These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

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

2

Benzonatate Toxicity in a Teenager Resulting in Coma, Seizures, and Severe Metabolic Acidosis  

PubMed Central

We report a benzonatate overdose in a teenager resulting in life-threatening toxicity to increase awareness of this overdose, and discuss recent pediatric warnings and labeling information provided by the US Food and Drug Administration (FDA). After an overdose of benzonatate, a 13-yr-old female presented to our emergency department with coma, seizures, hypotension, prolonged QT interval on electrocardiogram, and metabolic acidosis. Benzonatate is an antitussive medication with sodium channel-blocking properties and local anesthetic effects on the respiratory stretch receptors due to a tetracaine-like metabolite. Overdose is reported to cause coma, seizures, hypotension, tachycardia, ventricular dysrhythmias, and cardiac arrest. The FDA recently issued a Drug Safety Communication warning that accidental benzonatate ingestion in children younger than 10 years of age have increased risk of death and added the new information to the Warnings and Precautions section of benzonatate's label. PMID:23258970

Thimann, Daniel A.; Huang, Craig J.; Goto, Collin S.; Feng, Sing-Yi

2012-01-01

3

Metabolic acidosis and the progression of chronic kidney disease  

PubMed Central

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

2014-01-01

4

Severe metabolic acidosis secondary to coadministration of creatine and metformin, a case report.  

PubMed

It is known from studies in young athletes that creatine supplements have beneficial effects on muscular functional capacity, so it is being widely used as a performance-enhancing substance in both professional and amateur sports men and women. They are approved and considered relatively safe, but there have been a few case reports of renal dysfunction associated with their use. We present the case of a patient who developed acute renal failure and lactic acidosis while using creatine and metformin simultaneously. PMID:20223410

Saidi, Hossein; Mani, Mofidi

2010-03-01

5

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

6

Severe lactic acidosis as a presenting feature of pheochromocytoma.  

PubMed

High plasma concentrations of epinephrine and norepinephrine have the potential for generating substantial hyperlactatemia by virtue of their metabolic and vasoconstrictor effects; both these influences affect lactate metabolism in the direction of overproduction and underutilization. Nonetheless, lactic acidosis is not a recognized presenting feature of pheochromocytoma. In this report, we describe a patient with pheochromocytoma in whom the endogenous outpouring of epinephrine and norepinephrine resulted in severe lactic acidosis that featured prominently in the clinical presentation. Pheochromocytoma should be listed among the clinical entities associated with or predisposing to lactic acidosis. PMID:3631073

Madias, N E; Goorno, W E; Herson, S

1987-09-01

7

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.

Adeva-Andany, Maria M.; Fernandez-Fernandez, Carlos; Mourino-Bayolo, David; Castro-Quintela, Elvira; Dominguez-Montero, Alberto

2014-01-01

8

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

9

[Lactic acidosis in a child with acute severe asthma].  

PubMed

Lactic acidosis is a recognized event in adult patients with acute severe asthma (ASA). Only a few cases have been reported in children. Hereinafter is reported the case of a 2-year-old girl hospitalized in the pediatric intensive care unit for ASA, which was treated with high-flow oxygen therapy and intravenous methylprednisolone and salbutamol. During hospitalization, she had metabolic acidosis with a 7.29 pH, a 26mmHg hypocapnia, and a decrease in bicarbonates to 12 mmol/L. The anion gap was increased to 20 mmol/L and lactates to 8 mmol/L. The work-up for a congenital metabolic disease was normal. Progression was propitious with spontaneous improvement of lactic acidosis, and the child was discharged from the intensive care unit after 72 h. The origin of lactic acidosis during ASA seems to be multifactorial. Although its recovery can be spontaneous, it is important to know how to identify it because it can worsen respiratory symptoms and can lead to incongruous therapeutic escalation. PMID:25125034

Perrin, C; Savy, N; Lang, M; Caron, N; Labbé, A

2014-10-01

10

Metabolic acidosis inhibits soft tissue calcification in uremic rats  

Microsoft Academic Search

Metabolic acidosis is common in patients with chronic kidney disease, which is known to affect bone metabolism. We examined the effect of metabolic acidosis on the development of vascular and other soft-tissue calcifications in uremic rats treated with calcitriol. Extraskeletal calcification was measured in vivo, in control rats and rats with a remnant kidney model of uremia with or without

F J Mendoza; I Lopez; A Montes de Oca; J Perez; M Rodriguez; E Aguilera-Tejero

2008-01-01

11

Intractable metabolic acidosis in a child with propionic acidemia undergoing liver transplantation -a case report-  

PubMed Central

Propionic acidemia (PA) is a rare autosomal recessive disorder of metabolism caused by deficient activity of the mitochondrial enzyme propionyl-CoA carboxylase. The clinical manifestations are metabolic acidosis, poor feeding, lethargy, vomiting, osteoporosis, neurological dysfunction, pancytopenia, developmental retardation and cardiomyopathy. Liver transplantation has recently been considered as one of the treatment options for patients with PA. This case report describes several anesthetic considerations for patients with PA undergoing liver transplantation. Understanding the patient's status and avoiding events that may precipitate metabolic acidosis are important for anesthetic management of patients with PA. In conclusion, anesthesia should be focused on minimizing the severity of metabolic acidosis with following considerations: (1) maintaining optimal tissue perfusion by avoiding hypotension, (2) preventing hypoglycemia, and (3) providing bicarbonate to compensate for the acidosis. PMID:24101962

Ryu, Jiyoung; Shin, Young Hee; Gwak, Mi Sook; Kim, Gaab-Soo

2013-01-01

12

Dietary Acid Load and Metabolic Acidosis in Renal Transplant Recipients  

PubMed Central

Summary Background and objectives Acidosis is prevalent among renal transplant recipients (RTRs) and adversely affects cardiometabolic processes. Factors contributing to acidosis are graft dysfunction and immunosuppressive drugs. Little is known about the potential influence of diet on acidosis in RTRs. This study examined the association of metabolic acid load with acidosis and with cardiovascular risk factors in RTRs and aimed to identify dietary factors associated with acidosis. Design, participants, setting, & measurements 707 RTRs were included. Metabolic acid load was assessed by measuring 24-hour urinary net acid excretion (NAE; i.e., titratable acid + ammonium ? bicarbonate). Acidosis was defined as serum [HCO3?] < 24 mmol/L. BP and insulin resistance, reflected by hemoglobin A1c, were among cardiovascular risk factors. Diet was assessed with food-frequency questionnaires. Linear regression analysis was applied to investigate association between NAE and acidosis and between dietary factors and acidosis. Results Mean age ± SD was 53±13 years; 57% of patients were male. Acidosis was present in 31% of RTRs. NAE was associated with acidosis (serum HCO3?: ?=?0.61; serum pH: ?=?0.010; both P<0.001). Patients with high intake of animal protein (i.e., from meat, cheese, and fish) and low intake of fruits and vegetables had significantly lower serum HCO3? and serum pH. No associations were observed between NAE and cardiovascular risk factors, such as hypertension and insulin resistance. Conclusions In addition to conventional factors contributing to acidosis, diet might influence acid-base homeostasis in RTRs. Higher intake of fruits and vegetables and lower animal protein intake is associated with less acidosis in RTRs. PMID:22935845

Engberink, Marielle F.; Brink, Elizabeth J.; van Baak, Marleen A.; Joosten, Michel M.; Gans, Reinold O.B.; Navis, Gerjan; Bakker, Stephan J.L.

2012-01-01

13

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

14

Metabolic engineering of lactate dehydrogenase rescues mice from acidosis  

PubMed Central

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

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

2014-01-01

15

Effects of acute metabolic acidosis on renal, gut, liver, and muscle metabolism of glutamine and ammonia in the dog  

Microsoft Academic Search

Effects of acute metabolic acidosis on renal, gut, liver, and muscle metabolism of glutamine and ammonia in the dog. Previous studies have shown a rise in arterial glutamine in acute acidosis in the dog. In these experiments glutamine and ammonia metabolism was studied in anesthetized dogs during normal acid-base status and following acute hydrochloric acidosis to determine the mechanism for

Adrian Fine

1982-01-01

16

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

17

[The effect of metabolic acidosis on amino acid and keto acid metabolism in chronic renal failure].  

PubMed

The effect of metabolic acidosis (MA) on amino acid and keto acid metabolism was studied in fourteen patients with chronic renal failure (CRF) under the low protein diet (0.6-0.8 g/kgBW). The comparative study of five patients with renal tubular acidosis was carried out. Each patient was investigated before [MA(+)period] and after correction with sodium bicarbonate administration lasting 10 days [MA(-)period]. The correction of MA improved nitrogen balance and elevated plasma branched-chain amino acids (BCAA), keto acids (BCKA), glutamine and alanine concentrations. No effect was however, observed in change of plasma insulin and glucagon. Oral administration of the keto-analogues of BCKA [0.1 g/kgBW of alpha-ketoisovalerates (KIV) and alpha-keto-isocaproic acid (KIC)] is made for the purpose of investigating the change in the metabolic conversion rate to amino acids. As a result, MA (+) suppressed an increase in plasma KIV and KIC concentrations. Moreover, an increase in plasma valine and leucine concentrations were suppressed by MA (+). These results suggested that MA stimulates BCKA oxidation and suppresses the protein sparing effect of leucine and KIC, and accelerates the catabolism in CRF under the low protein diet. The correction of MA is ineffective in severe renal failure (serum creatinine above 10.0 mg/dl), because the other uremic factors appear to be affecting protein and amino acid metabolism. Therefore, it might be concluded that MA should be corrected at an earlier stage of CRF. PMID:2051649

Mochizuki, T

1991-02-01

18

Role of the endocrine pancreas in the kalemic response to acute metabolic acidosis in conscious dogs.  

PubMed Central

Metabolic acidosis due to organic acids infusion fails to elicit hyperkalemia. Although plasma potassium levels may rise, the increase is smaller than in mineral acid acidosis. The mechanisms responsible for the different effects of organic acid acidosis and mineral acid acidosis remain undefined, although dissimilar hormonal responses by the pancreas may explain dissimilar hormonal responses by the pancreas may explain the phenomena. To test this hypothesis, beta-hydroxybutyric acid (7 meq/kg) or hydrochloric acid (3 meq/kg) was infused over 30 min into conscious dogs (n = 12) with chronically implanted catheters in the portal, hepatic, and systemic circulation, and flow probes were placed around the portal vein and hepatic artery. Acid infusion studies in two groups of anesthetized dogs were also done to assess the urinary excretion of potassium (n = 14), and to evaluate the effects of acute suppression of renal electrolyte excretion on plasma potassium and on the release/uptake of potassium in peripheral tissues of the hindleg (n = 17). Ketoacid infusion caused hypokalemia and a significant increase in portal vein plasma insulin, from the basal level of 27 +/- 4 microU/ml to a maximum of 84 +/- 22 microU/ml at 10 min, without changes in glucagon levels. By contrast, mineral acid acidosis of similar severity resulted in hyperkalemia and did not increase portal insulin levels but enhanced portal glucagon concentration from control values of 132 +/- 25 pg/ml to 251 +/- 39 pg/ml at 40 min. A significant decrease in plasma glucose levels due to suppression of hepatic release was observed during ketoacid infusion, while no changes were observed with mineral acid infusion. Plasma flows in the portal vein and hepatic artery remained unchanged from control values in both acid infusion studies. Differences in renal potassium excretion were ruled out as determinants of the disparate kalemic responses to organic acid infusion compared with HCl acidosis. Evaluation of the arteriovenous potassium difference across the hindleg during ketoacid infusion demonstrates that peripheral uptake of potassium is unlikely to be responsible for the observed hypokalemia. Although the tissue responsible for the different kalemic responses could not be defined with certainty, the data are compatible with an hepatic role in response to alterations in the portal vein insulin and/or glucagon levels in both acid infusion studies. We propose that cellular uptake of potassium is enhanced by hyperinsulinemia in ketoacid infusion, and release of potassium results from increased glucagon levels in HCl acidosis. Whether the changes in plasma potassium that other types od organic acid acidosis produce are accounted for by a similar hormonal mechanism remains to be determined. PMID:3884666

Adrogue, H J; Chap, Z; Ishida, T; Field, J B

1985-01-01

19

Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR  

Microsoft Academic Search

Metabolic acidosis often accompanies low glomerular filtration rate and induces secretion of endothelin, which in turn might mediate kidney injury. Here we tested whether treatment of metabolic acidosis in patients with low glomerular filtration rate reduced the progression of kidney disease. Fifty-nine patients with hypertensive nephropathy and metabolic acidosis had their blood pressure reduced with regimens that included angiotensin-converting enzyme

Sorot Phisitkul; Apurv Khanna; Jan Simoni; Kristine Broglio; Simon Sheather; M Hasan Rajab; Donald E Wesson

2010-01-01

20

Acute diarrhea and metabolic acidosis caused by tuberculous vesico-rectal fistula.  

PubMed

Acquired vesico-rectal fistula is an uncommon complication of pelvic malignant tumors, surgical injury, inflammatory disorders such as tuberculosis infection, radiotherapy and less commonly diverticulum of the urinary tract. The fistula is often identified by urinary tract abnormalities such as dysuria, recurrent urinary tract infection, pneumaturia, and fecaluria. Here, we report an unusual case of a patient with a vesico-rectal fistula of tuberculous origin, presenting with severe acute diarrhea, metabolic acidosis, hyperchloremia and hypokalemia while with only mild urinary tract symptoms. The patient was cured by tuberculostatic therapy. PMID:25386096

Wei, Xiu-Qing; Zou, Yan; Wu, Zhi-E; Abassa, Kodjo-Kunale; Mao, Wei; Tao, Jin; Kang, Zhuang; Wen, Zhuo-Fu; Wu, Bin

2014-11-01

21

Acute diarrhea and metabolic acidosis caused by tuberculous vesico-rectal fistula  

PubMed Central

Acquired vesico-rectal fistula is an uncommon complication of pelvic malignant tumors, surgical injury, inflammatory disorders such as tuberculosis infection, radiotherapy and less commonly diverticulum of the urinary tract. The fistula is often identified by urinary tract abnormalities such as dysuria, recurrent urinary tract infection, pneumaturia, and fecaluria. Here, we report an unusual case of a patient with a vesico-rectal fistula of tuberculous origin, presenting with severe acute diarrhea, metabolic acidosis, hyperchloremia and hypokalemia while with only mild urinary tract symptoms. The patient was cured by tuberculostatic therapy. PMID:25386096

Wei, Xiu-Qing; Zou, Yan; Wu, Zhi-E; Abassa, Kodjo-Kunale; Mao, Wei; Tao, Jin; Kang, Zhuang; Wen, Zhuo-Fu; Wu, Bin

2014-01-01

22

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

23

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

PubMed

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

Dussol, Bertrand

2014-07-01

24

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

PubMed Central

Background Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. Methods We prospectively enrolled all under-five children (n?=?164) admitted to the Special Care Ward (SCW) of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n?=?98) and without metabolic acidosis (n?=?66). Results Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p?=?0.039) compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62–7.89, p?=?0.002), and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01–1.04, p?=?0.005). Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05) among the groups. Conclusion and Significance Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children. However, metabolic acidosis in young diarrheal children had no impact on the diagnostic clinical features of radiological pneumonia which underscores the importance of early initiation of appropriate antibiotics to combat morbidity and deaths in such population. PMID:22720060

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

2012-01-01

25

Effects of dopamine and dobutamine on hemodynamics and plasma catecholamine levels during severe lactic acid acidosis.  

PubMed

This study was designed to evaluate the effects of dopamine and dobutamine on hemodynamics and plasma catecholamine levels during experimental lactic acid acidosis in dogs. During the normal acid-base state (pH 7.4, PCO2 40 mm Hg), cardiac output and stroke volume were significantly increased and systemic vascular resistance was decreased by the infusion of dopamine or dobutamine 20 mcg/kg/min. Dobutamine produced identical changes in cardiac output, stroke volume, and systemic vascular resistance even during severe lactic acid acidosis (pH 7.0, PCO2 40 mm Hg). Dopamine, however, failed to increase cardiac output and stroke volume and to decrease systemic vascular resistance during lactic acidosis. The plasma norepinephrine level was elevated from 0.49 to 3.01 ng/ml during normal acid-based state and from 1.76 to 9.53 ng/ml during severe lactic acid acidosis by the infusion of dopamine. Dobutamine infusion did not affect the plasma norepinephrine level during normal acid-base state but reduced the level during lactic acid acidosis. The marked increase in plasma norepinephrine following dopamine infusion may explain both the decrease in cardiac output and the increase in systemic vascular resistance in response to dopamine infusion during severe lactic acid acidosis. These results indicate that dobutamine may be more useful than dopamine in improving cardiac output during severe acidosis. PMID:4053301

Kosugi, I; Tajimi, K

1985-01-01

26

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

27

Changes in subcellular distribution of the ammonia transporter, Rhcg, in response to chronic metabolic acidosis.  

PubMed

The primary mechanism by which the kidneys mediate net acid excretion is through ammonia metabolism. In the current study, we examined whether chronic metabolic acidosis, which increases ammonia metabolism, alters the cell-specific and/or the subcellular expression of the ammonia transporter family member, Rhcg, in the outer medullary collecting duct in the inner stripe (OMCDi). Chronic metabolic acidosis was induced in normal SD rats by HCl ingestion for 7 days; controls were pair-fed. The subcellular distribution of Rhcg was determined using immunogold electron microscopy and morphometric analyses. In intercalated cells, acidosis increased total Rhcg, apical plasma membrane Rhcg, and the proportion of total cellular Rhcg in the apical plasma membrane. Intracellular Rhcg decreased significantly, and basolateral Rhcg was unchanged. Because apical plasma membrane length increased in parallel with apical Rhcg immunolabel, apical plasma membrane Rhcg density was unchanged. In principal cells, acidosis increased total Rhcg, apical plasma membrane Rhcg, and the proportion of total cellular Rhcg in the apical plasma membrane while decreasing the intracellular proportion. In contrast to the intercalated cell, chronic metabolic acidosis did not significantly alter apical boundary length; accordingly, apical plasma membrane Rhcg density increased. In addition, basolateral Rhcg immunolabel increased in response to chronic metabolic acidosis. These results indicate that in the rat OMCDi 1) chronic metabolic acidosis increases apical plasma membrane Rhcg in both the intercalated cell and principal cell where it may contribute to enhanced apical ammonia secretion; 2) increased apical plasma membrane Rhcg results from both increased total protein and changes in the subcellular distribution of Rhcg; 3) the mechanism of Rhcg subcellular redistribution differs in intercalated and principal cells; and 4) Rhcg may contribute to regulated basolateral ammonia transport in the principal cell. PMID:16434569

Seshadri, Ramanathan M; Klein, Janet D; Smith, Tekla; Sands, Jeff M; Handlogten, Mary E; Verlander, Jill W; Weiner, I David

2006-06-01

28

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

PubMed Central

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 (NaHCO3) 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 ± Sx) was 7.362 ± 0.021 and 7.116 ± 0.032, partial pressure of carbon dioxide (Pco2, 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, Pco2 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 Pco2 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, Pco2 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

29

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

PubMed Central

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

2012-01-01

30

Effect of acute metabolic acidosis on transmembrane electrolyte gradients in individual renal tubule cells  

Microsoft Academic Search

We studied the effect of acute metabolic acidosis on potassium, sodium and chloride gradients across the apical membrane of proximal and distal tubule cells by determining electrolyte concentrations in individual cells and in tubule fluid employing electron microprobe analysis. Cellular measurements were performed on freeze-dried cryosections of the renal cortex, analysis of tubule fluid electrolyte concentrations on freeze-dried microdroplets of

F.-X. Beck; M. Schramm; A. Dörge; R. Rick; K. Thurau

1988-01-01

31

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

PubMed Central

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.

2013-01-01

32

Grocery Store Baking SodaA Source of Sodium Bicarbonate in the Management of Chronic Metabolic Acidosis  

Microsoft Academic Search

Oral sodium bicarbonate is used to treat metabolic acidosis in patients with renal tubular acidosis. Since infants and young children are unable to swallow tablets, those affected must ingest sodium bicarbonate in a powder or liquid form. Pharmacy-weighed sodium bicarbonate is expensive and inconvenient to obtain; some pharmacists are reluctant to provide it. We determined that the sodium bicarbonate contained

Beverley E. Booth; Jay Gates; R. Curtis Morris

1984-01-01

33

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

PubMed Central

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

2012-01-01

34

Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo  

PubMed Central

Intracellular acidosis is a profound negative regulator of myocardial performance. We hypothesized that titrating myofilament calcium sensitivity by a single histidine substituted cardiac troponin I (A164H) would protect the whole animal physiological response to acidosis in vivo. To experimentally induce severe hypercapnic acidosis, mice were exposed to a 40% CO2 challenge. By echocardiography, it was found that systolic function and ventricular geometry were maintained in cTnI A164H transgenic (Tg) mice. By contrast, non-Tg (Ntg) littermates experienced rapid and marked cardiac decompensation during this same challenge. For detailed hemodymanic assessment, Millar pressure-conductance catheterization was performed while animals were treated with a ?-blocker, esmolol, during a severe hypercapnic acidosis challenge. Survival and load-independent measures of contractility were significantly greater in Tg vs. Ntg mice. This assay showed that Ntg mice had 100% mortality within 5 min of acidosis. By contrast, systolic and diastolic function were protected in Tg mice during acidosis, and they had 100% survival. This study shows that, independent of any ?-adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains cardiac inotropic and lusitropic performance and markedly improves survival during severe acidosis in vivo.—Palpant, N. J., D'Alecy, L. G., Metzger, J. M. Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo. PMID:19141534

Palpant, Nathan J.; D'Alecy, Louis G.; Metzger, Joseph M.

2009-01-01

35

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

36

Acute effects of acidosis on protein and amino acid metabolism in perfused rat liver  

PubMed Central

Acidosis is frequently associated with protein wasting and derangements in amino acid metabolism. As its effect on protein metabolism is significantly modulated by other abnormal metabolic conditions caused by specific illnesses, it is difficult to separate out the effects on protein metabolism solely due to acidosis. The aim of the present study was to evaluate, using a model of isolated perfused rat liver, the direct response of hepatic tissue to acidosis. We have compared hepatic response to perfusion with a solution of pH 7.2 and 7.4 (controls). Parameters of protein and amino acid metabolism were measured using both recirculation and single-pass technique with 4,5-[3H]leucine, [1–14C]leucine and [1–14C]ketoisocaproate (ketoleucine) as tracers and on the basis of difference of amino acid levels in perfusion solution at the beginning and end of perfusion. In liver perfused with a solution of pH 7.2, we observed higher rates of proteolysis, protein synthesis, amino acid utilization and urea production. Furthermore, the liver perfused with a solution of pH 7.2 released a higher amount of proteins to perfusate than the liver perfused with a solution of pH 7.4. Enhanced decarboxylation of ketoisocaproate in liver perfused by a solution of a lower pH indicates increased catabolism of branched-chain amino acids (leucine, valine and isoleucine), decreased reamination of branched-chain keto acids to corresponding essential amino acids and increased ketogenesis from leucine. PMID:14632632

Holecek, Milan; Safranek, Roman; Rysava, Radana; Kadlcikova, Jana; Sprongl, Ludek

2003-01-01

37

A SYNDROME OF SEVERE HYPOGLYCEMIA AND ACIDOSIS IN YOUNG IMMUNOSUPPRESSED DIABETIC MONKEYS AND PIGS - ASSOCIATION WITH SEPSIS1  

PubMed Central

Background Large animals treated with immunosuppressive drugs for preclinical experiments of transplantation have increased risks of infection, which can be compounded by the induction of diabetes in these animals if islet transplantation is planned. Methods We report our experience with severe sepsis in two young cynomolgus monkeys and five pigs that were subjected to diabetes induction, immunosuppressive therapy +/? islet allotransplantation. Results In two monkeys and five pigs, infection was associated with a syndrome of profound hypoglycemia accompanied by severe acidosis, which was resistant to treatment. We do not believe this syndrome has been reported previously by others. Conclusions Despite treatment, this syndrome complicated the interpretation of blood glucose readings as a measure of islet graft function, and resulted in death or the need for euthanasia in all 7 animals. We tentatively suggest that the syndrome may be related to the presence of microorganisms that metabolize glucose and produce lactate. PMID:23128998

Zhou, Hao; van der Windt, Dirk J.; Dons, Eefje M.; Rigatti, Lora H.; Echeverri, Gabriel J.; Bottino, Rita; Wijkstrom, Martin; Wagner, Robert; Cooper, David K.C.

2012-01-01

38

Severe lactic acidosis and acute pancreatitis associated with cimetidine in a patient with type 2 diabetes mellitus taking metformin.  

PubMed

An 82-year-old woman with type 2 diabetes mellitus, hypertension, and unstable angina presented with severe lactic acidosis and acute kidney injury (AKI) accompanied by acute pancreatitis. Her medical history revealed that she had taken cimetidine for two weeks while taking other medications, including metformin. Continuous veno-venous hemodiafiltration (CVVHDF) was initiated under diagnosis of lactic acidosis due to metformin and AKI caused by cimetidine-induced acute pancreatitis. In three days of CVVHDF, the levels of serum biochemical markers of lactic acidosis and AKI improved and the patient's urine output reached over 1 L/day. The pancreatitis improved over time. PMID:24088760

Seo, Ji Ho; Lee, Da Young; Hong, Chang Woo; Lee, In Hee; Ahn, Ki Sung; Kang, Gun Woo

2013-01-01

39

Ammonia production by isolated mouse proximal tubules perfused in vitro. Effect of metabolic acidosis.  

PubMed Central

We examined the effects of metabolic acidosis in vivo and reduced bath and luminal pH in vitro on total NH3 (NH3 + NH+4) production rates by isolated mouse proximal tubule segments. Midproximal tubule segments were obtained from mice with NH4Cl-induced metabolic acidosis and from nonacidotic controls. The segments were perfused with modified Krebs-Ringer bicarbonate (KRB) buffer, incubated in KRB buffer containing 0.5 mM L-glutamine and 1.0 mM sodium acetate, and gassed with 95% O2 and 5% CO2. Isolated unperfused and perfused proximal tubules from acidotic mice produced total NH3 at higher rates than corresponding tubules from nonacidotic mice. Perfusion of the tubular lumen stimulated total NH3 production by tubules from both acidotic and nonacidotic mice. In contrast, lowering the bath pH to 7.0 by lowering the HCO3- concentration increased total NH3 production rates by tubules from nonacidotic mice but not by tubules from acidotic mice. Reducing the HCO3- concentration of the bath buffer to 10 mM while maintaining a pH of 7.4 had no significant effect on total NH3 production by tubules from nonacidotic mice. Lowering the luminal fluid pH by reducing the perfusate HCO-3 from 25 mM to 10, 5, or 1.2 mM while maintaining a bath pH of 7.4 lowered collected luminal fluid pH but had no effect on total NH3 production by proximal tubules from nonacidotic mice. These observations demonstrated that metabolic acidosis in vivo stimulated total NH3 production in isolated mouse proximal tubule segments and that low peritubular pH and HCO-3 stimulated total NH3 production by proximal tubule segments from nonacidotic mice in vitro. PMID:3722373

Nagami, G T; Sonu, C M; Kurokawa, K

1986-01-01

40

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

PubMed

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

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

2013-12-15

41

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

PubMed

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

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

2014-03-01

42

The SIRT1/HIF2? Axis Drives Reductive Glutamine Metabolism under Chronic Acidosis and Alters Tumor Response to Therapy.  

PubMed

Extracellular tumor acidosis largely results from an exacerbated glycolytic flux in cancer and cancer-associated cells. Conversely, little is known about how tumor cells adapt their metabolism to acidosis. Here, we demonstrate that long-term exposure of cancer cells to acidic pH leads to a metabolic reprogramming toward glutamine metabolism. This switch is triggered by the need to reduce the production of protons from glycolysis and further maintained by the NAD(+)-dependent increase in SIRT1 deacetylase activity to ensure intracellular pH homeostasis. A consecutive increase in HIF2? activity promotes the expression of various transporters and enzymes supporting the reductive and oxidative glutamine metabolism, whereas a reduction in functional HIF1? expression consolidates the inhibition of glycolysis. Finally, in vitro and in vivo experiments document that acidosis accounts for a net increase in tumor sensitivity to inhibitors of SIRT1 and glutaminase GLS1. These findings highlight the influence that tumor acidosis and metabolism exert on each other. Cancer Res; 74(19); 5507-19. ©2014 AACR. PMID:25085245

Corbet, Cyril; Draoui, Nihed; Polet, Florence; Pinto, Adan; Drozak, Xavier; Riant, Olivier; Feron, Olivier

2014-10-01

43

Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease  

Microsoft Academic Search

BACKGROUND: Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. CASE PRESENTATION: Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney

Johannes Jacobi; Susanne Schnellhardt; Mirian Opgenoorth; Kerstin U Amann; Axel Küttner; Axel Schmid; Kai-Uwe Eckardt; Karl F Hilgers

2010-01-01

44

Renal phosphaturia during metabolic acidosis revisited: molecular mechanisms for decreased renal phosphate reabsorption.  

PubMed

During metabolic acidosis (MA), urinary phosphate excretion increases and contributes to acid removal. Two Na(+)-dependent phosphate transporters, NaPi-IIa (Slc34a1) and NaPi-IIc (Slc34a3), are located in the brush border membrane (BBM) of the proximal tubule and mediate renal phosphate reabsorption. Transcriptome analysis of kidneys from acid-loaded mice revealed a large decrease in NaPi-IIc messenger RNA (mRNA) and a smaller reduction in NaPi-IIa mRNA abundance. To investigate the contribution of transporter regulation to phosphaturia during MA, we examined renal phosphate transporters in normal and Slc34a1-gene ablated (NaPi-IIa KO) mice acid-loaded for 2 and 7 days. In normal mice, urinary phosphate excretion was transiently increased after 2 days of acid loading, whereas no change was found in Slc34a1-/- mice. BBM Na/Pi cotransport activity was progressively and significantly decreased in acid-loaded KO mice, whereas in WT animals, a small increase after 2 days of treatment was seen. Acidosis increased BBM NaPi-IIa abundance in WT mice and NaPi-IIc abundance in WT and KO animals. mRNA abundance of NaPi-IIa and NaPi-IIc decreased during MA. Immunohistochemistry did not indicate any change in the localization of NaPi-IIa and NaPi-IIc along the nephron. Interestingly, mRNA abundance of both Slc20 phosphate transporters, Pit1 and Pit2, was elevated after 7 days of MA in normal and KO mice. These data demonstrate that phosphaturia during acidosis is not caused by reduced protein expression of the major Na/Pi cotransporters NaPi-IIa and NaPi-IIc and suggest a direct inhibitory effect of low pH mainly on NaPi-IIa. Our data also suggest that Pit1 and Pit2 transporters may play a compensatory role. PMID:18535837

Nowik, Marta; Picard, Nicolas; Stange, Gerti; Capuano, Paola; Tenenhouse, Harriet S; Biber, Jürg; Murer, Heini; Wagner, Carsten A

2008-11-01

45

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

PubMed Central

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

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

2014-01-01

46

Metabolic Acidosis Increases Intracellular Calcium in Bone Cells Through Activation of the Proton Receptor OGR1  

PubMed Central

Metabolic acidosis increases urine Ca without increasing intestinal absorption, leading to bone Ca loss. It is unclear how bone cells detect the increase in proton concentration. To determine which G protein-coupled proton sensing receptors are expressed in bone, PCR was performed, and products were detected for OGR1, TDAG8, G2A, and GPR4. We tested the hypothesis that the G protein-coupled proton sensor, OGR1, is an H+-sensing receptor in bone. To determine whether acid-induced bone resorption involves OGR1, we incubated mouse calvariae in neutral pH (NTL) or acidic (MET) medium ± the OGR1 inhibitor CuCl2. CuCl2 decreased MET-induced Ca efflux. We used fluorescent imaging of perfused bone cells to determine whether MET increases Cai. Perfusion with MET induced a rapid, flow-independent, increase in Cai in individual bone cells. To determine whether transfection of OGR1 into a heterologous cell type would increase Cai in response to H+, we perfused Chinese hamster ovary (CHO) cells transfected with mouse OGR1 cDNA. Perfusion with MET induced a rapid increase in Cai in OGR1-transfected CHO cells. These data indicate that OGR1 induces an increase in Cai in response to MET and is a prime candidate for an osteoblast proton sensor. PMID:18847331

Frick, Kevin K; Krieger, Nancy S; Nehrke, Keith; Bushinsky, David A

2009-01-01

47

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

48

Severe lactic acidosis and acute renal failure following ingestion of metformin and kerosene oil: a case report  

PubMed Central

Introduction Kerosene is a freely accessible hydrocarbon used in Sri Lankan (and other Asian) households for cooking and for lighting lamps. Kerosene poisoning is rarely reported among adults and its toxicological effects are not well known. Metformin is a commonly used oral hypoglycemic drug and its overdose leads primarily to lactic acidosis. Combined poisoning of metformin and kerosene and their interactions have not been reported. Case presentation An 18-year-old, previously healthy, unmarried Sinhalese woman was referred following ingestion of 17.5 g of metformin and approximately 200 mL of kerosene oil in a suicide attempt. She had vomiting, burning epigastric pain, and a hypoglycemic seizure (capillary blood glucose of 42 mg/dL). Subsequently, she developed severe lactic acidosis followed by acute renal insufficiency, was treated with sodium bicarbonate, and underwent intermittent hemodialysis with bicarbonate. She recovered completely. Conclusions This report proposes possible interactions that occur between metformin and kerosene that augment toxicity when the two are ingested together. It also stresses the importance of early treatment with intermittent hemodialysis in severe lactic acidosis with maintenance of blood glucose. PMID:22251748

2012-01-01

49

Handling of ammonium by the renal proximal tubule during acute metabolic acidosis.  

PubMed

The present studies were designed to assess the handling of ammonium (NH+4) by the proximal tubule during acute metabolic acidosis (AMA). After tubule fluid collections were obtained with micropuncture techniques and in situ pH was determined near the end of the proximal tubule, 0.2 N HCl was infused intravenously at 17 microliter X min-1 X 100 g body wt-1. Thirty to sixty minutes later, samples were obtained and pH measurements were made near the previous micropuncture sites. During AMA, urine pH fell and total acid excretion doubled due to an increase in NH+4 excretion from 581 +/- 63 to 1,153 +/- 61 nmol X min-1 X g kidney wt-1 (P less than 0.001). Acid excretion did not change in time controls. Tubule fluid NH+4 rose from 2.17 +/- 0.15 to 3.45 +/- 0.24 mM during acid infusion (P less than 0.001) and its delivery to the end of the proximal tubule nearly doubled (67.8 +/- 6.3 vs. 33.9 +/- 2.9 pmol X min X g kidney wt-1 before acid infusion, P less than 0.001). This increase in delivery during AMA was due to enhanced ammonia (NH3) entry into the proximal tubule. In situ pH determined near the end of the proximal tubule averaged 6.94 +/- 0.04 before acid infusion and did not change afterwards (6.87 +/- 0.05). These data are consistent with the hypothesis that in AMA the increase in NH+4 excretion is due primarily to an increase in the cortical production of NH3. PMID:6419622

Simon, E; Martin, D; Buerkert, J

1983-12-01

50

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

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

1985-08-01

51

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

52

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

53

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

54

Solvent abuse, toluene acidosis and diabetic ketoacidosis.  

PubMed

Solvent abuse in adolescents and young adults has been reported to cause a metabolic acidosis with a normal or increased anion gap (Streicher et al., 1981; Voights & Kaufman, 1983, Anonymous, 1988). We report a particularly severe clinical problem produced by the combination of toluene intoxication and diabetic ketoacidosis. PMID:1906715

Brown, J H; Hadden, D R; Hadden, D S

1991-03-01

55

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

56

Ethylene glycol poisoning: a rare but life-threatening cause of metabolic acidosis—a single-centre experience  

PubMed Central

Background. Intoxication with ethylene glycol happen all around the world and without rapid recognition and early treatment, mortality from this is high. Methods. In our study, we retrospectively analysed six cases of ethylene glycol intoxication in our department. We measured ethylene glycol or glycolate levels, lactate levels and calculated the osmolal and anion gap. Results. Data from six patients admitted to the nephrology department between 1999 and 2011 with ethylene glycol poisoning are reported. All patients were men. The mean pH on admission was 7.15 ± 0.20 and the anion and osmolal gap were elevated in five of six patients. Four patients had an acute kidney injury and one patient had an acute-on-chronic kidney injury. All patients survived and after being discharged, two patients required chronic intermittent haemodialysis. Interestingly, at the time of admission, all patients had elevated lactate levels but there was no linear regression between toxic levels and lactate levels and no linear correlation was found between initial lactate levels and anion gap and osmolal gap. Conclusions. The initial diagnosis of ethylene glycol poisoning is difficult and poisoning with ethylene glycol is rare but life threatening and needs rapid recognition and early treatment. Therefore, intoxication with ethylene glycol should not be misdiagnosed as lactic acidosis in patients with metabolic acidosis and elevated lactate levels.

