Sample records for severe metabolic acidosis

  1. Metabolic acidosis

    MedlinePLUS

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

  2. Diagnostic Challenge in a Patient with Severe Anion Gap Metabolic Acidosis

    PubMed Central

    Tan, Eugene M.; Kalimullah, Ejaaz; Sohail, M. Rizwan; Ramar, Kannan

    2015-01-01

    The approach to the patient with acute renal failure and elevated anion and osmolal gap is difficult. Differential diagnoses include toxic alcohol ingestion, diabetic or starvation ketoacidosis, or 5-oxoproline acidosis. We present a 76-year-old female with type 2 diabetes mellitus, who was found at home in a confused state. Laboratory analysis revealed serum pH 6.84, bicarbonate 5.8?mmol/L, pCO2 29?mmHg, anion gap 22.2?mmol/L, osmolal gap 17.4?mOsm/kg, elevated beta-hydroxybutyrate (4.2?mmol/L), random blood sugar 213?mg/dL, creatinine 2.1?mg/dL, and potassium 7.5?mmol/L with no electrocardiogram (EKG) changes. Fomepizole and hemodialysis were initiated for presumed ethylene glycol or methanol ingestion. Drug screens returned negative for ethylene glycol, alcohols, and acetaminophen, but there were elevated urine levels of acetone (11?mg/dL). The acetaminophen level was negative, and 5-oxoproline was not analyzed. After 5 days in the intensive care unit (ICU), her mental status improved with supportive care. She was discharged to a nursing facility. Though a diagnosis was not established, our patient's presentation was likely due to starvation ketosis combined with chronic acetaminophen ingestion. Acetone ingestion is less likely. Overall, our case illustrates the importance of systematically approaching an elevated osmolal and anion gap metabolic acidosis.

  3. Chronic metabolic acidosis destroys pancreas.

    PubMed

    Melamed, Peter; Melamed, Felix

    2014-11-01

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

  4. Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis

    PubMed Central

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

    2014-01-01

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

  5. Metabolic acidosis-induced insulin resistance and cardiovascular risk.

    PubMed

    Souto, Gema; Donapetry, Cristóbal; Calviño, Jesús; Adeva, Maria M

    2011-08-01

    Microalbuminuria has been conclusively established as an independent cardiovascular risk factor, and there is evidence of an association between insulin resistance and microalbuminuria, the former preceding the latter in prospective studies. It has been demonstrated that even the slightest degree of metabolic acidosis produces insulin resistance in healthy humans. Many recent epidemiological studies link metabolic acidosis indicators with insulin resistance and systemic hypertension. The strongly acidogenic diet consumed in developed countries produces a lifetime acidotic state, exacerbated by excess body weight and aging, which may result in insulin resistance, metabolic syndrome, and type 2 diabetes, contributing to cardiovascular risk, along with genetic causes, lack of physical exercise, and other factors. Elevated fruits and vegetables consumption has been associated with lower diabetes incidence. Diseases featuring severe atheromatosis and elevated cardiovascular risk, such as diabetes mellitus and chronic kidney failure, are typically characterized by a chronic state of metabolic acidosis. Diabetic patients consume particularly acidogenic diets, and deficiency of insulin action generates ketone bodies, creating a baseline state of metabolic acidosis worsened by inadequate metabolic control, which creates a vicious circle by inducing insulin resistance. Even very slight levels of chronic kidney insufficiency are associated with increased cardiovascular risk, which may be explained at least in part by deficient acid excretory capacity of the kidney and consequent metabolic acidosis-induced insulin resistance. PMID:21352078

  6. An unrecognised case of metabolic acidosis following neobladder augmentation cystoplasty

    PubMed Central

    Eldred-Evans, David; Khan, Fahd; Abbaraju, Jay; Sriprasad, Seshadri

    2015-01-01

    Introduction We present a case where there was a delay in the diagnosis of severe metabolic acidosis in a patient with an orthotopic neobladder. There are a growing number of patients with orthotopic neobladders and a wider range of clinicians are encountering these patients. A delay in the diagnosis can lead to significant morbidity but if identified early it can be easily treated. Presentation of case A 59-year old patient with a recent neobladder augmentation cystoplasty was admitted under the medical team with a metabolic acidosis which was incorrectly presumed to be secondary to urosepsis. His condition rapidly deteriorated until a surgical review identified hyperchloremic metabolic acidosis secondary to neobladder augmentation. The patient required admission to the intensive care unit where he was treated with intravenous alkalising therapy which produced rapid metabolic improvement. Following a full recovery, he underwent neo-bladder excision and ileal conduit formation. Discussion Hyperchloraemic metabolic acidosis develops due to the bowel segment absorbing urinary constituents including ammonium, hydrogen ions and chloride in exchange for sodium and bicarbonate. It can be diagnosed by careful interpretation of the arterial blood gas and calculation of the anion gap. This hyperchloraemic metabolic acidosis can be corrected with alkalizing agents combined with catheterisation. Conclusion Hyperchloremic metabolic acidosis is a well-established complication of urinary diversion. Patient with orthotopic neobladder with high residual urine and large capacity are at even higher risk of metabolic acidosis. This information should be clearly documented in the post-operative discharge documentation to ensure early recognition by non-specialists. PMID:25979515

