the metabolic network. We also found that 16 metabolites regulated by 130 enzymes in the metabolic network impacted neurobehavioral recovery. Using the Eigen-metabolome, we established a linear discrimination model to cluster rats with severe and mild SCI and control rats into separate groups and identify the interactive relationships between metabolic biomarkers in the global metabolic network. We identified 10 clusters in the global metabolic network and defined them as distinct metabolic disturbance domains of SCI. Metabolic paths such as retinal, glycerophospholipid, arachidonic acid metabolism; NAD–NADPH conversion process, tyrosine metabolism, and cadaverine and putrescine metabolism were included. In summary, we presented a novel interdisciplinary method that integrates metabolomics and global metabolic network analysis to visualize metabolic network disturbances after SCI. Our study demonstrated the systems biological study paradigm that integration of 1H-NMR, metabolomics, and global metabolic network analysis is useful to visualize complex metabolic disturbances after severe SCI. Furthermore, our findings may provide a new quantitative injury severity evaluation model for clinical use. PMID:24727691

Yang, Hao; Cohen, Mitchell Jay; Chen, Wei; Sun, Ming-Wei; Lu, Charles Damien

2014-01-01

385

[The Stewart model. "Modern" approach to the interpretation of the acid-base metabolism].  

PubMed

About twenty years ago, Peter Stewart had already published his modern quantitative approach to acid-base chemistry. According to his interpretations, the traditional concepts of the mechanisms behind the changes in acid-base balance are considerably questionable. The main physicochemical principle which must be accomplished in body fluids, is the rule of electroneutrality. There are 3 components in biological fluids which are subject to this principle: a)Water, which is only in minor parts dissociated into H+ and OH-, b)"strong", i.e. completely dissociated, electrolytes, which thus do not interact with other substances, and body substances, such as lactate, and c)"weak", i.e. incompletely dissociated, substances. Peter Stewart strictly distinguished between dependent and independent variables and thus indeed described a new order of acid-base chemistry. The 3 dependent variables (bicarbonate concentration [Bic(-)], pH, and with this also hydrogen ion concentration [H(+)]) can only change if the 3 independent variables allow this change. These 3 independent variables are: 1. Carbon dioxide partial pressure, 2.the total amount of all weak acids ([A-] (Stewart called these ATOT), and 3.strong ion difference (SID). [A(-)] can be calculated from the albumin (Alb) and the phosphate concentration (Pi): [A(-)]=[Alb x (0.123 x pH - 0.631)] + [Pi x (0.309 x pH - 0.469)]. An apparent SID (or "bedside" SID) can be calculated using measurable ion concentrations: SID=[Na(+)] + [K(+)] - [Cl(-)]-lactate. Regarding the metabolic disturbances of acid-base chemistry, according to Stewart's terminology, changes in pH, [H(+)], and [Bic(-)] are only possible if either SID or [A(-)] itself changes. If, for example, SID decreases (e.g. in case of hyperchloremia), this increase in independent negative charges leads to a decrease in dependent negative charges in terms of [Bic(-)] resulting in acidosis (and vice versa). Therefore, according to Stewart, the decrease in SID during hyperchloremic acidosis results from the increase in serum chloride concentration and is the causal mechanism behind this acidosis. Contrary for example, a decrease in [A(-)] (e. g. during hypoalbuminemia) leads to an increase in [Bic(-)] and therefore to an alcalosis (and vice versa). Thus, by Stewart's approach, completely new acid-base disturbances, like "hyperchloremic acidosis" or "hypoalbuminemic alcalosis" (which, of course, can also exist in combination) can be detected, which had been unrecognised by the classic acid-base concepts. Consequently, Stewart's analysis can lead to a better understanding of the mechanisms behind the changes in acid-base balance. PMID:15088097

Rehm, M; Conzen, P F; Peter, K; Finsterer, U

2004-04-01

386

Differing effects of 2 active dried yeast (Saccharomyces cerevisiae) strains on ruminal acidosis and methane production in nonlactating dairy cows.  