Kimmel, Martin; Alscher, Mark Dominik; Braun, Niko

2012-01-01

57

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

58

Endothelin-1/endothelin-B receptor-mediated increases in NHE3 activity in chronic metabolic acidosis  

PubMed Central

Decreases in blood pH activate NHE3, the proximal tubular apical membrane Na/H antiporter. In cultured renal epithelial cells, activation of the endothelin-B (ETB) receptor increases NHE3 activity. To examine the role of the ETB receptor in the response to acidosis in vivo, the present studies examined ETB receptor–deficient mice, rescued from neonatal lethality by expression of a dopamine ?-hydroxylase promoter/ETB receptor transgene (Tg/Tg:ETB–/– mice). In proximal tubule suspensions from Tg/Tg:ETB+/– mice, 10–8 M endothelin-1 (ET-1) increased NHE3 activity, but this treatment had no effect on tubules from Tg/Tg:ETB–/– mice. Acid ingestion for 7 days caused a greater decrease in blood HCO3– concentration in Tg/Tg:ETB–/– mice compared with Tg/Tg:ETB+/+ and Tg/Tg:ETB+/– mice. Whereas acid ingestion increased apical membrane NHE3 by 42–46% in Tg/Tg:ETB+/+ and Tg/Tg:ETB+/– mice, it had no effect on NHE3 in Tg/Tg:ETB–/– mice. In C57BL/6 mice, excess acid ingestion increased renal cortical preproET-1 mRNA expression 2.4-fold and decreased preproET-3 mRNA expression by 37%. On a control diet, Tg/Tg:ETB–/– mice had low rates of ammonium excretion, which could not be attributed to an inability to acidify the urine, as well as hypercitraturia, with increased titratable acid excretion. Acid ingestion increased ammonium excretion, citrate absorption, and titratable acid excretion to the same levels in Tg/Tg:ETB–/– and Tg/Tg:ETB+/+ mice. In conclusion, metabolic acidosis increases ET-1 expression, which increases NHE3 activity via the ETB receptor. PMID:11413164

Laghmani, Kamel; Preisig, Patricia A.; Moe, Orson W.; Yanagisawa, Masashi; Alpern, Robert J.

2001-01-01

59

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

PubMed Central

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

Walmsley, Scott J.; Freund, Dana M.

2012-01-01

60

Metformin-associated lactic acidosis precipitated by diarrhea.  

PubMed

Metformin-associated lactic acidosis (MALA) is a serious metabolic complication that occurs because of metformin accumulation in patients who become dehydrated or developed acute renal failure. Bicarbonate hemodialysis treatment should take place early in the course of management, especially in patients with severe metabolic acidosis who fail to respond to intravenous bicarbonate therapy or in whom renal failure is present. We report a case of MALA in which acute renal failure resulting from dehydration secondary to diarrhea and poor oral intake likely caused MALA. Early recognition of this condition and initiation of effective treatment can improve outcome. PMID:17667216

El-Hennawy, Adel S; Jacob, Sunitha; Mahmood, Aza K

2007-01-01

61

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

62

[Case of young woman with Graves' disease and incomplete distal renal tubular acidosis with severe progress and cardiac arrest].  

PubMed

Diagnostic of renal tubular disorders can be often difficult. Incomplete form of distal Renal Tubular Acidosis (dRta) in course of Graves' disease was de novo recognized in a young woman hospitalized with a deep deficiency of potassium in blood serum complicated with cardiac arrest. Series of tests assessing the types and severity of water-electrolyte, acid-base and thyroid disorders were performed during a complex diagnosis. During the treatment of acute phase of the disease we intensified efforts to maintain basic life functions and to eliminate deep water-electrolyte disturbances. In the second phase of the treatment we determined an underlying cause of the disease, recognized dRTA, and introduced a specific long-term electrolyte and hormonal therapy. To confirm the diagnosis oral test with ammonium chloride (Wrong-Davies' test) was performed. After completion of the diagnostic and therapeutic process, the patient was included in the nephrological supervision on an outpatient basis. The basic drug for the therapy was sodium citrate. After a year of observation and continuing treatment we evaluated therapeutic results as good and permanent. PMID:25154201

Klimm, Wojciech; Kade, Grzegorz; Spaleniak, Sebastian; Dubchak, Ivanna; Niemczyk, Stanis?aw

2014-07-01

63

Lactic acidosis in patients with cancer.  

PubMed

Lactic acidosis is the most common metabolic acidosis in hospitalized patients-the result from an underlying pathogenic process. To successfully manage lactic acid production, its cause needs to be eliminated. Patients with cancer have many risk factors for developing lactic acidosis, including the cancer diagnosis itself. Patients with lactic acidosis are critically ill, requiring an intense level of nursing care with accompanying frequent cardiopulmonary and renal assessments. The mortality rate from lactic acidosis is high. Therefore, appropriate nursing interventions may include end-of-life and palliative care. PMID:25253114

Held-Warmkessel, Jeanne; Dell, Deena Damsky

2014-10-01

64

Metabolic Multianalyte Microphysiometry Reveals Extracellular Acidosis is an Essential Mediator of Neuronal Preconditioning  

PubMed Central

Metabolic adaptation to stress is a crucial yet poorly understood phenomenon, particularly in the central nervous system (CNS). The ability to identify essential metabolic events which predict neuronal fate in response to injury is critical to developing predictive markers of outcome, for interpreting CNS spectroscopic imaging, and for providing a richer understanding of the relevance of clinical indices of stress which are routinely collected. In this work, real-time multianalyte microphysiometry was used to dynamically assess multiple markers of aerobic and anaerobic respiration through simultaneous electrochemical measurement of extracellular glucose, lactate, oxygen, and acid. Pure neuronal cultures and mixed cultures of neurons and glia were compared following a 90 min exposure to aglycemia. This stress was cytotoxic to neurons yet resulted in no appreciable increase in cell death in age-matched mixed cultures. The metabolic profile of the cultures was similar in that aglycemia resulted in decreases in extracellular acidification and lactate release in both pure neurons and mixed cultures. However, oxygen consumption was only diminished in the neuron enriched cultures. The differences became more pronounced when cells were returned to glucose-containing media upon which extracellular acidification and oxygen consumption never returned to baseline in cells fated to die. Taken together, these data suggest that lactate release is not predictive of neuronal survival. Moreover, they reveal a previously unappreciated relationship of astrocytes in maintaining oxygen uptake and a correlation between metabolic recovery of neurons and extracellular acidification. PMID:22860220

2012-01-01

65

Lactic acid permeation rate in working gastrocnemii of dogs during metabolic alkalosis and acidosis  

Microsoft Academic Search

In isolated, blood perfused, supramaximally stimulated, isotonically working gastrocnemii of dogs lactic acid (LA) output and O2-consumption (V O2) were measured according to the Fick principle. Simultaneously concentration of muscle tissue was determined at rest and at different times during exercise. In one series of experiments metabolic alkalosis was induced by infusions of THAM or Na bicarbonate. As a result

Hj. Hirche; V. Hombach; H. D. Langohr; U. Wacker; J. Busse

1975-01-01

66

Parallel adaptation of the rabbit renal cortical sodium/proton antiporter and sodium/bicarbonate cotransporter in metabolic acidosis and alkalosis.  

PubMed Central

Recent studies have shown that the bicarbonate reabsorptive capacity of the proximal tubule is increased in metabolic acidosis. For net bicarbonate reabsorption to be regulated, there may be changes in the rate of apical H+ secretion as well as in the basolateral base exit step. The present studies examined the rate of Na+/H+ exchange (acridine orange method) and Na+/HCO3 cotransport (22Na uptake) in apical and basolateral membranes prepared from the rabbit renal cortex by sucrose density gradient centrifugation. NH4Cl loading was used to produce acidosis (arterial pH, 7.27 +/- 0.03), and Cl-deficient diet with furosemide was used to produce alkalosis (arterial pH, 7.51 +/- 0.02). Maximal transport rate (Vmax) of Na+/H+ antiporter and Na+/HCO3 cotransporter were inversely related with plasma bicarbonate concentration from 6 to 39 mM. Furthermore, the maximal transport rates of both systems varied in parallel; when Vmax for the Na+/HCO3 cotransporter was plotted against Vmax for the Na+/H+ antiporter for each of the 24 groups of rabbits, the regression coefficient (r) was 0.648 (P less than 0.001). There was no effect of acidosis or alkalosis on affinity for Na+ of either transporter. We conclude that both apical and basolateral H+/HCO3 transporters adapt during acid-base disturbances, and that the maximal transport rates of both systems vary in parallel during such acid-base perturbations. PMID:3038953

Akiba, T; Rocco, V K; Warnock, D G

1987-01-01

67

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

Microsoft Academic Search

Although lactic acidosis is a prominent feature of solid tumors, we still have limited understanding of the mechanisms by which lactic acidosis influences metabolic phenotypes of cancer cells. We compared global transcriptional responses of breast cancer cells in response to three distinct tumor microenvironmental stresses: lactic acidosis, glucose deprivation, and hypoxia. We found that lactic acidosis and glucose deprivation trigger

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

2010-01-01

68

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

69

Phenylbutyrate Therapy for Pyruvate Dehydrogenase Complex Deficiency and Lactic Acidosis  

PubMed Central

Lactic acidosis is a build-up of lactic acid in the blood and tissues, which can be due to several inborn errors of metabolism as well as nongenetic conditions. Deficiency of pyruvate dehydrogenase complex (PDHC) is the most common genetic disorder leading to lactic acidosis. Phosphorylation of specific serine residues of the E1? subunit of PDHC by pyruvate dehydrogenase kinase (PDK) inactivates the enzyme, whereas dephosphorylation restores PDHC activity. We found that phenylbutyrate enhances PDHC enzymatic activity in vitro and in vivo by increasing the proportion of unphosphorylated enzyme through inhibition of PDK. Phenylbutyrate given to C57B6/L wild-type mice results in a significant increase in PDHC enzyme activity and a reduction of phosphorylated E1? in brain, muscle, and liver compared to saline-treated mice. By means of recombinant enzymes, we showed that phenylbutyrate prevents phosphorylation of E1? through binding and inhibition of PDK, providing a molecular explanation for the effect of phenylbutyrate on PDHC activity. Phenylbutyrate increases PDHC activity in fibroblasts from PDHC-deficient patients harboring various molecular defects and corrects the morphological, locomotor, and biochemical abnormalities in the noam631 zebrafish model of PDHC deficiency. In mice, phenylbutyrate prevents systemic lactic acidosis induced by partial hepatectomy. Because phenylbutyrate is already approved for human use in other diseases, the findings of this study have the potential to be rapidly translated for treatment of patients with PDHC deficiency and other forms of primary and secondary lactic acidosis. PMID:23467562

Ferriero, Rosa; Manco, Giuseppe; Lamantea, Eleonora; Nusco, Edoardo; Ferrante, Mariella I.; Sordino, Paolo; Stacpoole, Peter W.; Lee, Brendan; Zeviani, Massimo; Brunetti-Pierri, Nicola

2014-01-01

70

Metformin-associated acute kidney injury and lactic acidosis.  

PubMed

Objectives. Metformin is the preferred oral antidiabetic agent for type 2 diabetes. Lactic acidosis is described as a rare complication, usually during an acute kidney injury (AKI). Material and Methods. We conducted a prospective observational study of metformin-associated AKI cases during four years. 29 cases were identified. Previous renal function, clinical data, and outcomes were recorded. Results. An episode of acute gastroenteritis precipitated the event in 26 cases. Three developed a septic shock. Three patients died, the only related factor being liver dysfunction. More severe metabolic acidosis hyperkalemia and anemia were associated with higher probabilities of RRT requirement. We could not find any relationship between previous renal dysfunction and the outcome of the AKI. Conclusions. AKI associated to an episode of volume depletion due to gastrointestinal losses is a serious complication in type 2 diabetic patients on metformin. Previous renal dysfunction (mild-to-moderate CKD) has no influence on the severity or outcome. PMID:21792389

Arroyo, David; Melero, Rosa; Panizo, Nayara; Goicoechea, Marian; Rodríguez-Benítez, Patrocinio; Vinuesa, Soledad García; Verde, Eduardo; Tejedor, Alberto; Luño, José

2011-01-01

71

Metformin-Associated Acute Kidney Injury and Lactic Acidosis  

PubMed Central

Objectives. Metformin is the preferred oral antidiabetic agent for type 2 diabetes. Lactic acidosis is described as a rare complication, usually during an acute kidney injury (AKI). Material and Methods. We conducted a prospective observational study of metformin-associated AKI cases during four years. 29 cases were identified. Previous renal function, clinical data, and outcomes were recorded. Results. An episode of acute gastroenteritis precipitated the event in 26 cases. Three developed a septic shock. Three patients died, the only related factor being liver dysfunction. More severe metabolic acidosis hyperkalemia and anemia were associated with higher probabilities of RRT requirement. We could not find any relationship between previous renal dysfunction and the outcome of the AKI. Conclusions. AKI associated to an episode of volume depletion due to gastrointestinal losses is a serious complication in type 2 diabetic patients on metformin. Previous renal dysfunction (mild-to-moderate CKD) has no influence on the severity or outcome. PMID:21792389

Arroyo, David; Melero, Rosa; Panizo, Nayara; Goicoechea, Marian; Rodriguez-Benitez, Patrocinio; Vinuesa, Soledad Garcia; Verde, Eduardo; Tejedor, Alberto; Luno, Jose

2011-01-01

72

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; Ambuhl, P; Froissart, M; Bichara, M; Moe, O W; Alpern, R J; Paillard, M

1997-01-01

73

Mitochondrial myopathy with lactic acidosis and deficient activity of muscle succinate cytochrome- c -oxidoreductase  

Microsoft Academic Search

A male infant had severe muscular hypotonia from birth. Recurrent vomiting with dehydration and severe metabolic acidosis complicated the course. Elevated lactate (up to 12.3 mmol\\/l; nn30; n<15). In urine the concentrations of lactate, pyruvate, alanine and of several intermediates of the citric acid cycle were increased. In muscle, numerous disseminated “ragged red fibres” were found by light microscopy; muscle

A. W. Behbehani; H. Goebel; G. Osse; M. Gabriel; U. Langenbeck; J. Berden; R. Berger; R. B. H. Schutgens

1984-01-01

74

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

75

[Metformin-associated lactic acidosis: incidence, diagnosis, prognostic factors and treatment].  

PubMed

We describe the case of a patient with severe lactic acidosis, as well as presenting some data on its incidence, diagnosis, prognostic factors, and the most appropriate treatment. A 76 year-old male patient with diabetes on treatment with metformin, hypertension, dyslipaemia, and with mild cognitive impairment, was admitted to the Intensive Care Unit in a state of circulatory shock, requiring aggressive treatment with vasopressors and volume. The patient had acute kidney injury with an anuria of 3 days, probably secondary to dehydration to vomiting and to NSAIDs. As a result of the acute renal damage, the patient suffered a severe metformin-associated lactic acidosis. The rest of the causes of metabolic acidosis with an increased anion gap were ruled out, as well as a possible sepsis or rhabdomyolysis. Metformin-associated lactic acidosis is an uncommon metabolic condition, but with a high mortality. To reduce the mortality of these patients, it is important to make an early diagnosis using the clinical records, physical examination, and laboratory tests, with an early resuscitation with volume, vasopressors, bicarbonate, and renal replacement therapy. PMID:22609263

Vives, M; Romano, J; Stoll, E; Lafuente, A; Nagore, D; Monedero, P

2012-05-01

76

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

77

Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism.  

PubMed

A 43-year-old woman with drug-related blepharospasm was followed up for 22 months. She had undergone etizolam treatment for 19 years for indefinite complaints. We examined her cerebral glucose metabolism 5 times (between days 149 and 688 since presentation), using positron emission tomography, and identified regions of interest in the thalamus, caudate nucleus, putamen, and primary somatosensory area on both sides. The severity of the blepharospasm was evaluated by PET scanning using the Wakakura classification. Sixteen women (mean age 42.4 ± 11.7 years) were examined as normal controls. The thalamic glucose metabolism in our patient was significantly increased on days 149, 212, and 688. The severity of the blepharospasm was positively correlated with the thalamic glucose metabolism, suggesting that the severity of blepharospasms reflects thalamic activity. PMID:22110436

Murai, Hideki; Suzuki, Yukihisa; Kiyosawa, Motohiro; Wakakura, Masato; Mochizuki, Manabu; Ishiwata, Kiichi; Ishii, Kenji

2011-01-01

78

Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism  

PubMed Central

A 43-year-old woman with drug-related blepharospasm was followed up for 22 months. She had undergone etizolam treatment for 19 years for indefinite complaints. We examined her cerebral glucose metabolism 5 times (between days 149 and 688 since presentation), using positron emission tomography, and identified regions of interest in the thalamus, caudate nucleus, putamen, and primary somatosensory area on both sides. The severity of the blepharospasm was evaluated by PET scanning using the Wakakura classification. Sixteen women (mean age 42.4 ± 11.7 years) were examined as normal controls. The thalamic glucose metabolism in our patient was significantly increased on days 149, 212, and 688. The severity of the blepharospasm was positively correlated with the thalamic glucose metabolism, suggesting that the severity of blepharospasms reflects thalamic activity. PMID:22110436

Murai, Hideki; Suzuki, Yukihisa; Kiyosawa, Motohiro; Wakakura, Masato; Mochizuki, Manabu; Ishiwata, Kiichi; Ishii, Kenji

2011-01-01

79

Metformin-associated lactic acidosis in a low risk patient.  

PubMed

Metformin is an oral hypoglycemic agent belonging to the class of biguanides that are commonly used in the treatment of type II diabetes mellitus. Lactic acidosis is a rare but severe adverse reaction that occurs primarily in patients with contraindications such as renal failure. The case of a 71-year-old woman with type II diabetes, in whom severe metformin-associated lactic acidosis was precipitated by acute renal failure in the absence of pre-existing chronic renal failure or other absolute contraindications to biguanide use, is presented. Aggressive correction of the acidosis and prolonged dialysis resulted in a favourable outcome despite severe acidosis. The present case report shows that metformin-associated lactic acidosis can occur in patients without pre-existing renal insufficiency. Metformin should be temporarily stopped when acute renal failure occurs or is anticipated. PMID:11493939

Ellis, A K; Iliescu, E A

2001-01-01

80

Metformin-Associated Lactic Acidosis following Intentional Overdose Successfully Treated with Tris-Hydroxymethyl Aminomethane and Renal Replacement Therapy  

PubMed Central

A 43-year-old woman was brought to the hospital with severe metabolic acidosis (pH 6.56, bicarbonate 3?mmol/L, and lactate 18.4?mmol/L) and a serum creatinine of 162??mol/L with a serum potassium of 7.8?mmol/L. A delayed diagnosis of metformin-associated lactic acidosis was made, and she was treated with tris-hydroxymethyl aminomethane (THAM) and renal replacement therapy (RRT). Following a complete recovery, she admitted to ingesting 180 tablets (90 grams) of metformin. Her peak serum metformin concentration was 170??g/mL (therapeutic range 1-2??g/mL). Our case demonstrates an intentional metformin overdose resulting in lactic acidosis in a nondiabetic patient who was successfully treated with THAM and RRT. PMID:24533205

Lam, Ngan; Sekhon, Gurbir; House, Andrew A.

2012-01-01

81

A Review of metabolic staging in severely injured patients  

Microsoft Academic Search

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

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

2010-01-01

82

[Giant placental angioma with polyhydramnios, high level of alpha-fetoprotein and neonatal congenital lactic acidosis].  

PubMed

Placental tumors are rare in pregnancy. They cause nonspecific complications such as polyhydramnios, fetal anemia, fetal thrombocytopenia and cardiac decompensation with non-immunological hydrops fetalis. In the presented case a very large placental hemangioma was connected with polyhydramnios, premature delivery, fetal anemia and thrombocytopenia, maternal serum alpha fetoprotein elevation and congenital lactic acidosis. After delivery a severe state of the newborn was caused by oligovolemic shock. In the course of the disease the neonatal state steadily deteriorated mainly because of sepsis, cerebral hemorrhage and metabolic acidosis despite adequate therapy. The organic acids assessment in the blood serum of a newborn child showed a very strong signal of lactic acid and an increase in parahydroksyfenylolactic acid. Postmortal examination confirmed prematurity, respiratory distress syndrome, sepsis and cerebral hemorrhage. These symptoms probably resulted from the presence of a placental tumor of considerable size of 12 cm and congenital lactic acidosis, which to our knowledge, have not been described in the available literature until now. In conclusion it should be underlined, that there exists difficult to explain relationship between the presence of a placental haemangioma and severe metabolic changes resulting in high mortality and morbidity of the newborn. PMID:10715913

Piela, A; Witalis, J; Kruczek, A; Zawora, A; Lewandowska, M

1999-12-01

83

Metformin-induced lactic acidosis associated with acute renal failure.  

PubMed

A 69-year-old diabetic woman with diffuse atherosclerosis presented with acute renal failure due to contrast nephropathy and severe metformin-induced lactic acidosis. There was a discrepancy between the patient's elevated serum creatinine level, indicative of severe renal insufficiency, and her very low blood urea nitrogen content. It is postulated that the patient's extremely severe acidosis interfered with her hepatic urea generation, contributing to this unusual biochemical abnormality. PMID:8955764

Safadi, R; Dranitzki-Elhalel, M; Popovtzer, M; Ben-Yehuda, A

1996-01-01

84

Glucose and pyruvate metabolism in severe chronic obstructive pulmonary disease.  

PubMed

The mechanisms leading to weight loss in patients with chronic obstructive pulmonary disease (COPD) are poorly understood but may involve alterations in macronutrient metabolism. Changes in muscle oxidative capacity and lactate production during exercise suggest glucose metabolism may be altered in COPD subjects. The objective of this study was to determine differences in the rates of glucose production and clearance, the rate of glycolysis (pyruvate production), and oxidative and nonoxidative pyruvate disposal in subjects with severe COPD compared with healthy controls. The in vivo rates of glucose production and clearance were measured in 14 stable outpatients with severe COPD (seven with low and seven with preserved body mass indexes) and 7 healthy controls using an intravenous infusion of [(2)H(2)]glucose. Additionally, pyruvate production and oxidative and non-oxidative pyruvate disposal were measured using intravenous infusions of [(13)C]bicarbonate and [(13)C]pyruvate. Endogenous glucose flux and glucose clearance were significantly faster in the combined COPD subjects (P = 0.002 and P < 0.001, respectively). This difference remained significant when COPD subjects were separated by body mass index. Pyruvate flux and oxidation were significantly higher in the combined COPD subjects than controls (P = 0.02 for both), but there was no difference in nonoxidative pyruvate disposal or plasma lactate concentrations between the two groups. In subjects with severe COPD, there are alterations in glucose metabolism leading to increased glucose production and faster glucose metabolism by glycolysis and oxidation compared with controls. However, no difference in glucose conversion to lactate via pyruvate reduction is observed. PMID:22016370

Kao, Christina C; Hsu, Jean W-C; Bandi, Venkata; Hanania, Nicola A; Kheradmand, Farrah; Jahoor, Farook

2012-01-01

85

Glucose and pyruvate metabolism in severe chronic obstructive pulmonary disease  

PubMed Central

The mechanisms leading to weight loss in patients with chronic obstructive pulmonary disease (COPD) are poorly understood but may involve alterations in macronutrient metabolism. Changes in muscle oxidative capacity and lactate production during exercise suggest glucose metabolism may be altered in COPD subjects. The objective of this study was to determine differences in the rates of glucose production and clearance, the rate of glycolysis (pyruvate production), and oxidative and nonoxidative pyruvate disposal in subjects with severe COPD compared with healthy controls. The in vivo rates of glucose production and clearance were measured in 14 stable outpatients with severe COPD (seven with low and seven with preserved body mass indexes) and 7 healthy controls using an intravenous infusion of [2H2]glucose. Additionally, pyruvate production and oxidative and non-oxidative pyruvate disposal were measured using intravenous infusions of [13C]bicarbonate and [13C]pyruvate. Endogenous glucose flux and glucose clearance were significantly faster in the combined COPD subjects (P = 0.002 and P < 0.001, respectively). This difference remained significant when COPD subjects were separated by body mass index. Pyruvate flux and oxidation were significantly higher in the combined COPD subjects than controls (P = 0.02 for both), but there was no difference in nonoxidative pyruvate disposal or plasma lactate concentrations between the two groups. In subjects with severe COPD, there are alterations in glucose metabolism leading to increased glucose production and faster glucose metabolism by glycolysis and oxidation compared with controls. However, no difference in glucose conversion to lactate via pyruvate reduction is observed. PMID:22016370

Hsu, Jean W.-C.; Bandi, Venkata; Hanania, Nicola A.; Kheradmand, Farrah; Jahoor, Farook

2012-01-01

86

[Cure of experimental hyperlactatemia and lactic acidosis by sodium dichloroacetate].  

PubMed

Sodium dichloroacetate prevents and fights against the severe hyperlactatemia and lactic acidosis induced by phenformin, intense muscular work, hypoxia and by adrenalin perfusion. The beneficent effects of sodium dichloroacetate and insulin are additive. PMID:828559

Loubatières, A; Ribes, G; Rondot, A M

1976-12-20

87

[Correction of experimental hyperlactatemia and lactic acidosis by sodium dischloroacetate].  

PubMed

Sodium dichloroacetate prevents and fights against the severe hyperlactatemia and lactic acidosis induced by phenformin, intense muscular work, hypoxia and by adrenalin perfusion. The beneficent effects of sodium dichloroacetate and insulin are additive. PMID:826352

Loubatières, A; Ribes, G; Valette, G; Rondot, A M

1976-10-18

88

Metformin-induced lactic acidosis and acute pancreatitis precipitated by diuretic, celecoxib, and candesartan-associated acute kidney dysfunction.  

PubMed

Polypharmacy may lead to synergistic complications from the different medications. We report the case of a 50-year-old woman who was prescribed 11 drugs, including a diuretic, celecoxib, metformin, and candesartan, and who developed acute kidney dysfunction while on these drugs, manifesting as severe proteinuria, acute azotemia, hyperkalemia. The kidney injury caused the accumulation of metformin, leading to lactic acidosis and acute pancreatitis. Sodium bicarbonate hemodialysis not only improved the metabolic abnormalities but also hastened the removal of metformin. PMID:18259965

Audia, Pat; Feinfeld, Donald A; Dubrow, Alan; Winchester, James F

2008-02-01

89

The nephrologist's role in metformin-induced lactic acidosis.  

PubMed

Metformin is an antihyperglycemic agent commonly used in diabetic patients. It is very effective and is able to reduce the plasma glucose and HbA1C. However, in some patients, specially those with comorbidities, metformin can provoke severe lactic acidosis with high morbimortality. Treatment of the lactic acidosis induced by metformin is based on the use of supportive general measures; in severe cases, procedures of extrarrenal purification like hemodialysis or continuous hemodiafiltration have been successfully used. PMID:21959726

Gómez-Navarro, L; de Arriba, G; Sánchez-Heras, M; Pérez del Valle, K M; Hernández-Sevillano, B; Basterrechea, M A; Tallón, S; Torres-Guinea, M; Rodríguez-Palomares, J R

2011-01-01

90

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

PubMed Central

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

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

2014-01-01

91

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

92

Metformin-induced lactic acidosis in a type 2 diabetic patient with acute renal failure.  

PubMed

Metformin is a biguanide commonly used in type 2 diabetes mellitus (DM). Lactic acidosis, a potentially life-threatening metabolic disorder, may be due to a number of different causes, including metformin therapy. We present a case of a severe metformin-induced lactic acidosis in a patient with type 2 DM, admitted to the emergency department with a history of dehydration due to diarrhoea and complicated by acute renal failure. Patient complained malaise and severe weakness and was tachypneic (Kussmaul's respiration), agitated and confused, with a Glasgow Coma Scale score of 13/15. Heart rate was 75 b/min and blood pressure 110/80 mmHg. The pH was 6.87, HCO3- 3 mmol/l, lactate 15 mmol/l, potassium 6.9 mEq/l. The renal function was markedly impaired with a creatinine of 9.75 mg/dl, and pancreatic enzymes, amylase and lipase, were also increased in absence of abdominal pain. Patient was treated with intravenous fluids, bicarbonate infusion and haemodialysis with bicarbonate buffered replacement fluid. Clinical conditions improved rapidly, with a progressive normalization of the acid-base balance and the other laboratory data. Authors discuss the pathophysiologic mechanisms of these alterations with particular regard to the role played by metformin as potential cause of lactic acidosis. PMID:18463766

Di Grande, A; Vancheri, F; Giustolisi, V; Giuffrida, C; Narbone, G; Licata, M; Le Moli, C; Riccobene, S; Burgio, A; Bartolotta, S; Nigro, F; Cannone, V

2008-01-01

93

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

PubMed Central

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

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

2010-01-01

94

Examining the relationship between diet-induced acidosis and cancer  

PubMed Central

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

2012-01-01

95

Acidosis Promotes Bcl-2 Family-mediated Evasion of Apoptosis  

PubMed Central

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

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

2012-01-01

96

[Metformin-associated lactic acidosis in a patient with pre-existing risk factors].  

PubMed

Lactic acidosis is a serious clinical situation associated with a high case fatality rate. Lactic acidosis is particularly found in conditions with an insufficient supply of oxigen in the tissue. Other causes for lactic acidosis can be hepatic or renal insufficiency. For the therapy of overweight patients with type 2 diabetes metformin is the first choice if diet and physical training have been ineffective. Metformin, however, has the potential to increase serumlactate. Therefore its ability to cause lactic acidosis is controversely discussed. We present a 64-year-old female patient with metformin-associated lactic acidosis. She had several pre-existing risk factors to develop a lactic acidosis. On her referral to the hospital she suffered from acute renal failure which is considered to be a contraindication for the use of metformin. PMID:16190374

Becker, C; Luginbühl, A; Pittl, U; Schlienger, R

2005-09-01

97

[Metformin-associated lactic acidosis precipitated by acute renal failure].  

PubMed

In type II diabetes treated with metformin, lactic acidosis is a rare but severe complication. Commonly patients with lactic acidosis show signs of shock, tissue hypoxia, acute hepatic or renal failure and the link between metformin therapy and lactic acidosis may be coincidental, associated or causal. Excessive plasma metformin concentrations show that lactic acidosis is due to a toxicological mechanism. The case of a 65-year-old woman with type II diabetes, in whom severe type B2 lactic acidosis secondary to metformin was precipitated by acute renal failure, is presented. The association of diuretics with non-steroidal anti-inflammatory drugs and colchicine was responsible for a volume depletion and an acute renal failure. Initial serum creatinine was 643 micromol x l(-1) and arterial blood gas analysis revealed a pH of 7.01. Aggressive volume expansion and correction of the acidosis with intravenous bicarbonate therapy failed. At the intensive care unit, calculated anion gap was 35 mmol x l(-1) (normal range 10-18) and lactate concentration was 12.4 mmol x l(-1), liver profile was normal. Prolonged haemodialysis using bicarbonate dialysate resulted in a favourable outcome. Toxicology confirmed retrospectively the presence of a plasma concentration of metformine of 20 mg x l(-1) (normal <2). One month after this episode she has made a recovery of tubular necrosis, although no longer prescribed metformin. Metformin should be temporally stopped when acute renal failure occurs or is anticipated; patient with acute renal failure and high calculated anion gap should benefit from lactate measurements. Early bicarbonate haemodialysis is an adequate treatment of lactic acidosis caused by accumulation of metformin associated with acute renal failure PMID:12831972

Pertek, J P; Vidal, S; Mariot, J; Galy-Floc'h, M; Azoulay, E

2003-05-01

98

Association of metabolic syndrome with severity of coronary artery disease  

PubMed Central

Background: South Asians are more prone to develop metabolic syndrome (MetS). The additive predictive value of components of MetS for cardiovascular diseases is still debated. We undertook this study to evaluate the association of MetS and its components with severity of coronary artery disease (CAD). Materials and Methods: Three hundred patients with known coronary disease above the age of 25 years were included in this study. Blood samples were collected for biochemical markers. Patients were stratified into subjects with and without MetS (International Diabetes Federation, IDF, criteria) and severity of CAD (number of vessel involved). Results: Mean age of the patient in the study was 60.9 ± 12.4 years (male, M: 72%; female, F: 28%). MetS was present in 64% patients. Patients with MetS had more severe CAD compared to those without MetS. Triple vessel disease (TVD) was present in 62.5% of patients with MetS compared to 34.3% among without MetS (P < 0.0001). The percent number of patients with TVD showed increasing trend with increasing number of components of MetS (0-0%; 1-20%; 2-27.5%; 3-47.8%; 4-72.6%; 5-78.3%; Chi square for trend < 0.0001). Inflammatory markers [interleukin (IL) 6: 77.67 ± 79.48 vs. 41.21 ± 60.72 pg/ml, P < 0.0001; tumor nuclear factor (TNF)-?: 28.0 ± 47.49 vs 20.43 ± 24.5 pg/ml, P < 0.0001; high sensitive C-reactive protein (hsCRP): 14.30 ± 9.91 vs. 7.02 ± 7.18 mg/L, P < 0.0001], insulin resistance [homeostatic model analysis insulin resistance (HOMA-IR): 22.33 ± 23.37 vs. 10.86 ± 13.90, P < 0.0001] were higher and insulin sensitivity [quantitative insulin check index (QUICKI): 0.26 ± 0.03 vs. 0.30 ± 0.04, P < 0.0001] was significantly lower in subjects with MetS compared to subjects without MetS. Among lipids, total cholesterol were comparable but triglyceride (175 ± 42 vs. 179 ± 48 vs. 180 ± 47 mg/dl, P < 0.0001) was high and high-density lipoprotein (HDL; 44.72 ± 7.63 vs. 39.96 ± 8.70 vs. 36.05 ± 8.84, P < 0.0001) was low in subjects with TVD compared to others. Similarly, percentage of patients with diabetes (7.5% vs. 26.3% vs. 63.7%, P < 0.0001) and hypertension (34.3% vs. 56.6% vs. 77.7%, P < 0.0001) were higher in subjects with TVD compared to others. Conclusions: There is a strong correlation of MetS and its components with severity of CAD.

Mahalle, Namita; Garg, M. K.; Naik, Sadanand S.; Kulkarni, Mohan V.

2014-01-01

99

Lactic acidosis as a complication of ?-adrenergic aerosols.  

PubMed

Lactic acidosis is a marker of tissue hypoperfusion and impairs oxygen delivery. High lactate levels are associated with altered systemic hemodynamics, tissue hypoperfusion, and altered cellular metabolism. Increased lactate levels have also been reported as a complication of ?-adrenergic agents administered during asthma therapy. A 49-year-old woman with a prior diagnosis of asthma presented to the emergency department in respiratory distress. She immediately received, in 2 hours, 4 bronchodilator aerosols (ipratropium bromide 0.5 mg/2 mL and terbutaline 5 mg/2 mL) and methylprednisolone intravenous (120 mg). After these 4 aerosols, she was still dyspneic. First, arterial blood gases (pH 7.38; PCO2, 3.92 kPa; HCO3, 19.2 mmol/L) and arterial lactate (lactate, 7.96 mmol/L) were performed with a second series of 4 aerosols. Second, arterial blood gases (pH 7.29; PCO2, 4.01 kPa; HCO3, 15.4 mmol/L) and arterial lactate (lactate, 10.47 mmol/L) were performed at the end of the second series of aerosols. There was no hypoxemia, no inadequate cardiac output state, no anemia, no sepsis, and no use of biguanides. Previous studies have suggested that administration of ? agonists can lead to lactic acidemia in the absence of hypoxia or shock, but it is the highest level of lactate that we found in the literature. In sepsis and shock, lactic acidosis is used as a marker of disease severity. In this case, it is not necessarily the sign of an immediate gravity. PMID:21802882

Claret, Pierre-Géraud; Bobbia, Xavier; Boutin, Caroline; Rougier, Marion; de la Coussaye, Jean-Emmanuel

2012-09-01

100

A patient with foot ulcer and severe metabolic alkalosis.  

