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1

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

2

Metabolic acidosis  

MedlinePLUS

... diabetes Hyperchloremic acidosis: Results from excessive loss of sodium bicarbonate from the body. This can occur with severe ... aimed at the underlying condition. In some cases, sodium bicarbonate (the chemical in baking soda) may be given ...

3

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

4

Persistent metabolic acidosis and severe diarrhoea due to Artemisia absinthium poisoning.  

PubMed

Herbs have long been used in the treatment of various disorders in traditional medicine since ancient age. Artemisia absinthium, one of these herbs, has traditionally been used in different societies for antibiotic, antiparasitic, antifungal and antipyretic purposes. Here, we report a poisoning case of a 10-month-old male infant progressing with severe diarrhoea and persistent metabolic acidosis after ingesting home-prepared Artemisia absinthium extract which was given for the treatment of common cold. PMID:25823193

Kocaoglu, Celebi; Ozel, Ahmet

2014-09-01

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

Metabolic acidosis in maintenance dialysis patients: Clinical considerations  

Microsoft Academic Search

Metabolic acidosis in maintenance dialysis patients: Clinical considerations. Metabolic acidosis is a common consequence of advanced chronic renal failure (CRF) and maintenance dialysis (MD) therapies are not infrequently unable to completely correct the base deficit. In MD patients, severe metabolic acidosis is associated with an increased relative risk for death. The chronic metabolic acidosis of the severity commonly encountered in

RAJNISH MEHROTRA; Joel D. Kopple; MARSHA WOLFSON

2003-01-01

7

Activation of Intrarenal Renin-Angiotensin System during Metabolic Acidosis  

Microsoft Academic Search

Background: Chronic metabolic acidosis is a common metabolic disturbance and its clinical impact can be severe and extensive. The role and the change of the intrarenal renin-angiotensin system (RAS) during metabolic acidosis are uncertain, and whether acidosis can evoke inflammation remains unclear. Methods: Male Sprague-Dawley rats were fed with water containing 0.14 M NH4Cl to induce metabolic acidosis for 1

Hwee-Yeong Ng; Hung-Chun Chen; Yu-Che Tsai; Yu-Kun Yang; Chien-Te Lee

2011-01-01

8

[Non-lactic metabolic acidosis].  

PubMed

The definition of metabolic acidosis (MA) is a primary decrease in plasma bicarbonate concentration. The visceral consequences are largely dependent on the degree of acidosis and the rapidity of its onset; they have been studied mainly in animal studies and therefore, extrapolation to the clinical situation should be cautious. The MA can be classified in two groups according to whether the anionic serum gap is increased or normal (hyperchloremic acidosis). The etiologies of the first group are lactic acidosis, the cetoacidoses and renal failure. The hyperchloremic acidoses usually result from gastro-intestinal bicarbonate losses; the biochemical diagnosis of rarer causes of hyperchloremic acidosis is facilitated by measuring the serum potassium, urinary pH and the urinary anionic gap. Although all causes of MA must be treated, the use of bicarbonate should be discussed in each individual case. PMID:2237201

Offenstadt, G; Guidet, B; Staikowsky, F

1990-10-01

9

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

10

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

11

Metabolic acidosis: pathophysiology, diagnosis and management  

Microsoft Academic Search

Metabolic acidosis is characterized by a primary reduction in serum bicarbonate (HCO3?) concentration, a secondary decrease in the arterial partial pressure of carbon dioxide (PaCO2) of ?1 mmHg for every 1 mmol\\/l fall in serum HCO3? concentration, and a reduction in blood pH. Acute forms (lasting minutes to several days) and chronic forms (lasting weeks to years) of the disorder

Jeffrey A. Kraut; Nicolaos E. Madias

2010-01-01

12

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

13

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

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

2015-02-01

14

Use of anion gap in the evaluation of a patient with metabolic acidosis.  

PubMed

High anion gap (AG) metabolic acidosis, a common laboratory abnormality encountered in clinical practice, frequently is due to accumulation of organic acids such as lactic acid, keto acids, alcohol metabolites, and reduced kidney function. The cause of high AG metabolic acidosis often is established easily using historical and simple laboratory data. Despite this, several challenges in the diagnosis and management of high AG metabolic acidosis remain, including quantifying the increase in AG, understanding the relationship between changes in AG and serum bicarbonate level, and identifying the cause of high AG metabolic acidosis when common causes are ruled out. The present case was selected to highlight the importance of the correction of AG for serum albumin level, the use of actual baseline AG rather than mean normal AG, the relationship between changes in serum bicarbonate level and AG, and a systematic diagnostic approach to uncommon causes of high AG metabolic acidosis, such as 5-oxoproline acidosis (pyroglutamic acidosis). PMID:25132207

Vichot, Alfred A; Rastegar, Asghar

2014-10-01

15

Reported survival with severe mixed acidosis and hyperlactemia after toluene poisoning  

PubMed Central

Lactic acidosis is a recognized complication of the inhalant abuse such as toluene, especially in patients with renal insufficiency. We report a case of severe metabolic acidosis and hyperlactemia due to toluene sniffing. The favorable outcome, despite extremely poor clinical symptoms, signs, laboratory and radiological findings, was unexpected. Specific aspects of the clinical course are addressed. Toluene sniffing should be considered in evaluating sever metabolic acidosis. Favorable outcome could be achieved with early diagnosis and proper interventions. PMID:21655021

Omar, Amr S.; Rahman, Masood ur; Abuhasna, Said

2011-01-01

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

Propofol Infusion Associated Metabolic Acidosis in Patients Undergoing Neurosurgical Anesthesia: A Retrospective Study  

PubMed Central

Objective Propofol and volatile anesthesia have been associated with metabolic acidosis induced by increased lactate. This study was designed to evaluate changes in pH, base excess (BE), and lactate in response to different anesthetic agents and to characterize propofol infusion-associated lactic acidosis. Methods The medical records of patients undergoing neurosurgical anesthesia between January 2005 and September 2012 were examined. Patients were divided into 2 groups : those who received propofol (total intravenous anesthesia, TIVA) and those who received sevoflurane (balanced inhalation anesthesia, BIA) anesthesia. Propensity analysis was performed (1 : 1 match, n=47), and the characteristics of the patients who developed severe acidosis were recorded. Results In the matched TIVA and BIA groups, the incidence of metabolic acidosis (11% vs. 13%, p=1) and base excess (p>0.05) were similar. All patients in the TIVA group who developed severe acidosis did so within 4 hours of the initiation of propofol infusion, and these patients improved when propofol was discontinued. Conclusions The incidence of metabolic acidosis was similar during neurosurgical anesthesia with propofol or sevoflurane. In addition, severe acidosis associated with propofol infusion appears to be reversible when propofol is discontinued. PMID:25328651

Choi, Yoon Ji; Kim, Min Chul; Lim, Young Jin; Yoon, Suk Min; Yoon, Hei Ryeo

2014-01-01

18

Acidosis  

MedlinePLUS

... Respiratory acidosis develops when there is too much carbon dioxide (an acid) in the body. This type of ... when the body is unable to remove enough carbon dioxide through breathing. Other names for respiratory acidosis are ...

19

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

2015-01-01

20

Metabolic acidosis-induced hypercalcemia in an azotemic patient with primary hyperparathyroidism  

PubMed Central

A 58-year-old man with Stage 3b chronic kidney disease and primary hyperparathyroidism treated with cinacalcet was admitted for acute cholecystitis. A cholecystostomy tube was placed, estimated glomerular filtration rate decreased, metabolic acidosis developed and ionized calcium increased from 1.33 to 1.76 mM despite cinacalcet administration. A sodium bicarbonate infusion corrected the metabolic acidosis restoring ionized calcium to normal despite no improvement in renal function. The correlation between the increase in serum bicarbonate and decrease in ionized calcium was r = ?0.93, P < 0.001. In summary, severe hypercalcemia was attributable to metabolic acidosis increasing calcium efflux from bone while renal failure decreased the capacity to excrete calcium.

Rastegar, Mandana; Levine, Barton S.; Felsenfeld, Arnold J.

2014-01-01

21

Glutamine Transport in Rat Kidney Mitochondria in Metabolic Acidosis  

PubMed Central

In order to study factors regulating renal ammoniagenesis, the transport and metabolism of L-glutamine were studied in mitochondria from kidneys of control and acidotic rats. On incubation in 1 mM [14C]glutamine, there was production and accumulation of [14C]glutamate within the matrix space. However no [14C]glutamine was detected in the matrix space, even with 10 mM [14C]glutamine as substrate or with inhibition of glutamine deamidation (low temperature, p-chloromercuribenzoate, mersalyl). These results suggest that glutamine crosses the inner membrane by a carrier-mediated step and that this step is rate-limiting in glutamine deamidation. In chronic acidosis there is a fourfold increase in the uptake of radioactivity from [14C]glutamine, but not from ?-ketoglutarate, glutamate, or acetate. In 3-h acidosis, before any increase in extracted glutaminase levels, there is a significant and reproducible increase (39±3.8%, n = 25) in matrix uptake of radioactivity from [14C]glutamine and also an increased ammonia production (17±3.7%, n = 12). Administration of furosemide produces a similar degree of potassium depletion and a greater degree of sodium depletion over 3 h when compared to a 3-h acidosis. However, it produces no change in mitochondrial uptake of radioactivity. These results show that the adaptation of renal glutamine metabolism observed in acidosis is due to the acidosis and is demonstrable in isolated rat kidney mitochondria. The site of adaptation is in the carrier system, which transports glutamine across the inner membrane. The increased transport in acidosis delivers more glutamine to glutaminase, which results in the increased renal ammonia production. PMID:4834886

Adam, William; Simpson, David P.

1974-01-01

22

Autophagic clearance of mitochondria in the kidney copes with metabolic acidosis.  

PubMed

Metabolic acidosis, a common complication of CKD, causes mitochondrial stress by undefined mechanisms. Selective autophagy of impaired mitochondria, called mitophagy, contributes toward maintaining cellular homeostasis in various settings. We hypothesized that mitophagy is involved in proximal tubular cell adaptations to chronic metabolic acidosis. In transgenic mice expressing green fluorescent protein-tagged microtubule-associated protein 1 light chain 3 (GFP-LC3), NH4Cl loading increased the number of GFP puncta exclusively in the proximal tubule. In vitro, culture in acidic medium produced similar results in proximal tubular cell lines stably expressing GFP-LC3 and facilitated the degradation of SQSTM1/p62 in wild-type cells, indicating enhanced autophagic flux. Upon acid loading, proximal tubule-specific autophagy-deficient (Atg5-deficient) mice displayed significantly reduced ammonium production and severe metabolic acidosis compared with wild-type mice. In vitro and in vivo, acid loading caused Atg5-deficient proximal tubular cells to exhibit reduced mitochondrial respiratory chain activity, reduced mitochondrial membrane potential, and fragmented morphology with marked swelling in mitochondria. GFP-LC3-tagged autophagosomes colocalized with ubiquitinated mitochondria in proximal tubular cells cultured in acidic medium, suggesting that metabolic acidosis induces mitophagy. Furthermore, restoration of Atg5-intact nuclei in Atg5-deficient proximal tubular cells increased mitochondrial membrane potential and ammoniagenesis. In conclusion, metabolic acidosis induces autophagy in proximal tubular cells, which is indispensable for maintaining proper mitochondrial functions including ammoniagenesis, and thus for adapted urinary acid excretion. Our results provide a rationale for the beneficial effect of alkali supplementation in CKD, a condition in which autophagy may be reduced, and suggest a new therapeutic option for acidosis by modulating autophagy. PMID:24700866

Namba, Tomoko; Takabatake, Yoshitsugu; Kimura, Tomonori; Takahashi, Atsushi; Yamamoto, Takeshi; Matsuda, Jun; Kitamura, Harumi; Niimura, Fumio; Matsusaka, Taiji; Iwatani, Hirotsugu; Matsui, Isao; Kaimori, Junya; Kioka, Hidetaka; Isaka, Yoshitaka; Rakugi, Hiromi

2014-10-01

23

Lentiform fork sign: a magnetic resonance finding in a case of acute metabolic acidosis.  

PubMed

We report a 33 year-old woman addicted to chronic unspecified solvents abuse with stupor, respiratory disorders, tetraplegia and severe metabolic acidosis. On admission an unenhanced cranial CT scan showed symmetrical hypodensities of both lentiform nuclei. MR imaging performed 12 hours after stupor demonstrates bilateral putaminal hemorrhagic necrosis, bilateral external capsule, corona radiata and deep cerebellar hyperintensities with right cingulate cortex involvement. DWI reflected bilateral putaminal hyperintensities with restricted water diffusion as to citotoxic edema and development of vasogenic edema in the external capsule recalling a fork. On day twenty, after specific treatments MRI demonstrated a bilateral putaminal marginal enhancement. Bilateral putaminal necrosis is a characteristic but non-specific radiological finding of methanol poisoning. Lentiform Fork sign is a rare MRI finding reported in literature in 22 patients with various conditions characterized by metabolic acidosis. Vasogenic edema may be due to the differences in metabolic vulnerability between neurons and astrocytes. We postulate that metabolic acidosis could have an important role to generate this sign. PMID:24976195

Grasso, Daniela; Borreggine, Carmela; Perfetto, Francesco; Bertozzi, Vincenzo; Trivisano, Marina; Specchio, Luigi Maria; Grilli, Gianpaolo; Macarini, Luca

2014-06-01

24

Metabolic acidosis improves airway conductance in patients with asthma.  

PubMed

The objective was to investigate whether acute metabolic acidosis could cause bronchodilation in patients with asthma. Twelve patients with asthma (8 females, mean age 39 (+/- SD 12) years, forced expiratory volume in 1 second [FEV(1)] 93 [+/-9] % predicted, PC(20) 1.9 (+/-1.0) mg/mL) participated in a double-blind, placebo-controlled trial. Subjects ingested calculated amounts of ammonium chloride to induce acidosis or saline as placebo, in random order, each on a separate day. Airway resistance (R(aw)), specific airway conductance (sG(aw)), FEV(1), and PEF were measured as primary variables. To evaluate the consequences of alterations in bronchial contractility on the airway responsiveness, the histamine provocation test (PC(20)) was measured as secondary variable. The intervention resulted in a mean (SD) decrease in base excess from -0.5 (+/-1.4) to -3.9 (+/-1.1) mmol/L (p < 0.01) and a decrease in pH from 7.41 (+/-0.02) to 7.36 (+/-0.02) (p < 0.01). This caused a statistically significant increase in sG(aw) from 1.15 (+/-0.16) to 1.26 (+/-0.13) 1/kPa.s) (p < 0.05). Tendencies towards increase were found in PEF (7.79 (+/-2.2) versus 8.09 (+/-1.9) (NS, p = 0.10) and in FEV(1) (2.98 (+/-0.9) versus 3.06 (+/-0.9) (NS, p = 0.15). PC(20) did not change significantly. It was concluded that acute metabolic acidosis has a modest bronchodilating effect in patients with asthma. PMID:19728200

Brijker, F; van den Elshout, F J J; Bosch, F H; Heijdra, Y F; Folgering, H Th M

2009-09-01

25

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.

26

Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured ions  

Microsoft Academic Search

INTRODUCTION: Metabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis. METHODS: Eleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120

Dirk Bruegger; Gregor I Kemming; Matthias Jacob; Franz G Meisner; Christoph J Wojtczyk; Kristian B Packert; Peter E Keipert; N Simon Faithfull; Oliver P Habler; Bernhard F Becker; Markus Rehm

2007-01-01

27

Treatment of Metabolic Acidosis in Patients With CKD  

PubMed Central

Metabolic acidosis is a common complication of chronic kidney disease and believed to contribute to a number of sequelae, including bone disease, altered protein metabolism, skeletal muscle wasting, and progressive GFR loss. Small trials in animal models and humans suggest a role for alkali therapy to lessen these complications. Recent studies support this notion, although more definitive evidence is needed on the long-term benefits of alkali therapy and the optimal serum bicarbonate level. The role of dietary modification should also be given greater consideration. In addition, potential adverse effects of alkali treatment must be taken into consideration, including sodium retention and the theoretical concern of promoting vascular calcification. This teaching case summarizes the rationale for and the benefits and complications of base therapy in patients with chronic kidney disease. PMID:23932089

Chen, Wei; Abramowitz, Matthew K.

2013-01-01

28

The role of adenosine in rat coronary flow regulation during respiratory and metabolic acidosis  

Microsoft Academic Search

The role of adenosine in rat coronary flow regulation during acidosis was evaluated in isolated, perfused, Langendorff rat heart preparations exposed to brief periods of hypercapnic or metabolic acidosis. Acidosis resulted in increases in coronary flow rate, in conjunction with decreases in ventricular contractile tensions. Heart rates were non-significantly increased. Two non-selective adenosine antagonists, caffeine and 8-phenyltheophylline, markedly attenuated the

John W. Phillis; Dekun Song; Michael H. O'Regan

1998-01-01

29

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

30

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

PubMed

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 fractional delivery of sodium and calcium to the distal tubule, but not to the final urine. In comparison with normal dogs, dogs with chronic metabolic acidosis (induced by feeding ammonium chloride) showed an increase in proximal fluid reabsorption and a dissociation of calcium from sodium reabsorption more distally, leading to an increased delivery of calcium relative to sodium at the distal tubule and in the final urine. The infusion of sodium bicarbonate to correct chronic metabolic acidosis, both in intact and thyroparathyroidectomized (TPTX) dogs, reduced proximal fluid reabsorption and caused a selective enhancement of calcium reabsorption relative to sodium in the more distal nephron, resulting in a reversal of the dissociation observed in acidosis, both at the distal tubule and in the final urine. By contrastin fusion of sodium chloride in parathyroid-intact acidotic dogs did not reduce proximal fluid reabsorption or enhance tubular calcium reabsorption. In nonacidotic dogs, both intact and TPTX, infusion of sodium bicarconate to induce acute alkalosis resulted in selhese data demonstrate the presence of a component of tubular calcium reabsorption situated beyond the proximal tubule, which is inhibited by chronic (but not acute) metabolic acidosis and enhanced by metabolic alkalosis (or bicarbonate infusion) independently of parathyroid hormone. PMID:480784

Sutton, R A; Wong, N L; Dirks, J H

1979-05-01

31

Comparison of the alkalizing effects of bicarbonate precursors in calves with experimentally induced metabolic acidosis.  

PubMed

The aims of this study were to confirm whether commercial acetated Ringer's solution, which contains 28 mM of sodium acetate, is superior to commercial lactated Ringer's solution in alkalizing effects in calves with experimentally induced metabolic acidosis. Twenty calves with experimentally induced mild acidosis were intravenously administered isotonic saline, DL-lactated, L-lactated or acetated Ringer's solution at a dose of 80 ml/kg body weight (BW). The acetated Ringer's solution induced a significantly greater increase in venous HCO(3)(-) and base excess concentrations than the other fluids during the early phases of extracellular fluid replacement in mild metabolic acidosis. Therefore, the alkalizing effect of commercial acetated Ringer's solution is superior to commercial DL- and L-lactated Ringer's solution in treatment of mild metabolic acidosis in calves. PMID:19578293

Nakagawa, Mitsuhide; Suzuki, Kazuyuki; Takahashi, Fumito; Kamikatano, Kazuhiro; Koiwa, Masateru; Taguchi, Kiyoshi

2009-06-01

32

Differential Diagnosis of Nongap Metabolic Acidosis: Value of a Systematic Approach  

PubMed Central

Summary Nongap metabolic acidosis is a common form of both acute and chronic metabolic acidosis. Because derangements in renal acid-base regulation are a common cause of nongap metabolic acidosis, studies to evaluate renal acidification often serve as the mainstay of differential diagnosis. However, in many cases, information obtained from the history and physical examination, evaluation of the electrolyte pattern (to determine if a nongap acidosis alone or a combined nongap and high anion gap metabolic acidosis is present), and examination of the serum potassium concentration (to characterize the disorder as hyperkalemic or hypokalemic in nature) is sufficient to make a presumptive diagnosis without more sophisticated studies. If this information proves insufficient, indirect estimates or direct measurement of urinary NH4+ concentration, measurement of urine pH, and assessment of urinary HCO3? excretion can help in establishing the diagnosis. This review summarizes current information concerning the pathophysiology of this electrolyte pattern and the value and limitations of all of the diagnostic studies available. It also provides a systematic and cost-effective approach to the differential diagnosis of nongap metabolic acidosis. PMID:22403272

Madias, Nicolaos E.

2012-01-01

33

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

34

Isoniazid toxicity presenting as seizures and metabolic acidosis.  

PubMed Central

The presenting signs and symptoms of isoniazid toxicity are discussed, with a review of the complications and management of this metabolic encephalopathy with B6 pyridoxine. This study supports previous studies in finding that ingestion of more than 80 mg/kg body weight produces severe central nervous system symptoms that are rapidly reversed with intravenous administration of pyridoxine. PMID:2304098

Watkins, R. C.; Hambrick, E. L.; Benjamin, G.; Chavda, S. N.

1990-01-01

35

Infusion of sodium bicarbonate in experimentally induced metabolic acidosis does not provoke cerebrospinal fluid (CSF) acidosis in calves.  

PubMed

In a crossover study, 5 calves were made acidotic by intermittent intravenous infusion of isotonic hydrochloric acid (HCl) over approximately 24 h. This was followed by rapid (4 h) or slow (24 h) correction of blood pH with isotonic sodium bicarbonate (NaHCO(3)) to determine if rapid correction of acidemia produced paradoxical cerebrospinal fluid (CSF) acidosis. Infusion of HCl produced a marked metabolic acidosis with respiratory compensation. Venous blood pH (mean ± S(x)) was 7.362 ± 0.021 and 7.116 ± 0.032, partial pressure of carbon dioxide (Pco(2), torr) 48.8 ± 1.3 and 34.8 ± 1.4, and bicarbonate (mmol/L), 27.2 ± 1.27 and 11 ± 0.96; CSF pH was 7.344 ± 0.031 and 7.240 ± 0.039, Pco(2) 42.8 ± 2.9 and 34.5 ± 1.4, and bicarbonate 23.5 ± 0.91 and 14.2 ± 1.09 for the period before the infusion of hydrochloric acid and immediately before the start of sodium bicarbonate correction, respectively. In calves treated with rapid infusion of sodium bicarbonate, correction of venous acidemia was significantly more rapid and increases in Pco(2) and bicarbonate in CSF were also more rapid. However, there was no significant difference in CSF pH. After 4 h of correction, CSF pH was 7.238 ± 0.040 and 7.256 ± 0.050, Pco(2) 44.4 ± 2.2 and 34.2 ± 2.1, and bicarbonate 17.8 ± 1.02 and 14.6 ± 1.4 for rapid and slow correction, respectively. Under the conditions of this experiment, rapid correction of acidemia did not provoke paradoxical CSF acidosis. PMID:22754090

Abeysekara, Saman; Zello, Gordon A; Lohmann, Katharina L; Alcorn, Jane; Hamilton, Don L; Naylor, Jonathan M

2012-01-01

36

Equivalent metabolic acidosis with four colloids and saline on ex vivo haemodilution.  

PubMed

Colloid infusions can cause metabolic acidosis. Mechanisms and relative severity with different colloids are incompletely understood. We compared haemodilution acid-base effects of 4% albumin, 3.5% polygeline, 4% succinylated gelatin (all weak acid colloids, strong ion difference 12 mEq/l, 17.6 mEq/l and 34 mEq/l respectively), 6% hetastarch (non-weak acid colloid, strong ion difference zero) and 0.9% saline (crystalloid, strong ion difference zero). Gelatin weak acid properties were tracked via the strong ion gap. Four-step ex vivo dilutions of pre-oxygenated human venous blood were performed to a final [Hb] near 50% baseline. With each fluid, base excess fell to approximately -13 mEq/l. Base excess/[Hb] relationships across dilution were linear and direct (R2 > or = 0.96), slopes and intercepts closely resembling saline. Baseline strong ion gap was -0.3 (2.1) mEq/l. Post-dilution increases occurred in three groups: small with saline, hetastarch and albumin (to 3.5 (02) mEq/l, 4.3 (0.3) mEq/l, 3.3 (1.4) mEq/l respectively), intermediate with polygeline (to 12.2 (0.9) mEq/l) and greatest with succinylated gelatin (to 20.8 (1.4) mEq/l). We conclude that, despite colloid weak acid activity ranging from zero (hydroxyethyl starch) to greater than that of albumin with both gelatin preparations, ex vivo dilution causes a metabolic acidosis of identical severity to saline in each case. This uniformity reflects modifications to the albumin and gelatin saline vehicles, in part aimed at pH correction. By proportionally increasing the strong ion difference, these modifications counter deviations from pure saline effects caused by colloid weak acid activity. Extrapolation in vivo requires further investigation. PMID:19499860

Morgan, T J; Vellaichamy, M; Cowley, D M; Weier, S L; Venkatesh, B; Jones, M A

2009-05-01

37

Response of the mitochondrial proteome of rat renal proximal convoluted tubules to chronic metabolic acidosis.  

PubMed

Metabolic acidosis is a common clinical condition that is caused by a decrease in blood pH and bicarbonate concentration. Increased extraction and mitochondrial catabolism of plasma glutamine within the renal proximal convoluted tubule generates ammonium and bicarbonate ions that facilitate the excretion of acid and partially restore acid-base balance. Previous studies identified only a few mitochondrial proteins, including two key enzymes of glutamine metabolism, which are increased during chronic acidosis. A workflow was developed to characterize the mitochondrial proteome of the proximal convoluted tubule. Based upon the increase in specific activity of cytochrome c oxidase, the isolated mitochondria were enriched eightfold. Two-dimensional liquid chromatography coupled with mass spectrometry was utilized to compare mitochondrial-enriched samples from control and chronic acidotic rats. Proteomic analysis identified 901 proteins in the control and acidotic samples. Further analysis identified 37 peptides that contain an N-?-acetyl-lysine; of these, 22 are novel sites. Spectral counting analysis revealed 33 proteins that are significantly altered in abundance in response to chronic metabolic acidosis. Western blot analysis was performed to validate the calculated changes in abundance. Thus the current study represents the first comprehensive analysis of the mitochondrial proteome of the rat renal proximal convoluted tubule and its response to metabolic acidosis. PMID:23136003

Freund, Dana M; Prenni, Jessica E; Curthoys, Norman P

2013-01-15

38

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

39

Successfully Treated Calcific Uremic Arteriolopathy: Two Cases of a High Anion Gap Metabolic Acidosis with Intravenous Sodium Thiosulfate  

PubMed Central

Calcific uremic arteriolopathy (CUA) is a rare and potentially fatal disorder of calcification involving subcutaneous small vessels and fat in patients with renal insufficiency. We describe the successful use of intravenous sodium thiosulfate (STS) for the treatment of CUA in two patients. The first case was complicated by the development of a severe anion gap metabolic acidosis, which was accompanied by a seizure. Both patients had complete wound healing within five months. Although STS should be considered in the treatment of CUA, little is known about pharmacokinetics and additional studies are required to determine dosing strategies to minimize severe potential side effects. PMID:25506005

Rein, Joshua L.; Miyata, Kana N.; Dadzie, Kobena A.; Gruber, Steven J.; Sulica, Roxana; Winchester, James F.

2014-01-01

40

Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer  

PubMed Central

Abstract Maintenance of cellular pH homeostasis is fundamental to life. A number of key intracellular pH (pHi) regulating systems including the Na+/H+ exchangers, the proton pump, the monocarboxylate transporters, the HCO3? transporters and exchangers and the membrane-associated and cytosolic carbonic anhydrases cooperate in maintaining a pHi that is permissive for cell survival. A common feature of tumours is acidosis caused by hypoxia (low oxygen tension). In addition to oncogene activation and transformation, hypoxia is responsible for inducing acidosis through a shift in cellular metabolism that generates a high acid load in the tumour microenvironment. However, hypoxia and oncogene activation also allow cells to adapt to the potentially toxic effects of an excess in acidosis. Hypoxia does so by inducing the activity of a transcription factor the hypoxia-inducible factor (HIF), and particularly HIF-1, that in turn enhances the expression of a number of pHi-regulating systems that cope with acidosis. In this review, we will focus on the characterization and function of some of the hypoxia-inducible pH-regulating systems and their induction by hypoxic stress. It is essential to understand the fundamentals of pH regulation to meet the challenge consisting in targeting tumour metabolism and acidosis as an anti-tumour approach. We will summarize strategies that take advantage of intracellular and extracellular pH regulation to target the primary tumour and metastatic growth, and to turn around resistance to chemotherapy and radiotherapy. PMID:20015196

Chiche, Johanna; Brahimi-Horn, M Christiane; Pouysségur, Jacques

2010-01-01

41

Consequences and therapy of the metabolic acidosis of chronic kidney disease  

Microsoft Academic Search

Metabolic acidosis is common in patients with chronic kidney disease (CKD), particularly once the glomerular filtration rate\\u000a (GFR) falls below 25 ml\\/min\\/1.73 m2. It is usually mild to moderate in magnitude with the serum bicarbonate concentration ([HCO3?]) ranging from 12 to 23 mEq\\/l. Even so, it can have substantial adverse effects, including development or exacerbation of\\u000a bone disease, growth retardation in children, increased

Jeffrey A. Kraut; Nicolaos E. Madias

2011-01-01

42

Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts  

PubMed Central

In vivo, metabolic acidosis {decreased pH from decreased bicarbonate concentration ([HCO3?])} increases urine calcium (Ca) without increased intestinal Ca absorption, resulting in a loss of bone Ca. Conversely, respiratory acidosis [decreased pH from increased partial pressure of carbon dioxide (Pco2)] does not appreciably alter Ca homeostasis. In cultured bone, chronic metabolic acidosis (Met) significantly increases cell-mediated net Ca efflux while isohydric respiratory acidosis (Resp) does not. The proton receptor, OGR1, appears critical for cell-mediated, metabolic acid-induced bone resorption. Perfusion of primary bone cells or OGR1-transfected Chinese hamster ovary (CHO) cells with Met induces transient peaks of intracellular Ca (Cai). To determine whether Resp increases Cai, as does Met, we imaged Cai in primary cultures of bone cells. pH for Met = 7.07 ([HCO3?] = 11.8 mM) and for Resp = 7.13 (Pco2 = 88.4 mmHg) were similar and lower than neutral (7.41). Both Met and Resp induced a marked, transient increase in Cai in individual bone cells; however, Met stimulated Cai to a greater extent than Resp. We used OGR1-transfected CHO cells to determine whether OGR1 was responsible for the greater increase in Cai in Met than Resp. Both Met and Resp induced a marked, transient increase in Cai in OGR1-transfected CHO cells; however, in these cells Met was not different than Resp. Thus, the greater induction of Cai by Met in primary bone cells is not a function of OGR1 alone, but must involve H+ receptors other than OGR1, or pathways sensitive to Pco2, HCO3?, or total CO2 that modify the effect of H+ in primary bone cells. PMID:20504884

Bushinsky, David A.

2010-01-01

43

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

44

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

PubMed

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. PMID:25610283

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

2013-10-01

45

Distal renal tubular acidosis associated with Sjogren syndrome.  

PubMed

Renal tubular acidosis is a common cause of normal anion gap metabolic acidosis but these disorders can be easily missed or misdiagnosed. We highlight the approach to assessing renal tubular acidosis by discussing a case study with a temporal data set collected over more than 5 weeks. We highlight the principles and the necessary information required for a diagnosis of classic distal renal tubular acidosis. We also briefly review several aspects of type 1 renal tubular acidosis related to autoimmune disease, drugs and thyroid disorders. PMID:24330363

Lim, A K H; Choi, M J

2013-12-01

46

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

47

Neuronal expression of sodium/bicarbonate cotransporter NBCn1 (SLC4A7) and its response to chronic metabolic acidosis  

PubMed Central

The sodium-bicarbonate cotransporter NBCn1 (SLC4A7) is an acid-base transporter that normally moves Na+ and HCO3? into the cell. This membrane protein is sensitive to cellular and systemic pH changes. We examined NBCn1 expression and localization in the brain and its response to chronic metabolic acidosis. Two new NBCn1 antibodies were generated by immunizing a rabbit and a guinea pig. The antibodies stained neurons in a variety of rat brain regions, including hippocampal pyramidal neurons, dentate gyrus granular neurons, posterior cortical neurons, and cerebellar Purkinje neurons. Choroid plexus epithelia were also stained. Double immunofluorescence labeling showed that NBCn1 and the postsynaptic density protein PSD-95 were found in the same hippocampal CA3 neurons and partially colocalized in dendrites. PSD-95 was pulled down from rat brain lysates with the GST/NBCn1 fusion protein and was also coimmunoprecipitated with NBCn1. Chronic metabolic acidosis was induced by feeding rats with normal chow or 0.4 M HCl-containing chow for 7 days. Real-time PCR and immunoblot showed upregulation of NBCn1 mRNA and protein in the hippocampus of acidotic rats. NBCn1 immunostaining was enhanced in CA3 neurons, posterior cortical neurons, and cerebellar granular cells. Intraperitoneal administration of N-methyl-d-aspartate caused neuronal death determined by caspase-3 activity, and this effect was more severe in acidotic rats. Administering N-methyl-d-aspartate also inhibited NBCn1 upregulation in acidotic rats. We conclude that NBCn1 in neurons is upregulated by chronic acid loads, and this upregulation is associated with glutamate excitotoxicity. PMID:20147654

Park, Hae Jeong; Rajbhandari, Ira; Yang, Han Soo; Lee, Soojung; Cucoranu, Delia; Cooper, Deborah S.; Klein, Janet D.; Sands, Jeff M.

2010-01-01

48

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

49

The effect of metabolic acidosis on vitamin D metabolites and bone histology in uremic rats.  

PubMed

Biochemical data and skeletal histomorphometric measurements are presented for normal rats and for two groups of rats rendered uremic by partial nephrectomy. In one of these groups chronic acidosis was induced by the oral administration of hydrochloric acid. Uremic animals had higher urine calcium excretion rates and lower serum concentrations of vitamin D metabolites than normal rats. Chronic acid loading of uremic rats resulted in hypercalcemia, elevated serum parathyroid hormone concentrations, and a significant loss of trabecular bone in addition to the above changes. greater osteoclast densities and higher resorption surfaces wee seen in the uremic acidotic animals than in the other two groups. The acidotic uremic state induced more potent changes in calcium metabolism and bone structure than uremia alone. PMID:3924372

Chan, Y L; Savdie, E; Mason, R S; Posen, S

1985-03-01

50

Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured ions  

PubMed Central

Introduction Metabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis. Methods Eleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120 mLO2/kg body weight had evolved. Blood pH, partial pressure of carbon dioxide, and concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured at baseline, in shock, and during 3 hours post-therapy. Strong ion difference and the amount of weak plasma acid were calculated. To detect the presence of unmeasured anions, anion gap and strong ion gap were determined. Capillary electrophoresis was used to identify potential contributors to unmeasured anions. Results During induction of shock, pH decreased significantly from 7.41 to 7.19. The transient increase in lactate concentration from 1.5 to 5.5 mEq/L during shock was not sufficient to explain the transient increases in anion gap (+11.0 mEq/L) and strong ion gap (+7.1 mEq/L), suggesting that substantial amounts of unmeasured anions must have been generated. Capillary electrophoresis revealed increases in serum concentration of acetate (2.2 mEq/L), citrate (2.2 mEq/L), ?-ketoglutarate (35.3 ?Eq/L), fumarate (6.2 ?Eq/L), sulfate (0.1 mEq/L), and urate (55.9 ?Eq/L) after shock induction. Conclusion Large amounts of unmeasured anions were generated after hemorrhage in this highly standardized model of hemorrhagic shock. Capillary electrophoresis suggested that the hitherto unmeasured anions citrate and acetate, but not sulfate, contributed significantly to the changes in strong ion gap associated with induction of shock. PMID:18081930

Bruegger, Dirk; Kemming, Gregor I; Jacob, Matthias; Meisner, Franz G; Wojtczyk, Christoph J; Packert, Kristian B; Keipert, Peter E; Faithfull, N Simon; Habler, Oliver P; Becker, Bernhard F; Rehm, Markus

2007-01-01

51

Clinical utility of standard base excess in the diagnosis and interpretation of metabolic acidosis in critically ill patients.  

PubMed

The aims of this study were to determine whether standard base excess (SBE) is a useful diagnostic tool for metabolic acidosis, whether metabolic acidosis is clinically relevant in daily evaluation of critically ill patients, and to identify the most robust acid-base determinants of SBE. Thirty-one critically ill patients were enrolled. Arterial blood samples were drawn at admission and 24 h later. SBE, as calculated by Van Slyke's (SBE VS) or Wooten's (SBE W) equations, accurately diagnosed metabolic acidosis (AUC = 0.867, 95%CI = 0.690-1.043 and AUC = 0.817, 95%CI = 0.634-0.999, respectively). SBE VS was weakly correlated with total SOFA (r = -0.454, P < 0.001) and was similar to SBE W (r = -0.482, P < 0.001). All acid-base variables were categorized as SBE VS <-2 mEq/L or SBE VS <-5 mEq/L. SBE VS <-2 mEq/L was better able to identify strong ion gap acidosis than SBE VS <-5 mEq/L; there were no significant differences regarding other variables. To demonstrate unmeasured anions, anion gap (AG) corrected for albumin (AG A) was superior to AG corrected for albumin and phosphate (AG A+P) when strong ion gap was used as the standard method. Mathematical modeling showed that albumin level, apparent strong ion difference, AG A, and lactate concentration explained SBE VS variations with an R(2) = 0.954. SBE VS with a cut-off value of <-2 mEq/L was the best tool to diagnose clinically relevant metabolic acidosis. To analyze the components of SBE VS shifts at the bedside, AG A, apparent strong ion difference, albumin level, and lactate concentration are easily measurable variables that best represent the partitioning of acid-base derangements. PMID:18097497

Park, M; Taniguchi, L U; Noritomi, D T; Libório, A B; Braga, A L; Maciel, A T; Cruz-Neto, L M

2008-03-01

52

The prognostic value of blood pH and lactate and metformin concentrations in severe metformin-associated lactic acidosis  

PubMed Central

Aims Analysis of the prognostic values of blood pH and lactate and plasma metformin concentrations in severe metformin-associated lactic acidosis may help to resolve the following paradox: metformin provides impressive, beneficial effects but is also associated with life-threatening adverse effects. Research design and methods On the basis of 869 pharmacovigilance reports on MALA with available data on arterial pH and lactate concentration, plasma metformin concentration and outcome, we selected cases with a pH?10 mmol/L. Outcomes were compared with those described for severe metformin-independent lactic acidosis. Results Fifty-six patients met the above-mentioned criteria. The mean arterial pH and lactate values were 6.75?±?0.17 and 23.07?±?6.94 mmol/L, respectively. The survival rate was 53%, even with pH values as low as 6.5 and lactate and metformin concentrations as high as 35.3 mmol/L and 160 mg/L (normal?several triggering factors were combined. Sepsis, multidrug overdoses and the presence of at least two triggering factors for lactic acidosis were observed significantly more frequently in non-survivors (p?=?0.007, 0.04, and 0.005, respectively). This contrasts with a study of metformin-independent lactic acidosis in which there were no survivors, despite less severe acidosis on average (mean pH: 6.86). Conclusions In 56 cases of severe metformin-associated lactic acidosis, blood pH and lactate did not have prognostic value. One can reasonably rule out the extent of metformin accumulation as a prognostic factor. Ultimately, the determinants of metformin-associated lactic acidosis appear to be the nature and number of triggering factors. Strikingly, most patients survived - despite a mean pH that is incompatible with a favorable outcome under other circumstances. PMID:23587368

2013-01-01

53

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

PubMed Central

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 decrease in PCr (concomitant increase in ADP) in muscles with drop in pH occurs during incremental plantar flexion exercise. Methods Five male subjects performed a repetitive intermittent isometric plantar flexion exercise (6-s contraction/4-s relaxation). Exercise intensity was raised every 1 min by 10% maximal voluntary contraction (MVC), starting at 10% MVC until exhaustion. The measurement site was at the medial head of the gastrocnemius muscle. Changes in muscle PCr, inorganic phosphate (Pi), ADP, and pH were measured by 31P-magnetic resonance spectroscopy. o2mus was determined from the rate of decrease in oxygenated hemoglobin and/or myoglobin using near-infrared continuous wave spectroscopy under transient arterial occlusion. Electromyogram (EMG) was also recorded. Pulmonary oxygen uptake (o2pul ) was measured by the breath-by-breath gas analysis. Results EMG amplitude increased as exercise intensity progressed. In contrast, muscle PCr, ADP, o2mus, and o2pul did not change appreciably below 40% MVC, whereas above 40% MVC muscle PCr decreased, and ADP, o2mus, and o2pul increased as exercise intensity progressed, and above 70% MVC, changes in muscle PCr, ADP, o2mus, and o2pul accelerated with the decrease in muscle pH (~6.78). The kinetics of muscle PCr, ADP, o2mus, and o2pul were similar, and there was a close correlation between each pair of parameters (r = 0.969~0.983, p < 0.001). Conclusion With decrease in pH muscle oxidative metabolism accelerated and changes in intramuscular PCr and ADP accelerated during incremental intermittent isometric plantar flexion exercise. These results suggest that rapid changes in muscle PCr and/or ADP with mild acidosis stimulate accelerative muscle oxidative metabolism. PMID:15720727

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

2005-01-01

54

Targeted mutation of SLC4A5 induces arterial hypertension and renal metabolic acidosis.  

PubMed

The human SLC4A5 gene has been identified as a hypertension susceptibility gene based on the association of single nucleotide polymorphisms with blood pressure (BP) levels and hypertension status. The biochemical basis of this association is unknown particularly since no single gene variant was linked to hypertension in humans. SLC4A5 (NBCe2, NBC4) is expressed in the collecting duct of the kidney and acts as an electrogenic ion-transporter that transports sodium and bicarbonate with a 1:2 or 1:3 stoichiometry allowing bicarbonate reabsorption with relatively minor concurrent sodium uptake. We have mutated the Slc4a5 gene in mice, which caused a persistent increase in systolic and diastolic BP. Slc4a5 mutant mice also displayed a compensated metabolic acidosis and hyporeninemic hypoaldosteronism. Analysis of kidney physiology revealed elevated fluid intake and urine excretion and increased glomerular filtration rate. Transcriptome analysis uncovers possible compensatory mechanisms induced by SLC4A5 mutation, including upregulation of SLC4A7 and pendrin as well as molecular mechanisms associated with hypertension. Induction of metabolic alkalosis eliminated the BP difference between wild-type and Slc4a5 mutant mice. We conclude that the impairment of the function of SLC4A5 favors development of a hypertensive state. We reason that the loss of sodium-sparing bicarbonate reabsorption by SLC4A5 initiates a regulatory cascade consisting of compensatory bicarbonate reabsorption via other sodium-bicarbonate transporters (e.g. SLC4A7) at the expense of an increased sodium uptake. This will ultimately raise BP and cause hypoaldosteronism, thus providing a mechanistic explanation for the linkage of the SLC4A5 locus to hypertension in humans. PMID:22082831

Gröger, Nicole; Vitzthum, Helga; Fröhlich, Henning; Krüger, Marcus; Ehmke, Heimo; Braun, Thomas; Boettger, Thomas

2012-03-01

55

Acute metabolic acidosis in a GLUT2-deficient patient with Fanconi-Bickel syndrome: new pathophysiology insights.  