  7. Metabolic Acidosis-Induced Insulin Resistance and Cardiovascular Risk

    PubMed Central

    Souto, Gema; Donapetry, Cristóbal; Calviño, Jesús

    2011-01-01

    Abstract Microalbuminuria has been conclusively established as an independent cardiovascular risk factor, and there is evidence of an association between insulin resistance and microalbuminuria, the former preceding the latter in prospective studies. It has been demonstrated that even the slightest degree of metabolic acidosis produces insulin resistance in healthy humans. Many recent epidemiological studies link metabolic acidosis indicators with insulin resistance and systemic hypertension. The strongly acidogenic diet consumed in developed countries produces a lifetime acidotic state, exacerbated by excess body weight and aging, which may result in insulin resistance, metabolic syndrome, and type 2 diabetes, contributing to cardiovascular risk, along with genetic causes, lack of physical exercise, and other factors. Elevated fruits and vegetables consumption has been associated with lower diabetes incidence. Diseases featuring severe atheromatosis and elevated cardiovascular risk, such as diabetes mellitus and chronic kidney failure, are typically characterized by a chronic state of metabolic acidosis. Diabetic patients consume particularly acidogenic diets, and deficiency of insulin action generates ketone bodies, creating a baseline state of metabolic acidosisworsened by inadequate metabolic control, which creates a vicious circle by inducing insulin resistance. Even very slight levels of chronic kidney insufficiency are associated with increased cardiovascular risk, which may be explained at least in part by deficient acid excretory capacity of the kidney and consequent metabolic acidosis-induced insulin resistance. PMID:21352078

  8. Metabolic acidosis during parenteral nutrition: Pathophysiological mechanisms.

    PubMed

    Dounousi, Evangelia; Zikou, Xanthi; Koulouras, Vasilis; Katopodis, Kostas

    2015-05-01

    Total parenteral nutrition (TPN) is associated with metabolic complications including metabolic acidosis (MA), one of the main disorders of acid-base balance. The main causes involved in the appearance of MA during TPN administration are the metabolism of cationic amino acids and amino acids containing sulfuric acid (exogenous addition), the titratable acidity of the infused parenteral solution, the addition of acidificant agents (hydrochloric acid, acetic acid), thiamine deficiency, disruption of carbohydrate and lipid metabolic pathways and D-fructose administration. Moreover, hypophosphatemia that appears during TPN therapy contributes significantly to the maintenance of MA. This review describes in a comprehensive way the pathophysiological mechanisms involved in the appearance of MA induced by intravenous administration of TPN products most commonly used in critically ill-patients. PMID:25983433

  9. [End stage of chronic kidney disease and metabolic acidosis].

    PubMed

    Klaboch, J; Opatrná, S; Matoušovic, K; Schück, O

    2012-01-01

    Renal function disorder is inevitably associated with metabolic acidosis. An adult produces approximately 1 mmol of acids/kg of body weight every day (3 mmol/kg in children), derived from metabolization of proteins from food. Development of metabolic acidosis in patients with kidney disease is based on accumulation of acids and insufficient production of bicarbonates; alkaline loss represents a marginal issue here limited to patients with type II renal tubular acidosis only. The prevalence of this disorder increases with declining glomerular filtration (GFR) from 2% in patients with GFR 1.0-1.5 ml/s/1.73 m2 to 39% in patients with GFR < 0.3 ml/s/1.73 m2 or, alternatively, to 19% in patients with GFR 0.25-0.3 ml/s/1.73 m2. Notwithstanding the primary cause of the renal disease, declining GFR is associated with compensatory increase in ammoniac production in residual nephrons. This is an adaptive mechanism aimed at maintaining sufficient elimination of acids despite reduced volume of functional tissue. However, an increased ammoniac production simultaneously becomes a stimulus for activation of the complement via an alternative route and is thus one of the factors contributing, through this induced inflammation, to progression of tubular interstitial fibrosis that subsequently leads to further GFR reduction. Metabolic acidosis has a number of severe adverse effects on the organism, e.g. deterioration of kidney bone disease through stimulation of bone resorption and inhibition of bone formation, inhibition of vitamin D formation, increased muscle catabolism, reduced albumin production, glucose metabolism disorder, increased insulin resistance, reduced production of thyroid hormones, increased accumulation of ?2-microglobulin etc. Non-interventional studies suggest that alkali supplementation may slow down progression of chronic nephropathies. However, this approach, safe and inexpensive, has not been widely implemented in clinical practice yet. With respect to dialyzed patients, abnormal levels of bicarbonates are associated with increased mortality. Both metabolic acidosis and alkalosis, rather regularly seen in a considerable number of patients, have a negative effect on patient survival. Alkali substitution from a dialysis solution is the main pillar of metabolic acidosis management in patients on hemo- as well as peritoneal dialysis. Available technologies allow individualization of the treatment and this should be observed. PMID:23067161