PubMed

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

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

2012-01-01

101

Metformin overdose, but not lactic acidosis per se, inhibits oxygen consumption in pigs  

PubMed Central

Introduction Hepatic mitochondrial dysfunction may play a critical role in the pathogenesis of metformin-induced lactic acidosis. However, patients with severe metformin intoxication may have a 30 to 60% decrease in their global oxygen consumption, as for generalized inhibition of mitochondrial respiration. We developed a pig model of severe metformin intoxication to validate this clinical finding and assess mitochondrial function in liver and other tissues. Methods Twenty healthy pigs were sedated and mechanically ventilated. Ten were infused with a large dose of metformin (4 to 8 g) and five were not (sham controls). Five others were infused with lactic acid to clarify whether lactic acidosis per se diminishes global oxygen use. Arterial pH, lactatemia, global oxygen consumption (VO2) (metabolic module) and delivery (DO2) (cardiac output by thermodilution) were monitored for nine hours. Oxygen extraction was computed as VO2/DO2. Activities of the main components of the mitochondrial respiratory chain (complex I, II and III, and IV) were measured with spectrophotometry (and expressed relative to citrate synthase activity) in heart, kidney, liver, skeletal muscle and platelets taken at the end of the study. Results Pigs infused with metformin (6 ± 2 g; final serum drug level 77 ± 45 mg/L) progressively developed lactic acidosis (final arterial pH 6.93 ± 0.24 and lactate 18 ± 7 mmol/L, P < 0.001 for both). Their VO2 declined over time (from 115 ± 34 to 71 ± 30 ml/min, P < 0.001) despite grossly preserved DO2 (from 269 ± 68 to 239 ± 51 ml/min, P = 0.58). Oxygen extraction accordingly fell from 43 ± 10 to 30 ± 10% (P = 0.008). None of these changes occurred in either sham controls or pigs infused with lactic acid (final arterial pH 6.86 ± 0.16 and lactate 22 ± 3 mmol/L). Metformin intoxication was associated with inhibition of complex I in the liver (P < 0.001), heart (P < 0.001), kidney (P = 0.003), skeletal muscle (P = 0.012) and platelets (P = 0.053). The activity of complex II and III diminished in the liver (P < 0.001), heart (P < 0.001) and kidney (P < 0.005) while that of complex IV declined in the heart (P < 0.001). Conclusions Metformin intoxication induces lactic acidosis, inhibits global oxygen consumption and causes mitochondrial dysfunction in liver and other tissues. Lactic acidosis per se does not decrease whole-body respiration. PMID:22568883

2012-01-01

102

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

103

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

PubMed

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

Musoke, Philippa M; Fergusson, Pamela

2011-12-01

104

Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism  

Microsoft Academic Search

A 43-year-old woman with drug-related blepharospasm was followed up for 22 months. She had undergone etizolam treatment for 19 years for indefinite complaints. We examined her cerebral glucose metabolism 5 times (between days 149 and 688 since presentation), using positron emission tomography, and identified regions of interest in the thalamus, caudate nucleus, putamen, and primary somatosensory area on both sides.

Hideki Murai; Yukihisa Suzuki; Motohiro Kiyosawa; Masato Wakakura; Manabu Mochizuki; Kiichi Ishiwata; Kenji Ishii

2011-01-01

105

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

106

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

107

[Metformin-induced lactic acidosis due to acute renal failure].  

PubMed

Lactic acidosis is a serious but uncommon side effect of metformin use. We discuss the pathophysiological mechanisms of lactic acidosis with particular regard to the role played by the drug as a potential cause of the entity. We report on a severe case of this kind of drug toxicity in a patient with type 2 diabetes mellitus, admitted to the emergency department with acute renal failure symptoms. The diagnosis was supported by elevated serum levels of the biguanide, a procedure scarcely used in clinical practice. The management of this complication consists in drug discontinuation and hemodialysis with bicarbonate that provides symptomatic and ethiological treatment by removing both the lactate and the hypoglycemic agent from the serum. Since the symptoms of metformin-associated lactic acidosis are unspecific and its onset is subtle, a high level of suspicion is needed to establish an early diagnosis. PMID:21532654

Macías-Robles, M D; Maciá-Bobes, C; Yano-Escudero, R; Fernández-Diéguez, O; Alvarez-Lecue, O

2011-01-01

108

Extracorporeal membrane oxygenation support of a severe metabolic crisis in a child with methylmalonic acidemia.  

PubMed

A 9-year-old female, with mut phenotype of methylmalonic acidemia who developed severe vasoplegic shock during a metabolic crisis, was successfully supported with venoarterial extracorporeal membrane oxygenation. PMID:22711065

Stark, Ryan J; Naik-Mathuria, Bindi J; Lam, Fong W; Olutoye, Oluyinka O; Sutton, V Reid; Shekerdemian, Lara S

2012-01-01

109

Acidosis-Induced Zinc-Dependent Death of Cultured Cerebellar Granule Neurons  

Microsoft Academic Search

Severe acidosis caused death of cultured cerebellar granule neurons (CGNs). Acidosis was accompanied by a progressive increase\\u000a of the intracellular zinc ions ([Zn2+]i) and decrease of [Ca2+]i. Zn2+ chelator, N,N,N?,N?-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), prevented the increase of [Zn2+]i and acidosis-induced neuronal death. However, neuronal death was insensitive to blockade of ASIC1 channels with amiloride,\\u000a as CGNs display considerably lower expression of ASIC1a

Nikolay K. IsaevElena; Elena V. Stelmashook; Sergey V. Lukin; Dorette Freyer; Philipp Mergenthaler; Dmitry B. Zorov

2010-01-01

110

[Lactic acidosis: a complication of spinal cord injury in multiple trauma].  

PubMed

Large-dose methylprednisolone has been advocated to lessen neurologic deficits in spinal cord injury for nearly a decade despite confounding statistical results in the Second National Acute Spinal Cord Injury Study (NASCIS-2). Recent retrospective studies found lack of significant functional improvement, increases in the incidence of infectious complications and an increase in ventilated and intensive care days in steroid-treated groups. We report on five cases with severe hyperglycemia and nonketotic metabolic acidosis in otherwise non-diabetic patients with multiple blunt injuries and an associated spinal cord injury. Those adverse effects were induced by epinephrine and aggravated by methylprednisolone. We conclude that high-dose methylprednisolone should be avoided in multiple injured or otherwise compromised patients potentially needing catecholamine support. PMID:10925653

Hasse, W; Weidtmann, A; Voeltz, P

2000-06-01

111

Alcohol Consumption in the Severely Obese: Relationship with the Metabolic Syndrome  

Microsoft Academic Search

Objective: The aim of this study was to examine the association between the clinical and biochemical features of the metabolic syndrome and quantity and type of alcohol intake in the severely obese.Research Methods and Procedures: A cross-sectional study was performed in 486 consecutive severely obese subjects. Data on alcohol consumption was collected by serial clinical interviews and a questionnaire. The

John B. Dixon; Maureen E. Dixon; Paul E. O’Brien

2002-01-01

112

Acidosis, hypoxia and stress hormone release in response to one-minute inhalation of 80% CO2 in swine.  

PubMed

The study pertains to a series of investigations on the effects of CO2 inhalation as used for pre-slaughter anaesthesia in swine. Acid/base parameters, blood oxygen tension, plasma Na, K, Ca and stress hormone concentrations were monitored in Yorkshire swine before, during, and for 10 min after the animals were descended for 1 min into 80% CO2 in air. Severe respiratory acidosis (PaCO2 approximately 50 kPa, arterial pH approximately 6.6) and hypoxia (PaO2 approximately 4kPa) had developed after 45 s of the CO2 inhalation. The corresponding changes in venous blood were less drastic (PvCO2 approximately 17 kPa, pH 7.1, PvO2 approximately 4 kPa). Readjustment to PaCO2 approximately II kPa, arterial pH 7.2, and PaO2 approximately 13 kPa had occurred at 1 min post CO2. Four minutes later the respiratory acidosis had become converted into metabolic acidosis subjected to partial respiratory compensation (arterial pH 7.3 in the presence of moderate hypocapnia and hyperoxaemia). The cause of this metabolic acidosis (present also at 10 min post CO2) was apparently hypoxia-induced anaerobic metabolism (= lactic acid production). Apparently due to hydrogen ion transport into the cells in exchange for other cations, hyperkalaemia (K approximately 6.6 mmol l-1), and a 7 mmol l-1 increase in plasma Na had developed at 1.5 min later. The CO2 inhalation did not change the total plasma Ca significantly. The transport of the swine from the stable to the immediate pre-experimental situation induced a 3-fold increase in plasma cortisol concentration (PC, to approximately 130 mmol l-1). No further increase in PC occurred in response to the CO2 inhalation. It indicates that no additional emotional strain was imposed upon the animals during the CO2 exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3147571

Forslid, A; Augustinsson, O

1988-02-01

113

Malonyl coenzyme A decarboxylase deficiency. Clinical and biochemical findings in a second child with a more severe enzyme defect  

Microsoft Academic Search

A second child with a more severe deficiency of malonyl CoA decarboxylase is described. He is mildly mentally retarded and presented with vomiting, a seizure, hypoglycaemia and mild metabolic acidosis during a urinary tract infection. The urine contained increased, amounts of malonic, methylmalonic, succinic, adipic, glutaric and suberic acids. Mitochondrial malonyl CoA decarboxylase activity in cultured fibrobast extracts was 4%

E. A. Haan; R. D. Scholem; H. B. Croll; G. K. Brown

1986-01-01

114

Anesthetic management of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) during laparotomy  

Microsoft Academic Search

A 53-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) underwent\\u000a a gastrectomy. We administered bicarbonated Ringer's solution, which has a physiological concentration of bicarbonate. The\\u000a level of serum lactate did not increase significantly, and metabolic acidosis did not occur throughout surgery or for 3?h\\u000a after surgery. Aggressive warming was needed to maintain normothermia, presumably because the

Nobuko Sasano; Yoshihito Fujita; MinHye So; Kazuya Sobue; Hiroshi Sasano; Hirotada Katsuya

2007-01-01

115

New Metabolic Phenotypes in Laminopathies: LMNA Mutations in Patients with Severe Metabolic Syndrome  

Microsoft Academic Search

Context: Mutations in the LMNA gene are responsible for several laminopathies, including lipodystrophies, with complex genotype\\/ phenotype relationships. Objective, Design, Setting, and Patients: Sequencing of the LMNA coding regions in 277 unrelated adults investigated for lipodystrophy and\\/or insulin resistance revealed 17 patients with substitutions at codon 482 observed in typical Dunnigan's familial partial lipodystrophy and 10 patients with other mutations.

Aurelie Decaudain; Marie-Christine Vantyghem; Bruno Guerci; Annie-Claude Hecart; Martine Auclair; Yves Reznik; Pierre-Henri Ducluzeau; Bruno Donadille; Celeste Lebbe; Veronique Bereziat; Jacqueline Capeau; Olivier Lascols; Corinne Vigouroux

2010-01-01

116

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

PubMed

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

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

2013-01-01

117

Inhaled ?-agonist therapy and respiratory muscle fatigue as under-recognised causes of lactic acidosis.  

PubMed

A 49-year-old man with chronic obstructive pulmonary disease (COPD) presented with significant tachypnoea, fevers, productive cough and increased work of breathing for the previous 4 days. Laboratory data showed elevated lactate of 3.2 mEq/L. Continuous inhaled ipratropium and albuterol nebuliser treatments were administered. Lactate levels increased to 5.5 and 3.9 mEq/L, at 6 and 12 h, respectively. No infectious source was found and the lactic acidosis cleared as the patient improved. The lactic acidosis was determined to be secondary to respiratory muscle fatigue and inhaled ?-agonist therapy, two under-recognised causes of lactic acidosis in patients presenting with respiratory distress. Lactic acidosis is commonly used as a clinical marker for sepsis and shock, but in the absence of tissue hypoperfusion and severe hypoxia, alternative aetiologies for elevated levels should be sought to avoid unnecessary and potentially harmful medical interventions. PMID:24127377

Lau, Emily; Mazer, Jeffrey; Carino, Gerardo

2013-01-01

118

Effects of hyperbaric oxygenation therapy on cerebral metabolism and intracranial pressure in severely brain injured patients  

Microsoft Academic Search

OBJECT: Hyperbaric oxygenation (HBO) therapy has been shown to reduce mortality by 50% in a prospective randomized trial of severely brain injured patients conducted at the authors' institution. The purpose of the present study was to determine the effects of HBO on cerebral blood flow (CBF), cerebral metabolism, and intracranial pressure (ICP), and to determine the optimal HBO treatment paradigm.

Sarah B. Rockswold; Gaylan L. Rockswold; Janet M. Vargo; Carla A. Erickson; Richard L. Sutton; Thomas A. Bergman; Michelle H. Biros

2001-01-01

119

Rumen microbiome composition determined using two nutritional models of subacute ruminal acidosis.  

PubMed

Subacute ruminal acidosis (SARA) is a metabolic disease in dairy cattle that occurs during early and mid-lactation and has traditionally been characterized by low rumen pH, but lactic acid does not accumulate as in acute lactic acid acidosis. It is hypothesized that factors such as increased gut permeability, bacterial lipopolysaccharides, and inflammatory responses may have a role in the etiology of SARA. However, little is known about the nature of the rumen microbiome during SARA. In this study, we analyzed the microbiome of 64 rumen samples taken from eight lactating Holstein dairy cattle using terminal restriction fragment length polymorphisms (TRFLP) of 16S rRNA genes and real-time PCR. We used rumen samples from two published experiments in which SARA had been induced with either grain or alfalfa pellets. The results of TRFLP analysis indicated that the most predominant shift during SARA was a decline in gram-negative Bacteroidetes organisms. However, the proportion of Bacteroidetes organisms was greater in alfalfa pellet-induced SARA than in mild or severe grain-induced SARA (35.4% versus 26.0% and 16.6%, respectively). This shift was also evident from the real-time PCR data for Prevotella albensis, Prevotella brevis, and Prevotella ruminicola, which are members of the Bacteroidetes. The real-time PCR data also indicated that severe grain-induced SARA was dominated by Streptococcus bovis and Escherichia coli, whereas mild grain-induced SARA was dominated by Megasphaera elsdenii and alfalfa pellet-induced SARA was dominated by P. albensis. Using discriminant analysis, the severity of SARA and degree of inflammation were highly correlated with the abundance of E. coli and not with lipopolysaccharide in the rumen. We thus suspect that E. coli may be a contributing factor in disease onset. PMID:19783747

Khafipour, Ehsan; Li, Shucong; Plaizier, Jan C; Krause, Denis O

2009-11-01

120

Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children.  

PubMed

Investigation of 31 of Roma patients with congenital lactic acidosis (CLA) from Bulgaria identified homozygosity for the R446* mutation in the PDHX gene as the most common cause of the disorder in this ethnic group. It accounted for around 60% of patients in the study and over 25% of all CLA cases referred to the National Genetic Laboratory in Bulgaria. The detection of a homozygous patient from Hungary and carriers among population controls from Romania and Slovakia suggests a wide spread of the mutation in the European Roma population. The clinical phenotype of the twenty R446* homozygotes was relatively homogeneous, with lactic acidosis crisis in the first days or months of life as the most common initial presentation (15/20 patients) and delayed psychomotor development and/or seizures in infancy as the leading manifestations in a smaller group (5/20 patients). The subsequent clinical picture was dominated by impaired physical growth and a very consistent pattern of static cerebral palsy-like encephalopathy with spasticity and severe to profound mental retardation seen in over 80% of cases. Most patients had a positive family history. We propose testing for the R446* mutation in PDHX as a rapid first screening in Roma infants with metabolic acidosis. It will facilitate and accelerate diagnosis in a large proportion of cases, allow early rehabilitation to alleviate the chronic clinical course, and prevent further affected births in high-risk families. PMID:25087164

Ivanov, Ivan S; Azmanov, Dimitar N; Ivanova, Mariya B; Chamova, Teodora; Pacheva, Ilyana H; Panova, Margarita V; Song, Sharon; Morar, Bharti; Yordanova, Ralitsa V; Galabova, Fani K; Sotkova, Iglika G; Linev, Alexandar J; Bitchev, Stoyan; Shearwood, Anne-Marie J; Kancheva, Dalia; Gabrikova, Dana; Karcagi, Veronika; Guergueltcheva, Velina; Geneva, Ina E; Bozhinova, Veneta; Stoyanova, Vili K; Kremensky, Ivo; Jordanova, Albena; Savov, Aleksey; Horvath, Rita; Brown, Matthew A; Tournev, Ivailo; Filipovska, Aleksandra; Kalaydjieva, Luba

2014-01-01

121

Metabolic Implications of Severe Burn Injuries and Their Management: A Systematic Review of the Literature  

Microsoft Academic Search

Background  Severe burn patients are some of the most challenging critically ill patients, with an extreme state of physiologic stress\\u000a and an overwhelming systemic metabolic response. A major component of severe burn injury is a hypermetabolic state associated\\u000a with protein losses and a significant reduction of lean body mass. The second prominent component is hyperglycemia. Reversal\\u000a of the hypermetabolic response by

Bishara S. Atiyeh; S. William A. Gunn; Saad A. Dibo

2008-01-01

122

The brain in extreme respiratory acidosis  

Microsoft Academic Search

It is presently debated how much cellular acidosis contributes to brain cell damage during ischemia and hypoxia. To study the influence of acidosis occurring in the absence of energy failure, extreme hypercapnia was produced in anesthetized, artificially ventilated, and well oxygenated rats by increasing the inspired CO2 concentration until arterialPCO2 reached 150 or 300 mm Hg. At these CO2 tensions

L. Paljärvi; B. Söderfeldt; H. Kalimo; Y. Olsson; B. K. Siesjö

1982-01-01

123

Occult metformin toxicity in three patients with profound lactic acidosis.  

PubMed

There are 20.8 million Americans with diabetes, and metformin is the most commonly prescribed oral diabetes agent. A review of our metformin experience highlights common pitfalls that lead to life-threatening or fatal poisonings. We describe 3 patients with metformin toxicity; 2 of 3 patients were prescribed metformin despite end-stage renal disease (ESRD). Case 1: a 40-year-old woman presented after a polysubstance overdose. Within 8 h, vomiting and lethargy developed; a profound acidosis, pH 6.95, pCO(2) 26, pO(2) 195, and elevated serum lactate 21 mmol/L (ref 0.5-1.6 mmol/L) were noted. Further inquiry revealed that the patient had ingested metformin. She was intubated; bicarbonate therapy and hemodialysis were initiated; however, she became hypotensive and died. A metformin level was 150 ?g/mL (therapeutic 1-2 ?g/mL). Case 2: a 69-year-old woman with non-insulin-dependent diabetes mellitus (NIDDM) and ESRD presented to the Emergency Department (ED), having missed dialysis. She was sluggish and complained of abdominal pain; an acidosis, pH 7.37, pCO(2) 20, pO(2) 171; anion gap 38, and elevated serum lactate 18.9 mmol/L were noted. Hemodialysis was initiated when it was revealed that she took metformin daily. She improved rapidly and a metformin level was 27.4 ?g/mL. Case 3: a 57-year-old woman with a history of NIDDM and ESRD presented with dyspnea. Laboratory studies showed pH 7.03, pCO(2) 21, pO(2) 99; anion gap 36, and lactate 16 mmol/L. Bicarbonate therapy and hemodialysis were initiated after discovering that she had recently been prescribed metformin. She had a fatal cardiac arrest after dialysis was completed. We describe 3 ED patients with occult metformin toxicity diagnosed after laboratory results showed an anion gap metabolic acidosis and elevated lactate levels. All patients had lethargy, vomiting, or abdominal pain, also suggesting sepsis or mesenteric infarction. Despite sodium bicarbonate therapy and hemodialysis, metformin-associated lactic acidosis was fatal in 2 of 3 patients. Emergency Physicians must be vigilant to recognize metformin toxicity in patients at high risk for metformin-associated lactic acidosis. PMID:18571361

Perrone, Jeanmarie; Phillips, Carolyn; Gaieski, David

2011-03-01

124

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

125

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

PubMed

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

Fitzgibbons, L J; Snoey, E R

1999-01-01

126

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

127

Optogenetic Countering of Glial Acidosis Suppresses Glial Glutamate Release  

E-print Network

Neuron Report Optogenetic Countering of Glial Acidosis Suppresses Glial Glutamate Release upon ischemia: acidosis and liberation of excess glutamate, which leads to excitotoxicity. However, cellular source of glutamate and its release mecha- nism upon ischemia remained unknown. Here we show

Newman, Eric A.

128

Modifications in cerebral lipid metabolism by severe glucose deprivation during aging.  

PubMed

Severe glucose deprivation causes extensive derangement of phospholipids, fatty acids and free fatty acids in cerebral cortex of rats of different ages. The hypoglycemia-induced cerebral loss of phospholipids and fatty acids persists after 60 min recovery. Changes in individual classes of lipids are largely affected by aging. In fact, during glucose deprivation and recovery, in adult animals no preferential loss of polyunsaturated fatty acids and ethanolamine phosphoglycerides occurs, suggesting that the loss could be related to oxidative rather than to peroxidative degradation. On the contrary, in senescent rats the quoted events occur, suggesting the hypothesis of a possible peroxidation of cerebral lipids. Pretreatment with some agents is performed to elucidate the aging mode of action. Papaverine (acting on macrocirculation) is uneffective, while raubasine (acting on microcirculation and metabolism) and almitrine (acting on oxygen availability) interfere with the phospholipid and fatty acid metabolism, their action being different according to the rat age. PMID:3683727

Benzi, G; Pastoris, O; Tentoni, S; Villa, R F

1987-01-01

129

Traditional anthropometric parameters still predict metabolic disorders in women with severe obesity.  

PubMed

It is well established that fat distribution rather than the total quantity of fat is the major determinant of cardiovascular risk in overweight subjects. However, it is not known whether the concept of fat distribution still makes sense in severely obese subjects. Particularly, the role of visceral fat accumulation and/or of adipocyte hypertrophy in insulin resistance (IR) has not been studied in this population. Therefore, the aim of this study was to clarify the determinants of metabolic disorders in severely obese women. We performed a cross-sectional study in 237 severely obese women (BMI >35 kg/m(2)). We assessed total body fat mass and fat distribution by anthropometric measurements (BMI and waist-to-hip ratio (WHR)) and by dual-energy X-ray absorptiometry (DXA). In 22 women, we measured subcutaneous and visceral adipocyte size on surgical biopsies. Mean BMI was 44 +/- 7 kg/m(2) (range 35-77), mean age 37 +/- 11 years (range 18-61). Lipid parameters (triglycerides, high-density lipoprotein cholesterol) and IR markers (fasting insulin and homeostasis model assessment (HOMA) index) correlated with fat distribution, whereas inflammatory parameters (C-reactive protein, fibrinogen) correlated only with total fat mass. An association was observed between android fat distribution and adipocyte hypertrophy. Visceral adipocyte hypertrophy was associated with both IR and hypertension, whereas subcutaneous fat-cell size was linked only to hypertension. Our results obtained in a large cohort of women showed that fat distribution still predicts metabolic abnormalities in severe obesity. Furthermore, we found a cluster of associations among fat distribution, metabolic syndrome (MS), and adipocyte hypertrophy. PMID:19851304

Ledoux, Séverine; Coupaye, Muriel; Essig, Marie; Msika, Simon; Roy, Carine; Queguiner, Isabelle; Clerici, Christine; Larger, Etienne

2010-05-01

130

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

PubMed Central

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

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

2013-01-01

131

Feeling blue with metformin-associated lactic acidosis.  

PubMed

An active 66-year-old diabetic woman presented with a 5-day history of vomiting and abdominal pain, refractory shock and acute kidney injury (AKI). There was concomitant ACE inhibitor (ACEi) use and metformin toxicity with severe lactic acidosis. She suffered a pulseless electrical activity (PEA) cardiac arrest within 30 min of arrival to the Medical Admissions Unit. Despite a serum pH of 6.57 she was successfully resuscitated. She remained haemodynamically unstable even with fluid resuscitation, inotropic support and haemodiafiltration, yet made a full and rapid recovery following the introduction of a methylene blue infusion. PMID:23456165

Plumb, Benjamin; Parker, Alex; Wong, Paul

2013-01-01

132

Interactions between sleep, circadian function, and glucose metabolism: implications for risk and severity of diabetes.  

PubMed

Sleep disturbances, including sleep insufficiency and sleep fragmentation, have been linked to abnormal glucose metabolism and increased diabetes risk. Well-controlled laboratory studies have provided insights regarding the underlying mechanisms. Several large prospective studies suggest that these sleep disturbances are associated with an increased risk of incident diabetes. Obstructive sleep apnea, which combines sleep fragmentation and hypoxemia, is a major risk factor for insulin resistance and possibly diabetes. Whether glycemic control in type 2 diabetes patients can be improved by treating sleep apnea remains controversial. Recently, sleep disturbances during pregnancy and their relationship to gestational diabetes and hyperglycemia have received considerable attention owing to potential adverse effects on maternal and fetal health. Additionally, evidence from animal models has identified disruption of the circadian system as a putative risk factor for adverse metabolic outcomes. The purpose of this review is to provide an update on the current state of knowledge linking sleep disturbances, circadian dysfunction, and glucose metabolism. Experimental, prospective, and interventional studies are discussed. PMID:24628249

Reutrakul, Sirimon; Van Cauter, Eve

2014-04-01

133

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

134

Enkephalins and hormonal-metabolic reactions in experimental stress depending on its severity  

SciTech Connect

The aim of this investigation was to study the action of enkephalins on changes in hormonal-metabolic constants in stress of varied severity. Catecholamine excretion with the urine was determined fluorometrically, serum cortisol and insulin concentrations were measured radioimmunologically and glucose was determined by the standard orthotoluidine method. The results of the investigation indicate that enkephalins have a modulating effect on various hormonal mechanisms of adaptation stress. The results confirm that the physiological action of the peptide regulator depends on the functional state of the biological systems and it may differ sharply, even to the extent of diametrically opposite effects.

Lishmanov, Y.B.; Alekminskaya, L.A.; Lasukova, T.V.

1985-08-01

135

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

Microsoft Academic Search

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

Leslie J. Fitzgibbons; Eric R. Snoey

1999-01-01

136

[Metformin-associated lactic acidosis remains a serious complication of metformin therapy].  

PubMed

We report 4 cases of lactic acidosis in diabetic patients usually treated with metformin. For the first 3 patients, the clinical history was similar because lactic acidosis was precipitated by gastro-intestinal disorders whereas all of them were simultaneously treated with several nephrotoxic drugs. These 3 patients presented with acute renal failure on arrival at hospital. Their issue was fatal whereas any obvious cause of overproduction of lactate was found. The fourth case, which was due to a voluntary intoxication, was the only one presenting with a favourable evolution. The metformin plasma and red blood cell levels were performed for 2 of 4 patients and confirmed the overdose. These observations remind that metformin-associated lactic acidosis remains a serious complication, and that medical doctors must respect strictly contra-indications and guidelines for withdrawing metformin. PMID:12831973

Orban, J C; Giunti, C; Levraut, J; Grimaud, D; Ichai, C

2003-05-01

137

Bench-to-bedside review: Hypercapnic acidosis in lung injury - from 'permissive' to 'therapeutic'  

Microsoft Academic Search

ABSTRACT: Modern ventilation strategies for patients with acute lung injury and acute respiratory distress syndrome frequently result in hypercapnic acidosis (HCA), which is regarded as an acceptable side effect ('permissive hypercapnia'). Multiple experimental studies have demonstrated advantageous effects of HCA in several lung injury models. To date, however, human trials studying the effect of carbon dioxide per se on outcome

Marloes M Ijland; Leo M Heunks; Johannes G van der Hoeven

2010-01-01

138

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

139

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

PubMed Central

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

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

2013-01-01

140

[Lactic acidosis and acute abdomen from biguanide intoxication].  

PubMed

Metformin, an anti-hyperglycaemic drug, reduces mortality in obese patients with a non-insulin-dependent diabetes mellitus type II (United Kingdom Prospective Diabetes Study) and is therefore recommended as the first line therapy. A metformin-associated lactic acidosis due to accumulation or intoxication is a rare but severe complication with a mortality rate of up to 50%. The main clinical symptoms are unspecific and the patient may present with acute abdominal pain and reduced consciousness. This can easily be misinterpreted and may lead to a wrong diagnosis. Only a thorough clinical examination and exact analysis of laboratory values in combination with the medical history and chronic medication will allow a correct diagnosis. We report a case of a 79-year-old female patient whose clinical symptoms were initially interpreted as an acute intestinal ischemia. A progressively deteriorating haemodynamic state led to an exploratory laparotomy. Postoperatively, the correct diagnosis of a metformin-associated lactic acidosis due to acute renal failure was made. In the course of the ICU stay the condition improved after bicarbonate haemodialysis and the patient was discharged 11 days after admission. PMID:14991192

Moerer, O; Barwing, J; Neumann, P

2004-02-01

141

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

142

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

PubMed

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

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

1993-08-01

143

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

144

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

145

Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets  

Microsoft Academic Search

To clarify species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) we measured the activity of four DEHP-metabolizing enzymes (lipase, UDP-glucuronyltransferase (UGT), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH)) in several organs (the liver, lungs, kidneys, and small intestine) of mice (CD-1), rats (Sprague–Dawley), and marmosets (Callithrix jacchus). Lipase activity, measured by the rate of formation of mono(2-ethylhexyl) phthalate (MEHP)

Yuki Ito; Hiroshi Yokota; Ruisheng Wang; Osamu Yamanoshita; Gaku Ichihara; Hailan Wang; Yoshimasa Kurata; Kenji Takagi; Tamie Nakajima

2005-01-01

146

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

147

Fanconi's syndrome and distal (type 1) renal tubular acidosis in a patient with primary Sjögren's syndrome with monoclonal gammopathy of undetermined significance.  

PubMed

Tubulointerstitial nephritis is a well-recognized complication in primary Sjögrens syndrome. Fanconi's syndrome is a far less frequent complication compared with distal tubular dysfunction. We here describe a 49-year-old woman with primary Sjögren's syndrome. In 1997, she was diagnosed with primary Sjögren's syndrome with tubulointerstitial nephritis, and was then treated with oral prednisolone for the tubulointerstitial nephritis. In 2002, she was referred to our hospital because of progressive fatigue. At that time, biclonal spike on serum protein (IgG-kappa and IgA-kappa) and Bence-Jones protein in urine were found. Bone marrow aspiration showed 1.0% plasma cell infiltration. Thus, a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) was made. In 2004, she was again admitted to our hospital because of mild renal dysfunction and hypokalemia. Laboratory evaluation showed inappropriate, alkaline urine in hyperchloremic metabolic acidosis and a positive urine anion gap, indicating the presence of distal (Type 1) renal tubular acidosis (RTA). The urine concentration defect was also found. Further studies revealed proximal tubular dysfunction, including renal glycosuria, generalized aminoaciduria, phosphaturia, uricosuria and proximal RTA. The kidney biopsy represented diffuse and severe tubulointerstitial nephritis with dense infiltrates of lymphocytes and IgA and K light chain-positive plasma cells. No findings of multiple myeloma or malignant lymphoma were observed. In conclusion, our patient had Sjögren's syndrome with MGUS and exhibited dysfunction of both proximal tubule (Fanconi's syndrome) and distal tubule, which may be attributed to diffuse tubulointerstitial nephritis. PMID:16792139

Kobayashi, T; Muto, S; Nemoto, J; Miyata, Y; Ishiharajima, S; Hironaka, M; Asano, Y; Kusano, E

2006-06-01

148

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

149

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

150

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

PubMed

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

Soliz, Jose; Lim, Jeffrey; Zheng, Gang

2014-01-01

151

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

PubMed Central

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

Lim, Jeffrey

2014-01-01

152

Acute toxicity of methyl isocyanate in mammals. II. Induction of hyperglycemia, lactic acidosis, uraemia, and hypothermia in rats  

Microsoft Academic Search

When rats were administered methyl isocyanate (MIC) by inhalation or subcutaneous route it produced severe hyperglycemia, clinical lactic acidosis, highly elevated plasma urea, and reduced plasma cholinesterase activity with unaltered erythrocytc acetyl cholinesterase activity. Irrespective of the route of administration, MIC also caused severe hypothermia, which was not ameliorated by prior administration of atropine sulphate. Acute toxic effects of MIC

K. Jeevaratnam; R. Vijayaraghavan; M. P. Kaushik; C. S. Vaidyanathant

1990-01-01

153

Functional metabolomics uncovers metabolic alterations associated to severe oxidative stress in MCF7 breast cancer cells exposed to ascididemin.  

PubMed

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

154

Severe dietary lysine restriction affects growth and body composition and hepatic gene expression for nitrogen metabolism in growing rats.  

PubMed

Dietary lysine restriction may differentially affect body growth and lipid and nitrogen metabolism, depending on the degree of lysine restriction. This study was conducted to examine the effect of dietary lysine restriction on growth and lipid and nitrogen metabolism with two different degree of lysine restriction. Isocaloric amino acid-defined diets containing 1.4% lysine (adequate), 0.70% lysine (50% moderate lysine restriction) and 0.35% lysine (75% severe lysine restriction) were fed from the age of 52 to 77 days for 25 days in male Sprague-Dawley rats. The 75% severe lysine restriction increased (p < 0.05) food intake, but retarded (p < 0.05) growth, increased (p < 0.05) liver and muscle lipid contents and abdominal fat accumulation, increased (p < 0.05) blood urea nitrogen levels and mRNA levels of the serine-synthesizing 3-phosphoglycerate dehydrogenase gene, but decreased (p < 0.05) urea cycle arginase gene mRNA levels. In contrast, the 50% lysine restriction did not significantly (p > 0.05) affect body growth and lipid and nitrogen metabolism. Our results demonstrate that severe 75% lysine restriction has detrimental effects on body growth and deregulate lipid and nitrogen metabolism. PMID:23441935

Kim, J; Lee, K S; Kwon, D-H; Bong, J J; Jeong, J Y; Nam, Y S; Lee, M S; Liu, X; Baik, M

2014-02-01

155

Effect of increasing metabolic syndrome score on atherosclerotic risk profile and coronary artery disease angiographic severity  

Microsoft Academic Search

The metabolic syndrome (MS) is a frequent cause of coronary artery disease (CAD), and recently the National Cholesterol Education Program Adult Treatment Panel III suggested its diagnosis in the presence of 3 to 5 quantitatively defined markers. Because the consequences of the MS are likely related to the number and diversity of markers, we studied the relation between the number

B. Charles Solymoss; Martial G Bourassa; Lucien Campeau; Allan Sniderman; Michel Marcil; Jacques Lespérance; Sylvie Lévesque; Susan Varga

2004-01-01

156

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

PubMed Central

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

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

2002-01-01

157

Stunned myocardium after rapid correction of acidosis. Increased oxygen cost of contractility and the role of the Na(+)-H+ exchange system.  

PubMed

Left ventricular (LV) contractile dysfunction during acidosis has been reported to be almost reversible in crystalloid-perfused hearts after correction of acidosis. In contrast, we have found that, in blood-perfused hearts, contractile function is paradoxically depressed after correction of acidosis with a transient overshoot of contractility during the recovery of pH. To clarify the mechanism of this phenomenon, we measured the LV contractility index (Emax) and the relation between myocardial oxygen consumption (VO2) and systolic pressure-volume area (PVA, a measure of the LV total mechanical energy) before and after induction and rapid correction of acidosis by CO2 loading (pH 7.00) and unloading in 13 excised cross-circulated canine hearts. During the rapid correction of acidosis in six control hearts, a severe transient overshoot of Emax (404% of acidosis) occurred. However, after correction of acidosis, Emax and PVA were lower than the preacidosis values by 46% (P < .01) and 44% (P < .01) at the same LV volume. When the preacidosis Emax level was restored by Ca2+ infusion, the VO2 intercept (PVA-independent VO2) of the linear VO2-PVA relation exceeded the control value by 18% (P < .05) with an unchanged slope. In addition, the oxygen cost of contractility, defined as the slope of the relation between PVA-independent VO2 and Emax, increased by 83% (P < .01) after correction of acidosis, indicating that postacidosis myocardium requires higher VO2 for nonmechanical activities for a unit increase in Emax. Then, we hypothesized that these mechanoenergetic disorders after rapid correction of acidosis would result from Ca2+ overload via accelerated Na(+)-Ca2+ exchange due to the heavily operating Na(+)-H+ exchange system at the time of rapid pH recovery. To examine this hypothesis, dimethylamiloride, a selective Na(+)-H+ exchange inhibitor, was administered just before the correction of acidosis in the other seven hearts. The administration of dimethylamiloride completely prevented both the mechanical and energetic disorders after correction of acidosis. We conclude that rapid recovery of pH paradoxically depresses myocardial contractility and increases the oxygen cost of contractility through an activation of the Na(+)-H+ exchange system. PMID:8156628

Hata, K; Takasago, T; Saeki, A; Nishioka, T; Goto, Y

1994-05-01

158

Lipoatrophy and severe metabolic disturbance in mice with fat-specific deletion of PPAR?.  

PubMed

Adipose tissue is an important metabolic organ, the dysfunction of which is associated with the development of obesity, diabetes mellitus, and cardiovascular disease. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR?) is considered the master regulator of adipocyte differentiation and function. Although its cell-autonomous role in adipogenesis has been clearly demonstrated in cell culture, previous fat-specific knockouts of the murine PPAR? gene did not demonstrate a dramatic phenotype in vivo. Here, using Adipoq-Cre mice to drive adipose-specific recombination, we report a unique fat-specific PPAR? knockout (PPAR? FKO) mouse model with almost no visible brown and white adipose tissue at age 3 mo. As a consequence, PPAR? FKO mice had hugely enlarged pancreatic islets, massive fatty livers, and dramatically elevated levels of blood glucose and serum insulin accompanied by extreme insulin resistance. PPAR? FKO mice also exhibited delayed hair coat formation associated with absence of dermal fat, disrupted mammary gland development with loss of mammary fat pads, and high bone mass with loss of bone marrow fat, indicating the critical roles of adipose PPAR? in these tissues. Together, our data reveal the necessity of fat PPAR? in adipose formation, whole-body metabolic homeostasis, and normal development of fat-containing tissues. PMID:24167256

Wang, Fenfen; Mullican, Shannon E; DiSpirito, Joanna R; Peed, Lindsey C; Lazar, Mitchell A

2013-11-12

159

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 ...