PubMed

Fifteen ruminally cannulated, nonlactating Holstein cows were used to measure the effects of 2 strains of Saccharomyces cerevisiae, fed as active dried yeasts, on ruminal pH and fermentation and enteric methane (CH(4)) emissions. Nonlactating cows were blocked by total duration (h) that their ruminal pH was below 5.8 during a 6-d pre-experimental period. Within each block, cows were randomly assigned to control (no yeast), yeast strain 1 (Levucell SC), or yeast strain 2 (a novel strain selected for enhanced in vitro fiber degradation), with both strains (Lallemand Animal Nutrition, Montréal, QC, Canada) providing 1 × 10(10) cfu/head per day. Cows were fed once daily a total mixed ration consisting of a 50:50 forage to concentrate ratio (dry matter basis). The yeast strains were dosed via the rumen cannula daily at the time of feeding. During the 35-d experiment, ruminal pH was measured continuously for 7 d (d 22 to 28) by using an indwelling system, and CH(4) gas was measured for 4 d (d 32 to 35) using the sulfur hexafluoride tracer gas technique (with halters and yokes). Rumen contents were sampled on 2 d (d 22 and 26) at 0, 3, and 6h after feeding. Dry matter intake, body weight, and apparent total-tract digestibility of nutrients were not affected by yeast feeding. Strain 2 decreased the average daily minimum (5.35 vs. 5.65 or 5.66), mean (5.98 vs. 6.24 or 6.34), and maximum ruminal pH (6.71 vs. 6.86 or 6.86), and prolonged the time that ruminal pH was below 5.8 (7.5 vs. 3.3 or 1.0 h/d) compared with the control or strain 1, respectively. The molar percentage of acetate was lower and that of propionate was greater in the ruminal fluid of cows receiving strain 2 compared with cows receiving no yeast or strain 1. Enteric CH(4) production adjusted for intake of dry matter or gross energy, however, did not differ between either yeast strain compared with the control but it tended to be reduced by 10% when strain 2 was compared with strain 1. The study shows that different strains of S. cerevisiae fed as active dried yeasts vary in their ability to modify the rumen fermentative pattern in nonlactating dairy cows. Because strain 2 tended (when compared with strain 1) to lower CH(4) emissions but increase the risk of acidosis, it may be prudent to further evaluate this strain in cattle fed high-forage diets, for which the risk of acidosis is low but CH(4) emissions are high. PMID:21524535

Chung, Y-H; Walker, N D; McGinn, S M; Beauchemin, K A

2011-05-01

387

Modulation of the cost of pHi regulation during metabolic depression: a (31)P-NMR study in invertebrate (Sipunculus nudus) isolated muscle.  

PubMed

Extracellular acidosis has been demonstrated to play a key role in the process of metabolic depression under long-term environmental stress, exemplified in the marine invertebrate Sipunculus nudus. These findings led to the hypothesis that acid-base regulation is associated with a visible cost depending on the rate and mode of H(+)-equivalent ion exchange. To test this hypothesis, the effects of different ion-transport inhibitors on the rate of pH recovery during hypercapnia, on energy turnover and on steady-state acid-base variables were studied in isolated body wall musculature of the marine worm Sipunculus nudus under control conditions (pHe 7.90) and during steady-state extracellular acidosis (pHe 7.50 or 7.20) by in vivo (31)P-NMR and oxygen consumption analyses. During acute hypercapnia (2 % CO(2)), recovery of pHi was delayed at pHe 7.5 compared with pHe 7.9. Inhibition of the Na(+)/H(+)-exchanger by 5-(N,N-dimethyl)-amiloride (DMA) at pHe 7.5 delayed recovery even further. This effect was much smaller at pHe 7.9. Inhibition of anion exchange by the addition of the transport inhibitor 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) prevented pH recovery at pHe 7.5 and delayed recovery at pHe 7.9, in accordance with an effect on Na(+)-dependent Cl(-)/HCO(3)(-) exchange. The effects of ouabain, DIDS and DMA on metabolic rate were reduced at low pHe, thereby supporting the conclusion that acidosis caused the ATP demand of Na(+)/K(+)-ATPase to fall. This reduction occurred via an inhibiting effect on both Na(+)/H(+)- and Na(+)-dependent Cl(-)/HCO(3)(-) (i.e. Na(+)/H(+)/Cl(-)/HCO(3)(-)) exchange in accordance with a reduction in the ATP demand for acid-base regulation during metabolic depression. Considering the ATP stoichiometries of the two exchangers, metabolic depression may be supported by the predominant use of Na(+)/H(+)/Cl(-)/HCO(3)(-) exchange under conditions of extracellular acidosis. PMID:10903156