  10. Acute kidney injury, hyperosmolality and metabolic acidosis associated with lorazepam

    Microsoft Academic Search

    Irfan Yusufzai; Anna Sullivan; Charles Graeber; Tausif Zar

    2007-01-01

    Background A 54-year-old male with a history of multiple admissions for alcohol intoxication was admitted to hospital with right flank pain. He received a high-dose lorazepam infusion for alcohol withdrawal during hospitalization and developed severe hyperosmolality, high anion gap metabolic acidosis, and acute kidney injury on his eighth day of hospitalization.Investigations Serum chemistries, arterial blood gas analysis, and measurement of

  11. Metabolic acidosis in a pediatric patient receiving topiramate.

    PubMed

    Malik, Razia; Iacoune, John

    2003-10-01

    Topiramate is an anticonvulsant that is labeled for the management of several seizure types in children >2 years of age. With the exception of cognitive dysfunction, nephrolithiasis, weight loss, and paresthesia, adverse effects in children are similar to other those noted with other anticonvulsants. We describe a 33-month-old child with complex partial seizures and secondary generalization who received topiramate 45 mg orally twice daily (6.2 mg/kg/d) for approximately 4 weeks before admission. He developed asymptomatic metabolic acidosis that was evidenced by a decrease in HCO(3) (-), which was unresponsive to treatment with sodium bicarbonate. The child was weaned off topiramate and the metabolic acidosis resolved 48 hours after its discontinuation. PMID:23118685

  12. Greater inhibition of in vitro bone mineralization with metabolic than respiratory acidosis

    Microsoft Academic Search

    Stuart M Sprague; Nancy S Krieger; David A Bushinsky

    1994-01-01

    Greater inhibition of in vitro bone mineralization with metabolic than respiratory acidosis. At a similar decrement in pH, acidosis produced by lowering the concentration of medium bicarbonate (metabolic acidosis) induces greater net calcium efflux from cultured neonatal mouse calvariae than acidosis produced by increasing the partial pressure of carbon dioxide (respiratory acidosis). This differential effect is due, at least in

  13. Cellular mechanisms of bone resorption induced by metabolic acidosis.

    PubMed

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

    2003-01-01

    Metabolic acidosis increases urine calcium excretion without an increase in intestinal calcium absorption, resulting in a net loss of bone mineral. In vitro metabolic acidosis induces bone calcium efflux initially by physicochemical dissolution and subsequently by cell-mediated mechanisms involving inhibition of osteoblasts and stimulation of osteoclasts. In bone, prostaglandins (PGs) are important mediators of bone resorption and we have recently determined that acid-induced bone resorption is mediated by PGs. Utilizing neonatal mouse calvariae in culture, we found that decreasing pH by a reduction in bicarbonate concentration, a model of metabolic acidosis, induced an increase in net calcium efflux and in medium prostaglandin E2 (PGE2) levels, both of which were inhibited in the presence of indomethacin. There was a direct correlation between calcium flux and medium PGE2. If pH is lowered to a comparable degree by an increase in pCO2 to model respiratory acidosis, there was no significant stimulation of net calcium efflux from the calvariae and no stimulation of PGE2 production. We have also shown that metabolic acidosis alters osteoblastic expression of a specific osteoclastogenic factor, RANKL, and this response is also PG dependent. Incubation of calvariae in acid medium stimulated expression of RANKL RNA in parallel with the increased calcium flux. Both responses were inhibited in the presence of indomethacin. Thus metabolic, but not respiratory, acidosis induces production of bone PGE2, which mediates acid-induced bone resorption. PMID:14629607

  14. Acidosis

    MedlinePLUS

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

  15. A rare metabolic complication of acute lymphoblastic leukemia in childhood: lactic acidosis.

    PubMed

    Gökçe, Müge; Unal, Sule; Gül?en, Hayriye; Ba?aran, Ozge; Cetin, Mualla; Gümrük, Fatma; Be?ba?, Nesrin; Gürgey, Aytemiz

    2012-01-01

    A 13-year-old boy presented with nausea, fatigue, weight loss, and bone pain for two months. Complete blood count and serum renal and liver function tests were all normal. Blood gas analysis revealed severe metabolic acidosis with high anion gap. Lactate level was 61.2 mmol/L. Abdominal ultrasonography yielded bilateral nephromegaly and hepatomegaly with increased echogenicity. Peripheral blood smear revealed 2% blasts. Bone marrow aspiration showed 'Common ALL Antigen'-negative acute lymphoblastic leukemia by flow cytometric analysis. Metabolic acidosis dissolved as soon as chemotherapy was begun. Lactic acidosis at the presentation of acute lymphoblastic leukemia--especially with low tumor burden--is a very rare and almost always fatal complication. Our patient is still alive and in remission, which is a point of interest in this child. PMID:22397045

  16. Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding.