160

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

161

Alveolar macrophage function in rats with severe protein calorie malnutrition. Arachidonic acid metabolism, cytokine release, and antimicrobial activity.  

PubMed

To investigate the effects of protein calorie malnutrition (PCM) on alveolar macrophage function, we measured antimicrobial activity, IL-1 and TNF production, and arachidonic acid metabolism in alveolar macrophages of infant rats with moderate and severe PCM. Groups of weanling male rats were fed a diet containing 0.8% protein (PCM) or 24% protein (control). A third group (pair fed) was fed limited amounts of the control diet that matched the mean daily dietary intake of the PCM group. After 4 wk on the diets, alveolar macrophages from all three groups functioned similarly with respect to surface adherence, phagocytosis and killing of Listeria monocytogenes, release of hydrogen peroxide and superoxide anion, and production of IL-1 and TNF. In contrast, Listeria-stimulated alveolar macrophages from the PCM group exhibited a marked shift in arachidonic acid metabolism, with impaired production of leukotriene B4 and enhanced release of thromboxane B2 and PGE2. The membrane arachidonic acid content and the uptake of [3H]arachidonate by alveolar macrophages did not differ among the three groups. The shift toward the cyclooxygenase pathway was not seen after 2 wk of dietary restriction and was reversed if PCM animals were fed the control diet for 1 wk. Thus, PCM does not affect the antimicrobial activity or cytokine production of alveolar macrophages, but causes alterations in arachidonic acid metabolism that may interfere with the modulatory functions of alveolar macrophages. PMID:2104909

Skerrett, S J; Henderson, W R; Martin, T R

1990-02-01

162

Putrescine Catabolism is a Metabolic Response to Several Stresses in Escherichia coli  

PubMed Central

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

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

2013-01-01

163

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

Microsoft Academic Search

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

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

2004-01-01

164

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

Microsoft Academic Search

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

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

2009-01-01

165

Early lactic acidosis associated with linezolid therapy in paediatric patients.  

PubMed

Linezolid, an oxazolidinone class antibiotic, is used to treat Gram-positive infections, including those due to meticillin-resistant staphylococci and vancomycin-resistant enterococci. In paediatric clinical trials, the frequency of possible linezolid-related adverse events ranged from 18.8% to 25.6%. The most commonly reported side effects are gastrointestinal disturbances, headache, rash and liver function alterations. Lactic acidosis has been reported as a side effect of linezolid treatment, and limited data suggest it may be more common in children. We report on our experience of treating 50 children aged 1 month to years with linezolid. Eight patients (16%) developed lactic acidosis and another eight (16%) had lactic acidaemia without acidosis. Onset of lactic acidaemia (median 1.5 days; range 1-72 days) and lactic acidosis (median 2 days; range 1-13 days) tended to be early. Being an ICU patient and requiring mechanical ventilation significantly increased the risk of lactic acidaemia or acidosis (OR=22.75, 95% CI 4.24-122.09; OR=32.67, 95% CI 5.83-183.19, respectively; P<0.001). All 16 patients were able to continue linezolid treatment. Linezolid therapy was effective (microbiologic and/or clinical cure) in 39 patients (78%). Nine patients died whilst receiving linezolid treatment; the deaths were not considered to be a result of linezolid treatment failure. Two patients who did not respond clinically to linezolid recovered after their treatment was changed to vancomycin. Linezolid use in children appears to be as safe and effective as in adults. However, lactic acidosis appears to be more common, and occur earlier, in children. PMID:25182713

Ozkaya-Parlakay, Aslinur; Kara, Ates; Celik, Melda; Ozsurekci, Yasemin; Karadag Oncel, Eda; Ceyhan, Mehmet; Cengiz, Ali Bulent

2014-10-01

166

Metformin-associated lactic acidosis precipitated by acute renal failure.  

PubMed

Metformin-associated lactic acidosis (MALA) is a rare but serious clinical entity. It is almost always seen in patients with a serious underlying medical disorder, most often a degree of renal impairment or other factors that are known to predispose to the lactic acidosis. We report a case of MALA in which acute renal failure resulting from hypovolemia secondary to acute gastroenteritis likely precipitated the condition. Early recognition of this condition and initiation of treatment are important. Bicarbonate hemodialysis is the treatment of choice. PMID:16415668

Shenoy, Chetan

2006-01-01

167

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

168

Acidosis counteracts the negative inotropic effect of K+ on ventricular muscle strips from the toad Bufo marinus.  

PubMed

Strenuous activity is associated with acidosis, increased extracellular potassium concentration ([K+]o), and elevated levels of circulating catecholamines. Acidosis and elevated [K+]o are normally considered harmful to cardiac function, and a high sympathetic tone on the heart may lead to arrhythmia. During activity, however, the heart must be able to increase rate and strength of contraction. While the individual effects of [K+]o, acidosis, and adrenaline on contractile properties of cardiac muscle have been characterized for some ectothermic species, less information is available on their interactions. Here we examine the isolated and combined effects of [K+]o, acidosis, and adrenaline on ventricular muscle strips from the toad Bufo marinus. This study showed that increased [K+]o significantly reduced twitch force, while lactic acid significantly increased twitch force and more than counteracted the negative inotropic effects of elevated [K+]o. There was no inotropic effect of Na-lactate (neutralized lactic acid), which suggests that lactic acid stimulated twitch force through reduced pH and not by serving as a substrate. Adrenaline had a positive effect on twitch force in all preparations. Irrespective of treatment, twitch force decreased as stimulation rate increased. During high [K+]o, there was a severe reduction in maximal frequency of toad ventricular strips that was not alleviated by lactic acidosis and/or adrenaline, which suggests that high [K+]o influences twitch force and maximal rate by different mechanisms. In vivo levels of lactic acid, [K+]o, adrenaline, and heart rate previously observed during forced activity in Bufo did not significantly affect the contractile properties of heart muscle strips in vitro. Thus, although [K+]o significantly decreased twitch force, this detrimental effect was more than counteracted by the positive inotropic effect of lactic acid and adrenaline. PMID:15095242

Andersen, Johnnie Bremholm; Gesser, Hans; Wang, Tobias

2004-01-01

169

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

170

Subacute ruminal acidosis (SARA) in grazing Irish dairy cows  

Microsoft Academic Search

Subacute ruminal acidosis (SARA) is a significant production disease of dairy cattle. Previous concerns have been raised over the occurrence of SARA in pasture-fed dairy cattle and the potential consequences of laminitis and lameness. Highly digestible perennial rye grass contains high concentrations of rapidly fermentable carbohydrate and low concentrations of physical effective fibre that may result in SARA. This study

Luke O’Grady; Michael L. Doherty; Finbar J. Mulligan

2008-01-01

171

Metformin-associated lactic acidosis (MALA): case report.  

PubMed

Metformin is the first-line therapy for the treatment of diabetes mellitus. In certain conditions lactic acidosis (MALA) can occur. Starting with a case report of a 62-year-old woman presenting with abdominal pain, we bring this complication to attention, describing its pathogenesis and its management. This underlines the need for thoughtful use of metformin. PMID:22145278

Hofkens, P J; De Winter, S; Vanbrabant, P

2011-01-01

172

Genetics Home Reference: Renal tubular acidosis with deafness  

MedlinePLUS

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

173

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

PubMed Central

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

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

2010-01-01

174

Monitoring of metformin-induced lactic acidosis in a diabetic patient with acute kidney failure and effect of hemodialysis.  

PubMed

Metformin associated lactic acidosis (MALA) is a serious complication occurring especially in elderly patients given high doses of the drug. We report a non-fatal case of MALA with pronounced acidosis (pH 6.76, lactate 30.81 mmol/l) and high metformin concentrations (127 mg/l) in a patient who had developed acute renal failure after undergoing an operation. Multiple measurements of biological parameters and metformin blood concentrations showed the effectiveness of repeated hemodialysis sessions on metformin elimination. Cases previously reported with such a severe MALA were associated with a high mortality rate. We show that close monitoring in an intensive care unit together with prompt and repeated dialysis sessions can lead to a favorable outcome. PMID:23149294

Laforest, Claire; Saint-Marcoux, Franck; Amiel, Jean-Bernard; Pichon, Nicolas; Merle, Louis

2013-02-01

175

Effects of low-dose hydrochlorothiazide on urolithiasis and bone metabolism in severely disabled individuals: a pilot study.  

PubMed

To clarify the effects of hydrochlorothiazide (HCT) on calcium metabolism in subjects with severe motor and intellectual disabilities (SMID), we examined four patients (16-48years old) with a history of urolithiasis and/or bone fracture and increased urinary calcium/creatinine ratio (U-Ca/Cr). U-Ca/Cr, blood markers of bone turnover, and bone-mineral density (BMD) were measured before and after administration of low-dose HCT (0.25-0.5mg/kg/day). Three months after the initiation of HCT, U-Ca/Cr decreased in all patients, but this effect was less evident at 9-18months. Bone-turnover marker of bone-specific alkaline phosphatase also showed a tendency to decrease, but BMD remained unchanged during the follow-up period. In SMID patients, HCT is beneficial for the treatment of hypercalciuria but its effects can be transient in certain cases. HCT may also ameliorate the increase in bone turnover, but its effects on the prevention of bone fractures remain uncertain. Hyponatremia is the most frequent and significant adverse effect of HCT, for which a close observation is mandatory in HCT application for patients with SMID. PMID:20702052

Ikeda, Chizuru; Saito, Yoshiaki; Sukigara, Sayuri; Sakuma, Hiroshi; Sugai, Kenji; Komaki, Hirofumi; Sasaki, Masayuki

2011-05-01

176

Devastating metabolic brain disorders of newborns and young infants.  

PubMed

Metabolic disorders of the brain that manifest in the neonatal or early infantile period are usually associated with acute and severe illness and are thus referred to as devastating metabolic disorders. Most of these disorders may be classified as organic acid disorders, amino acid metabolism disorders, primary lactic acidosis, or fatty acid oxidation disorders. Each disorder has distinctive clinical, biochemical, and radiologic features. Early diagnosis is important both for prompt treatment to prevent death or serious sequelae and for genetic counseling. However, diagnosis is often challenging because many findings overlap and may mimic those of more common neonatal conditions, such as hypoxic-ischemic encephalopathy and infection. Ultrasonography (US) may be an initial screening method for the neonatal brain, and magnetic resonance (MR) imaging is the modality of choice for evaluating metabolic brain disorders. Although nonspecific imaging findings are common in early-onset metabolic disorders, characteristic patterns of brain involvement have been described for several disorders. In addition, diffusion-weighted images may be used to characterize edema during an acute episode of encephalopathy, and MR spectroscopy depicts changes in metabolites that may help diagnose metabolic disorders and assess response to treatment. Imaging findings, including those of advanced MR imaging techniques, must be closely reviewed. If one of these rare disorders is suspected, the appropriate biochemical test or analysis of the specific gene should be performed to confirm the diagnosis. PMID:25208279

Yoon, Hyun Jung; Kim, Ji Hye; Jeon, Tae Yeon; Yoo, So-Young; Eo, Hong

2014-01-01

177

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

178

Metformin lactic acidosis, acute renal failure and rofecoxib.  

PubMed

A patient with acute renal failure associated with lactic acidosis as a result of concurrent treatment with metformin is described. Rofecoxib may have been a precipitating factor. The risk of renal failure with the use of traditional NSAIDs is well known. However, what is less well appreciated is the role that the COX 2 inhibitors may play in the development of renal failure which, when it occurs in a patient on metformin, can lead to a potentially disastrous outcome. PMID:14633764

Price, G

2003-12-01

179

Mechanism of diminished contractile response to catecholamines during acidosis  

SciTech Connect

To examined mechanisms of diminished contractile response to catecholamines during acidosis, the authors studied contractile properties, {beta}-adrenergic receptor properties, and intracellular pH of intact, cultured myocardial cells from chick embryo ventricle at pH 7.4 and 6.8. On changing the superfusing buffer from pH 7.4 to 6.8 there was a decline in contractile amplitude to 80% of control by 20 min. Fluorimetrically determined intracellular pH declined over a similar time course from 7.11 {plus minus} 0.05 to 6.96 {plus minus} 0.07. After 45 min at pH 6.8 the contractile response to 1 {mu}M isoproterenol was less than half of the response at pH 7.4. Antagonist and agonist ligand-binding properties of the {beta}-adrenergic receptor were determined in the intact cells under conditions identical to those for the contractility studies. With the use of the hydrophilic antagonist ({sup 3}H)CGP-12177 that selectively labels cell-surface receptors, agonist competition studies demonstrated that acidosis had no significant effect on antagonist or agonist affinity but decreased {beta}-receptor number from 21 {plus minus} 3 to 11 {plus minus} 3 fmol/mg protein. It is probably that a decline in the number of {beta}-receptors on the cell surface contributes to contractile hyporesponsiveness to catecholamines during acidosis.

Marsh, J.D.; Margolis, T.I.; Kim, D. (Brigham and Women's Hospital, Boston, MA (USA) Harvard Medical School, Boston, MA (USA))

1988-01-01

180

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

181

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

PubMed Central

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

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

2013-01-01

182

Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury  

Microsoft Academic Search

INTRODUCTION: The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism. METHODS: In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 ?l\\/min, collecting

Roman Meierhans; Markus Béchir; Silke Ludwig; Jutta Sommerfeld; Giovanna Brandi; Christoph Haberthür; Reto Stocker; John F Stover

2010-01-01

183

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

PubMed

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

Dawson, Neal J; Storey, Kenneth B

2012-04-01

184

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

PubMed Central

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

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

2013-01-01

185

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

186

The Influence of Extracellular Acidosis on the Effect of IKr Blockers  

Microsoft Academic Search

Background: Myocardial infarction causes the acidification of the cellular environment and the resultant acidosis maybe arrhythmogenic. The effect of acidosis on the action of antiar-rhythmic drugs, an important issue in the antiarrhythmic drug therapy after myocardial infarction, remains to be studied.Methods: To evaluate the effect of acidosis on rectifier potassium current (Ikr) blockers, the human ether-a-go-go-related gene (HERG), which encodes

Congrong Lin; Xiaogang Ke; Ivana Cvetanovic; Vasant Ranade; John Somberg

2005-01-01

187

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

Microsoft Academic Search

was applied for comparative metabolic network analysis of a genealogy of five successive generations of lysine-producing Corynebacterium glutamicum. The five strains examined (C. glutamicum ATCC 13032, 13287, 21253, 21526, and 21543) were previously obtained by random mutagenesis and selection. Throughout the genealogy, the lysine yield in batch cultures increased markedly from 1.2 to 24.9% relative to the glucose uptake flux.

Christoph Wittmann; Elmar Heinzle

2002-01-01

188

Influence of kick frequency on metabolic efficiency and performance at a severe intensity in international monofin-swimmers  

Microsoft Academic Search

The aim of this study was to examine the effect of kick frequency on metabolic efficiency and performance in elite monofin-swimmers at the surface. Seven participants of international calibre were requested to perform three separate Time Limit exercises conducted at an intensity corresponding to 97.5% of the velocity at the maximal oxygen uptake. The first Time Limit exercise was systematically

Fabrice Vercruyssen; Guillaume Boitel; Morgan Alberty; Xavier Nesi; Lionel Bourdon; Jeanick Brisswalter

2012-01-01

189

Acidosis slows electrical conduction through the atrio-ventricular node.  

PubMed

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

190

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

191

Acute renal failure and metformin-associated lactic acidosis following colonoscopy.  

PubMed

Two patients with type 2 DM developed acute kidney injury and lactic acidosis following colonoscopy despite withholding metformin. We recommend that DM patients on metformin also withhold ACEI, ARB until their dehydration is reversed after colonoscopy. This should reduce the risk of acute renal failure (ARF) and of lactic acidosis. PMID:24877743

Hussain, Mohammad I; Hall, Bruce M; Depczynski, Barbara; Connor, Susan J

2014-07-01

192

Does glucose infusion exacerbate metformin-associated lactate acidosis? A case report.  

PubMed

Metformin-associated lactate acidosis is a rare, but life-threatening complication of a widely prescribed medication. We describe here a case of metformin-associated lactate acidosis that rapidly deteriorated probably as a consequence of concomitant glucose infusion that was initiated to correct sulphonylurea-induced hypoglycemia. PMID:19427052

Brouwers, M C G J; Schaper, N; Keeris, L

2009-07-01

193

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

SciTech Connect

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.

Montgomery, J.A.; Mamer, O.A.

1989-01-01

194

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

195

Seizure-induced damage to substantia nigra and globus pallidus is accompanied by pronounced intra- and extracellular acidosis  

SciTech Connect

Status epilepticus of greater than 30-min duration in rats gives rise to a conspicuous lesion in the substantia nigra pars reticulata (SNPR) and globus pallidus (GP). The objective of the present study was to explore whether the lesion, which encompasses necrosis of both neurons and glial cells, is related to intra- and extracellular acidosis. Using the flurothyl model previously described to produce seizures, we assessed regional pH values with the autoradiographic 5,5-dimethyl(2-14C)oxazolidine-2,4-dione technique. Regional pH values were assessed in animals with continuous seizures for 20 and 60 min, as well as in those allowed to recover for 30 and 120 min after seizure periods of 20 or 60 min. In additional animals, changes in extracellular fluid pH (pHe) were measured with ion-selective microelectrodes, and extracellular fluid (ECF) volume was calculated from the diffusion profile for electrophoretically administered tetramethylammonium. In structures such as the neocortex and the hippocampus, which show intense metabolic activation during seizures, status epilepticus of 20- and 60-min duration was accompanied by a reduction of the composite tissue pH (pHt) of 0.2-0.3 unit. Recovery of pHt was observed upon termination of seizures. In SNPR and in GP, the acidosis was marked to excessive after 20 and 60 min of seizures (delta pHt approximately 0.6 after 60 min).

Inamura, K.; Smith, M.L.; Hansen, A.J.; Siesjoe, B.K. (Univ. of Lund (Sweden))

1989-12-01

196

Rumen motility in experimental acidosis of the rumen in sheep.  

PubMed

In rumen acidosis, induced by infusion of saccharose solution and solutions of different volatile fatty acids and lactic acid into the rumen, and during induced disturbances of acid-base equilibrium in the arterial blood the motility of the dorsal sac of the rumen, the pH of rumen content and the indices of acid-base equilibrium in the arterial blood were investigated. The pH and the indices were determined by the micromethod of Astrup with an Acid-Base-Cart ABC-1 unit. During saccharose-induced acidosis of the rumen the pH of its content was decreased and its motility was strongly inhibited. Acidification of rumen content corresponded to the dissociation constant of a given acid. The motility of the rumen was inhibited most strongly by butyric acid, followed with regard of this effect by acetic acid, propionic acid and lactic acid. It was found that hydrogen ions as well as anions and non-dissociated forms of acids produced in the rumen were responsible for inhibition of this motility and that the rise in the concentration of hydrogen ions in the blood had no inhibitory effect on the motility of the rumen. PMID:41404

Cebrat, E

1979-01-01

197

Metformin-associated lactic acidosis in diabetic patients with acute renal failure. A critical analysis of its pathogenesis and prognosis.  

PubMed

To determine the respective role of metformin accumulation and tissue hypoxia in triggering metformin-associated lactic acidosis (MALA), we measured plasma (PM) and red blood cell (RM) metformin concentrations in 14 patients with MALA and in 58 diabetic patients on well-tolerated chronic metformin treatment. In this control group RM was 0.9 +/- 0.5 mg/l. In MALA, lactic acidosis was of comparable severity whether there was significant cellular metformin accumulation (9 patients with severe renal failure) or not (5 patients with less severe renal failure). Factors of hypoxia were found in all patients except three with isolated anuria and major metformin accumulation. Early mortality was low in patients with metformin accumulation (no rapid death with the exception of two patients with end-stage hepatic failure) whereas it was high in those with metformin accumulation (4 patients died rapidly). In conclusion, MALA is not always associated with metformin accumulation. The prognosis of MALA depends mainly not upon the degree of metformin accumulation but rather upon the severity of hypoxic factors. PMID:7800245

Lalau, J D; Lacroix, C; De Cagny, B; Fournier, A

1994-01-01

198

Evidence for the involvement of several cytochromes P-450 in the first steps of caffeine metabolism by human liver microsomes.  

PubMed

Caffeine biotransformation and four monooxygenase activities involving cytochrome P-450IA2, namely ethoxy- and methoxyresorufin O-dealkylases, phenacetin O-deethylase, and acetanilide 4-hydroxylation were studied in 25 human liver microsomes. All these activities were highly significantly intercorrelated (r greater than 0.72, p less than 0.001) and correlated with the level of immunoreactive P-450IA2 content (r greater than 0.65; p less than 0.001). P-450IA content was measured by immunoblotting with anti-rat P-450 beta-naphthoflavone-B, an antibody that detects only a single band corresponding to P-450IA2. The formation rate of two caffeine metabolites, namely paraxathine and theobromine, was correlated with the four monooxygenase activities measured and P-450IA2-specific content (r greater than 0.75). However, inhibition studies of caffeine metabolism by phenacetin, a specific substrate of P-450IA2, clearly indicated that only the N-3 demethylation of caffeine was supported by this enzyme. These in vitro data demonstrate that P-450IA2 is predominantly responsible for the major metabolic pathway of caffeine and that the formation of other demethylated metabolites is mediated, at least partly, by other P-450 enzymes. PMID:1680620

Berthou, F; Flinois, J P; Ratanasavanh, D; Beaune, P; Riche, C; Guillouzo, A

1991-01-01

199

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

PubMed Central

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

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

1989-01-01

200

X-linked adrenoleukodystrophy: very long-chain fatty acid metabolism is severely impaired in monocytes but not in lymphocytes.  

PubMed

X-linked adrenoleukodystrophy (X-ALD) is a fatal neurodegenerative disease caused by mutations in the ABCD1 gene, encoding a member of the peroxisomal ABC transporter family. The ABCD1 protein transports CoA-activated very long-chain fatty acids (VLCFAs) into peroxisomes for degradation via ?-oxidation. In the severest form, X-ALD patients suffer from inflammatory demyelination of the brain. As the extent of the metabolic defect in the main immune cells is unknown, we explored their phenotypes concerning mRNA expression pattern of the three peroxisomal ABC transporters, VLCFA accumulation and peroxisomal ?-oxidation. In controls, ABCD1 expression was high in monocytes, intermediate in B cells and low in T cells; ABCD2 expression was extremely low in monocytes, intermediate in B cells and highest in T cells; ABCD3 mRNA was equally distributed. In X-ALD patients, the expression patterns remained unaltered; accordingly, monocytes, which lack compensatory VLCFA transport by ABCD2, displayed the severest biochemical phenotype with a 6-fold accumulation of C26:0 and a striking 70% reduction in peroxisomal ?-oxidation activity. In contrast, VLCFA metabolism was close to control values in B cells and T cells, supporting the hypothesis that sufficient ABCD2 is present to compensate for ABCD1 deficiency. Thus, the vulnerability of the main immune cell types is highly variable in X-ALD. Based on these results, we propose that in X-ALD the halt of inflammation after allogeneic hematopoietic stem cell transplantation relies particularly on the replacement of the monocyte lineage. Additionally, these findings support the concept that ABCD2 is a target for pharmacological induction as an alternative therapeutic strategy. PMID:24363066

Weber, Franziska D; Wiesinger, Christoph; Forss-Petter, Sonja; Regelsberger, Günther; Einwich, Angelika; Weber, Willi H A; Köhler, Wolfgang; Stockinger, Hannes; Berger, Johannes

2014-05-15

201

Microvillus inclusion disease as a cause of severe protracted diarrhea in infants.  

PubMed

There are many etiologies responsible for severe intractable diarrhea in infancy, for instance, autoimmune enteropathy, microvillus inclusion disease, tufting enteropathy, food allergy, post-enteritis syndrome, chronic intestinal pseudo-obstruction, Hirschsprung's disease, intestinal lymphangiectasia, congenital sodium or chloride diarrhea, and congenital enzymatic deficiency. This article reports a case of microvillus inclusion disease in a Thai patient. He presented with severe intractable watery diarrhea with persistent metabolic acidosis. After extensive investigation, the diagnosis of microvillus inclusion disease was made, based on the ultrastructural findings of microvillus inclusions in the cytoplasm of the enterocyte on electron microscopic study. Various treatments were introduced to the patient without clinical improvement, including cholestyramine, metronidazole, probiotics, and octreotide. He was dependent on total parenteral nutrition and subsequently died from TPN-related complications. Even though it is a rare disease, it should be considered if an infant has chronic secretory diarrhea. PMID:11800313

Ukarapol, N; Chotinaruemol, S; Lertprasertsuk, N; Wongsawasdi, L

2001-09-01

202

Lactic acidosis due to metformin therapy in a low risk patient.  

PubMed

A 55 year old diabetic women treated with chlorpropamide and metformin for three years presented with acute oliguric renal failure and lactic acidosis from which she died. The plasma metformin level was very high suggesting that the lactic acidosis was caused by the drug. There were no contraindications to metformin therapy and renal function was normal three months previously. This case demonstrates that lactic acidosis can occur as a result of metformin therapy in the absence of pre-existing risk factors. PMID:3174542

Tymms, D J; Leatherdale, B A

1988-03-01

203

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

PubMed

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

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

2014-09-01

204

A subset of dysregulated metabolic and survival genes is associated with severity of hepatic steatosis in obese Zucker rats[S  

PubMed Central

We aimed to characterize the primary abnormalities associated with fat accumulation and vulnerability to hepatocellular injury of obesity-related fatty liver. We performed functional analyses and comparative transcriptomics of isolated primary hepatocytes from livers of obese insulin-resistant Zucker rats (comprising mild to severe hepatic steatosis) and age-matched lean littermates, searching for novel genes linked to chronic hepatic steatosis. Of the tested genome, 1.6% was identified as steatosis linked. Overexpressed genes were mainly dedicated to primary metabolism (100%), signaling, and defense/acute phase (?70%); detoxification, steroid, and sulfur metabolism (?65%) as well as cell growth/proliferation and protein synthesis/transformation (?70%) genes were downregulated. The overexpression of key genes involved in de novo lipogenesis, fatty acid and glycerolipid import and synthesis, as well as acetyl-CoA and cofactor provision was paralleled by enhanced hepatic lipogenesis and production of large triacylglycerol-rich VLDL. Greatest changes in gene expression were seen in those encoding the lipogenic malic enzyme (up to 7-fold increased) and cell-to-cell interacting cadherin 17 (up to 8-fold decreased). Among validated genes, fatty acid synthase, stearoyl-CoA desaturase 1, fatty acid translocase/Cd36, malic enzyme, cholesterol-7? hydroxylase, cadherin 17, and peroxisome proliferator-activated receptor ? significantly correlated with severity of hepatic steatosis. In conclusion, dysregulated expression of metabolic and survival genes accompany hepatic steatosis in obese insulin-resistant rats and may render steatotic hepatocytes more vulnerable to cell injury in progressive nonalcoholic fatty liver disease. PMID:19783528

Buque, Xabier; Martinez, Maria Jose; Cano, Ainara; Miquilena-Colina, Maria E.; Garcia-Monzon, Carmelo; Aspichueta, Patricia; Ochoa, Begona

2010-01-01

205

A rare cause of severe diarrhoea diagnosed by urine metabolic screening: aromatic L-amino acid decarboxylase deficiency.  

PubMed

A 15-year-old Chinese male with infantile-onset hypotonia, developmental delay, ptosis, and oculogyric episodes presented with a history of chronic diarrhoea since the age of 5 years. At presentation, he had an exacerbation of diarrhoeal symptoms resulting in dehydration and malnutrition with a concurrent severe chest infection. In view of his infantile-onset hypotonia, oculogyric crises, and protracted diarrhoea, an autonomic disturbance related to neurotransmitters was suspected. Urine organic acid profiling was compatible with aromatic L-amino acid decarboxylase deficiency. The diagnosis was confirmed based on cerebrospinal fluid analysis and genetic mutation analysis. The patient was treated with a combination of bromocriptine, selegiline, and pyridoxine; a satisfactory reduction in diarrhoea ensued. Our report highlights the importance of urine organic acid screening in infantile-onset hypotonia, especially when accompanied by oculogyric crises, and severe diarrhoea which could manifest as a result of autonomic disturbance. PMID:24714172

Lee, L K; Cheung, K M; Cheng, W W; Ko, C H; Lee, Hencher H C; Ching, C K; Mak, Chloe M

2014-04-01

206

Inborn errors of cobalamin absorption and metabolism.  

PubMed

Derivatives of cobalamin (vitamin B(12)) are required for activity of two enzymes in humans. Adenosylcobalamin is required for activity of mitochondrial methylmalonylCoA mutase and methylcobalamin is required for activity of cytoplasmic methionine synthase. Deficiency in cobalamin, or inability to absorb cobalamin normally, can result in accumulation of methylmalonic acid and homocysteine in blood and urine. Methylmalonic acidemia can result in metabolic acidosis which in severe cases may be fatal. Hyperhomocysteinemia along with hypomethioninemia can result in hematologic (megaloblastic anemia, neutropenia, thrombocytopenia) and neurologic (subacute combined degeneration of the cord, dementia, psychosis) defects. Inborn errors affecting cobalamin absorption (inherited intrinsic factor deficiency, Imerslund–Gra¨ sbeck syndrome) and transport (transcobalamin deficiency) have been described. A series of inborn errors of intracellular cobalamin metabolism, designated cblA-cblG, have been differentiated by complementation analysis. These can give rise to isolated methylmalonic acidemia (cblA, cblB, cblD variant 2), isolated hyperhomocysteinemia (cblD variant 1, cblE, cblG) or combined methylmalonic acidemia and hyperhomocysteinemia (cblC, classic cblD, cblF). All these disorders are inherited as autosomal recessive traits. The genes underlying each of these disorders have been identified. Two other disorders, haptocorrin deficiency and transcobalamin receptor deficiency, have been described, but it is not clear that they have any consistent clinical phenotype. PMID:21312325

Watkins, David; Rosenblatt, David S

2011-02-15

207

Functional interaction between responses to lactic acidosis and hypoxia regulates genomic transcriptional outputs.  

PubMed

Within solid tumor microenvironments, lactic acidosis, and hypoxia each have powerful effects on cancer pathophysiology. However, the influence that these processes exert on each other is unknown. Here, we report that a significant portion of the transcriptional response to hypoxia elicited in cancer cells is abolished by simultaneous exposure to lactic acidosis. In particular, lactic acidosis abolished stabilization of HIF-1? protein which occurs normally under hypoxic conditions. In contrast, lactic acidosis strongly synergized with hypoxia to activate the unfolded protein response (UPR) and an inflammatory response, displaying a strong similarity to ATF4-driven amino acid deprivation responses (AAR). In certain breast tumors and breast tumor cells examined, an integrative analysis of gene expression and array CGH data revealed DNA copy number alterations at the ATF4 locus, an important activator of the UPR/AAR pathway. In this setting, varying ATF4 levels influenced the survival of cells after exposure to hypoxia and lactic acidosis. Our findings reveal that the condition of lactic acidosis present in solid tumors inhibits canonical hypoxia responses and activates UPR and inflammation responses. Furthermore, these data suggest that ATF4 status may be a critical determinant of the ability of cancer cells to adapt to oxygen and acidity fluctuations in the tumor microenvironment, perhaps linking short-term transcriptional responses to long-term selection for copy number alterations in cancer cells. PMID:22135092

Tang, Xiaohu; Lucas, Joseph E; Chen, Julia Ling-Yu; LaMonte, Gregory; Wu, Jianli; Wang, Michael Changsheng; Koumenis, Constantinos; Chi, Jen-Tsan

2012-01-15

208

The metabolic toxicities of antiretroviral therapy.  

PubMed

Since the adoption of highly active antiretroviral therapy (HAART) in the mid-1990s, certain metabolic toxicities have been increasingly recognized. These include a fat redistribution syndrome (lipohypertrophy, lipoatrophy), hyperlipidaemia, altered glucose metabolism and insulin resistance, mitochondrial toxicity (presenting as anaemia, myopathy, pancreatitis, neuropathy, hepatic steatosis and lactic acidosis), and bone density abnormalities (osteoporosis and osteonecrosis). Metabolic complications are principally reported with protease inhibitors and nucleoside reverse transcriptase inhibitors, but may be seen with all classes of antiretroviral therapy. In this review, we summarize the epidemiology, pathogenesis and management of these various toxicities. PMID:11516363

Herman, J S; Easterbrook, P J

2001-09-01

209

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

PubMed Central

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

2014-01-01

210

Utility of the modified ATP III defined metabolic syndrome and severe obesity as predictors of insulin resistance in overweight children and adolescents: a cross-sectional study  

PubMed Central

Background The rising prevalence of obesity and metabolic syndrome (MetS) has received increased attention since both place individuals at risk for Type II diabetes and cardiovascular disease. Insulin resistance (IR) has been implicated in the pathogenesis of obesity and MetS in both children and adults and is a known independent cardiovascular risk factor. However measures of IR are not routinely performed in children while MetS or severe obesity when present, are considered as clinical markers for IR. Objective The study was undertaken to assess the utility of ATPIII defined metabolic syndrome (MetS) and severe obesity as predictors of insulin resistance (IR) in a group of 576 overweight children and adolescents attending a pediatric obesity clinic in Brooklyn. Methods Inclusion criteria were children ages 3–19, and body mass index > 95th percentile for age. MetS was defined using ATP III criteria, modified for age. IR was defined as upper tertile of homeostasis model assessment (HOMA) within 3 age groups (3–8, n = 122; 9–11, n = 164; 12–19, n = 290). Sensitivity, specificity, positive predictive values and odds ratios (OR) with 95% confidence intervals (CI) were calculated within age groups for predicting IR using MetS and severe obesity respectively. Results MetS was present in 45%, 48% and 42% of the respective age groups and significantly predicted IR only in the oldest group (OR = 2.0, 95% CI 1.2, 3.4; p = .006). Sensitivities were <55%; specificities <63% and positive predictive values ? 42% in all groups. Severe obesity was significantly associated with IR in both the 9–11 (p = .002) and 12–18 (p = .01) groups but positive predictive values were nonetheless ? 51% for all groups. Conclusion The expression of IR in overweight children and adolescents is heterogeneous and MetS or severe obesity may not be sufficiently sensitive and specific indicators of insulin resistance. In addition to screening for MetS in overweight children markers for IR should be routinely performed. Further research is needed to establish threshold values of insulin measures in overweight children who may be at greater associated risk of adverse outcomes whether or not MetS is present. PMID:17300718

Dhuper, Sarita; Cohen, Hillel W; Daniel, Josephine; Gumidyala, Padmasree; Agarwalla, Vipin; St Victor, Rosemarie; Dhuper, Sunil

2007-01-01

211

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

PubMed Central

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

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

1991-01-01

212

Extracellular acidosis accelerates bone resorption by enhancing osteoclast survival, adhesion, and migration.  

PubMed

Acidic extracellular pH promotes osteoporotic bone loss by osteoclast activation. However, the change of osteoclastic cell behavior in acidosis-stimulated bone resorption process is unknown. We found that lowering extracellular pH induced an increase in the survival, adhesion, and migration of mature osteoclasts with a full actin ring, leading to enhanced pit formation on dentine slices. Acidosis upregulated osteopontin, which is an Arg-Gly-Asp (RGD) motif-containing matrix protein secreted from osteoclasts and acts as a common modulator for their survival, adhesion, and migration. A synthetic RGD peptide treatment blocked acidosis-induced osteoclast adhesion and migration, likely by competing with the RGD motif-containing extracellular matrix proteins for cell surface integrin binding. We finally observed that acidosis was associated with activation of osteoclast survival/adhesion/migration-related Pyk2, Cbl-b, and Src signals. Collectively, the findings indicate that extracellular acidosis stimulates bone resorption by extending osteoclast survival and facilitating osteoclast adhesion and migration. PMID:22244876

Ahn, Heejin; Kim, Jin Man; Lee, Kyunghee; Kim, Hyunsoo; Jeong, Daewon

2012-02-01

213

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

PubMed Central

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

Lonien, Joachim; Schwender, Jörg

2009-01-01

214

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

215

Disruption of Glycerol Metabolism by RNAi Targeting of Genes Encoding Glycerol Kinase Results in a Range of Phenotype Severity in Drosophila  

PubMed Central

In Drosophila, RNAi targeting of either dGyk or dGK can result in two alternative phenotypes: adult glycerol hypersensitivity or larval lethality. Here we compare these two phenotypes at the level of glycerol kinase (GK) phosphorylation activity, dGyk and dGK-RNA expression, and glycerol levels. We found both phenotypes exhibit reduced but similar levels of GK phosphorylation activity. Reduced RNA expression levels of dGyk and dGK corresponded with RNAi progeny that developed into glycerol hypersensitive adult flies. However, quantification of dGyk/dGK expression levels for the larval lethality phenotype revealed unexpected levels possibly due to a compensatory mechanism between dGyk and dGK or RNAi inhibition. The enzymatic role of glycerol kinase converts glycerol to glycerol 3-phosphate. As expected, elevated glycerol levels were observed in larvae that went on to develop into glycerol hypersensitive adults. Interestingly, larvae that died before eclosion revealed extremely low glycerol levels. Further characterization identified a wing phenotype that is enhanced by a dGpdh null mutation, indicating disrupted glycerol metabolism underlies the wing phenotype. In humans, glycerol kinase deficiency (GKD) exhibits a wide range of phenotypic variation with no obvious genotype-phenotype correlations. Additionally, disease severity often does not correlate with GK phosphorylation activity. It is intriguing that both human GKD patients and our GKD Drosophila model show a range of phenotype severity. Additionally, the lack of correlation between GK phosphorylation and dGyk/dGK-RNA expression with phenotypic severity suggests further study including understanding the alternative functions of the GK protein, could provide insights into the complex pathogenic mechanism observed in human GKD patients. PMID:24039719

Wightman, Patrick J.; Jackson, George R.; Dipple, Katrina M.