PubMed

Fanconi-Bickel syndrome is a rare autosomal-recessive disorder caused by mutations in the SLC2A2 gene coding for the glucose transporter protein 2 (GLUT2). Major manifestations include hepatomegaly, glucose intolerance, post-prandial hypoglycaemia and renal disease that usually presents as proximal tubular acidosis associated with proximal tubule dysfunction (renal Fanconi syndrome). We report a patient harbouring a homozygous mutation of SLC2A2 who presented a dramatic exacerbation of metabolic acidosis in the context of a viral infection, owing to both ketosis and major urinary bicarbonate loss. The kidney biopsy revealed nuclear and cytoplasmic accumulation of glycogen in proximal tubule cells, a lack of expression of GLUT2, and major defects of key proteins of the proximal tubule such as megalin, cubilin and the B2 subunit of H(+)-ATPase. These profound alterations of the transport systems most likely contributed to proximal tubule alterations and profound bicarbonate loss. PMID:25165176

Mihout, Fabrice; Devuyst, Olivier; Bensman, Albert; Brocheriou, Isabelle; Ridel, Christophe; Wagner, Carsten A; Mohebbi, Nilufar; Boffa, Jean-Jacques; Plaisier, Emmanuelle; Ronco, Pierre

2014-09-01

56

Consequences and therapy of the metabolic acidosis of chronic kidney disease  

PubMed Central

Metabolic acidosis is common in patients with chronic kidney disease (CKD), particularly once the glomerular filtration rate (GFR) falls below 25 ml/min/1.73 m2. It is usually mild to moderate in magnitude with the serum bicarbonate concentration ([HCO3?]) ranging from 12 to 23 mEq/l. Even so, it can have substantial adverse effects, including development or exacerbation of bone disease, growth retardation in children, increased muscle degradation with muscle wasting, reduced albumin synthesis with a predisposition to hypoalbuminemia, resistance to the effects of insulin with impaired glucose tolerance, acceleration of the progression of CKD, stimulation of inflammation, and augmentation of ?2-microglobulin production. Also, its presence is associated with increased mortality. The administration of base to patients prior to or after initiation of dialysis leads to improvement in many of these adverse effects. The present recommendation by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) is to raise serum [HCO3?] to ?22 mEq/l, whereas Caring for Australians with Renal Impairment (CARI) recommends raising serum [HCO3?] to >22 mEq/l. Base administration can potentially contribute to volume overload and exacerbation of hypertension as well as to metastatic calcium precipitation in tissues. However, sodium retention is less when given as sodium bicarbonate and sodium chloride intake is concomitantly restricted. Results from various studies suggest that enhanced metastatic calcification is unlikely with the pH values achieved during conservative base administration, but the clinician should be careful not to raise serum [HCO3?] to values outside the normal range. PMID:20526632

Kraut, Jeffrey A.

2010-01-01

57

Contribution of individual superficial nephron segments to ammonium handling in chronic metabolic acidosis in the rat. Evidence for ammonia disequilibrium in the renal cortex.  

PubMed Central

Ammonia entry along surface nephron segments of rats was studied with micropuncture techniques under control and chronic metabolic acidosis conditions. Tubule fluid was collected successively from sites at the end and beginning of the distal tubule and at the end of the proximal tubule of the same nephron. During chronic metabolic acidosis, ammonium excretion doubled. As anticipated, the ammonium concentration (TFNH+4) was significantly higher in proximal tubule fluid during acidosis, and ammonium delivery to end proximal sites increased from 19.4 +/- 2.3 to 34.0 +/- 3.2 pmol/min (P less than 0.001). Although chronic acidosis did not affect TFNH+4 at the beginning of the distal tubule, ammonium delivery to the end of the distal tubule increased from 5.72 +/- 0.97 to 9.88 +/- 0.97 pmol/min. In both control and acidotic groups ammonium delivery was lower (P less than 0.001) to end distal sites than to end proximal sites, indicating net loss in the intervening segment. This loss was greater during chronic metabolic acidosis (23.9 +/- 3.3 vs. 13.6 +/- 2.0 pmol/min in controls, P less than 0.025). In both groups net entry of ammonia, in similar amounts, occurred along the distal tubule (P less than 0.05). In situ pH averaged 6.80 +/- 0.05 at end proximal tubule sites and fell to 6.54 +/- 0.08 at the beginning of the distal tubule (P less than 0.005). Chronic metabolic acidosis did not affect these measurements. The calculated free ammonia at the end of the proximal tubule rose from 9.3 +/- 2.2 to 21 +/- 9 microM (P less than 0.005) during chronic metabolic acidosis, and was also higher at beginning distal sites during acidosis (8.8 +/- 2.4 vs. 2.7 +/- 0.7 microM in controls, P less than 0.05). In both groups ammonia values for the beginning distal tubule fluid were lower than for end proximal tubule fluid. Thus, loss of ammonium in the loop segment is enhanced by chronic metabolic acidosis. Distal entry of ammonia is markedly less than along the proximal tubule and does not change in chronic metabolic acidosis, and ammonia permeabilities for the proximal and distal segments of surface nephrons seem different. PMID:4031074

Simon, E; Martin, D; Buerkert, J

1985-01-01

58

Sympathetic activation in exercise is not dependent on muscle acidosis. Direct evidence from studies in metabolic myopathies  

NASA Technical Reports Server (NTRS)

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 sympathetic activation to muscle, microneurographic measurements of muscle sympathetic nerve activity (MSNA) were obtained from the peroneal nerve. MSNA was measured during static handgrip exercise at 30% of maximal voluntary contraction force to exhaustion in patients in whom exercise-induced muscle acidosis is absent (seven myophosphorylase deficient patients; MD [McArdle's disease], and one patient with muscle phosphofructokinase deficiency [PFKD]), augmented (one patient with mitochondrial myopathy [MM]), or normal (five healthy controls). Muscle pH was monitored by 31P-magnetic resonance spectroscopy during handgrip exercise in the five control subjects, four MD patients, and the MM and PFKD patients. With handgrip to exhaustion, the increase in MSNA over baseline (bursts per minute [bpm] and total activity [%]) was not impaired in patients with MD (17+/-2 bpm, 124+/-42%) or PFKD (65 bpm, 307%), and was not enhanced in the MM patient (24 bpm, 131%) compared with controls (17+/-4 bpm, 115+/-17%). Post-handgrip ischemia studied in one McArdle patient, caused sustained elevation of MSNA above basal suggesting a chemoreflex activation of MSNA. Handgrip exercise elicited an enhanced drop in muscle pH of 0.51 U in the MM patient compared with the decrease in controls of 0.13+/-0.02 U. In contrast, muscle pH increased with exercise in MD by 0.12+/-0.05 U and in PFKD by 0.01 U. In conclusion, patients with glycogenolytic, glycolytic, and oxidative phosphorylation defects show normal muscle sympathetic nerve responses to static exercise. These findings indicate that muscle acidosis is not a prerequisite for sympathetic activation in exercise.

Vissing, J.; Vissing, S. F.; MacLean, D. A.; Saltin, B.; Quistorff, B.; Haller, R. G.; Blomqvist, C. G. (Principal Investigator)

1998-01-01

59

Incidence, prevalence, severity, and risk factors for ruminal acidosis in feedlot steers during backgrounding, diet transition, and finishing.  

PubMed

The objective of this study was to determine the incidence, prevalence, severity, and risk factors for ruminal acidosis in feedlot steers during backgrounding, diet transition, and finishing. Steers were purchased from a local auction market (n = 250; mean ± SD; 330 ± 20.0 kg initial BW) and were grouped together with 28 steers fitted with a ruminal cannula (248 ± 25.5 kg initial BW). Steers were randomly allocated to 1 of 8 pens (3 to 4 cannulated steers per pen with a total of 35 steers/pen). The feeding period (143 d) was divided into 4 phases: backgrounding (BKGD; d 1 to 20), diet transition (TRAN; d 21 to 40), and the first (FIN1; d 41 to 91) and second half (FIN2; d 92 to 143) of finishing. The BKGD diet contained (% DM) barley silage (45.7%), barley grain (41.6%), canola meal (4.2%), and a pelleted mineral and vitamin supplement (8.5%). Steers were transitioned to a finishing diet containing (% DM) barley silage (5%), barley grain (80.9%), canola meal (4.9%), and a pelleted mineral and vitamin supplement (9.2%) using 4 transition diets. Feed was offered to achieve 5% refusals (as-is basis). Ruminal pH was recorded in cannulated steers every 10 min throughout the study, and feed refusals and BW were recorded at 2 wk intervals. Mean ruminal pH (P < 0.01) was 6.4, 6.3, 6.2, and 6.0 ± 0.01 during the BKGD, TRAN, FIN1, and FIN2, respectively. The duration (P < 0.01) pH < 5.5 was 4.1, 12.1, 78.7, and 194 ± 9.4 min/d during BKGD, TRAN, FIN1, and FIN2, respectively. Using a threshold of ruminal pH < 5.5 for at least 180 min to diagnose ruminal acidosis, incidence was defined as the number of times steers experienced ruminal acidosis during each period and prevalence was defined as the percentage of steers that experienced acidosis during each period. On average, the incidence rate (P < 0.01) of ruminal acidosis was 0.1, 0.3, 6.7, and 14.8 ± 0.97 episodes during BKGD, TRAN, FIN1, and FIN2, respectively. In the same order, the prevalence (P < 0.01) was 0.7, 1.7, 15.4, and 37.8 ± 2.0%. Based on multiple regression, factors associated with prevalence of ruminal acidosis and the duration pH < 5.5 were feeding phase (P < 0.01) and DMI (P < 0.01). Overall, the greatest incidence, prevalence, and severity of ruminal acidosis were observed towards the end of the finishing phase and were associated with days on feed and DMI. PMID:24879761

Castillo-Lopez, E; Wiese, B I; Hendrick, S; McKinnon, J J; McAllister, T A; Beauchemin, K A; Penner, G B

2014-07-01

60

Hypokalemic quadriparesis and rhabdomyolysis as a rare presentation of distal renal tubular acidosis.  

PubMed

Distal renal tubular acidosis is a syndrome of abnormal urine acidification and is characterized by hyperchloremic metabolic acidosis, hypokalemia, hypercalciurea, nephrocalcinosis and nephrolithiasis. Despite the presence of persistent hypokalemia, acute muscular paralysis is rarely encountered in males. Here, we will report an eighteen year old male patient who presented with flaccid quadriparesis and was subsequently found to have rhabdomyolysis, severe short stature, skeletal deformities and primary distal renal tubular acidosis. PMID:25250276

Ahmad Bhat, Manzoor; Ahmad Laway, Bashir; Mustafa, Farhat; Shafi Kuchay, Mohammad; Mubarik, Idrees; Ahmad Palla, Nazir

2014-01-01

61

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

62

Type IV renal tubular acidosis and spironolactone therapy in the elderly.  

PubMed Central

Spironolactone therapy is a well-known cause of hyperkalaemia, but in susceptible patient, it may also be associated with metabolic acidosis. We report a case of severe renal tubular acidosis (Type IV) with life-threatening hyperkalaemia caused by spironolactone, and discuss the mechanisms by which this may occur. PMID:8290440

O'Connell, J. E.; Colledge, N. R.

1993-01-01

63

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

64

[Tubular renal acidosis].  

PubMed

Renal tubular acidosis (RTAs) are a group of metabolic disorders characterized by metabolic acidosis with normal plasma anion gap. There are three main forms of RTA: a proximal RTA called type II and a distal RTA (type I and IV). The RTA type II is a consequence of the inability of the proximal tubule to reabsorb bicarbonate. The distal RTA is associated with the inability to excrete the daily acid load and may be associated with hyperkalaemia (type IV) or hypokalemia (type I). The most common etiology of RTA type IV is the hypoaldosteronism. The RTAs can be complicated by nephrocalcinosis and obstructive nephrolithiasis. Alkalinization is the cornerstone of treatment. PMID:24070792

Seidowsky, A; Moulonguet-Doleris, L; Hanslik, T; Yattara, H; Ayari, H; Rouveix, E; Massy, Z A; Prinseau, J

2014-01-01

65

Respiratory acidosis  

MedlinePLUS

... as bicarbonate, that help restore the body's acid-base balance. Acute respiratory acidosis is a condition in ... Effros RM, Swenson ER. Acid-base balance. In: Mason RJ, Broaddus CV, ... of Respiratory Medicine . 5th ed. Philadelphia, PA: Elsevier ...

66

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

67

Oral Sodium Bicarbonate for the Treatment of Metabolic Acidosis in Peritoneal Dialysis Patients: A Randomized Placebo-Control Trial  

Microsoft Academic Search

Acidosis causes malnutrition in peritoneal dialysis (PD) patients. The effect of oral bicarbonate in PD patients with Kt\\/V 2.1 has not been studied. We randomly assigned 60 PD patients with acidosis and Kt\\/V 2.1 to oral sodium bicarbonate (0.9 g thrice daily) or placebo. Patients were fol- lowed for 12 mo. We compared their nutritional status, includ- ing subjective global

CHEUK-CHUN SZETO; TERESA YUK-HWA WONG; KAI-MING CHOW; CHI-BON LEUNG; PHILIP KAM-TAO LI

68

Relationship of severity of subacute ruminal acidosis to rumen fermentation, chewing activities, sorting behavior, and milk production in lactating dairy cows fed a high-grain diet.  

PubMed

The objectives of the current study were to evaluate the variation in severity of subacute ruminal acidosis (SARA) among lactating dairy cows fed a high-grain diet and to determine factors characterizing animals that are tolerant to high-grain diets. Sixteen ruminally cannulated late-lactating dairy cows (days in milk=282 ± 33.8; body weight=601 ± 75.9 kg) were fed a high-grain diet consisting of 35% forage and 65% concentrate mix. After 17 d of diet adaptation, chewing activities were monitored for a 24-h period and ruminal pH was measured every 30s for 72 h. Acidosis index, defined as the severity of SARA (area of pH <5.8) divided by dry matter intake (DMI), was determined for individual animals to assess the severity of SARA normalized for a feed intake level. Although all cows were fed the same diet, minimum pH values ranged from 5.16 to 6.04, and the acidosis index ranged from 0.0 to 10.9 pH · min/kg of DMI. Six cows with the lowest acidosis index (0.04 ± 0.61 pH · min/kg) and 4 with the highest acidosis index (7.67 ± 0.75 pH · min/kg) were classified as animals that were tolerant and susceptible to the high-grain diet, respectively. Total volatile fatty acid concentration and volatile fatty acid profile were not different between the groups. Susceptible animals sorted against long particles, whereas tolerant animals did not (sorting index=87.6 vs. 97.9, respectively). However, the tolerant cows had shorter total chewing time (35.8 vs. 45.1 min/kg of DMI). In addition, although DMI, milk yield, and milk component yields did not differ between the groups, milk urea nitrogen concentration was higher for tolerant cows compared with susceptible cows (12.8 vs. 8.6 mg/dL), which is possibly attributed to less organic matter fermentation in the rumen of tolerant cows. These results suggest that a substantial variation exists in the severity of SARA among lactating dairy cows fed the same high-grain diet, and that cows tolerant to the high-grain diet might be characterized by less sorting behavior but less chewing time, and higher milk urea nitrogen concentration. PMID:24612805

Gao, X; Oba, M

2014-05-01

69

Metabolic Management of Severe Acute Pancreatitis  

Microsoft Academic Search

.   The metabolic management of severe acute pancreatitis involves early identification of patients with severe pancreatitis,\\u000a aggressive fluid resuscitation, organ support, and careful monitoring in an intensive care environment. Recent evidence has\\u000a helped to define the roles of enteral feeding, prophylactic antibiotics, endoscopic retrograde cholangiopancreatography, computed\\u000a tomography, and fine-needle aspiration for bacteriology. The most difficult decision in the management of

John A. Windsor; Hisham Hammodat

2000-01-01

70

Metabolic and hormonal effects of exercise in the severely streptozotocin-diabetic rat  

Microsoft Academic Search

Summary  Metabolic and hormonal changes during muscular exercise were studied in streptozotocin (65 mg\\/kg) — diabetic rats. The untreated,\\u000a non-fasted animals ran in a rotating cage for 30 min, and blood, liver and pancreatic specimens were taken before, immediately\\u000a after and\\/or two hrs after exercise. The slight pre-exercise acidosis of the diabetic rats changed during exercise to a marked\\u000a acidosis due

V. A. Koivisto; H. K. Åkerblom; M. K. Kiviluoto

1974-01-01

71

Interaction between bunk management and monensin concentration on finishing performance, feeding behavior, and ruminal metabolism during an acidosis challenge with feedlot cattle.  

PubMed

Two commercial feedlot experiments and a metabolism study were conducted to evaluate the effects of monensin concentrations and bunk management strategies on performance, feed intake, and ruminal metabolism. In the feedlot experiments, 1,793 and 1,615 steers were used in Exp. 1 and 2, respectively, in 18 pens for each experiment (six pens/treatment). Three treatments were evaluated: 1) ad libitum bunk management with 28.6 mg/kg monensin and clean bunk management strategies with either 2) 28.6 or 3) 36.3 mg/kg monensin. In both experiments, 54 to 59% of the clean bunk pens were clean at targeted clean time, or 2200, compared with 24 to 28% of the ad libitum pens. However, only 13% of the pens were clean by 2000 in Exp. 1 (summer), whereas 44% of the pens in Exp. 2 (winter) were clean by 2000. In Exp. 1, bunk management and monensin concentration did not affect carcass-adjusted performance. In Exp. 2, steers fed ad libitum had greater DMI (P < 0.01) and carcass-adjusted ADG (P < 0.01) but feed efficiency (P > 0.13) similar to that of clean bunk-fed steers. Monensin concentration had no effect on carcass-adjusted performance (P > 0.20) in either experiment. A metabolism experiment was conducted with eight fistulated steers in a replicated 4 x 4 Latin square acidosis challenge experiment. An acidosis challenge was imposed by feeding 125% of the previous day's DMI, 4 h later than normal. Treatments consisted of monensin concentrations (mg/kg) of 0, 36.7, 48.9, or 36.7 until challenged and switched to 48.9 on the challenge day and 4 d following. Each replicate of the Latin square was managed with separate bunk management strategies (clean bunk or ad libitum). Feeding any concentration of monensin increased number of meals and decreased DMI rate (%/h) (P < 0.12) for the 4 d following the acidosis challenge. Meal size, pH change, and pH variance were lower (P < 0.10) for steers fed monensin with clean bunk management. However, no monensin effect was observed for steers fed ad libitum. Bunk management strategy has the potential to decrease DMI and ADG when steers managed on a clean bunk program are restricted relative to traditional, ad libitum bunk programs. Monensin helps control intake patterns for individuals, but increasing concentration above currently approved levels in this study seemed to have little effect. PMID:14601891

Erickson, G E; Milton, C T; Fanning, K C; Cooper, R J; Swingle, R S; Parrott, J C; Vogel, G; Klopfenstein, T J

2003-11-01

72

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

73

Fuel metabolism during severe rowing exercise  

SciTech Connect

Eight elite oarsmen were studied during and after six min of severe ergometer exercise. Power output averaged 380 +/- 28 watts. Serial venous blood samples and gas exchange measurements were obtained during exercise. In 4 of the 8 subjects, a primed periodic oral dose of the tracer (6,6-/sup 2/H/sub 2/)glucose was used to determine the effects of severe exercise on glucose metabolism. During exercise, the levels of lactate progressively increased to 12.2 +/- 1.3 mM (SE). There was little change in isotopic glucose enrichment during exercise (from 2.95 +/- 0.30 to 2.55 +/- 0.23 atom percent excess, APE). During recovery, isotopic glucose enrichment decreased significantly to 1.40 +/- 0.14 APE, indicating a substantial post-exercise plasma glucose flux. There were significant post-exercise increases in plasma glucose accumulation (from 84 +/- 5 to 131 +/- 3 mg/dl) and insulin concentration (0.57 +/- 0.08 to 1.34 +/- 0.15 ng/ml). These results suggest that muscle glycogen is the primary source of fuel during six minutes of maximal rowing exercise.

Hoyt, R.W.; Lubowitz, J.; Asakura, T.; Stein, T.P.

1986-03-01

74

[Estimation of the severity of metabolic disorders in children with newly diagnosed insulin dependent diabetes mellitus (IDDM)].  

PubMed

The objective of this study was to estimate the severity of metabolic disorders at onset in children with insulin dependent diabetes mellitus (IDDM). Biochemical results taken at onset of IDDM were analysed in 158 children on their admission. Metabolic acidosis was found in 37.97% of those and ketoacidosis was confirmed in 18.99% children. Mean values of biochemical parameters are similar to those reported in the others European countries. The most severe changes of the acid-base balance parameters were observed in youngest children (1-4 y.o) living in the rural areas (pH, 7.22, HCO3- 10.2 mmol/l, BE - 16.06 mmol/l, p=0.05); this should suggest that those children are watchfully observed and IDDM should be always be considered as a possible cause of any alarming symptoms which occur. PMID:12878797

Charemska, Dorota; Przybyszewski, Borys; Klonowska, Bozenna

2003-01-01

75

A homozygous mutation in LYRM7/MZM1L associated with early onset encephalopathy, lactic acidosis, and severe reduction of mitochondrial complex III activity.  

PubMed

Mutations in nuclear genes associated with defective complex III (cIII) of the mitochondrial respiratory chain are rare, having been found in only two cIII assembly factors and, as private changes in single families, three cIII structural subunits. Recently, human LYRM7/MZM1L, the ortholog of yeast MZM1, has been identified as a new assembly factor for cIII. In a baby patient with early onset, severe encephalopathy, lactic acidosis and profound, isolated cIII deficiency in skeletal muscle, we identified a disease-segregating homozygous mutation (c.73G>A) in LYRM7/MZM1L, predicting a drastic change in a highly conserved amino-acid residue (p.Asp25Asn). In a mzm1? yeast strain, the expression of a mzm1(D25N) mutant allele caused temperature-sensitive respiratory growth defect, decreased oxygen consumption, impaired maturation/stabilization of the Rieske Fe-S protein, and reduced complex III activity and amount. LYRM7/MZM1L is a novel disease gene, causing cIII-defective, early onset, severe mitochondrial encephalopathy. PMID:24014394

Invernizzi, Federica; Tigano, Marco; Dallabona, Cristina; Donnini, Claudia; Ferrero, Ileana; Cremonte, Maurizio; Ghezzi, Daniele; Lamperti, Costanza; Zeviani, Massimo

2013-12-01

76

Chronic metabolic acidosis enhances NHE-3 protein abundance and transport activity in the rat thick ascending limb by increasing NHE-3 mRNA.  

PubMed Central

Chronic metabolic acidosis (CMA) is associated with an adaptive increase in the bicarbonate absorptive capacity of the rat medullary thick ascending limb (MTAL). To specify whether NHE-3, the apical MTAL Na/H exchanger, is involved in this adaptation, NHE-3 mRNA was quantified by a competitive RT-PCR using an internal standard which differed from the wild-type NHE-3 mRNA by an 80-bp deletion. CMA increased NHE-3 mRNA from 0.025+/-0.003 to 0.042+/-0.009 amol/ng total RNA (P < 0.005). NHE-3 transport activity was measured as the initial proton flux rate calculated from the Na-dependent cell pH recovery of Na-depleted acidified MTAL cells in the presence of 50 microM HOE694 which specifically blocks NHE-1, the basolateral MTAL NHE isoform. CMA caused a 68% increase in NHE-3 transport activity (P < 0.001). In addition, CMA was associated with a 71% increase in NHE-3 protein abundance (P < 0.05) as determined by Western blot analysis on MTAL membranes using a polyclonal antiserum directed against a cytoplasmic epitope of rat NHE-3. Thus, NHE-3 adapts to CMA in the rat MTAL via an increase in the mRNA transcript that enhances NHE-3 protein abundance and transport activity. PMID:9011571

Laghmani, K; Borensztein, P; Ambühl, P; Froissart, M; Bichara, M; Moe, O W; Alpern, R J; Paillard, M

1997-01-01

77

RELATIONSHIP OF ACIDOSIS TO OTHER FEEDLOT AILMENTS l ,2  

Microsoft Academic Search

SUMMARY Laminitis often follows lactic acidosis and is accompanied by increased blood and rumen histamine. However, since histamine is poorly absorbed and absorbed histamine is rapidly metabolized, and since high levels of oral histamine have not produced laminitis, it is unlikely that ruminal histamine causes lami- nitis. Lactic acidosis leads to rumenitis, which, in turn, leads to liver abscesses because

B. E. Brent

2010-01-01

78

Amelioration of Hyperchloremic Acidosis with Furosemide Therapy in Patients with Chronic Renal Insufficiency and Type 4 Renal Tubular Acidosis  

Microsoft Academic Search

In hypoaldosteronemic patients with chronic renal insufficiency, administration of a mineralocorticoid steroid such as fludrocortisone can ameliorate hyperkalemia and metabolic acidosis, but this therapy is not always safe owing to the deleterious consequences of extracellular fluid volume expansion resulting from mineralocorticoid-induced sodium chloride retention. In the present study of 8 patients with renal hyperchloremic acidosis, mild hyperkalemia and chronic glomerular

Anthony Sebastian; Morris Schambelan; James M. Sutton

1984-01-01

79

Blood glucose threshold and the metabolic responses to incremental exercise tests with and without prior lactic acidosis induction  

Microsoft Academic Search

This study compared the metabolic–ventilatory responses and the glycemic threshold identified during lactate minimum (LM)\\u000a and individual anaerobic threshold (IAT) tests. In addition, the ability to determine the anaerobic power, aerobic–anaerobic\\u000a transition (Trans) (e.g. ventilatory threshold; VT) and the maximal oxygen consumption (V?O2max) all within a single incremental treadmill test (IT) was investigated. Fifteen physically fit men [25.9 (5.5) years; 77.4

Herbert Gustavo Simões; Carmen S. G. Campbell; Michael R. Kushnick; Akiko Nakamura; Christos S. Katsanos; Vilmar Baldissera; Robert J. Moffatt

2003-01-01

80

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

81

Distal renal tubular acidosis and amelogenesis imperfecta: A rare association.  

PubMed

Renal tubular acidosis (RTA) is characterized by a normal anion gap with hyperchloremic metabolic acidosis. Primary distal RTA (type I) is the most common RTA in children. Childhood presentation of distal RTA includes vomiting, failure to thrive, metabolic acidosis, and hypokalemia. Amelogenesis imperfecta (AI) represents a condition where the dental enamel and oral tissues are affected in an equal manner resulting in the hypoplastic or hypopigmented teeth. We report a 10-year-old girl, previously asymptomatic presented with the hypokalemic paralysis and on work-up found out to have type I RTA. The discoloration of teeth and enamel was diagnosed as AI. PMID:24339526

Ravi, P; Ekambaranath, T S; Arasi, S Ellil; Fernando, E

2013-11-01

82

Renal Tubular Acidosis  

MedlinePLUS

... the blood and cause problems. When this happens, it's called renal tubular acidosis (RTA) . Without treatment, RTA can affect a child's growth and cause kidney stones , fatigue, muscle weakness, ...

83

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

84

On the Mechanism of Toluene-Induced Renal Tubular Acidosis  

Microsoft Academic Search

This study was aimed to investigate the pathogenesis of toluene-induced renal tubular acidosis (RTA). In 5 individuals addicted to toluene sniffing we documented the occurrence of hypokalemia and hyperchloremic metabolic acidosis associated with inability to lower urine pH below 5.5 (6.06 ± 0.24). Overall kidney bicarbonate reabsorption was normal or enhanced, a feature characteristic of the distal form of RTA

D. C. Batlle; S. Sabatini; N. A. Kurtzman

1988-01-01

85

[Exertion-induced lactic acidosis in celiac artery stenosis].  

PubMed

A well-trained young male developed effort-induced dyspnea due to marked lactic acidosis. In the absence of cardiopulmonary problems, enzyme defects, primary hepatopathy or myopathy, abdominal angiography revealed subtotal stenosis, and duplex sonography (15 years later) total occlusion, of the celiac trunk associated with hepatic steal syndrome. We suggest that the marked, effort-induced lactic acidosis may be a metabolic consequence of Dunbar syndrome (stenosis of the celiac trunk due to compression by the crura diaphragmatica). PMID:2315654

Jungo, O

1990-03-10

86

Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring  

PubMed Central

Abstract Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH. However, it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance. In this study, we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice. ApoCIII transgenic mice with severe hypertriglyceridemia were mated with non-transgenic control mice to obtain 4 types of offspring: maternal non-transgenic control and maternal transgenic offspring, and paternal control and paternal transgenic offspring. Plasma triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG) and fasting insulin (FINS) were measured. ApoCIII overexpression caused severe hypertriglyceridemia, but the transgenic female mice had unaltered fertility with normal pregnancy and birth of pups. The 4 groups of offspring had similar birth weight and growth rate. The plasma TG of maternal and paternal transgenic offspring were nearly 40-fold higher than maternal and paternal control mice, but there was no difference in plasma TG between maternal and paternal transgenic offspring. Although the FPG of the 4 groups of animals had no difference, the maternal transgenic mice showed impaired glucose tolerance, increased FINS levels and higher homeostasis model assessment insulin resistance index (HOMA-IR) than the other 3 groups. In conclusion, maternally inherited hypertriglyceridemia in ApoCIII transgenic mice displayed impaired glucose tolerance, hyperinsulinemia and increased HOMA-R, while paternally inherited hypertriglyceridemia did not have such impacts. PMID:25859267

Ma, Ya-Hong; Yu, Caiguo; Kayoumu, Abudurexiti; Guo, Xin; Ji, Zhili; Liu, George

2015-01-01

87

Klinefelter's syndrome with renal tubular acidosis: impact on height.  

PubMed

A 19-year-old Indian man presented with a history of proximal muscle weakness, knock knees and gynaecomastia. On examination he had features of rickets and bilateral small testes. Karyotyping revealed a chromosomal pattern of 47,XXX, confirming the diagnosis of Klinefelter's syndrome. He was also found to have hyperchloraemic metabolic acidosis with hypokalaemia, hypophosphataemia, phosphaturia and glycosuria, which favoured a diagnosis of proximal renal tubular acidosis. Patients with Klinefelter's syndrome typically have a tall stature due to androgen deficiency, resulting in unfused epiphyses and an additional X chromosome. However, this patient had a short stature due to associated proximal renal tubular acidosis. To the best of our knowledge, this is the second case of Klinefelter's syndrome with short stature due to associated renal tubular acidosis reported in the literature. This report highlights the need to consider other causes when patients with Klinefelter's syndrome present with a short stature. PMID:20358137

Jebasingh, F; Paul, T V; Spurgeon, R; Abraham, S; Jacob, J J

2010-02-01

88

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

89

Hemodynamic and Metabolic Correlates of Perinatal White Matter Injury Severity  

PubMed Central

Background and Purpose Although the spectrum of perinatal white matter injury (WMI) in preterm infants is shifting from cystic encephalomalacia to milder forms of WMI, the factors that contribute to this changing spectrum are unclear. We hypothesized that the variability in WMI quantified by immunohistochemical markers of inflammation could be correlated with the severity of impaired blood oxygen, glucose and lactate. Methods We employed a preterm fetal sheep model of in utero moderate hypoxemia and global severe but not complete cerebral ischemia that reproduces the spectrum of human WMI. Since there is small but measurable residual brain blood flow during occlusion, we sought to determine if the metabolic state of the residual arterial blood was associated with severity of WMI. Near the conclusion of hypoxia-ischemia, we recorded cephalic arterial blood pressure, blood oxygen, glucose and lactate levels. To define the spectrum of WMI, an ordinal WMI rating scale was compared against an unbiased quantitative image analysis protocol that provided continuous histo-pathological outcome measures for astrogliosis and microgliosis derived from the entire white matter. Results A spectrum of WMI was observed that ranged from diffuse non-necrotic lesions to more severe injury that comprised discrete foci of microscopic or macroscopic necrosis. Residual arterial pressure, oxygen content and blood glucose displayed a significant inverse association with WMI and lactate concentrations were directly related. Elevated glucose levels were the most significantly associated with less severe WMI. Conclusions Our results suggest that under conditions of hypoxemia and severe cephalic hypotension, WMI severity measured using unbiased immunohistochemical measurements correlated with several physiologic parameters, including glucose, which may be a useful marker of fetal response to hypoxia or provide protection against energy failure and more severe WMI. PMID:24416093

Riddle, Art; Maire, Jennifer; Cai, Victor; Nguyen, Thuan; Gong, Xi; Hansen, Kelly; Grafe, Marjorie R.; Hohimer, A. Roger; Back, Stephen A.

2013-01-01

90

D-Lactic acidosis 25 years after bariatric surgery due to Salmonella enteritidis  

Microsoft Academic Search

D-lactic acidosis is a rare complication that occurs in patients with short bowel syndrome due to surgical intestine resection for treatment of obesity. The clinical presentation is characterized by neurologic symptoms and high anion gap metabolic acidosis. The incidence of this syndrome is unknown, probably because of misdiagnosis and sometimes symptoms may be incorrectly attributed to other causes. Therapy is

Antonietta Gigante; Liborio Sardo; Maria Ludovica Gasperini; Antonio Molinaro; Oliviero Riggio; Alessandro Laviano; Antonio Amoroso

91

Short stature, hyperkalemia and acidosis: A defect in renal transport of potassium  

Microsoft Academic Search

Short stature, hyperkalemia, and acidosis: A defect in renal transport of potassium. An eleven-year-old boy presented with short stature, hyperkalemia, and metabolic acidosis. No endocrine cause for a short stature could be demonstrated. Renal function, as assessed by inulin and PAH clearances, concentrating and diluting capacity, and ability to acidify the urine and to excrete net acid, was normal. No

Adrian Spitzer; Chester M Edelmann; Lee D Goldberg; Philip H Henneman

1973-01-01

92

Understanding lactic acidosis in paracetamol (acetaminophen) poisoning  

PubMed Central

Paracetamol (acetaminophen) is one of the most commonly taken drugs in overdose in many areas of the world, and the most common cause of acute liver failure in both the UK and USA. Paracetamol poisoning can result in lactic acidosis in two different scenarios. First, early in the course of poisoning and before the onset of hepatotoxicity in patients with massive ingestion; a lactic acidosis is usually associated with coma. Experimental evidence from studies in whole animals, perfused liver slices and cell cultures has shown that the toxic metabolite of paracetamol, N-acetyl-p-benzo-quinone imine, inhibits electron transfer in the mitochondrial respiratory chain and thus inhibits aerobic respiration. This occurs only at very high concentrations of paracetamol, and precedes cellular injury by several hours. The second scenario in which lactic acidosis can occur is later in the course of paracetamol poisoning as a consequence of established liver failure. In these patients lactate is elevated primarily because of reduced hepatic clearance, but in shocked patients there may also be a contribution of peripheral anaerobic respiration because of tissue hypoperfusion. In patients admitted to a liver unit with paracetamol hepatotoxicity, the post-resuscitation arterial lactate concentration has been shown to be a strong predictor of mortality, and is included in the modified King's College criteria for consideration of liver transplantation. We would therefore recommend that post-resuscitation lactate is measured in all patients with a severe paracetamol overdose resulting in either reduced conscious level or hepatic failure. PMID:21143497

Shah, Anoop D; Wood, David M; Dargan, Paul I

2011-01-01

93

Understanding lactic acidosis in paracetamol (acetaminophen) poisoning.  

PubMed

Paracetamol (acetaminophen) is one of the most commonly taken drugs in overdose in many areas of the world, and the most common cause of acute liver failure in both the UK and USA. Paracetamol poisoning can result in lactic acidosis in two different scenarios. First, early in the course of poisoning and before the onset of hepatotoxicity in patients with massive ingestion; a lactic acidosis is usually associated with coma. Experimental evidence from studies in whole animals, perfused liver slices and cell cultures has shown that the toxic metabolite of paracetamol, N-acetyl-p-benzo-quinone imine, inhibits electron transfer in the mitochondrial respiratory chain and thus inhibits aerobic respiration. This occurs only at very high concentrations of paracetamol, and precedes cellular injury by several hours. The second scenario in which lactic acidosis can occur is later in the course of paracetamol poisoning as a consequence of established liver failure. In these patients lactate is elevated primarily because of reduced hepatic clearance, but in shocked patients there may also be a contribution of peripheral anaerobic respiration because of tissue hypoperfusion. In patients admitted to a liver unit with paracetamol hepatotoxicity, the post-resuscitation arterial lactate concentration has been shown to be a strong predictor of mortality, and is included in the modified King's College criteria for consideration of liver transplantation. We would therefore recommend that post-resuscitation lactate is measured in all patients with a severe paracetamol overdose resulting in either reduced conscious level or hepatic failure. PMID:21143497

Shah, Anoop D; Wood, David M; Dargan, Paul I

2011-01-01

94

Hyperchloremic acidosis during grand mal seizure lactic acidosis  

Microsoft Academic Search

Objective  To evaluate the prevalence and the mechanism of hyperchloremic acidosis component (HC1A) during lactic acidosis secondary\\u000a to grand mal seizures.\\u000a \\u000a \\u000a \\u000a Design  Retrospective study.\\u000a \\u000a \\u000a \\u000a Setting  Medical intensive care unit in a university hospital.\\u000a \\u000a \\u000a \\u000a Patients  35 patients admitted for grand mal seizures with lactic acidosis (pH2 2 <8 kPa).\\u000a \\u000a \\u000a \\u000a Measurements  HC1A was defined by the ratio: excess anion gap\\/HCO3 deficit (?AG\\/?TCO2) <0.8. A difference in the

F. Brivet; M. Bernardin; P. Cherin; J. Chalas; P. Galanaud; J. Dormont

1994-01-01

95

Water, acidosis, and experimental pyelonephritis  

PubMed Central

The effect of water restriction and ammonium chloride acidosis on the course of Escherichia coli pyelonephritis was determined in the nonobstructed kidney of the rat. To alter the chemical composition of the renal medulla, water intake was reduced in rats to one-half the normal daily intake. Water restriction increased the incidence of coliform pyelonephritis. Systemic acidosis, produced by giving a 300 mM solution of ammonium chloride, increased urinary osmolality to values comparable to water restriction and also predisposed to pyelonephritis. However, when rats were fed the same solution of ammonium chloride but were allowed access to tap water ad lib., urinary osmolality values were comparable to those observed in normal animals, and susceptibility to pyelonephritis was reduced or eliminated despite a degree of systemic acidosis similar to that observed in rats fed ammonium chloride solution without access to tap water. These results suggest that water diuresis may overcome the inactivation of complement produced by ammonium chloride acidosis and that renal medullary hypertonicity, produced by either water restriction or ammonium chloride acidosis, is a major determinant of this tissue's unique susceptibility to infection. PMID:4902827

Andriole, Vincent T.

1970-01-01

96

Severe malnutrition and metabolic complications of HIV-infected children in the antiretroviral era: clinical care and management in resource-limited settings1234  

PubMed Central

More than 2 million children globally are living with HIV infection and >90% of these reside in sub-Saharan Africa. Severe acute malnutrition (SAM) remains a major problem for HIV-infected children who live in resource-limited settings (RLS), and SAM is an important risk factor for mortality. SAM in HIV-infected children is associated with complications including electrolyte disorders, micronutrient deficiencies, and severe infections, which contribute to the high mortality. Access to antiretroviral therapy (ART) has significantly improved the survival of HIV-infected children, although the response to ART of children with SAM remains undocumented in the literature. Immune and virologic responses to ART in RLS are similar to those of infected children in resource-rich settings, but delays in initiation of therapy have led to a high early mortality. Antiretroviral drug toxicities have been described in children who receive therapy and may affect their quality of life and long-term survival. Metabolic complications of ART include lipodystrophy, dyslipidemia, lactic acidosis, insulin resistance, and osteopenia. These complications have been well described in adults and children from developed countries, but data from RLS are limited, and these complications may be compounded by SAM. In this article we review the epidemiology, clinical presentation, and complications of SAM in HIV-infected children and the metabolic complications of HIV-infected children in the era of ART, and discuss future research priorities for RLS. PMID:22089437

Fergusson, Pamela

2011-01-01

97

Metformin-associated lactic acidosis.  

PubMed

: Metformin is the most commonly prescribed oral antidiabetic agent. Despite a good safety profile in most patients with diabetes, the risk of metformin-associated lactic acidosis is real if safety guidelines are ignored. Experience with 3 cases of metformin-associated lactic acidosis is reported. Two cases were caused by inappropriate use of metformin in the presence of renal, cardiac and hepatic failure and 1 case followed an intentional overdose. The literature was reviewed on the clinical presentation, prevalence, pathogenesis, prognosis and management of metformin-associated lactic acidosis. This report highlights the importance of proper patient selection, clinical and laboratory monitoring and recommendation on when to stop the drug in ambulatory and hospitalized patients to prevent this unusual but potentially lethal complication. PMID:24326619

Pasquel, Francisco J; Klein, Robin; Adigweme, Adaeze; Hinedi, Ziad; Coralli, Richard; Pimentel, Juan L; Umpierrez, Guillermo E

2015-03-01

98

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

99

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

100

Acidosis in the critically ill - balancing risks and benefits to optimize outcome.  

PubMed

Acidosis is associated with poor outcome in critical illness. However, acidosis - both hypercapnic and metabolic - has direct effects that can limit tissue injury induced by many causes. There is also a clear potential for off-target harm with acute exposure (for example, raised intracranial pressure, pulmonary hypertension), and with exposure for prolonged periods (for example, increased risk of infection) or at high doses. Ongoing comprehensive determination of molecular, cellular and physiologic impact across a range of representative pathologies will allow us to understand better the risks and benefits of hypercapnia and acidosis during critical illness. PMID:25029442

Curley, Gerard F; Laffey, John G

2014-01-01

101

Evidence for a Detrimental Effect of Bicarbonate Therapy in Hypoxic Lactic Acidosis  

Microsoft Academic Search

Lactic acidosis, a clinical syndrome caused by the accumulation of lactic acid, is characterized by lactate concentration in blood greater than 5 mM. Therapy usually consists of intravenous sodium bicarbonate (NaHCO3), but resultant mortality is greater than 60 percent. The metabolic and systemic effects of NaHCO3 therapy of hypoxic lactic acidosis in dogs were studied and compared to the effects

Helmut Graf; William Leach; Allen I. Arieff

1985-01-01

102

Clinical approach to renal tubular acidosis in adult patients.  

PubMed

Renal tubular acidosis (RTA) is a group of disorders observed in patients with normal anion gap metabolic acidosis. There are three major forms of RTA: A proximal (type II) RTA and two types of distal RTAs (type I and type IV). Proximal (type II) RTA originates from the inability to reabsorb bicarbonate normally in the proximal tubule. Type I RTA is associated with inability to excrete the daily acid load and may present with hyperkalaemia or hypokalaemia. The most prominent abnormality in type IV RTA is hyperkalaemia caused by hypoaldosteronism. This article extensively reviews the mechanism of hydrogen ion generation from metabolism of normal diet and various forms of RTA leading to disruptions of normal acid-base handling by the kidneys. PMID:21314872

Reddy, P

2011-03-01

103

Bovine Acidosis: Implications on Laminitis  

Microsoft Academic Search

Bovine lactic acidosis syndrome is associated with large increases of lactic acid in the rumen, which result from diets that are high in ruminally available carbohydrates, or forage that is low in effective fiber, or both. The syndrome involves two separate anatom- ical areas, the gastrointestinal tract and body fluids, and is related to the rate and extent of lactic

James E. Nocek

1997-01-01

104

[Physiopathology and clinical aspects of type IV renal tubular acidosis].  