    PubMed

    De Robertis, E; Kozek-Langenecker, S A; Tufano, R; Romano, G M; Piazza, O; Zito Marinosci, G

    2015-01-01

    Acidosis, hypothermia and hypocalcaemia are determinants for morbidity and mortality during massive hemorrhages. However, precise pathological mechanisms of these environmental factors and their potential additive or synergistic anticoagulant and/or antiplatelet effects are not fully elucidated and are at least in part controversial. Best available evidences from experimental trials indicate that acidosis and hypothermia progressively impair platelet aggregability and clot formation. Considering the cell-based model of coagulation physiology, hypothermia predominantly prolongs the initiation phase, while acidosis prolongs the propagation phase of thrombin generation. Acidosis increases fibrinogen breakdown while hypothermia impairs its synthesis. Acidosis and hypothermia have additive effects. The effect of hypocalcaemia on coagulopathy is less investigated but it appears that below the cut-off of 0.9 mmol/L, several enzymatic steps in the plasmatic coagulation system are blocked while above that cut-off effects remain without clinical sequalae. The impact of environmental factor on hemostasis is underestimated in clinical practice due to our current practice of using routine coagulation laboratory tests such as partial thromboplastin time or prothrombin time, which are performed at standardized test temperature, after pH correction, and upon recalcification. Temperature-adjustments are feasible in viscoelastic point-of-care tests such as thrombelastography and thromboelastometry which may permit quantification of hypothermia-induced coagulopathy. Rewarming hypothermic bleeding patients is highly recommended because it improves patient outcome. Despite the absence of high-quality evidence, calcium supplementation is clinical routine in bleeding management. Buffer administration may not reverse acidosis-induced coagulopathy but may be essential for the efficacy of coagulation factor concentrates such as recombinant activated factor VII. PMID:24608516

  17. Osteoblastic intracellular pH and calcium in metabolic and respiratory acidosis

    Microsoft Academic Search

    Yaacov Ori; Soo Gil Lee; Nancy S Krieger; David A Bushinsky

    1995-01-01

    Osteoblastic intracellular pH and calcium in metabolic and respiratory acidosis. In vitro metabolic acidosis (Met) induces greater bone mineral resorption than respiratory acidosis (Resp). Met, but not Resp, inhibits osteoblasts which control many aspects of osteoclastic function. To determine whether at a similar decrement in extracellular pH, Met and Resp would induce different changes in intracellular pH (pHi) and\\/or intracellular

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

    E-print Network

    Bennett, Albert F.

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

  19. Sulfatides are required for renal adaptation to chronic metabolic acidosis

    PubMed Central

    Stettner, Paula; Bourgeois, Soline; Marsching, Christian; Traykova-Brauch, Milena; Porubsky, Stefan; Nordström, Viola; Hopf, Carsten; Koesters, Robert; Sandhoff, Roger; Wiegandt, Herbert; Wagner, Carsten A.; Gröne, Hermann-Josef; Jennemann, Richard

    2013-01-01

    Urinary ammonium excretion by the kidney is essential for renal excretion of sufficient amounts of protons and to maintain stable blood pH. Ammonium secretion by the collecting duct epithelia accounts for the majority of urinary ammonium; it is driven by an interstitium-to-lumen NH3 gradient due to the accumulation of ammonium in the medullary and papillary interstitium. Here, we demonstrate that sulfatides, highly charged anionic glycosphingolipids, are important for maintaining high papillary ammonium concentration and increased urinary acid elimination during metabolic acidosis. We disrupted sulfatide synthesis by a genetic approach along the entire renal tubule. Renal sulfatide-deficient mice had lower urinary pH accompanied by lower ammonium excretion. Upon acid diet, they showed impaired ammonuria, decreased ammonium accumulation in the papilla, and chronic hyperchloremic metabolic acidosis. Expression levels of ammoniagenic enzymes and Na+-K+/NH4+-2Cl? cotransporter 2 were higher, and transepithelial NH3 transport, examined by in vitro microperfusion of cortical and outer medullary collecting ducts, was unaffected in mutant mice. We therefore suggest that sulfatides act as counterions for interstitial ammonium facilitating its retention in the papilla. This study points to a seminal role of sulfatides in renal ammonium handling, urinary acidification, and acid–base homeostasis. PMID:23716689