2013-01-01

216

Metformin-associated lactic acidosis and acute renal failure in a type 2 diabetic patient.  

PubMed

Metformin belongs to a class of drugs known as the biguanides that are widely used in the treatment of type 2 diabetes mellitus. Its association with lactic acidosis is well established, although rare. Metformin-associated lactic acidosis is recognized as a potentially lethal condition that can occur in patients with contraindications to the drug, such as renal dysfunction, liver diseases, alcoholism, and cardiopulmonary diseases. In these cases, the plasma concentration of metformin is not necessarily abnormally high. We describe a 75-year-old diabetic woman with acute renal failure and life-threatening lactic acidosis due to metformin intoxication. Clinical manifestations included vomiting, diarrhea, hypothermia, hypotension and transitory blindness. Her initial renal function was recovered after hemodialysis and she was discharged 3 months after admission. PMID:14604317

Chu, Chen-Kuo; Chang, Yao-Tien; Lee, Bor-Jen; Hu, Sung-Yuan; Hu, Wei-Hsiung; Yang, Dar-Yu

2003-08-01

217

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

218

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes unveiled by valproate  

PubMed Central

Valproic acid (VPA) is widely used as an anti-epileptic drug. The primary mechanism of VPA toxicity is interference with mitochondrial beta-oxidation, and it can exacerbate an underlying mitochondrial cytopathy. We report a case of Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes unmasked by use of Sodium Valproate in a 12-year-old boy who presented with headache and seizures. There was precipitation of encephalopathy, myopathy, lactic acidosis, and hepatic damage within two days of valproate use, after withdrawing of which there was a remarkable clinical and biochemical recovery. PMID:24082934

Chaudhry, Neera; Patidar, Yogesh; Puri, Vinod

2013-01-01

219

Lactic acidosis induced by metformin in a chronic hemodialysis patient with diabetes mellitus type 2.  

PubMed

Metformin is a biguanide group oral antidiabetic drug used for the treatment of type 2 diabetes mellitus. Nausea, vomiting, diarrhea, abdominal pain, and anorexia are the most common adverse effects encountered during treatment. Lactic acidosis is a serious side effect seen with metformin use, and while the incidence of lactic acidosis is similar to other oral antidiabetics, metformin is not recommended to patients with certain risk factors, such as cardiovascular, pulmonary, and renal and liver failure. We describe a chronic hemodialysis patient treated with metformin, presenting to the nephrology department with altered mental status. PMID:24299454

Altun, Eda; Kaya, Bülent; Payda?, Saime; Sar?akçal?, Bar??; Karayaylal?, Ibrahim

2014-04-01

220

[Fatal case of metformin-induced lactic acidosis after urography in a diabetic patient (author's transl)].  

PubMed

The authors report a new case of lactic-acidosis in a diabetic patient receiving metformin. This patient, after urography developed an acute renal failure and a fatal lactic acidosis. Risks of urography in diabetic patients and guidelines for use of metformin are recalled; careful assessment of risk versus benefit for every proposed urography in diabetic patients never use metformin if creatinin is over 140 micromoles/liter, if an urography must be undergone, metformin must be stopped 3 days before urography and resumed only 3 days after it, if renal function allows it. PMID:6244670

Jamet, P; Lebas de Lacour, J C; Christoforov, B; Stern, M

221

Point of care testing for antiretroviral therapy-related lactic acidosis in resource-poor settings.  

PubMed

Lactic acidosis is a rare but potentially life-threatening complication of antiretroviral therapy (ART) and is commonly considered in the differential diagnosis of patients on ART. In the developing world, definitive diagnosis by laboratory measurement of lactate may be impossible. Point-of-care devices are available that provide simple, accurate measurements of lactic acid levels at relatively low cost. Their use in an HIV treatment programme in rural Haiti has greatly assisted clinical decision-making in patients with symptoms suggestive of lactic acidosis. PMID:16514312

Ivers, Louise C; Mukherjee, Joia S

2006-03-21

222

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

E-print Network

such as Cyclosporine or Tacrolimus, recurrence of the original disease, which caused their native kidneys to fail, and transplant glomerulopathy. Definitive diagnosis in failed transplants is performed with biopsies (11). Acid-base balance End stage renal disease can...

Vyduna, Jennifer Lynn

2012-12-31

223

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

224

Prolonged hemodialysis for severe metformin intoxication.  

PubMed

Lactic acidosis is a rare and often lethal complication of metformin therapy. We describe a patient who ingested at least 52 g, and possibly more, of metformin and presented with severe lactic acidosis and acute renal failure. He was treated with prolonged hemodialysis: a 3.5 h treatment that did not result in significant clinical improvement, followed by an additional 31 h treatment. With this treatment regimen, his lactate levels gradually decreased and his clinical status improved. A metformin level drawn approximately 25 h after the initiation of the second hemodialysis treatment was still elevated at about five times the upper therapeutic limit. It is suggested that prolonged dialysis is indicated in patients with severe metformin overdose, particularly those with renal failure. In patients whose cardiovascular status permits, prolonged hemodialysis should be strongly considered. PMID:21529276

Rifkin, Stephen I; McFarren, Christopher; Juvvadi, Raghu; Weinstein, Samuel S

2011-01-01

225

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

226

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

227

L-type Ca2+ channel blocker attenuates impairment induced by acidosis in hippocampal neurons.  

PubMed

Accumulation of acid in the brain during ischemia may contribute to the activation of voltage-gated Ca2+ channels and subsequent neuronal injury. However, information regarding the role of L-type Ca2+ channel under acidosis remains unclear. In the present study, we examined the role of L-type Ca2+ channel in acidosis induced neuronal death and subsequent pathogenesis events responsible for neuron degeneration. Here we report that preincubation of cells with nifedipine (5 microM, 10 microM), an inhibitor of L-type Ca2+ channel markedly reduced neuronal death induced by moderate extracellular acidosis (pH 6.5) on cultured hippocampus neurons. Furthermore, nifedipine decreased the hippocampus neuronal swelling, as well as the accumulation of Ca2+ and collapse of mitochondrial membrane potential induced by acidosis. These findings demonstrate that pharmacological inhibition of L-type Ca2+ channel would attenuate neuronal degeneration caused by toxic low pH exposure in rat hippocampus neuron. PMID:24380238

Zeng, Xianghui; Zhang, Yanli; Qing, Chen; Zhang, Hongbin

2013-11-01

228

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

229

Unique astrocytic inclusion in a 2 month-old baby showing Leigh-like brain lesions with lactic acidosis.  

PubMed

An unique cytoplasmic inclusion was found in astrocytes of a 2-month-old female baby who showed Leigh-like brain lesions with lactic acidosis, hypoglycemia and hepatomegaly. Although a defective enzyme was not determined, a metabolic disorder was suggested from clinicopathological observations. Symmetrically distributed lesions consisting of marked gliosis and proliferation of capillaries were observed in the basal ganglia, thalami and tegmentum. The astrocytic cytoplasmic inclusion was exclusively found in the cerebral and cerebellar white matter, where myelination was immature. The inclusion was round and eosinophilic, and positive for glial fibrillary acidic protein, vimentin, alphaB-crystallin, S-100 protein and microtubule associated protein 1B, immunohistochemically. An electron microscopic examination revealed an accumulation of intermediate filaments, ribosome and rough endoplasmic reticulum in the inclusion. The characteristic of this inclusion is different from that of other reported inclusions. The inclusion showed positive immunoreaction against CuZn superoxide dismutase, catalase, advanced glycation end-product and 4-hydroxy-2-nonenal antibodies, which suggest that oxidative stress is involved in the genesis of the inclusion. PMID:10838110

Yamamoto, T; Armstrong, D; Shibata, N; Kato, Y; Kobayashi, M

2000-06-01

230

Compensatory regulation of the sodium/phosphate cotransporters NaPi-IIc (SCL34A3) and Pit-2 (SLC20A2) during Pi deprivation and acidosis.  

PubMed

The role of four Pi transporters in the renal handling of Pi was analyzed using functional and molecular methods. The abundance of NaPi-IIa, NaPi-IIc, and Pit-2 was increased by 100% in kidney from rats on a 0.1% Pi diet, compared to a 0.6% Pi diet. Pit-1 was not modified. Type II-mediated Pi uptake in Xenopus oocytes increased as the pH of the uptake medium increased, and the opposite occurred with Pit-1 and Pit-2. At pH 6.0, Pi uptake mediated through type II was approximately 10% of the uptake at pH 7.5, but the uptake through Pit-2 was 250% of the activity at pH 7.5. Real brush-border membrane vesicles (BBMV) responded to pH changes following the same pattern as type II transporters. Adaptation to a 0.1% Pi diet was accompanied by a 65% increase in the V (max) of BBMV Pi transport at pH 7.5, compared to a 0.6% Pi diet. The increase was only 11% at pH 6.0. Metabolic acidosis increased the expression of NaPi-IIc and Pit-2 in animals adapted to a low Pi diet, and phosphaturia was only observed in control diet animals. The combination of the pH effect, Pi adaptation, and metabolic acidosis suggests very modest involvement of Pit-2 in renal Pi handling. Real-time PCR and mathematical analyses of transport findings suggest that NaPi-IIa RNA accounts for 95% of all Pi transporters and that type II handles 97% of Pi transport at pH 7.5 and 60% of Pi transport at pH 6.0, depending on the pH and the physiological conditions. PMID:19841935

Villa-Bellosta, Ricardo; Sorribas, Víctor

2010-02-01

231

Diffuse large B-cell lymphoma: A metabolic disorder?  

PubMed Central

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

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

2013-01-01

232

Transient Acidosis during Early Reperfusion Attenuates Myocardium Ischemia Reperfusion Injury via PI3k-Akt-eNOS Signaling Pathway  

PubMed Central

In this paper, we concluded that transient acidosis reperfusion conferred cardioprotection against myocardial ischemia reperfusion injury in isolated rat hearts through activating PI3K-Akt-eNOS pathway. PMID:24312696

Qiao, Xin; Xu, Jinjin; Yang, Qing-Jun; Du, Yun; Lei, Shaoqing; Liu, Zhi-Hong; Liu, Xinwei; Liu, Huimin

2013-01-01

233

Utility of the modified ATP III defined metabolic syndrome and severe obesity as predictors of insulin resistance in overweight children and adolescents: a cross-sectional study  

Microsoft Academic Search

BACKGROUND: The rising prevalence of obesity and metabolic syndrome (MetS) has received increased attention since both place individuals at risk for Type II diabetes and cardiovascular disease. Insulin resistance (IR) has been implicated in the pathogenesis of obesity and MetS in both children and adults and is a known independent cardiovascular risk factor. However measures of IR are not routinely

Sarita Dhuper; Hillel W Cohen; Josephine Daniel; Padmasree Gumidyala; Vipin Agarwalla; Rosemarie St Victor; Sunil Dhuper

2007-01-01

234

Rumen microbial and fermentation characteristics are affected differently by bacterial probiotic supplementation during induced lactic and subacute acidosis in sheep  

PubMed Central

Background Ruminal disbiosis induced by feeding is the cause of ruminal acidosis, a digestive disorder prevalent in high-producing ruminants. Because probiotic microorganisms can modulate the gastrointestinal microbiota, propionibacteria- and lactobacilli-based probiotics were tested for their effectiveness in preventing different forms of acidosis. Results Lactic acidosis, butyric and propionic subacute ruminal acidosis (SARA) were induced by feed chalenges in three groups of four wethers intraruminally dosed with wheat, corn or beet pulp. In each group, wethers were either not supplemented (C) or supplemented with Propionibacterium P63 alone (P) or combined with L. plantarum (Lp?+?P) or L. rhamnosus (Lr?+?P). Compared with C, all the probiotics stimulated lactobacilli proliferation, which reached up to 25% of total bacteria during wheat-induced lactic acidosis. This induced a large increase in lactate concentration, which decreased ruminal pH. During the corn-induced butyric SARA, Lp?+?P decreased Prevotella spp. proportion with a concomitant decrease in microbial amylase activity and total volatile fatty acids concentration, and an increase in xylanase activity and pH. Relative to the beet pulp-induced propionic SARA, P and Lr?+?P improved ruminal pH without affecting the microbial or fermentation characteristics. Regardless of acidosis type, denaturing gradient gel electrophoresis revealed that probiotic supplementations modified the bacterial community structure. Conclusion This work showed that the effectiveness of the bacterial probiotics tested depended on the acidosis type. Although these probiotics were ineffective in lactic acidosis because of a deeply disturbed rumen microbiota, some of the probiotics tested may be useful to minimize the occurrence of butyric and propionic SARA in sheep. However, their modes of action need to be further investigated. PMID:22812531

2012-01-01

235

Primary hyperparathyroidism and proximal renal tubular acidosis: Report of two cases  

PubMed Central

Two cases of primary hyperparathyroidism due to single parathyroid adenomas presented with the additional feature of hyperchloremic acidosis. The defect in urinary acidification responsible was not of the distal or gradient-limited type since both patients could lower urine pH adequately. However, there was a defect of bicarbonate reabsorption, an abnormality referred to as the proximal or rate-limited type of renal tubular acidosis. It is suggested that this defect represents an exaggeration of the physiological effect of parathormone on bicarbonate reabsorption and may be responsible for the frequent finding of hyperchloremia in association with primary hyperparathyroidism as well as for the urinary bicarbonate-wasting associated with a variety of causes of secondary hyperparathyroidism. PMID:5012229

Siddiqui, Abdullah A.; Wilson, Douglas R.

1972-01-01

236

[Remarks on the metabolic evaluation of renal lithiasis].  

PubMed

Metabolic studies include certain routine investigations but which may be more or less limited or extended according to the individual case on the basis of its severity and the chemical nature of calculi. These studies are based upon the following data: analysis of one or more stones, aided and guided by methodical macroscopic examination; urine microscopy; study of urine pH which should be done by the patient himself on several samples during the 24-hour period; blood and urine calcium/phosphate balance, without omitting the measurement of urinary urea which provides information concerning protein intake and indicates its influence; oxalate balance studies and hyperoxaluria are correlated with cases of lithiasis when stones contain only calcium oxalate or a mixture of oxalate and calcium phosphate; uric acid balance, where once again the measurement of urinary urea is of fundamental importance and shows that all cases of hyperuricuria are related to a diet excessively rich in meat; urinary cystine levels with the need for a Brand reaction almost routinely in all lithiasis sufferers; electrolyte studies which may reveal a renal tubular acidosis syndrome, in fact rare; and, finally, in certain cases a magnesium balance may show a decreased erythrocyte magnesium. PMID:6725970

Thomas, J

1984-01-01

237

A mouse model for distal renal tubular acidosis reveals a previously unrecognized role of the V-ATPase a4 subunit in the proximal tubule.  

PubMed

The V-ATPase is a multisubunit complex that transports protons across membranes. Mutations of its B1 or a4 subunit are associated with distal renal tubular acidosis and deafness. In the kidney, the a4 subunit is expressed in intercalated cells of the distal nephron, where the V-ATPase controls acid/base secretion, and in proximal tubule cells, where its role is less clear. Here, we report that a4 KO mice suffer not only from severe acidosis but also from proximal tubule dysfunction with defective endocytic trafficking, proteinuria, phosphaturia and accumulation of lysosomal material and we provide evidence that these findings may be also relevant in patients. In the inner ear, the a4 subunit co-localized with pendrin at the apical side of epithelial cells lining the endolymphatic sac. As a4 KO mice were profoundly deaf and displayed enlarged endolymphatic fluid compartments mirroring the alterations in pendrin KO mice, we propose that pendrin and the proton pump co-operate in endolymph homeostasis. Thus, our mouse model gives new insights into the divergent functions of the V-ATPase and the pathophysiology of a4-related symptoms. PMID:22933323

Hennings, J Christopher; Picard, Nicolas; Huebner, Antje K; Stauber, Tobias; Maier, Hannes; Brown, Dennis; Jentsch, Thomas J; Vargas-Poussou, Rosa; Eladari, Dominique; Hübner, Christian A

2012-10-01

238

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

Microsoft Academic Search

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

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

2001-01-01

239

Lactic acidosis, potassium, and the heart rate deflection point in professional road cyclists  

Microsoft Academic Search

Objective: To determine the influence of lactic acidosis, the Bohr effect, and exercise induced hyperkalaemia on the occurrence of the heart rate deflection point (HRDP) in elite (professional) cyclists.Methods: Sixteen professional male road cyclists (mean (SD) age 26 (1) years) performed a ramp test on a cycle ergometer (workload increases of 5 W\\/12 s, averaging 25 W\\/min). Heart rate (HR),

A Luci?a; J Hoyos; A Santalla; M Pe?rez; A Carvajal; J L Chicharro

2002-01-01

240

Acute phosphate depletion and in vitro rat proximal tubule injury: Protection by glycine and acidosis  

Microsoft Academic Search

Acute phosphate depletion and in vitro rat proximal tubule injury: Protection by glycine and acidosis.The effects of phosphate (PO4) removal from Krebs Henseleit buffer on freshly isolated rat proximal tubules (rPT) were assessed by measuring Ca2+ uptake (nmol\\/mg protein), cellular adenosine triphosphate (ATP) (nmol\\/mg), tissue K+ content (nmol\\/mg) and lactate dehydrogenase (LDH) as an index of cell integrity. Ca2+ uptake

Antonio R P Almeida; Jack F M Wetzels; Derek Bunnachak; Thomas J Burke; Cidio Chaimovitz; William S Hammond; Robert W Schrier

1992-01-01

241

Topical acetylsalicylic, salicylic acid and indomethacin suppress pain from experimental tissue acidosis in human skin  

Microsoft Academic Search

Topically applied acetylsalicylic acid (ASA), salicylic acid (SA) and indomethacin were tested in an experimental pain model that provides direct nociceptor excitation through cutaneous tissue acidosis. In 30 volunteers, sustained burning pain was produced in the palmar forearm through a continuous intradermal pressure infusion of a phosphate-buffered isotonic solution (pH 5.2). In 5 different, double-blind, randomized cross-over studies with 6

Kay H. Steen; Peter W. Reeh; Hans W. Kreysel

1995-01-01

242

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

243

Hypercapnic respiratory acidosis: A protective or harmful strategy for critically ill newborn foals?  

PubMed Central

This paper reviews both the beneficial and adverse effects of permissive hypercapnic respiratory acidosis in critically ill newborn foals. It has been shown that partial carbon dioxide pressure (PCO2) above the traditional safe range (hypercapnia), has beneficial effects on the physiology of the respiratory, cardiovascular, and nervous system in neonates. In human neonatal critical care medicine permissive hypercapnic acidosis is generally well-tolerated by patients and is more beneficial to their wellbeing than normal carbon dioxide (CO2) pressure or normocapnia. Even though adverse effects of hypercapnia have been reported, especially in patients with central nervous system pathology and/or chronic infection, critical care clinicians often artificially increase PCO2 to take advantage of its positive effects on compromised neonate tissues. This is referred to as therapeutic hypercapnia. Hypercapnic respiratory acidosis is common in critically ill newborn foals and has traditionally been considered as not beneficial. A search of online scientific databases was conducted to survey the literature on the effects of hypercapnia in neonates, with emphasis on newborn foals. The dynamic status of safety levels of PCO2 and data on the effectiveness of different carbon dioxide levels are not available for newborn foals and should be scientifically determined. Presently, permissive hypercapnia should be implemented or tolerated cautiously in compromised newborn foals and its use should be based on relevant data from adult horses and other species. PMID:23543953

Vengust, Modest

2012-01-01

244

Misexpression of a Chloroplast Aspartyl Protease Leads to Severe Growth Defects and Alters Carbohydrate Metabolism in Arabidopsis1[C][W  

PubMed Central

The crucial role of carbohydrate in plant growth and morphogenesis is widely recognized. In this study, we describe the characterization of nana, a dwarf Arabidopsis (Arabidopsis thaliana) mutant impaired in carbohydrate metabolism. We show that the nana dwarf phenotype was accompanied by altered leaf morphology and a delayed flowering time. Our genetic and molecular data indicate that the mutation in nana is due to a transfer DNA insertion in the promoter region of a gene encoding a chloroplast-located aspartyl protease that alters its pattern of expression. Overexpression of the gene (oxNANA) phenocopies the mutation. Both nana and oxNANA display alterations in carbohydrate content, and the extent of these changes varies depending on growth light intensity. In particular, in low light, soluble sugar levels are lower and do not show the daily fluctuations observed in wild-type plants. Moreover, nana and oxNANA are defective in the expression of some genes implicated in sugar metabolism and photosynthetic light harvesting. Interestingly, some chloroplast-encoded genes as well as genes whose products seem to be involved in retrograde signaling appear to be down-regulated. These findings suggest that the NANA aspartic protease has an important regulatory function in chloroplasts that not only influences photosynthetic carbon metabolism but also plastid and nuclear gene expression. PMID:22987884

Paparelli, Eleonora; Gonzali, Silvia; Parlanti, Sandro; Novi, Giacomo; Giorgi, Federico M.; Licausi, Francesco; Kosmacz, Monika; Feil, Regina; Lunn, John E.; Brust, Henrike; van Dongen, Joost T.; Steup, Martin; Perata, Pierdomenico

2012-01-01

245

In vivo indices for predicting acidosis risk of grains in cattle: Comparison with in vitro methods.  

PubMed

Our objective was to evaluate a near-infrared reflectance spectroscopy (NIRS) used in the feed industry to estimate the potential for grains to increase the risk of ruminal acidosis. The existing NIRS calibration was developed from in sacco and in vitro measures in cattle and grain chemical composition measurements. To evaluate the existing model, 20 cultivars of 5 grain types were fed to 40 Holstein heifers using a grain challenge protocol and changes in rumen VFA, ammonia, lactic acids, and pH that are associated with acidosis were measured. A method development study was performed to determine a grain feeding rate sufficient to induce non-life threatening but substantial ruminal changes during grain challenge. Feeding grain at a rate of 1.2% of BW met these criteria, lowering rumen pH (P = 0.01) and increasing valerate (P < 0.01) and propionate concentrations (P = 0.01). Valerate was the most discriminatory measure indicating ruminal change during challenge. Heifers were assigned using a row by column design in an in vivo study to 1 of 20 grain cultivars and were reassigned after a 9 d period (n = 4 cattle/treatment). The test grains were dry rolled oats (n = 3), wheat (n = 6), barley (n = 4), triticale (n = 4), and sorghum (n = 3) cultivars. Cattle were adapted to the test grain and had ad libitum access to grass silage 11 d before the challenge. Feed was withheld for 14 h before challenge feeding with 0.3 kg DM of silage followed by the respective test grain fed at 1.2% of BW. A rumen sample was taken by stomach tube 5, 65, 110, 155, and 200 min after grain consumption. The rumen is not homogenous and samples of rumen fluid obtained by stomach tube will differ from those gained by other methods. Rumen pH was measured immediately; individual VFA, ammonia, and D- and L-lactate concentrations were analyzed later. Rumen pH (P = 0.002) and all concentrations of fermentation products differed among grains (P = 0.001). A previously defined discriminant score calculated at 200 min after challenge was used to rank grains for acidosis risk. A significant correlation between the discriminant score and the NIRS ranking (r = 0.731, P = 0.003) demonstrated the potential for using NIRS calibrations for predicting acidosis risk of grains in cattle. The overall rankings of grains for acidosis risk were wheat > triticale > barley > oats > sorghum. PMID:23482574

Lean, I J; Golder, H M; Black, J L; King, R; Rabiee, A R

2013-06-01

246

Acidosis during early reperfusion prevents myocardial stunning in perfused ferret hearts.  

PubMed Central

Cellular calcium overload figures prominently in the pathogenesis of the contractile dysfunction observed after brief periods of ischemia (myocardial stunning). Because acidosis is known to antagonize Ca influx and the intracellular binding of Ca, we reasoned that acidosis during reperfusion might prevent Ca overload and ameliorate functional recovery. We measured developed pressure (DP) and 31P-nuclear magnetic resonance spectra in 26 isovolumic Langendorff-perfused ferret hearts. After 15 min of global ischemia, hearts were reperfused either with normal solution (2 mM [Ca]o, Hepes-buffered, pH 7.4 bubbled with 100% O2; n = 6) or with acidic solutions (pH 6.6 during 0-3 min, pH 7.0 during 4-6 min) before returning to the normal perfusate (n = 7). Ventricular function after 30 min of reperfusion was much greater in the acidic group (105 +/- 5 mmHg at 2 mM [Ca]o) than in the unmodified reperfusion group (79 +/- 7 mmHg, P less than 0.001); similar differences in DP were found over a broad range of [Ca]o (0.5-5 mM, P less than 0.001) and during maximal Ca2+ activation (P less than 0.001). Intramyocardial pH (pHi) was lower in the acidic group than in the unmodified group during early reperfusion, but not at steady state. Phosphate compounds were comparable in both groups. To clarify whether the protective effect of acidosis is due to intracellular or extracellular pH, we produced selective intracellular acidosis during early reperfusion by exposure to 10 mM NH4Cl for 6 min just before ischemia (n = 6). For the first 12 min of reperfusion with NH4Cl-free solution (pH = 7.4), pHi was decreased relative to the unmodified group. Recovery of DP was practically complete, and maximal Ca2+-activated pressure was comparable to that in a nonischemic control group (n = 5). These results indicate that transient intracellular acidosis can prevent myocardial stunning, presumably owing to a reduction of Ca influx into cells and/or competition of H+ for intracellular Ca2+ binding sites during early reperfusion. PMID:3417873

Kitakaze, M; Weisfeldt, M L; Marban, E

1988-01-01

247

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

248

Interstrain differences in the severity of liver injury induced by a choline- and folate-deficient diet in mice are associated with dysregulation of genes involved in lipid metabolism.  

PubMed

Nonalcoholic fatty liver disease (NAFLD) is a major health problem and a leading cause of chronic liver disease in the United States and developed countries. In humans, genetic factors greatly influence individual susceptibility to NAFLD. The goals of this study were to compare the magnitude of interindividual differences in the severity of liver injury induced by methyl-donor deficiency among individual inbred strains of mice and to investigate the underlying mechanisms associated with the variability. Feeding mice a choline- and folate-deficient diet for 12 wk caused liver injury similar to NAFLD. The magnitude of liver injury varied among the strains, with the order of sensitivity being A/J ? C57BL/6J ? C3H/HeJ < 129S1/SvImJ ? CAST/EiJ < PWK/PhJ < WSB/EiJ. The interstrain variability in severity of NAFLD liver damage was associated with dysregulation of genes involved in lipid metabolism, primarily with a down-regulation of the peroxisome proliferator receptor ? (PPAR?)-regulated lipid catabolic pathway genes. Markers of oxidative stress and oxidative stress-induced DNA damage were also elevated in the livers but were not correlated with severity of liver damage. These findings suggest that the PPAR?-regulated metabolism network is one of the key mechanisms determining interstrain susceptibility and severity of NAFLD in mice. PMID:22872676

Tryndyak, Volodymyr; de Conti, Aline; Kobets, Tetyana; Kutanzi, Kristy; Koturbash, Igor; Han, Tao; Fuscoe, James C; Latendresse, John R; Melnyk, Stepan; Shymonyak, Svitlana; Collins, Leonard; Ross, Sharon A; Rusyn, Ivan; Beland, Frederick A; Pogribny, Igor P

2012-11-01

249

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

PubMed Central

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 p90RSK (90 kDa ribosomal S6 kinase) were determined by Western blotting. This revealed a time-dependent transient phosphorylation of both ERK1/2 and p90RSK by intracellular acidosis (intracellular pH ?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 ?6.8 to ?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

2006-01-01

250

Insulin regulates the expression of several metabolism-related genes in the liver and primary hepatocytes of rainbow trout (Oncorhynchus mykiss).  

PubMed

Rainbow trout have a limited ability to use dietary carbohydrates efficiently and are considered to be glucose intolerant. Administration of carbohydrates results in persistent hyperglycemia and impairs post-prandial down regulation of gluconeogenesis despite normal insulin secretion. Since gluconeogenic genes are mainly under insulin control, we put forward the hypothesis that the transcriptional function of insulin as a whole may be impaired in the trout liver. In order to test this hypothesis, we performed intraperitoneal administration of bovine insulin to fasted rainbow trout and also subjected rainbow trout primary hepatocytes to insulin and/or glucose stimulation. We demonstrate that insulin was able to activate Akt, a key element in the insulin signaling pathway, and to regulate hepatic metabolism-related target genes both in vivo and in vitro. In the same way as in mammals, insulin decreased mRNA expression of gluconeogenic genes, including glucose 6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBPase) and phosphoenolpyruvate carboxykinase (PEPCK). Insulin also limited the expression of carnitine palmitoyltransferase 1 (CPT1), a limiting enzyme of fatty acid beta-oxidation. In vitro studies revealed that, as in mammals, glucose is an important regulator of some insulin target genes such as the glycolytic enzyme pyruvate kinase (PK) and the lipogenic enzyme fatty acid synthase (FAS). Interestingly, glucose also stimulates expression of glucokinase (GK), which has no equivalent in mammals. This study demonstrates that insulin possesses the intrinsic ability to regulate hepatic gene expression in rainbow trout, suggesting that other hormonal or metabolic factors may counteract some of the post-prandial actions of insulin. PMID:18626086

Plagnes-Juan, Elisabeth; Lansard, Marine; Seiliez, Iban; Médale, Françoise; Corraze, Geneviève; Kaushik, Sadasivam; Panserat, Stéphane; Skiba-Cassy, Sandrine

2008-08-01

251

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

PubMed

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

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

2012-05-01

252

A Case of Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MEALS) Syndrome with Intracardiac Thrombus  

PubMed Central

Myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a multisystem clinical syndrome manifested by mitochondrial myopathy, encephalopathy, lactic acidosis and recurrent stroke-like episodes. A 27-year-old female with MELAS syndrome presented with cerebral infarction. Echocardiography revealed a thrombus attached to the apex of the hypertrophied left ventricle, with decreased systolic function. The embolism of the intracardiac thrombus might have been the cause of stroke. There should be more consideration given to the increased possibility of intracardiac thrombus formation when a MELAS patient with cardiac involvement is encountered. PMID:23613701

Joo, Jung-Chul; Seol, Myung Do; Yoon, Jin Won; Lee, Young Soo; Kim, Dong-Keun; Choi, Yong Hoon; Ahn, Hyo Seong

2013-01-01

253

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, Clement; Bevengut, Michelle; Fasano, Caroline; Vigneault, Erika; Mestikawy, Salah El; Hilaire, Gerard

2010-01-01

254

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

255

Disturbance of apolipoprotein B100 containing lipoprotein metabolism in severe hyperlipidemic and lipodystrophic HIV patients on combined antiretroviral therapy: evidences of insulin resistance effect.  

PubMed

The aim was to study the mechanisms involved in the dyslipidemia associated with lipodystrophy in HIV infected patients on antiretroviral therapy (ART). We investigated the in vivo kinetics of apolipoprotein B100 (apoB) containing lipoproteins using a 14 h primed constant infusion of [5,5,5, (2)H(3)] leucine and compartmental modelling in normolipidemic without lipodystrophy (7 patients, NLD) or dyslipidemic with lipodystrophy (7 patients, LD) treated with ART. Subjects in group LD showed higher plasma triglycerides (5.73+/-3.58 vs 1.29+/-0.54 g/L, p<0.005), total cholesterol (2.98+/-0.95 vs 1.74+/-0.26 g/L, p<0.05), apoB (1.49+/-1.11 vs 0.51+/-0.11 g/L, p<0.005) and apolipoprotein CIII in apoB containing lipoproteins (117.7+/-42.2 vs 22.6+/-23.9 g/L, p<0.005). LD subjects exhibited an insulin resistant as observed by higher HOMA (3.44+/-1.62 vs 1.60+/-0.61, p<0.05). They exhibited an increase in VLDL (1.24+/-0.33 vs 0.80+/-0.21 mg/kg/h, p<0.05), decrease in IDL (0.20+/-0.10 vs 0.48+/-0.24 mg/kg/h, p<0.05) and no difference in LDL (0.38+/-0.19 vs 0.45+/-0.25 mg/kg/h) production rate. LD subject also showed a dramatic decrease in transformation of VLDL to IDL (0.013+/-0.010 vs 0.258+/-0.206 h(-1), p<0.005) and IDL to LDL (0.088+/-0.093 vs 0.366+/-0.189 h(-1), p<0.05) and a decrease in fractional catabolic rate (FCR) of VLDL (0.199+/-0.132 vs 0.555+/-0.398 h(-1), p<0.05), IDL (0.110+/-0.08 vs 0.523+/-0.275 h(-1), p<0.05) and LDL (0.010+/-0.005 vs 0.025+/-0.014 h(-1), p<0.05). These disturbances, overproduction and an overall delayed catabolism of apoB, are similar to those observed using the same protocol in insulin resistant subjects. Our study suggests that metabolic disturbance of apoB100 observed in lipodystrophic HIV in combined antiretroviral therapy are consecutive to insulin resistance induced by the treatment. PMID:18991738

Ouguerram, Khadija; Zair, Yassine; Billon, Stéphanie; Chétiveaux, Maud; Brunet-François, Cécile; Ngohou-Bach, Kalyane; Allavena, Clotilde; Reliquet, Veronique; Milpied, Brigitte; Magot, Thierry; Raffi, François; Krempf, Michel

2008-11-01

256

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

PubMed

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

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

2014-04-01

257

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

258

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

259

Genetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy.  

PubMed

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

260

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

261

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

262

Thiamine deficiency as a single cause of life-threatening lactic acidosis in a patient with acute axonal polyneuropathy  

Microsoft Academic Search

SIMI 2009 We present a patient without a history of alcohol abuse with an acute axonal polyneuropathy in combination with a sudden lactic acidosis in whom by exclusion a thiamine deficiency could be established as the only cause of his illness. A 56-year-old man presented with muscle weakness increasing during the prior 4 weeks. He had a history of myocardial

Petronella Johanna Van den Berg; Peter J. Bijlstra; Geert J. F. Brekelmans

2009-01-01

263

Extracellular Acidosis Stimulates NHE2 Expression through Activation of Transcription Factor Egr-1 in the Intestinal Epithelial Cells  

PubMed Central

Na+/H+ exchangers (NHEs) play important roles in regulating internal pH (pHi), cell volume and neutral Na+ absorption in the human intestine. Earlier studies have shown that low extracellular pH (pHe) and metabolic acidosis increases the expression and function of NHE1-3 genes. However, transcriptional mechanisms involved remained unknown. Therefore, we investigated the molecular mechanisms underlying acid-induced NHE2 expression in C2BBe1 and SK-CO15 intestinal epithelial cells. Assessing total RNA and protein by RT-PCR and Western blot analysis, respectively, displayed significant increases in the NHE2 mRNA and protein levels in cells exposed to acidic media (pH 6.5 and 6.7) compared to normal medium. Acid treatment was also associated with a significant enhancement in NHE2 transport activity. Quantification of the heterogeneous nuclear RNA indicated that the rate of NHE2 transcription was increased in response to acid. Furthermore, acid caused a significant increase in NHE2 promoter activity confirming transcriptional upregulation. Through functional and mutational studies the acid-response element was mapped to a 15-nucleotide GC-rich sequence at bp ?337 to ?323 upstream from the transcription start site. We previously identified this element as an overlapping Egr-1/Sp1/Egr-1 motif that was essential for the NHE2 upregulation by mitogen-induced transcription factor Egr-1. Cells exposed to acid exhibited a temporal increase in Egr-1 mRNA and protein expression. These events were followed by Egr-1 nuclear accumulation, as detected by immunofluorescence microscopy, and potentiated its in vitro and in vivo interaction with the NHE2 promoter. Disruption of ESE motif and knockdown of Egr-1 expression by targeted small interfering RNA abrogated the acid-induced NHE2 transcriptional activity. These data indicate that the acid-dependent NHE2 stimulation is implemented by transcriptional upregulation of NHE2 via acid-induced Egr-1 in the intestinal epithelial cells. PMID:24376510

Jeong, Jong-Jin; Kumar, Anoop; Dudeja, Pradeep K.; Malakooti, Jaleh

2013-01-01

264

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

PubMed

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

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

2014-11-01

265

Factors associated with thrombocytopenia in severe leptospirosis (Weil's disease)  

PubMed Central

OBJECTIVE: This study was conducted to investigate factors associated with thrombocytopenia in a large cohort of patients with leptospirosis in an endemic area. METHODS: This retrospective study included 374 consecutive patients with leptospirosis who were admitted to tertiary hospitals in Fortaleza, Brazil. All patients had a diagnosis of severe leptospirosis (Weil's disease). Acute kidney injury was defined according to the RIFLE criteria. Thrombocytopenia was defined as a platelet count <100,000/mm3. RESULTS: A total of 374 patients were included, with a mean age of 36.1±15.5 years, and 83.4% were male. Thrombocytopenia was present at the time of hospital admission in 200 cases (53.5%), and it developed during the hospital stay in 150 cases (40.3%). The patients with thrombocytopenia had higher frequencies of dehydration (53% vs. 35.3%, p?=?0.001), epistaxis (5.7% vs. 0.8%, p?=?0.033), hematemesis (13% vs. 4.6%, p?=?0.006), myalgia (91.5% vs. 84.5%, p?=?0.038), hematuria (54.8% vs. 37.6%, p?=?0.011), metabolic acidosis (18% vs. 9.2%, p?=?0.016) and hypoalbuminemia (17.8% vs. 7.5%, p?=?0.005). The independent risk factors associated with thrombocytopenia during the hospital stay were lengthy disease (OR: 1.2, p?=?0.001) and acute kidney injury (OR: 6.6, p?=?0.004). Mortality was not associated with thrombocytopenia at admission (12.5% vs. 12.6%, p?=?1.000) or during the hospital stay (12.6% vs. 11.3%, p?=?0.748). CONCLUSIONS: Thrombocytopenia is a frequent complication in leptospirosis, and this condition was present in more than half of patients at the time of hospital admission. Lengthy disease and acute kidney injury are risk factors for thrombocytopenia. There was no significant association between thrombocytopenia and mortality. PMID:24519201

Daher, Elizabeth F.; Silva, Geraldo B.; Silveira, Charles O.; Falcao, Felipe S.; Alves, Marilia P.; Mota, Jorio A. A. A.; Lima, Joyce B.; Mota, Rosa M. S.; Vieira, Ana Patricia F.; da Justa Pires Neto, Roberto; Liborio, Alexandre B.