Pörtner, H O; Bock, C; Reipschläger, A

2000-08-01

388

Cytoadherence in paediatric malaria: ABO blood group, CD36, and ICAM1 expression and severe Plasmodium falciparum infection.  

PubMed

As a leading cause of childhood mortality worldwide, selection pressure by Plasmodium falciparum continues to shape the human genome. Severe disturbances within the microcirculation result from the adhesion of infected erythrocytes to host receptors on monocytes, platelets, and endothelium. In this prospective study, we compared expression of all major host cytoadhesion receptors among Ugandan children presenting with uncomplicated malaria (n = 1078) versus children with severe malaria (n = 855), including cerebral malaria (n = 174), severe anaemia (n = 522), and lactic acidosis (n = 154). We report a significant survival advantage attributed to blood group O and increased monocyte expression of CD36 and ICAM1 (CD54). The high case fatality rate syndromes of cerebral malaria and lactic acidosis were associated with high platelet CD36 expression and thrombocytopenia, and severe malaria anaemia was characterized by low ICAM1 expression. In a logistic regression model of disease severity, odds ratios for the mitigating effects of blood group O, CD36, and ICAM1 phenotypes were greater than that of sickle haemoglobin. Host genetic adaptations to Plasmodium falciparum suggest new potential malaria treatment strategies. PMID:22909232

Cserti-Gazdewich, Christine M; Dhabangi, Aggrey; Musoke, Charles; Ssewanyana, Isaac; Ddungu, Henry; Nakiboneka-Ssenabulya, Deborah; Nabukeera-Barungi, Nicolette; Mpimbaza, Arthur; Dzik, Walter H

2012-10-01

389

Persistence of acidosis in alloxan-induced diabetic rats treated with the juice of Asystasia gangetica leaves  

PubMed Central

Background: Diabetes mellitus is gradually becoming a global health burden leading to an increase in the search for herbal hypoglycemic agents as alternatives to synthetic ones. Asystasia gangetica is one of the herbs used in folklore system of medicine for managing hypoglycaemia associated with diabetes. Materials and Methods: The influence of the juice of A. gangetica leaf on alloxan-induced diabetic rats was assessed by treating diabetic rats with 25%, 50% and 75% fresh juice and glibenclamide for 5 weeks. Afterwards, the plasma concentrations of glucose, triacylglycerols, total cholesterol, high-density lipoprotein (HDL) cholesterol, thiobarbituric acid reactive substances and bicarbonate were assayed spectrophotometrically. Results: Treatment of the diabetic rats with the juice significantly (P < 0.05) reduced the elevated plasma levels of glucose to a level not significantly (P > 0.05) different from that of glibenclamide. The juice also significantly (P < 0.05) reduced the plasma lipid peroxidation and improved the lipid profile, as indicated by a significant (P < 0.05) reduction in the total cholesterol: HDL cholesterol ratio. However, there was a significant (P < 0.05) rise in the level of bicarbonate as result of the juice treatment from 28.15 ± 2.82 mmol/l in normal control to 60.83 ± 17.46 mmol/l in diabetic control and to 122.20 ± 34.68 mmol/l, 120.95 ± 35.09 mmol/l and 115.85 ± 11.79 mmol/l in 25%, 50% and 75% juice, respectively. Conclusion: Therefore, this inability of A. gangetica to prevent acidosis detracts from the potential of its usefulness in managing diabetes. PMID:21472075

Rotimi, Solomon O.; Omotosho, Omolola E.; Rotimi, Oluwakemi A.