PubMed

Type IV Renal tubular acidosis (RTA) is a syndrome whose physiopathological and clinical peculiarities have been described in the last decade. This syndrome can be associated with several pathological conditions characterized by reduced aldosterone activity of which hyporeninemic hypoaldosteronism is the most frequent. Type IV RTA originates in a defect in the distal nephron responsible for hydrogen and kalium ion secretion. Renal hyperchloremic acidosis and hyperkalemia are evident; the net acid secretion is decreased especially because of the urinary reduction in ammonia. Besides the behaviour of the spontaneous humoral parameters, the diagnosis of RTA is based on the tests that explore distal nephron acidification. PMID:2441325

D'Asaro, S; Lo Presti, R; Caimi, G

1987-08-15

105

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...

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

Respiratory muscle strength and muscle endurance are not affected by acute metabolic acidemia.  

PubMed

Respiratory muscle fatigue in asthma and chronic obstructive lung disease (COPD) contributes to respiratory failure with hypercapnia, and subsequent respiratory acidosis. Therapeutic induction of acute metabolic acidosis further increases the respiratory drive and, therefore, may diminish ventilatory failure and hypercapnia. On the other hand, it is known that acute metabolic acidosis can also negatively affect (respiratory) muscle function and, therefore, could lead to a deterioration of respiratory failure. Moreover, we reasoned that the impact of metabolic acidosis on respiratory muscle strength and respiratory muscle endurance could be more pronounced in COPD patients as compared to asthma patients and healthy subjects, due to already impaired respiratory muscle function. In this study, the effect of metabolic acidosis was studied on peripheral muscle strength, peripheral muscle endurance, airway resistance, and on arterial carbon dioxide tension (PaCO(2)). Acute metabolic acidosis was induced by administration of ammonium chloride (NH(4)Cl). The effect of metabolic acidosis was studied on inspiratory and expiratory muscle strength and on respiratory muscle endurance. Effects were studied in a randomized, placebo-controlled cross-over design in 15 healthy subjects (4 male; age 33.2 +/- 11.5 years; FEV(1) 108.3 +/- 16.2% predicted), 14 asthma patients (5 male; age 48.1 +/- 16.1 years; FEV(1) 101.6 +/- 15.3% predicted), and 15 moderate to severe COPD patients (9 male; age 62.8 +/- 6.8 years; FEV(1) 50.0 +/- 11.8% predicted). An acute metabolic acidemia of BE -3.1 mmol x L(-1) was induced. Acute metabolic acidemia did not significantly affect strength or endurance of respiratory and peripheral muscles, respectively. In all subjects airway resistance was significantly decreased after induction of metabolic acidemia (mean difference -0.1 kPa x sec x L(-1) [95%-CI: -0.1 - -0.02]. In COPD patients PaCO(2) was significantly lowered during metabolic acidemia (mean difference -1.73 mmHg [-3.0 - -0.08]. In healthy subjects and in asthma patients no such effect was found. Acute metabolic acidemia did not significantly decrease respiratory or peripheral muscle strength, respectively muscle endurance in nomal subjects, asthma, or COPD patients. Metabolic acidemia significantly decreased airway resistance in asthma and COPD patients, as well as in healthy subjects. Moreover, acute metabolic acidemia slightly improved blood gas values in COPD patients. The results suggest that stimulation of ventilation in respiratory failure, by induction of metabolic acidemia will not lead to deterioration of the respiratory failure. PMID:19624691

Nizet, Tessa A C; Heijdra, Yvonne F; van den Elshout, Frank J J; van de Ven, Marjo J T; Bosch, Frank H; Mulder, Paul H; Folgering, Hans Th M

2009-11-01

108

Association between pH-weighted endogenous amide proton chemical exchange saturation transfer MRI and tissue lactic acidosis during acute ischemic stroke  

PubMed Central

The ischemic tissue becomes acidic after initiation of anaerobic respiration, which may result in impaired tissue metabolism and, ultimately, in severe tissue damage. Although changes in the major cerebral metabolites can be studied using magnetic resonance (MR) spectroscopy (MRS)-based techniques, their spatiotemporal resolution is often not sufficient for routine examination of fast-evolving and heterogeneous acute stroke lesions. Recently, pH-weighted MR imaging (MRI) has been proposed as a means to assess tissue acidosis by probing the pH-dependent chemical exchange of amide protons from endogenous proteins and peptides. In this study, we characterized acute ischemic tissue damage using localized proton MRS and multiparametric imaging techniques that included perfusion, diffusion, pH, and relaxation MRI. Our study showed that pH-weighted MRI can detect ischemic lesions and strongly correlates with tissue lactate content measured by 1H MRS, indicating lactic acidosis. Our results also confirmed the correlation between apparent diffusion coefficient and lactate; however, no significant relationship was found for perfusion, T1, and T2. In summary, our study showed that optimized endogenous pH-weighted MRI, by sensitizing to local tissue pH, remains a promising tool for providing a surrogate imaging marker of lactic acidosis and altered tissue metabolism, and augments conventional techniques for stroke diagnosis. PMID:21386856

Sun, Phillip Zhe; Cheung, Jerry S; Wang, Enfeng; Lo, Eng H

2011-01-01

109

Seizure Termination by Acidosis Depends on ASIC1a  

PubMed Central

SUMMARY Most seizures stop spontaneously. However, the molecular mechanisms remain unknown. Earlier observations that seizures reduce brain pH and that acidosis inhibits seizures indicated that acidosis halts epileptic activity. Because acid–sensing ion channel–1a (ASIC1a) shows exquisite sensitivity to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a to terminate seizures. Disrupting mouse ASIC1a increased the severity of chemoconvulsant–induced seizures, whereas overexpressing ASIC1a had the opposite effect. ASIC1a did not affect seizure threshold or onset, but shortened seizure duration and prevented progression. CO2 inhalation, long known to lower brain pH and inhibit seizures, also required ASIC1a to interrupt tonic–clonic seizures. Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone. These findings identify ASIC1a as a key element in seizure termination when brain pH falls. The results suggest a molecular mechanism for how the brain stops seizures and suggest new therapeutic strategies. PMID:18536711

Ziemann, Adam E.; Schnizler, Mikael K.; Albert, Gregory W.; Severson, Meryl A.; Howard, Matthew A.; Welsh, Michael J.; Wemmie, John A.

2008-01-01

110

Acute metabolic brain changes following traumatic brain injury and their relevance to clinical severity and outcome  

Microsoft Academic Search

Background: Conventional MRI can provide critical information for care of patients with traumatic brain injury (TBI), but MRI abnormalities rarely correlate to clinical severity and outcome. Previous magnetic resonance spectroscopy studies have reported clinically relevant brain metabolic changes in patients with TBI. However, these changes were often assessed a few to several days after the trauma, with a consequent variation

Silvia Marino; Ettore Zei; Marco Battaglini; Cesare Vittori; Antonella Buscalferri; Placido Bramanti; Antonio Federico; Nicola De Stefano

2007-01-01

111

Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome.  

PubMed

Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L. PMID:25193912

El Ati, Zohra; Fatma, Lilia Ben; Boulahya, Ghada; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Beji, Soumaya; Zouaghi, Karim; Moussa, Fatma Ben

2014-09-01

112

Renal potassium wasting in renal tubular acidosis (RTA)  

PubMed Central

In two patients with classic renal tubular acidosis (RTA) and in two patients with RTA associated with the Fanconi syndrome, renal potassium wasting persisted despite sustained correction of acidosis: (a) during moderate degrees of hypokalemia, daily urinary excretion of potassium exceeded 80 mEq in each patient; (b) during more severe degrees of hypokalemia, daily urinary excretion of potassium exceeded 40 mEq in two patients and 100 mEq in another. These urinary excretion rates of potassium are more than twice those observed in potassium-depleted normal subjects with even minimal degrees of hypokalemia. The persistence of renal potassium wasting may have resulted in part from hyperaldosteronism, since urinary aldosterone was frankly increased in two patients and was probably abnormally high in the others relative to the degree of their potassium depletion. The hyperaldosteronism persisted despite sustained correction of acidosis, a normal sodium intake, and no reduction in measured plasma volume, and was not associated with hypertension; its cause was not defined. In the two patients with classic RTA, neither renal potassium wasting nor hyperaldosteronism could be explained as a consequence of a gradient restriction on renal H+ - Na+ exchange because the urinary pH remained greater than, or approximately equal to, the normal arterial pH or considerably greater than the minimal urinary pH attained during acidosis. The findings provide no support for the traditional view that renal potassium wasting in either classic RTA or RTA associated with the Fanconi syndrome is predictably corrected solely by sustained correction of acidosis with alkali therapy. PMID:5101785

Sebastian, Anthony; McSherry, Elisabeth; Morris, R. Curtis

1971-01-01

113

Management of moderate to severe psoriasis in patients with metabolic comorbidities.  

PubMed

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

114

Manipulations of the metabolic response for management of patients with severe surgical illness: review.  

PubMed

The metabolic response to severe surgical illness is complex and varied. Much recent laboratory and clinical research has focused on increasing our understanding of the metabolic response and the development of new therapies designed to modify this response. Antiinflammatory agents can target harmful aspects of the metabolic response; the immune system can be stimulated; and anabolic factors can be used in an attempt to enhance recovery. The nutritional support of the surgical patient remains crucial, but the effects of new additives are being studied in a variety of surgical conditions. As yet, few of these "novel" agents have found an established role in the management of surgical patients. This review focuses on many "novel" agents or those that do not yet have a clearly defined role in surgical illness. Clinical trials in the areas of severe sepsis, major surgical trauma, and major elective surgery have been emphasized. PMID:10773122

Connolly, A B; Vernon, D R

2000-06-01

115

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

116

Effect of induced ruminal acidosis on blood variables in heifers  

PubMed Central

Background Ruminal acidosis is responsible for the onset of different pathologies in dairy and feedlot cattle, but there are major difficulties in the diagnosis. This study modelled the data obtained from various blood variables to identify those that could indicate the severity of ruminal acidosis. Six heifers were fed three experimental rations throughout three periods. The diets were characterised by different starch levels: high starch (HS), medium starch (MS) and low starch, as the control diet (CT). Ruminal pH values were continuously measured using wireless sensors and compared with pH measurements obtained by rumenocentesis. Blood samples were analysed for complete blood count, biochemical profile, venous blood gas, blood lipopolysaccharide (LPS) and LPS-binding proteins (LBP). Results The regression coefficient comparing the ruminal pH values, obtained using the two methods, was 0.56 (P = 0.040). Feeding the CT, MS and HS led to differences in the time spent below the 5.8, 5.5 and 5.0 pH thresholds and in several variables, including dry matter intake (7.7 vs. 6.9 vs. 5.1 kg/d; P = 0.002), ruminal nadir pH (5.69 vs. 5.47 vs. 5.44; P = 0.042), mean ruminal pH (6.50 vs. 6.34 vs. 6.31; P = 0.012), haemoglobin level (11.1 vs. 10.9 vs. 11.4 g/dL; P = 0.010), platelet count (506 vs. 481 vs. 601; P = 0.008), HCO3- (31.8 vs. 31.3 vs. 30.6 mmol/L; P = 0.071) and LBP (5.9 vs. 9.5 vs. 10.5 ?g/mL; P < 0.001). A canonical discriminant analysis (CDA) was used to classify the animals into four ruminal pH classes (normal, risk of acidosis, subacute ruminal acidosis and acute ruminal acidosis) using haemoglobin, mean platelet volume, ?-hydroxybutyrate, glucose and reduced haemoglobin. Conclusions Although additional studies are necessary to confirm the reliability of these discriminant functions, the use of plasma variables in a multifactorial model appeared to be useful for the evaluation of ruminal acidosis severity. PMID:23647881

2013-01-01

117

Severe acute oxidant exposure: morphological damage and aerobic metabolism in the lung  

SciTech Connect

Groups of male rats were exposed to acute doses of oxygen, ozone, or paraquat which produced equivalent mortality (25-30%) over a 28 day post-exposure period. Quantitative evaluation of morphological changes indicated the primary response to be edema and inflammation with only slight fibrosis being apparent by the end of the observation period. Aerobic pulmonary metabolism was inhibited in lungs from animals exposed to oxygen and ozone as evidenced by decreased oxygen consumption; however, this was transient and O/sub 2/ consumption returned to normal within 24 hours after removal from the exposure chamber. Conversely, treatment with paraquat caused an immediate, transient stimulation of O/sub 2/ consumption. Glucose metabolism was unaltered by the gas exposures and, as previously reported, was initially stimulated by paraquat treatment. In vitro, only paraquat altered both O/sub 2/ consumption and glucose metabolism when added to lung slice preparations; ozone had no effect. Oxygen did not alter O/sub 2/ consumption but caused a slight biphasic response in glucose metabolism. Aerobic metabolism is relatively unchanged by these doses of oxygen and ozone which result in the death of 25-30% of all treated animals. Even though paraquat produces similar morphologic changes, it may represent a more severe metabolic insult than ''equivalent'' doses of oxygen or ozone. Also, if interstitial pulmonary fibrosis is a desired result of experimental exposure, rats may not be a suitable model for oxidant induced lung injury.

Montgomery, M.R.; Teuscher, F.; LaSota, I.; Niewoehner, D.E.

1986-09-01

118

[Correction of metabolic hypoxia in patients with severe burn injury and septic toxemia].  

PubMed

The clinical efficacy of the preparation reamberin in correction of metabolic hypoxia in patients with severe thermal burn injury under septicotoxemia was studied. It was established high efficacy of the preparation in the correction of the antioxidant defense system, its considerable antitoxic activity. Established role of reamberin in maintaining the functioning of the humoral detoxication systems, and antimicrobial resistance in patients with severe thermal injury. PMID:23610818

Kozinets, G P; Osadchaia, O I; Tsygankov, V P; Isaenko, N P; Zhernov, A A; Boiarskaia, A M

2012-12-01

119

Fatal lactic acidosis possibly related to ganciclovir therapy in a renal transplant patient?  

PubMed Central

Ganciclovir is widely prescribed in renal transplant patients for the prevention or treatment of herpes and cytomegalovirus (CMV) infections. Side-effects are usually represented by hematological disorders, and particularly leucopenia. We report a case of severe and fatal lactic acidosis developing in a 76-year-old renal transplant woman, a few days after ganciclovir has been introduced to treat CMV pneumonia. Usual etiologies of lactic acidosis were ruled out. A high lactate/pyruvate molecular ratio was suggestive of a respiratory chain dysfunction. With the analogy to nucleoside analogues-related lactic acidosis, we suggest that ganciclovir may exceptionally be responsible for respiratory chain dysfunction and subsequent lactic acidosis, and we discuss potential risk factors in our patient.

Wittebole, Xavier; Morelle, Johann; Vincent, Marie-Françoise; Hantson, Philippe

2015-01-01

120

Retal tubular acidosis complicated with hypokalemic periodic paralysis  

Microsoft Academic Search

Three Chinese girls with hypokalemic periodic paralysis secondary to different types of renal tubular acidosis are presented. One girl has primary distal renal tubular acidosis complicated with nephrocalcinosis. Another has primary Sjögren syndrome with distal renal tubular acidosis, which occurs rarely with hypokalemic periodic paralysis in children. The third has an isolated proximal renal tubular acidosis complicated with multiple organ

Ying-Chao Chang; Chao-Chang Huang; Yuan-Yow Chiou; Chin-Yin Yu

1995-01-01

121

Impaired Urinary Ammonium Excretion in Patients With Isolated Proximal Renal Tubular Acidosis  

Microsoft Academic Search

During previous studies in patients with isolated prox- imal renal tubular acidosis (pRTA), the rates of urinary ammonium excretion were considered inappro- priately low for their state of chronic metabolic aci- dosis. These observations were made while the pa- tients were on a normal diet as well as when they were undergoing a short ammonium chloride test. Because these findings

Luis G. Brenes; Marta I. Sanchez

122

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

123

Mechanisms in hyperkalemic renal tubular acidosis.  

PubMed

The form of renal tubular acidosis associated with hyperkalemia is usually attributable to real or apparent hypoaldosteronism. It is therefore a common feature in diabetes and a number of other conditions associated with underproduction of renin or aldosterone. In addition, the close relationship between potassium levels and ammonia production dictates that hyperkalemia per se can lead to acidosis. Here I describe the modern relationship between molecular function of the distal portion of the nephron, pathways of ammoniagenesis, and hyperkalemia. PMID:19193780

Karet, Fiona E

2009-02-01

124

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

125

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

126

Differential influence of arterial blood glucose on cerebral metabolism following severe traumatic brain injury  

Microsoft Academic Search

Introduction  Maintaining arterial blood glucose within tight limits is beneficial in critically ill patients. Upper and lower limits of\\u000a detrimental blood glucose levels must be determined.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  In 69 patients with severe traumatic brain injury (TBI), cerebral metabolism was monitored by assessing changes in arterial\\u000a and jugular venous blood at normocarbia (partial arterial pressure of carbon dioxide (paCO2) 4.4 to 5.6 kPa),

Monika Holbein; Markus Béchir; Silke Ludwig; Jutta Sommerfeld; Silvia R Cottini; Marius Keel; Reto Stocker; John F Stover

2009-01-01

127

Type 2 Diabetes Mellitus and the Metabolic Syndrome Following Sleeve Gastrectomy in Severely Obese Subjects  

Microsoft Academic Search

Background  Data on the effectiveness of sleeve gastrectomy in improving or resolving type 2 diabetes mellitus (T2DM) and the metabolic\\u000a syndrome (MS) are scarce.\\u000a \\u000a \\u000a \\u000a Methods  A twelve-month prospective study on the changes in glucose homeostasis and the MS in 91 severely obese T2DM subjects undergoing\\u000a laparoscopic SG (SG; n?=?39) or laparoscopic Roux-en-Y gastric bypass (GBP; n?=?52), matched for DM duration, type of

J. Vidal; A. Ibarzabal; F. Romero; S. Delgado; D. Momblán; L. Flores; A. Lacy

2008-01-01

128

Ruminal Acidosis in Feedlot: From Aetiology to Prevention  

PubMed Central

Acute ruminal acidosis is a metabolic status defined by decreased blood pH and bicarbonate, caused by overproduction of ruminal D-lactate. It will appear when animals ingest excessive amount of nonstructural carbohydrates with low neutral detergent fiber. Animals will show ruminal hypotony/atony with hydrorumen and a typical parakeratosis-rumenitis liver abscess complex, associated with a plethora of systemic manifestations such as diarrhea and dehydration, liver abscesses, infections of the lung, the heart, and/or the kidney, and laminitis, as well as neurologic symptoms due to both cerebrocortical necrosis and the direct effect of D-lactate on neurons. In feedlots, warning signs include decrease in chewing activity, weight, and dry matter intake and increase in laminitis and diarrhea prevalence. The prognosis is quite variable. Treatment will be based on the control of systemic acidosis and dehydration. Prevention is the most important tool and will require normalization of ruminal pH and microbiota. Appropriate feeding strategies are essential and involve changing the dietary composition to increase neutral detergent fiber content and greater particle size and length. Appropriate grain processing can control the fermentation rate while additives such as prebiotics or probiotics can help to stabilize the ruminal environment. Immunization against producers of D-lactate is being explored. PMID:25489604

Hernández, Joaquín; Benedito, José Luis; Abuelo, Angel; Castillo, Cristina

2014-01-01

129

PHYSIOLOGICAL EFFECTS OF ACIDOSIS ON FEEDLOT CATTLE 1  

Microsoft Academic Search

SUMMARY The physiological effects of lactic acidosis in feedlot cattle may range from temporary in- appetence to acute physiological alterations terminating in death. Physiopathology resulting from ruminal accumulation and subsequent absorption of lactic acid include rumen stasis, diarrhea and dehydration, systemic acidosis and, in acute forms of lactic acidosis, cardio- vascular and respiratory failure. The rate of lactic acid absorption

T. L. Huber

130

Acquired distal renal tubular acidosis in man  

Microsoft Academic Search

Summary Distal renal tubular acidosis (dRTA) may complicate renal transplantation, liver cirrhosis, and obstructive uropathy. Indeed, its occurrence may be an early clue to an episode of rejection of the graft or to obstructive uropathy. The mechanism in most patients with dRTA is impaired distal secretion of protons. In some patients, however, back leak of protons from tubular lumen to

O. S. Better

1982-01-01

131

Proximal Renal Tubular Acidosis in Pregnancy  

Microsoft Academic Search

Renal tubular acidosis is usually associated with chronic renal conditions and is rarely encountered in pregnancy. It may be inherited causing osteomalacia and rickets in children or acquired following autoimmune diseases or following exposure to nephrotoxic agents. It is known to worsen during pregnancy and if left untreated may cause maternal and foetal morbidity or death. We report a 28-year-old

C. J. Firmin; T. F. Kruger; R. Davids

2007-01-01

132

Atp6v0a4 knockout mouse is a model of distal renal tubular acidosis with hearing loss, with additional extrarenal phenotype  

PubMed Central

Autosomal recessive distal renal tubular acidosis (dRTA) is a severe disorder of acid–base homeostasis, often accompanied by sensorineural deafness. We and others have previously shown that mutations in the tissue-restricted a4 and B1 subunits of the H+-ATPase underlie this syndrome. Here, we describe an Atp6v0a4 knockout mouse, which lacks the a4 subunit. Using ?-galactosidase as a reporter for the null gene, developmental a4 expression was detected in developing bone, nose, eye, and skin, in addition to that expected in kidney and inner ear. By the time of weaning, Atp6v0a4?/? mice demonstrated severe metabolic acidosis, hypokalemia, and early nephrocalcinosis. Null mice were hypocitraturic, but hypercalciuria was absent. They were severely hearing-impaired, as shown by elevated auditory brainstem response thresholds and absent endocochlear potential. They died rapidly unless alkalinized. If they survived weaning with alkali supplementation, treatment could later be withdrawn, but ?/? animals remained acidotic with alkaline urine. They also had an impaired sense of smell. Heterozygous animals were biochemically normal until acid-challenged, when they became more acidotic than +/+ animals. This mouse model recapitulates the loss of H+-ATPase function seen in human disease and can provide additional insights into dRTA and the physiology of the a4 subunit. PMID:22872862

Norgett, Elizabeth E.; Golder, Zoe J.; Lorente-Cánovas, Beatriz; Ingham, Neil; Steel, Karen P.; Karet Frankl, Fiona E.

2012-01-01

133

Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy  

PubMed Central

Mammalian target of rapamycin (mTOR) is a key regulator of cell growth that associates with raptor and rictor to form the mTOR complex 1 (mTORC1) and mTORC2, respectively. Raptor is required for oxidative muscle integrity, whereas rictor is dispensable. In this study, we show that muscle-specific inactivation of mTOR leads to severe myopathy, resulting in premature death. mTOR-deficient muscles display metabolic changes similar to those observed in muscles lacking raptor, including impaired oxidative metabolism, altered mitochondrial regulation, and glycogen accumulation associated with protein kinase B/Akt hyperactivation. In addition, mTOR-deficient muscles exhibit increased basal glucose uptake, whereas whole body glucose homeostasis is essentially maintained. Importantly, loss of mTOR exacerbates the myopathic features in both slow oxidative and fast glycolytic muscles. Moreover, mTOR but not raptor and rictor deficiency leads to reduced muscle dystrophin content. We provide evidence that mTOR controls dystrophin transcription in a cell-autonomous, rapamycin-resistant, and kinase-independent manner. Collectively, our results demonstrate that mTOR acts mainly via mTORC1, whereas regulation of dystrophin is raptor and rictor independent. PMID:20008564

Risson, Valérie; Mazelin, Laetitia; Roceri, Mila; Sanchez, Hervé; Moncollin, Vincent; Corneloup, Claudine; Richard-Bulteau, Hélène; Vignaud, Alban; Baas, Dominique; Defour, Aurélia; Freyssenet, Damien; Tanti, Jean-François; Le-Marchand-Brustel, Yannick; Ferrier, Bernard; Conjard-Duplany, Agnès; Romanino, Klaas; Bauché, Stéphanie; Hantaï, Daniel; Mueller, Matthias; Kozma, Sara C.; Thomas, George; Rüegg, Markus A.; Ferry, Arnaud; Pende, Mario; Bigard, Xavier; Koulmann, Nathalie

2009-01-01

134

Down-sizing of neuronal network activity and density of presynaptic terminals by pathological acidosis are efficiently prevented by Diminazene Aceturate.  

PubMed

Local acidosis is associated with neuro-inflammation and can have significant effects in several neurological disorders, including multiple sclerosis, brain ischemia, spinal cord injury and epilepsy. Despite local acidosis has been implicated in numerous pathological functions, very little is known about the modulatory effects of pathological acidosis on the activity of neuronal networks and on synaptic structural properties. Using non-invasive MRI spectroscopy we revealed protracted extracellular acidosis in the CNS of Experimental Autoimmune Encephalomyelitis (EAE) affected mice. By multi-unit recording in cortical neurons, we established that acidosis affects network activity, down-sizing firing and bursting behaviors as well as amplitudes. Furthermore, a protracted acidosis reduced the number of presynaptic terminals, while it did not affect the postsynaptic compartment. Application of the diarylamidine Diminazene Aceturate (DA) during acidosis significantly reverted both the loss of neuronal firing and bursting and the reduction of presynaptic terminals. Finally, in vivo DA delivery ameliorated the clinical disease course of EAE mice, reducing demyelination and axonal damage. DA is known to block acid-sensing ion channels (ASICs), which are proton-gated, voltage-insensitive, Na(+) permeable channels principally expressed by peripheral and central nervous system neurons. Our data suggest that ASICs activation during acidosis modulates network electrical activity and exacerbates neuro-degeneration in EAE mice. Therefore pharmacological modulation of ASICs in neuroinflammatory diseases could represent a new promising strategy for future therapies aimed at neuro-protection. PMID:25499583

de Ceglia, Roberta; Chaabane, Linda; Biffi, Emilia; Bergamaschi, Andrea; Ferrigno, Giancarlo; Amadio, Stefano; Del Carro, Ubaldo; Mazzocchi, Nausicaa; Comi, Giancarlo; Bianchi, Veronica; Taverna, Stefano; Forti, Lia; D'Adamo, Patrizia; Martino, Gianvito; Menegon, Andrea; Muzio, Luca

2015-03-01

135

Associations between genetic variants and the severity of metabolic syndrome in subjects with type 2 diabetes.  

PubMed

Metabolic syndrome (MetS) includes obesity, dyslipidemia, elevated blood pressure, and dysglycemia. Subjects with type 2 diabetes (T2D) exhibit features of MetS. The etiology of MetS is complex, involving both environmental and genetic factors. In this study, we examined the role of specific candidate genetic variants on the severity of MetS in T2D subjects. A total of 240 T2D subjects aged 35-64 years were recruited. Waist circumstance, plasma triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, and blood pressure were measured to define MetS. Subjects were divided into 4 groups according to MetS components. Target genes involved in fibrotic and inflammatory processes, insulin and diabetes, cell growth and proliferation, and hypertension were genotyped. A total of 13 genes and 103 single-nucleotide polymorphisms (SNPs) were analyzed to evaluate their genetic association with MetS severity in T2D subjects. Univariate ordinal logistic regression using a dominant model (homozygous for the major allele vs carriers of the minor allele) revealed 6 SNP markers within 4 genes with genotypes associated with MetS risk. For the SNP genotypes of rs362551 (SNAP25), rs3818569 (RXRG), rs1479355, rs1570070 (IGF2R), and rs916829 (ABCC8), heterozygotes showed a lower risk of MetS compared with the reference group. In addition, the CC genotype was comparable to the TT genotype for rs3777411. There was no gender-specific effect. In conclusion, our results suggest that among the Han Chinese population, several SNPs increase the risk of severe MetS in T2D subjects. Further study in a large population should be conducted. PMID:25867398

Chen, Y L; Pei, D; Hung, Y J; Lee, C H; Hsiao, F C; Wu, C Z; Lin, J D; Hsu, C H; Chang, J B; Hsieh, C H

2015-01-01

136

Regional cerebral metabolic patterns demonstrate the role of anterior forebrain mesocircuit dysfunction in the severely injured brain  

PubMed Central

Although disorders of consciousness (DOCs) demonstrate widely varying clinical presentations and patterns of structural injury, global down-regulation and bilateral reductions in metabolism of the thalamus and frontoparietal network are consistent findings. We test the hypothesis that global reductions of background synaptic activity in DOCs will associate with changes in the pattern of metabolic activity in the central thalamus and globus pallidus. We compared 32 [18F]fluorodeoxyglucose PETs obtained from severely brain-injured patients (BIs) and 10 normal volunteers (NVs). We defined components of the anterior forebrain mesocircuit on high-resolution T1-MRI (ventral, associative, and sensorimotor striatum; globus pallidus; central thalamus and noncentral thalamus). Metabolic profiles for BI and NV demonstrated distinct changes in the pattern of uptake: ventral and association striatum (but not sensorimotor) were significantly reduced relative to global mean uptake after BI; a relative increase in globus pallidus metabolism was evident in BI subjects who also showed a relative reduction of metabolism in the central thalamus. The reversal of globus pallidus and central thalamus profiles across BIs and NVs supports the mesocircuit hypothesis that broad functional (or anatomic) deafferentation may combine to reduce central thalamus activity and release globus pallidus activity in DOCs. In addition, BI subjects showed broad frontoparietal metabolic down-regulation consistent with prior studies supporting the link between central thalamic/pallidal metabolism and down-regulation of the frontoparietal network. Recovery of left hemisphere frontoparietal metabolic activity was further associated with command following. PMID:24733913

Fridman, Esteban A.; Beattie, Bradley J.; Broft, Allegra; Laureys, Steven; Schiff, Nicholas D.

2014-01-01

137

Regional cerebral metabolic patterns demonstrate the role of anterior forebrain mesocircuit dysfunction in the severely injured brain.  

PubMed

Although disorders of consciousness (DOCs) demonstrate widely varying clinical presentations and patterns of structural injury, global down-regulation and bilateral reductions in metabolism of the thalamus and frontoparietal network are consistent findings. We test the hypothesis that global reductions of background synaptic activity in DOCs will associate with changes in the pattern of metabolic activity in the central thalamus and globus pallidus. We compared 32 [(18)F]fluorodeoxyglucose PETs obtained from severely brain-injured patients (BIs) and 10 normal volunteers (NVs). We defined components of the anterior forebrain mesocircuit on high-resolution T1-MRI (ventral, associative, and sensorimotor striatum; globus pallidus; central thalamus and noncentral thalamus). Metabolic profiles for BI and NV demonstrated distinct changes in the pattern of uptake: ventral and association striatum (but not sensorimotor) were significantly reduced relative to global mean uptake after BI; a relative increase in globus pallidus metabolism was evident in BI subjects who also showed a relative reduction of metabolism in the central thalamus. The reversal of globus pallidus and central thalamus profiles across BIs and NVs supports the mesocircuit hypothesis that broad functional (or anatomic) deafferentation may combine to reduce central thalamus activity and release globus pallidus activity in DOCs. In addition, BI subjects showed broad frontoparietal metabolic down-regulation consistent with prior studies supporting the link between central thalamic/pallidal metabolism and down-regulation of the frontoparietal network. Recovery of left hemisphere frontoparietal metabolic activity was further associated with command following. PMID:24733913

Fridman, Esteban A; Beattie, Bradley J; Broft, Allegra; Laureys, Steven; Schiff, Nicholas D

2014-04-29

138

The Severity of Ultrasonographic Findings in Nonalcoholic Fatty Liver Disease Reflects the Metabolic Syndrome and Visceral Fat Accumulation  

Microsoft Academic Search

BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is closely associated with the metabolic syndrome.AIM:We evaluated the association among the metabolic syndrome, visceral fat accumulation, and the severity of fatty liver with a new scoring system of ultrasonographic findings in apparently healthy Japanese adults.METHODS:Subjects consisted of 94 patients who received liver biopsy and 4,826 participants who were selected from the general population. Two

Masahide Hamaguchi; Takao Kojima; Yoshito Itoh; Yuichi Harano; Kota Fujii; Tomoaki Nakajima; Takahiro Kato; Noriyuki Takeda; Junichi Okuda; Kazunori Ida; Yutaka Kawahito; Toshikazu Yoshikawa; Takeshi Okanoue

2007-01-01

139

INFLUENCE OF ACIDOSIS ON RUMEN FUNCTION 1  

Microsoft Academic Search

SUMMARY Acute acidosis problems in ruminants is the result of excessive consumption of fermentable carbohydrates which causes a non-physiological reduction in pH and the production of a toxic factor(s). The low ruminal pH is the result of the production of large quantities of volatile fatty acids as well as other acids (such as lactic, which has a pK of 3.7)

Leonard L. Slyter

2010-01-01

140

Ruminant Nutrition Symposium: Productivity, digestion, and health responses to hindgut acidosis in ruminants.  

PubMed

Microbial fermentation of carbohydrates in the hindgut of dairy cattle is responsible for 5 to 10% of total-tract carbohydrate digestion. When dietary, animal, or environmental factors contribute to abnormal, excessive flow of fermentable carbohydrates from the small intestine, hindgut acidosis can occur. Hindgut acidosis is characterized by increased rates of production of short-chain fatty acids including lactic acid, decreased digesta pH, and damage to gut epithelium as evidenced by the appearance of mucin casts in feces. Hindgut acidosis is more likely to occur in high-producing animals fed diets with relatively greater proportions of grains and lesser proportions of forage. In these animals, ruminal acidosis and poor selective retention of fermentable carbohydrates by the rumen will increase carbohydrate flow to the hindgut. In more severe situations, hindgut acidosis is characterized by an inflammatory response; the resulting breach of the barrier between animal and digesta may contribute to laminitis and other disorders. In a research setting, effects of increased hindgut fermentation have been evaluated using pulse-dose or continuous abomasal infusions of varying amounts of fermentable carbohydrates. Continuous small-dose abomasal infusions of 1 kg/d of pectin or fructans into lactating cows resulted in decreased diet digestibility and decreased milk fat percentage without affecting fecal pH or VFA concentrations. The decreased diet digestibility likely resulted from increased bulk in the digestive tract or from increased digesta passage rate, reducing exposure of the digesta to intestinal enzymes and epithelial absorptive surfaces. The same mechanism is proposed to explain the decreased milk fat percentage because only milk concentrations of long-chain fatty acids were decreased. Pulse-dose abomasal fructan infusions (1 g/kg of BW) into steers resulted in watery feces, decreased fecal pH, and increased fecal VFA concentrations, without causing an inflammatory response. Daily 12-h abomasal infusions of a large dose of starch (~4 kg/d) have also induced hindgut acidosis as indicated by decreased fecal pH and watery feces. On the farm, watery or foamy feces or presence of mucin casts in feces may indicate hindgut acidosis. In summary, hindgut acidosis occurs because of relatively high rates of large intestinal fermentation, likely due to digestive dysfunction in other parts of the gut. A better understanding of the relationship of this disorder to other animal health disorders is needed. PMID:21415422

Gressley, T F; Hall, M B; Armentano, L E

2011-04-01

141

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

142

Multifractal Analysis of Fetal Heart Rate Variability in Fetuses with and without Severe  

E-print Network

Multifractal Analysis of Fetal Heart Rate Variability in Fetuses with and without Severe Acidosis multifractal analysis of fetal heart rate (FHR) variability in fetuses with and without acidosis during labor and nonacidotic fetuses, independently from FHR pattern. KEYWORDS: Acidosis, fetal heart rate, labor, multifractal

Abry, Patrice

143

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

144

Is lactic acidosis a cause of exercise induced hyperventilation at the respiratory compensation point?  

PubMed Central

Objectives: The respiratory compensation point (RCP) marks the onset of hyperventilation ("respiratory compensation") during incremental exercise. Its physiological meaning has not yet been definitely determined, but the most common explanation is a failure of the body's buffering mechanisms which leads to metabolic (lactic) acidosis. It was intended to test this experimentally. Methods: During a first ramp-like exercise test on a cycle ergometer, RCP (range: 2.51–3.73 l*min–1 oxygen uptake) was determined from gas exchange measurements in five healthy subjects (age 26–42; body mass index (BMI) 20.7–23.9 kg*m–2; VO2peak 51.3–62.1 ml*min–1*kg–1). On the basis of simultaneous determinations of blood pH and base excess, the necessary amount of bicarbonate to completely buffer the metabolic acidosis was calculated. This quantity was administered intravenously in small doses during a second, otherwise identical, exercise test. Results: In each subject sufficient compensation for the acidosis, that is, a pH value constantly above 7.37, was attained during the second test. A delay but no disappearance of the hyperventilation was present in all participants when compared with the first test. RCP occurred on average at a significantly (p = 0.043) higher oxygen uptake (+0.15 l*min–1) compared with the first test. Conclusions: For the first time it was directly demonstrated that exercise induced lactic acidosis is causally involved in the hyperventilation which starts at RCP. However, it does not represent the only additional stimulus of ventilation during intense exercise. Muscle afferents and other sensory inputs from exercising muscles are alternative triggering mechanisms. PMID:15388552

Meyer, T; Faude, O; Scharhag, J; Urhausen, A; Kindermann, W

2004-01-01

145

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

146

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

147

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

148

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

149

Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity  

Microsoft Academic Search

Background  The relationship between relative metabolic disturbances and developmental disorders is an emerging research focus. This study\\u000a compares the nutritional and metabolic status of children with autism with that of neurotypical children and investigates\\u000a the possible association of autism severity with biomarkers.\\u000a \\u000a \\u000a \\u000a \\u000a Method  Participants were children ages 5-16 years in Arizona with Autistic Spectrum Disorder (n = 55) compared with non-sibling,\\u000a neurotypical

James B Adams; Tapan Audhya; Sharon McDonough-Means; Robert A Rubin; David Quig; Elizabeth Geis; Eva Gehn; Melissa Loresto; Jessica Mitchell; Sharon Atwood; Suzanne Barnhouse; Wondra Lee

2011-01-01

150

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

151

Metformin-associated lactic acidosis presenting as an ischemic gut in a patient who then survived a cardiac arrest: a case report  

PubMed Central

Introduction Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. It is recognized as a potential complication of metformin use, particularly in patients with risk factors such as renal dysfunction, liver disease, and heavy alcohol ingestion. These conditions are associated with systemic hypoxemia, which may be caused by cardiorespiratory disease, major surgery, sepsis, dehydration, old age, and overdose. The reported frequency of lactic acidosis is 0.06 per 1000 patient-years, mostly in patients with predisposing factors. This case is important because it details the seriousness of metformin-associated lactic acidosis in a critically ill patient and because, to the best of our knowledge, our patient survived with minimal residual defect despite experiencing a cardiac arrest. Case presentation A 66-year-old Caucasian woman presented to our hospital with profound lactic acidosis, which was initially thought to be ischemic gut. She then survived an in-hospital pulseless electrical activity arrest. Conclusion Metformin-associated lactic acidosis is a diagnosis by exclusion; however, a high degree of clinical suspicion supplemented by prompt multisystem organ support can significantly influence the outcome in critically ill patients. PMID:24884658

2014-01-01

152

Optimal correction of acidosis changes progression of dialysis osteodystrophy  

Microsoft Academic Search

Optimal correction of acidosis changes progression of dialysis osteodystrophy. To investigate an eventual role of acidosis on hemodialysis osteodystrophy we prospectively studied 21 patients who were dialyzed with different amounts of bicarbonate in the dialysate for 18 months. According to the level of bone formation rate (BFR) on a prestudy bone biopsy, patients were split in two subgroups. Inside these

Alfred Lefebvre; Marie Christine de Vernejoul; Jean Gueris; Bernard Goldfarb; Anne Marie Graulet; Caroline Morieux

1989-01-01

153

Evidence for a Detrimental Effect of Bicarbonate Therapy in Hypoxic Lactic Acidosis  

NASA Astrophysics Data System (ADS)

Lactic acidosis, a clinical syndrome caused by the accumulation of lactic acid, is characterized by lactate concentration in blood greater than 5 mM. Therapy usually consists of intravenous sodium bicarbonate (NaHCO3), but resultant mortality is greater than 60 percent. The metabolic and systemic effects of NaHCO3 therapy of hypoxic lactic acidosis in dogs were studied and compared to the effects of sodium chloride or no therapy. Sodium bicarbonate elevated blood lactate concentrations to a greater extent than did either sodium chloride or no treatment. Despite the infusion of NaHCO3, both arterial pH and bicarbonate concentration decreased by a similar amount in all three groups of dogs. Additional detrimental effects of NaHCO3 were observed on the cardiovascular system, including decreases in cardiac output and blood pressure that were not observed with either sodium chloride or no treatment. Thus there is evidence for a harmful effect of NaHCO3 in the treatment of hypoxic lactic acidosis.

Graf, Helmut; Leach, William; Arieff, Allen I.

1985-02-01

154

Cardiovascular Fitness, Insulin Resistance and Metabolic Syndrome in Severely Obese Prepubertal Italian Children  

Microsoft Academic Search

Aim: To evaluate if insulin resistance (IR) and metabolic syndrome (MS) were associated with poor cardiovascular fitness in very obese prepubertal Italian subjects. Methods: Children referred to the Endocrinology and Diabetes Unit of Bambino Gesù Children’s Hospital underwent an OGTT with glucose and insulin assays. QUICKI, ISI and HOMA-IR were calculated. Total and HDL cholesterol, triglycerides and percentage of body

Claudia Brufani; Armando Grossi; Danilo Fintini; Rossana Fiori; Graziamaria Ubertini; Diego Colabianchi; Paolo Ciampalini; Alberto Tozzi; Fabrizio Barbetti; Marco Cappa

2008-01-01

155

Increased prevalence of the metabolic syndrome in patients with moderate to severe psoriasis  

Microsoft Academic Search

The role of chronic inflammation causing metabolic and vascular disorders is increasingly recognized. It is hypothesized that proinflammatory cytokines contribute to atherogenesis, peripheral insulin resistance, and the development of hypertension and type II diabetes. Psoriasis as a chronic inflammatory skin disorder is characterized by a variety of immunologic and inflammatory changes and may similarly predispose for those disorders. The objective

Dorothea M. Sommer; Stefan Jenisch; Michael Suchan; Enno Christophers; Michael Weichenthal

2007-01-01

156

N-3 polyunsaturated fatty acids regulate lipid metabolism through several inflammation mediators: mechanisms and implications for obesity prevention  

Microsoft Academic Search

Obesity is a growing problem that threatens the health and welfare of a large proportion of the human population. The n-3 polyunsaturated fatty acids (PUFA) are dietary factors that have potential to facilitate reduction in body fat deposition and improve obesity-induced metabolic syndromes. The n-3 PUFA up-regulate several inflammation molecules including serum amyloid A (SAA), tumor necrosis factor-? (TNF-?) and

Chen C. Tai; Shih T. Ding

2010-01-01

157

[The role of lactate acidosis in the development and treatment of various neurologic syndromes in children and adolescents].  

PubMed

The aim of the study was to detect the role of lactate acidosis, also to find the share of mitochondrial insufficiency in development of various neurologic syndromes in children and adolescents. The detection of cellular energetic metabolism and acid based imbalance is also important for finding the specific method of management. We have studied 200 patients with various degree of neurodevelopment delay with epilepsy and epileptic syndromes, headache, vertigo, early strokes, floppy infant syndrome, atrophy of ophthalmic nerve, cataracta, neurosensory deafness, systemic myopathy, cerebral palsy. In 27% of cases with various ages we have detected lactate acidosis and increase level of pyruvate. Mitochondrial insufficiency was seen in 8% of cases which gives us opportunity to find the specific method of treatment in this group of patients. Each patient with neurological symptoms requires correction of parameters of energetic and oxidative metabolism. PMID:25802453

Arveladze, G; Geladze, N; Sanikidze, T; Khachapuridze, N; Bakhtadze, S

2015-02-01

158

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

2015-03-01

159

Haploinsufficiency of the ammonia transporter Rhcg predisposes to chronic acidosis: Rhcg is critical for apical and basolateral ammonia transport in the mouse collecting duct.  