2014-01-01

266

The Role of Metformin in Metformin-Associated Lactic Acidosis (MALA): Case Series and Formulation of a Model of Pathogenesis.  

PubMed

BACKGROUND: Lactic acidosis is an adverse event associated with metformin usage. Patients with metformin-associated lactic acidosis (MALA), however, often have other conditions contributing to the event. The relative contribution of metformin is often unclear. MALA is usually diagnosed without measuring the plasma concentrations of metformin. OBJECTIVES: The objectives of this study were, first, to examine the plasma concentrations of metformin, lactate and creatinine and the arterial pH of patients with suspected MALA and, second, to review critically the mechanisms of MALA. METHODS: Patients who were suspected of having MALA were identified during the period October 2008-September 2011. Repeated blood samples were collected to determine the plasma concentrations of lactate, metformin and creatinine. The pH of arterial blood was also measured on several occasions in each patient. RESULTS: Patients (n = 15; 9 female, 6 male) were 70 ± 12 years of age. There was one acute metformin overdose (estimated dose 5 g). Metformin was undetectable in one patient and one patient had therapeutic concentrations of metformin on admission (<5 mg/L). There were ten patients with chronic kidney disease, whereby the estimated glomerular filtration rate (eGFR) was less than 60 mL/min/1.73 m(2) before the acidotic event. Metformin doses ranged from 1 to 3 g daily (excluding the deliberate overdose). On admission, the mean plasma concentration of metformin on admission was 29.8 ± 19.1 mg/L (mean ± SD), the mean lactate concentration was 12.9 ± 6.1 mmol/L and the mean pH was 7 ± 0.2. The mean creatinine concentration on admission was 481 ± 225 ?mol/L. The main pre-admission symptoms were vomiting and diarrhoea (n = 12). There were linear relationships between venous lactate, venous creatinine and arterial pH, with the venous plasma concentrations of metformin in most patients. Three patients died but metformin was unlikely to have been a significant factor. DISCUSSION AND REVIEW: Most patients with MALA presented to the hospital with high metformin concentrations. The following factors appear to have been involved in the development of MALA in these patients: vomiting and diarrhoea, acute kidney injury, high doses or excessive accumulation of metformin, and acute disease states leading to tissue hypoxia. The extent of metformin accumulation in patients with MALA can be determined by investigating the concentrations of metformin. We suggest that the development of MALA is due to a positive feedback system involving one or more of these factors. While nausea is a common adverse effect of metformin, vomiting and diarrhoea out of the ordinary is a clear first sign of MALA. In this condition, dosage with metformin should be stopped and patients should receive urgent medical attention. PMID:23549904

Duong, Janna K; Furlong, Timothy J; Roberts, Darren M; Graham, Garry G; Greenfield, Jerry R; Williams, Kenneth M; Day, Richard O

2013-04-01

267

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

PubMed Central

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

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

2012-01-01

268

Regulation of intracellular pH in cnidarians: response to acidosis in Anemonia viridis.  

PubMed

The regulation of intracellular pH (pHi) is a fundamental aspect of cell physiology that has received little attention in studies of the phylum Cnidaria, which includes ecologically important sea anemones and reef-building corals. Like all organisms, cnidarians must maintain pH homeostasis to counterbalance reductions in pHi, which can arise because of changes in either intrinsic or extrinsic parameters. Corals and sea anemones face natural daily changes in internal fluids, where the extracellular pH can range from 8.9 during the day to 7.4 at night. Furthermore, cnidarians are likely to experience future CO?-driven declines in seawater pH, a process known as ocean acidification. Here, we carried out the first mechanistic investigation to determine how cnidarian pHi regulation responds to decreases in extracellular and intracellular pH. Using the anemone Anemonia viridis, we employed confocal live cell imaging and a pH-sensitive dye to track the dynamics of pHi after intracellular acidosis induced by acute exposure to decreases in seawater pH and NH?Cl prepulses. The investigation was conducted on cells that contained intracellular symbiotic algae (Symbiodinium sp.) and on symbiont-free endoderm cells. Experiments using inhibitors and Na?-free seawater indicate a potential role of Na?/H? plasma membrane exchangers (NHEs) in mediating pHi recovery following intracellular acidosis in both cell types. We also measured the buffering capacity of cells, and obtained values between 20.8 and 43.8 mM per pH unit, which are comparable to those in other invertebrates. Our findings provide the first steps towards a better understanding of acid-base regulation in these basal metazoans, for which information on cell physiology is extremely limited. PMID:24256552

Laurent, Julien; Venn, Alexander; Tambutté, Éric; Ganot, Philippe; Allemand, Denis; Tambutté, Sylvie

2014-02-01

269

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

PubMed

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

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

2014-02-01

270

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

271

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

272

Targeting the metabolic microenvironment of tumors.  

PubMed

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 neoangiogenesis. 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 preclinical 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

2012-01-01

273

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

PubMed Central

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

2013-01-01

274

Effect of severe normocapnic hypoxia on renal function in growth-restricted newborn piglets.  

PubMed

To examine the effects of intrauterine growth restriction and acute severe oxygen deprivation on renal blood flow (RBF), renovascular resistance (RVR), and renal excretory functions in newborns, studies were conducted on 1-day-old anesthetized piglets divided into groups of normal weight (NW, n = 14) and intrauterine growth-restricted (IUGR, n = 14) animals. Physiological parameters, RBF, RVR, and urinary flow, were similar in NW and IUGR piglets, but glomerular filtration rate (GFR) and filtration fraction were significantly less in IUGR animals (P < 0.05). An induced 1-h severe hypoxia (arterial PO(2) = 19 +/- 4 mmHg) resulted in, for both groups, a pronounced metabolic acidosis, strongly reduced RBF, and increased fractional sodium excretion (FSE; P < 0.05) with a less-pronounced increase of RVR and arterial catecolamines in IUGR piglets. Of significance was a smaller decrease in RBF for IUGR piglets (P < 0.05). Early recovery showed a transient period of diuresis with increased osmotic clearance and elevated FSE in both groups (P < 0.05). However, GFR and renal O(2) delivery remained reduced in NW piglets (P < 0.05). We conclude that, in newborn IUGR piglets, RBF is maintained, although GFR is compromised. Severe hypoxemia induces similar alterations of renal excretion in newborn piglets. However, the less-pronounced RBF reduction during hypoxemia indicates an improved adaptation of newborn IUGR piglets on periods of severely disturbed oxygenation. Furthermore, newborn piglets reestablish the ability for urine concentration and adequate sodium reabsorption early after reoxygenation so that a sustained acute renal failure was prevented. PMID:10956260

Bauer, R; Walter, B; Zwiener, U

2000-09-01

275

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

276

Hypercapnia causes cellular oxidation and nitrosation in addition to acidosis: implications for CO2 chemoreceptor function and dysfunction  

PubMed Central

Cellular mechanisms of CO2 chemoreception are discussed and debated in terms of the stimuli produced during hypercapnic acidosis and their molecular targets: protons generated by the hydration of CO2 and dissociation of carbonic acid, which target membrane-bound proteins and lipids in brain stem neurons. The CO2 hydration reaction, however, is not the only reaction that CO2 undergoes that generates molecules capable of modifying proteins and lipids. Molecular CO2 also reacts with peroxynitrite (ONOO?), a reactive nitrogen species (RNS), which is produced from nitric oxide (•NO) and superoxide (•O2?). The CO2/ONOO? reaction, in turn, produces additional nitrosative and oxidative reactive intermediates. Furthermore, protons facilitate additional redox reactions that generate other reactive oxygen species (ROS). ROS/RNS generated by these redox reactions may act as additional stimuli of CO2 chemoreceptors since neurons in chemosensitive areas produce both •NO and •O2? and, therefore, ONOO?. Perturbing •NO, •O2?, and ONOO? activities in chemosensitive areas modulates cardiorespiration. Moreover, neurons in at least one chemosensitive area, the solitary complex, are stimulated by cellular oxidation. Together, these data raise the following two questions: 1) do pH and ROS/RNS work in tandem to stimulate CO2 chemoreceptors during hypercapnic acidosis; and 2) does nitrosative stress and oxidative stress contribute to CO2 chemoreceptor dysfunction? To begin considering these two issues and their implications for central chemoreception, this minireview has the following three goals: 1) summarize the nitrosative and oxidative reactions that occur during hypercapnic acidosis and isocapnic acidosis; 2) review the evidence that redox signaling occurs in chemosensitive areas; and 3) review the evidence that neurons in the solitary complex are stimulated by cellular oxidation. PMID:20150563

2010-01-01

277

Wolff-Parkinson-White Syndrome in a Patient With Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes Syndrome  

PubMed Central

Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a multisystem disorder, which is clinically characterized by encephalopathy, dementia, seizures and stroke-like episodes. Multiple organs can be affected and cardiac involvement often dominates the clinical picture because of its high energy requirement. We report a case of a 21-year-old woman with MELAS syndrome who had pre-excitation ECG and one episode of tachycardia attack. PMID:22194764

Lee, Min-Ho; Sung, Young-Jun; Yoon, Jung-Han; Kim, Jiyeong; Oh, Il-Young; Choi, Eue-Keun

2011-01-01

278

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

279

Hypoxia and Acidosis Independently Up-Regulate Vascular Endothelial Growth Factor Transcription in Brain Tumors in Vivo1  

Microsoft Academic Search

Hypoxia and acidosis are hallmarks of tumors as well as critical deter- minants of response to treatments. They can upregulate vascular endo- thelial growth factor (VEGF) in vitro. However, the relationship between tissue oxygen partial pressure (pO2)\\/pH and VEGF transcription in vivo is not known. Thus, we developed a novel in vivo microscopy technique to simultaneously measure VEGF promoter activity,

Dai Fukumura; Lei Xu; Yi Chen; Takeshi Gohongi; Brian Seed; Rakesh K. Jain

2001-01-01

280

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

PubMed Central

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

Kumar, Arvind; Raina, Vinod

2014-01-01

281

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

PubMed Central

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

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

2014-01-01

282

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

PubMed

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

Dong, Biao; Zhou, Honglan; Han, Conghui; Yao, Jufang; Xu, Longmei; Zhang, Ming; Fu, Yaowen; Xia, Qiang

2014-01-01

283

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, Maria Daniella; Alarcon, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Caceres, Dante Daniel; Hidalgo, Maria Angelica

2014-01-01

284

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

285

Lactate metabolism: a new paradigm for the third millennium  

PubMed Central

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

Gladden, L B

2004-01-01

286

Metabolically induced heteroplasmy shifting and L-arginine treatment reduce the energetic defect in a neuronal-like model of MELAS  

PubMed Central

The m.3243A>G variant in the mitochondrial tRNALeu (UUR) gene is a common mitochondrial DNA (mtDNA) mutation. Phenotypic manifestations depend mainly on the heteroplasmy, i.e. the ratio of mutant to normal mtDNA copies. A high percentage of mutant mtDNA is associated with a severe, life-threatening neurological syndrome known as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). MELAS is described as a neurovascular disorder primarily affecting the brain and blood vessels, but the pathophysiology of the disease is poorly understood. We developed a series of cybrid cell lines at two different mutant loads: 70% and 100% in the nuclear background of a neuroblastoma cell line (SH-SY5Y). We investigated the impact of the mutation on the metabolism and mitochondrial respiratory chain activity of the cybrids. The m.3243A>G mitochondrial mutation induced a metabolic switch towards glycolysis in the neuronal cells and produced severe defects in respiratory chain assembly and activity. We used two strategies to compensate for the biochemical defects in the mutant cells: one consisted of lowering the glucose content in the culture medium, and the other involved the addition of L-arginine. The reduction of glucose significantly shifted the 100% mutant cells towards the wild-type, reaching a 90% mutant level and restoring respiratory chain complex assembly. The addition of L-arginine, a nitric oxide (NO) donor, improved complex I activity in the mutant cells in which the defective NO metabolism had led to a relative shortage of NO. Thus, metabolically induced heteroplasmy shifting and L-arginine therapy may constitute promising therapeutic strategies against MELAS. PMID:22306605

Desquiret-Dumas, Valerie; Gueguen, Naig; Barth, Magalie; Chevrollier, Arnaud; Hancock, Saege; Wallace, Douglas C; Amati-Bonneau, Patrizia; Henrion, Daniel; Bonneau, Dominique; Reynier, Pascal; Procaccio, Vincent

2012-01-01

287

Early respiratory acidosis is a new risk factor for pneumonia after lung resection.  

PubMed

Postoperative pneumonia (POP) is a life-threatening complication of lung resection (LR). Its risk factors, bacteriological profile and outcome are not well known. The aims of this study were to describe the outcome and causal bacteria and to identify risk factors for POP. We reviewed all cases admitted to intensive care after LR. Clinical parameters, operative and postoperative data were recorded. POP was suspected on the basis of fever, radiographic infiltrate, and either leucocytosis or purulent sputum. The diagnosis was confirmed by culture of a respiratory sample. Risk factors for POP were identified by univariate and multivariate analysis. We included 159 patients in this study. POP was diagnosed in 23 patients (14.4%) and was associated with a higher hospital mortality rate (30% versus 5%, P = 0.0007) and a longer hospital stay. Members of the Enterobacteriaceae and Pseudomonas species were the most frequently identified pathogens. Early respiratory acidosis (ERA; OR, 2.94; 95% CI, 1.1-8.1), blood transfusion (OR, 3.8; 95% CI, 1.1-13.1), bilobectomy (OR, 7.26; 95% CI, 1.2-43.1) and smoking history (OR, 1.84; 95% CI, 1.1-3) were identified as independent risk factors. ERA may be a risk factor for POP and could serve as a target for therapeutic interventions. PMID:22184462

Planquette, Benjamin; Le Pimpec-Barthes, Françoise; Trinquart, Ludovic; Meyer, Guy; Riquet, Marc; Sanchez, Olivier

2012-03-01

288

Low Temperature-Induced Cytoplasmic Acidosis in Cultured Mung Bean (Vigna radiata [L.] Wilczek) Cells.  

PubMed Central

Cold-induced changes in vivo in the cytoplasmic pH of suspension-cultured cells of mung bean (Vigna radiata [L.] Wilczek) were investigated by fluorescence-ratio imaging cryomicroscopy with special reference to the variations in the chilling sensitivity of cells during the growth cycle. Because of the preferential localization of the fluorophore in the cytoplasm under specified conditions and the ideal response of fluorescence to pH, fluorescein diacetate allows measurements to be made of temporal changes in cytoplasmic pH at low temperature. A remarkable difference was demonstrated in the cold-induced changes in cytoplasmic pH between cells at the early and late stages of exponential growth. The cells at the early stage of exponential growth were most sensitive to chilling, and the cytoplasmic pH decreased dramatically within a short period of incubation at 0[deg]C, decreasing from 7.4 to 6.8 after 4 h and to 6.3 after 18 h. The cells at the late stage of exponential growth were chilling tolerant, and no significant decrease in the cytoplasmic pH was observed during the incubation at 0[deg]C for 24 h or even longer. From the results presented here, it appears that cold-induced cytoplasmic acidosis is characteristic of chilling-sensitive mung bean suspension-cultured cells. PMID:12232153

Yoshida, S.

1994-01-01

289

Toxicokinetics of metformin-associated lactic acidosis with continuous renal replacement therapy.  

PubMed

A 70-year-old diabetic male patient with a baseline serum creatinine of 1.4 mg/dL presented with nausea and vomiting. He was diagnosed with metformin-associated lactic acidosis and acute kidney injury. He was managed with continuous veno-venous hemodiafiltration (CVVHDF). By measuring metformin concentration at different time intervals, we calculated the apparent volume of distribution of metformin at 34.7 L. The decline in serum metformin followed single-compartment first-order kinetics with an elimination rate constant of 0.0418/h and a serum half-life of 16.5 h; no metformin rebound was seen after discontinuation of CVVHDF. Using the previously calculated volume of distribution we calculated the expected serum metformin concentration 25 h post CVVHDF to be 3.0-3.7 ?g/mL. The measured serum metformin of 3.4 ?g/ml fell within the predicted range. During CVVHDF, dialyzer metformin clearance approximates 88.7 % of dialyzer urea clearance and 90.1 % of dialyzer creatinine clearance. PMID:22926933

Mujtaba, Muhammad; Geara, Abdallah Sassine; Madhrira, Machaiah; Agarwala, Rajesh; Anderson, Herman; Cheng, Jen-Tse; Mohan, Sumit

2012-12-01

290

Treatment options for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome.  

PubMed

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare neurodegenerative disease caused by the decreased ability of cells to produce sufficient energy in the form of adenosine 5'-triphosphate. Although it is one of the most common maternally inherited mitochondrial disorders, its exact incidence is unknown. Caused most frequently by an A-to-G point mutation at the 3243 position in the mitochondrial DNA, MELAS syndrome has a broad range of clinical manifestations and a highly variable course. The classic neurologic characteristics include encephalopathy, seizures, and stroke-like episodes. In addition to its neurologic manifestations, MELAS syndrome exhibits multisystem effects including cardiac conduction defects, diabetes mellitus, short stature, myopathy, and gastrointestinal disturbances. Unfortunately, no consensus guidelines outlining standard drug regimens exist for this syndrome. Many of the accepted therapies used in treating MELAS syndrome have been identified through a small number of clinical trials or isolated case reports. Currently, the drugs most often used include antioxidants and various vitamins aimed at minimizing the demands on the mitochondria and supporting and maximizing their function. Some of the most frequently prescribed agents include coenzyme Q(10), l-arginine, B vitamins, and levocarnitine. Although articles describing MELAS syndrome are available, few specifically target education for clinical pharmacists. This article will provide pharmacists with a practical resource to enhance their understanding of MELAS syndrome in order to provide safe and effective pharmaceutical care. PMID:20973690

Santa, Kristin M

2010-11-01

291

Hemostatic resuscitation for massive hemorrhage with warm fresh whole blood in a patient with severe blunt trauma.  

PubMed

A 24-year-old male Navy soldier was struck on the left thigh by a ruptured cable and was subsequently thrown into the sea. Initial evaluation showed an Injury Severity Score of 34. Core body temperature was 34.1°C. Laboratory data included a hemoglobin level of 4.5 g/dL and a hematocrit of 13.3%. Prothrombin time was prolonged (>100 seconds), international normalized ratio was elevated (9.99), and partial thromboplastin time was elevated (>180 seconds). The patient was treated for hypothermia, coagulopathy, and metabolic acidosis during resuscitation. The patient was transfused with 16,320 mL of blood during the first 24 hours following the accident, including 4500 mL (18 units) of warm fresh whole blood (WFWB) donated by the patient's military colleagues. The patient was successfully resuscitated, and the injured leg was salvaged. Component therapy can afford replacement of specific deficiencies or requirements, decrease the risk of transfusion-transmitted infectious diseases, and improve resource utilization. However, a protocol of early transfusion with WFWB should be considered during resuscitation following massive hemorrhage in specific conditions such as battle fields or urgent situations. PMID:25300438

Liu, Yuan-Hao; Chao, Chia-Sheng; Chang, Yee-Phoung; Chin, Hsien-Kuo

2014-10-01

292

Convergent signaling by acidosis and receptor activator of NF-?B ligand (RANKL) on the calcium/calcineurin/NFAT pathway in osteoclasts  

PubMed Central

Systemic acidosis has detrimental effects on the skeleton, and local acidosis coincides with bone destruction in inflammatory and metastatic diseases. Acidification dramatically enhances osteoclastic resorption, although the underlying mechanism has remained elusive. We investigated the effect of acidosis on the osteoclastogenic transcription factor NFATc1, which upon dephosphorylation translocates from the cytoplasm to nuclei. Lowering extracellular pH dramatically increased accumulation of NFATc1 in nuclei of rat and rabbit osteoclasts to levels comparable with those induced by the proresorptive cytokine receptor activator of NF-?B ligand (RANKL). Activation of NFATc1 by RANKL was mediated by means of prolonged stimulation of the Ca2+/calmodulin-dependent protein phosphatase, calcineurin. In contrast, NFATc1 activation by acidosis involved stimulation of calcineurin and suppression of NFATc1 inactivation. Acidosis, like RANKL, induced transient elevation of cytosolic free Ca2+ concentration ([Ca2+]i), which persisted in Ca2+-free media and was abolished by inhibition of phospholipase C or depletion of intracellular Ca2+ stores. Real-time-PCR of osteoclast-like cells generated from RAW 264.7 cells revealed high levels of expression of ovarian cancer G protein-coupled receptor 1, which links extracellular acidification to elevation of [Ca2+]i. In addition, the calcineurin inhibitor cyclosporin A suppressed the stimulatory effect of acidification on resorption, implicating NFAT in mediating the actions of acidosis on osteoclast activity. In summary, acidification and RANKL induce signals in osteoclasts that converge on the Ca2+/calcineurin/NFAT pathway. Acidosis acts directly on osteoclasts to activate NFATc1 and stimulate resorption. PMID:15695591

Komarova, Svetlana V.; Pereverzev, Alexey; Shum, Jonathan W.; Sims, Stephen M.; Dixon, S. Jeffrey

2005-01-01

293

Acute toxicity, distribution and metabolism of 2,4,6-trinitrophenol (picric acid) in Fischer 344 rats. (Reannouncement with new availability information)  

SciTech Connect

Picric acid (2,4,6-trinitrophenol) is widely used in industry, by the military, and as a research/clinical chemistry reagent. Characterization of the toxicity of this chemical has been limited. Thus the acute toxicity, distribution, and metabolism of picric acid were investigated using Fischer 344 rats. The LD50 for picric acid following oral dosing of male and female rats was established as 290 and 200 mg/kg, respectively. Blood gas analysis indicated severe acidosis during acute intoxication. Metabolism of picric acid was limited to reduction of nitro groups to amines. Metabolites isolated from urine included N-acetylisopicramic acid (14.8%), picramic acid (18.5%), N-acetylpicramic acid (4.7%), and unidentified components (2.4%). Approximately 60% of the parent picric acid was excreted unchanged. The plasma half-life for picric acid was 13.4h with a gut absorption coefficient(ka) of 0.069h-1. Twenty-four hours following oral administration of (14 C) picric acid (100 mg/kg), the primary depots of radioactivity (per gram tissue basis) were blood, spleen, kidney, liver lung, and testes. Respective tissue/blood ratios were 0.37, 0.31, 0.28, 0.26, and 0.22. All other tissue assayed had partition ratios < 0.20, with brain and adipose tissue having the least amount of radioactivity.

Wyman, J.F.; Serve, M.P.; Hobson, D.W.; Lee, L.H.; Uddin, D.

1992-12-31

294

Metabolic Syndrome  

MedlinePLUS

... metabolic syndrome fact sheet hOW is the metAbOlic syndrOme treAted? Increasing physical activity and losing weight are the best ways to begin to manage your condition. Medications can also treat risk factors such as ... factors for the metabolic syndrome, talk with your doctor. Your doctor can run ...

295

Bovine rumen epithelium undergoes rapid structural adaptations during grain-induced subacute ruminal acidosis.  

PubMed

Alterations in rumen epithelial structure and function during grain-induced subacute ruminal acidosis (SARA) are largely undescribed. In this study, four mature nonlactating dairy cattle were transitioned from a high-forage diet (HF; 0% grain) to a high-grain diet (HG; 65% grain). After feeding the HG diet for 3 wk, the cattle were transitioned back to the original HF diet, which was fed for an additional 3 wk. Continuous ruminal pH was measured on a weekly basis, and rumen papillae were biopsied during the baseline and at the first and final week of each diet. The mean, minimum, and maximum daily ruminal pH were depressed (P < 0.01) in the HG period compared with the HF period. During the HG period, SARA was diagnosed only during week 1, indicating ruminal adaptation to the HG diet. Microscopic examination of the papillae revealed a reduction (P < 0.01) in the stratum basale, spinosum, and granulosum layers, as well as total depth of the epithelium during the HG period. The highest (P < 0.05) papillae lesion scores were noted during week 1 when SARA occurred. Biopsied papillae exhibited a decline in cellular junctions, extensive sloughing of the stratum corneum, and the appearance of undifferentiated cells near the stratum corneum. Differential mRNA expression of candidate genes, including desmoglein 1 and IGF binding proteins 3, 5, and 6, was detected between diets using qRT-PCR. These results suggest that the structural integrity of the rumen epithelium is compromised during grain feeding and is associated with the differential expression of genes involved in epithelial growth and structure. PMID:21451145

Steele, Michael A; Croom, Jim; Kahler, Melissa; AlZahal, Ousama; Hook, Sarah E; Plaizier, Kees; McBride, Brian W

2011-06-01

296

Oxidative Metabolism in Muscle  

Microsoft Academic Search

Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and

M. Ferrari; T. Binzoni; V. Quaresima

1997-01-01

297

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

298

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

PubMed

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 used and treatments applied. The most common diagnoses believed to occur were ketosis (26%), rumen acidosis (22%) abomasal disorders (16%), subclinical hypocalcaemia (15%) and milk fever (15%). Subclinical rumen acidosis was considered to be a commonly occurring underlying condition with significant importance as a cause of reduced appetite. Inadequate feeding strategies were considered to be a main cause of subclinical rumen acidosis. However, the veterinary practitioners were apparently reluctant to imply checking of feeding mangement in their diagnostic work. Possibel reasons for this are discussed. According to the national dairy health recording system subclinical rumen acidosis was rarely reported as a diagnosis among attended cases. Apparently, signs and manifestations of the condition were unclear to the practitioners. It is proposed that the discrepancy is partly due to a lack of precise diagnostic tools available to veterinary practitioners at present and partly due to a missing examination of farm specific feeding management. PMID:11765242

Enemark, J M; Jørgensen, R J

2001-11-01

299

Dysregulated lipid metabolism in cancer  

PubMed Central

Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. The changes of expression and activity of lipid metabolizing enzymes are directly regulated by the activity of oncogenic signals. The dependence of tumor cells on the dysregulated lipid metabolism suggests that proteins involved in this process are excellent chemotherapeutic targets for cancer treatment. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered lipid metabolic pathways in cancer cells. Further understanding of dysregulated lipid metabolism and its associated signaling pathways will help us to better design efficient cancer therapeutic strategy. PMID:22937213

Zhang, Feng; Du, Guangwei

2012-01-01

300

Altered Glutamatergic Metabolism Associated with Punctate White Matter Lesions in Preterm Infants  

PubMed Central

Preterm infants (?10% of all births) are at high-risk for long-term neurodevelopmental disabilities, most often resulting from white matter injury sustained during the neonatal period. Glutamate excitotoxicity is hypothesized to be a key mechanism in the pathogenesis of white matter injury; however, there has been no in vivo demonstration of glutamate excitotoxicity in preterm infants. Using magnetic resonance spectroscopy (MRS), we tested the hypothesis that glutamate and glutamine, i.e., markers of glutamatergic metabolism, are altered in association with punctate white matter lesions and “diffuse excessive high signal intensity” (DEHSI), the predominant patterns of preterm white matter injury. We reviewed all clinically-indicated MRS studies conducted on preterm infants at a single institution during a six-year period and determined the absolute concentration of glutamate, glutamine, and four other key metabolites in the parietal white matter in 108 of those infants after two investigators independently evaluated the studies for punctate white matter lesions and DEHSI. Punctate white matter lesions were associated with a 29% increase in glutamine concentration (p?=?0.002). In contrast, there were no differences in glutamatergic metabolism in association with DEHSI. Severe DEHSI, however, was associated with increased lactate concentration (p?=?0.001), a marker of tissue acidosis. Findings from this study support glutamate excitotoxicity in the pathogenesis of punctate white matter lesions, but not necessarily in DEHSI, and suggest that MRS provides a useful biomarker for determining the pathogenesis of white matter injury in preterm infants during a period when neuroprotective agents may be especially effective. PMID:23468888

Wisnowski, Jessica L.; Bluml, Stefan; Paquette, Lisa; Zelinski, Elizabeth; Nelson, Marvin D.; Painter, Michael J.; Damasio, Hanna; Gilles, Floyd; Panigrahy, Ashok

2013-01-01

301

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

302

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

303

Beta-alanine supplementation reduces acidosis but not oxygen uptake response during high-intensity cycling exercise.  

PubMed

The oral ingestion of beta-alanine, the rate-limiting precursor in carnosine synthesis, has been shown to elevate the muscle carnosine content. Carnosine is thought to act as a physiologically relevant pH buffer during exercise but direct evidence is lacking. Acidosis has been hypothesised to influence oxygen uptake kinetics during high-intensity exercise. The present study aimed to investigate whether oral beta-alanine supplementation could reduce acidosis during high-intensity cycling and thereby affect oxygen uptake kinetics. 14 male physical education students participated in this placebo-controlled, double-blind study. Subjects were supplemented orally for 4 weeks with 4.8 g/day placebo or beta-alanine. Before and after supplementation, subjects performed a 6-min cycling exercise bout at an intensity of 50% of the difference between ventilatory threshold (VT) and VO(2peak). Capillary blood samples were taken for determination of pH, lactate, bicarbonate and base excess, and pulmonary oxygen uptake kinetics were determined with a bi-exponential model fitted to the averaged breath-by-breath data of three repetitions. Exercise-induced acidosis was significantly reduced following beta-alanine supplementation compared to placebo, without affecting blood lactate and bicarbonate concentrations. The time delay of the fast component (Td(1)) of the oxygen uptake kinetics was significantly reduced following beta-alanine supplementation compared to placebo, although this did not reduce oxygen deficit. The parameters of the slow component did not differ between groups. These results indicate that chronic beta-alanine supplementation, which presumably increased muscle carnosine content, can attenuate the fall in blood pH during high-intensity exercise. This may contribute to the ergogenic effect of the supplement found in some exercise modes. PMID:19841932

Baguet, Audrey; Koppo, Katrien; Pottier, Andries; Derave, Wim

2010-02-01

304

Indirect measures of human vagal withdrawal during head-up tilt with and without a respiratory acidosis  

Microsoft Academic Search

Human ECG records were analyzed during supine (SUP) rest and whole body 80° head-up tilt (HUT), with a respiratory acidosis\\u000a (5%CO2) and breathing room air (RA). HUT increased heart rate in both conditions (RASUP 60 ± 13 vs. RAHUT 79 ± 16; 5%CO2SUP 63 ± 12 vs. 5%CO2HUT 79 ± 14 beats min?1) and decreased mean R–R interval, with no changes in the R–R interval standard deviation. When

S. J. Brown; T. Mundel; M. Barnes; J. A. Brown

2009-01-01

305

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

306

Physiological and metabolic adaptations of Potamogeton pectinatus L. tubers support rapid elongation of stem tissue in the absence of oxygen.  

PubMed

Tubers of Potamogeton pectinatus L., an aquatic pondweed, over-winter in the anoxic sediments of rivers, lakes and marshes. Growth of the pre-formed shoot that emerges from the tuber is remarkably tolerant to anoxia, with elongation of the stem occurring faster when oxygen is absent. This response, which allows the shoot to reach oxygenated waters, occurs despite a 69-81% reduction in the rate of ATP production, and it is underpinned by several physiological and metabolic adaptations that contribute to efficient energy usage. First, extension of the pre-formed shoot is the result of cell expansion, without the accumulation of new cellular material. Secondly, after over-wintering, the tuber and pre-formed shoot have the enzymes necessary for a rapid fermentative response at the onset of growth under anoxia. Thirdly, the incorporation of [(35)S]methionine into protein is greatly reduced under anoxia. The majority of the anoxically synthesized proteins differ from those in aerobically grown tissue, implying an extensive redirection of protein synthesis under anoxia. Finally, anoxia-induced cytoplasmic acidosis is prevented to an unprecedented degree. The adaptations of this anoxia-tolerant plant tissue emphasize the importance of the mechanisms that balance ATP production and consumption in the absence of oxygen. PMID:16284407

Dixon, M H; Hill, S A; Jackson, M B; Ratcliffe, R G; Sweetlove, L J

2006-01-01

307

Acetyl coenzyme A-dependent metabolic activation of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl and several carcinogenic N-hydroxy arylamines in relation to tissue and species differences, other acyl donors, and arylhydroxamic acid-dependent acyltransferases.  

PubMed

The metabolic activation of several carcinogenic N-hydroxy (N-OH)-arylamines by cytosolic S-acetyl coenzyme A (AcCoA)-dependent enzymes was examined in tissues and species susceptible to arylamine carcinogenesis. Comparisons of the AcCoA-dependent activity were also made with known cytosolic arylhydroxamic acid-dependent acyltransferases and with the ability of different acyl donors to mediate the binding of N-OH-arylamines to DNA. With rat hepatic cytosol, AcCoA-dependent DNA binding was demonstrated for several [3H]N-OH-arylamines, in the order: N-OH-3,2'-dimethyl-4-aminobiphenyl (N-OH-DMABP), N-OH-2-aminofluorene (N-OH-AF) greater than N-OH-4-aminobiphenyl greater than N-OH-N'-acetylbenzidine greater than N-OH-2-naphthylamine; N-OH-N-methyl-4-amino-azobenzene was not a substrate. No activity was detected in dog hepatic or bladder cytosol with any of the N-OH-arylamines tested. Using either N-OH-DMABP or N-OH-AF and rat hepatic cytosol, activation to DNA-bound products was also detected with acetoacetyl- and propionyl-CoA but not with folinic acid or six other acyl CoA's. However, p-nitrophenyl acetate which is known to generate acetyl-enzyme intermediates effectively replaced AcCoA. Subcellular fractionation of rat liver showed that the AcCoA-dependent DNA-binding of N-OH-DMABP with cytosol was 5 times greater than that obtained with the microsomal or mitochondrial/nuclear fractions. Furthermore, the cytosolic activity was insensitive to inhibition by the esterase/deacetylase inhibitor, paraoxon; while the activity of the other subcellular fractions was completely inhibited (greater than 95%). AcCoA-dependent activation of N-OH-DMABP was also detected with rat tissue cytosols from intestine, mammary gland and kidney, which like the liver, are targets for arylamine-induced tumorigenesis. Using N-OH-DMABP, AcCoA-dependent DNA-binding activity was also detected in the hepatic cytosols from several species in the order: rabbit greater than hamster greater than rat, human greater than guinea pig greater than mouse. In contrast, the arylhydroxamic acid, N-OH-N-acetyl-DMABP, was not activated to a DNA-binding metabolite by the hepatic cytosolic N,O-acyltransferase of any of these species, thus suggesting that the AcCoA-mediated binding of N-OH-DMABP results from the direct formation of N-acetoxy-DMABP. With N-OH-AF as the substrate, the AcCoA-dependent activation was in the order: rabbit greater than guinea pig, hamster greater than mouse greater than human, rat.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3708755

Flammang, T J; Kadlubar, F F

1986-06-01

308

Targeting cancer metabolism.  