2011-01-01

390

Acid-base metabolism: implications for kidney stones formation.  

PubMed

The physiology and pathophysiology of renal H+ ion excretion and urinary buffer systems are reviewed. The main focus is on the two major conditions related to acid-base metabolism that cause kidney stone formation, i.e., distal renal tubular acidosis (dRTA) and abnormally low urine pH with subsequent uric acid stone formation. Both the entities can be seen on the background of disturbances of the major urinary buffer system, NH3+ <--> NH4+. On the one hand, reduced distal tubular secretion of H+ ions results in an abnormally high urinary pH and either incomplete or complete dRTA. On the other hand, reduced production/availability of NH4+ is the cause of an abnormally low urinary pH, which predisposes to uric acid stone formation. Most recent research indicates that the latter abnormality may be a renal manifestation of the increasingly prevalent metabolic syndrome. Despite opposite deviations from normal urinary pH values, both the dRTA and uric acid stone formation due to low urinary pH require the same treatment, i.e., alkali. In the dRTA, alkali is needed for improving the body's buffer capacity, whereas the goal of alkali treatment in uric acid stone formers is to increase the urinary pH to 6.2-6.8 in order to minimize uric acid crystallization. PMID:16411127

Hess, Bernhard

2006-04-01

391

Acid-base regulation, metabolism and energetics in sipunculus nudus as a function of ambient carbon dioxide level  

PubMed

Changes in the rates of oxygen consumption and ammonium excretion, in intra- and extracellular acid-base status and in the rate of H+-equivalent ion transfer between animals and ambient water were measured during environmental hypercapnia in the peanut worm Sipunculus nudus. During exposure to 1 % CO2 in air, intracellular and coelomic plasma PCO2 values rose to levels above those expected from the increase in ambient CO2 tension. Simultaneously, coelomic plasma PO2 was reduced below control values. The rise in PCO2 also induced a fall in intra- and extracellular pH, but intracellular pH was rapidly and completely restored. This was achieved during the early period of hypercapnia at the expense of a non-respiratory increase in the extracellular acidosis. The pH of the extracellular space was only partially compensated (by 37 %) during long-term hypercapnia. The net release of basic equivalents under control conditions turned to a net release of protons to the ambient water before a net, albeit reduced, rate of base release was re-established after a new steady state had been achieved with respect to acid-base parameters. Hypercapnia also affected the mode and rate of metabolism. It caused the rate of oxygen consumption to fall, whereas the rate of ammonium excretion remained constant or even increased, reflecting a reduction of the O/N ratio in both cases. The transient intracellular acidosis preceded a depletion of the phosphagen phospho-l-arginine, an accumulation of free ADP and a decrease in the level of Gibbs free energy change of ATP hydrolysis, before replenishment of phosphagen and restoration of pHi and energy status occurred in parallel. In conclusion, long-term hypercapnia in vivo causes metabolic depression, a parallel shift in acid-base status and increased gas partial pressure gradients, which are related to a reduction in ventilatory activity. The steady-state rise in H+-equivalent ion transfer to the environment reflects an increased rate of production of protons by metabolism. This observation and the reduction of the O/N ratio suggest that a shift to protein/amino acid catabolism has taken place. Metabolic depression prevails, with completely compensated intracellular acidosis during long-term hypercapnia eliminating intracellular pH as a significant factor in the regulation of metabolic rate in vivo. Fluctuating levels of the phosphagen, of free ADP and in the ATP free energy change values independent of pH are interpreted as being correlated with oscillating ATP turnover rates during early hypercapnia and as reflecting a tight coupling of ATP turnover and energy status via the level of free ADP. PMID:9390935

PORtner; ReipschlAGerY; n

1998-01-01

392

Gut blood flow in fish during exercise and severe hypercapnia.  