PubMed

Ammonia secretion by the collecting duct (CD) is critical for acid-base homeostasis and, when defective, causes distal renal tubular acidosis (dRTA). The Rhesus protein RhCG mediates NH(3) transport as evident from cell-free and cellular models as well as from Rhcg-null mice. Here, we investigated in a Rhcg mouse model the metabolic effects of Rhcg haploinsufficiency, the role of Rhcg in basolateral NH(3) transport, and the mechanisms of adaptation to the lack of Rhcg. Both Rhcg(+/+) and Rhcg(+/-) mice were able to handle an acute acid load, whereas Rhcg(-/-) mice developed severe metabolic acidosis with reduced ammonuria and high mortality. However, chronic acid loading revealed that Rhcg(+/-) mice did not fully recover, showing lower blood HCO(3)(-) concentration and more alkaline urine. Microperfusion studies demonstrated that transepithelial NH(3) permeability was reduced by 80 and 40%, respectively, in CDs from Rhcg(-/-) and Rhcg(+/-) mice compared with controls. Basolateral membrane permeability to NH(3) was reduced in CDs from Rhcg(-/-) mice consistent with basolateral Rhcg localization. Rhcg(-/-) responded to acid loading with normal expression of enzymes and transporters involved in proximal tubular ammoniagenesis but reduced abundance of the NKCC2 transporter responsible for medullary accumulation of ammonium. Consequently, tissue ammonium content was decreased. These data demonstrate a role for apical and basolateral Rhcg in transepithelial NH(3) transport and uncover an incomplete dRTA phenotype in Rhcg(+/-) mice. Haploinsufficiency or reduced expression of RhCG may underlie human forms of (in)complete dRTA. PMID:23281477

Bourgeois, Soline; Bounoure, Lisa; Christensen, Erik I; Ramakrishnan, Suresh K; Houillier, Pascal; Devuyst, Olivier; Wagner, Carsten A

2013-02-22

160

Relationship between regional brain metabolism, illness severity and age in depressed subjects.  

PubMed

We sought to examine the effects of age, depression chronicity, and treatment responsiveness on glucose metabolism in a large well-characterized sample of depressed men and a psychiatrically unaffected control group. The subjects were unmedicated, symptomatic, right-handed males (n=66) who met DSM-IV criteria for a major depressive episode in the context of a major depressive disorder (MDD, n=66) and never depressed, right-handed, healthy control subjects (HC, n=24). Subjects in the MDD group were subsequently classified as responders, or non-responders to a six-week trial of paroxetine monotherapy (20-60 mg). Statistical parametric mapping (SPM) was used to analyze the relationship between age and cerebral glucose metabolism (18-fluorodeoxyglucose positron emission tomography) and the modulation by treatment responsivity and a history of prior depressive episodes. Metabolic activity in the rostral and dorsal anterior cingulate cortex showed a significant negative correlation with age in MDD, but not in HC. Non-response to treatment and previous depressive episodes were associated with a higher degree of age-dependent hypometabolism in the rostral and anterior cingulate cortex. The age-dependent changes documented herein may influence the distinct clinical presentation and treatment response described in older-age depression. PMID:17574393

Konarski, Jakub Z; Kennedy, Sidney H; McIntyre, Roger S; Rafi-Tari, Shahryar; Soczynska, Joanna K; Mayberg, Helen S

2007-08-15

161

Comparison of the effects of intravenous administration of isotonic and hypertonic sodium bicarbonate solutions on venous acid-base status in dehydrated calves with strong ion acidosis.  

PubMed

OBJECTIVE-To compare the effects of IV administration of isotonic (1.3%) and hypertonic (8.4%) sodium bicarbonate (NaHCO(3)) solutions on acid-base status in dehydrated calves with strong ion (metabolic) acidosis. DESIGN-Randomized controlled clinical trial. ANIMALS-50 calves with diarrhea and severe dehydration. PROCEDURES-Calves were randomly assigned to receive isotonic NaHCO(3) solution (65 mL/kg [29.5 mL/lb], IV) over 3 hours (n = 30) or hypertonic NaHCO(3) solution (10 mL/kg [4.5 mL/lb], IV) over 20 minutes (20). Blood samples were collected at 0 hours (immediately prior to solution administration) and at 0.5, 1, 2, and 4 hours after administration began. Samples were submitted for blood gas analysis, serum biochemical analysis, and determination of blood Na(+), K(+), and Cl(-) concentrations and percentage change in plasma volume. RESULTS-Calves that received isotonic NaHCO(3) solution had an increase in venous blood pH, HCO(3) concentration, and base excess; a small, transient increase in Po(2); and no change in Pco(2) within 4 hours after administration began. Calves that received hypertonic NaHCO(3) solution had an immediate increase in venous blood pH, HCO(3) concentration, and base excess; a small, transient increase Pco(2); and no change in Po(2) within 0.5 hours after treatment began. Plasma volume increased to a greater extent following administration of isotonic solution than after administration of hypertonic solution. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of 8.4% NaHCO(3) solution in small volumes provided fast and effective improvement of severe acid-base abnormalities in calves with severe strong ion acidosis but did not improve hydration status as well as administration of a larger volume of isotonic NaHCO(3) solution. PMID:20470072

Coskun, Alparslan; Sen, Ismail; Guzelbektes, Hasan; Ok, Mahmut; Turgut, Kursat; Canikli, Sebnem

2010-05-15

162

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

163

Carbamazepine substitution in severe partial epilepsy: implication of autoinduction of metabolism.  

PubMed Central

Established partial seizures are often refractory to treatment and many patients receive polypharmacy. An attempt was made to improve seizure control with the substitution of carbamazepine (CBZ) for existing treatment in 7 consecutive unremitting cases of partial epilepsy referred by their physicians as 'intractable'. This produced a significant improvement in control of partial (P less than 0.02) and secondary generalized (P less than 0.01) seizures, with 5 patients experiencing a 50% or greater reduction in seizure frequency. A single patient suffered a generalized seizure during the period of changeover. In 3 cases auto-induction of CBZ metabolism resulted in temporary loss of seizure control which was restored by an increase in dose. A policy of planned substitution of CBZ in partial epilepsy previously regarded as intractable may be successful in selected patients. The possible deleterious effect of CBZ auto-induction should be anticipated. PMID:3932988

Macphee, G. J.; Brodie, M. J.

1985-01-01

164

Primary Role of Hyperkalemia in the Acidosis of Hyporeninemic Hypoaldosteronism  

Microsoft Academic Search

A 65-year-old woman with mild renal insufficiency had persistent hyperkalemia and hyperchloremic acidosis. Her plasma aldosterone level was relatively low for her hyperkalemia, and her urine pH was low. Fludrocortisone acetate administration corrected both hyperkalemia and acidosis by increasing urinary excretion of potassium and net acid, implicating deficient mineralocorticoid activity in the distal renal tubule in this patient. During this

Osamu Matsuda; Hiroshi Nonoguchi; Kimio Tomita; Tatsuo Shiigai; Takashi Ida; Shinsuke Shinohara; Terukuni Ideura; Jugoro Takeuchi

1988-01-01

165

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

166

Combined 1 H and 31 P MR spectroscopic imaging: impaired energy metabolism in severe carotid stenosis and changes upon treatment  

Microsoft Academic Search

Object  To evaluate if combined 1H and 31P MR spectroscopic imaging (MRSI) before and after treatment of severe internal carotid artery (ICA) stenosis detects significant\\u000a changes in energy metabolism in the basal ganglia of both hemispheres.\\u000a \\u000a \\u000a \\u000a Materials and methods  A group of 14 patients with high-grade ICA stenosis and 11 healthy control subjects were examined with 2D 1H MRSI and 3D 31P

E. Hattingen; H. Lanfermann; S. Menon; T. Neumann-Haefelin; R. DuMesnil de Rochement; M. Stamelou; G. U. Höglinger; J. Magerkurth; U. Pilatus

2009-01-01

167

Metabolism  

MedlinePLUS

... Some metabolic diseases and conditions include: Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism is caused ... or through surgery or radiation treatments. Hypothyroidism (pronounced: hi-po-THIGH-roy-dih-zum) . Hypothyroidism is caused ...

168

Hemodynamic and metabolic basis of impaired exercise tolerance in patients with severe left ventricular dysfunction  

SciTech Connect

Hemodynamic and metabolic changes were measured at rest and during exercise in 23 patients with chronic heart failure and in 6 control subjects. Exercise was limited by leg fatigue in both groups and capacity was 40% lower in the patients with failure. At rest, comparing patients with control subjects, heart rate and right atrial and pulmonary wedge pressure were higher; cardiac output, stroke volume and work indexes and ejection fraction were lower; mean arterial and right atrial pressure and systemic resistance were similar. During all phases of exercise in patients with heart failure, pulmonary wedge pressure and systemic vascular resistance were higher and pulmonary vascular resistance remained markedly elevated compared with values in control subjects. Cardiac output was lower in the patients with failure, but appeared to have the same physiologic distribution in both groups during exercise. Although arterial-femoral venous oxygen content difference was higher in patients with heart failure, this increase did not compensate for the reduced blood flow. Even though the maximal oxygen consumption was significantly reduced, femoral venous lactate and pH values were higher than values in control subjects, but femoral venous pH was similar in both groups at their respective levels of maximal exercise. Ejection fraction was lower in those with heart failure at rest and did not increase with exercise. Ventilation in relation to oxygen consumption was higher in patients with failure than in control subjects.

Roubin, G.S.; Anderson, S.D.; Shen, W.F.; Choong, C.Y.; Alwyn, M.; Hillery, S.; Harris, P.J.; Kelly, D.T. (Hallstrom Institute of Cardiology, Sydney, New South Wales (Australia))

1990-04-01

169

Novel Mutation Causing Derepression of Several Enzymes of Sulfur Metabolism in Neurospora crassa  

PubMed Central

A group of enzymes of sulfur metabolism (arylsulfatase, cholinesulfatase, and a number of others) are normally repressed in Neurospora crassa by an abundant supply of a “favored” sulfur source such as methionine or inorganic sulfate. A mutant called sconc was isolated in which the formation of each of these enzymes is largely or completely nonrepressible. The structural genes for three of these enzymes have been mapped; sconc is not linked to any of them. It is also not linked to cys-3, another gene which is involved in control of the same group of enzymes. Two alleles of the structural gene for arylsulfatase [ars+ and ars(UFC-220)] produce electrophoretically distinguishable forms of arylsulfatase. Heterokaryons with the constitution sconc ars+ + scon+ars(UFC-220) were prepared. These heterokaryons produce both forms of arylsulfatase under conditions of sulfur limitation, but produce only the wild-type (ars+) form under conditions of sulfur abundance. When the alleles of ars and scon are in the opposite relationship, only the ars(UFC-220) form of arylsulfatase can be detected under conditions of sulfur abundance. Thus the effect of the sconc mutation seems to be limited to its own nucleus. The implications of these findings are discussed. Images PMID:4257980

Burton, Earl G.; Metzenberg, Robert L.

1972-01-01

170

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...

171

Distal renal tubular acidosis with multiorgan autoimmunity: a case report.  

PubMed

A 61-year-old woman with a history of pernicious anemia presented with progressive muscle weakness and dysarthria. Hypokalemic paralysis (serum potassium, 1.4 mEq/L) due to distal renal tubular acidosis (dRTA) was diagnosed. After excluding several possible causes, dRTA was considered autoimmune. However, the patient did not meet criteria for any of the autoimmune disorders classically associated with dRTA. She had very high antibody titers against parietal cells, intrinsic factor, and thyroid peroxidase (despite normal thyroid function). The patient consented to a kidney biopsy, and acid-base transporters, anion exchanger type 1 (AE1), and pendrin were undetectable by immunofluorescence. Indirect immunofluorescence detected diminished abundance of AE1- and pendrin-expressing intercalated cells in the kidney, as well as staining by the patient's serum of normal human intercalated cells and parietal cells expressing the adenosine triphosphatase hydrogen/potassium pump (H(+)/K(+)-ATPase) in normal human gastric mucosa. The dRTA likely is caused by circulating autoantibodies against intercalated cells, with possible cross-reactivity against structures containing gastric H(+)/K(+)-ATPase. This case demonstrates that in patients with dRTA without a classic autoimmune disorder, autoimmunity may still be the underlying cause. The mechanisms involved in autoantibody development and how dRTA can be caused by highly specific autoantibodies against intercalated cells have yet to be determined. PMID:25533600

van den Wildenberg, Maria J; Hoorn, Ewout J; Mohebbi, Nilufar; Wagner, Carsten A; Woittiez, Arend-Jan; de Vries, Peter A M; Laverman, Gozewijn D

2015-04-01

172

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

173

Severe hyperkalemia as a complication of timolol, a topically applied beta-adrenergic antagonist  

SciTech Connect

Severe hyperkalemia occurred in a patient with radiation pneumonitis and glaucoma shortly after beginning prednisone therapy. There was no evidence of renal failure, diabetes, acidosis, increased potassium intake, or significant tissue trauma. Medications having adverse effects on potassium metabolism were considered, and the patient's use of timolol maleate eyedrops was discontinued. His serum potassium level normalized despite continuation of the prednisone therapy. He became hyperkalemic on rechallenge with timolol and normokalemic following its withdrawal. This case indicates that the potential for beta-blocker-induced hyperkalemia exists even with topical appreciation.

Swenson, E.R.

1986-06-01

174

Primary role of hyperkalemia in the acidosis of hyporeninemic hypoaldosteronism.  

PubMed

A 65-year-old woman with mild renal insufficiency had persistent hyperkalemia and hyperchloremic acidosis. Her plasma aldosterone level was relatively low for her hyperkalemia, and her urine pH was low. Fludrocortisone acetate administration corrected both hyperkalemia and acidosis by increasing urinary excretion of potassium and net acid, implicating deficient mineralocorticoid activity in the distal renal tubule in this patient. During this medication urinary ammonium excretion increased, but urine pH remained low, so that urinary titratable acid excretion did not decrease. On the other hand, correction of hyperkalemia by administration of a potassium-calcium exchange resin alone also resolved the acidosis by increasing urinary ammonium excretion. This increment exceeded the decrement of urinary titratable acid excretion, which was caused by raised urine pH secondary to increased urinary ammonium excretion, and resulted in increase of net acid excretion. Thus, in this patient, hyperkalemia appears to be a decisive causative factor in the acidosis, with deficient mineralocorticoid effect only contributing in part to the reduction of net acid excretion and the acidosis. PMID:3398981

Matsuda, O; Nonoguchi, H; Tomita, K; Shiigai, T; Ida, T; Shinohara, S; Ideura, T; Takeuchi, J

1988-01-01

175

Mitochondrial uncoupling reduces exercise capacity despite several skeletal muscle metabolic adaptations.  

PubMed

The effects of mitochondrial uncoupling on skeletal muscle mitochondrial adaptation and maximal exercise capacity are unknown. In this study, rats were divided into a control group (CTL, n = 8) and a group treated with 2,4-dinitrophenol, a mitochondrial uncoupler, for 28 days (DNP, 30 mg·kg(-1)·day(-1) in drinking water, n = 8). The DNP group had a significantly lower body mass (P < 0.05) and a higher resting oxygen uptake (Vo2, P < 0.005). The incremental treadmill test showed that maximal running speed and running economy (P < 0.01) were impaired but that maximal Vo2 (Vo2max) was higher in the DNP-treated rats (P < 0.05). In skinned gastrocnemius fibers, basal respiration (V0) was higher (P < 0.01) in the DNP-treated animals, whereas the acceptor control ratio (ACR, Vmax/V0) was significantly lower (P < 0.05), indicating a reduction in OXPHOS efficiency. In skeletal muscle, DNP activated the mitochondrial biogenesis pathway, as indicated by changes in the mRNA expression of PGC1-? and -?, NRF-1 and -2, and TFAM, and increased the mRNA expression of cytochrome oxidase 1 (P < 0.01). The expression of two mitochondrial proteins (prohibitin and Ndufs 3) was higher after DNP treatment. Mitochondrial fission 1 protein (Fis-1) was increased in the DNP group (P < 0.01), but mitofusin-1 and -2 were unchanged. Histochemical staining for NADH dehydrogenase and succinate dehydrogenase activity in the gastrocnemius muscle revealed an increase in the proportion of oxidative fibers after DNP treatment. Our study shows that mitochondrial uncoupling induces several skeletal muscle adaptations, highlighting the role of mitochondrial coupling as a critical factor for maximal exercise capacities. These results emphasize the importance of investigating the qualitative aspects of mitochondrial function in addition to the amount of mitochondria. PMID:24336883

Schlagowski, A I; Singh, F; Charles, A L; Gali Ramamoorthy, T; Favret, F; Piquard, F; Geny, B; Zoll, J

2014-02-15

176

Genetics Home Reference: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes  

MedlinePLUS

... Most people with MELAS have a buildup of lactic acid in their bodies, a condition called lactic acidosis. ... gene ; hemiparesis ; incidence ; inherit ; inheritance ; inherited ; involuntary ; kidney ; lactic acid ; lactic acidosis ; maternal ; maternal inheritance ; mitochondria ; mutation ; myoclonus ; ...

177

Myopathy, lactic acidosis, and sideroblastic anemia: a new syndrome.  

PubMed

We describe 2 sibs (brother and sister) with myopathy, sideroblastic anemia, lactic acidosis, mental retardation, microcephaly, high palate, high philtrum, distichiasis, and micrognathia. Very low levels of cytochromes a, b, and c were detected in the patients' muscle mitochondria. Deposition of iron within the mitochondria of bone marrow erythroblasts was observed on electron microscopy. Irregular and enlarged mitochondria with paracrystalline inclusions were also seen on electron microscopy of the patients' muscle specimen. Examination of DNA from the affected sibs showed no deletions in the mitochondrial DNA nor the mutations identified in the syndromes of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) or myoclonus, and epilepsy associated with rugged-red fibers (MERRF). Since the parents were first cousins and 2 of 6 sibs (male and female) were affected, we suggest that the syndrome expressed by our patients represents a previously unknown autosomal recessive disorder that includes mitochondrial myopathy, lactic acidosis, and sideroblastic anemia. PMID:7726239

Inbal, A; Avissar, N; Shaklai, M; Kuritzky, A; Schejter, A; Ben-David, E; Shanske, S; Garty, B Z

1995-01-30

178

Intermittent Cold-Blood Cardioplegia and Its Impact on Myocardial Acidosis during Coronary Bypass Surgery.  

PubMed

Background?The purpose of the study was to assess the degree of myocardial acidosis in patients undergoing elective coronary bypass surgery, in whom intermittent cold-blood cardioplegia (ICBC) was used for myocardial protection. The results of this study are presented in comparison to those of a previous trial conducted by the same investigators, using a similar methodology, but with intermittent warm-blood cardioplegia (IWBC). Patients and Methods?In 15 patients undergoing elective myocardial revascularization with ICBC for myocardial protection, metabolic changes of global ischemia indicators, lactate and pH values (measured simultaneously in coronary sinus and arterial blood) were analyzed. Lactate concentrations and pH values were measured at the beginning and the end of each cardioplegia administration, and the change-overtime analysis of the values was performed. For comparison with the results of the previous study (IWBC method) consisting of 12 patients, the analysis of variance with repeated measurements, including tests for a crossover, group, and time effect were used. Results?Using the ICBC method, as compared with IWBC, no significant difference in the lactate production was observed during the first two successive cardioplegia administrations. During the third and fourth administrations, especially at the end of reperfusions, ICBC patients had a significantly lower lactate release and higher pH values, as compared with IWBC patients. Conclusion?Our results suggest that ICBC has an inhibiting effect on potentially progressive myocardial acidosis during cross-clamp period. PMID:25423313

Borowski, Andreas; Godehardt, Erhard; Paprotny, Gerrit; Kurt, Muhammed

2014-11-25

179

Comparison of gas exchange, lactate, and lactic acidosis thresholds in patients with chronic obstructive pulmonary disease.  

PubMed

During an incremental exercise test, three consequences of the onset of anaerobic metabolism can be observed: rise in blood lactate (lactate threshold, LT); fall in standard bicarbonate (lactic acidosis threshold, LAT); nonlinear increase in CO2 output (V-slope gas exchange threshold, GET). We compared these thresholds in 31 patients with COPD. We found that the GET and LAT overestimated the LT. A better relationship was found between LAT and GET, even though GET was significantly higher than LAT (by 124 ml/min; p < 0.0001). However, since the bias is appreciably greater at lower LAT values (likely because VCO2 kinetics are slower than VO2 kinetics), we separated the studies into two groups: (A) tests where LAT occurred within the first 2 min of the increasing work rate period, and (B) tests where LAT occurred after 2 min. For Group A, there was a substantial bias between LAT and GET (323 ml/min, p < 0.0001), whereas the bias was much smaller (only 5.4%, though statistically significant) for Group B (57 ml/min, p < 0.01). We conclude that when lactic acidosis occurs after the first 2 min of incremental exercise, the GET closely approximates the point at which blood bicarbonate begins to fall. PMID:8368633

Patessio, A; Casaburi, R; Carone, M; Appendini, L; Donner, C F; Wasserman, K

1993-09-01

180

Intracellular Acidosis Enhances the Excitability of Working Muscle  

NASA Astrophysics Data System (ADS)

Intracellular acidification of skeletal muscles is commonly thought to contribute to muscle fatigue. However, intracellular acidosis also acts to preserve muscle excitability when muscles become depolarized, which occurs with working muscles. Here, we show that this process may be mediated by decreased chloride permeability, which enables action potentials to still be propagated along the internal network of tubules in a muscle fiber (the T system) despite muscle depolarization. These results implicate chloride ion channels in muscle function and emphasize that intracellular acidosis of muscle has protective effects during muscle fatigue.

Pedersen, Thomas H.; Nielsen, Ole B.; Lamb, Graham D.; Stephenson, D. George

2004-08-01

181

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

182

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

183

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.

184

Acute Renal Response to Rapid Onset Respiratory Acidosis  

PubMed Central

Renal strong ion compensation to chronic respiratory acidosis has been established but the nature of the response to acute respiratory acidosis is not well defined. We hypothesized that the response to acute respiratory acidosis in sheep is a rapid increase in the difference in renal fractional excretions of chloride and sodium (FeCl-FeNa). Inspired CO2 concentrations were increased for one hour to alter significantly PaCO2 and pHa from 32 ± 1 mm Hg and 7.52 ± 0.02 to 74 ± 2 mm Hg and 7.22 ± 0.02, respectively. FeCl-FeNa increased significantly from 0.372 ± 0.206 to 1.240 ± 0.217 % and returned to baseline at two hours when PaCO2 and pHa were 37 ± 0.6 mm Hg and 7.49 ± 0.01, respectively. Arterial pH and FeCl-FeNa were significantly correlated. We conclude that the kidney responds rapidly to acute respiratory acidosis, within 30 mins of onset, by differential reabsorption of sodium and chloride. PMID:21423296

Ramadoss, Jayanth; Stewart, Randolph H.; Cudd, Timothy A.

2011-01-01

185

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

186

Ruminant Nutrition Symposium: Acidosis: new insights into the persistent problem.  

PubMed

The Ruminant Nutrition Symposium titled "Acidosis: New insights into the persistent problem" was held at the Joint Annual Meeting of the American Dairy Science Association, American Society of Animal Science, Poultry Science Association, Asociación Mexicana de Producción Animal, Western Section-ASAS, and the Canadian Society of Animal Science in Denver, Colorado, July 11 to 15, 2010. The objective of the symposium was to provide the ruminant nutrition community with new insights and perspectives from recent research findings on acidosis. Under modern production systems, ruminants are fed high-grain diets to maximize their energy intake and productivity. However, feeding highly fermentable diets often causes excess fermentation and results in accumulation of fermentation acids in the rumen, leading to a decrease in feed intake, poor feed efficiency, liver abscesses, and lameness in feedlot cattle or lactating dairy cows. Although our understanding of nutritional factors (i.e., effects of type and processing method of grains and importance of physically effective fiber) affecting rumen pH have increased substantially over the past few decades, rumen acidosis has continued to be a common problem in the ruminant livestock industry. The symposium program was organized to review recent research findings in acidosis with more emphasis on physiological aspects, and provide novel insights into the persistent problem. PMID:21148789

Oba, M; Wertz-Lutz, A E

2011-04-01

187

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

188

Why are dairy cows not able to cope with the subacute ruminal acidosis?  

PubMed

One of the largest challenges for the dairy industry is to provide cows with a diet which is highly energetic but does not negatively affect their rumens' functions. In highly productive dairy cows, feeding diets rich in readily fermentable carbohydrates provides energy precursors needed for maximum milk production, but simultaneously decreases ruminal pH, leading to a widespread prevalence of subacute ruminal acidosis. Maximizing milk production without triggering rumen acidosis still challenges dairy farmers, who try to prevent prolonged bouts of low ruminal pH mainly by proper nutrition and management practices. The animals try to avoid overeating fermentable feeds, as it causes negative consequences by disturbing digestive processes. The results of several experiments show that ruminants, including sheep and beef cattle, are able to modify some aspects of feeding behaviour in order to adjust nutrient intake to their needs and simultaneously prevent physiological disturbances. Particularly, such changes (e.g., increased preference for fibrous feeds, reduced intake of concentrates) were observed in animals, which were trying to prevent the excessive drop of rumen fluid pH. Thanks to a specific mechanism called "the postingestive feedback", animals should be able to work out such a balance in intake, so they do not suffer either from hunger or from negative effects of over-ingesting the fermentable carbohydrates. This way, an acidosis should not be a frequent problem in ruminants. However, prolonged periods of excessively decreased rumen pH are still a concern in dairy cows. It raises a question, why the regulation of feed intake by postingestive feedback does not help to maintain stable rumen environment in dairy cows? PMID:24597322

Brzozowska, A M; Sloniewski, K; Oprzadek, J; Sobiech, P; Kowalski, Z M

2013-01-01

189

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

190

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

191

Substitution of calcium carbonate for aluminum hydroxide in patients on hemodialysis. Effects on acidosis, on parathyroid function, and on calcemia.  

PubMed

Substitution of calcium carbonate for aluminum hydroxide in patients on dialysis: effects on acidosis, parathyroid function, and calcemia. We studied the effects of substituting CaCO3 for aluminum-containing gels on metabolic acidosis and on the response of the parathyroid glands in 11 patients treated with chronic hemodialysis. The 8 men and 3 women were clinically stable, were known to be compliant, and had no clinical evidence of aluminum overload; they were not receiving vitamin D supplements; and they had been on dialysis for an average of 65.6 months (range: 13-188 months). After 3 weeks of CaCO3 administration plasma phosphate concentration remained well controlled, and plasma calcium concentration increased from 9.2 +/- 0.2 (2.3 +/- 0.1 mmol/l) to 10.1 +/- 0.2 mg/dl (2.5 +/- 0.1 mmol/l). Predialysis plasma bicarbonate concentration increased from 19.7 +/- 0.6 to 21.9 +/- 0.6 mmol/l. Plasma aluminum concentration decreased from 78.7 +/- 12.5 to 48.5 +/- 3.9 micrograms/l. Plasma PTH level increased from 2.0 +/- 0.7 to 3.3 +/- 0.8 ng/ml despite the concurrent increase in plasma calcium levels. All values returned to control levels following discontinuation of CaCO3 and resumption of aluminum gels. We conclude: (1) In addition to controlling hyperphosphatemia and increasing plasma calcium concentration, CaCO3 ameliorates metabolic acidosis. (2) Avoidance of oral aluminum intake is followed by prompt lowering of plasma aluminum levels. (3) PTH levels paradoxically increase despite the increment in plasma calcium concentration. The hypercalcemia seen with CaCO3 administration may be due, in part, to transient parathyroid hypersecretion that develops when aluminum administration is discontinued. PMID:2500612

Anelli, A; Brancaccio, D; Damasso, R; Padovese, P; Gallieni, M; Garella, S

1989-01-01

192

Metabolic studies of transient tyrosinemia in premature infants  

NASA Technical Reports Server (NTRS)

The recently developed technique of gas chromatography-mass spectrometry supported by computer has considerably improved the analysis of physiologic fluids. This study attempted to demonstrate the value of this system in the investigation of metabolite patterns in urine in two metabolic problems of prematurity, transient tyrosinemia and late metabolic acidosis. Serial 24-hr urine specimens were analyzed in 9 infants. Transient tyrosinemia, characterized by 5- 10-fold increases over basal excretion of tyrosine, p-hydroxyphenyllactate, and p-hydroxyphenylpyruvate in urine, was noted in five of the infants. Late metabolic acidosis was seen in four infants, but bore no relation to transient tyrosinemia.

Fernbach, S. A.; Summons, R. E.; Pereira, W. E.; Duffield, A. M.

1975-01-01

193

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

194

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

195

Metformin-Associated Lactic Acidosis: Predisposing Factors and Outcome  

PubMed Central

Background Metformin is considered the first choice oral treatment for type 2 diabetes patients in the absence of contraindications. Rarely, life-threatening complications associated with metformin treatment are seen in some patients with underlying diseases. The aim of this study was to further investigate the clinical profiles and risk factors for metformin-associated lactic acidosis (MALA) and the treatment modalities according to survival. Methods To identify MALA, we performed a retrospective study in seven diabetic patients who were taking metformin and had been diagnosed with lactic acidosis at Inha University Hospital between 1995 and 2012. For each patient, we recorded the age, sex, daily metformin dosage, laboratory test results, admission diagnosis, and risk factors. Also, concurrent conditions, treatment modalities, and outcomes were evaluated. Results Six patients had risk factors for lactic acidosis before admission. All patients had renal impairment on admission as a precipitating risk factor. Five patients survived and two patients died despite early renal replacement therapy. Older patients tended to have a poorer prognosis. Conclusion Renal function must be monitored in elderly type 2 diabetes mellitus patients with underlying diseases and conditions causing renal impairment who begin metformin treatment. Accurate recognition of MALA and initiation of renal replacement are essential for treatment. PMID:25827460

Kim, Min Ju; Han, Ju Young; Shin, Jun Young; Kim, Shin Il; Lee, Jeong Min; Hong, Seongbin; Kim, So Hun; Kim, Yong Seong

2015-01-01

196

Acute metabolic effects of exercise in bodybuilders using anabolic steroids  

Microsoft Academic Search

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.

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

1989-01-01

197

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

198

The severity of coronary atherosclerosis in diabetic and non-diabetic metabolic syndrome patients diagnosed according to different criteria and undergoing elective angiography  

Microsoft Academic Search

Our aim in this study was to evaluate the relationship between metabolic syndrome (MS) as defined by different criteria and\\u000a the severity of coronary lesions in a sample of diabetic and non-diabetic patients undergoing elective coronary angiography.\\u000a All patients had blood and urine tests, physical examinations were performed before angiography, and finally they were classified\\u000a based on three criteria (World

S. Ertek; A. F. Cicero; M. Cesur; M. Akcil; T. Altuner Kayhan; U. Avcioglu; M. E. Korkmaz

2011-01-01

199

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

200

Different patterns of testicular in vitro metabolism of (/sup 14/C)testosterone in several Betta (Anabantoidei, Belontiidae) species  

SciTech Connect

Testicular tissues of Betta picta, Betta smaragdina, and the short-finned variety of Betta splendens were incubated with (/sup 14/C)testosterone at 27 degrees for 120 min and the metabolites were isolated and characterized by paper and thin-layer chromatography and eventually by crystallization to constant specific activity. The metabolic profiles of the species were totally different. The short-finned B. splendens formed mainly 11-ketotestosterone (51.4%) as does the veiltail variety. B. smaragdina was the only species which formed considerable amounts of conjugates (24.3%), whereas in B. picta almost exclusively reduced (5 beta-) compounds (66.2%) were metabolites of testosterone. The results are discussed to be attributable to differences in testicular steroid metabolism. The significance of this observation remains unclear.

Leitz, T.

1987-07-01

201

Different patterns of testicular in vitro metabolism of [14C]testosterone in several Betta (Anabantoidei, Belontiidae) species.  

PubMed

Testicular tissues of Betta picta, Betta smaragdina, and the short-finned variety of Betta splendens were incubated with [14C]testosterone at 27 degrees for 120 min and the metabolites were isolated and characterized by paper and thin-layer chromatography and eventually by crystallization to constant specific activity. The metabolic profiles of the species were totally different. The short-finned B. splendens formed mainly 11-ketotestosterone (51.4%) as does the veiltail variety. B. smaragdina was the only species which formed considerable amounts of conjugates (24.3%), whereas in B. picta almost exclusively reduced (5 beta-) compounds (66.2%) were metabolites of testosterone. The results are discussed to be attributable to differences in testicular steroid metabolism. The significance of this observation remains unclear. PMID:3623068

Leitz, T

1987-07-01

202

Measurement of urinary free and acylcarnitines: quantitative acylcarnitine profiling in normal humans and in several patients with metabolic errors.  

PubMed

A method for determining urinary concentrations of carnitine and acylcarnitine esters is described that employs fast atom bombardment mass spectrometry, stable isotope dilution techniques, and a novel deutero-methyl esterification that permits unambiguous identification and quantitation of free carnitine and acylcarnitines. It is rapid, does not require chromatographic or other isolation procedures, and is immune to analyte losses in sample preparation. Urinary concentrations are reported for adult control subjects and for others with various metabolic disorders. PMID:2653103

Montgomery, J A; Mamer, O A

1989-01-01

203

Prevalence and risk factors of metabolic syndrome in obese children and adolescents: the role of the severity of obesity  

Microsoft Academic Search

The present study was performed to determine the prevalence of metabolic syndrome (MS) and its risk factors in obese children\\u000a and adolescents. The study included 352 obese children and adolescents (body mass index [BMI]???95th percentile) aged between\\u000a 2 and 19 years. The diagnosis of MS was made according to the criteria adapted from the World Health Organization (WHO) and\\u000a the National

Yasar Sen; Nurgun Kandemir; Ayfer Alikasifoglu; Nazli Gonc; Alev Ozon

2008-01-01

204

Impact of the metabolic syndrome and its individual components on risk and severity of coronary heart disease  

Microsoft Academic Search

The clinical use of criteria for metabolic syndrome (MetS) and its individual components with respect to risk prediction of\\u000a coronary heart disease (CHD) remains uncertain. In this study, we investigated whether and to what extent MetS and its individual\\u000a components were related to risk for CHD. A total of 1,028 subjects, who had undergone coronary angiography or were diagnosed\\u000a as

Yifei Zhang; Jie Hong; Weiqiong Gu; Minghui Gui; Ying Chen; Yu Zhang; Zhenni Chi; Weiqing Wang; Xiaoying Li; Guang Ning

2009-01-01

205

Acidosis slows electrical conduction through the atrio-ventricular node  

PubMed Central

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis. PMID:25009505

Nisbet, Ashley M.; Burton, Francis L.; Walker, Nicola L.; Craig, Margaret A.; Cheng, Hongwei; Hancox, Jules C.; Orchard, Clive H.; Smith, Godfrey L.

2014-01-01

206

Effect of several doses of zeolite A on feed intake, energy metabolism and on mineral metabolism in dairy cows around calving.  

PubMed

The object of the present study was to determine the influence of different zeolite A doses on dry matter intake (DMI) and mineral metabolism, and to evaluate an optimum dosage for preventing hypocalcaemia. Eighty pregnant dry cows were assigned to four groups (I-IV). They were fed a total mixed ration (TMR) ad libitum. Groups II, III and IV received an average daily dose of 12, 23 and 43 g zeolite A/kg DM for the last 2 weeks prepartum. Individually DMI was recorded daily. Blood and urine samples were taken before, during and after zeolite A supplementation. Serum was analysed for Ca, Mg, P(i), K, non-esterified fatty acids and beta-hydroxybutyrate (BHB). Urine was analysed for Ca, Mg, P(i), K and net acid-base excretion (NABE). After calving, milk yield (fat corrected milk) and milk composition were determined. During zeolite A supplementation, mean DMI of Group IV (7.3 +/- 1.3 kg/cow/day) was significantly lower compared to Groups I-III (10.1, 10.9, 9.5 kg/cow/day). The reduced feed intake of Group IV resulted in significantly increased BHB as well as decreased NABE after calving. Zeolite A supplementation in higher doses (III and IV) had a stabilizing effect on Ca metabolism around calving for older cows, whereas cows in Groups I and II showed a subclinical hypocalcaemia. The mean serum Mg concentration decreased significantly in older cows in Group IV at calving. The mean P(i) concentration in cows of Group IV decreased into ranges of hypophosphataemia already 1 week after beginning of zeolite A feeding. The mean DMI postpartum as well as the milk yield was not affected by zeolite A supplementation. Feeding of 23 g zeolite A/kg DM TMR prepartum proved to be an adequate dosage for reducing subclinical hypocalcaemia frequency without significant effects on feed intake and P(i) concentration in serum. PMID:19320935

Grabherr, H; Spolders, M; Fürll, M; Flachowsky, G

2009-04-01

207

Type-B lactic acidosis associated with progressive multiple myeloma  

PubMed Central

We report a 64-year-old lady with stage II, Immunoglobulin-G lambda multiple myeloma (MM) (standard risk), who presented with type-B lactic acidosis (LA), and multi-organ dysfunction associating myeloma progression, and ending in imminent death. In the context of literature review of all previously reported similar cases, this report highlights and discusses the association of type-B LA and MM (especially progressive disease), and also emphasizes the poor outcome. Early recognition of this condition with intensive supportive care, and treatment of multiple myeloma may improve outcomes. PMID:25719593

Abdullah, Sameer Y.; Ali, Moaath K.; Sabha, Marwa M.

2015-01-01

208

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

209

A combined high CYP2D6-CYP2C19 metabolic capacity is associated with the severity of suicide attempt as measured by objective circumstances.  

PubMed

This study examined, for the first time, whether a high CYP2D6-CYP2C19 metabolic capacity combination increases the likelihood of suicidal intent severity in a large study cohort. Survivors of a suicide attempt (n=587; 86.8% women) were genotyped for CYP2C19 (*2, *17) and CYP2D6 (*3, *4, *4xN, *5, *6, *10, wtxN) genetic variation and evaluated with the Beck Suicide Intent Scale (SIS). Patients with a high CYP2D6-CYP2C19 metabolic capacity showed an increased risk for a severe suicide attempt (P<0.01) as measured by the SIS-objective circumstance subscale (odds ratio (OR)=1.37; 95% confidence interval (CI)=1.05-1.78; P=0.02) after adjusting for confounders (gender, age, level of studies, marital status, mental disorders, tobacco use, family history of suicide, personal history of attempts and violence of the attempt). Importantly, the risk was greater in those without a family history of suicide (OR=1.82; CI=1.19-2.77; P=0.002). Further research is warranted to evaluate whether the observed relationship is mediated by the role of CYP2D6 and CYP2C19 involvement in the endogenous physiology or drug metabolism or both. PMID:25113522

Peñas-Lledó, E; Guillaume, S; Naranjo, M E G; Delgado, A; Jaussent, I; Blasco-Fontecilla, H; Courtet, P; LLerena, A

2015-04-01

210

Acidosis, lactate, electrolytes, muscle enzymes, and other factors in the blood of Sus scrofa following repeated TASER exposures.  

PubMed

Repeated exposure to electro-muscular incapacitating devices could result in repetitive, sustained muscle contraction, with little or no muscle recovery period. Therefore, rhabdomyolysis and other physiological responses, including acidosis, hyperkalaemia, and altered levels of muscle enzymes in the blood, would be likely to occur. Experiments were performed to investigate effects of repeated exposures of TASER International's Advanced TASER X26 on muscle contraction and resultant changes in blood factors in an anaesthetized swine model. A total of 10 animals were used. Six swine were exposed for 5 s, followed by a 5-s period of no exposure, repeatedly for 3 min. (In five of the animals, after a 1-h delay, a second 3-min exposure period was added.) The remaining four animals were used for an additional pilot study. All four limbs of each animal exhibited contraction even though the electrodes were positioned in areas at some distances from the limbs. The degree of muscle contraction generated during the second exposure period was significantly lower than that in the first exposure series. This finding was consistent with previous studies showing that prolonged activity in skeletal muscle will eventually result in a decline of force production. There were some similarities in blood sample changes in the current experiments with previous studies of muscular exercise. Thus problems concerning biological effects of repeated TASER exposures may be related, not directly to the "electric output" per se, but rather to the resulting contraction of muscles (and related interruption of respiration) and subsequent sequelae. Transient increases in hematocrit, potassium, and sodium were consistent with previous reports in the literature dealing with studies of muscle stimulation or exercise. It is doubtful that these short-term elevations would have any serious health consequences in a healthy individual. Blood pH was significantly decreased for 1h following exposure, but subsequently returned toward a normal level. Leg muscle contractions and decreases in respiration each appeared to contribute to the acidosis. Lactate was highly elevated, with a slow return (time course greater than 1 h) to baseline. Other investigators have reported profound metabolic acidosis during restraint-associated cardiac arrest. Since restraint often occurs immediately after TASER exposure, this issue should be considered in further development of deployment concepts. On the basis of the results of the current studies, the repeated use of electro-muscular incapacitating devices in a short period of time is, at least, feasible, with the caveat that some medical monitoring of subjects may be required (to observe factors such as lactate and acidosis). PMID:16289999

Jauchem, James R; Sherry, Clifford J; Fines, David A; Cook, Michael C

2006-08-10

211

Neural Correlates of the Severity of Cocaine, Heroin, Alcohol, MDMA and Cannabis Use in Polysubstance Abusers: A Resting-PET Brain Metabolism Study  

PubMed Central

Introduction Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used. Methods Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used. Results The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex. Conclusions Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients. PMID:22768136

Moreno-López, Laura; Stamatakis, Emmanuel A.; Fernández-Serrano, Maria José; Gómez-Río, Manuel; Rodríguez-Fernández, Antonio; Pérez-García, Miguel; Verdejo-García, Antonio

2012-01-01

212

Tirilazad Pretreatment Improves Early Cerebral Metabolic and Blood Flow Recovery from Hyperglycemic Ischemia  

Microsoft Academic Search

Summary: Acidosis may augment cerebral ischemic injury by promoting lipid peroxidation. We tested the hypothesis that when acidosis is augmented by hyperglyce-mia, pretreatment with the 21-aminosteroid tirilazad mes-ylate (U74006F), a potent inhibitor of lipid peroxidation in vitro, improves early cerebral metabolic recovery. In a randomized, blinded study, anesthetized dogs received either tirilazad mesylate (1 mg\\/kg plus 0.2 mg\\/kg\\/h; n =

Yuichi Maruki; Raymond C. Koehler; Jeffrey R. Kirsch; Kathleen K. Blizzard; Richard J. Traystman

1995-01-01

213

[Damage control applied to severe maxillofacial trauma].  