  20. Citrate Reverses Cyclosporin A-Induced Metabolic Acidosis and Bone Resorption in Rats

    Microsoft Academic Search

    Shuichi Tsuruoka; George J. Schwartz; Takashi Ioka; Hisashi Yamamoto; Hitoshi Ando; Akio Fujimura

    2005-01-01

    Background: Cyclosporine A (CsA) causes distal renal tubular acidosis (RTA) and osteoporosis. We have recently reported that the reduction of nitric oxide (NO) exacerbates this condition. Distal RTA may deplete bone mineral due to the chronic buffering of acid in the blood. The interaction of CsA and NO in causing metabolic acidosis and bone demineralization has not been studied previously.

  1. Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone.

    PubMed

    Krieger, Nancy S; Culbertson, Christopher D; Kyker-Snowman, Kelly; Bushinsky, David A

    2012-08-01

    Fibroblast growth factor 23 (FGF23) significantly increases with declining renal function, leading to reduced renal tubular phosphate reabsorption, decreased 1,25-dihydroxyvitamin D, and increased left ventricular hypertrophy. Elevated FGF23 is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the mechanisms by which it is regulated are not clear. Patients with chronic kidney disease have decreased renal acid excretion leading to metabolic acidosis, which has a direct effect on bone cell activity. We hypothesized that metabolic acidosis would directly increase bone cell FGF23 production. Using cultured neonatal mouse calvariae, we found that metabolic acidosis increased medium FGF23 protein levels as well as FGF23 RNA expression at 24 h and 48 h compared with incubation in neutral pH medium. To exclude that the increased FGF23 was secondary to metabolic acidosis-induced release of bone mineral phosphate, we cultured primary calvarial osteoblasts. In these cells, metabolic acidosis increased FGF23 RNA expression at 6 h compared with incubation in neutral pH medium. Thus metabolic acidosis directly increases FGF23 mRNA and protein in mouse bone. If these results are confirmed in humans with chronic kidney disease, therapeutic interventions to mitigate acidosis, such as bicarbonate administration, may also lower levels of FGF23, decrease left ventricular hypertrophy, and perhaps even decrease mortality. PMID:22647635

  2. Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone

    PubMed Central

    Culbertson, Christopher D.; Kyker-Snowman, Kelly; Bushinsky, David A.

    2012-01-01

    Fibroblast growth factor 23 (FGF23) significantly increases with declining renal function, leading to reduced renal tubular phosphate reabsorption, decreased 1,25-dihydroxyvitamin D, and increased left ventricular hypertrophy. Elevated FGF23 is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the mechanisms by which it is regulated are not clear. Patients with chronic kidney disease have decreased renal acid excretion leading to metabolic acidosis, which has a direct effect on bone cell activity. We hypothesized that metabolic acidosis would directly increase bone cell FGF23 production. Using cultured neonatal mouse calvariae, we found that metabolic acidosis increased medium FGF23 protein levels as well as FGF23 RNA expression at 24 h and 48 h compared with incubation in neutral pH medium. To exclude that the increased FGF23 was secondary to metabolic acidosis-induced release of bone mineral phosphate, we cultured primary calvarial osteoblasts. In these cells, metabolic acidosis increased FGF23 RNA expression at 6 h compared with incubation in neutral pH medium. Thus metabolic acidosis directly increases FGF23 mRNA and protein in mouse bone. If these results are confirmed in humans with chronic kidney disease, therapeutic interventions to mitigate acidosis, such as bicarbonate administration, may also lower levels of FGF23, decrease left ventricular hypertrophy, and perhaps even decrease mortality. PMID:22647635

  3. Treatment options for lactic acidosis and metabolic crisis in children with mitochondrial disease.

    PubMed

    Danhauser, Katharina; Smeitink, Jan A M; Freisinger, Peter; Sperl, Wolfgang; Sabir, Hemmen; Hadzik, Berit; Mayatepek, Ertan; Morava, Eva; Distelmaier, Felix

    2015-05-01

    The mitochondrial pyruvate oxidation route is a tightly regulated process, which is essential for aerobic cellular energy production. Disruption of this pathway may lead to severe neurometabolic disorders with onset in early childhood. A frequent finding in these patients is acute and chronic lactic acidemia, which is caused by increased conversion of pyruvate via the enzyme lactate dehydrogenase. Under stable clinical conditions, this process may remain well compensated and does not require specific therapy. However, especially in situations with altered energy demands, such as febrile infections or longer periods of fasting, children with mitochondrial disorders have a high risk of metabolic decompensation with exacerbation of hyperlactatemia and severe metabolic acidosis. Unfortunately, no controlled studies regarding therapy of this critical condition are available and clinical outcome is often unfavorable. Therefore, the aim of this review was to formulate expert-based suggestions for treatment of these patients, including dietary recommendations, buffering strategies and specific drug therapy. However, it is important to keep in mind that a specific therapy for the underlying metabolic cause in children with mitochondrial diseases is usually not available and symptomatic therapy especially of severe lactic acidosis has its ethical limitations. PMID:25687154