PubMed

The understanding that oncogenes can have profound effects on cellular metabolism and the discovery of mutations and alterations in several metabolism-related enzymes--isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2), succinate dehydrogenase (SDH), fumarate hydratase (FH), and pyruvate kinase M2 (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. Among intermediary metabolism enzymes, mutations in SDH occur in gastointestinal stromal tumors and result in a pseudohypoxic metabolic milieu. 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

2012-10-15

309

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

310

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

311

Severity of rotavirus gastroenteritis in an Indian population: report from a 3 year surveillance study.  

PubMed

This study investigated the severity of rotavirus gastroenteritis (RVGE) in hospitalized children less than 60 months of age and compared severity in the first five months of life to severity in children 6 to 23 months of age. Results from a 3 year surveillance study show an early peak of rotavirus disease, with 117 (31%) RVGE hospitalizations in children <6 months old. Higher incidence of severe dehydration, acidemia and acidosis at admission and prolonged hospitalization >7 days were seen in infants 0-5 months of age. The findings support the need for consideration of timely immunization or an accelerated immunization schedule with a birth dose to protect this vulnerable age. PMID:25091679

Mathew, Ann; Rao, P S Sundar; Sowmyanarayanan, Thuppal V; Kang, Gagandeep

2014-08-11

312

Structural control of metabolic flux.  

PubMed

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

Sajitz-Hermstein, Max; Nikoloski, Zoran

2013-01-01

313

Subacute ruminal acidosis challenge changed in situ degradability of feedstuffs in dairy goats.  

PubMed

This study investigated the effects of wheat-induced subacute ruminal acidosis (SARA) on rumen bacterial populations and in situ degradabilities of NDF, starch, and crude protein of feeds. Four multiparous dairy goats (BW=60±3.3kg) fitted with ruminal cannulas were assigned to a 2×2 crossover design (28-d treatment periods separated by a 7-d washout interval). The treatment diets consisted of 2 levels of cracked wheat: 0 (control, corn based concentrate) and 35% (diet-induced SARA, wheat-based concentrate), with a constant forage- (45% alfalfa hay and 5% corn silage of DM) to-concentrate (50% of DM) ratio. Results indicate that diets with a 35% wheat decreased ruminal pH (6.21 vs. 5.98) and increased the duration (1.13 vs. 4.72h/d) and area (0.12 vs. 0.78 pH × h/d) of ruminal pH below 5.6 and induced SARA. The SARA increased ruminal total volatile fatty acid concentration, from 105.0 to 123.8mM, and decreased the acetate molar proportion (62.8 vs. 56.6mol/100mol) and the acetate-to-propionate ratio (3.5 vs. 2.8). Compared with the control group, SARA decreases the relative abundance of Fibrobacter succinogenes (-59.3%) and Ruminococcus flavefaciens (-68.4%), whereas it increased Succinimonas amylolytica (198.1%) and Ruminobacter amylophilus (125.2%). The SARA decreased 24- and 48-h dry matter (DM) and neutral detergent fiber (NDF) degradabilities of corn silage. The 48-h degradabilities of DM (51.0 vs. 48.2%) and NDF (40.3 vs. 36.0%) in alfalfa hay were not affected by SARA, but the SARA tended to reduce the 24-h DM (49.6 vs. 46.3%) and NDF (37.8 vs. 33.2%) degradabilities. The effective ruminal degradabilities of DM and NDF in alfalfa hay and corn silage were reduced during SARA. In situ degradability parameters of DM and starch of wheat were not affected by SARA, but starch degradability of corn (9.5 vs. 13.3%/h) increased. The SARA reduced in situ 12-h degradabilities of DM and crude protein of soybean meal and extruded soybean without affecting the degradabilities of the other protein supplements (corn gluten meal, cottonseed meal, corn dried distillers grains with solubles, rapeseed meal, and wheat germ meal). These results indicated that the cracked wheat-induced SARA reduced the degradation of NDF in roughages and that of protein in soybean meal (-19.8%) and extruded soy (-18.9%) and increased the starch degradability in corn, due to the increased amylolytic bacteria and decreased cellulolytic bacteria counts in the rumen. PMID:24913652

Li, Fei; Cao, Yangchun; Liu, Nannan; Yang, Xinjian; Yao, Junhu; Yan, Dabing

2014-08-01

314

Severe storms  

NASA Technical Reports Server (NTRS)

An overview of severe storms given by a representative of the U.S. Department of Commerce/NOAA and how they affect aviation is presented. What is being done and the organizations responsible for the work in this area are briefly discussed. A partial list of the things that the representative feels need to be done is also presented.

Connolly, J. W.

1978-01-01

315

Effects of 36 hour fasting on GH\\/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency  

Microsoft Academic Search

OBJECTIVE: Reduction of growth hormone (GH) secretion in obesity probably reflects neuroendocrine and metabolic abnormalities. Even short-term fasting stimulates GH secretion and distinguishes normal from hypopituitary subjects with growth hormone deficiency (GHD). Marked weight loss improves GH secretion in obesity but the effect of fasting is controversial. We studied the effects of a 36 h fasting on the GH\\/IGF-I axis

M Maccario; G Aimaretti; S Grottoli; C Gauna; F Tassone; G Corneli; R Rossetto; Z Wu; CJ Strasburger; E Ghigo

2001-01-01

316

Effects of acute alkalosis and acidosis on performance: a meta-analysis.  

PubMed

Ingestion of agents that modify blood buffering action may affect high-intensity performance. Here we present a meta-analysis of the effects of acute ingestion of three such agents - sodium bicarbonate, sodium citrate and ammonium chloride - on performance and related physiological variables (blood bicarbonate, pH and lactate). A literature search yielded 59 useable studies with 188 observations of performance effects. To perform the mixed-model meta-analysis, all performance effects were converted into a percentage change in mean power and were weighted using standard errors derived from exact p-values, confidence limits (CLs) or estimated errors of measurement. The fixed effects in the meta-analytic model included the number of performance-test bouts (linear), test duration (log linear), blinding (yes/no), competitive status (athlete/nonathlete) and sex (male/female). Dose expressed as buffering mmoL/kg/body mass (BM) was included as a strictly proportional linear effect interacted with all effects except blinding. Probabilistic inferences were derived with reference to thresholds for small and moderate effects on performance of 0.5% and 1.5%, respectively. Publication bias was reduced by excluding study estimates with a standard error >2.7%. The remaining 38 studies and 137 estimates for sodium bicarbonate produced a possibly moderate performance enhancement of 1.7% (90% CL?±?2.0%) with a typical dose of 3.5?mmoL/kg/BM (?0.3?g/kg/BM) in a single 1-minute sprint, following blinded consumption by male athletes. In the 16 studies and 45 estimates for sodium citrate, a typical dose of 1.5?mmoL/kg/BM (?0.5?g/kg/BM) had an unclear effect on performance of 0.0% (±1.3%), while the five studies and six estimates for ammonium chloride produced a possibly moderate impairment of 1.6% (±1.9%) with a typical dose of 5.5?mmoL/kg/BM (?0.3?g/kg/BM). Study and subject characteristics had the following modifying small effects on the enhancement of performance with sodium bicarbonate: an increase of 0.5% (±0.6%) with a 1?mmoL/kg/BM increase in dose; an increase of 0.6% (±0.4%) with five extra sprint bouts; a reduction of 0.6% (±0.9%) for each 10-fold increase in test duration (e.g. 1-10 minutes); reductions of 1.1% (±1.1%) with nonathletes and 0.7% (±1.4%) with females. Unexplained variation in effects between research settings was typically ±1.2%. The only noteworthy effects involving physiological variables were a small correlation between performance and pre-exercise increase in blood bicarbonate with sodium bicarbonate ingestion, and a very large correlation between the increase in blood bicarbonate and time between sodium citrate ingestion and exercise. The approximate equal and opposite effects of sodium bicarbonate and ammonium chloride are consistent with direct performance effects of pH, but sodium citrate appears to have some additional metabolic inhibitory effect. Important future research includes studies of sodium citrate ingestion several hours before exercise and quantification of gastrointestinal symptoms with sodium bicarbonate and citrate. Although individual responses may vary, we recommend ingestion of 0.3-0.5?g/kg/BM sodium bicarbonate to improve mean power by 1.7% (±2.0%) in high-intensity races of short duration. PMID:21923200

Carr, Amelia J; Hopkins, Will G; Gore, Christopher J

2011-10-01

317

Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion: Importance of the osmolal gap  

Microsoft Academic Search

Ethylene glycol poisoning classically presents as a metabolic acidosis with an increased anion gap. Metabolism of ethylene glycol to organic acids, and increased production of lactate, are responsible for the increased gap. We report the case of an alcohol user who consumed ethanol and ethylene glycol concurrently, and presented without acidosis, with a normal anion gap. Several hours later, when

Khawaja A. Ammar; Paul S. Heckerling

1996-01-01

318

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

PubMed Central

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

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

2014-01-01

319

Metabolic Myopathies  

MedlinePLUS

... muscles. [Metabolism refers to chemical reactions that provide energy and nutrients, or substances necessary for health and ... occur when muscle cells don’t get enough energy. Without enough energy, the muscle lacks enough fuel ...

320

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

321

Metabolic Syndrome  

Microsoft Academic Search

Metabolic syndrome” refers to the phenomenon of risk factor clustering and is presumed to reflect a unifying underlying pathophysiology.\\u000a Clustering commonly occurs in the setting of obesity, insulin resistance and a sedentary lifestyle. Currently there are five\\u000a different criteria for metabolic syndrome, all of which are associated with increased risk of diabetes or cardiovascular disease.\\u000a Therapeutic lifestyle change that focuses

James B. Meigs

322

Oxidative metabolism in muscle.  

PubMed Central

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

Ferrari, M; Binzoni, T; Quaresima, V

1997-01-01

323

A human autoantibody to renal collecting duct cells associated with thyroid and gastric autoimmunity and possibly renal tubular acidosis.  

PubMed Central

A complement fixing autoantibody reacting with certain renal collecting duct cells, possibly so called dark cells, is described in 113 patients. Clinically, the antibody was strongly associated with thyroid disorders and pernicious anaemia. The patients also showed a markedly increased frequency of thyroid antibodies and antibodies to gastric parietal cells and to intrinsic factor. One of the patients had a distal renal tubular acidosis (RTA) and pernicious anaemia. The antibody was also found in all of three other patients with either latent or manifest RTA. RTA is associated with various immunological diseases, and the renal collecting duct cell antibody may turn out to be a marker of this disorder, either involved in its pathogenesis or representing a secondary phenomenon. PMID:6339124

Gaarder, P I; Heier, H E

1983-01-01

324

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

Microsoft Academic Search

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

Alan A. Wanderer

325

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

326

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.

Forde, Evan B.

2004-04-01

327

Muscle carnosine metabolism and beta-alanine supplementation in relation to exercise and training.  

PubMed

Carnosine is a dipeptide with a high concentration in mammalian skeletal muscle. It is synthesized by carnosine synthase from the amino acids L-histidine and beta-alanine, of which the latter is the rate-limiting precursor, and degraded by carnosinase. Recent studies have shown that the chronic oral ingestion of beta-alanine can substantially elevate (up to 80%) the carnosine content of human skeletal muscle. Interestingly, muscle carnosine loading leads to improved performance in high-intensity exercise in both untrained and trained individuals. Although carnosine is not involved in the classic adenosine triphosphate-generating metabolic pathways, this suggests an important role of the dipeptide in the homeostasis of contracting muscle cells, especially during high rates of anaerobic energy delivery. Carnosine may attenuate acidosis by acting as a pH buffer, but improved contractile performance may also be obtained by improved excitation-contraction coupling and defence against reactive oxygen species. High carnosine concentrations are found in individuals with a high proportion of fast-twitch fibres, because these fibres are enriched with the dipeptide. Muscle carnosine content is lower in women, declines with age and is probably lower in vegetarians, whose diets are deprived of beta-alanine. Sprint-trained athletes display markedly high muscular carnosine, but the acute effect of several weeks of training on muscle carnosine is limited. High carnosine levels in elite sprinters are therefore either an important genetically determined talent selection criterion or a result of slow adaptation to years of training. beta-Alanine is rapidly developing as a popular ergogenic nutritional supplement for athletes worldwide, and the currently available scientific literature suggests that its use is evidence based. However, many aspects of the supplement, such as the potential side effects and the mechanism of action, require additional and thorough investigation by the sports science community. PMID:20199122

Derave, Wim; Everaert, Inge; Beeckman, Sam; Baguet, Audrey

2010-03-01

328

ER Stress Modulates Cellular Metabolism  

PubMed Central

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

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

2011-01-01

329

Metabolic analyzer  

NASA Technical Reports Server (NTRS)

The metabolic analyzer was designed to support experiment M171. It operates on the so-called open circuit method to measure a subject's metabolic activity in terms of oxygen consumed, carbon dioxide produced, minute volume, respiratory exchange ratio, and tidal volume or vital capacity. The system operates in either of two modes. (1) In Mode I, inhaled respiratory volumes are actually measured by a piston spirometer. (2) In Mode II, inhaled volumes are calculated from the exhaled volume and the measured inhaled and exhaled nitrogen concentrations. This second mode was the prime mode for Skylab. Following is a brief description of the various subsystems and their operation.

Lem, J. D.

1977-01-01

330

Metabolic cardiomyopathies  

PubMed Central

The energy needed by cardiac muscle to maintain proper function is supplied by adenosine Ariphosphate primarily (ATP) production through breakdown of fatty acids. Metabolic cardiomyopathies can be caused by disturbances in metabolism, for example diabetes mellitus, hypertrophy and heart failure or alcoholic cardiomyopathy. Deficiency in enzymes of the mitochondrial ?-oxidation show a varying degree of cardiac manifestation. Aberrations of mitochondrial DNA lead to a wide variety of cardiac disorders, without any obvious correlation between genotype and phenotype. A completely different pathogenetic model comprises cardiac manifestation of systemic metabolic diseases caused by deficiencies of various enzymes in a variety of metabolic pathways. Examples of these disorders are glycogen storage diseases (e.g. glycogenosis type II and III), lysosomal storage diseases (e.g. Niemann-Pick disease, Gaucher disease, I-cell disease, various types of mucopolysaccharidoses, GM1 gangliosidosis, galactosialidosis, carbohydrate–deficient glycoprotein syndromes and Sandhoff's disease). There are some systemic diseases which can also affect the heart, for example triosephosphate isomerase deficiency, hereditary haemochromatosis, CD 36 defect or propionic acidaemia. PMID:11298185

Guertl, Barbara; Noehammer, Christa; Hoefler, Gerald

2000-01-01

331

Effects of partial mixed rations and supplement amounts on milk production and composition, ruminal fermentation, bacterial communities, and ruminal acidosis.  

PubMed

Late-lactation Holstein cows (n=144) that were offered 15kg dry matter (DM)/cow per day of perennial ryegrass to graze were randomized into 24 groups of 6. Each group contained a fistulated cow and groups were allocated to 1 of 3 feeding strategies: (1) control (10 groups): cows were fed crushed wheat grain twice daily in the milking parlor and ryegrass silage at pasture; (2) partial mixed ration (PMR; 10 groups): PMR that was isoenergetic to the control diet and fed twice daily on a feed pad; (3) PMR+canola (4 groups): a proportion of wheat in the PMR was replaced with canola meal to produce more estimated metabolizable protein than other groups. Supplements were fed to the control and PMR cows at 8, 10, 12, 14, or 16kg of DM/d, and to the PMR+canola cows at 14 or 16kg of DM/d. The PMR-fed cows had a lower incidence of ruminal acidosis compared with controls, and ruminal acidosis increased linearly and quadratically with supplement fed. Yield of milk fat was highest in the PMR+canola cows fed 14 or 16kg of total supplement DM/d, followed by the PMR-fed cows, and was lowest in controls fed at these amounts; a similar trend was observed for milk fat percentage. Milk protein yield was higher in the PMR+canola cows fed 14 or 16kg of total supplement DM/d. Milk yield and milk protein percentage were not affected by feeding strategy. Milk, energy-corrected milk, and milk protein yields increased linearly with supplement fed, whereas milk fat percentage decreased. Ruminal butyrate and d-lactate concentrations, acetate-to-propionate ratio, (acetate + butyrate)/propionate, and pH increased in PMR-fed cows compared with controls for all supplement amounts, whereas propionate and valerate concentrations decreased. Ruminal acetate, butyrate, and ammonia concentrations, acetate-to-propionate ratio, (acetate + butyrate)/propionate, and pH linearly decreased with amounts of supplement fed. Ruminal propionate concentration linearly increased and valerate concentration linearly and quadratically increased with supplement feeding amount. The Bacteroidetes and Firmicutes were the dominant bacterial phyla identified. The Prevotellaceae, Ruminococcaceae, and Lachnospiraceae were the dominant bacterial families, regardless of feeding group, and were influenced by feeding strategy, supplement feeding amount, or both. The Veillonellaceae family decreased in relative abundance in PMR-fed cows compared with controls, and the Streptococcaeae and Lactobacillaceae families were present in only minor relative abundances, regardless of feeding group. Despite large among- and within-group variation in bacterial community composition, distinct bacterial communities occurred among feeding strategies, supplement amounts, and sample times and were associated with ruminal fermentation measures. Control cows fed 16kg of DM of total supplement per day had the most distinct ruminal bacterial community composition. Bacterial community composition was most significantly associated with supplement feeding amount and ammonia, butyrate, valerate, and propionate concentrations. Feeding supplements in a PMR reduced the incidence of ruminal acidosis and altered ruminal bacterial communities, regardless of supplement feeding amount, but did not result in increased milk measures compared with isoenergetic control diets component-fed to late-lactation cows. PMID:24997657

Golder, H M; Denman, S E; McSweeney, C; Wales, W J; Auldist, M J; Wright, M M; Marett, L C; Greenwood, J S; Hannah, M C; Celi, P; Bramley, E; Lean, I J

2014-09-01

332

Role of bicarbonate in pH recovery from intracellular acidosis in the guinea-pig ventricular myocyte.  

PubMed Central

1. Intracellular pH (pHi) was recorded ratiometrically in isolated guinea-pig ventricular myocytes using the pH-sensitive fluoroprobe, carboxy-SNARF-1 (carboxy-seminaphthorhodafluor). 2. Following an intracellular acid load (10 mM NH4 Cl removal), pHi recovery in HEPES-buffered Tyrode solution was inhibited by 1.5 mM amiloride (Na(+)-H+ antiport blocker). In the presence of amiloride, switching from HEPES buffer to HCO3-/CO2 (pHo of both solutions = 7.4) stimulated a pHi recovery towards more alkaline levels. 3. Amiloride-resistant, HCO(3-)-dependent pHi recovery was inhibited by removal of external Na+ (replaced by N-methyl-D-glucamine), whereas removal of external Cl- (replaced by glucuronate, leading to depletion of internal Cl-), removal of external K+, or decreasing external Ca2+ by approximately tenfold had no inhibitory effect. These results suggest that the amiloride-resistant recovery is due to a Na(+)-HCO3- cotransport into the cell. 4. The stilbene derivative DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid, 500 microM) slowed Na(+)-HCO(3-)-dependent pHi recovery. 5. Intracellular pH increased in Cl(-)-free solution and this increase still occurred in Na(+)-free solution indicating that it is not caused via Na(+)-HCO3- symport and is more likely to be due to Cl- efflux in exchange for HCO3- influx on a sarcolemmal Cl(-)-HCO3- exchanger. The lack of any significant pHi recovery from intracellular acidosis in Na(+)-free solution suggests that this exchanger does not contribute to acid-equivalent extrusion. 6. Possible voltage sensitivity and electrogenicity of the co-transport were examined by using the whole-cell patch clamp technique in combination with SNARF-1 recordings of pHi. Stepping the holding potential from -110 to -40 mV did not affect amiloride-resistant pHi recovery from acidosis. Moreover, following an intracellular acid load, the activation of Na(+)-HCO3- co-influx (by switching from HEPES to HCO3-/CO2 buffer) produced no detectable outward current (outward current would be expected if the coupling of HCO3- with Na+ were > 1.0). 7. Intracellular intrinsic buffering power (beta i) was assessed as a function of pHi (beta i computed from the decrease of pHi following reduction of extracellular NH4 Cl in amiloride-containing solution). beta i in the ventricular myocyte increases roughly linearly with a decrease in pHi according the following equation: beta i = -28(pHi) +222.6. 8. Comparison of acid-equivalent efflux via Na(+)-HCO3- symport and Na(+)-H+ antiport showed that, following an intracellular acidosis, the symport accounts for about 40% of total acid efflux, the other 60% being carried by the antiport.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1302269

Lagadic-Gossmann, D; Buckler, K J; Vaughan-Jones, R D

1992-01-01

333

Metabolic alkalosis and myoclonus  

Microsoft Academic Search

This is the first case reported of vomiting-induced metabolic alkalosis associated with myoclonus. The report describes an unusual presentation of myoclonus secondary to acid-base disturbance caused by recreational drug-induced vomiting. The severe derangement of hyponatraemia, hypokalaemia, and alkalosis appears to have been reasonably well tolerated due to the gradual onset and relatively long history. The causes, mechanism, and management of

P Simons; I Nadra; P G McNally

2003-01-01

334

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.

Niazi, Masooma

2014-01-01

335

Type IV renal tubular acidosis following resolution of acute kidney injury and disseminated intravascular coagulation due to hump-nosed viper bite  

PubMed Central

Hump-nosed viper bite can cause acute kidney injury (AKI) and disseminated intravascular coagulation. In some patients, it can cause chronic kidney disease necessitating life-long renal replacement therapy. Lack of effective antivenom makes the management of these patients difficult. A 51-year-old Sri Lankan male was admitted with AKI and disseminated intravascular coagulation following a hump-nosed viper bite. He made a complete recovery with blood product support and hemodialysis. Renal biopsy was performed as his renal recovery was prolonged which revealed patchy tubular atrophy and interstitial inflammation suggestive of subacute interstitial nephritis. Later, he presented with hyperkalemic paralysis and acidosis. A diagnosis of late onset type 4 renal tubular acidosis was made and he responded well to a course of fludrocortisone. PMID:23960348

Karunarathne, S.; Udayakumara, Y.; Govindapala, D.; Fernando, H.

2013-01-01

336

Heart Metabolic Disturbances in Cardiovascular Diseases  

Microsoft Academic Search

Myocardial function depends on adenosine triphosphate (ATP) supplied by oxidation of several substrates. In the adult heart, this energy is obtained primarily from fatty acid oxidation through oxidative phosphorylation. However, the energy source may change depending on several factors such as substrate availability, energy demands, oxygen supply, and metabolic condition of the individual. Surprisingly, the role of energy metabolism in

Karla Carvajal; Rafael Moreno-Sánchez

2003-01-01

337

The promotion of catecholamine release in rainbow trout, Salmo gairdneri, by acute acidosis: interactions between red cell pH and haemoglobin oxygen-carrying capacity.  

PubMed

A fall in blood pH was generated either by infusion of HCl or by reducing gill ventilation and raising blood PCO2 in rainbow trout, Salmo gairdneri Richardson. The acute acidosis resulting from HCl infusion caused an increase in plasma adrenaline and noradrenaline concentrations, the adrenaline increase being proportional to the decrease in blood pH. Fish subjected to a prolonged respiratory acidosis, caused by a reduction in gill ventilation, showed no increase in catecholamines 24 h after the change in gill ventilation. We suggest that catecholamine levels increase in response to a pH decrease, but if acidotic conditions are maintained, circulating catecholamines return to low levels. There was a much smaller decrease in erythrocytic pH with a fall in plasma pH when catecholamine levels were high. This ameliorating effect of catecholamines on erythrocytic pH during a plasma acidosis maintains the oxygen-carrying capacity of the haemoglobin. If erythrocytic pH was decreased by increasing blood PCO2 in vitro, then there was a fall in haemoglobin oxygen-carrying capacity which was proportional to the reduction in pH. We conclude that catecholamines are released into the blood in proportion to the fall in blood pH but if the pH is maintained the circulating catecholamines return to their initial low levels. The elevated catecholamine concentrations in blood safeguard against any impairment of haemoglobin oxygen-carrying capacity by maintaining erythrocytic pH in the face of a plasma acidosis. PMID:3091753

Boutilier, R G; Iwama, G K; Randall, D J

1986-07-01

338

Cellular Metabolism  

NSDL National Science Digital Library

This is a lesson about the evidence for life on other planets. Learners will play a game to examine processes in cellular metabolism and explore both direct and indirect evidence for fingerprints of life. Includes teacher notes, learning objectives, and assessment of prior knowledge and preconceptions. This is Lesson 2 in Exploring Deep-Subsurface Life. Earth Analogues for Possible Life on Mars: Lessons and Activities.

339

Metabolic syndrome  

Microsoft Academic Search

The metabolic syndrome is like an elephant, and any literary review of its importance is shamefully reduced to an examination\\u000a of tusks, trunk, and tail. Evidence continues to mount that this diminutive approach is an incorrect management strategy for\\u000a such a large problem. Diet and lifestyle are effective strategies, but they must effectively compete with behaviors that have\\u000a instant gratification.

Margo A. Denke

2002-01-01

340

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

341

[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

342

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

343

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

344

Severe hypoglycaemia, metabolic control and diabetes management in children with type 1 diabetes in the decade after the Diabetes Control and Complications Trial – a large-scale multicentre study  

Microsoft Academic Search

Hypoglycaemia is frequently the limiting factor in achieving optimal glycaemic control. Therefore, insulin therapy, the incidence of hypoglycaemia, and glycaemic control were investigated in 6309 unselected children with type 1 diabetes in a large-scale multicentre study. Using standardised computer-based documentation, the incidence of severe hypoglycaemia, HbA1 c levels, insulin regimen, diabetes duration, and the number of patients attending a treatment

Verena M. Wagner; Matthias Grabert; Reinhard W. Holl

2005-01-01

345

Validation of the difference in urine and blood carbon dioxide tension during bicarbonate loading as an index of distal nephron acidification in experimental models of distal renal tubular acidosis.  

PubMed Central

Recent classifications of the several pathophysiologic types of distal renal tubular acidosis (secretory, voltage dependent, and gradient) have been based on the response of acidification parameters to a series of provocative maneuvers in vivo and in vitro. A reduction in the difference in urine and blood CO2 tension during bicarbonate loading (U-B pCO2 gradient), a widely applied parameter, has been employed as an index of reduced distal nephron proton secretion. This study was designed to test the validity of the U-B pCO2 gradient in a variety of experimental models of distal renal tubular acidosis by measuring and comparing disequilibrium pH (a direct technique to detect H+ secretion in situ) with the pCO2 in the papillary collecting duct of the rat in vivo during bicarbonate loading. Chronic amiloride, lithium chloride, and amphotericin-B administration, and the post-obstructed kidney models were employed. Amiloride resulted in an acidification defect which did not respond to sulfate infusion (urine pH = 6.15 +/- 0.08), and was associated with an obliteration of the acid disequilibrium pH (-0.26 +/- 0.05- -0.08 +/- 0.03) and reduction in papillary pCO2 (116.9 +/- 3.2 - 66.9 +/- 2.5 mmHg). The defect induced by lithium administration responded to Na2SO4 (urine pH = 5.21 +/- 0.06) but was similar to amiloride with respect to the observed reduction in disequilibrium pH (-0.04 +/- 0.02) and pCO2 (90.3 +/- 3.0 mmHg). The post-obstructed kidney model was characterized by an abnormally alkaline urine pH unresponsive to sulfate (6.59 +/- 0.06) and a reduction in disequilibrium pH (+0.02 +/- 0.06) and pCO2 (77.6 +/- 3.6 mmHg). Amphotericin-B resulted in a gradient defect as characterized by excretion of an acid urine after infusion of sodium sulfate (5.13 +/- 0.06). Unlike other models, however, amphotericin-B was associated with a significant acid disequilibrium pH (-0.11 +/- 0.05) and an appropriately elevated urine pCO2 (119.8 +/- 6.4 mmHg) which did not differ from the respective values in control rats. Thus, these findings support the use of the U-B pCO2 as a reliable means of demonstrating impaired distal nephron proton secretion in secretory and voltage-dependent forms of distal renal tubular acidosis (RTA) and supports the view that proton secretion is not impaired in gradient forms of distal RTA. PMID:3921566

DuBose, T D; Caflisch, C R

1985-01-01

346

OXYGEN DEFICIENCY AND ROOT METABOLISM: Injury and Acclimation Under Hypoxia and Anoxia.  

PubMed

Oxygen deficiency in the rooting zone occurs with poor drainage after rain or irrigation, causing depressed growth and yield of dryland species, in contrast with native wetland vegetation that tolerates such conditions. This review examines how roots are injured by O2 deficiency and how metabolism changes during acclimation to low concentrations of O2. In the root apical meristem, cell survival is important for the future development; metabolic changes under anoxia help maintain cell survival by generating ATP anaerobically and minimizing the cytoplasmic acidosis associated with cell death. Behind the apex, where cells are fully expanded, ethylene-dependent death and lysis occurs under hypoxia to form continuous, gas-filled channels (aerenchyma) conveying O2 from the leaves. This selective sacrifice of cells may resemble programmed cell death and is distinct from cell death caused by anoxia. Evidence concerning alternative possible mechanisms of anoxia tolerance and avoidance is presented. PMID:15012263

Drew, Malcolm C.

1997-06-01

347

Use of a pediatric oxygenator integrated in a veno-venous hemofiltration circuit to remove CO2: A case report in a severe burn patient with refractory hypercapnia.  

PubMed

Acute respiratory distress syndrome management is currently based on lung protective ventilation. Such strategy may lead to hypercapnic acidosis. We report a case of refractory hypercapnia in a severe burn adult, treated with simplified veno-venous extracorporeal carbon dioxide removal technique. We integrated a pediatric oxygenator in a continuous veno-venous hemofiltration circuit. This technique, used during at least 96h, was feasible, sure and efficient with carbon dioxide removal rate up to 32%. PMID:24685066

Rousseau, Anne-Françoise; Damas, Pierre; Renwart, Ludovic; Amand, Théo; Erpicum, Marie; Morimont, Philippe; Dubois, Bernard; Massion, Paul B

2014-11-01

348

Unchanged muscle fiber conduction velocity relates to mild acidosis during exhaustive bicycling  

Microsoft Academic Search

Muscle fiber conduction velocity (MFCV) has often been shown to decrease during standardized fatiguing isometric contractions.\\u000a However, several studies have indicated that the MFCV may remain constant during fatiguing dynamic exercise. It was investigated\\u000a if these observations can be related to the absence of a large decrease in pH and if MFCV can be considered as a good indicator\\u000a of

J. P. J. Schmitz; J. P. van Dijk; P. A. J. Hilbers; K Nicolaij; J. A. L. Jeneson; D. F. Stegeman

2011-01-01

349

Targeting cellular metabolism to improve cancer therapeutics  

PubMed Central

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

350

[Clinical evidence for metabolic surgery].  

PubMed

The metabolic effect of bariatric surgery is well-established and is considered to be self-evident in morbidly obese patients with a body mass index (BMI) >?40 kg/m(2). Metabolic surgery performed on patients with obesity grades II (BMI 35-40 kg/m(2)) and I (BMI 30-35 kg/m(2)) according to the World Health Organization (WHO) has increased in recent years; however, the indications for metabolic surgery in obesity grades I and II are currently under debate due to insufficient evidence. In the last 5 years several highly qualified randomized clinical trials have been published which evaluated the effect of metabolic surgery in patients with obesity grades I and II in comparison to conservative therapy. Based on these data the efficacy of metabolic surgery in short-term follow-up (12-36 months) is unquestionable when compared to conservative therapy according to the current guidelines. Besides improved glycemic control and remission of diabetes, metabolic surgery has the potential to have a positive influence on diabetic complications, such as diabetic retinopathy, nephropathy and polyneuropathy, as well as on comorbidities, such as arterial hypertension and dyslipidemia. Future clinical trials should address the long-term (>?36 months) effects of metabolic surgery, patient selection criteria and choice of procedure. PMID:25315339

Senft, J D; Billeter, A T; Fischer, L; Müller-Stich, B P

2014-11-01

351

Is osteoarthritis a metabolic disease?  

PubMed

Obesity, together with aging and injury, is among the main risk factors for osteoarthritis. Obesity-related osteoarthritis can affect not only the weight-bearing joints, but also the hands, suggesting a role for circulating mediators released by the adipose tissue and known as adipokines. Thus, osteoarthritis may have a systemic metabolic component. Evidence from both epidemiological and biological studies support the concept of metabolic osteoarthritis, defined as a broad clinical phenotype that includes obesity-related osteoarthritis. Thus, osteoarthritis can be related to metabolic syndrome or to an accumulation of metabolic abnormalities. In addition, studies have demonstrated associations linking osteoarthritis to several components of the metabolic syndrome, such as hypertension and type 2 diabetes, independently from obesity or any of the other known risk factors for osteoarthritis. Both in vitro and in vitro findings indicate a deleterious effect of lipid and glucose abnormalities on cartilage homeostasis. Chronic low-grade inflammation is a feature shared by osteoarthritis and metabolic disorders and may contribute to the genesis of both. Thus, osteoarthritis is emerging as a disease that has a variety of phenotypes including a metabolic phenotype, in addition to the age-related and injury-related phenotypes. PMID:24176735

Sellam, Jérémie; Berenbaum, Francis

2013-12-01

352

[Metabolic therapy for heart failure].  

PubMed

Heart failure may promote metabolic changes such as insulin resistance, in part through neurohumoral activation, and determining an increased utilization of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation have been shown to be increased in patients with heart failure. The result is depletion of myocardial ATP, phosphocreatine and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. To date, the most effective metabolic treatments include several pharmacological agents that directly inhibit fatty acid oxidation. The results of current research are supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with heart failure. Trimetazidine is the most studied drug in this context. Several small studies have evidenced the usefulness of such additional therapeutic tools for heart failure. More specifically, recent meta-analyses and a multicenter retrospective study have shown that additional use of trimetazidine in patients with heart failure, along with symptoms and cardiac function improvement, also provides a significant protective effect on all-cause mortality, cardiovascular events and hospitalization due to cardiac causes. Nevertheless, the exact role of metabolic therapy in heart failure is yet to be established, and a large multicenter randomized trial is necessary. PMID:25072544

Loiacono, Ferdinando; Alberti, Luca; Lauretta, Ludovica; Puccetti, Patrizia; Silipigni, Carmen; Margonato, Alberto; Fragasso, Gabriele

2014-01-01

353

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

354

Metabolism and biochemistry in hypogravity  

NASA Astrophysics Data System (ADS)

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.

355

Mice Lacking Protein Kinase C Beta Present Modest Increases in Systolic Blood Pressure and NH4Cl-Induced Metabolic Acidosis  

Microsoft Academic Search

The conventional protein kinase C isoenzyme ? (PKC-?) is expressed in various structures of mouse kidney. To get insights into the function, PKC-? knockout (–\\/–) and wild-type (+\\/+) mice were studied. Under basal conditions, PKC-?–\\/– mice exhibited a higher systolic blood pressure (in awake mice), normal plasma concentrations of Na+ and K+, and normal plasma pH. Urine osmolality and 24-hour

Li-Jun Yao; Michael Leitges; Volker Vallon

2006-01-01

356

Anion gap, anion gap corrected for albumin, base deficit and unmeasured anions in critically ill patients: implications on the assessment of metabolic acidosis and the diagnosis of hyperlactatemia  

Microsoft Academic Search

BACKGROUND: Base deficit (BD), anion gap (AG), and albumin corrected anion gap (ACAG) are used by clinicians to assess the presence or absence of hyperlactatemia (HL). We set out to determine if these tools can diagnose the presence of HL using cotemporaneous samples. METHODS: We conducted a chart review of ICU patients who had cotemporaneous arterial blood gas, serum chemistry,

Lakhmir S Chawla; Shirley Shih; Danielle Davison; Christopher Junker; Michael G Seneff

2008-01-01

357

Consequences of CO2 acidosis for transmembrane Na+ transport and membrane current in rabbit cardiac Purkinje fibres.  