PubMed

Damage control is defined by the extreme emergency implementation of a first resuscitation and surgical step, during which there is no attempt at repairing lesions but only at restoring adequate physiological function. In recent years, "damage control" has considerably improved the management of polytrauma patients, especially in war surgery. Respiratory distress or hemorrhagic shock requirements are critical maxillofacial emergencies. We present the specificities of "damage control" management for patients with severe maxillofacial trauma. Some clinical and biological criteria have been defined to choose "damage control" strategy, in patients presenting with life-threatening facial hemorrhage after facial trauma. A rapid initial stage restores vital functions. Airways are maintained and secured: oro-tracheal intubation, cricothyroidotomy, surgical tracheotomy. Facial bleeding is controlled with various means: oronasal packing, angiographic embolization, selective ligation then external carotid artery if necessary. The resuscitation step stabilizes the lethal triad: hypothermia, coagulopathy, metabolic acidosis. The second step that comes in later is a surgical repair of facial injuries. "Damage control" can be adequately applied to the management of patients with severe maxillofacial trauma. PMID:24507725

Laversanne, S; Pierrou, C; Haen, P; Brignol, L; Thiéry, G

2014-02-01

214

Diagnosis and Treatment of Metabolic Alkalosis  

Microsoft Academic Search

\\u000a 1.?Primary metabolic alkalosis should be distinguished from metabolic compensation to respiratory acidosis.\\u000a \\u000a 2.?Measurement of urine chloride concentration is essential for diagnosis and treatment.\\u000a \\u000a \\u000a 3.?Metabolic alkalosis with low urine chloride (chloride responsive) represents an appropriate renal response to H+ and Cl– losses from non-renal sites (GI, skin).\\u000a \\u000a \\u000a \\u000a 4.?Metabolic alkalosis with high urine chloride (chloride unresponsive) should prompt an evaluation for renal

Wayne R. Waz

215

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

216

Glucose metabolism in severe malaria: Minimal model analysis of the intravenous glucose tolerance test incorporating a stable glucose label  

Microsoft Academic Search

Basal plasma glucose is usually increased in uncomplicated malaria, implying insulin resistance. If the infection progresses, the risk of hypoglycemia will increase as host glucose production becomes insufficient for host\\/parasite demand. To assess the relative contribution of insulin-mediated and non—insulin-mediated glucose disposal to plasma glucose levels in severe malaria, we studied six healthy controls (two males and four females; mean

T. Q. Binh; T. M. E. Davis; W. Johnston; L. T. A. Thu; R. Boston; P. T. Danh; T. K. Anh

1997-01-01

217

Impaired renal conservation of sodium and chloride during sustained correction of systemic acidosis in patients with type 1, classic renal tubular acidosis.  

PubMed Central

In 10 patients with classic renal tubular acidosis in whom correction of acidosis was sustained with orally administered potassium bicarbonate, renal conservation of sodium was evaluated when dietary intake of sodium was restricted to 9--13 meq/day. In five patients, renal conservation of sodium was impaired by at least one criterion of impairment. In the remaining patients, renal conservation of sodium appeared to be relatively well-maintained, but an impairment could not be excluded. In each of six patients studied during induced water diuresis, including two in whom renal conservation of sodium was not unequivocally impaired, the minimal urinary concentrations of sodium were inappropriately high and the urinary excretion rates of sodium were flow-dependent. These results provide direct evidence that an abnormality in renal transport of sodium can occur in classic renal tubular acidosis, and compel a reconsideration of the pathophysiology of disordered renal transport of sodium in this disorder. The results indicate that in at least some patients with classic renal tubular acidosis impaired renal conservation of sodium is not exclusively a reversible consequence of the renal acidification defect. These findings raise the question whether renal transport of sodium is unimpaired in any patients with classic renal tubular acidosis. In the presently studied patients, the impairment in renal conservation of sodium appeared to be in part the consequence of an impaired ability of the vasopressin-responsive segments of the distal nephron to generate and maintain appropriately steep transepithelial sodium concentration gradients. PMID:783200

Sebastian, A; McSherry, E; Morris, R C

1976-01-01

218

Association of serum chemerin levels with the severity of coronary artery disease in patients with metabolic syndrome  

PubMed Central

Objectives: The newly identified adipokine chemerin has been shown to be associated with the components of MetS, inflammation and insulin resistance. In this study, the relationship between serum chemerin levels and the presence and severity of coronary artery disease (CAD) was evaluated in patients with MetS. Methods: The study population consisted of 84 MetS patients (43 patients with CAD and 41 without CAD), who had coronary angiography for suspected coronary artery disease, and 46 healthy individuals as a control group. Angiographic CAD was defined as ? 50% luminal diameter stenosis of at least one major epicardial coronary artery. The severity of CAD was determined by the Gensini score. Serum chemerin levels were measured with enzyme linked immunosorbent assay (ELISA). Results: Serum chemerin levels were significantly higher in patients with MetS (n=84) than those in the control group (120.47±25.32 vs. 90.4±11.4 ng/ml P < 0.001). In addition, MetS patients with CAD had higher chemerin levels than MetS patients without CAD (128.7±26.6 vs. 115.7±15.2 ng/ml, P < 0.001). Serum chemerin levels had a significant positive correlation with the Gensini score (r=0.58, P < 0.001). Multivariate logistic regression demonstrated that serum high-density lipoprotein cholesterol (HDL-C) and chemerin levels were significant and independent predictors for determining the presence of angiographic CAD (OR=1.009, 95% CI: 0.972-1.057; P=0.003 and OR=0.925, 95% CI: 0.896-0.922; P < 0.001, respectively). Conclusion: This study demonstrated that in patients with MetS, chemerin levels were higher in patients with CAD than patients without CAD and also showed a significant positive correlation with CAD severity. PMID:25664056

Aksan, Gökhan; ?nci, Sinan; Nar, Gökay; Soylu, Korhan; Gedikli, Ömer; Yüksel, Serkan; Özdemir, Metin; Nar, Rukiye; Meriç, Murat; ?ahin, Mahmut

2014-01-01

219

A Retrospective Analysis of the Haemodynamic and Metabolic Effects of Fluid Resuscitation in Vietnamese Adults with Severe Falciparum Malaria  

PubMed Central

Background Optimising the fluid resuscitation of patients with severe malaria is a simple and potentially cost-effective intervention. Current WHO guidelines recommend central venous pressure (CVP) guided, crystalloid based, resuscitation in adults. Methods Prospectively collected haemodynamic data from intervention trials in Vietnamese adults with severe malaria were analysed retrospectively to assess the responses to fluid resuscitation. Results 43 patients were studied of whom 24 received a fluid load. The fluid load resulted in an increase in cardiac index (mean increase: 0.75 L/min/m2 (95% Confidence interval (CI): 0.41 to 1.1)), but no significant change in acid-base status post resuscitation (mean increase base deficit 0.6 mmol/L (95% CI: ?0.1 to 1.3). The CVP and PAoP (pulmonary artery occlusion pressure) were highly inter-correlated (rs?=?0.7, p<0.0001), but neither were correlated with acid-base status (arterial pH, serum bicarbonate, base deficit) or respiratory status (PaO2/FiO2 ratio). There was no correlation between the oxygen delivery (DO2) and base deficit at the 63 time-points where they were assessed simultaneously (rs?=??0.09, p?=?0.46). Conclusions In adults with severe falciparum malaria there was no observed improvement in patient outcomes or acid-base status with fluid loading. Neither CVP nor PAoP correlated with markers of end-organ perfusion or respiratory status, suggesting these measures are poor predictors of their fluid resuscitation needs. PMID:22022406

Bethell, Delia; Mai, Nguyen Thi Hoang; Chau, Tran Thi Hong; Chuong, Ly Van; Loc, Pham Phu; Sinh, Dinh Xuan; Dondorp, Arjen; White, Nicholas; Hien, Tran Tinh; Day, Nicholas

2011-01-01

220

Management of severe malaria: results from recent trials.  

PubMed

Globally, malaria remains a substantial public health burden with an estimated 349-552 million clinical cases of P. falciparum malaria each year--leading to 780,000 deaths directly attributable to the disease. Whilst the outcome from severe malaria in Africa children remains poor, recent developments in the management of malaria have come from two key sources--the introduction of new, safe and rapidly-effective anti-malarials and high quality evidence from two of the largest clinical trials ever conducted in African children with severe malaria. As a result, the time-honoured anti-malarial treatment for severe malaria, quinine, will now be replaced by artesunate, a water-soluble artemisinin derivative. Supportive care, specifically the management of shock, has been informed by a large late phase clinical trial which concluded that bolus resuscitation is harmful and therefore should be avoided in children with severe malaria, including the high risk group with severe metabolic acidosis and advanced shock. PMID:23654072

Olupot-Olupot, Peter; Maitland, Kathryn

2013-01-01

221

Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction.  

PubMed

Genetic defects in the purine salvage enzyme adenosine deaminase (ADA) lead to severe combined immunodeficiency (SCID) with profound depletion of T, B, and natural killer cell lineages. Human leukocyte antigen-matched allogeneic hematopoietic stem cell transplantation (HSCT) offers a successful treatment option. However, individuals who lack a matched donor must receive mismatched transplants, which are associated with considerable morbidity and mortality. Enzyme replacement therapy (ERT) for ADA-SCID is available, but the associated suboptimal correction of immunological defects leaves patients susceptible to infection. Here, six children were treated with autologous CD34-positive hematopoietic bone marrow stem and progenitor cells transduced with a conventional gammaretroviral vector encoding the human ADA gene. All patients stopped ERT and received mild chemotherapy before infusion of gene-modified cells. All patients survived, with a median follow-up of 43 months (range, 24 to 84 months). Four of the six patients recovered immune function as a result of engraftment of gene-corrected cells. In two patients, treatment failed because of disease-specific and technical reasons: Both restarted ERT and remain well. Of the four reconstituted patients, three remained off enzyme replacement. Moreover, three of these four patients discontinued immunoglobulin replacement, and all showed effective metabolic detoxification. All patients remained free of infection, and two cleared problematic persistent cytomegalovirus infection. There were no adverse leukemic side effects. Thus, gene therapy for ADA-SCID is safe, with effective immunological and metabolic correction, and may offer a viable alternative to conventional unrelated donor HSCT. PMID:21865538

Gaspar, H Bobby; Cooray, Samantha; Gilmour, Kimberly C; Parsley, Kathryn L; Zhang, Fang; Adams, Stuart; Bjorkegren, Emma; Bayford, Jinhua; Brown, Lucinda; Davies, E Graham; Veys, Paul; Fairbanks, Lynette; Bordon, Victoria; Petropoulou, Theoni; Petropolou, Theoni; Kinnon, Christine; Thrasher, Adrian J

2011-08-24

222

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

223

Blueberries and Metabolic Syndrome  

Technology Transfer Automated Retrieval System (TEKTRAN)

Metabolic Syndrome is a cluster of metabolic disorders that increase the risk of cardiovascular diseases. Type 2 diabetes, elevated blood pressure, and atherogenic dyslipidemia are among the metabolic alterations that predispose the individual to several adverse cardiovascular complications. The hea...

224

Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3  

PubMed Central

Coronary artery disease leads to injury and loss of myocardial tissue by deprivation of blood flow (ischemia) and is a major underlying cause of heart failure. Prolonged ischemia causes necrosis and apoptosis of cardiac myocytes and vascular cells; however, the mechanisms of ischemia-mediated cell death are poorly understood. Ischemia is associated with both hypoxia and acidosis due to increased glycolysis and lactic acid production. We recently reported that hypoxia does not induce cardiac myocyte apoptosis in the absence of acidosis. We now report that hypoxia-acidosis-associated cell death is mediated by BNIP3, a member of the Bcl-2 family of apoptosis-regulating proteins. Chronic hypoxia induced the expression and accumulation of BNIP3 mRNA and protein in cardiac myocytes, but acidosis was required to activate the death pathway. Acidosis stabilized BNIP3 protein and increased the association with mitochondria. Cell death by hypoxia-acidosis was blocked by pretreatment with antisense BNIP3 oligonucleotides. The pathway included extensive DNA fragmentation and opening of the mitochondrial permeability transition pore, but no apparent caspase activation. Overexpression of wild-type BNIP3, but not a translocation-defective mutant, activated cardiac myocyte death only when the myocytes were acidic. This pathway may figure significantly in muscle loss during myocardial ischemia. PMID:12226479

Kubasiak, Lori A.; Hernandez, Olga M.; Bishopric, Nanette H.; Webster, Keith A.

2002-01-01

225

Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3.  

PubMed

Coronary artery disease leads to injury and loss of myocardial tissue by deprivation of blood flow (ischemia) and is a major underlying cause of heart failure. Prolonged ischemia causes necrosis and apoptosis of cardiac myocytes and vascular cells; however, the mechanisms of ischemia-mediated cell death are poorly understood. Ischemia is associated with both hypoxia and acidosis due to increased glycolysis and lactic acid production. We recently reported that hypoxia does not induce cardiac myocyte apoptosis in the absence of acidosis. We now report that hypoxia-acidosis-associated cell death is mediated by BNIP3, a member of the Bcl-2 family of apoptosis-regulating proteins. Chronic hypoxia induced the expression and accumulation of BNIP3 mRNA and protein in cardiac myocytes, but acidosis was required to activate the death pathway. Acidosis stabilized BNIP3 protein and increased the association with mitochondria. Cell death by hypoxia-acidosis was blocked by pretreatment with antisense BNIP3 oligonucleotides. The pathway included extensive DNA fragmentation and opening of the mitochondrial permeability transition pore, but no apparent caspase activation. Overexpression of wild-type BNIP3, but not a translocation-defective mutant, activated cardiac myocyte death only when the myocytes were acidic. This pathway may figure significantly in muscle loss during myocardial ischemia. PMID:12226479

Kubasiak, Lori A; Hernandez, Olga M; Bishopric, Nanette H; Webster, Keith A

2002-10-01

226

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

227

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

228

Corneal acidosis during contact lens wear: effects of hypoxia and CO2.  

PubMed

The effects of tear-film hypoxia and contact lens wear on human in vivo stromal pH was tested using a non-invasive fluorometric technique. Hypoxia was produced by exposing the normal open eye to 100% nitrogen gas passed through tight-fitting goggles. Stromal pH dropped from 7.53 +/- 0.02 to 7.34 +/- 0.03 (n = 12, +/- SD) within 90 min of nitrogen gas exposure, t1/2 = 20 min. After removing the goggles, stromal pH returned to baseline in 35 min, t1/2 = 10 min. Wearing a thick hydrogel contact lens which caused a tear PO2 less than or equal to 2 mm Hg with the eyes open, reduced stromal pH from 7.55 +/- 0.02 to 7.15 +/- 0.04 (n = 12, +/- SD) in 80 min, t1/2 = 9.5 min. After removing the lens, baseline pH was reached in 40 min, t1/2 = 4.5 min. The stromal pH differences between hypoxia (N2 only) and contact lens wear were not due to differences in tear temperature between the two procedures (contact lens wear 32 +/- 1.5 degrees C, goggles 33 +/- 1.0 degrees C). However exposing the eye to 95% nitrogen-5% carbon dioxide reduced stromal pH to 7.16 +/- 0.05 (n = 7, +/- SD) in 80 min, t1/2 = 8 min, which was similar to that produced during contact lens wear. These experiments show that contact lens wear causes corneal acidosis by: (1) the production of protons from hypoxic metabolism, and (2) the accumulation of carbon dioxide behind the lens due to low lens CO2 transmissibility. PMID:3114167

Bonanno, J A; Polse, K A

1987-09-01

229

Mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes (MELAS) with prominent degeneration of the intestinal wall and cactus-like cerebellar pathology.  

PubMed

A 67-year-old woman had frequent subacute ileus, hearing difficulty, muscle atrophy and stroke-like episodes. Computed tomography revealed multiple low-density areas, which did not correlate with the vascular supply, in the cerebral cortex. She had metabolic disturbance comprising lactic acidosis and elevated pyruvate level. Her skeletal muscle biopsy specimen showed ragged-red fibers, and mitochondrial DNA analysis revealed a point mutation at position 3243, findings consistent with MELAS. Examination of her small intestine revealed a necrotic zone and numerous abnormal large mitochondria in the smooth muscle cells, vascular media and endothelium, and intestinal ganglion cells. The cerebral cortex showed multiple microcystic necrotic foci in cerebral cortex. Cactus-like pathology resembling the changes associated with Menkes' kinky hair disease and torpedoes were observed in the cerebellar Purkinje cells. The intestinal dysmotility due to MELAS and cerebellar changes were presumed to be associated with a disturbance of copper metabolism. PMID:11078225

Mori, O; Yamazaki, M; Ohaki, Y; Arai, Y; Oguro, T; Shimizu, H; Asano, G

2000-12-01

230

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

231

Afobazole modulates neuronal response to ischemia and acidosis via activation of sigma-1 receptors.  

PubMed

Afobazole is an anxiolytic medication that has been previously shown to be neuroprotective both in vitro and in vivo. However, the mechanism(s) by which afobazole can enhance neuronal survival remain poorly understood. Experiments were carried out to determine whether afobazole can decrease intracellular calcium overload associated with ischemia and acidosis and whether the effects of afobazole are mediated via interaction of the compound with ? receptors. Fluorometric Ca(2+) imaging was used to resolve how application of afobazole affects intracellular Ca(2+) handling in cortical neurons. Application of afobazole significantly depressed, in a concentration-dependent and reversible manner, the intracellular Ca(2+) overload resulting from in vitro ischemia and acidosis. The IC(50) for afobazole inhibition of ischemia-evoked intracellular Ca(2+) overload was considerably less than that for the inhibition of [Ca(2+)](i) increases induced by acidosis. However, afobazole maximally inhibited only 70% of the ischemia-evoked intracellular Ca(2+) overload but effectively abolished intracellular Ca(2+) increases produced by acidosis. The effects of afobazole on ischemia- and acidosis-induced intracellular Ca(2+) dysregulation were inhibited by preincubating the neurons in the irreversible, pan-selective ?-receptor antagonist, metaphit. Moreover, the effects of afobazole on intracellular Ca(2+) increases triggered by acidosis and ischemia were blocked by the selective ?-1-receptor antagonists, BD 1063 and BD 1047, respectively. Experiments examining the effects of afobazole on neuronal survival in response to ischemia showed that afobazole was neuroprotective. Taken together, these data suggest that afobazole regulates intracellular Ca(2+) overload during ischemia and acidosis via activation of ?-1 receptors. This mechanism is probably responsible for afobazole-mediated neuroprotection. PMID:21715562

Cuevas, Javier; Behensky, Adam; Deng, Wei; Katnik, Christopher

2011-10-01

232

Ruminal acidosis challenge impact on ruminal temperature in feedlot cattle.  

PubMed

The objective of this experiment was to determine if ruminal temperature rise coincides with pH reduction using an acidosis challenge model. Twelve ruminally cannulated steers (518 ± 28 kg BW) were administered ruminal temperature-monitoring devices that recorded temperature every 2 min. Steers were fed a 63% concentrate diet at 1.6% BW for 20 d before being randomly assigned to 1 of 3 acidosis challenge treatments: no dietary change (CON), one-half of daily DMI replaced with cracked corn (HALF), or all of daily DMI replaced with cracked corn (CORN). The challenge was initiated by ruminally dosing steers with their treatment diets. Ruminal pH and rectal temperatures (T(rec)) were recorded every 3 h for 72 h. All steers were offered CON diets at 24 and 48 h after challenge. Ruminal pH showed a treatment × day effect (P = 0.01). Ruminal pH of CORN steers was lower (P = 0.03) than that of HALF steers on d 1, was lower (P ? 0.004) than that of HALF and CON steers on d 2, and tended to be lower (P ? 0.10) than that of HALF and CON steers on d 3. Treatment did not affect (P ? 0.42) RecT. Ruminal temperature (T(rum)) showed a treatment · d(-1) · h(-1) after feeding interaction (P < 0.01). At 3 h after challenge, T(rum) of CORN and HALF steers was higher (P ? 0.01) than that of CON steers. On d 2, T(rum) of CORN steers was higher (P ? 0.03) than that of CON between 6 and 12 h after feeding. From 15 to 21 h after feeding on d 2, T(rum) of HALF steers was higher (P < 0.01) than that of CORN and CON steers. On d 3, at the time of feeding until 3 h later, T(rum) of CORN steers was lower (P ? 0.04) than that of all other steers. Rectal temperature was correlated (P ? 0.01) with T(rum) on all days for CON and CORN steers. Ruminal pH was negatively correlated (P ? 0.04) with T(rec) on d 2 and T(rum) on d 1 in CORN steers, and T(rum) was negatively correlated (P ? 0.02) with ruminal pH in HALF and CON steers on d 1 and 3, respectively. The amount of time above T(rum) of 39.0°C or 39.45°C was correlated (P ? 0.05) with the time spent below a ruminal pH of 5.5 in CORN steers; however, time above T(rum) of 39.0°C did not differ (P = 0.87) among treatments. Results indicate that there is a negative relationship between T(rum) and ruminal pH during an acidotic episode; therefore, T(rum) monitoring can detect a potential acidotic episode. PMID:22408086

Wahrmund, J L; Ronchesel, J R; Krehbiel, C R; Goad, C L; Trost, S M; Richards, C J

2012-08-01

233

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

234

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

235

Developmental factors in the contractile response of rabbit urinary bladder: effect of anoxia and extracellular acidosis.  

PubMed

Previous studies have demonstrated that the mechanism of excitation contraction coupling changes with normal development in rabbit urinary bladder smooth muscle. The present study was designed to determine whether there were any differences in the effects of anoxia and extracellular acidosis in response to field stimulation, bethanechol and KCl between mature (8 weeks) and neonatal (3 days) rabbit bladder smooth muscle. Bladder smooth muscle strips from mature and neonatal New Zealand White rabbits were mounted in organ baths and bathed in oxygenated Tyrode's solution. Anoxia was produced by changing the gas mixture to 95% nitrogen/5% CO2 and the effects on contractility were determined at different times after initiation of anoxia. The extracellular acidosis was produced by decreasing the buffer's NaHCO3 concentration. We conclude that bladder smooth muscle does not exhibit an age-specific ability to counteract the effects of anoxia or acidosis as is seen in the developing rabbit myocardium. Instead it appears that the purinergic mechanisms of contraction are much more sensitive to the effects of anoxia or acidosis. Neonatal bladder smooth muscle exhibits a greater drop in contractility with anoxia or acidosis at low frequency (2 Hz) field stimulation; we attribute this to the fact that neonatal bladder smooth muscle has a greater purinergic component in its response to field stimulation. These differences in the responses to anoxia and pH reflect alternate mechanisms of pharmacologic activation, and not inherent differences in the biochemistry of the maturing smooth muscle. PMID:7662816

Yoon, J Y; Zderic, S A; Duckett, J W; Snyder, H M; Levin, R M

1995-01-01

236

[Generalized saturnine paralysis. Discovery of a double congenital disease: glucose-6-phosphate dehydrogenase deficiency (new variant) and distal tubular acidosis].  

PubMed

A case of severe lead poisoning with haemolytic anemia, extensive polyneuropathy and arterial hypertension is reported in a patient for whom G-6-P-D deficiency and renal tubular acidosis were discovered. Both traits were present in his family. Incomplete regression of paralysis and persistant biological abnormalities after chelating treatment were demonstrative of heavy saturnine load even though the toxic exposure was brief. The role of the two deficiencies in the mechanism of intoxication is discussed: facilitation of haemolysis by enzymopathy and bone lead redistribution resulting from osteolysis probably due to the tubulopathy. The authors emphasize the fact that thorough and serial biological investigation is essential in the discovery of factors which may precipitate lead poisoning, as well as in the determination of follow-up criteria of efficient toxic epuration with sufficient delay. Typing of the enzyme has led to the identification of a new variant of glucose-6-phosphate dehydrogenase deficiency. PMID:931243

Nouailhat, F; Kaplan, J C; Giudicelli, Y; Bourdain, J C; Junien, C; Combes, A; Giraud, A

1977-11-01

237

The plasticizer benzyl butyl phthalate (BBP) alters the ecdysone hormone pathway, the cellular response to stress, the energy metabolism, and several detoxication mechanisms in Chironomus riparius larvae.  

PubMed

Butyl benzyl phthalate (BBP) has been extensively used worldwide as a plasticizer in the polyvinyl chloride (PVC) industry and the manufacturing of many other products, and its presence in the aquatic environment is expected for decades. In the present study, the toxicity of BBP was investigated in Chironomus riparius aquatic larvae. The effects of acute 24-h and 48-h exposures to a wide range of BBP doses were evaluated at the molecular level by analysing changes in genes related to the stress response, the endocrine system, the energy metabolism, and detoxication pathways, as well as in the enzyme activity of glutathione S-transferase. BBP caused a dose and time-dependent toxicity in most of the selected biomarkers. 24-h exposures to high doses affected larval survival and lead to a significant response of several heat-shock genes (hsp70, hsp40, and hsp27), and to a clear endocrine disrupting effect by upregulating the ecdysone receptor gene (EcR). Longer treatments with low doses triggered a general repression of transcription and GST activity. Furthermore, delayed toxicity studies were specially relevant, since they allowed us to detect unpredictable toxic effects, not immediately manifested after contact with the phthalate. This study provides novel and interesting results on the toxic effects of BBP in C. riparius and highlights the suitability of this organism for ecotoxicological risk assessment, especially in aquatic ecosystems. PMID:25725395

Herrero, Óscar; Planelló, Rosario; Morcillo, Gloria

2015-06-01

238

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

PubMed Central

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

239

Carbenoxolone Treatment Ameliorated Metabolic Syndrome in WNIN/Ob Obese Rats, but Induced Severe Fat Loss and Glucose Intolerance in Lean Rats  

PubMed Central

Background 11beta-hydroxysteroid dehydrogenase type 1 (11?-HSD1) regulates local glucocorticoid action in tissues by catalysing conversion of inactive glucocorticoids to active glucocorticoids. 11?-HSD1 inhibition ameliorates obesity and associated co-morbidities. Here, we tested the effect of 11?-HSD inhibitor, carbenoxolone (CBX) on obesity and associated comorbidities in obese rats of WNIN/Ob strain, a new animal model for genetic obesity. Methodology/Principal Findings Subcutaneous injection of CBX (50 mg/kg body weight) or volume-matched vehicle was given once daily for four weeks to three month-old WNIN/Ob lean and obese rats (n?=?6 for each phenotype and for each treatment). Body composition, plasma lipids and hormones were assayed. Hepatic steatosis, adipose tissue morphology, inflammation and fibrosis were also studied. Insulin resistance and glucose intolerance were determined along with tissue glycogen content. Gene expressions were determined in liver and adipose tissue. CBX significantly inhibited 11?-HSD1 activity in liver and adipose tissue of WNIN/Ob lean and obese rats. CBX significantly decreased body fat percentage, hypertriglyceridemia, hypercholesterolemia, insulin resistance in obese rats. CBX ameliorated hepatic steatosis, adipocyte hypertrophy, adipose tissue inflammation and fibrosis in obese rats. Tissue glycogen content was significantly decreased by CBX in liver and adipose tissue of obese rats. Severe fat loss and glucose- intolerance were observed in lean rats after CBX treatment. Conclusions/Significance We conclude that 11?-HSD1 inhibition by CBX decreases obesity and associated co-morbidities in WNIN/Ob obese rats. Our study supports the hypothesis that inhibition of 11?-HSD1 is a key strategy to treat metabolic syndrome. Severe fat loss and glucose -intolerance by CBX treatment in lean rats suggest that chronic 11?-HSD1 inhibition may lead to insulin resistance in normal conditions. PMID:23284633

Prasad Sakamuri, Siva Sankara Vara; Sukapaka, Mahesh; Prathipati, Vijay Kumar; Nemani, Harishankar; Putcha, Uday Kumar; Pothana, Shailaja; Koppala, Swarupa Rani; Ponday, Lakshmi Raj Kumar; Acharya, Vani; Veetill, Giridharan Nappan; Ayyalasomayajula, Vajreswari

2012-01-01

240

Metabolic Changes after Urinary Diversion  

PubMed Central

Urinary diversion is performed on a regular basis in urological practice. Surgeons tend to underestimate the metabolic effects of any type of diversion. From the patient's perspective, diarrhea is the most bothersome complaint after urinary diversion. This might be accompanied by malabsorption syndromes, such as vitamin B12 deficiency. Electrolyte abnormalities can occur frequently such as hyperchloremic metabolic acidosis, or less frequently such as hypokalemia, hypocalcaemia, and hypomagnesaemia. Bone health is at risk in patients with urinary diversion. Some patients might benefit from vitamin D and calcium supplementation. Many patients are also subject to urinary calculus formation, both at the level of the upper urinary tract as in intestinal reservoirs. Urinary diversion can affect hepatic metabolism, certainly in the presence of urea-splitting bacteria. The kidney function has to be monitored prior to and lifelong after urinary diversion. Screening for reversible causes of renal deterioration is an integral part of the followup. PMID:21687576

Van der Aa, Frank; Joniau, Steven; Van Den Branden, Marcel; Van Poppel, Hein

2011-01-01

241

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

242

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

243

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

244

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

245

Metabolic acidosis induced by Plasmodium falciparum intraerythrocytic stages alters blood–brain barrier integrity  

Microsoft Academic Search

The pathogenesis of cerebral malaria (CM) remains largely unknown. There is growing evidence that combination of both parasite and host factors could be involved in blood–brain barrier (BBB) breakdown. However, lack of adequate in vitro model of human BBB so far hampered molecular studies. In this article, we propose the use of hCMEC\\/D3 cells, a well-established human cerebral microvascular endothelial

Sergine Zougbédé; Florence Miller; Philippe Ravassard; Angelita Rebollo; Liliane Cicéron; Pierre-Olivier Couraud; Dominique Mazier; Alicia Moreno

2011-01-01

246

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

E-print Network

or punctured tubes leaking into the box. Cold packs were placed on top to maintain preservation. A Styrofoam lid was placed on top of the contents. An itemized list of contents was placed between the Styrofoam lid and the outer box. The box was sealed...

Vyduna, Jennifer Lynn

2012-12-31

247

A 44-year-old woman with metabolic acidosis, high anion gap, and delayed neurologic deterioration.  

PubMed

A 44-year-old woman was brought to the ED from John F. Kennedy International Airport. The patient was returning with her son from a 3-month visit to Bangladesh. Her journey started with a 4-h flight from Dhaka, Bangladesh to Dubai, United Arab Emirates. She consumed 240 mL of whiskey during the flight. This was followed by a 14-h flight from Dubai to New York. According to the patient's son, she did not consume any alcohol during the second flight. The patient was in her usual state of health with normal mentation throughout her journey. Upon landing, she started complaining of shortness of breath. After disembarking, she was witnessed to have seizure-like activity with involuntary passage of urine, following which she collapsed. The patient was intubated by emergency medical services in the field. PMID:25560868

Vakil, Abhay; Upadhyay, Hinesh; Sherani, Khalid; Cervellione, Kelly; Trepeta, Scott; Patel, Mahendra C

2015-01-01

248

Experimental acute rumen acidosis in sheep: consequences on clinical, rumen, and gastrointestinal permeability conditions and blood chemistry.  

PubMed

Acute acidosis was induced in sheep, and gastrointestinal permeability was assessed by using lactulose as a permeability marker. Metabolism was evaluated by monitoring blood metabolites. Four rams (72.5 ± 4.6 kg BW) were used in a 2 × 2 changeover design experiment. The experimental period lasted 96 h from -24 to 72 h. After 24 h of fasting (from -24 to 0 h) for both controls and acidosis-induced rams (ACID), 0.5 kg of wheat flour was orally dosed at 0 and 12 h of the experimental period to ACID, while the basal diet (grass hay, ad libitum) was restored to control. At 24 h, a lactulose solution (30 g of lactulose in 200 mL of water) was orally administered. Blood samples were collected at -24, 0, 24, 48, and 72 h of the experimental periods for the analysis of metabolic profiles and during the 10 h after lactulose dosage to monitor lactulose changes in blood. In addition, rumen and fecal samples were collected at 24 h of the experimental period. The acidotic challenge markedly reduced (P < 0.01) rumen pH and VFA but increased rumen d- and l-lactic acid (P < 0.01). Concurrently, a decrease of fecal pH and VFA occurred in ACID (P < 0.01), together with an abrupt increase (P < 0.01) of lactate and fecal alkaline phosphatase. Blood lactulose was significantly increased in ACID peaking 2 h after lactulose dosage. Blood glucose, ?-hydroxybutyrate, Ca, K, Mg, and alkaline phosphatase showed a significant reduction (P < 0.05) at 24 h, whereas urea and NEFA declined (P < 0.05) from 48 to 72 h. A strong inflammatory acute phase response with oxidative stress in ACID group was observed from 24 to 72 h; higher values of haptoglobin (P < 0.01) were measured from 24 to 72 h and of ceruloplasmin from 48 (P < 0.05) to 72 h (P < 0.01). Among the negative acute phase reactants, plasma albumin, cholesterol, paraoxonase, and Zn concentration also decreased (P < 0.05) in ACID at different time points between 24 and 72 h after acidotic challenge start. A rise (P < 0.05) of reactive oxygen metabolites and a drop of vitamin E (P < 0.01) between 24 and 72 h were indicative of oxidative stress in ACID. The perturbation of these blood metabolites suggests that acute acidosis was effectively induced by our model. The increase of lactulose in blood in ACID indicates that gastrointestinal permeability for the marker increased and the large increment after 2 h from dosage suggests that most of the passage occurred through the rumen or abomasal walls. PMID:24987080

Minuti, A; Ahmed, S; Trevisi, E; Piccioli-Cappelli, F; Bertoni, G; Jahan, N; Bani, P

2014-09-01

249

Effects of the neurological wake-up test on clinical examination, intracranial pressure, brain metabolism and brain tissue oxygenation in severely brain-injured patients  

PubMed Central

Introduction Daily interruption of sedation (IS) has been implemented in 30 to 40% of intensive care units worldwide and may improve outcome in medical intensive care patients. Little is known about the benefit of IS in acutely brain-injured patients. Methods This prospective observational study was performed in a neuroscience intensive care unit in a tertiary-care academic center. Twenty consecutive severely brain-injured patients with multimodal neuromonitoring were analyzed for levels of brain lactate, pyruvate and glucose, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and brain tissue oxygen tension (PbtO2) during IS trials. Results Of the 82 trial days, 54 IS-trials were performed as interruption of sedation and analgesics were not considered safe on 28 days (34%). An increase in the FOUR Score (Full Outline of UnResponsiveness score) was observed in 50% of IS-trials by a median of three (two to four) points. Detection of a new neurologic deficit occurred in one trial (2%), and in one-third of IS-trials the trial had to be stopped due to an ICP-crisis (> 20 mmHg), agitation or systemic desaturation. In IS-trials that had to be aborted, a significant increase in ICP and decrease in PbtO2 (P < 0.05), including 67% with critical values of PbtO2 < 20 mmHg, a tendency to brain metabolic distress (P < 0.07) was observed. Conclusions Interruption of sedation revealed new relevant clinical information in only one trial and a large number of trials could not be performed or had to be stopped due to safety issues. Weighing pros and cons of IS-trials in patients with acute brain injury seems important as related side effects may overcome the clinical benefit. PMID:23186037

2012-01-01

250

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

251

Hypoxia and acidosis activate cardiac myocyte death through the Bcl2 family protein BNIP3  

Microsoft Academic Search

Coronary artery disease leads to injury and loss of myocardial tissue by deprivation of blood flow (ischemia) and is a major underlying cause of heart failure. Prolonged ischemia causes necrosis and apoptosis of cardiac myocytes and vascular cells; however, the mechanisms of ischemia-mediated cell death are poorly understood. Ischemia is associated with both hypoxia and acidosis due to increased glycolysis

Lori A. Kubasiak; Olga M. Hernandez; Nanette H. Bishopric; Keith A. Webster

2002-01-01

252

EFFECT OF LASALOCID, MONENSIN OR THIOPEPTIN ON LACTIC ACIDOSIS IN CATTLE 1'2'3  

Microsoft Academic Search

Summary Lasalocid, monensin or thiopeptin was ad- ministered intraruminally each at .33, .65 or 1.3 mg\\/kg body weight and evaluated for its effectiveness in preventing experimentally in- duced lactic acidosis in cattle. Four rumen- fistulated cattle were used for each dosage level and the design was a 4 x 4 Latin square with each animal receiving lasalocid, monensin, thiopeptin or

T. G. Nagaraja; T. B. Avery; E. E. Bartley; S. K. Roof

253

RELATIONSHIP OF RUMEN GRAM-NEGATIVE BACTERIA AND FREE ENDOTOXIN TO LACTIC ACIDOSIS IN CATTLE x  

Microsoft Academic Search

SUMMARY Feeding grain to animals not adapted to grain resulted in a marked increase in the .\\/ . concentration of free endotoxln m the rumen. Endotoxin concentration increased 15 to 18 times within 12 hr after lactic acidosis was induced through grain engorgement. The increase was accompanied by a shift from predominantly gram-negative to gram-positive bacteria. Data from in vitro

T. G. Nagaraja; E. E. Bartley; L. R. Fina; H. D. Anthony

2010-01-01

254

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

255

Feeding Wet Corn Gluten Feed to Reduce Subacute Acidosis in Cattle1  

Microsoft Academic Search

Two experiments were conducted to evaluate the effects of feeding wet corn gluten feed (WCGF) on subacute acidosis in cattle. In Exp. 1, 60 individually fed yearling steers (270 ± 22 kg BW) were used in a 5 × 2 factorial arrangement of treatments. Steers were assigned to one of five dietary treatments: 1 ) dry-rolled corn (DRC), 2 )

C. R. Krehbiel; R. A. Stock; D. W. Herold; D. H. Shain; G. A. Ham; J. E. Carulla

2010-01-01

256

Effects of acute respiratory acidosis on water and electrolyte transport in the human ileum.  

PubMed

Animal experiments have shown that acute respiratory acidosis stimulates water, Na and Cl absorption and HCO3 secretion in the ileum. The aim of this study was to investigate whether the human ileum also responds to changes in systemic acid-base balance. Seven healthy volunteers (mean age 24, range 21-29 years) underwent segmental ileal perfusion using a multi-lumen tube assembly with a proximal occluding balloon. A 30 cm test segment was perfused under steady state conditions with a plasma-like electrolyte solution containing PEG as a non-absorbable volume marker. After a control period, respiratory acidosis (blood pCO2 56.2 mmHg, pH 7.29 and [HCO3] 26.4 mmol l-1) was induced by CO2-breathing over a period of 50 min. Acute respiratory acidosis stimulated net HCO3 secretion in patients secreting HCO3 and reduced absorption in patients exhibiting net HCO3 absorption. These changes were immediate and appeared to be at least partly reversible. Net water, Na, K and Cl movement were not affected. The data suggest that HCO3 transport in the human ileum responds to acute respiratory acidosis. PMID:8500512

Eherer, A J; Petritsch, W; Berger, J; Hinterleitner, T; Charney, A N; Krejs, G J

1993-04-01

257

Dental Aspect of Distal Tubular Renal Acidosis with Genu Valgum Secondary to Rickets: A Case Report  

PubMed Central

Distal renal tubular acidosis is a disease that occurs when the kidneys do not remove acid properly into the urine, leaving the blood too acidic (called acidosis). Distal renal tubular acidosis (type I RTA) is caused by a defect in the kidney tubes that causes acid to build up in the bloodstream. It ultimately results rickets which include chronic skeletal pain, in skeletal deformities, skeletal fractures. Rickets is among the most frequent childhood diseases in many developing countries. Dental problems in rickets include delayed eruption of permanent teeth, premature fall of deciduous teeth, defects in structure of teeth, enamel defects in permanent teeth (hypoplastic), pulp defects, intraglobular dentine, and caries tooth. Herewith, reported a case of distal tubular renal acidosis with genu valgum secondary to rickets, with pain and extraoral swelling associated with right and left mandibular 1st permanent molars. Teeth were infected with pulp without being involved with caries. Radiographically cracks in enamel and dentin were observed. Pulp revascularization with 46 and root canal treatment was done for 36 with followup of 1 year. PMID:22567455

Bahadure, Rakesh N.; Thosar, Nilima; Kriplani, Ritika; Baliga, Sudhindra; Fulzele, Punit

2012-01-01

258

Acidosis and hypercalciuria: renal mechanisms affecting calcium, magnesium and sodium excretion in the sheep.  

PubMed

1. Observations were made on the excretion of calcium and magnesium by the sheep's kidney following manipulation of the acid-base status.2. Intravascular administration of a synthetic solution resembling saliva abolished the naturally occurring acidosis in sheep during feeding, and it also prevented the normal onset of post-prandial hypercalciuria and hypermagnesiuria.3. Non-respiratory acidosis (induced by infusion of hydrochloric acid) and respiratory acidosis arising from inhalation of 6% (v/v) CO(2) in air both caused an acute increase in calcium excretion.4. Measurement of filtered loads showed that feeding exerted an effect on the functional characteristics of the sheep's kidney. The renal clearances of calcium and magnesium increased, whereas sodium clearance decreased.5. Experimental conditions were arranged so that variations in acid-base status could be imposed at a time when the filtered load of calcium was declining.6. With hydrochloric acid-acidosis the renal excretion of calcium increased, despite a steady fall in the filtered load. With sodium bicarbonate alkalosis, the filtered load and the renal excretion of calcium decreased in unison.7. These variations in calcium excretion were not accompanied by corresponding changes in the excretion of sodium.8. It is concluded that the renal tubules in the sheep are sensitive to acid-base status and that they respond to a lowering of the blood pH by decreasing the tubular reabsorption of filtered calcium. PMID:5499811

Stacy, B D; Wilson, B W

1970-10-01

259

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

260

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

261

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

262

Dynamic scenario of metabolic pathway adaptation in tumors and therapeutic approach  

PubMed Central

Cancer cells need to regulate their metabolic program to fuel several activities, including unlimited proliferation, resistance to cell death, invasion and metastasis. The aim of this work is to revise this complex scenario. Starting from proliferating cancer cells located in well-oxygenated regions, they may express the so-called “Warburg effect” or aerobic glycolysis, meaning that although a plenty of oxygen is available, cancer cells choose glycolysis, the sole pathway that allows a biomass formation and DNA duplication, needed for cell division. Although oxygen does not represent the primary font of energy, diffusion rate reduces oxygen tension and the emerging hypoxia promotes “anaerobic glycolysis” through the hypoxia inducible factor-1?-dependent up-regulation. The acquired hypoxic phenotype is endowed with high resistance to cell death and high migration capacities, although these cells are less proliferating. Cells using aerobic or anaerobic glycolysis survive only in case they extrude acidic metabolites acidifying the extracellular space. Acidosis drives cancer cells from glycolysis to OxPhos, and OxPhos transforms the available alternative substrates into energy used to fuel migration and distant organ colonization. Thus, metabolic adaptations sustain different energy-requiring ability of cancer cells, but render them responsive to perturbations by anti-metabolic agents, such as inhibitors of glycolysis and/or OxPhos.

Peppicelli, Silvia; Bianchini, Francesca; Calorini, Lido

2015-01-01

263

Angiopoietin-2 associations with the underlying infection and sepsis severity.  