PubMed

This paper reviews the effects of exercise and hypercapnia on blood flow to the splanchnic circulation. Brief struggling behaviours are known to decrease blood flow to the gut (GBF). Likewise, prolonged swimming in unfed fish has been shown to reduce GBF in proportion to the increased oxygen uptake. Therefore, the normal postprandial increase in GBF theoretically should be impaired whenever fish are active. However, indirect evidence suggests that GBF is spared to some degree when fed fish swim continuously but at a cost (10-15%) to their critical swimming speed. Severe respiratory acidosis can be created by the new intensive aquaculture settings that use oxygen injection into re-circulated water. The only study so far to examine the effects of severe hypercapnia on GBF and its regulation showed that routine GBF and alpha-adrenergic control of GBF remained normal in unfed white sturgeon (Acipenser transmontanus). However, severe hypercapnia produced a hyperactive state and increased sensitivity of GBF to struggling. As a result, routine GBF was maintained for a short period of time. Thus, environmental changes such as severe hypercapnia can indirectly impact GBF through altered struggling behaviour, but the implications of the overall reduction in GBF to food assimilation have yet to be established. PMID:11246044

Farrell, A P; Thorarensen, H; Axelsson, M; Crocker, C E; Gamperl, A K; Cech, J J

2001-03-01

393

Cytoprotective effects of acidosis via heat shock protein HSP27 against the anticancer drug doxorubicin.  

PubMed

Drug resistance continues to be a stumbling block in achieving better cure rates in several cancers. Doxorubicin is commonly used in treatment of a wide range of cancers. The aim of this study was to look into the mechanisms of how low ambient pH may contribute to down-regulation of apoptotic pathways in a gastric tumour cell line. Low pH culture conditions were found to dramatically prolong cell survival after doxorubicin treatment, an effect that was in part reversed by co-incubation with the specific p38 mitoge-activated protein kinase (MAP kinase) inhibitor SB203580, only mildly inhibited by blockade of the multi-drug resistance 1 (MDR1) transporter, but completely abolished by siRNA-mediated knockdown of the heat shock protein 27 (HSP27). In conclusion, acidic pH causes less accumulation of cytotoxic drug in the nucleus of adeno gastric carcinoma (AGS) cells and HSP27-dependent decrease in FasR-mediated gastric epithelial tumour cell apoptosis. PMID:20730553

Singh, Anurag Kumar; Manns, Michael P; Seidler, Ursula

2011-03-01

394

Estimation of the true incidence of lactic acidosis within the Lighthouse Clinic cohort, and the likely magnitude of missed diagnoses in the region  

PubMed Central

Introduction Lactic acidosis is one of the most serious side effects associated with ART, most commonly associated with stavudine. Clinical features are non-specific and specialist laboratory capabilities are essential to confirm the diagnosis, making under-diagnosis likely in resource-constrained settings. Lighthouse Trust is a tertiary referral ART centre with over 23,500 patients on ART. The adjacent University of North Carolina Project laboratory, also serving Kamuzu Central Hospital, has been the only site processing lactate tests in Central Zone for many years. Our objective was to quantify the true incidence within our cohort, and estimate the likely degree of historical missed diagnoses from less central ART clinics. Methods All high lactate results between June 2010 and June 2013 were treated as cases, and cross referenced with the Lighthouse database. Patients transferring in to Lighthouse within one month prior to diagnosis were assumed to have been referred due to their lactic acidosis, and moved to the Central Zone cohort to avoid referral bias. Routinely collected quarterly ART cohort data for both Lighthouse and the entire Central Zone were analyzed. Results Over the three-year period, from within the Lighthouse cohort, there were 138 cases: 74% were female, median duration on ART was 14 months (IQR 10–26), and 98.5% were attributable to stavudine (only two cases to zidovudine). Over this period, the average number of patients taking stavudine at Lighthouse was 10,960 (3,600 on zidovudine). For the whole Central Zone (minus Lighthouse patients) there were 61,000 on stavudine (4,830 on zidovudine), yet only 124 cases of lactic acidosis were apparently diagnosed from within this cohort. Conclusions Although cases may, of course, also have been missed at Lighthouse, as a tertiary referral centre the rate observed is likely to be closer to the true incidence. Over the three years, with 138 cases from the 10,960 patients taking stavudine at Lighthouse, it is likely that somewhere in the region of 700 additional cases occurred amongst the 61,000 patients elsewhere in the Central Zone. This equates to somewhere in the region of 550 missed diagnoses or 80% of all cases. Given that the clinical sequelae of undiagnosed lactic acidosis are either death or at best ART default, this provides further vindication for the decision to phase out stavudine in Malawi. PMID:25394065