  4. Severe metformin intoxication with lactic acidosis in an adolescent

    Microsoft Academic Search

    Martin Lacher; Maren Hermanns-Clausen; Karsten Haeffner; Matthias Brandis; Martin Pohl

    2005-01-01

    A 15-year-old healthy girl ingested 38.25 g (0.55 g\\/kg body weight) of metformin in a suicide attempt. Subsequently she developed lactic acidosis and moderate renal failure. An initial session of haemodialysis was able to treat the acidosis and reduce the toxic level of metformin. Nevertheless, a further increase in serum lactate was observed during and after the first dialysis treatment. A second

  5. Citrate metabolism in blood transfusions and its relationship due to metabolic alkalosis and respiratory acidosis

    PubMed Central

    Li, Kai; Xu, Yuan

    2015-01-01

    Metabolic alkalosis commonly results from excessive hydrochloric acid (HCl), potassium (K+) and water (H2O) loss from the stomach or through the urine. The plasma anion gap increases in non-hypoproteinemic metabolic alkalosis due to an increased negative charge equivalent on albumin and the free ionized calcium (Ca++) content of plasma decreases. The mean citrate load in all patients was 8740±7027 mg from 6937±6603 mL of transfused blood products. The citrate load was significantly higher in patients with alkalosis (9164±4870 vs. 7809±3967, P < 0.05). The estimated mean total citrate administered via blood and blood products was calculated as 43.2±34.19 mg/kilogram/day. In non-massive and frequent blood transfusions, the elevated carbon dioxide output has been shown to occur. Due to citrate metabolism causes intracellular acidosis. As a result of intracellular acidosis compensation, decompensated metabolic alkalosis + respiratory acidosis and electrolyte imbalance may develop, blood transfusions may result in certain complications.

  6. Hyperammonaemia with distal renal tubular acidosis

    PubMed Central

    Miller, S; Schwartz, G

    1997-01-01

    ?? The case is reported of an infant with hyperammonaemia secondary to severe distal renal tubular acidosis. A clinical association between increased concentrations of ammonia in serum and renal tubular acidosis has not previously been described. In response to acidosis the infant's kidneys presumably increased ammonia synthesis but did not excrete ammonia, resulting in hyperammonaemia. The patient showed poor feeding, frequent vomiting, and failure to thrive, but did not have an inborn error of metabolism. This case report should alert doctors to consider renal tubular acidosis in the differential diagnosis of severely ill infants with metabolic acidosis and hyperammonaemia.?? PMID:9487970

  7. Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside.

    PubMed

    Kimmoun, Antoine; Novy, Emmanuel; Auchet, Thomas; Ducrocq, Nicolas; Levy, Bruno

    2015-01-01

    Lactic acidosis is a very common biological issue for shock patients. Experimental data clearly demonstrate that metabolic acidosis, including lactic acidosis, participates in the reduction of cardiac contractility and in the vascular hyporesponsiveness to vasopressors through various mechanisms. However, the contributions of each mechanism responsible for these deleterious effects have not been fully determined and their respective consequences on organ failure are still poorly defined, particularly in humans. Despite some convincing experimental data, no clinical trial has established the level at which pH becomes deleterious for hemodynamics. Consequently, the essential treatment for lactic acidosis in shock patients is to correct the cause. It is unknown, however, whether symptomatic pH correction is beneficial in shock patients. The latest Surviving Sepsis Campaign guidelines recommend against the use of buffer therapy with pH ?7.15 and issue no recommendation for pH levels <7.15. Furthermore, based on strong experimental and clinical evidence, sodium bicarbonate infusion alone is not recommended for restoring pH. Indeed, bicarbonate induces carbon dioxide generation and hypocalcemia, both cardiovascular depressant factors. This review addresses the principal hemodynamic consequences of shock-associated lactic acidosis. Despite the lack of formal evidence, this review also highlights the various adapted supportive therapy options that could be putatively added to causal treatment in attempting to reverse the hemodynamic consequences of shock-associated lactic acidosis. PMID:25887061