PubMed

Angiopoietin-2 (Ang-2) is an important mediator in sepsis. We have previously shown that endotoxemia levels are related to the underlying infection and affect septic patients' outcome. Based on this background we now investigated if circulating Ang-2 (cAng-2) and monocyte Ang-2 expression in septic patients are associated with the underlying infection and organ failure. We measured cAng-2 in 288 septic patients (121 with sepsis, 167 with severe sepsis/septic shock) at less than 24h post study inclusion (day 1) and on days 3 and 7. Peripheral blood mononuclear cells (PBMCs) were additionally isolated; Ang-2 gene expression was estimated by means of real-time PCR. Levels of cAng-2 were higher under severe sepsis and septic shock, as compared to uncomplicated sepsis; PBMC Ang-2 copies were higher in severe sepsis. On day 1, cAng-2 and Ang-2 gene copies were greater under severe sepsis/septic shock in sufferers from all types of infections with the exception of community-acquired pneumonia and ventilator-associated pneumonia. cAng-2 increased proportionally to the number of failing organs, and was higher under metabolic acidosis and acute coagulopathy as compared to no failing organ. On day 1, copies of Ang-2 were higher in survivors, whereas cAng-2 was higher in non-survivors. In a large cohort of septic patients, cAng-2 kinetics appears associated with the underlying infection and organ failure type. PMID:25748839

Lymperopoulou, Korina; Velissaris, Dimitrios; Kotsaki, Antigone; Antypa, Elli; Georgiadou, Sara; Tsaganos, Thomas; Koulenti, Despina; Paggalou, Evgenia; Damoraki, Georgia; Karagiannidis, Napoleon; Orfanos, Stylianos E

2015-05-01

264

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

Microsoft Academic Search

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

Aishe Chen; Lixue Dong; Nancy R. Leffler; Adam S. Asch; Owen N. Witte; Li V. Yang

2011-01-01

265

Extracellular acidosis impairs P2Y receptor-mediated Ca(2+) signalling and migration of microglia.  

PubMed

Microglia are the resident macrophage and immune cell of the brain and are critically involved in combating disease and assaults on the brain. Virtually all brain pathologies are accompanied by acidosis of the interstitial fluid, meaning that microglia are exposed to an acidic environment. However, little is known about how extracellular acidosis impacts on microglial function. The activity of microglia is tightly controlled by 'on' and 'off' signals, the presence or absence of which results in generation of distinct phenotypes in microglia. Activation of G protein coupled purinergic (P2Y) receptors triggers a number of distinct behaviours in microglia, including activation, migration, and phagocytosis. Using pharmacological tools and fluorescence imaging of the murine cerebellar microglia cell line C8B4, we show that extracellular acidosis interferes with P2Y receptor-mediated Ca(2+) signalling in these cells. Distinct P2Y receptors give rise to signature intracellular Ca(2+) signals, and Ca(2+) release from stores and Ca(2+) influx are differentially affected by acidotic conditions: Ca(2+) release is virtually unaffected, whereas Ca(2+) influx, mediated at least in part by store-operated Ca(2+) channels, is profoundly inhibited. Furthermore, P2Y1 and P2Y6-mediated stimulation of migration is inhibited under conditions of extracellular acidosis, whereas basal migration independent of P2Y receptor activation is not. Taken together, our results demonstrate that an acidic microenvironment impacts on P2Y receptor-mediated Ca(2+) signalling, thereby influencing microglial responses and responsiveness to extracellular signals. This may result in altered behaviour of microglia under pathological conditions compared with microglial responses in healthy tissue. PMID:25623949

Langfelder, Antonia; Okonji, Emeka; Deca, Diana; Wei, Wei-Chun; Glitsch, Maike D

2015-04-01

266

Hypercapnia and acidosis during the thoracoscopic repair of oesophageal atresia and congenital diaphragmatic hernia.  

PubMed

Thoracoscopic operations in neonates, such as repair of oesophageal atresia and tracheooesophageal fistula or congenital diaphragmatic hernia, can be associated with intraoperative acidosis and hypercapnia in the absence of hypoxia. These derangements in intraoperative gas exchanges seem to be related to the insufflation and absorption of medical CO2. The effects on the developing brain are unknown, and further prospective investigations are needed to elucidate whether different strategies should be implemented to avoid these intraoperative problems. PMID:25638611

Pierro, Agostino

2015-02-01

267

Ruminal Microbial and Fermentative Changes Associated with Experimentally Induced Subacute Acidosis in Steers1  

Microsoft Academic Search

We used six ruminally cannulated steers in a two-period crossover design to study ruminal fermentative and microbial changes as- sociated with induced subacute acidosis. Steers were adapted to either an 80% alfalfa hay (hay-adapted)- or corn grain (grain-adapted)-based concentrate diet. After feed was withheld for 24 h, steers were overfed with an all-grain diet at 3.5 × NEm daily for

D. W. Goad; C. L. Goad; T. G. Nagaraja

268

Isoflurane-induced acidosis depresses basal and PGE(2)-stimulated duodenal bicarbonate secretion in mice.  

PubMed

When running in vivo experiments, it is imperative to keep arterial blood pressure and acid-base parameters within the normal physiological range. The aim of this investigation was to explore the consequences of anesthesia-induced acidosis on basal and PGE(2)-stimulated duodenal bicarbonate secretion. Mice (strain C57bl/6J) were kept anesthetized by a spontaneous inhalation of isoflurane. Mean arterial blood pressure (MAP), arterial acid-base balance, and duodenal mucosal bicarbonate secretion (DMBS) were studied. Two intra-arterial fluid support strategies were used: a standard Ringer solution and an isotonic Na(2)CO(3) solution. Duodenal single perfusion was used, and DMBS was assessed by back titration of the effluent. PGE(2) was used to stimulate DMBS. In Ringer solution-infused mice, isoflurane-induced acidosis became worse with time. The blood pH was 7.15-7.21 and the base excess was about -8 mM at the end of experiments. The continuous infusion of Na(2)CO(3) solution completely compensated for the acidosis. The blood pH was 7.36-7.37 and base excess was about 1 mM at the end of the experiment. Basal and PGE(2)-stimulated DMBS were markedly greater in animals treated with Na(2)CO(3) solution than in those treated with Ringer solution. MAP was slightly higher after Na(2)CO(3) solution infusion than after Ringer solution infusion. We concluded that isoflurane-induced acidosis markedly depresses basal and PGE(2)-stimulated DMBS as well as the responsiveness to PGE(2), effects prevented by a continuous infusion of Na(2)CO(3). When performing in vivo experiments in isoflurane-anesthetized mice, it is recommended to supplement with a Na(2)CO(3) infusion to maintain a normal acid-base balance. PMID:17158257

Sjöblom, Markus; Nylander, Olof

2007-03-01

269

Oxygen consumption is depressed in patients with lactic acidosis due to biguanide intoxication  

PubMed Central

Introduction Lactic acidosis can develop during biguanide (metformin and phenformin) intoxication, possibly as a consequence of mitochondrial dysfunction. To verify this hypothesis, we investigated whether body oxygen consumption (VO2), that primarily depends on mitochondrial respiration, is depressed in patients with biguanide intoxication. Methods Multicentre retrospective analysis of data collected from 24 patients with lactic acidosis (pH 6.93 ± 0.20; lactate 18 ± 6 mM at hospital admission) due to metformin (n = 23) or phenformin (n = 1) intoxication. In 11 patients, VO2 was computed as the product of simultaneously recorded arterio-venous difference in O2 content [C(a-v)O2] and cardiac index (CI). In 13 additional cases, C(a-v)O2, but not CI, was available. Results On day 1, VO2 was markedly depressed (67 ± 28 ml/min/m2) despite a normal CI (3.4 ± 1.2 L/min/m2). C(a-v)O2 was abnormally low in both patients either with (2.0 ± 1.0 ml O2/100 ml) or without (2.5 ± 1.1 ml O2/100 ml) CI (and VO2) monitoring. Clearance of the accumulated drug was associated with the resolution of lactic acidosis and a parallel increase in VO2 (P < 0.001) and C(a-v)O2 (P < 0.05). Plasma lactate and VO2 were inversely correlated (R2 0.43; P < 0.001, n = 32). Conclusions VO2 is abnormally low in patients with lactic acidosis due to biguanide intoxication. This finding is in line with the hypothesis of inhibited mitochondrial respiration and consequent hyperlactatemia. PMID:20170489

2010-01-01

270

Effects of bacterial direct-fed microbials and yeast on site and extent of digestion, blood chemistry, and subclinical ruminal acidosis in feedlot cattle.  

PubMed

Two studies were conducted to determine whether a bacterial direct-fed microbial (DFM) alone or with yeast could minimize the risk of acidosis and improve feed utilization in feedlot cattle receiving high-concentrate diets. Eight ruminally cannulated steers, previously adapted to a high-concentrate diet, were used in crossover designs to study the effects of DFM on feed intake, ruminal pH, ruminal fermentation, blood characteristics, site and extent of digestion, and microbial protein synthesis. Steers were provided ad libitum access to a diet containing steam-rolled barley, barley silage, and a protein-mineral supplement (87, 8, and 5% on a DM basis, respectively). In Exp. 1, treatments were control vs. the lactic-acid producing bacterium Enterococcus faecium EF212 (EF; 6 x 10(9) cfu/d). In Exp. 2, treatments were control vs EF (6 x 10(9) cfu/d) and yeast (Saccharomyces cerevisiae; 6 x 10(9) cfu/d). Supplementing feedlot cattle diets with EF in Exp. 1 increased (P < 0.05) propionate and (P < 0.05) decreased butyrate concentrations, decreased the nadir of ruminal pH (P < 0.05), enhanced the flow of feed N (P < 0.10) to the duodenum but reduced that of microbial N (P < 0.10), reduced (P < 0.10) intestinal digestion of NDF, and increased (P < 0.10) fecal coliform numbers. Other than the increase in propionate concentrations that signify an increase in energy precursors for growth, the other metabolic changes were generally considered to be undesirable. In Exp. 2, providing EF together with yeast abolished most of these undesirable effects. Combining EF with yeast increased the DM digestion of corn grain incubated in sacco, but there were no effects on altering the site or extent of nutrient digestion. The diets used in this study were highly fermentable, and the incidence of subclinical ruminal acidosis, defined as steers with ruminal pH below 5.5 for prolonged periods of time, was high. Supplementing the diet with EF, with or without yeast, had limited effects on reducing ruminal acidosis. It seems that cattle adapted to high-grain diets are able to maintain relatively high feed intake and high fiber digestion despite low ruminal pH. The Enterococcus faecium bacterium and yeast used in this study were of limited value for feedlot cattle already adapted to high-grain diets. PMID:12817511

Beauchemin, K A; Yang, W Z; Morgavi, D P; Ghorbani, G R; Kautz, W; Leedle, J A Z

2003-06-01

271

Application of Research Findings and Summary of Research Needs: Bud Britton Memorial Symposium on Metabolic Disorders of Feedlot Cattle1  

Microsoft Academic Search

Updated research findings with acido- sis, feedlot bloat, liver abscesses, and sudden death syndromes were presented at the Bud Britton Memorial Symposium on Metabolic Disorders of Feed- lot 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 polioen- cephalomalacia, examination of the effects

M. L. Galyean; K. S. Eng

272

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

273

Lactic acidosis after concomitant treatment with metformin and tenofovir in a patient with HIV infection.  

PubMed

We present an uncommon case of lactic acidosis after concomitant administration of Metformin and Tenofovir. This is a 74-year-old man with a history of diabetes mellitus receiving treatment with metformin. He had coronary artery disease and HIV infection treated with emtricitabine, tenofovir and recently started on efavirenz. He presented with zoster-like abdominal pain, tachypnoea, nausea and vomiting. On clinical examination, the patient was afebrile, hypotensive and tachycardic, he was markedly dehydrated and oliguric. The abdomen was soft, tender on palpation, not distended without rebound tenderness. The arterial blood gases revealed marked lactic acidosis and the laboratory tests on admission showed acute renal failure. The patient received nine treatments of slow continuous veno-venous hemofiltration (CVVHF). Despite the prolonged period of anuria, urine output progressively improved after 25 days and serum biochemical parameters of renal function returned to normal within 40 days. Health professionals must be aware of this uncommon effect in patients on antiretroviral treatment. Prompt initiation of CVVHF resulted in resolution of both lactic acidosis and renal failure. PMID:21288314

Aperis, Georgios; Paliouras, Christos; Zervos, Angelos; Arvanitis, Antonios; Alivanis, Polichronis

2011-03-01

274

Risk Factors for Acute Kidney Injury in Severe Rhabdomyolysis  

PubMed Central

Background Acute kidney injury (AKI) is a life-threatening complication of severe rhabdomyolysis. This study was conducted to assess risk factors for AKI and to develop a risk score for early prediction. Methods Retrospective observational cohort study with a 9-year follow-up, carried out in an acute-care teaching-affiliated hospital. A total of 126 patients with severe rhabdomyolysis defined as serum creatine kinase (CK) > 5,000 IU/L fulfilled the inclusion criteria. Univariate and logistic regression analyses were performed to determine risk factors for AKI. Based on the values obtained for each variable, a risk score and prognostic probabilities were estimated to establish the risk for developing AKI. Results The incidence of AKI was 58%. Death during hospitalization was significantly higher among patients with AKI, compared to patients without AKI (19.2% vs 3.6%, p?=?0.008). The following variables were independently associated with AKI: peak CK (odds ratio [OR] 4.9, 95%CI 1.4-16.8), hypoalbuminemia (< 33 mg/dL, [OR 5.1, 95%CI 1.4-17-7]), metabolic acidosis (OR 5.3, 95%CI 1.4-20.3), and decreased prothrombin time (OR 4.4, 95% CI 1.3-14.5). A risk score for AKI was calculated for each patient, with an OR of 1.72 (95%CI 1.45-2.04). The discrimination value of the predictive model was established by means of a ROC curve, with the area under the curve of 0.871 (p<0.001). Conclusions The identification of independent factors associated with AKI and a risk score for early prediction of this complication in patients with severe rhabdomyolysis may be useful in clinical practice, particularly to implement early preventive measures. PMID:24367578

Rodríguez, Eva; Soler, María J.; Rap, Oana; Barrios, Clara; Orfila, María A.; Pascual, Julio

2013-01-01

275

Effects on ionized calcium of a correction of acidosis with alkalinizing agents. A rational basis for the administration of calcium in cardiac resuscitation.  

PubMed

The effects on the ionized calcium concentration of a correction of various forms of acidosis with sodium bicarbonate or (tris-hydroxymethyl)aminomethane (THAM) were investigated in vitro in human plasma. Calculation of least square regression equations of ionized calcium (m mol) on pH yielded the following regression coefficients: hydrochloric acidosis: -0.65 +/- 0.06; lactic acidosis: -0.27 +/- 0.05; hydrochloric acidosis corrected with sodium bicarbonate: -0.65 +/- 0.02; lactic acidosis corrected with sodium bicarbonate: -0.51 +/- 0.03. The results indicate that after correction of lactic acidosis the ionized calcium concentration will be below the control values while pH is restored to the normal range. This effect is even more pronounced when THAM is used. The findings point to the need for calcium administration in cardiac resuscitation. PMID:1275999

Schaer, H

1976-04-01

276

Japanese cases of acute onset diabetic ketosis without acidosis in the absence of glutamic acid decarboxylase autoantibody.  

PubMed

We report consecutive Japanese patients presented with acute onset diabetic ketosis who had negative glutamic acid decarboxylase autoantibody (GADAb) to clarify the clinical characteristics of them. A total of consecutive 1,296 in-patients with newly diagnosed diabetes mellitus, who were admitted to our center from April 2003 to October 2008, were analyzed. Among them, 17 patients who presented with acute onset diabetic ketosis without acidosis, and found to be negative for GADAb, were included. They showed male preponderance (n = 15). Ten patients had history of excessive ingestion of sugar-containing soft drink. Patients who successfully withdrew insulin therapy by 6 months (n = 7) showed significantly higher insulin secretion capacity and higher body mass index at the time of diagnosis than those who continued insulin therapy at least for 6 months (n = 10). These findings suggest that some of Japanese patients who presented with acute onset diabetic ketosis and negative for GADAb share several clinical characteristics with atypical type 2 diabetes such as ketosis-prone diabetes and "soft-drink ketosis," but others do not. PMID:20960264

Iwasaki, Yorihiro; Hamamoto, Yoshiyuki; Kawasaki, Yukiko; Ikeda, Hiroki; Honjo, Sachiko; Wada, Yoshiharu; Koshiyama, Hiroyuki

2010-04-01

277

Novel AE1 mutations in recessive distal renal tubular acidosis. Loss-of-function is rescued by glycophorin A.  

PubMed Central

The AE1 gene encodes band 3 Cl-/HCO3- exchangers that are expressed both in the erythrocyte and in the acid-secreting, type A intercalated cells of the kidney. Kidney AE1 contributes to urinary acidification by providing the major exit route for HCO3- across the basolateral membrane. Several AE1 mutations cosegregate with dominantly transmitted nonsyndromic renal tubular acidosis (dRTA). However, the modest degree of in vitro hypofunction exhibited by these dRTA-associated mutations fails to explain the disease phenotype in light of the normal urinary acidification associated with the complete loss-of-function exhibited by AE1 mutations linked to dominant spherocytosis. We report here novel AE1 mutations linked to a recessive syndrome of dRTA and hemolytic anemia in which red cell anion transport is normal. Both affected individuals were triply homozygous for two benign mutations M31T and K56E and for the loss-of-function mutation, G701D. AE1 G701D loss-of-function was accompanied by impaired trafficking to the Xenopus oocyte surface. Coexpression with AE1 G701D of the erythroid AE1 chaperonin, glycophorin A, rescued both AE1-mediated Cl- transport and AE1 surface expression in oocytes. The genetic and functional data both suggest that the homozygous AE1 G701D mutation causes recessively transmitted dRTA in this kindred with apparently normal erythroid anion transport. PMID:9854053

Tanphaichitr, V S; Sumboonnanonda, A; Ideguchi, H; Shayakul, C; Brugnara, C; Takao, M; Veerakul, G; Alper, S L

1998-01-01

278

[Metabolic syndrome].  

PubMed

The metabolic syndrome consists of a cluster of metabolic diseases which often coexist: abdominal obesity, glucoseintolerance, diabetes mellitus type II, dyslipidemia, hypertension and impaired fibrinolysis. The common pathophysiologic link of these diseases in insulin resistance. All clinical disorders of the metabolic syndrome are risk factors for the vascular system. Since several diseases are present at the same time the risk for atherosclerotic complications such as coronary artery disease and apoplexy is potentiated. As a consequence the costs for direct and indirect health care are high. Besides a genetic predisposition the metabolic syndrome is mainly caused by the typical life style in industrialized countries with high energy and fat intake, physical inactivity, alcohol consumption, smoking, and stress. Therefore, prophylaxis and therapy imply the removal of these factors. In order to be successful experienced physicians and motivated patients are prerequisites. Even more affective than therapy is prophylaxis which is, however, not established in Germany. The metabolic syndrome is up to now not identified as a major health problem neither by the medical profession nor by health insurances and politicians. An effective therapy and prophylaxis would induce far-reaching changes in our health system and diminish health costs. PMID:9082643

Wirth, A; Rothenfelde, B

1996-12-01

279

The lethal form of Cushing's in 7B2 null mice is caused by multiple metabolic and hormonal abnormalities.  

PubMed

The neuroendocrine-specific protein 7B2, which serves as a molecular escort for proPC2 in the secretory pathway, promotes the production of enzymatically active PC2 and may have non-PC2 related endocrine roles. Mice null for 7B2 exhibit a lethal phenotype with a complex Cushing's-like pathology, which develops from intermediate lobe ACTH hypersecretion as a consequences of interruption of PC2-mediated peptide processing as well as undefined consequences of the loss of 7B2. In this study we investigated the endocrine and metabolic alterations of 7B2 null mice from pathological and biochemical points of view. Our results show that 7B2 nulls exhibit a multisystem disorder that includes severe pathoanatomical and histopathologic alterations of vital organs, including the heart and spleen but most notably the liver, in which massive steatosis and necrosis are observed. Metabolic derangements in glucose metabolism result in glycogen and fat deposition in liver under conditions of chronic hypoglycemia. Liver failure is also likely to contribute to abnormalities in blood coagulation and blood chemistry, such as lactic acidosis. A hypoglycemic crisis coupled with respiratory distress and intensive internal thrombosis most likely results in rapid deterioration and death of the 7B2 null. PMID:12021197

Sarac, Miroslav S; Zieske, Arthur W; Lindberg, Iris

2002-06-01

280

Effects of acute metabolic acid-base changes and furosemide on magnesium excretion in rats.  

PubMed

The effect of acute metabolic acid-base changes on renal magnesium transport is not well defined. We have examined renal magnesium handling in three groups of ten acutely thyroparathyroidectomized rats infused with isotonic NaCl (controls), NH4Cl (acidosis), and NaHCO3 (alkalosis). To define the interactions of furosemide with acid-base changes and in an attempt to localize the site of action of acidosis and alkalosis on tubular magnesium transport, the rats were studied in a second phase after administration of a maximal dose of furosemide. Before furosemide, the blood pH was 7.40 in the controls, 7.27 (P less than 0.001) in the acidotic rats, and 7.56 (P less than 0.001) in the alkalotic rats. The filtered magnesium load was not significantly different in the three groups, but fractional excretion of magnesium (FEMg) was 33.7%, 37.4%, and 13.3% in the controls, the acidosis group, and the alkalosis group, respectively. Following furosemide, the blood pH was unchanged in each group, but FEMg increased significantly to 55.4%, 71.1% (P less than 0.01 compared with controls), and 41.4% (P less than 0.01 compared with controls) in the controls, the acidotic rats, and the alkalotic rats, respectively. These data indicate that metabolic alkalosis per se enhances renal magnesium transport, and this effect is also evident after blockade of loop magnesium reabsorption by a maximal dose of furosemide. Acidosis per se does not significantly alter magnesium transport, but an inhibitory effect of acidosis on magnesium reabsorption becomes evident when distal magnesium delivery is greatly increased by furosemide. These interactions suggest that metabolic acid-base changes and furosemide may influence magnesium reabsorption at different tubule sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6621362

Marone, C C; Sutton, R A

1983-11-01

281

Ras triggers acidosis-induced activation of the extracellular-signal-regulated kinase pathway in cardiac myocytes.  

PubMed

In cardiac myocytes, sustained (3 min) intracellular acidosis activates the ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway and, through this pathway, increases sarcolemmal NHE (Na+/H+ exchanger) activity [Haworth, McCann, Snabaitis, Roberts and Avkiran (2003) J. Biol. Chem. 278, 31676-31684]. In the present study, we aimed to determine the time-dependence, pH-dependence and upstream signalling mechanisms of acidosis-induced ERK1/2 activation in ARVM (adult rat ventricular myocytes). Cultured ARVM were subjected to intracellular acidosis for up to 20 min by exposure to NH4Cl, followed by washout with a bicarbonate-free Tyrode solution containing the NHE1 inhibitor cariporide. After the desired duration of intracellular acidosis, the phosphorylation status of ERK1/2 and its downstream effector p90(RSK) (90 kDa ribosomal S6 kinase) were determined by Western blotting. This revealed a time-dependent transient phosphorylation of both ERK1/2 and p90(RSK) by intracellular acidosis (intracellular pH approximately 6.6), with maximum activation occurring at 3 min and a return to basal levels by 20 min. When the degree of intracellular acidosis was varied from approximately 6.8 to approximately 6.5, maximum ERK1/2 phosphorylation was observed at an intracellular pH of 6.64. Inhibition of MEK1/2 [MAPK (mitogen-activated protein kinase)/ERK kinase 1/2) by pre-treatment of ARVM with U0126 or adenoviral expression of dominant-negative D208A-MEK1 protein prevented the phosphorylation of ERK1/2 by sustained intracellular acidosis, as did inhibition of Raf-1 with GW 5074 or ZM 336372. Interference with Ras signalling by the adenoviral expression of dominant-negative N17-Ras protein or with FPT III (farnesyl protein transferase inhibitor III) also prevented acidosis-induced ERK1/2 phosphorylation, whereas inhibiting G-protein signalling [by adenoviral expression of RGS4 or Lsc, the RGS domain of p115 RhoGEF (guanine nucleotide-exchange factor)] or protein kinase C (with bisindolylmaleimide I) had no effect. Our data show that, in ARVM, sustained intracellular acidosis activates ERK1/2 through proximal activation of the classical Ras/Raf/MEK pathway. PMID:16831126

Haworth, Robert S; Dashnyam, Semjidmaa; Avkiran, Metin

2006-11-01

282

Episodic, transient systemic acidosis delays evolution of the malignant phenotype: Possible mechanism for cancer prevention by increased physical activity  

PubMed Central

Background The transition from premalignant to invasive tumour growth is a prolonged multistep process governed by phenotypic adaptation to changing microenvironmental selection pressures. Cancer prevention strategies are required to interrupt or delay somatic evolution of the malignant invasive phenotype. Empirical studies have consistently demonstrated that increased physical activity is highly effective in reducing the risk of breast cancer but the mechanism is unknown. Results Here we propose the hypothesis that exercise-induced transient systemic acidosis will alter the in situ tumour microenvironment and delay tumour adaptation to regional hypoxia and acidosis in the later stages of carcinogenesis. We test this hypothesis using a hybrid cellular automaton approach. This model has been previously applied to somatic evolution on epithelial surfaces and demonstrated three phases of somatic evolution, with cancer cells escaping in turn from the constraints of limited space, nutrient supply and waste removal. In this paper we extend the model to test our hypothesis that transient systemic acidosis is sufficient to arrest, or at least delay, transition from in situ to invasive cancer. Conclusions Model simulations demonstrate that repeated episodes of transient systemic acidosis will interrupt critical evolutionary steps in the later stages of carcinogenesis resulting in substantial delay in the evolution to the invasive phenotype. Our results suggest transient systemic acidosis may mediate the observed reduction in cancer risk associated with increased physical activity. Reviewers This article was reviewed by Natalia Komarova (nominated by Marek Kimmel), Heiko Enderling (nominated by Marek Kimmel), Mark Little (nominated by Marek Kimmel) and Yang Kuang. PMID:20406440

2010-01-01

283

Functional effects of a tropomyosin mutation linked to FHC contribute to maladaptation during acidosis  

PubMed Central

Familial Hypertrophic Cardiomyopathy (FHC) is a leading cause of sudden cardiac death among young athletes but the functional effects of the myofilament mutations during FHC-associated ischemia and acidosis, due in part to increased extravascular compressive forces and microvascular dysfunction, are not well characterized. We tested the hypothesis that the FHC-linked tropomyosin (Tm) mutation Tm-E180G alters the contractile response to acidosis via increased myofilament Ca2+ sensitivity. Intact papillary muscles from transgenic (TG) mice expressing Tm-E180G and exposed to acidic conditions (pH 6.9) exhibited a significantly smaller decrease in normalized isometric tension compared to non-transgenic (NTG) preparations. Times to peak tension and to 90% of twitch force relaxation in TG papillary muscles were significantly prolonged. Intact single ventricular TG myocytes demonstrated significantly less inhibition of unloaded shortening during moderate acidosis (pH 7.1) than NTG myocytes. The peak Ca2+ transients were not different for TG or NTG at any pH tested. The time constant of re-lengthening was slower in TG myocytes, but not the rate of Ca2+ decline. TG detergent-extracted fibers demonstrated increased Ca2+ sensitivity of force and maximal tension compared to NTG at both normal and acidic pH (pH 6.5). Tm phosphorylation was not different between TG and NTG muscles at either pH. Our data indicate that acidic pH diminished developed force in hearts of TG mice less than in NTG due to their inherently increased myofilament Ca2+ sensitivity, thus potentially contributing to altered energy demands and increased propensity for contractile dysfunction. PMID:21047515

Sheehan, Katherine A.; Arteaga, Grace M.; Hinken, Aaron C.; Dias, Fernando A.; Ribeiro, Cibele; Wieczorek, David F.; Solaro, R. John; Wolska, Beata M.

2010-01-01

284

Monitoring emergence from coma following severe brain injury in an octogenarian using behavioural indicators, electrophysiological measures and metabolic studies: a demonstration of the potential for good recovery in older adults.  

PubMed

This case study describes a multi-disciplinary investigation of the emergence from coma of an 80-year old female (KE) following severe traumatic brain injury. The relationship between cognitive/behavioural ability and the integrity of cerebral function was assessed using neuropsychological measures, positron emission tomography, electroencephalography, somatosensory evoked potentials and trans-cranial magnetic stimulation. These investigations were performed as KE was beginning to emerge from coma (4 weeks) and, again, approximately 1 year following brain injury, when she was judged to have achieved her maximum level of recovery. Neuropsychological measures revealed improvement during the first year post-injury in KE's speed of information processing, memory and executive abilities. Electrophysiological and metabolic studies indicated a restoration of functional integrity that was consistent with the gradual recovery in higher brain function documented using behavioural procedures. This case study demonstrates the rehabilitation potential of pre-morbidly healthy older adults following severe traumatic brain injury. PMID:16195187

Crossley, M; Shiel, A; Wilson, B; Coleman, M R; Gelling, L; Fryer, T; Boniface, S; Pickard, J

2005-08-20

285

Effect of rapid or gradual grain adaptation on subacute acidosis and feed intake by feedlot cattle.  

PubMed

The effects of grain adaptation protocol on subacute acidosis and feed intake by cattle were studied in a completely randomized experiment using 12 crossbred heifers (384 +/- 25 kg BW). The dietary proportion of concentrate was increased from 40 to 90% (DM basis) either by rapid adaptation (65% concentrate diet fed for 3 d) or by gradual adaptation (five intermediate diets containing 48.3, 56.7, 65.0, 73.3, and 81.7% concentrate, fed for 3 d each). Feed intake and ruminal pH (by indwelling ruminal electrodes) were monitored over 20 d. Mean daily pH variables did not differ (P > or = 0.10) between treatments on any of the 3 or 4 d that 65 or 90% concentrate was fed. Variances of a number of pH variables were greater (P < 0.05) for rapidly adapted heifers than for those on the gradual adaptation protocol during adaptation to 65 and 90% concentrate. Mean hourly pH did not differ over the first 24 h of adaptation to 65% concentrate, but variance of hourly pH tended (P < 0.10) to be greater for rapidly adapted than for gradually adapted heifers for eight of the first 24 h. On the first day of feeding 90% concentrate, ruminal pH tended (P = 0.07) to be less at 11 and 12 h after feeding with rapid adaptation than with gradual adaptation. Variance of hourly pH increased steadily in rapidly adapted heifers from 6 h after feeding onward. Ruminal VFA concentration and osmolality did not differ between treatments. Ruminal lactate concentration was < 1 mM, except in two rapidly adapted heifers and one gradually adapted heifer after introduction to 90% concentrate. Adaptation method did not affect DMI or day-to-day variation in DMI. Detection of acidosis was associated with increased variance in ruminal pH variables. A range of individual responses to grain challenge was observed, but current management strategies for preventing acidosis in pens of cattle are based on responses of the most susceptible individuals. A better understanding of factors governing individual responses to acidotic challenge may allow for the development of more effective acidosis prevention practices. PMID:15827257

Bevans, D W; Beauchemin, K A; Schwartzkopf-Genswein, K S; McKinnon, J J; McAllister, T A

2005-05-01

286

Central Diabetes Insipidus, Central Hypothyroidism, Renal Tubular Acidosis and Dandy-Walker Syndrome: New Associations  

PubMed Central

Dandy-Walker syndrome (DWS) is a rare brain malformation involving the cerebellum, and the fluid filled spaces around it, usually detected during the antenatal period or the early infancy. Clinically, it is characterized by mental retardation, developmental delay as well as cerebellar ataxia. It has been frequently associated with other conditions such as congenital heart diseases, primary hypothyroidism, and other disorders of the central nervous, gastrointestinal, genitourinary, and orthopedic systems. In this report, we describe a 3-month-old Saudi boy with the rare association of DWS with central diabetes insipidus, congenital central hypothyroidism, and type-2 renal tubular acidosis.

Alafif, MM; Aljaid, SS; Al-Agha, AE

2015-01-01

287

Central diabetes insipidus, central hypothyroidism, renal tubular acidosis and dandy-walker syndrome: new associations.  

PubMed

Dandy-Walker syndrome (DWS) is a rare brain malformation involving the cerebellum, and the fluid filled spaces around it, usually detected during the antenatal period or the early infancy. Clinically, it is characterized by mental retardation, developmental delay as well as cerebellar ataxia. It has been frequently associated with other conditions such as congenital heart diseases, primary hypothyroidism, and other disorders of the central nervous, gastrointestinal, genitourinary, and orthopedic systems. In this report, we describe a 3-month-old Saudi boy with the rare association of DWS with central diabetes insipidus, congenital central hypothyroidism, and type-2 renal tubular acidosis. PMID:25861538

Alafif, M M; Aljaid, S S; Al-Agha, A E

2015-01-01

288

Metabolic Syndrome  

MedlinePLUS

... page from the NHLBI on Twitter. What Is Metabolic Syndrome? Metabolic (met-ah-BOL-ik) syndrome is the ... three metabolic risk factors to be diagnosed with metabolic syndrome. A large waistline. This also is called abdominal ...

289

Metabolic alkalosis transition in renal proximal tubule cells facilitates an increase in CYP27B1, while blunting responsiveness to PTH  

Technology Transfer Automated Retrieval System (TEKTRAN)

Parathyroid hormone (PTH) is the central activator of renal proximal 1-alpha-hydroxylase (CYP27B1), the enzyme responsible for synthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Past studies have documented a disruption of CYP27B1 activity in chronic metabolic acidosis in vivo, while simulated ac...

290

Relation of Apparent Diffusion Coefficient Changes and Metabolic Disturbances After 1 Hour of Focal Cerebral Ischemia and at Different Reperfusion Phases in Rats  

Microsoft Academic Search

Changes in apparent diffusion coefficients (ADC) were compared with alterations of adenosine triphosphate (ATP) concentration and pH in different phases of transient focal cerebral ischemia to study the ADC threshold for breakdown of energy metabolism and tissue acidosis during ischemia and reperfusion. Male Wistar rats underwent 1 hour of middle cerebral artery occlusion without recirculation (n = 3) or with

Laszlo Olah; Stefan Wecker; Mathias Hoehn

2001-01-01

291

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

292

Role of metabolically active drugs in the management of ischemic heart disease.  

PubMed

This article reviews the fundamentals of myocardial energy metabolism and selectively outlines the use of several metabolically active drug therapies in the treatment of ischemic heart disease. These drugs - ranolazine, trimetazidine, dichloroacetate (DCA), glucose-insulin-potassium (GIK) solutions, and L-carnitine - have mechanisms of action distinct from traditional anti-ischemic drugs. These agents work by shifting myocardial energy metabolism away from fatty acids toward glucose as a source of fuel. Because these agents are well tolerated and do not affect heart rate or blood pressure, they conceivably could supplement traditional anti-ischemic drug therapy with little risk. The background, rationale for use, and published literature on each agent is reviewed, and the outcomes of pertinent clinical trials are discussed. In the case of ranolazine, data suggest benefit in the treatment of stable angina pectoris, particularly with sustained release formulations. Trimetazidine appears to have similar physiologic effects to ranolazine, and it is effective as monotherapy and as additive therapy in patients with chronic ischemic heart disease. DCA improves acidosis in critically ill patients and, likewise, improves myocardial hemodynamics in those with chronic coronary artery disease and congestive heart failure; however, its metabolism is variable and clinical data on its use in chronic ischemic heart disease are limited. GIK solutions have been shown to be beneficial in animal and human models of ischemia and acute myocardial infarction, and they offer an inexpensive means by which to improve the oxidation of glucose in the heart. Lastly, a large body of literature suggests a benefit with L-carnitine in a number of cardiovascular illnesses, including ischemic heart disease. Clinical trial data in acute myocardial infarction are promising and have prompted the initiation of a large-scale mortality trial. PMID:14728049

Schofield, R S; Hill, J A

2001-01-01

293

Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits  

SciTech Connect

A study of the combined effects of intravenous infusion of the recombinant cytokines beta-interleukin 1 (IL-1) and alpha-tumor necrosis factor (TNF) on energy substrate metabolism in awake, conditioned, adult rabbits was performed. After a 2-h basal or control period, 48-h fasted rabbits were administered TNF and IL-1 as a bolus (5 micrograms/kg) followed by a continuous intravenous infusion (25 ng.kg-1.min-1) for 3 h. Significant increases in plasma lactate (P less than 0.01), glucose (P less than 0.01), and triglycerides (P less than 0.05) occurred during the combined infusion of IL-1 and TNF, whereas neither cytokine alone had no effect. There was a 33% increase in the rate of glucose appearance (P less than 0.05), but glucose clearance was not altered compared with the control period. Glucose oxidation increased during the combined cytokine infusion period and glucose recycling increased by 600% (P less than 0.002). Lactic acidosis and decreased oxygen consumption, as a result of the cytokine infusions, indicated development of anaerobic glycolytic metabolism. A reduction in the activity state of hepatic mitochondrial pyruvate dehydrogenase (65 vs. 82% in control animals, P less than 0.05) was consistent with the observed increase in anaerobic glycolysis. Thus the combined infusion of IL-1 and TNF in rabbits produces metabolic manifestations seen in severe injury and sepsis in human patients and, as such, may account for the profound alterations of energy metabolism seen in these conditions.

Tredget, E.E.; Yu, Y.M.; Zhong, S.; Burini, R.; Okusawa, S.; Gelfand, J.A.; Dinarello, C.A.; Young, V.R.; Burke, J.F.

1988-12-01

294

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

295

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

296

Effects of interval and continuous training on O2 uptake kinetics during severe-intensity exercise initiated from an elevated metabolic baseline.  

PubMed

The purpose of this study was to test the hypothesis that Vo2 kinetics would be speeded to a greater extent following repeated sprint training (RST), compared with continuous endurance training (ET), in the transition from moderate- to severe-intensity exercise. Twenty-three recreationally active subjects were randomly assigned to complete six sessions of ET (60-110 min of moderate-intensity cycling) or RST (four to seven 30-s all-out Wingate tests) over a 2-wk period. Subjects completed three identical work-to-work cycling exercise tests before and after the intervention period, consisting of baseline cycling at 20 W followed by sequential step increments to moderate- and severe-intensity work rates. The severe-intensity bout was continued to exhaustion on one occasion and was followed by a 60-s all-out sprint on another occasion. Phase II pulmonary Vo2 kinetics were speeded by a similar magnitude in both the lower (ET pre, 28 ± 4; ET post, 22 ± 4 s; RST pre, 25 ± 8; RST post, 20 ± 7 s) and upper (ET pre, 50 ± 10; ET post, 39 ± 11 s; RST pre, 54 ± 7; RST post, 40 ± 11 s) steps of the work-to-work test following ET and RST (P < 0.05). The tolerable duration of exercise and the total amount of sprint work completed in the exercise performance test were also similarly enhanced by ET and RST (P < 0.05). Therefore, ET and RST provoked comparable improvements in Vo2 kinetics and exercise performance in the transition from an elevated baseline work rate, with RST being a more time-efficient approach to elicit these adaptations. PMID:24526579

Da Boit, Mariasole; Bailey, Stephen J; Callow, Steven; Dimenna, Fred J; Jones, Andrew M

2014-04-15

297

Recurrent Anion Gap Acidosis: An Unusual Presentation of X-Linked Adrenoleukodystrophy in a Five-year-old Male  

PubMed Central

We are presenting a five-year-old male with recurrent anion gap acidosis. During his last admission, it was detected that he had elevated VLCFA and the evaluation discovered that he had X-linked Adrenooleukodystrophy. He had the Addisonian only phenotype without any clinical or radiographic CNS findings. We were unable to find any other reports of this presentation of ALD. If the work-up of recurrent anion gap acidosis does not uncover an etiology, X-linked ALD should be considered in the differential diagnosis. PMID:23926373

Schwab, Joel; Pena, Loren; Sigman, Laura; Waggoner, Darrel

2010-01-01

298

Clinical spectrum and treatment outcome of severe malaria caused by Plasmodium vivax in 18 children from northern India  

PubMed Central

Objective The study was intended to document the clinical profile and treatment outcome of severe malaria caused by Plasmodium vivax (P.vivax) in children hospitalized in a tertiary care centre of northern India. Methods This prospective observational study was performed among children admitted with severe malaria at a tertiary care referral hospital of northern India from January 2012 to December 2012. Information was recorded pertaining to clinical symptoms at presentation, examination findings, biochemical and hematological investigation, and treatment outcome. Presence of malarial parasite on thick and thin smears and/or positive parasite lactate dehydrogenase (p-LDH) based rapid malaria antigen test was considered diagnostic of ‘malaria’. Based on the etiology, children were categorized into three groups: P.vivax, Plasmodium falciparum (P. falciparum) and mixed infection. Children diagnosed with ‘severe malaria’ (World Health Organization, 2000), were started on intravenous artesunate followed by artemether-lumefantrine combination. Results Thirty-five children with a diagnosis of severe malaria were enrolled [18 (51.4%) P. vivax, nine (25.7%) mixed infection, eight (22.8%) P. falciparum]. Clinical features of severe vivax malaria (n?=?18) were abnormal sensorium [9 (50%)], multiple seizures [8 (44.4%)], jaundice [5 (27.8%)], severe anaemia [5 (27.8%)], and shock [3 (16.7%)]. Two children [2/18 (11.1%)] infected with P. vivax had died of cerebral malaria, acute respiratory distress syndrome, shock, and metabolic acidosis. The clinical presentation and outcome of severe vivax malaria was found to be similar to severe malaria caused by P. falciparum and mixed infection, except for higher chances of severe anaemia among the children infected with P. falciparum (P?=?0.04). Conclusion The present study highlights P. vivax as an increasingly recognized causative agent for severe malaria in children from Rohtak, with similar clinical presentation and outcome to that caused by P. falciparum. PMID:23816514

Gehlawat, Virender Kumar; Arya, Vandana; Kaushik, Jaya Shankar; Gathwala, Geeta

2013-01-01

299

Respiratory signaling of locus coeruleus neurons during hypercapnic acidosis in the bullfrog, Lithobates catesbeianus.  

PubMed

The locus coeruleus (LC) in the brainstem senses alterations in CO(2)/pH and influences ventilatory adjustments that restore blood gas values to starting levels in bullfrogs (Lithobates catesbeianus). We hypothesized that neurons of the bullfrog LC are sensitive to changes in CO(2)/pH and that chemosensitive responses are intrinsic to individual neurons. In addition, we hypothesized putative respiratory control neurons of the bullfrog LC would be stimulated by hypercapnic acidosis within physiological ranges of P(CO(2))/pH. 84% of LC neurons depolarized and increased firing rates during exposure to hypercapnic acidosis (HA). A pH dose response curve shows LC neurons from bullfrogs increase firing rates during physiologically relevant CO(2)/pH changes. With chemical synapses blocked, half of chemosensitive neurons lost sensitivity to HA; however, gap junction blockade did not alter chemosensitive responses. Intrinsically chemosensitive neurons increased input resistance during HA. These data demonstrate that majority of neurons within the bullfrog LC elicit robust firing responses during physiological ?CO(2)/pH, likely enabling adjustment of acid-base balance through breathing. PMID:23146875

Santin, J M; Hartzler, L K

2013-02-01

300

Fluoxetine Treatment Abolishes the In Vitro Respiratory Response to Acidosis in Neonatal Mice  

PubMed Central

Background To secure pH homeostasis, the central respiratory network must permanently adapt its rhythmic motor drive to environment and behaviour. In neonates, it is commonly admitted that the retrotrapezoid/parafacial respiratory group of neurons of the ventral medulla plays the primary role in the respiratory response to acidosis, although the serotonergic system may also contribute to this response. Methodology/Principal Findings Using en bloc medullary preparations from neonatal mice, we have shown for the first time that the respiratory response to acidosis is abolished after pre-treatment with the serotonin-transporter blocker fluoxetine (25–50 µM, 20 min), a commonly used antidepressant. Using mRNA in situ hybridization and immunohistology, we have also shown the expression of the serotonin transporter mRNA and serotonin-containing neurons in the vicinity of the RTN/pFRG of neonatal mice. Conclusions These results reveal that the serotonergic system plays a pivotal role in pH homeostasis. Although obtained in vitro in neonatal mice, they suggest that drugs targeting the serotonergic system should be used with caution in infants, pregnant women and breastfeeding mothers. PMID:21048979

Voituron, Nicolas; Shvarev, Yuri; Menuet, Clément; Bevengut, Michelle; Fasano, Caroline; Vigneault, Erika; Mestikawy, Salah El; Hilaire, Gérard

2010-01-01

301

Severe valproic acid intoxication: case study on the unbound fraction and the applicability of extracorporeal elimination.  