Speight, Colin; Gabriel, Layout; Phiri, Sam; Tweya, Hannock; Sutherland, Rebecca

2014-01-01

395

Severe scoliosis in a patient with severe methylenetetrahydrofolate reductase deficiency.  

PubMed

Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessively inherited inborn error of folate metabolism. We report a new patient with severe MTHFR deficiency who presented at age 4months with early onset severe scoliosis associated with severe hypotonia. Markedly decreased MTHFR enzyme activity (0.3nmoles CHO/mg protein/h; reference range>9) and compound heterozygous mutations (c. 1304T>C; p.Phe435Ser and c.1539dup; p.Glu514Argfs?24) in the MTHFR gene confirmed the diagnosis. She was treated with vitamin B12, folic acid and betaine supplementation and showed improvements in her developmental milestones and hypotonia. To the best of our knowledge, this is the first patient with MTHFR deficiency reported with severe early onset scoliosis. Despite the late diagnosis and treatment initiation, she showed favorable short-term neurodevelopmental outcome. This case suggests that homocysteine measurement should be included in the investigations of patients with developmental delay, hypotonia and scoliosis within first year of life prior to organizing genetic investigations. PMID:24726568

Munoz, Tatiana; Patel, Jinesh; Badilla-Porras, Ramses; Kronick, Jonathan; Mercimek-Mahmutoglu, Saadet

2015-01-01

396

Insights into acidosis-induced regulation of SLC26A4 (pendrin) and SLC4A9 (AE4) transporters using three-dimensional morphometric analysis of ?-intercalated cells.  

PubMed

The purpose of this study was to examine the three-dimensional (3-D) expression and distribution of anion transporters pendrin (SLC26A4) and anion exchanger (AE)4 (SLC4A9) in ?-intercalated cells (?-ICs) of the rabbit cortical collecting duct (CCD) to better characterize the adaptation to acid-base disturbances. Confocal analysis and 3-D reconstruction of ?-ICs, using identifiers of the nucleus and zona occludens, permitted the specific orientation of cells from normal, acidotic, and recovering rabbits, so that adaptive changes could be quantified and compared. The pendrin cap likely mediates apical Cl(-)/HCO3 (-) exchange, but it was also found beneath the zona occludens and in early endosomes, some of which may recycle back to the apical membrane via Rab11a(+) vesicles. Acidosis reduced the size of the pendrin cap, observed as a large decrease in cap volume above and below the zona occludens, and the volume of the Rab11a(+) apical recycling compartment. Correction of the acidosis over 12-18 h reversed these changes. Consistent with its proposed function in the basolateral exit of Na(+) via Na(+)-HCO3 (-) cotransport, AE4 was expressed as a barrel-like structure in the lateral membrane of ?-ICs. Acidosis reduced AE4 expression in ?-ICs, but this was rapidly reversed during the recovery from acidosis. The coordinate regulation of pendrin and AE4 during acidosis and recovery is likely to affect the magnitude of acid-base and possibly Na(+) transport across the CCD. In conclusion, acidosis induces a downregulation of AE expression in ?-ICs and a diminished pr