  8. Isoniazid toxicity presenting as seizures and metabolic acidosis.

    PubMed Central

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

    1990-01-01

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

  9. Role of Acidosis in Renal Osteomalacia

    Microsoft Academic Search

    M. Cochran; B. E. C. Nordin

    1969-01-01

    Of nine patients with uraemic osteomalacia, the underlying renal lesion was pyelonephritis in seven. All of the patients were characterized by impairment of acidifying power and severe metabolic acidosis. It is suggested that metabolic acidosis may be a definite factor in the pathogenesis of uraemic osteomalacia, possibly by reducing the proportion of trivalent phosphate in the plasma and\\/or by reducing

  10. Evaluation of urine acidification by urine anion gap and urine osmolal gap in chronic metabolic acidosis

    Microsoft Academic Search

    Gheun-Ho Kim; Jin Suk Han; Yon Su Kim; Kwon Wook Joo; Suhnggwon Kim; Jung Sang Lee

    1996-01-01

    To investigate the clinical significance of urine anion gap and urine osmolal gap as indirect markers of urine acidification in chronic metabolic acidosis, we evaluated urine ammonium (NH4+), net acid excretion (NAE), urine anion gap (Na+ + K+ ? Cl?), and urine osmolal gap (urine osmolality ? [2(Na+ + K+) + urea]) in 24 patients with chronic renal failure (CRF),

  11. [Gastric emptying and metabolic acidosis. III. Study of gastric retention of a sodium citrate solution using an experimental model of metabolic acidosis in rats].

    PubMed

    Baracat, E C; Collares, E F

    1992-01-01

    The gastric emptying of sodium citrate solution 0.25 mEq/ml was studied in rats with metabolic acidosis induced by orogastric infusion of 0.5 M ammonium chloride solution. Two control groups were used: one infused with 0.5 M sodium chloride and the other with water. The 3 solutions content was 2 ml/100 g weight of the animal. Six hours after the infusion, there was a moderate metabolic acidosis in the group with ammonium citrate. This 6 hour interval marked the beginning of the gastric emptying study. The test meal (sodium citrate 0.25 mEq/ml) was utilized containing 6 mg% red fenol as a marker. The gastric emptying of sodium citrate was studied at 5, 10, 20 and 30 minutes after the infusion, and the results showed no differences between the 3 groups. The data suggest that the duodenal receptors to pH were more effective do determine the pattern of gastric response than the acidosis. PMID:1339143

  12. Expression of rat renal Na/H antiporter mRNA levels in response to respiratory and metabolic acidosis.

    PubMed Central

    Krapf, R; Pearce, D; Lynch, C; Xi, X P; Reudelhuber, T L; Pouysségur, J; Rector, F C

    1991-01-01

    The mammalian proximal tubule is an important mediator of the renal adaptive response to systemic acidosis. In chronic metabolic and respiratory acidosis the bicarbonate reabsorptive (or proton secretory) capacity is increased. This increase is mediated, at least in part, by an increase in Vmax of the luminal Na/H antiporter. To determine whether this adaptation involves increased mRNA expression, Na/H antiporter mRNA levels were measured by Northern analysis in renal cortex of rats with metabolic (6 mmol/kg body wt NH4Cl for 2 or 5 d) and respiratory (10% CO2/air balanced for 2 or 5 d) acidosis and of normal, pair-fed rats. Na/H antiporter mRNA levels were unchanged after 2 d of both metabolic and respiratory acidosis. After 5 d, however, Na/H antiporter mRNA expression was increased 1.76 +/- 0.12-fold in response to metabolic acidosis (P less than 0.005, n = 8), but was not different from normal in response to respiratory acidosis: 1.1 +/- 0.2 (NS, n = 8). Thus, the renal adaptive response to metabolic acidosis involves increased cortical Na/H antiporter mRNA levels. In contrast, the enhanced proximal tubule Na/H antiporter activity and bicarbonate reabsorption in respiratory acidosis seem to involve mechanisms other than increased Na/H antiporter gene expression. Images PMID:1846882

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  15. Effect of collecting duct-specific deletion of both Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg) on renal response to metabolic acidosis.

    PubMed

    Lee, Hyun-Wook; Verlander, Jill W; Handlogten, Mary E; Han, Ki-Hwan; Weiner, I David