PubMed

Among anticonvulsants, valproic acid (VPA) is cited as the most frequent cause of unintentional and intentional intoxications. Symptoms of VPA intoxication are diverse and are related to VPA plasma concentration. Although total plasma concentrations of less than 450 mg/l produce limited toxicity, severe intoxications (>850 mg/l) can induce coma and are ultimately life threatening. A 32-year-old comatose woman was admitted to the ICU at our hospital; she suffered from hypotension, respiratory depression, hypoglycaemia, sinus bradycardia, hyperammonaemia, metabolic acidosis, and her core body temperature was 33.7 degrees C. The total VPA plasma concentration was 1244 mg/l with an increased unbound fraction of 85%. After we administered multiple doses of activated charcoal, she underwent continuous veno-venous haemofiltration to reduce the plasma VPA concentration. As the total concentration decreased, the unbound fraction also decreased. Within 20 h of admission, the patient made a full recovery. In cases of VPA intoxication, protein-binding saturation and drug characteristics render extracorporeal elimination, an effective technique for eliminating the unbound drug. Its application should be considered, depending on clinical symptoms, VPA concentration (>300 mg/l), albumin concentration and ammonia concentration (>400 micromol/l). The application of this technique should be weighed against its risks. This case illustrates the clinical significance of applying continuous veno-venous haemofiltration in VPA intoxication because of protein-binding saturation, and suggests when extracorporeal elimination should be considered. PMID:19424075

van den Broek, Marcel P H; Sikma, Maaike A; Ververs, Tessa F; Meulenbelt, Jan

2009-12-01

302

Platelet activating factor receptor antagonist improves survival and attenuates eicosanoid release in severe endotoxemia.  

PubMed Central

Exogenous platelet activating factor (PAF) causes hypotension, plasma extravasation, metabolic acidosis, and death. These effects are similar to those of endotoxin as well as the eicosanoids. A specific PAF receptor antagonist, BN52021, was used to determine its effects on the hemodynamic events, the eicosanoid production, and on survival in severe rat endotoxemia. Endotoxin alone significantly produced hypotension, prostaglandins (TxB2, PGE2) release, and death. In contrast pretreatment with BN52021, a specific PAF receptor antagonist, significantly altered the hypotension, significantly attenuated the eicosanoid release, and improved the survival rate (p less than 0.01). These findings suggest that PAF receptor activation is an early event in endotoxemia. Eicosanoid release in endotoxemia could be related to PAF synthesis and PAF receptor activation. These findings support the hypothesis that there may be an intimate relationship between PAF and the eicosanoids and that in endotoxemia some of the effects of PAF may be mediated via the cyclo-oxygenase pathway. PMID:2178565

Fletcher, J R; DiSimone, A G; Earnest, M A

1990-01-01

303

Renal acidosis  

Microsoft Academic Search

Renal acidification. The renal acidification process regulates acid-base balance by regulating the concentration of plasma bicarbonate [1]. In normal man the renal acidification process operates to maintain plasma bicarbonate at physiologic concentrations. By way of accomplishing this, the acidification process a) reclaims all filtered bicarbonate and b) excretes an amount of acid equal to the amount of nonvolatile acid produced

R Curtis Morris; Anthony Sebastian; Elisabeth McSherry

1972-01-01

304

Effects of direct-fed microbial supplementation on ruminal acidosis, digestibility, and bacterial protein synthesis in continuous culture  

Microsoft Academic Search

A study was conducted to determine whether a bacterial direct-fed microbial (DFM) alone or with yeast could be used to minimize the risk of ruminal acidosis and to improve utilization of a feedlot cattle diet containing high concentrate. A dual effluent continuous culture (CC) system was used to investigate the effects of DFM on fermentation, digestibility, and microbial protein synthesis

W. Z Yang; K. A Beauchemin; D. D Vedres; G. R Ghorbani; D Colombatto; D. P Morgavi

2004-01-01

305

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=35-45 mmHg), ventilated with 0.03%CO2+21%O2+balancedN2; (2) hypercapnic acidosis (HC, PaCO2=60-70 mmHg), 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

306

Acidosis, lactate, electrolytes, muscle enzymes, and other factors in the blood of Sus scrofa following repeated TASER ® exposures  

Microsoft Academic Search

Repeated exposure to electro-muscular incapacitating devices could result in repetitive, sustained muscle contraction, with little or no muscle recovery period. Therefore, rhabdomyolysis and other physiological responses, including acidosis, hyperkalaemia, and altered levels of muscle enzymes in the blood, would be likely to occur. Experiments were performed to investigate effects of repeated exposures of TASER® International's Advanced TASER® X26 on muscle

James R. Jauchem; Clifford J. Sherry; David A. Fines; Michael C. Cook

2006-01-01

307

Deficiency of dihydrolipoyl dehydrogenase (a component of the pyruvate and alpha-ketoglutarate dehydrogenase complexes): a cause of congenital chronic lactic acidosis in infancy.  

PubMed

A male child died at 7 months of age with progressive neurologic deterioration and persistent metabolic acidosis. Investigations during life showed this child to have elevated blood pyruvate, lactate, and alpha-ketoglutarate as well as elevation of branched chain amino acids and occasional hypoglycemia. Cofactor therapy using either thiamine-HCl (2 g/kg/24 hr) or thiamine tetrahydrofurfuryl disulfide had no measurable effect on the clinical or biochemical status of the patient. Tissue taken postmortem showed normal levels of key gluconeogenic enzymes but a deficiency in the activity of pyruvate dehydrogenase in all tissues tested (liver, brain, kidney, skeletal muscle, and heart). Examination of the individual activities of pyruvate dehydrogenase complex showed pyruvate decarboxylase (E1) to be normal in liver and other tissues. Dihydrolipoyl dehydrogenase (E3), on the other hand, was deficient in all tissues tested. alpha-Ketoglutarate dehydrogenase complex, which depends of E3 for its total activity, was also deficient in all tissues tested. The absence of this enzyme id discussed in relation to the clinical and biochemical status of the patient. PMID:413089

Robinson, B H; Taylor, J; Sherwood, W G

1977-12-01

308

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

309

Magnetic resonance spectroscopy reveals an impaired brain metabolic profile in mice resistant to cerebral malaria infected with Plasmodium berghei ANKA.  

PubMed

Malaria is a major cause of morbidity and mortality with an annual death toll exceeding one million. Severe malaria is a complex multisystem disorder, including one or more of the following complications: cerebral malaria, anemia, acidosis, jaundice, respiratory distress, renal insufficiency, coagulation anomalies, and hyperparasitemia. Using a combined in vivo/in vitro metabolic-based approach, we investigated the putative pathogenic effects of Plasmodium berghei ANKA on brain, in a mouse strain developing malaria but resistant to cerebral malaria. The purpose was to determine whether the infection could cause a brain dysfunction distinct from the classic cerebral syndrome. Mice resistant to cerebral malaria were infected with P. berghei ANKA and explored during both the symptomless and the severe stage of the disease by using in vivo brain magnetic resonance imaging and spectroscopy. The infected mice did not present the lesional and metabolic hallmarks of cerebral malaria. However, brain dysfunction caused by anemia, parasite burden, and hepatic damage was evidenced. We report an increase in cerebral blood flow, a process allowing temporary maintenance of oxygen supply to brain despite anemia. Besides, we document metabolic anomalies affecting choline-derived compounds, myo-inositol, glutamine, glycine, and alanine. The choline decrease appears related to parasite proliferation. Glutamine, myo-inositol, glycine, and alanine variations together indicate a hepatic encephalopathy, a finding in agreement with the liver damage detected in mice, which is also a feature of the human disease. These results reveal the vulnerability of brain to malaria infection at the severe stage of the disease even in the absence of cerebral malaria. PMID:17369263

Penet, Marie-France; Kober, Frank; Confort-Gouny, Sylviane; Le Fur, Yann; Dalmasso, Christiane; Coltel, Nicolas; Liprandi, Agnès; Gulian, Jean-Marc; Grau, Georges E; Cozzone, Patrick J; Viola, Angèle

2007-05-11

310

Metabolic neuropathies  

MedlinePLUS

Neuropathy - metabolic ... can be caused by many different things. Metabolic neuropathy may be caused by: A problem with the ... one of the most common causes of metabolic neuropathies. People who are at the highest risk of ...

311

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury.  

PubMed

Hypercapnic acidosis may attenuate ventilator-induced lung oxidative stress injury and alveolar cell apoptosis, but the underlying mechanisms are poorly understood. We examined the effects of hypercapnic acidosis on the role of apoptosis signal-regulating kinase 1 (ASK1), which activates the c-Jun N-terminal kinase (JNK) and p38 cascade in both apoptosis and oxidative reactions, in high-pressure ventilation stimulated rat lungs. Rats were ventilated with a peak inspiratory pressure (PIP) of 30 cmH2O for 4 h and randomly given FiCO2 to achieve normocapnia (PaCO2 at 35-45 mm Hg) or hypercapnia (PaCO2 at 80-100 mm Hg); normally ventilated rats with PIP of 15 cmH2O were used as controls. Lung injury was quantified by gas exchange, microvascular leaks, histology, levels of inflammatory cytokines, and pulmonary oxidative reactions. Apoptosis through the ASK1-JNK/p38 mitogen-activated protein kinase (MAPK) cascade in type II alveolar epithelial cells (AECIIs) were evaluated by examination of caspase-3 activation. The results showed that injurious ventilation caused significant lung injury, including deteriorative oxygenation, changes of histology, and the release of inflammatory cytokines. In addition, the high-pressure mechanical stretch also induced apoptosis and caspase-3 activation in the AECIIs. Hypercapnia attenuated these responses, suppressing the ASK1 signal pathways with its downstream kinase phosphorylation of p38 MAPK and JNK, and caspase-3 activation. Thus, hypercapnia can attenuate cell apoptosis and oxidative stress damage in rat lungs during injurious ventilation, at least in part, due to the suppression of the ASK1-JNK/p38 MAPK pathways. PMID:24126891

Yang, Wan-Chao; Song, Chun-Yu; Wang, Nan; Zhang, Li-Li; Yue, Zi-Yong; Cui, Xiao-Guang; Zhou, Hua-Cheng

2013-12-01

312

The effects of acidosis and bicarbonate on action potential repolarization in canine cardiac Purkinje fibers  

PubMed Central

Studies were performed on canine cardiac Purkinje fibers to evaluate the effects of acidosis and bicarbonate (HCO3) on action potential repolarization. Extracellular pH (pHe) was reduced from 7.4 to 6.8 by increasing carbon dioxide (CO2) concentration from 4 to 15% in a HCO3- buffered solution or by NaOH titration in a Hepes-buffered solution. Both types of acidosis produced a slowing of the rate of terminal repolarization (i.e., period of repolarization starting at about -60 mV and ending at the maximum diastolic potential) with an attendant increase in action potential duration of 10--20 ms. This was accompanied by a reduction in the maximum diastolic potential of 2--8 mV. In contrast, if the same pH change was made by keeping CO2 concentration constant and lowering extracellular HCO3 from 23.7 to 6.0 mM, in addition to the slowing of terminal repolarization, the plateau was markedly prolonged resulting in an additional 50- to 80-ms increase in action potential duration. If pHe was held constant at 7.4 and HCO3 reduced from 23.7 mM to 0 (Hepes-buffered solution), the changes in repolarization were nearly identical to those seen in 6.0 mM HCO3 except that terminal repolarization was unchanged. This response was unaltered by doubling the concentration of Hepes. Reducing HCO3 to 12.0 mM produced changes in repolarization of about one-half the magnitude of those in 6.0 mM HCO3. These findings suggest that in Purkinje fibers, HCO3 either acts as a current that slows repolarization or modulates the ionic currents responsible for repolarization. PMID:438770

1979-01-01

313

Prevalence and consequences of subacute ruminal acidosis in German dairy herds  

PubMed Central

Background The prevalence and the clinical consequences of subacute ruminal acidosis (SARA) in dairy cows are still poorly understood. In order to evaluate the prevalence of SARA, 26 German dairy farms were included in a field study. In each herd, between 11 and 14 lactating dairy cows were examined for their ruminal pH using rumenocentesis. Milk production data and farm management characteristics were recorded. Each farm was scored for lameness prevalence among lactating animals, and body condition score was recorded three times four to five weeks apart in all animals examined. Farms were grouped on basis of ruminal pH and compared for lameness, body condition, milk production parameters and style of management. Animals were grouped on basis of their measured ruminal pH and compared accordingly for milk production parameters and body condition score. Results Of 315 cows examined, 63 individuals (20%) exhibited a ruminal pH of???5.5 at time of rumenocentesis. Of 26 farms examined, eleven farms had three or more of their cows experiencing a ruminal pH of???5.5 and were classified as likely experiencing subacute ruminal acidosis. These farms tended to be bigger than the others and offered less lying space to the lactating cows. There was no clear tendency regarding lameness. Among individual cows, animals with a low ruminal pH of???5.5 were found to be in significantly poorer body condition than animals with higher pH values (p?

2013-01-01

314

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

315

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

316

Fuzzy-Evolutionary Synergism in an Intelligent Medical Diagnosis System  

E-print Network

distinguished into metabolic acidosis, metabolic alkalosis, respiratory acidosis, respiratory alkalosis for patients' life. There are two main acid-base balance disturbances, acidosis and alkalosis, further

317

Localization and hormonal control of serine dehydratase during metabolic acidosis differ markedly from those of phosphoenolpyruvate carboxykinase in rat kidney  

Microsoft Academic Search

Serine dehydratase (SDH) is abundant in the rat liver but scarce in the kidney. When administrated with dexamethasone, the renal SDH activity was augmented 20-fold, whereas the hepatic SDH activity was affected little. In situ hybridization and immunohistochemistry revealed that SDH was localized to the proximal straight tubule of the nephron. To address the role of this hormone, rats were

Tohru Masuda; Hirofumi Ogawa; Takako Matsushima; Seiichi Kawamata; Masakiyo Sasahara; Kazunari Kuroda; Yasuhiro Suzuki; Yoshimi Takata; Mitsuaki Yamazaki; Fusao Takusagawa; Henry C. Pitot

2003-01-01

318

Contribution of Malate and Amino Acid Metabolism to Cytoplasmic pH Regulation in Hypoxic Maize Root Tips Studied Using Nuclear Magnetic Resonance Spectroscopy 1  

PubMed Central

31P-, 13C-, and 15N-nuclear magnetic resonance spectroscopy were used to determine the roles of malate, succinate, Ala, Asp, Glu, Gln, and ?-aminobutyrate (GABA) in the energy metabolism and regulation of cytoplasmic pH in hypoxic maize (Zea mays L.) root tips. Nitrogen status was manipulated by perfusing root tips with ammonium sulfate prior to hypoxia; this pretreatment led to enhanced synthesis of Ala early in hypoxia, and of GABA at later times. We show that: (a) the ability to regulate cytoplasmic pH during hypoxia is not significantly affected by enhanced Ala synthesis. (b) Independent of nitrogen status, decarboxylation of Glu to GABA is greatest after several hours of hypoxia, as metabolism collapses. (c) Early in hypoxia, cytoplasmic malate is in part decarboxylated to pyruvate (leading to Ala, lactate, and ethanol), and in part converted to succinate. It appears that activation of malic enzyme serves to limit cytoplasmic acidosis early in hypoxia. (d) Ala synthesis in hypoxic root tips under these conditions is due to transfer of nitrogen ultimately derived from Asp and Gln, present in oxygenated tissue. We describe the relative contributions of glycolysis and malate decarboxylation in providing Ala carbons. (e) Succinate accumulation during hypoxia can be attributed to metabolism of Asp and malate; this flux to succinate is energetically negligible. There is no detectable net flux from Glc to succinate during hypoxia. The significance of the above metabolic reactions relative to ethanol and lactate production, and to flooding tolerance, is discussed. The regulation of the patterns of metabolism during hypoxia is considered with respect to cytoplasmic pH and redox state. PMID:16668665

Roberts, Justin K. M.; Hooks, Mark A.; Miaullis, Aaron P.; Edwards, Shaune; Webster, Cecelia

1992-01-01

319

An under-recognized complication of treatment of acute severe asthma.  

PubMed

A 39-year-old man presented to the emergency department (ED) in severe respiratory distress. He had a prior diagnosis of brittle asthma and had been admitted on several occasions but never previously ventilated. Therapy given in the first 3 hours of arrival included nebulized salbutamol (5 mg, x5), ipratropium bromide (0.5 mg), intravenous hydrocortisone (200 mg), and magnesium sulfate (2 g). His arterial blood gases continued to deteriorate. He was then given an intravenous bolus of salbutamol (250 microg) and heliox via facemask. His worsening status necessitated invasive ventilation. His hypercapnia and resultant respiratory acidosis improved rapidly, but there was a concurrent accumulation of lactic acid resulting in acidemia. This patient had lactic acidosis as a direct effect of administration of salbutamol. The development of hazardous salbutamol-induced toxicity in acute severe asthma is discussed. PMID:18410827

Creagh-Brown, Ben C; Ball, Jonathan

2008-05-01

320

Energy substrate metabolism in pyruvate dehydrogenase complex deficiency.  

PubMed

Pyruvate dehydrogenase (PDH) deficiency is an inherited disorder of carbohydrate metabolism, resulting in lactic acidosis and neurological dysfunction. In order to provide energy for the brain, a ketogenic diet has been tried. Both the disorder and the ketogenic therapy may influence energy production. The aim of the study was to assess hepatic glucose production, lipolysis and resting energy expenditure (REE) in an infant, given a ketogenic diet due to neonatal onset of the disease. Lipolysis and glucose production were determined for two consecutive time periods by constant-rate infusions of [1,1,2,3,3-²H?]-glycerol and [6,6-²H²]-glucose. The boy had been fasting for 2.5 h at the start of the sampling periods. REE was estimated by indirect calorimetry. Rates of glucose production and lipolysis were increased compared with those of term neonates. REE corresponded to 60% of normal values. Respiratory quotient (RQ) was increased, indicating a predominance of glucose oxidation. Blood lactate was within the normal range. Several mechanisms may underlie the increased rates of glucose production and lipolysis. A ketogenic diet will result in a low insulin secretion and reduced peripheral and hepatic insulin sensitivity, leading to increased production of glucose and decreased peripheral glucose uptake. Surprisingly, RQ was high, indicating active glucose oxidation, which may reflect a residual enzyme activity, sufficient during rest. Considering this, a strict ketogenic diet might not be the optimal choice for patients with PDH deficiency. We propose an individualised diet for this group of patients aiming at the highest glucose intake that each patient will tolerate without elevated lactate levels. PMID:24914713

Stenlid, Maria Halldin; Ahlsson, Fredrik; Forslund, Anders; von Döbeln, Ulrika; Gustafsson, Jan

2014-11-01

321

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

322

An in vitro rat diaphragmatic fatigue model induced by combined hypoxic and hypercapnic acidosis and the effect of salmeterol  

Microsoft Academic Search

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

Xu Xuanli; Zhou Jianying; Yang Qiuhuo; Fang Liben; Xie Qiangmin; Shen Yueliang

2006-01-01

323

Novel compound heterozygous SLC4A1 mutations in Thai patients with autosomal recessive distal renal tubular acidosis  

Microsoft Academic Search

Background: Mutations in the SLC4A1 gene have been found to cause either autosomal dominant (AD) or autosomal recessive (AR) distal renal tubular acidosis (dRTA). The SLC4A1 mutations causing AD dRTA were reported in white patients, whereas those associated with AR dRTA were often found in Southeast Asia. Here, the authors report additional novel SLC4A1 mutations in 3 patients with AR

Suchai Sritippayawan; Achra Sumboonnanonda; Somkiat Vasuvattakul; Thitima Keskanokwong; Nunghathai Sawasdee; Atchara Paemanee; Peti Thuwajit; Prapon Wilairat; Sumalee Nimmannit; Prida Malasit; Pa-thai Yenchitsomanus

2004-01-01

324

Acidosis, lactate, electrolytes, muscle enzymes, and other factors in the blood of Sus scrofa following repeated TASER1 exposures  

Microsoft Academic Search

Repeated exposure to electro-muscular incapacitating devices could result in repetitive, sustained muscle contraction, with little or no muscle recovery period. Therefore, rhabdomyolysis and other physiological responses, including acidosis, hyperkalaemia, and altered levels of muscle enzymes in the blood, would be likely to occur. Experiments were performed to investigate effects of repeated exposures of TASER1 International's Advanced TASER1 X26 on muscle

James R. Jauchem; Clifford J. Sherry; David A. Fines; Michael C. Cook

2006-01-01

325

N-glycosylation of Acid-sensing Ion Channel 1a Regulates its Trafficking and Acidosis-induced Spine Remodeling  

PubMed Central

Acid-sensing ion channel-1a (ASIC1a) is a potential therapeutic target for multiple neurological diseases. We studied here ASIC1a glycosylation and trafficking, two poorly understood processes that are pivotal in determining the functional outcome of an ion channel. We found that most ASIC1a in the mouse brain was fully glycosylated. Inhibiting glycosylation with Tunicamycin reduced ASIC1a surface trafficking, dendritic targeting and acid-activated current density. N-glycosylation of the two glycosylation sites, Asn393 and Asn366, has differential effects on ASIC1a biogenesis. Maturation of Asn393 increased ASIC1a surface and dendritic trafficking, pH sensitivity and current density. In contrast, glycosylation of Asn366 was dispensable for ASIC1a function and may be a rate-limiting step in ASIC1a biogenesis. Lastly, we revealed that acidosis reduced the density and length of dendritic spines in a time- and ASIC1a-dependent manner. ASIC1a N366Q, which showed increased glycosylation and dendritic targeting, potentiated acidosis-induced spine loss. Conversely, ASIC1a N393Q, which had diminished dendritic targeting and inhibited ASIC1a current dominant-negatively, had the opposite effect. These data tie N-glycosylation of ASIC1a with its trafficking. More importantly, revealing a site-specific effect of acidosis on dendritic spines suggests an important role of these processes in regulating synaptic plasticity and long-term consequences in diseases that generate acidosis. PMID:22442073

Jing, Lan; Chu, Xiang-Ping; Jiang, Yu-Qing; Collier, Daniel M; Wang, Bin; Jiang, Qian; Snyder, Peter M; Zha, Xiang-ming

2012-01-01

326

Evaluating tumor metastatic potential by imaging intratumoral acidosis via pH-activatable near-infrared fluorescent probe.  

PubMed

Metastasis accounts for the vast majority of cancer deaths. To minimize metastasis-associated mortality, it is crucially important to evaluate the metastatic potential (M.P.), that is, defined as a tendency of a primary tumor to colonize a distant organ. Dysregulated pH in solid tumors, especially the acidification of extracellular pH (pHe ) promotes dormant metastasis by driving protease-mediated digestion, disrupting cell-matrix interaction and increasing migration of cancer cells. Therefore, imaging intratumoral acidosis creates a unique opportunity to evaluate the M.P. In this work, a novel pH activatable probe was developed, in which two near-infrared (NIR) fluorophores were conjugated via a flexible and acid liable linkage. While the fluorescence of this probe is quenched due to intramolecular dimeric aggregate under neutral environment, the cleavage of pH liable linkage with the concomitant disruption of aggregates in acidic tumor microenvironment results in a remarkable fluorescence enhancement. This probe not only visualized the primary tumors with high target to background (T/B) signal ratio in vivo, but also revealed the correlation between the M.P. and acidosis distribution pattern in tumor. While the acidosis locate dispersedly at tumor periphery in highly metastatic tumor, it distribute more widely in lowly metastatic tumor and the acidification degree increases substantially from the margin to core areas. This pH activatable NIR fluorescent probe holds the potential to evaluate the M.P., monitor the therapeutic response and predict the prognosis by delineating acidosis in tumors. PMID:25155456

Wang, Lu; Fan, Zhichao; Zhang, Jingye; Changyi, Yinzhi; Huang, Cuiyun; Gu, Yanjuan; Xu, Ziyao; Tang, Zhijia; Lu, Weiyue; Wei, Xunbin; Li, Cong

2015-02-15

327

Carnosine inhibits carbonic anhydrase IX-mediated extracellular acidosis and suppresses growth of HeLa tumor xenografts  

PubMed Central

Background Carbonic anhydrase IX (CA IX) is a transmembrane enzyme that is present in many types of solid tumors. Expression of CA IX is driven predominantly by the hypoxia-inducible factor (HIF) pathway and helps to maintain intracellular pH homeostasis under hypoxic conditions, resulting in acidification of the tumor microenvironment. Carnosine (?-alanyl-L-histidine) is an anti-tumorigenic agent that inhibits the proliferation of cancer cells. In this study, we investigated the role of CA IX in carnosine-mediated antitumor activity and whether the underlying mechanism involves transcriptional and translational modulation of HIF-1? and CA IX and/or altered CA IX function. Methods The effect of carnosine was studied using two-dimensional cell monolayers of several cell lines with endogenous CA IX expression as well as Madin Darby canine kidney transfectants, three-dimensional HeLa spheroids, and an in vivo model of HeLa xenografts in nude mice. mRNA and protein expression and protein localization were analyzed by real-time PCR, western blot analysis, and immunofluorescence staining, respectively. Cell viability was measured by a flow cytometric assay. Expression of HIF-1? and CA IX in tumors was assessed by immunohistochemical staining. Real-time measurement of pH was performed using a sensor dish reader. Binding of CA IX to specific antibodies and metabolon partners was investigated by competitive ELISA and proximity ligation assays, respectively. Results Carnosine increased the expression levels of HIF-1? and HIF targets and increased the extracellular pH, suggesting an inhibitory effect on CA IX-mediated acidosis. Moreover, carnosine significantly inhibited the growth of three-dimensional spheroids and tumor xenografts compared with untreated controls. Competitive ELISA showed that carnosine disrupted binding between CA IX and antibodies specific for its catalytic domain. This finding was supported by reduced formation of the functional metabolon of CA IX and anion exchanger 2 in the presence of carnosine. Conclusions Our results indicate that interaction of carnosine with CA IX leads to conformational changes of CA IX and impaired formation of its metabolon, which in turn disrupts CA IX function. These findings suggest that carnosine could be a promising anticancer drug through its ability to attenuate the activity of CA IX. PMID:24886661

2014-01-01

328

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

329

Acute metabolic response in myocardial infarction  

PubMed Central

Acute myocardial infarction is viewed as a severe trauma causing a generalized metabolic reaction; an acute emotional stress with further metabolic implications; and a localized wound in which there is an acute increase in carbohydrate metabolism, followed by protein synthetic reactions leading to scar formation. The metabolic response is vital to the patient's successful adaptation to his myocardial infarction. PMID:4324636

Opie, L. H.

1971-01-01

330

Evolution of Metabolism  

NASA Astrophysics Data System (ADS)

This chapter is devoted to the discussion of the evolution of metabolism, with a particular focus towards redox metabolism and the utilization of redox energy by life. We will deal with various aspects of metabolism that involve direct interaction with, and the extraction of energy from, the environment (catabolic metabolism) and will talk briefly of the reactions that affect mineral formation and dissolution. However, we will de-emphasize the aspects related to the formation of complex molecules and organisms. To some, it will be refreshingly brief; to others, somewhat superficial. This is unavoidable, as our knowledge of the details of the evolution of metabolism is at best slim. However, by piecing together aspects of the properties and history of the Earth and coupling these with what we know of today's metabolism, it is possible to at least frame several different hypotheses that, with time, should be possible to test and modify so that the next writing of this chapter might contain some intellectual entrees and not just the appetizers. Any discussion of metabolic evolution must occur in concert with a consideration of the Earth - the understanding of the forces that drove the co-evolution of life and Earth can be achieved only by considering them together. This theme will pervade this chapter, and any real understanding of the evolution of metabolism must be inexorably coupled to, and consistent with, the geological record of the Earth.The first aspect of evolution concerns the metabolic participants as we know them now (i.e., a definition of metabolic diversity), and the second concerns the sequence of events that have led to this remarkable metabolic diversity. The first part is fairly straightforward: a discussion of the domains of life, and the metabolic achievements that are expressed in the various domains, and relating metabolism to biogeochemical processes whenever possible. The second part is much more problematic. While it is possible to make up nearly any story regarding the evolution of metabolism (and nearly all have been attempted!), the starting point of life is not known (great debates still rage as to the nature and origin of the first living systems), and it is not a trivial matter to specify the sequence and timing of metabolic innovations. As will be discussed below, genetic and genomic data have revealed that genetic exchange between organisms has been so pervasive that it has essentially uncoupled the evolution of taxonomic groups from the evolution of metabolic processes, thus, obscuring the evolutionary trail with blurred signals. Given these challenges, it may be prudent at this time to admit what we do not know, and lay out the challenges for the coming years.

Nealson, K. H.; Rye, R.

2003-12-01

331

The effects of active dried and killed dried yeast on subacute ruminal acidosis, ruminal fermentation, and nutrient digestibility in beef heifers.  

PubMed

The study addressed the importance of yeast (Saccharomyces cerevisiae) viability for reducing the incidence of subacute ruminal acidosis (SARA) and improving total tract nutrient digestibility in beef heifers. Six ruminally cannulated beef heifers (680 ± 50 kg BW) were used in a replicated 3 × 3 Latin square design and were fed a diet consisting of 40% barley silage, 10% chopped grass hay, and 50% barley grain-based concentrate (DM basis). Treatments were 1) no yeast (Control), 2) active dried yeast (ADY; 4 g providing 10(10) cfu/g; AB Vista, Marlborough, UK), and 3) killed dried yeast (KDY; 4 g autoclaved ADY). The treatments were directly dosed via the ruminal cannula daily at the time of feeding. The periods consisted of 2 wk of adaptation (d 1 to 14) and 7 d of measurements (d 15 to 21). Ruminal pH was continuously measured (d 15 to 21) using an indwelling system. Ruminal contents were sampled on d 15 and 17 at 0, 3, 6, 9, and 12 h after feeding. Total tract nutrient digestibility was measured using an external marker (YbCl3) from d 15 to 19. No treatment difference was observed for DMI (P = 0.86). Yeast supplementation (ADY and KDY) tended to increase total tract digestibility of starch (P = 0.07) whereas no effects were observed on digestibility of other nutrients. Both ADY and KDY elevated minimum (P < 0.01) and mean ruminal pH (P = 0.02) whereas no effects were observed on maximum pH (P = 0.12). Irrespective of its viability, yeast supplementation was effective in reducing time that ruminal pH was below 5.8 (P < 0.01) and 5.6 (P < 0.01). No treatment differences were observed for the ruminal VFA profile and lactate concentration. No treatment differences were observed on the relative population size of Streptococcus bovis, Fibrobacter succinogenes, and Megasphaera elsdenii (P > 0.10); however, the proportion of Ruminococcus flavefaciens in solid fraction of digesta was greater with KDY (P = 0.05). The study demonstrates the positive effects of yeast, irrespective of its viability, in reducing the severity of SARA. However, further studies are required to evaluate the importance of yeast viability for other dietary conditions, particularly when the risk of acidosis is high. PMID:24398831

Vyas, D; Uwizeye, A; Mohammed, R; Yang, W Z; Walker, N D; Beauchemin, K A

2014-02-01

332

Exercise hypoxemia and the effects of increased inspiratory oxygen concentration in severe chronic obstructive pulmonary disease.  

PubMed

Exercise-associated oxygen desaturation in severe chronic obstructive pulmonary disease (COPD) remains a topic of unknown prognostic and clinical relevance and of unknown therapeutic importance. Furthermore, exercise limitation in these patients is due to multifactorial interaction of respiratory, cardiac, circulatory and 'peripheral' mechanisms. For the evaluation of the role of the oxygen-dependent mechanisms of exercise limitation we studied 14 stable patients with severe COPD (FEV1 32% pred., FEV1/VC 41%, thoracic gas volume of 180% pred.) and mean Pa O2 64 mm Hg by a stage 1 cycle exercise test during breathing room air (FiO2 0.21) and hyperoxic (FiO2 0.35) air. The measurements were performed by an open system using a low dead space valve (55 ml) measuring real-time breath by breath oxygen consumption (VO2) via a differential oxygen sensor, expired carbon dioxide (VCO2), ventilation (VE), oxygen pulse and oxygen saturation in both conditions. With FiO2 0.21 the mean exercise limitation was restricted to 37 (+/- 14) W and the VO2 to 11.7 (+/- 2.4) ml/kg/min with peak oxygen desaturation of 86.4 (+/- 3.2). With FiO2 0.35 the patients achieved a significant increase of workload to 55 (+/- 12.4) W and of VO2 to 14.9 (+/- 2.9) ml/kg/min. Despite the complete abolition of exercise desaturation by FIO2 0.35 the mean peak ventilation of 261/min (+/- 5.1) vs. 27 l/min (+/- 4.1) remained unaltered and therefore the restriction of the ventilatory pump limited the exercise ability. The effects of FiO2 0.35 occurred in these patients at submaximum exercise and may be related to reduction of ventilatory cost of energy and delayed onset of metabolic acidosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7800956

Mitlehner, W; Kerb, W

1994-01-01

333

Epigenetics and metabolism.  

PubMed

The molecular signatures of epigenetic regulation and chromatin architectures are fundamental to genetically determined biological processes. Covalent and post-translational chemical modification of the chromatin template can sensitize the genome to changing environmental conditions to establish diverse functional states. Recent interest and research focus surrounds the direct connections between metabolism and chromatin dynamics, which now represents an important conceptual challenge to explain many aspects of metabolic dysfunction. Several components of the epigenetic machinery require intermediates of cellular metabolism for enzymatic function. Furthermore, changes to intracellular metabolism can alter the expression of specific histone methyltransferases and acetyltransferases conferring widespread variations in epigenetic modification patterns. Specific epigenetic influences of dietary glucose and lipid consumption, as well as undernutrition, are observed across numerous organs and pathways associated with metabolism. Studies have started to define the chromatin-dependent mechanisms underlying persistent and pathophysiological changes induced by altered metabolism. Importantly, numerous recent studies demonstrate that gene regulation underlying phenotypic determinants of adult metabolic health is influenced by maternal and early postnatal diet. These emerging concepts open new perspectives to combat the rising global epidemic of metabolic disorders. PMID:25677519

Keating, Samuel T; El-Osta, Assam

2015-02-13

334

The Metabolic Syndrome  

Microsoft Academic Search

\\u000a The National Cholesterol Education Program’s Adult Treatment Panel III (ATP III) report [1] added the metabolic syndrome,\\u000a a multidimensional risk factor for cardiovascular disease (CVD), as a coequal partner of elevated low-density lipoprotein\\u000a (LDL) cholesterol for risk-reduction therapies. Interest in the metabolic syndrome has increased greatly since the publication\\u000a of the ATP III report. There are several aspects to the

Scott M. Grundy

335

Metabolic Syndrome  

MedlinePLUS

... you know? One in five Americans has the metabolic syndrome. WhO is At risk fOr the metAbOlic syndrOme? The syndrome runs in families and is more ... High blood pressure Most people who have the metabolic syndrome feel healthy and may not have any signs ...

336

Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNA(Leu(UUR)) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.  

PubMed Central

Cytoplasts from two unrelated patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) harboring an A----G transition at nucleotide position 3243 in the tRNA(Leu(UUR)) gene of the mitochondrial genome were fused with human cells lacking endogenous mitochondrial DNA (mtDNA) (rho 0 cells). Selected cybrid lines, containing less than 15 or greater than or equal to 95% mutated genomes, were examined for differences in genetic, biochemical, and morphological characteristics. Cybrids containing greater than or equal to 95% mutant mtDNA, but not those containing normal mtDNA, exhibited decreases in the rates of synthesis and in the steady-state levels of the mitochondrial translation products. In addition, NADH dehydrogenase subunit 1 (ND 1) exhibited a slightly altered mobility on polyacrylamide gel electrophoresis. The mutation also correlated with a severe respiratory chain deficiency. A small but consistent increase in the steady-state levels of an RNA transcript corresponding to 16S rRNA + tRNA(Leu(UUR)) + ND 1 genes was detected. However, there was no evidence of major errors in processing of the heavy-strand-encoded transcripts or of altered steady-state levels or ratios of mitochondrial rRNAs or mRNAs. These results provide evidence for a direct relationship between the tRNALeu(UUR) mutation and the pathogenesis of this mitochondrial disease. Images PMID:1732728

King, M P; Koga, Y; Davidson, M; Schon, E A

1992-01-01

337

Severe Weather  

ERIC Educational Resources Information Center

Educating the public about safety issues related to severe weather is part of the National Oceanic and Atmospheric Administration's (NOAA) mission. This article deals with a poster entitled, "Severe Weather," that has been created by NOAA to help educate the public about hazardous weather conditions. The four types of severe weather highlighted in…

Forde, Evan B.

2004-01-01

338

Severe Weather  

ERIC Educational Resources Information Center

Educating the public about safety issues related to severe weather is part of the National Oceanic and Atmospheric Administration's (NOAA) mission. This month's insert, Severe Weather, has been created by NOAA to help educate the public about hazardous weather conditions. The four types of severe weather highlighted in this poster are hurricanes,…

Forde, Evan B.

2004-01-01

339

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

340

Extracellular acidosis activates ASIC-like channels in freshly isolated cerebral artery smooth muscle cells  

PubMed Central

Recent studies suggest that certain acid-sensing ion channels (ASIC) are expressed in vascular smooth muscle cells (VSMCs) and are required for VSMC functions. However, electrophysiological evidence of ASIC channels in VSMCs is lacking. The purpose of this study was to test the hypothesis that isolated cerebral artery VSMCs express ASIC-like channels. To address this hypothesis, we used RT-PCR, Western blotting, immunolabeling, and conventional whole cell patch-clamp technique. We found extracellular H+-induced inward currents in 46% of cells tested (n = 58 of 126 VSMCs, pH 6.5–5.0). The percentage of responsive cells and the current amplitude increased as the external H+ concentration increased (pH6.0, n = 28/65 VSMCs responsive, mean current density = 8.1 ± 1.2 pA/pF). Extracellular acidosis (pH6.0) shifted the whole cell reversal potential toward the Nernst potential of Na+ (n = 6) and substitution of extracellular Na+ by N-methyl-d-glucamine abolished the inward current (n = 6), indicating that Na+ is a major charge carrier. The broad-spectrum ASIC blocker amiloride (20 ?M) inhibited proton-induced currents to 16.5 ± 8.7% of control (n = 6, pH6.0). Psalmotoxin 1 (PcTx1), an ASIC1a inhibitor and ASIC1b activator, had mixed effects: PcTx1 either 1) abolished H+-induced currents (11% of VSMCs, 5/45), 2) enhanced or promoted activation of H+-induced currents (76%, 34/45), or 3) failed to promote H+ activation in nonresponsive VSMCs (13%, 6/45). These findings suggest that freshly dissociated cerebral artery VSMCs express ASIC-like channels, which are predominantly formed by ASIC1b. PMID:20181928

Chung, Wen-Shuo; Farley, Jerry M.; Swenson, Alyssa; Barnard, John M.; Hamilton, Gina; Chiposi, Rumbidzayi

2010-01-01

341

Non-specific inhibition of ischemia- and acidosis-induced intracellular calcium elevations and membrane currents by ?-phenyl-N-tert-butylnitrone, butylated hydroxytoluene and trolox.  

PubMed

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

342

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

343

Targeting Cancer Metabolism  

PubMed Central

The understanding that oncogenes can have profound effects on cellular metabolism and the discovery of mutations and alterations in several metabolism-related enzymes (IDH1, IDH2, SDH, FH, PKM2) has renewed interest in cancer metabolism and renewed hope of taking therapeutic advantage of cancer metabolism. Otto Warburg observed that aerobic glycolysis was a characteristic of cancer cells. More than 50-years later, we understand that aerobic glycolysis and uptake of glutamine and glycine allow cancer cells to produce energy (ATP) and the nucleotides, amino acids and lipids required for proliferation. Expression of the MYC oncogene drives the increase in cellular biomass facilitating proliferation. PKM2 expression in cancer cells stimulates aerobic glycolysis. Amongst intermediary metabolism enzyme, mutations in succinate dehydrogenase (SDH) occur in gastointestinal stromal tumors and result in a pseudohypoxic metabolic milieu. Fumarate hydratase (FH) mutations lead to a characteristic renal cell carcinoma. Isocitrate dehydrogenase (IDH1/2) mutations have been found in leukemias, gliomas, prostate cancer, colon cancer, thyroid cancer and sarcomas. These recently recognized oncogenic metabolic lesions may be selective targets for new anticancer therapeutics. PMID:23071355

Teicher, Beverly A.; Linehan, W. Marston; Helman, Lee J.

2012-01-01

344

Metabolic cutis laxa syndromes.  

PubMed

Cutis laxa is a rare skin disorder characterized by wrinkled, redundant, inelastic and sagging skin due to defective synthesis of elastic fibers and other proteins of the extracellular matrix. Wrinkled, inelastic skin occurs in many cases as an acquired condition. Syndromic forms of cutis laxa, however, are caused by diverse genetic defects, mostly coding for structural extracellular matrix proteins. Surprisingly a number of metabolic disorders have been also found to be associated with inherited cutis laxa. Menkes disease was the first metabolic disease reported with old-looking, wrinkled skin. Cutis laxa has recently been found in patients with abnormal glycosylation. The discovery of the COG7 defect in patients with wrinkled, inelastic skin was the first genetic link with the Congenital Disorders of Glycosylation (CDG). Since then several inborn errors of metabolism with cutis laxa have been described with variable severity. These include P5CS, ATP6V0A2-CDG and PYCR1 defects. In spite of the evolving number of cutis laxa-related diseases a large part of the cases remain genetically unsolved. In metabolic cutis laxa syndromes the clinical and laboratory features might partially overlap, however there are some distinct, discriminative features. In this review on metabolic diseases causing cutis laxa we offer a practical approach for the differential diagnosis of metabolic cutis laxa syndromes. PMID:21431621

Mohamed, Miski; Kouwenberg, Dorus; Gardeitchik, Thatjana; Kornak, Uwe; Wevers, Ron A; Morava, Eva

2011-08-01

345

Severe Asthma  

PubMed Central

The National Heart, Lung, and Blood Institute Severe Asthma Research Program (SARP) has characterized over the past 10 years 1,644 patients with asthma, including 583 individuals with severe asthma. SARP collaboration has led to a rapid recruitment of subjects and efficient sharing of samples among participating sites to conduct independent mechanistic investigations of severe asthma. Enrolled SARP subjects underwent detailed clinical, physiologic, genomic, and radiological evaluations. In addition, SARP investigators developed safe procedures for bronchoscopy in participants with asthma, including those with severe disease. SARP studies revealed that severe asthma is a heterogeneous disease with varying molecular, biochemical, and cellular inflammatory features and unique structure–function abnormalities. Priorities for future studies include recruitment of a larger number of subjects with severe asthma, including children, to allow further characterization of anatomic, physiologic, biochemical, and genetic factors related to severe disease in a longitudinal assessment to identify factors that modulate the natural history of severe asthma and provide mechanistic rationale for management strategies. PMID:22095547

Erzurum, Serpil C.; Bleecker, Eugene R.; Calhoun, William J.; Castro, Mario; Comhair, Suzy A. A.; Chung, Kian Fan; Curran-Everett, Douglas; Dweik, Raed A.; Fain, Sean B.; Fitzpatrick, Anne M.; Gaston, Benjamin M.; Israel, Elliot; Hastie, Annette; Hoffman, Eric A.; Holguin, Fernando; Levy, Bruce D.; Meyers, Deborah A.; Moore, Wendy C.; Peters, Stephen P.; Sorkness, Ronald L.; Teague, W. Gerald; Wenzel, Sally E.; Busse, William W.