PubMed Central

1. The influence of sarcolemmal Na(+)-H+ exchange on intracellular Na+ activity (aiNa), intracellular pH (pHi) and membrane holding current (Ih) was investigated in rabbit cardiac Purkinje fibres. pHi and aiNa were measured with liquid sensor ion-selective microelectrodes. A two-microelectrode voltage clamp was used while recording pHi or aiNa.pHi was varied by alternating a nominally CO2-free HEPES buffer and a CO2-HCO3-buffer. 2. The intrinsic buffer capacity was calculated from the decrease in pHi after addition of CO2. The most accurate estimate was obtained when transmembrane pHi regulation was blocked and equalled 18.4 +/- 1.0 mequiv H+/pH unit (mean +/- S.E.M.). 3. aiNa started to rise when pHi fell below 7.0. A hyperpolarization paralleled the increase in aiNa. The magnitude of the rise in aiNa and the hyperpolarization were steeply dependent on pHi. 4. Inhibition of the Na(+)-K+ pump by K(+)-free superfusion increased aiNa. The rate of rise in aiNa was highly dependent on pHi. The rates of rise in 5% (pHi = 7.00 +/- 0.03), 7% (pHi = 6.89 +/- 0.04) and 15% CO2 (pHi = 6.74 +/- 0.02) at constant external pH (pHo) relative to the rate in HEPES solution (pHi = 7.24 +/- 0.02) were: 1.5 +/- 0.2, 2.4 +/- 0.1 and 3.1 +/- 0.2. The acid-induced rise in aiNa was abolished by 2 mM-amiloride. 5. Extracellular acidosis slowed down the recovery of pHi and depressed the rate of rise in aiNa upon intracellular acidification. When both pHi and pHo were decreased to 6.7 the acid-dependent rate increase fell to about 10% of the value found at pHo 7.4. 6. The tetrodotoxin (TTX)-sensitive Na+ current was not influenced by the change in pHi in the range 6.7-7.2. 7. Intracellular acidosis was associated with an early aiNa-independent depolarization and an inward shift in Ih. Current-voltage plots revealed that the initial inward current shift reversed at -81.5 mV on average, showed inward rectification and was largely depressed in the presence of 1 mM-Ba2+. These observations indicate a decrease in K+ conductance when pHi falls. 8. The increase in aiNa elicited a Na(+)-K+ pump-dependent outward current which could override the initial aiNa-independent current shift. At a pHo of 6.7 the initial fall in Ih remained, while the secondary outward current was largely depressed. 9. The rate of active Na+ extrusion and Na(+)-K+ pump current were suppressed by about 30% at pHi 6.7 compared to pHi 7.2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2120426

Bielen, F V; Bosteels, S; Verdonck, F

1990-01-01

358

High concentrate-induced subacute ruminal acidosis (SARA) increases plasma acute phase proteins (APPs) and cortisol in goats.  

PubMed

The aim of this study was to investigate changes of stress status in dairy goats induced to subacute ruminal acidosis (SARA). The level of acute phase proteins (APPs) including haptoglobin (HP) and serum amyloid A (SAA) in plasma and their mRNA expression in liver, as well as plasma cortisol and genes expression of key factors controlling cortisol synthesis in adrenal cortex were compared between SARA and control goats. SARA was induced by feeding high concentrate diet (60% concentrate of dry matter) for 3 weeks (SARA, n=6), while control goats (Con, n=6) received a low concentrate diet (40% concentrate of dry matter) during the experimental time. SARA goats showed ruminal pH below 5.8 for more than 3 h per day, which was significantly lower than control goats (pH>6.0). SARA goats demonstrated a significant increase of hepatic HP and SAA mRNA expression (P<0.05), and the level of HP but not SAA in plasma was markedly increased compared with control (P<0.05). The level of cortisol in plasma showed a trend to increase in SARA goats (0.050.05). These results suggested that SARA goats experienced a certain stress status, exhibiting an increase in HP production and cortisol secretion. PMID:24852750

Jia, Y Y; Wang, S Q; Ni, Y D; Zhang, Y S; Zhuang, S; Shen, X Z

2014-09-01

359

Incomplete distal renal tubular acidosis from a heterozygous mutation of the V-ATPase B1 subunit.  

PubMed

Congenital distal renal tubular acidosis (RTA) from mutations of the B1 subunit of V-ATPase is considered an autosomal recessive disease. We analyzed a distal RTA kindred with a truncation mutation of B1 (p.Phe468fsX487) previously shown to have failure of assembly into the V1 domain of V-ATPase. All heterozygous carriers in this kindred have normal plasma HCO3 (-) concentrations and thus evaded the diagnosis of RTA. However, inappropriately high urine pH, hypocitraturia, and hypercalciuria were present either individually or in combination in the heterozygotes at baseline. Two of the heterozygotes studied also had inappropriate urinary acidification with acute ammonium chloride loading and an impaired urine-blood Pco2 gradient during bicarbonaturia, indicating the presence of a H(+) gradient and flux defects. In normal human renal papillae, wild-type B1 is located primarily on the plasma membrane, but papilla from one of the heterozygote who had kidney stones but not nephrocalcinosis showed B1 in both the plasma membrane as well as diffuse intracellular staining. Titration of increasing amounts of the mutant B1 subunit did not exhibit negative dominance over the expression, cellular distribution, or H(+) pump activity of wild-type B1 in mammalian human embryonic kidney-293 cells and in V-ATPase-deficient Saccharomyces cerevisiae. This is the first demonstration of renal acidification defects and nephrolithiasis in heterozygous carriers of a mutant B1 subunit that cannot be attributable to negative dominance. We propose that heterozygosity may lead to mild real acidification defects due to haploinsufficiency. B1 heterozygosity should be considered in patients with calcium nephrolithiasis and urinary abnormalities such as alkalinuria or hypocitraturia. PMID:25164082

Zhang, Jianning; Fuster, Daniel G; Cameron, Mary Ann; Quiñones, Henry; Griffith, Carolyn; Xie, Xiao-Song; Moe, Orson W

2014-11-01

360

Impact of subacute ruminal acidosis on the diversity of liquid and solid-associated bacteria in the rumen of goats.  

PubMed

This study was aimed to investigate the impact of subacute ruminal acidosis (SARA) on the diversity of liquid (LAB) and solid-associated bacteria (SAB) following high-grain feeding. Six ruminally cannulated goats were divided into two groups: one group was fed a hay diet (COD), and the other group was fed a high grain diet (SAID). Rumen liquids and rumen solids were sampled after 2 weeks adaption. SARA was diagnosed with a pH below 5.8 for 8 h. SAID decreased ruminal pH (P < 0.001) and increased the acetate (P = 0.017), propionate (P = 0.001), butyrate (P < 0.001) and total volatile fatty acid (P < 0.001) concentration in rumen compared with the COD. Denaturing gradient gel electrophoresis fingerprints analysis revealed a clear separation between both the diet and the fraction of rumen digesta in bacterial communities. Pyrosequencing analysis showed that the proportion of phylum Bacteroidetes in the SAID-LAB and SAID-SAB communities was less than in the COD group, whereas the SAID group had a greater percentage of Firmicutes in both the LAB and SAB libraries. UniFrac analyses and a Venn diagram revealed a large difference between the two diets in the diversity of rumen bacterial communities. Overall, our findings revealed that SARA feeding did alter the community structure of rumen liquids and rumen solids. Thus, manipulation of dietary factors, such as ratio of forage to concentrate may have the potential to alter the microbial composition of rumen liquid and rumen solid. PMID:24068532

Huo, Wenjie; Zhu, Weiyun; Mao, Shengyong

2014-02-01

361

THE INFLUENCE OF EXPERIMENTAL ANAEMIA ON BLOOD ACIDBASE REGULATION IN VIVO AND IN VITRO IN THE STARRY FLOUNDER (PLATICHTHYS STELLATUS) AND THE RAINBOW TROUT (SALMO GAIRDNERI)  

Microsoft Academic Search

SUMMARY Severe experimental anaemia caused a rise in Pc0 and an associated fall in pH (respiratory acidosis) in arterial and venous blood of both flounder and trout in vivo. In some trout, but not in flounder, there was also a rise in blood lactate, indicating metabolic acidosis. In vitro, blood buffer capacities declined with haematocrit, a factor which contributed to

CHRIS M. WOOD; D. G. McDONALD

362

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 risk factors for ... Syndrome • Home • About Metabolic Syndrome • Why Metabolic Syndrome Matters • Your Risk for Metabolic Syndrome • Symptoms & Diagnosis • Prevention & ...

363

Targeting glucose metabolism in patients with cancer.  

PubMed

Nearly a century ago, Otto Warburg made the astute observation that the metabolic properties of cancer cells differ markedly from those of normal cells. Several decades passed before the concept of exploiting cancer cell metabolism came into clinical practice with the advent of chemotherapy, the underlying principle of which is to target rapidly dividing cells by interfering with critical processes that are all, on some level, driven by cell metabolism. Although chemotherapy can be quite effective, success rates are highly variable and the adverse effects associated with treatment often outweigh the benefits due to the fact that chemotherapy is indiscriminately cytotoxic against all rapidly dividing cells, cancerous or healthy. During the past several years, a more intricate understanding of cancer cell metabolism has permitted the development of targeted therapies that aim to specifically target cancer cells and spare healthy tissue by exploiting the altered metabolism of cancer cells. The identification of new metabolic targets and the subsequent development of small-molecule inhibitors of metabolic enzymes have demonstrated the utility and promise of targeting cancer cell metabolism as an anticancer strategy. This review summarizes recent advances in the identification and characterization of several metabolic enzymes as emerging anticancer targets. PMID:24374503

Elf, Shannon E; Chen, Jing

2014-03-15

364

The duration of time that beef cattle are fed a high-grain diet affects feed sorting behavior both before and after acute ruminal acidosis,2.  

PubMed

The objective of this study was to determine how duration of time that cattle are fed a high-grain diet affects feed sorting, both before and after an episode of acute ruminal acidosis. Sixteen Angus heifers (261 ± 6.1 kg; BW ± SEM) were assigned to 1 of 4 blocks and fed a backgrounding (BG) diet (60% forage, DM basis). Within block, heifers were randomly assigned to 1 of 2 treatments differing in days fed a high-grain (HG; 9% forage, DM basis, fed ad libitum) diet before a ruminal acidosis challenge: 34 d for long adapted (LA) and 8 d for short adapted (SA). Ruminal acidosis was induced by restricting feed to 50% of DMI as a proportion of BW (determined individually for each heifer) for 24 h followed by an intraruminal infusion of ground barley at 10% of DMI as a proportion of BW measured before feed restriction. Feed and orts were sampled during the BG period, the first 26 d on the HG diet (only for LA cattle), the 8-d baseline (BASE) period, on the day of the ruminal acidosis challenge (CH), and during 2 consecutive 8-d recovery periods (REC1 and REC2) for each heifer and subjected to particle size analysis: 19-mm (long), 8-mm (medium), and 1.18-mm (short) screens and a pan (fine). On the BG diet, sorting for medium particles tended to be greater (104.2 vs. 102.1%; P = 0.07) for LA heifers than SA heifers, while sorting against short particles was greater (98.2 vs. 100.0%; P = 0.05) for LA heifers. During the first 26 d on the HG diet, LA cattle sorted for (P < 0.001) long (118.8%), medium (117.8%), and short (104.1%) particles and sorted against (P < 0.001) fine particles (45.3%). This sorting pattern was consistent for LA heifers during BASE period, CH day, and recovery periods, across which SA heifers exhibited less sorting (P ? 0.1). Greater duration of pH < 5.5 during the BASE period was associated with greater sorting for long particles (R(2) = 0.75, P = 0.01) in LA heifers and for long (R(2) = 0.49, P = 0.05) and medium (R(2) = 0.88, P < 0.001) particles in SA heifers. Long-adapted heifers linearly increased the extent of sorting for long (P = 0.007) and medium (P < 0.001) particles and against fine particles (P = 0.05) during the days following the challenge to a greater extent than SA heifers. Overall, the results demonstrate that longer-term exposure of beef heifers to a HG diet, which caused persistent low rumen pH, influenced feed sorting of heifers, both before and after an induced bout of acute ruminal acidosis, in a manner that would help attenuate the effects of acidosis. PMID:24663165

DeVries, T J; Schwaiger, T; Beauchemin, K A; Penner, G B

2014-04-01

365

Eremophila glabra is an Australian plant that reduces lactic acid accumulation in an in vitro glucose challenge designed to simulate lactic acidosis in ruminants.  

PubMed

Lactic acidosis is a major welfare issue affecting animal health and production systems such as dairy and feedlot beef. We used two bioassays to identify bioactive plants of Australia with the potential to prevent acidosis in ruminants. In the first bioassay, a potentially acidotic environment was induced by adding glucose to rumen fluid and pH and gas production were used to estimate the effect on acid production and microbial fermentation after 5-h incubation. Australian plants (n = 104) were screened for their ability to prevent a decline in the pH without inhibiting normal gas production, and five plants namely Eremophila glabra, Kennedia eximia, Acacia saligna, Acacia decurrens and Kennedia prorepens with such properties were identified. We investigated further the two top ranking plants, E. glabra and K. prorepens, in the second bioassay to determine the extent of their effect in vitro, by extending the incubation to 24 h and measuring d-lactate, and volatile fatty acids (VFA) in addition to pH and gas production. These were measured at 0, 5, 10, 16 and 24 h after inoculation. Eremophila glabra maintained pH values that were higher and d-lactate concentrations that were lower than the control (P < 0.001), and comparable to the antibiotic-protected environment (AB; 12 ?g of virginiamycin/ml). Eremophila glabra and AB treatments did not restrict fermentation, as judged by gas production and VFA. Kennedia prorepens slowed the decline in pH and reduced the accumulation of lactate but inhibited gas production. We concluded that, in vitro, E. glabra was effective at controlling events that can lead to acidosis and the effect was comparable to that of virginiamycin, while K. prorepens was less effective than E. glabra and also inhibited fermentation. PMID:22444901

Hutton, P; White, C L; Durmic, Z; Vercoe, P E

2009-09-01

366

Heteromeric ASIC channels composed of ASIC2b and ASIC1a display novel channel properties and contribute to acidosis-induced neuronal death  

PubMed Central

Acid-sensing ion channel (ASIC) subunits associate to form homomeric or heteromeric proton-gated ion channels in neurons throughout the nervous system. The ASIC1a subunit plays an important role in establishing the kinetics of proton-gated currents in the central nervous system and activation of ASIC1a homomeric channels induces neuronal death following local acidosis that accompanies cerebral ischemia. The ASIC2b subunit is expressed in the brain in a pattern that overlaps ASIC1a, yet the contribution of ASIC2b has remained elusive. We find that co-expression of ASIC2b with ASIC1a in Xenopus oocytes results in novel proton-gated currents with properties distinct from ASIC1a homomeric channels. In particular, ASIC2b/1a heteromeric channels are inhibited by the non-selective potassium channel blockers tetraethylammonium (TEA) and barium. In addition, steady-state desensitization is induced at more basic pH values and Big Dynorphin sensitivity is enhanced in these unique heteromeric channels. Cultured hippocampal neurons show proton-gated currents consistent with ASIC2b contribution and these currents are lacking in neurons from mice with an ACCN1 (ASIC2) gene disruption. Finally, we find that these ASIC2b/1a heteromeric channels contribute to acidosis-induced neuronal death. Together, our results show that ASIC2b confers unique properties to heteromeric channels in central neurons. Further, these data indicate that ASIC2, like ASIC1, plays a role in acidosis-induced neuronal death and implicate the ASIC2b/1a subtype as a novel pharmacological target to prevent neuronal injury following stroke. PMID:21715637

Sherwood, Thomas W.; Lee, Kirsten G.; Gormley, Matthew G.; Askwith, Candice C.

2011-01-01

367

Post-ischemic early acidosis in cardiac postconditioning modifies the activity of antioxidant enzymes, reduces nitration, and favors protein S-nitrosylation  

Microsoft Academic Search

Postconditioning (PostC) modifies the early post-ischemic pH, redox environment, and activity of enzymes. We hypothesized\\u000a that early acidosis in PostC may affect superoxide dismutase (SOD) and catalase (CAT) activities, may reduce 3-nitrotyrosine\\u000a (3-NT) protein levels, and may increase S-nitrosylated (SNO) protein levels, thus deploying its protective effects. To verify\\u000a this hypothesis, we studied the early (7th min) and late (120th

Claudia Penna; Maria-Giulia Perrelli; Francesca Tullio; Francesca Moro; Maria Laura Parisella; Annalisa Merlino; Pasquale Pagliaro

368

Estimation of the true incidence of lactic acidosis within the Lighthouse Clinic cohort, and the likely magnitude of missed diagnoses in the region  

PubMed Central

Introduction Lactic acidosis is one of the most serious side effects associated with ART, most commonly associated with stavudine. Clinical features are non-specific and specialist laboratory capabilities are essential to confirm the diagnosis, making under-diagnosis likely in resource-constrained settings. Lighthouse Trust is a tertiary referral ART centre with over 23,500 patients on ART. The adjacent University of North Carolina Project laboratory, also serving Kamuzu Central Hospital, has been the only site processing lactate tests in Central Zone for many years. Our objective was to quantify the true incidence within our cohort, and estimate the likely degree of historical missed diagnoses from less central ART clinics. Methods All high lactate results between June 2010 and June 2013 were treated as cases, and cross referenced with the Lighthouse database. Patients transferring in to Lighthouse within one month prior to diagnosis were assumed to have been referred due to their lactic acidosis, and moved to the Central Zone cohort to avoid referral bias. Routinely collected quarterly ART cohort data for both Lighthouse and the entire Central Zone were analyzed. Results Over the three-year period, from within the Lighthouse cohort, there were 138 cases: 74% were female, median duration on ART was 14 months (IQR 10–26), and 98.5% were attributable to stavudine (only two cases to zidovudine). Over this period, the average number of patients taking stavudine at Lighthouse was 10,960 (3,600 on zidovudine). For the whole Central Zone (minus Lighthouse patients) there were 61,000 on stavudine (4,830 on zidovudine), yet only 124 cases of lactic acidosis were apparently diagnosed from within this cohort. Conclusions Although cases may, of course, also have been missed at Lighthouse, as a tertiary referral centre the rate observed is likely to be closer to the true incidence. Over the three years, with 138 cases from the 10,960 patients taking stavudine at Lighthouse, it is likely that somewhere in the region of 700 additional cases occurred amongst the 61,000 patients elsewhere in the Central Zone. This equates to somewhere in the region of 550 missed diagnoses or 80% of all cases. Given that the clinical sequelae of undiagnosed lactic acidosis are either death or at best ART default, this provides further vindication for the decision to phase out stavudine in Malawi.

Speight, Colin; Gabriel, Layout; Phiri, Sam; Tweya, Hannock; Sutherland, Rebecca

2014-01-01

369

Friedrich Nietzsche (1844-1900): a classical case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome?  

PubMed

Friedrich Nietzsche was one of the most influential and profound German philosophers. After prolonged illness, he died at the age of 55 in Weimar, Germany. The interest in his medical biography has always been strong while the cause of his illness and death has remained a mystery, intriguing philosophers as well as physicians. The diagnosis of syphilis proposed in the 19th century has been controversial until today and many other diagnoses have been discussed. This paper suggests that Nietzsche suffered from mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome. PMID:19723969

Koszka, Christiane

2009-08-01

370

Metabolic myopathies.  

PubMed

Disorders of glycogen, lipid or mitochondrial metabolism may cause two main clinical syndromes, namely (1) progressive weakness (eg, acid maltase, debrancher enzyme, and brancher enzyme deficiencies among the glycogenoses; long- and very-long-chain acyl-CoA dehydrogenase (LCAD, VLCAD), and trifunctional enzyme deficiencies among the fatty acid oxidation (FAO) defects; and mitochondrial enzyme deficiencies) or (2) acute, recurrent, reversible muscle dysfunction with exercise intolerance and acute muscle breakdown or myoglobinuria (with or without cramps) (eg, phosphorylase (PPL), phosphorylase b kinase (PBK), phosphofructokinase (PFK), phosphoglycerate kinase (PGK), phosphoglycerate mutase (PGAM), and lactate dehydrogenase (LDH) among the glycogenoses and carnitine palmitoyltransferase II (CPT II) deficiency among the disorders of FAO or (3) both (eg, PPL, PBK, PFK among the glycogenoses; LCAD, VLCAD, short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD), and trifunctional enzyme deficiencies among the FAO defects; and multiple mitochondrial DNA (mtDNA) deletions). Myoadenylate deaminase deficiency, a purine nucleotide cycle defect, is somewhat controversial and is characterized by exercise-related cramps leading rarely to myoglobinuria. PMID:8795843

Tein, I

1996-06-01

371

Metabolic distance estimation based on principle component analysis of metabolic turnover.  

PubMed

Visualization of metabolic dynamism is important for various types of metabolic studies including studies on optimization of bio-production processes and studies of metabolism-related diseases. Many methodologies have been developed for metabolic studies. Among these, metabolic turnover analysis (MTA) is often used to analyze metabolic dynamics. MTA involves observation of changes in the isotopomer ratio of metabolites over time following introduction of isotope-labeled substrates. MTA has several advantages compared with (13)C-metabolic flux analysis, including the diversity of applicable samples, the variety of isotope tracers, and the wide range of target pathways. However, MTA produces highly complex data from which mining useful information becomes difficult. For easy understanding of MTA data, a new approach was developed using principal component analysis (PCA). The resulting PCA score plot visualizes the metabolic distance, which is defined as distance between metabolites on the real metabolic map. And the score plot gives us some hints of interesting metabolism for further study. We used this method to analyze the central metabolism of Saccharomyces cerevisiae under moderated aerobic conditions, and time course data for 77 isotopomers of 14 metabolites were obtained. The PCA score plot for this dataset represented a metabolic map and indicated interesting phenomena such as activity of fumarate reductase under aerated condition. These findings show the importance of a multivariate analysis to MTA. In addition, because the approach is not biased, this method has potential application for analysis of less-studied pathways and organisms. PMID:24680283

Nakayama, Yasumune; Putri, Sastia P; Bamba, Takeshi; Fukusaki, Eiichiro

2014-09-01

372

Epigenetic methylations and their connections with metabolism.  

PubMed

Metabolic pathways play fundamental roles in several processes that regulate cell physiology and adaptation to environmental changes. Altered metabolic pathways predispose to several different pathologies ranging from diabetes to cancer. Specific transcriptional programs tightly regulate the enzymes involved in cell metabolism and dictate cell fate regulating the differentiation into specialized cell types that contribute to metabolic adaptation in higher organisms. For these reasons, it is of extreme importance to identify signaling pathways and transcription factors that positively and negatively regulate metabolism. Genomic organization allows a plethora of different strategies to regulate transcription. Importantly, large evidence suggests that the quality of diet and the caloric regimen can influence the epigenetic state of our genome and that certain metabolic pathways are also epigenetically controlled reveling a tight crosstalk between metabolism and epigenomes. Here we focus our attention on methylation-based epigenetic reactions, on how different metabolic pathways control these activities, and how these can influence metabolism. Altogether, the recent discoveries linking these apparent distant areas reveal that an exciting field of research is emerging. PMID:23456257

Chiacchiera, Fulvio; Piunti, Andrea; Pasini, Diego

2013-05-01

373

Metabolic effects of hypergravity on experimental animals  

NASA Technical Reports Server (NTRS)

Several experiments concerned with the exposure of animals to acute or chronic centrifugation are described. The effects of hypergravity particularly discussed include the decreased growth rate and body weight, increased metabolic rate, skeletal deformation, and loss of body fat.

Oyama, J.

1982-01-01

374

The Tangled Circuitry of Metabolism and Apoptosis  

PubMed Central

For single cell organisms, nutrient uptake and metabolism are at the crux of their most basic decision of whether to grow or divide. In metazoans, cell fate decisions are more complex: organismal homeostasis must be strictly maintained by balancing cell proliferation and death. Despite this increased complexity, cell fate within multicellular organisms is also influenced by metabolism; recent studies, triggered in part be an interest tumor metabolism, are beginning to illuminate the mechanisms through which proliferation, death, and metabolism are intertwined. In particular, work on Bcl-2 family proteins suggests that the signaling pathways governing metabolism and apoptosis are inextricably linked. Here, we review the crosstalk between these pathways, emphasizing recent work that illustrates the emerging dual nature of several core apoptotic proteins in regulating both metabolism and cell death. PMID:23395270

Andersen, Joshua L.; Kornbluth, Sally

2013-01-01

375

A Diagnostic Algorithm for Metabolic Myopathies  

PubMed Central

Metabolic myopathies comprise a clinically and etiologically diverse group of disorders caused by defects in cellular energy metabolism, including the breakdown of carbohydrates and fatty acids to generate adenosine triphosphate, predominantly through mitochondrial oxidative phosphorylation. Accordingly, the three main categories of metabolic myopathies are glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders due to respiratory chain impairment. The wide clinical spectrum of metabolic myopathies ranges from severe infantile-onset multisystemic diseases to adult-onset isolated myopathies with exertional cramps. Diagnosing these diverse disorders often is challenging because clinical features such as recurrent myoglobinuria and exercise intolerance are common to all three types of metabolic myopathy. Nevertheless, distinct clinical manifestations are important to recognize as they can guide diagnostic testing and lead to the correct diagnosis. This article briefly reviews general clinical aspects of metabolic myopathies and highlights approaches to diagnosing the relatively more frequent subtypes (Fig. 1). PMID:20425236

Berardo, Andres; DiMauro, Salvatore

2010-01-01

376

[Metabolic therapy of postperitoneal intoxication].  

PubMed

This clinico-laboratory study showed that antihypoxant remaxol promoted normalization of lipid metabolism in acute peritonitis and significantly reduced membrane-destabilizing events. This resulted in rapid elimination of the inflammatory process in the abdominal cavity and lowering of the intensity of endogenous intoxication. This beneficial effect decreased the severity of myocardial lesions and resulted in the normalization of erythrocyte function. It is concluded that the regulatory action of remaxol on lipid metabolism is due to its ability to control free radicals in lipid peroxidation and reduce phospholipase A2 activity. PMID:23285765

Vlasov, A P; Anaskin, S G; Vlasova, T I; Chivisov, S M; Shibitov, V A; Potyanova, I V; Selentsov, P V

2012-01-01

377

Glucose Metabolism Following Severe Hemorrhage in the Conscious Dog.  

National Technical Information Service (NTIS)

The kinetics of glucose utilization before and after major hemorrhage was investigated by the primed infusion technique in eight conscious dogs given glucose-UC(14) alone or in combination with glucose-2-H(3). Following hemorrhage, arterial glucose concen...

R. Wiener, J. J. Spitzer

1973-01-01

378

Spermatozoa: models for studying regulatory aspects of energy metabolism  

Microsoft Academic Search

Spermatozoa are highly specialized cells, and they offer advantages for studying several basic aspects of metabolic control such as the role of adenosine triphosphate-(ATP)-homeostasis for cell function, the mechanisms of fatigue and metabolic depression, the metabolic channelling through the cytoplasm and the organization and regulation of glycolytic enzymes. Spermatozoa of four species with different reproductive modes are, introduced and the

G. Kamp; G. Büsselmann; J. Lauterwein

1996-01-01

379

Gut blood flow in fish during exercise and severe hypercapnia.  

PubMed

This paper reviews the effects of exercise and hypercapnia on blood flow to the splanchnic circulation. Brief struggling behaviours are known to decrease blood flow to the gut (GBF). Likewise, prolonged swimming in unfed fish has been shown to reduce GBF in proportion to the increased oxygen uptake. Therefore, the normal postprandial increase in GBF theoretically should be impaired whenever fish are active. However, indirect evidence suggests that GBF is spared to some degree when fed fish swim continuously but at a cost (10-15%) to their critical swimming speed. Severe respiratory acidosis can be created by the new intensive aquaculture settings that use oxygen injection into re-circulated water. The only study so far to examine the effects of severe hypercapnia on GBF and its regulation showed that routine GBF and alpha-adrenergic control of GBF remained normal in unfed white sturgeon (Acipenser transmontanus). However, severe hypercapnia produced a hyperactive state and increased sensitivity of GBF to struggling. As a result, routine GBF was maintained for a short period of time. Thus, environmental changes such as severe hypercapnia can indirectly impact GBF through altered struggling behaviour, but the implications of the overall reduction in GBF to food assimilation have yet to be established. PMID:11246044

Farrell, A P; Thorarensen, H; Axelsson, M; Crocker, C E; Gamperl, A K; Cech, J J

2001-03-01

380

Renal Tubular Acidosis  

MedlinePLUS

... Tract Infections (UTIs) Chronic Kidney Diseases Life With Lupus Urinary Tract Infections Definition: Kidney Kidney Stones Kidney Disease Kidneys and Urinary Tract Glomerulonephritis Blood in the ...

381

Metformin, cancer and glucose metabolism.  

PubMed

Metformin is the first-line treatment for type 2 diabetes. Results from several clinical studies have indicated that type 2 diabetic patients treated with metformin might have a lower cancer risk. One of the primary metabolic changes observed in malignant cell transformation is an increased catabolic glucose metabolism. In this context, once it has entered the cell through organic cation transporters, metformin decreases mitochondrial respiration chain activity and ATP production that, in turn, activates AMP-activated protein kinase, which regulates energy homeostasis. In addition, metformin reduces cellular energy availability and glucose entrapment by inhibiting hexokinase-II, which catalyses the glucose phosphorylation reaction. In this review, we discuss recent findings on molecular mechanisms that sustain the anticancer effect of metformin through regulation of glucose metabolism. In particular, we have focused on the emerging action of metformin on glycolysis in normal and cancer cells, with a drug discovery perspective. PMID:25273809

Salani, Barbara; Del Rio, Alberto; Marini, Cecilia; Sambuceti, Gianmario; Cordera, Renzo; Maggi, Davide

2014-12-01

382

A dynamic mechanistic model of lactic acid metabolism in the rumen.  

PubMed

Current feed evaluation systems for ruminants are too imprecise to describe diets in terms of their acidosis risk. The dynamic mechanistic model described herein arises from the integration of a lactic acid (La) metabolism module into an extant model of whole-rumen function. The model was evaluated using published data from cows and sheep fed a range of diets or infused with various doses of La. The model performed well in simulating peak rumen La concentrations (coefficient of determination = 0.96; root mean square prediction error = 16.96% of observed mean), although frequency of sampling for the published data prevented a comprehensive comparison of prediction of time to peak La accumulation. The model showed a tendency for increased La accumulation following feeding of diets rich in nonstructural carbohydrates, although less-soluble starch sources such as corn tended to limit rumen La concentration. Simulated La absorption from the rumen remained low throughout the feeding cycle. The competition between bacteria and protozoa for rumen La suggests a variable contribution of protozoa to total La utilization. However, the model was unable to simulate the effects of defaunation on rumen La metabolism, indicating a need for a more detailed description of protozoal metabolism. The model could form the basis of a feed evaluation system with regard to rumen La metabolism. PMID:24565322

Mills, J A N; Crompton, L A; Ellis, J L; Dijkstra, J; Bannink, A; Hook, S; Benchaar, C; France, J

2014-04-01

383

Metabolism of extracellular pyrophosphate.  

PubMed

Accumulation of excess inorganic pyrophosphate in cartilage matrix leads to calcium pyrophosphate dihydrate crystal deposits. Recent animal and human studies now support a role for physiologic extracellular pyrophosphate levels in preventing ectopic apatite calcification in joints and extracellular tissues. Extracellular pyrophosphate is likely generated by ectoenzymes and/or is a consequence of transport of intracellular pyrophosphate to the extracellular space. Generation of pyrophosphate by chondrocytes is modulated by aging, several soluble growth factors and cytokines, and transglutaminase. The transduction mechanisms involved in regulating pyrophosphate metabolism include protein kinase C and adenylyl cyclase. It appears that regulation of extracellular pyrophosphate levels within a narrow range is complex and necessary for appropriate mineral homeostasis in articular and nonarticular tissues. PMID:12707586

Ryan, Lawrence M; Rosenthal, Ann K

2003-05-01

384

Severe alkalosis and hypokalemia with stanozolol misuse.  

PubMed

Stanozolol is a popular androgenic anabolic steroid, used by body builders and athletes for physical performance enhancement. There are few data on its potential adverse effects and no documented cases of it causing severe electrolyte imbalance. Here, we report a patient presenting to a tertiary care emergency department with reduced conscious level, profound hypokalemia, and severe metabolic alkalosis, resulting from stanozolol misuse. This is the first such case reported. PMID:24521609

Maini, Alexander A N; Maxwell-Scott, Hector; Marks, Daniel J B

2014-02-01

385

Metabolic complications and treatment of perinatally HIV-infected children and adolescents  

PubMed Central

The benefits of long-term antiretroviral therapy (ART) are recognized all over the world with infected children maturing into adults and HIV infection becoming a chronic illness. However, the improved survival is associated with serious metabolic complications, including lipodystrophy (LD), dyslipidemia, insulin resistance, lactic acidosis and bone loss. In addition, the dyslipidemia mainly seen with protease inhibitors may increase the risk of cardiovascular disease in adulthood and potentially in children as they mature into adults. Nucleoside reverse transcriptase inhibitors, particularly stavudine, zidovudine and didanosine are linked to development of LD and lactic acidosis. Perinatally infected children initiate ART early in life; they require lifelong therapy with multiple drug regimens leading to varying toxicities, all potentially impacting their quality of life. LD has a significant impact on the mental health of older children and adolescents leading to poor self-image, depression and subsequent poor adherence to therapy. Reduced bone mineral density (BMD) is reported in both adults and children on ART with the potential for children to develop more serious bone complications than adults due to their rapid growth spurts and puberty. The role of vitamin D in HIV-associated osteopenia and osteoporosis is not clear and needs further study. Most resource-limited settings are unable to monitor lipid profiles or BMD, exposing infected children and adolescents to on-going toxicities with unclear long-term consequences. Improved interventions are urgently needed to prevent and manage these metabolic complications. Longitudinal cohort studies in this area should remain a priority, particularly in resource-limited settings where the majority of infected children reside. PMID:23782481

Barlow-Mosha, Linda; Ross Eckard, Allison; McComsey, Grace A; Musoke, Philippa M

2013-01-01

386

The 1986 Borden award lecture. The role of the kidney in amino acid metabolism and nutrition.  

PubMed

Measurement of the arteriovenous differences for free amino acids across rat kidney reveals that glycine and citrulline are removed and serine and arginine are added to the circulation. In addition, glutamine is taken up in large quantities by kidneys of animals that need to excrete large quantities of acid (e.g., diabetic animals, NH4Cl-fed animals, and animals fed a high protein diet). Glutamine is the major precursor of urinary ammonia and thus renal glutamine metabolism plays a key role in acid-base homeostasis. This process occurs primarily in the cells of the convoluted proximal tubule. Glutamine carbon is converted to glucose in acidotic rats and is totally oxidized in dogs. Regulation of glutamine metabolism occurs at two levels: acute regulation and chronic regulation. Acute regulation is, in part, mediated through a fall in intracellular [H+]. This activates alpha-ketoglutarate dehydrogenase and, ultimately, glutaminase. Chronic regulation involves induction of key enzymes, including, in the rat, glutaminase, glutamate dehydrogenase, and phosphoenolpyruvate carboxykinase. During the acidosis of prolonged starvation, the kidneys' requirement for glutamine must be met from muscle proteolysis and thus becomes a drain on lean body mass. Serine synthesis occurs by two separate pathways: from glycine by the combined actions of the glycine cleavage enzyme and serine hydroxymethyltransferase and from gluconeogenic precursors using the phosphorylated-intermediate pathway. Both pathways are located in the cells of the proximal tubule. Conversion of glycine to serine is ammoniagenic and the activity of the glycine cleavage enzyme is increased in acidosis. The function of serine synthesis by the phosphorylated-intermediate pathway is not apparent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3329568

Brosnan, J T

1987-12-01

387

Metabolic experiments on Spacelab-4  

NASA Technical Reports Server (NTRS)

Studies of human metabolism are being considered in five experiments. These investigations address physiological effects of zero gravity which have become evident in previous manned space flights, namely, negative Na, Ca and N balances, the resorption of bone, loss of red cell mass, cephalad migration of body fluids, and a shift in water balance. Although these effects have been fairly well established by pre- and postflight measurements, details of the mechanism by which they occur remain largely unknown. Moreover, the data collected inflight, particularly during the first few hours of weightlessness, have been severely limited both in the amount of quantitative information obtained and with respect to the relative simplicity of the experimental techniques employed. During the Spacelab 4 mission, the acute stage of the response to zero gravity will be the main focus of attention of several experiments. Measurements conducted later in the mission will center on the adaptive phase of metabolic responses.

Leach, C. S.

1982-01-01

388

Metabolically healthy obesity--does it exist?  

PubMed

The prevalence of obesity has been increasing worldwide over the past 30 years and is a major public health concern. Obesity is known to be associated with metabolic disturbances including insulin resistance and inflammation; however, there is a subset of obese subjects who have normal metabolic profiles, and they have been identified as the metabolically healthy obese (MHO). Several studies have described MHO as obese individuals who have high levels of insulin sensitivity and the absence of diabetes, dyslipidemia, or hypertension. The prevalence of MHO varies from 20 to 30% among obese individuals. This review will discuss the MHO phenotype; the differences between MHO and metabolically unhealthy obese (MUO) individuals; and the possible underlying mechanisms including adipocyte differentiation, immune regulation, and cellular energy metabolism. PMID:25092577

Boonchaya-anant, Patchaya; Apovian, Caroline M

2014-10-01

389

Engineering complex metabolic pathways in plants.  

PubMed

Metabolic engineering can be used to modulate endogenous metabolic pathways in plants or introduce new metabolic capabilities in order to increase the production of a desirable compound or reduce the accumulation of an undesirable one. In practice, there are several major challenges that need to be overcome, such as gaining enough knowledge about the endogenous pathways to understand the best intervention points, identifying and sourcing the most suitable metabolic genes, expressing those genes in such a way as to produce a functional enzyme in a heterologous background, and, finally, achieving the accumulation of target compounds without harming the host plant. This article discusses the strategies that have been developed to engineer complex metabolic pathways in plants, focusing on recent technological developments that allow the most significant bottlenecks to be overcome. PMID:24579989

Farré, Gemma; Blancquaert, Dieter; Capell, Teresa; Van Der Straeten, Dominique; Christou, Paul; Zhu, Changfu