2012-01-01

346

Involvement of the cystic fibrosis transmembrane conductance regulator in the acidosis-induced efflux of ATP from rat skeletal muscle  

PubMed Central

The present study was performed to investigate the effect of acidosis on the efflux of ATP from skeletal muscle. Infusion of lactic acid to the perfused hindlimb muscles of anaesthetised rats produced dose-dependent decreases in pH and increases in the interstitial ATP of extensor digitorum longus (EDL) muscle: 10 mm lactic acid reduced the venous pH from 7.22 ± 0.04 to 6.97 ± 0.02 and increased interstitial ATP from 38 ± 8 to 67 ± 11 nm. The increase in interstitial ATP was well-correlated with the decrease in pH (r2 = 0.93; P < 0.05). Blockade of cellular uptake of lactic acid using ?-cyano-hydroxycinnamic acid abolished the lactic acid-induced ATP release, whilst infusion of sodium lactate failed to depress pH or increase interstitial ATP, suggesting that intracellular pH depression, rather than lactate, stimulated the ATP efflux. Incubation of cultured skeletal myoblasts with 10 mm lactic acid significantly increased the accumulation of ATP in the bathing medium from 0.46 ± 0.06 to 0.76 ± 0.08 ?m, confirming the skeletal muscle cells as the source of the released ATP. Acidosis-induced ATP efflux from the perfused muscle was abolished by CFTRinh-172, a specific inhibitor of the cystic fibrosis transmembrane conductance regulator (CFTR), or glibenclamide, an inhibitor of both KATP channels and CFTR, but it was not affected by atractyloside, an inhibitor of the mitochondrial ATP transporter. Silencing of the CFTR gene using an siRNA abolished the acidosis-induced increase in ATP release from cultured myoblasts. CFTR expression on skeletal muscle cells was confirmed using immunostaining in the intact muscle and Western blotting in the cultured cells. These data suggest that depression of the intracellular pH of skeletal muscle cells stimulates ATP efflux, and that CFTR plays an important role in the release mechanism. PMID:20819945

Tu, Jie; Le, Gengyun; Ballard, Heather J

2010-01-01

347

Uncovering transcriptional regulation of metabolism by using metabolic network topology  

PubMed Central

Cellular response to genetic and environmental perturbations is often reflected and/or mediated through changes in the metabolism, because the latter plays a key role in providing Gibbs free energy and precursors for biosynthesis. Such metabolic changes are often exerted through transcriptional changes induced by complex regulatory mechanisms coordinating the activity of different metabolic pathways. It is difficult to map such global transcriptional responses by using traditional methods, because many genes in the metabolic network have relatively small changes at their transcription level. We therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns in the metabolic network that follow a common transcriptional response. Thus, the algorithm enables identification of so-called reporter metabolites (metabolites around which the most significant transcriptional changes occur) and a set of connected genes with significant and coordinated response to genetic or environmental perturbations. We find that cells respond to perturbations by changing the expression pattern of several genes involved in the specific part(s) of the metabolism in which a perturbation is introduced. These changes then are propagated through the metabolic network because of the highly connected nature of metabolism. PMID:15710883

Patil, Kiran Raosaheb; Nielsen, Jens

2005-01-01

348

Crossover effects of acidosis on the recovery of neuronal function following glucose-oxygen deprivation in rat hippocampal slices  

Microsoft Academic Search

The present study was designed to determine whether acidosis modifies the effect of simulated ischemia on neuronal function.\\u000a Hippocampal evoked potentials were recorded in vitro from the CA1 region after stimulation of the Schaffer collaterals and\\u000a the change in the evoked potentials was analyzed in response to glucose-oxygen deprivation under variable acid-base conditions\\u000a ranging from pH 7.4 to pH 4.5.

Yuji Morimoto; Takeyasu Yamamura; Osamu Kemmotsu

1994-01-01

349

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

350

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

351

Distal Renal Tubular Acidosis, Hypokalemic Paralysis, Nephrocalcinosis, Primary Hypothyroidism, Growth Retardation, Osteomalacia and Osteoporosis Leading to Pathological Fracture: A Case Report  

PubMed Central

Renal tubular acidosis (RTA) is a constellation of syndromes arising from different derangements of tubular acid transport. Recent advances in the biology of urinary acidification have allowed us to discern various molecular mechanisms responsible for these syndromes. RTA often presents as renal stone disease with nephrocalcinosis, ricket/osteomalacia and growth retardation in children with ultimate short stature in adulthood. The case reported here has features of distal renal tubular acidosis (dRTA), hypokalemic paralysis, primary hypothyroidism, growth retardation, osteomalacia and osteopenia leading to stress fracture. All these features presenting in a single case (as in our case) is a rare occurrence, so far other cases of distal renal tubular acidosis (dRTA) have been reported. PMID:22043434

Basak, Ramen C.; Sharkawi, Khairy Mostafa; Rahman, Mohammad Mizanur; Swar, Mayada Mohammad

2011-01-01

352

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

353

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

354

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

355

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

356

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

357

[Myocardial metabolism abnormalities during ischemia and reperfusion].  

PubMed

Normal cardiac function requires adequate oxygen and substrate (fatty acids, glucose lactate) supply for the energetic requirements of the myocardium. Ischaemia induces abnormalities in the production and excretion of products of myocardial metabolism. During ischaemia, the equilibrium which exists during aerobic respiration between the beta-oxidation of fatty acids and carbohydrates and which generates ATP is disturbed. Pyruvate oxidation and beta-oxidation of fatty acids decrease, and ATP is mainly produced by anaerobic glycolysis. Under these conditions, intracellular glycogen is mobilised, the lactate and protons accumulate in the cardiomyocyte. If reperfusion occurs before irreversible lesions are produced, then functional recovery is possible and is mostly dependant on the type of energetic substrate available. Circulating fatty acids are produced in large quantities after ischaemia: their beta-oxidation, which is then the principal source of ATP, may contribute to the aggravation of contractile dysfunction during reperfusion and accentuate or generate arrhythmias. The decoupling between acceleration of anaerobic glycolysis and the defect of pyruvirate oxidation (inhibition of pyruvirate dehydrogenase) participate in a significant fashion to the accumulation of protons. Rapid correction of intracellular acidosis during reperfusion by activation of the Na+/H+ exchanger, coupled with the accumulation of intracellular Na+ induces a deleterious calcium overload via the Na+/Ca++ exchanger. These different aspects of intracellular metabolism constitute pharmacological targets for the development of future cardio-protective agents. PMID:11227723

Argaud, L; Ovize, M

2000-01-01

358

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

359

Metabolic Myopathies  

MedlinePLUS

... that affect the body’s muscles. [Metabolism refers to chemical reactions that provide energy and nutrients, or substances necessary ... made in cells from sugars or fats by chemical reactions called pathways. Normally, most ATP is produced in ...

360

Familial occurrence of intestinal obstruction in children with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)  

Microsoft Academic Search

The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is an uncommon neuromuscular disorder caused by mitochondrial dysfunctions that result in headaches, seizures, and progressive dementia. The authors describe a clinical case study of gastrointestinal manifestations in a pedigree with MELAS, in which all three children, ages 11, 8, and 6, demonstrated acute onset of intestinal obstruction. They

Takashi Shimotake; Taizo Furukawa; Katsuhiro Inoue; Naomi Iwai; Yoshihiro Takeuchi

1998-01-01

361

The SR Protein SC35 Is Responsible for Aberrant Splicing of the E1  Pyruvate Dehydrogenase mRNA in a Case of Mental Retardation with Lactic Acidosis  

Microsoft Academic Search

Received 6 December 2004\\/Returned for modification 4 January 2005\\/Accepted 14 January 2005 Pyruvate dehydrogenase (PDH) complex deficiency is a major cause of lactic acidosis and Leigh's encepha- lomyelopathies in infancy and childhood, resulting in early death in the majority of patients. Most of the molecular defects have been localized in the coding regions of the E1 PDH gene. Recently, we

Mathieu Gabut; Manuele Mine ´; C. Marsac; M. Brivet; J. Tazi; J. Soret

2005-01-01

362

Nutrition: Subclinical rumen acidosis as a cause of reduced appetite in newly calved dairy cows in Denmark: Results of a poll among Danish dairy practitioners  

Microsoft Academic Search

A questionnaire survey was conducted among Danish dairy practitioners to investigate reduced appetite and its relation to subclinical rumen acidosis in post partum dairy cows. The 115 practitioners who responded provided service to 325,300 cows representing 46% of the national herd. Results are presented and discussed in relation to the practitioners beliefs regarding occurrence and value of the diagnostic methods

J. M. D. Enemark; R. J. Jørgensen

2001-01-01

363

Metabolic Engineering  

Microsoft Academic Search

Metabolic engineering is a powerful methodology aimed at intelligently designing new biological\\u000a pathways, systems, and ultimately phenotypes through the use of recombinant DNA technology. Built\\u000a largely on the theoretical and computational analysis of chemical systems, the field has evolved to\\u000a incorporate a growing number of genome scale experimental tools. This combination of rigorous\\u000a analysis and quantitative molecular biology methods has endowed metabolic

R. Michael Raab; Keith Tyo; Gregory Stephanopoulos

364

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

365

Active dry Saccharomyces cerevisiae can alleviate the effect of subacute ruminal acidosis in lactating dairy cows.  

PubMed

The objective of the study was to determine the effect of active dry Saccharomyces cerevisiae (ADSC) supplementation on dry matter intake, milk yield, milk components, ruminal pH, and microbial community during a dietary regimen that leads to subacute ruminal acidosis (SARA). Sixteen multiparous, rumen-cannulated lactating Holstein cows were randomly assigned to 1 of 2 dietary treatments that included ADSC (Biomate; AB Vista, Marlborough, UK; 8 × 10(10) cfu/head per day) or control. During wk 1 to 6, all cows received a high-forage (HF) diet (77:23, forage:concentrate). Cows were then abruptly switched during wk 7 to a high-grain (HG) diet (49:51, forage:concentrate) and remained on the HG until the end of wk 10. Feed intake and milk yields were recorded daily. Ruminal pH was recorded continuously using an indwelling system for 1 to 2 d per week during the pre-experimental phase, and wk 6, 7, and 10. Ruminal digesta samples were collected at the end of the experiment and analyzed for relative change in microbial communities using real-time quantitative PCR. Cows were considered to have SARA if the duration below pH 5.6 was ?300 min/d. Ruminal pH during wk 6 (HF plateau) was not different across treatments (15 ± 46 min/d at pH <5.6). The dietary regimen successfully induced SARA during wk 7 (transition from HF to HG diet), and ruminal pH (551 ± 46 min/d at pH <5.6) was not different across treatments. However, cows receiving ADSC had an improved ruminal pH (122 ± 57 vs. 321 ± 53 min/d at pH <5.6) during wk 10 (HG plateau) compared with control. Additionally, cows receiving ADSC had a better dry matter intake (23.3 ± 0.66 vs. 21.6 ± 0.61 kg/d) and 4% fat-corrected milk yield (29.6 ± 1.2 vs. 26.5 ± 1.2 kg/d) than control cows during the HG phase (wk 8 to 10). During HG feeding, cows receiving ADSC had greater total volatile fatty acid and propionate concentrations (175 ± 7.5 vs. 154 ± 7.5 and 117 ± 6.1 vs. 94 ± 5.7 mM for ADSC and control, respectively) and lower acetate:propionate ratio (0.26 ± 0.5 vs. 0.36 ± 0.05 for ADSC and control, respectively). Microbial analyses conducted on samples collected during wk 10 showed that cows supplemented with S. cerevisiae had a 9-fold, 2-fold, 6-fold, 1.3-fold, and 8-fold increase in S. cerevisiae, Fibrobacter succinogenes, Anaerovibrio lipolytica, Ruminococcus albus, and anaerobic fungi, respectively, which suggested an increase in cellulolytic microbes within the rumen. Cows supplemented with ADSC had 2.2-fold reduction in Prevotella albensis, which is a gram-negative bacterium predominant during SARA. Prevotella spp. are suggested to be an important source of lipopolysaccharide responsible for inflammation within the rumen. Cows supplemented with ADSC had a 2.3-fold increase in Streptococcus bovis and a 12-fold reduction in Megasphaera elsdenii. The reduction in M. elsdenii may reflect lower concentration of lactic acid within the rumen for ADSC cows. In conclusion, ADSC supplementation to dairy cows was demonstrated to alleviate the condition of SARA caused by abrupt dietary changes from HF to HG, and can potentially improve rumen function, as indicated by greater numbers of cellulolytic microorganisms within the rumen. PMID:25282426

AlZahal, O; Dionissopoulos, L; Laarman, A H; Walker, N; McBride, B W

2014-12-01

366

Effect of steam-flaked sorghum grain density on performance, mill production rate, and subacute acidosis in feedlot steers.  

PubMed

Two trials were conducted to determine the effects of steam-flaked sorghum grain bulk density on animal performance, cost of production, and propensity to induce ruminal acidosis in feedlot steers. In Trial 1, 336 yearling steers (343 kg; SEM = .346) were fed diets for 125 d that contained sorghum grain (82.5%, DM basis) flaked to .283 (L), .322 (M), or .361 (H) kg/L (i.e., 22, 25, and 28 lb/bu). Steers fed L consumed 3.2% less DM than those fed H (linear, P < .05), resulting in 6.9% lower ADG (linear, P = .02) and 3.6% lower gain efficiency (linear, P < .15). Sorghum grain flaked to M and L had 16 and 46% greater starch gelatinization than H (measured using differential scanning calorimetry; linear, P = .002). Dressing percentage increased linearly (P < .05) with increasing flake density, but no other carcass measurements were affected by treatment. Increasing flake density increased mill production rate linearly (P < .01), resulting in the lowest energy usage per unit of flaked grain for the H treatment. Trial 2 was an acidosis challenge study that incorporated six ruminally cannulated steers (422 kg; SEM = .129) into a replicated 3 x 3 Latin square experiment. Reducing flake density resulted in linear reductions in ruminal pH following intake challenge at 3, 33, and 36 h after the d-12 challenge (P < .05). There was a linear increase in the area between the pH vs time curve and a line at pH 5.5 (P < .01) and 5.0 (P = .09) with decreasing flake density (28.0, 25.2, and 18.2 pH-hours below 5.5 and 9.6, 7.3, and 3.9 pH-hours below 5.0 for L, M, and H, respectively). Cattle consuming L also tended to have higher VFA concentrations (mM) at 36 h after challenge (P = .12). There was no significant treatment effect on ruminal lactate. Flaking sorghum grain to .283 and .322 kg/L resulted in reduced intake and poorer animal performance compared with .361 kg/L (58.7% starch gelatinization), higher susceptibility to subacute acidosis, and higher costs of production. PMID:9374296

Reinhardt, C D; Brandt, R T; Behnke, K C; Freeman, A S; Eck, T P

1997-11-01

367

Pearson disease in an infant presenting with severe hypoplastic anemia, normal pancreatic function, and progressive liver failure.  

PubMed

Pearson disease is a rare, usually fatal, mitochondrial disorder affecting primarily the bone marrow and the exocrine pancreas. We report a previously healthy 10-week-old girl who presented with profound macrocytic anemia followed by pancytopenia, synthetic liver dysfunction with liver steatosis, and metabolic acidosis with high lactate levels. She had no pancreatic involvement. Multiple cytoplasmic vacuoles in myelocytes and monocytes were seen upon microscopic evaluation of the bone marrow. Genetic analysis of the mitochondrial genome revealed a 5 kbp deletion, thus establishing the diagnosis of Pearson disease. PMID:23588341

Shapira, Adi; Konopnicki, Muriel; Hammad-Saied, Mohammed; Shabad, Evelyn

2014-07-01

368

Severe Weather  

NSDL National Science Digital Library

Educating the public about safety issues related to severe weather is part of the National Oceanic and Atmospheric Administration's (NOAA) mission. The National Weather Service (NWS)--which is part of NOAA and its parent agency, the Department of Commerce--is charged with the critical responsibility of observing and reporting the weather and with issuing forecasts and warnings of weather and floods in the interest of national safety and economy. Through a massive network of weather-monitoring and reporting stations around the globe, including land, sea, air, and space-borne instruments, NWS scientists constantly assimilate all of the reliable weather data available. Much of this data are then used in numerical computer models of the atmosphere that help to accurately describe and interpret current conditions and produce the best possible forecasts of future weather.

Evan B. Forde

2004-04-01

369

Ca++-sensitizing mutations in troponin, P(i), and 2-deoxyATP alter the depressive effect of acidosis on regulated thin-filament velocity.  

PubMed

Repeated, intense contractile activity compromises the ability of skeletal muscle to generate force and velocity, resulting in fatigue. The decrease in velocity is thought to be due, in part, to the intracellular build-up of acidosis inhibiting the function of the contractile proteins myosin and troponin; however, the underlying molecular basis of this process remains poorly understood. We sought to gain novel insight into the decrease in velocity by determining whether the depressive effect of acidosis could be altered by 1) introducing Ca(++)-sensitizing mutations into troponin (Tn) or 2) by agents that directly affect myosin function, including inorganic phosphate (Pi) and 2-deoxy-ATP (dATP) in an in vitro motility assay. Acidosis reduced regulated thin-filament velocity (VRTF) at both maximal and submaximal Ca(++) levels in a pH-dependent manner. A truncated construct of the inhibitory subunit of Tn (TnI) and a Ca(++)-sensitizing mutation in the Ca(++)-binding subunit of Tn (TnC) increased VRTF at submaximal Ca(++) under acidic conditions but had no effect on VRTF at maximal Ca(++) levels. In contrast, both Pi and replacement of ATP with dATP reversed much of the acidosis-induced depression of VRTF at saturating Ca(++). Interestingly, despite producing similar magnitude increases in VRTF, the combined effects of Pi and dATP were additive, suggesting different underlying mechanisms of action. These findings suggest that acidosis depresses velocity by slowing the detachment rate from actin but also by possibly slowing the attachment rate. PMID:24651988

Longyear, Thomas J; Turner, Matthew A; Davis, Jonathan P; Lopez, Joseph; Biesiadecki, Brandon; Debold, Edward P

2014-05-01

370

Metabolic evaluation in first-time renal stone formers in North India: a single center study.  

PubMed

The risk of stone recurrence in first-time stone formers (FTSF) varies from 26% to 53%. There is no consensus regarding metabolic evaluation in these individuals. We evaluated the metabolic abnormalities in first-time renal stone forming patients in North India. Thirty-nine patients, (29 males and 10 females with mean age 39.3 ± 12.9 years) who presented with nephrolithiasis for the first time were evaluated. We evaluated the calcium homeostasis [serum corrected total calcium, phosphorous, creatinine, alkaline phosphatase, albumin, parathormone (iPTH), 25-hydroxy cholecalciferol (25(OH)D 3 ), 1-25 di-hydroxy cholecalciferol (1,25(OH) 2 D 3 )] and performed the calcium load test also. Two 24-h urine collections were taken for citrate, oxalate, calcium and uric acid. Ammonium chloride loading test for diagnosis of distal renal tubular acidosis was performed in all patients. For each of the diagnostic categories, descriptive statistics were computed for all biochemical variables. A two-tailed P-value <0.05 was regarded as significant. Metabolic abnormalities were detected in 92.3% of the patients (n = 39) studied. Of them, almost 60% had two or more metabolic abnormalities. The most common metabolic abnormality was hypo-citraturia (82%), followed by hyper-oxaluria (56%) and hyper-calciuria (41%). Five percent of the patients had incomplete renal tubular acidosis, signifying the importance of the ammonium chloride loading test in patients with renal stones. None of the study patients were detected to have primary hyperparathyroidism. In three patients, the etiology could not be detected. Our findings suggest that an underlying disorder is present in majority of first-time renal stone formers. Intervention with appropriate treatment can prevent recurrences. Hence, comprehensive metabolic evaluation is recommended in all FTSF. PMID:23816746

Joshi, Akhil; Gupta, Sushil Kumar; Srivastava, Aneesh

2013-07-01

371

Reduced Tc-99m DMSA uptake in a patient with renal tubular acidosis: effect of acid-base imbalance.  

PubMed

Tc-99m dimercaptosuccinic acid (DMSA) is used as a renal cortical imaging agent to detect parenchymal abnormalities especially in children. Kidney uptake of DMSA provides an index for evaluation of a functional tubular mass, which depends on the renal blood flow and proximal tubular cell membrane transport function. We here report a boy with renal tubular acidosis, which has noticeably reduced uptake on his Tc-99m DMSA scintigraphy, despite a totally normal Tc-99m MAG-3 study. The case reported here clearly demonstrates a situation in which renal uptake of DMSA may be dissociated from a functional renal mass and the importance of acid-base balance which alters Tc-99m DMSA uptake. PMID:12508844

Caglar, Meltem; Topalo?lu, Rezan

2002-11-01

372

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

373

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

PubMed Central

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 monitored by thermodilution and ultrasonic flow probes, respectively. A tonometer in the ileum was used for measurement of mucosal pH. Onset of endotoxin challenge was followed by bosentan administration (to eight pigs) two hours later. ?Results—Endotoxin infusion reduced cardiac index and systemic oxygen delivery; bosentan restored these parameters. The reduced mean arterial blood pressure and renal blood flow remained unaffected by bosentan. The profound reduction in gut oxygen delivery in response to endotoxin was completely abolished by bosentan. Bosentan significantly improved the notably deteriorated intestinal mucosal pH and mucosal-arterial PCO2 gap. The mucosal-portal vein PCO2 gap, used to monitor the mucosa in relation to the gut as a whole (including the spleen and pancreas), was also greatly increased by endotoxaemia and significantly reversed by bosentan. ?Conclusion—Bosentan completely restored the profound endotoxin induced reductions in systemic and gut oxygen delivery with a concomitant reversal of intestinal mucosal acidosis. Results suggest that endothelin is involved in the pronounced perfusion disturbances seen in the gut in endotoxic shock. Bosentan may prove useful in reducing gut ischaemia in septic shock. ?? Keywords: splanchnic circulation; septic shock; tonometry; pHi; PCO2 gap; endothelin-1 PMID:9659167

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

1998-01-01

374

Oral versus intravenous rehydration therapy in severe gastroenteritis.  

PubMed Central

A controlled, randomised trial comparing the results of oral rehydration therapy with those of intravenous fluid treatment in 470 children with severe gastroenteritis was undertaken. The oral rehydration therapy was divided into two phases--a rehydration phase that used high sodium isotonic fluid at 40 ml/kg per hour and a maintenance phase using low sodium isotonic fluid (sodium 40, potassium 30, bicarbonate 25, chloride 45, and dextrose 130 mmol/l). The results indicate that oral rehydration treatment, used according to this protocol, is successful in treating severe diarrhoea and dehydration, and has considerable advantages over intravenous fluid therapy in reducing complications associated with the treatment of hypernatraemia, in promoting rapid correction of hypokalaemia and acidosis, in decreasing the duration of diarrhoea, and in promoting a greater weight gain at hospital discharge. PMID:3901934

Sharifi, J; Ghavami, F; Nowrouzi, Z; Fouladvand, B; Malek, M; Rezaeian, M; Emami, M

1985-01-01

375

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

376

Modeling of Zymomonas mobilis central metabolism for novel metabolic engineering strategies.  

PubMed

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

377

Metabolic Disorders  

MedlinePLUS

... your body's fuel. Your body can use this fuel right away, or it can store the energy in your body tissues, such as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body disrupt this process. When this ...

378

Metabolic Syndrome  

MedlinePLUS

... syndrome can lead to. Back Continue Changing Your Course In the case of metabolic syndrome, making a couple of lifestyle changes is the best way to keep yourself on a track to good health. Here are the top ones: Drop excess pounds. If you're overweight, ...

379

Metabolic Syndrome  

MedlinePLUS

... your waist Not all doctors agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is a hormone your body produces to help you turn sugar from food into energy for your body. If you are insulin resistant, ...

380

[Metabolic syndrome and skin diseases].  

PubMed

Skin symptoms were originally described only in some components of the metabolic syndrome (e.g. in obesity, diabetes and polycystic ovary syndrome). In the last years several skin symptoms were described also in the metabolic syndrome. These relations were mostly described between psoriasis and metabolic syndrome, where perhaps common pathogenetic mechanisms are present. Even more important is the fact that physical activity, weight loss and diet treatment can have a common positive effect on both diseases. Also some drugs can influence both diseases together. PMID:18724527

Svacina, S

2008-01-01

381

Glucagon-like peptide-1(7-36) amide (GLP-1) enhances insulin-stimulated glucose metabolism in 3T3-L1 adipocytes: one of several potential extrapancreatic sites of GLP-1 action.  

PubMed

We investigated the effects of glucagon-like peptide-1(7-36) amide, GLP-1, on glucose metabolism in 3T3-L1 adipocytes and we used polymerase chain reaction to search for the presence of GLP-1 receptors in various rat tissues. GLP-1 at 1 nM significantly increased insulin-mediated 2-deoxyglucose uptake by 40% while having no effect on basal uptake. In conjunction with the elevated uptake, the insulin-dependent incorporation of 14C-glucose into fatty acids was also increased. Moreover, neither glycogen synthesis nor insulin binding to its receptor were affected by GLP-1. In addition to the presence of GLP-1 receptor in pancreas we found messenger RNA for this receptor in brain, kidney, heart, fat, skeletal muscle, liver, and intestine. This study indicates that GLP-1, in addition to its well known effect of stimulating insulin secretion, may improve insulin responsiveness by promoting fatty acid synthesis in adipose cells and possibly modulating insulin signaling in other insulin sensitive tissues. PMID:7956929

Egan, J M; Montrose-Rafizadeh, C; Wang, Y; Bernier, M; Roth, J

1994-11-01

382

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

383

Metabolic comorbidities and psoriasis.  

PubMed

Psoriasis is a chronic inflammatory, immune-mediated skin disease, which affects 2%-3% of the population worldwide. Chronic plaque psoriasis is frequently associated with metabolic diseases including diabetes, obesity, dyslipidemia, metabolic syndrome and nonalcoholic fatty liver disease. Although the causal relationship between metabolic comorbidities and psoriasis has not yet been completely proven, it appears that shared genetic links, common environmental factors and/or common inflammatory pathways may underlie the development of psoriasis and comorbidities. The presence of comorbidities has important implications in the global approach to patients with psoriasis. Traditional systemic anti-psoriatic agents could negatively affect cardio-metabolic comorbidities, and may have important interactions with drugs commonly used by psoriatic patients. In contrast, the recent findings that the risk of myocardial infarction is reduced in patients with rheumatoid arthritis who respond to anti-TNF-? therapy compared to non-responders, supports the hypothesis that the anti-inflammatory effect of TNF-? blockers might reduce the cardiovascular risk potentially also in psoriasis patients. Finally, patients with moderate to severe psoriasis should be treated promptly and effectively, and should be encouraged to drastically correct their modifiable cardiovascular risk factors, in particular obesity and smoking habit. PMID:21251450

Gisondi, Paolo; Ferrazzi, Anna; Girolomoni, Giampiero

2010-01-01

384

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

385

Effect of feed delivery fluctuations and feeding time on ruminal acidosis, growth performance, and feeding behavior of feedlot cattle.  

PubMed

Research was conducted to determine whether fluctuations in the amount of feed delivered and timing of feeding affect ruminal pH and growth of feedlot cattle. In Exp. 1, the effects of constant (C) vs. fluctuating (F) daily feed delivery on ruminal pH were assessed in a crossover experiment (two 28-d periods) involving six mature, ruminally cannulated steers. The diet consisted of 86.8% barley grain, 4.9% supplement, and 8.3% barley silage (DM basis) and was offered ad libitum for 2 wk to estimate DMI by individual steers. Steers in group C were offered a constant amount of feed daily equal to their predetermined DMI, whereas steers in group F were offered 10% more or less than their predetermined DMI on a rotating 3-d schedule. Ruminal pH of each steer was measured continuously via an indwelling electrode placed in the rumen during the last 6 d of each period. Mean pH tended to be lower (0.10 units) for F than C (5.63 vs. 5.73; P = 0.15), and ruminal pH of steers in group F tended to remain below 5.8 (P = 0.03) or 5.5 (P = 0.14) for greater proportions of the day than steers in group C. Inconsistent delivery of feed lowered ruminal pH, suggesting increased risk of subclinical acidosis. In Exp. 2, a 2 x 2 factorial was used to study the effects of pattern (C vs. F) and feeding time (morning [0900] vs. evening [2100]) on the feeding behavior and performance of 234 (310 +/- 23 kg) Charolais x Hereford beef steers during backgrounding and finishing phases over 209 d. One pen per treatment was equipped with a radio frequency identification (GrowSafe Systems Ltd., Airdrie, Canada) system that monitored bunk attendance by each steer throughout the trial. Pattern of feed delivery did not affect (P = 0.16) DMI (7.36 kg/d), ADG (1.23 kg/d), G:F (0.17), or time spent at the bunk (141 min/d), nor were pattern of feed delivery x time of feeding interactions observed (P = 0.18). Late feeding increased (P < 0.05) daily DMI (7.48 vs. 7.26 kg), ADG (1.28 vs. 1.00 kg/d), and G:F (0.21 vs. 0.15). These studies indicate that the risk of subclinical acidosis was increased with fluctuating delivery of feed, but the greater risk of acidosis did not impair growth performance by feedlot cattle. Consequently, daily intake fluctuations of 10% DMI or less that do not alter overall intake by feedlot cattle are unlikely to have any negative consequences on growth performance. PMID:15542483

Schwartzkopf-Genswein, K S; Beauchemin, K A; McAllister, T A; Gibb, D J; Streeter, M; Kennedy, A D

2004-11-01

386

[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

387

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

Microsoft Academic Search

The objective of this study was to evaluate the ef- fect 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,

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

2009-01-01

388

Effects of Monensin on Ruminal Forage Degradability and Total Tract Diet Digestibility in Lactating Dairy Cows During Grain-Induced Subacute Ruminal Acidosis  

Microsoft Academic Search

The effects of monensin premix supplementation on ruminal pH characteristics and forage degradability, and total tract diet digestibility during grain-induced subacute ruminal acidosis (SARA) in lactating dairy cows receiving a total mixed ration were investigated. Six multiparous, rumen-fistulated Holstein cows were used in a 2-treatment, 2-period (5 wk per period) cross- over design. During wk 5 (d 29 to 35)

J. K. Osborne; T. Mutsvangwa; O. Alzahal; T. F. Duffield; R. Bagg; P. Dick; G. Vessie; B. W. McBride

2004-01-01

389

Giardia Metabolism  

Microsoft Academic Search

\\u000a This chapter describes key aspects of our basic knowledge of Giardia metabolism. It is well known that this organism has minimal biosynthetic capacity: it lacks de novo lipid, de novo purine,\\u000a and de novo pyrimidine syntheses (relying solely on salvage pathways). Giardia also lacks mitochondria and cytochrome-mediated oxidative phosphorylation and thus trophozoites use glycolysis (from glucose\\u000a only) and the arginine

Edward L. Jarroll; Harry van Keulen; Timothy A. Paget; Donald G. Lindmark

390

Grapefruit juice improves glycemic control but exacerbates metformin-induced lactic acidosis in non-diabetic rats.  

PubMed

Recent clinical studies have indicated that grapefruit juice (GFJ) improves insulin resistance and reduces weight gain in humans. The effect of GFJ on glucose tolerance and metformin-induced lactic acidosis in normal, non-diabetic in rats is hereby investigated. Three groups (A, B, C) of 20 male Wistar rats each, were treated with stepwise, escalated oral doses of 0, 1.0, 2.0, 3.0 (group A), and 3.0 ml/kg body weight (groups B and C) of GFJ. Group C rats additionally received 250 mg/kg body weight of metformin. All the animals were sacrificed after 14 days of treatment. Fasting blood glucose levels were significantly (P < 0.0001) lower in GFJ-treated test (2.9 +/- 0.4 mmol/L) compared with control (3.7 +/- 0.39 mmol/L) rats, but 1.5-hr plasma insulin levels were similar. GFJ alone or in combination with metformin, significantly (P < 0.05) lowered blood glucose levels compared with control animals. Blood lactic acid levels were similar in GFJ-treated test (2.81 +/- 1.4 mmol/L) and control (2.54 +/- 0.7 mmol/L) rats, respectively, but were significantly increased (P = 0.0079) in rats that were treated with either metformin alone (5.38 +/- 2.53 mmol/L) or in combination with GFJ (8.31 +/- 3.48 mmol/L). Metformin concentration in liver tissue was significantly higher (P < 0.05) in GFJ-treated (397 +/- 19 microg/g) than in control (280 +/- 15 microg/g) rats, respectively. Plasma metformin levels were comparable between the control (95 +/- 8.1 microg/ml) and GFJ-treated test (108 +/- 20 microg/ml) rats, respectively. Liver tissue metformin concentrations and plasma lactic acid levels showed significant correlation in both control (P = 0.0122; r(2) = 0.9080) and GFJ-treated test rats (P = 0.0005; r(2) = 0.9893). Although GFJ may be beneficial to diabetic patients, it may exacerbate lactic acidosis in diabetic patients taking metformin concurrently. PMID:20094639

Owira, P M O; Ojewole, J A O

2009-11-01

391

Targeting cellular metabolism to improve cancer therapeutics.  

PubMed

The metabolic properties of cancer cells diverge significantly from those of normal cells. Energy production in cancer cells is abnormally dependent on aerobic glycolysis. In addition to the dependency on glycolysis, cancer cells have other atypical metabolic characteristics such as increased fatty acid synthesis and increased rates of glutamine metabolism. Emerging evidence shows that many features characteristic to cancer cells, such as dysregulated Warburg-like glucose metabolism, fatty acid synthesis and glutaminolysis are linked to therapeutic resistance in cancer treatment. Therefore, targeting cellular metabolism may improve the response to cancer therapeutics and the combination of chemotherapeutic drugs with cellular metabolism inhibitors may represent a promising strategy to overcome drug resistance in cancer therapy. Recently, several review articles have summarized the anticancer targets in the metabolic pathways and metabolic inhibitor-induced cell death pathways, however, the dysregulated metabolism in therapeutic resistance, which is a highly clinical relevant area in cancer metabolism research, has not been specifically addressed. From this unique angle, this review article will discuss the relationship between dysregulated cellular metabolism and cancer drug resistance and how targeting of metabolic enzymes, such as glucose transporters, hexokinase, pyruvate kinase M2, lactate dehydrogenase A, pyruvate dehydrogenase kinase, fatty acid synthase and glutaminase can enhance the efficacy of common therapeutic agents or overcome resistance to chemotherapy or radiotherapy. PMID:23470539

Zhao, Y; Butler, E B; Tan, M

2013-01-01

392

Flux-Balance Modeling of Plant Metabolism  

PubMed Central

Flux-balance modeling of plant metabolic networks provides an important complement to 13C-based metabolic flux analysis. Flux-balance modeling is a constraints-based approach in which steady-state fluxes in a metabolic network are predicted by using optimization algorithms within an experimentally bounded solution space. In the last 2?years several flux-balance models of plant metabolism have been published including genome-scale models of Arabidopsis metabolism. In this review we consider what has been learnt from these models. In addition, we consider the limitations of flux-balance modeling and identify the main challenges to generating improved and more detailed models of plant metabolism at tissue- and cell-specific scales. Finally we discuss the types of question that flux-balance modeling is well suited to address and its potential role in metabolic engineering and crop improvement. PMID:22645533

Sweetlove, Lee J.; Ratcliffe, R. George

2011-01-01

393

Alterations of Metabolic Genes and Metabolites in Cancer  

PubMed Central

Altered metabolic regulation has long been observed in human cancer and broadly used in the clinic for tumor detection. Two recent findings—the direct regulation of metabolic enzymes by frequently mutated cancer genes and frequent mutations of several metabolic enzymes themselves in cancer—have renewed interest in cancer metabolism. Supporting a causative role of altered metabolic enzymes in tumorigenesis, abnormal levels of several metabolites have been found to play a direct role in cancer development. The alteration of metabolic genes and metabolites offer not only new biomarkers for diagnosis and prognosis, but also potential new targets for cancer therapy. PMID:22306135

Oermann, Eric K.; Wu, Jing; Guan, Kun-Liang; Xiong, Yue

2012-01-01

394

Alterations of metabolic genes and metabolites in cancer.  

PubMed

Altered metabolic regulation has long been observed in human cancer and broadly used in the clinic for tumor detection. Two recent findings--the direct regulation of metabolic enzymes by frequently mutated cancer genes and frequent mutations of several metabolic enzymes themselves in cancer--have renewed interest in cancer metabolism. Supporting a causative role of altered metabolic enzymes in tumorigenesis, abnormal levels of several metabolites have been found to play a direct role in cancer development. The alteration of metabolic genes and metabolites offer not only new biomarkers for diagnosis and prognosis, but also potential new targets for cancer therapy. PMID:22306135

Oermann, Eric K; Wu, Jing; Guan, Kun-Liang; Xiong, Yue

2012-06-01

395

Metabolic control of cell death  

PubMed Central

Summary Beyond their contribution to basic metabolism, the major cellular organelles, in particular mitochondria, can determine whether cells respond to stress in an adaptive or suicidal manner. Thus, mitochondria can continuously adapt their shape to changing bioenergetic demands as they are subjected to quality control by autophagy, or they can undergo a lethal permeabilization process that initiates apoptosis. Along similar lines, multiple proteins involved in metabolic circuitries including oxidative phosphorylation and transport of metabolites across membranes may participate in the regulated or catastrophic dismantling of organelles. Many factors that were initially characterized as cell death regulators are now known to physically or functionally interact with metabolic enzymes. Thus, several metabolic cues regulate the propensity of cells to activate self-destructive programs, in part by acting on nutrient sensors. This suggests the existence of “metabolic checkpoints” that dictate cell fate in response to metabolic fluctuations. Here, we discuss recent insights into the intersection between metabolism and cell death regulation that have major implications for the comprehension and manipulation of unwarranted cell loss. PMID:25237106

Green, Douglas R.; Galluzzi, Lorenzo; Kroemer, Guido

2014-01-01

396

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

397

Heteroplasmic mitochondrial DNA mutation in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.  

PubMed

A 16-year-old female presented with clinical, morphologic and molecular features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Her early development was normal. Starting from the age of 14 years, she experienced recurrent episodes of headaches, with vomiting, seizures, transient right hemiparesis and decreased visual acuity. Computed tomographic brain scans revealed calcification in the bilateral basal ganglia. Biopsied specimens from her left biceps brachii and rectus femoris muscles revealed ragged-red fibers and strong succinate dehydrogenase-reactive blood vessels. Electron microscopy revealed paracrystalline inclusions in muscle mitochondria. Analysis of mitochondrial DNA (mtDNA) from blood, hair follicles and muscle specimens showed an A to G point mutation at nucleotide position 3,243 in the transfer RNA(Leu(UUR)). The proportion of mutant mtDNA in the patient's blood was 43%, in hair follicles 62% and in muscle 82%. The patient was followed up for 4 years and had progressive mental deterioration and died of an episode of status epilepticus. This patient and 5 other MELAS patients reported in Taiwan are compared. PMID:7613232

Chiang, L M; Jong, Y J; Huang, S C; Tsai, J L; Pang, C Y; Lee, H C; Wei, Y H

1995-01-01

398

Proximal renal tubular acidosis mediated by mutations in NBCe1-A: unraveling the transporter's structure-functional properties  

PubMed Central

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

399

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

400

Metabolic pancreatitis: Etiopathogenesis and management.  

PubMed

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

2013-09-01

401

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

402

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

403

Hypokalemic rhabdomyolysis: an unusual presentation of Sjogren's syndrome.  

PubMed

Hypokalaemic rhabdomyolysis represents a medical emergency requiring rapid diagnosis and appropriate aetiological treatment. Renal tubular acidosis is a common cause of hypokalemia which can be idiopathic or secondary to systemic disorders such as Sjogren's syndrome. It can remain asymptomatic or manifest with metabolic abnormalities including hypokalemia paralysis, hypocalcaemia and hyperchloremic metabolic acidosis. Rhabdomyolysis presenting with severe hypokalemia as the first manifestation of Sjogren's syndrome is rare. We report a case of a 59-year-old woman who presented to our department with severe weakness of all limbs. Laboratory examination demonstrated hypokalemic rhabdomyolysis caused by distal renal tubular acidosis. Investigations revealed Sjogren's syndrome as the underlying cause of the metabolic disorders. PMID:24165505

Cherif, Eya; Ben Hassine, Lamia; Kechaou, Ines; Khalfallah, Narjess

2013-01-01

404

Why Metabolic Syndrome Matters  

MedlinePLUS

Why Metabolic Syndrome Matters Updated:Jul 24,2014 Metabolic syndrome may be diagnosed when a patient has a cluster of ... Diabetes High Blood Pressure My Life Check Heart360® Metabolic Syndrome • Home • About Metabolic Syndrome • Why Metabolic Syndrome Matters • ...

405

Diagnosis, Clinical Presentation, and In-Hospital Mortality of Severe Malaria in HIV-Coinfected Children and Adults in Mozambique  

PubMed Central

Background.?Severe falciparum malaria with human immunodeficiency virus (HIV) coinfection is common in settings with a high prevalence of both diseases, but there is little information on whether HIV affects the clinical presentation and outcome of severe malaria. Methods.?HIV status was assessed prospectively in hospitalized parasitemic adults and children with severe malaria in Beira, Mozambique, as part of a clinical trial comparing parenteral artesunate versus quinine (ISRCTN50258054). Clinical signs, comorbidity, complications, and disease outcome were compared according to HIV status. Results.?HIV-1 seroprevalence was 11% (74/655) in children under 15 years and 72% (49/68) in adults with severe malaria. Children with HIV coinfection presented with more severe acidosis, anemia, and respiratory distress, and higher peripheral blood parasitemia and plasma Plasmodium falciparum histidine-rich protein-2 (PfHRP2). During hospitalization, deterioration in coma score, convulsions, respiratory distress, and pneumonia were more common in HIV-coinfected children, and mortality was 26% (19/74) versus 9% (53/581) in uninfected children (P < .001). In an age- and antimalarial treatment–adjusted logistic regression model, significant, independent predictors for death were renal impairment, acidosis, parasitemia, and plasma PfHRP2 concentration. Conclusions.?Severe malaria in HIV-coinfected patients presents with higher parasite burden, more complications, and comorbidity, and carries a higher case fatality rate. Early identification of HIV coinfection is important for the clinical management of severe malaria. PMID:22752514

Hendriksen, Ilse C. E.; Ferro, Josefo; Montoya, Pablo; Chhaganlal, Kajal D.; Seni, Amir; Gomes, Ermelinda; Silamut, Kamolrat; Lee, Sue J.; Lucas, Marcelino; Chotivanich, Kesinee; Fanello, Caterina I.; Day, Nicholas P. J.; White, Nicholas J.; von Seidlein, Lorenz; Dondorp, Arjen M.

2012-01-01

406

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 prof