    2014-02-15

    The Rhesus (Rh) glycoproteins, Rh B and Rh C Glycoprotein (Rhbg and Rhcg, respectively), are ammonia-specific transporters expressed in renal distal nephron and collecting duct sites that are necessary for normal rates of ammonia excretion. The purpose of the current studies was to determine the effect of their combined deletion from the renal collecting duct (CD-Rhbg/Rhcg-KO) on basal and acidosis-stimulated acid-base homeostasis. Under basal conditions, urine pH and ammonia excretion and serum HCO3(-) were similar in control (C) and CD-Rhbg/Rhcg-KO mice. After acid-loading for 7 days, CD-Rhbg/Rhcg-KO mice developed significantly more severe metabolic acidosis than did C mice. Acid loading increased ammonia excretion, but ammonia excretion increased more slowly in CD-Rhbg/Rhcg-KO and it was significantly less than in C mice on days 1-5. Urine pH was significantly more acidic in CD-Rhbg/Rhcg-KO mice on days 1, 3, and 5 of acid loading. Metabolic acidosis increased phosphenolpyruvate carboxykinase (PEPCK) and Na(+)/H(+) exchanger NHE-3 and decreased glutamine synthetase (GS) expression in both genotypes, and these changes were significantly greater in CD-Rhbg/Rhcg-KO than in C mice. We conclude that 1) Rhbg and Rhcg are critically important in the renal response to metabolic acidosis; 2) the significantly greater changes in PEPCK, NHE-3, and GS expression in acid-loaded CD-Rhbg/Rhcg-KO compared with acid-loaded C mice cause the role of Rhbg and Rhcg to be underestimated quantitatively; and 3) in mice with intact Rhbg and Rhcg expression, metabolic acidosis does not induce maximal changes in PEPCK, NHE-3, and GS expression despite the presence of persistent metabolic acidosis. PMID:24338819

  16. Effect of collecting duct-specific deletion of both Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg) on renal response to metabolic acidosis

    PubMed Central

    Lee, Hyun-Wook; Verlander, Jill W.; Handlogten, Mary E.; Han, Ki-Hwan

    2013-01-01

    The Rhesus (Rh) glycoproteins, Rh B and Rh C Glycoprotein (Rhbg and Rhcg, respectively), are ammonia-specific transporters expressed in renal distal nephron and collecting duct sites that are necessary for normal rates of ammonia excretion. The purpose of the current studies was to determine the effect of their combined deletion from the renal collecting duct (CD-Rhbg/Rhcg-KO) on basal and acidosis-stimulated acid-base homeostasis. Under basal conditions, urine pH and ammonia excretion and serum HCO3? were similar in control (C) and CD-Rhbg/Rhcg-KO mice. After acid-loading for 7 days, CD-Rhbg/Rhcg-KO mice developed significantly more severe metabolic acidosis than did C mice. Acid loading increased ammonia excretion, but ammonia excretion increased more slowly in CD-Rhbg/Rhcg-KO and it was significantly less than in C mice on days 1–5. Urine pH was significantly more acidic in CD-Rhbg/Rhcg-KO mice on days 1, 3, and 5 of acid loading. Metabolic acidosis increased phosphenolpyruvate carboxykinase (PEPCK) and Na+/H+ exchanger NHE-3 and decreased glutamine synthetase (GS) expression in both genotypes, and these changes were significantly greater in CD-Rhbg/Rhcg-KO than in C mice. We conclude that 1) Rhbg and Rhcg are critically important in the renal response to metabolic acidosis; 2) the significantly greater changes in PEPCK, NHE-3, and GS expression in acid-loaded CD-Rhbg/Rhcg-KO compared with acid-loaded C mice cause the role of Rhbg and Rhcg to be underestimated quantitatively; and 3) in mice with intact Rhbg and Rhcg expression, metabolic acidosis does not induce maximal changes in PEPCK, NHE-3, and GS expression despite the presence of persistent metabolic acidosis. PMID:24338819

  17. Effect of metabolic acidosis on white-tailed deer antler development.

    PubMed

    Campbell, T A; Hewitt, D G

    2000-01-01

    Metabolic acidosis can result when herbivores consume browse diets high in plant secondary compounds. One mechanism for buffering excess acid is the mobilization of calcium and other alkaline salts from the skeletal system. White-tailed deer (Odocoileus virginianus) and other cervids consuming browse during antler formation may use minerals essential for antler development as buffers, resulting in altered antler characteristics. Our research objectives were to examine the effects of metabolic acidosis on mineral metabolism, acid-base homeostasis, and antler development in white-tailed deer. Fifteen male white-tailed deer were assigned to one of three diets: 2% NH(4)Cl, 3% commercial tannic acid, or a basal ration without additive. Two feeding trials were completed on each deer to determine nutrient use. Urine pH and the percentage of urinary nitrogen excreted as NH+4 varied by diet. No significant diet or trial effects occurred for nitrogen, calcium, phosphorus, magnesium, or sodium use. Urinary calcium excretion varied between diets. No dietary differences were observed for antler characteristics. The NH(4)Cl diet induced metabolic acidosis but did not alter antler development in white-tailed deer. Skeletal mineral reserves and mineral intake appeared sufficient to buffer excess acids and support antler development. PMID:11121351

  18. Changes in bone sodium and carbonate in metabolic acidosis and alkalosis in the dog

    PubMed Central

    Burnell, James M.

    1971-01-01

    Metabolic acidosis and alkalosis were produced in adult dogs over 5- to 10-day periods. Midtibial cortical bone was analyzed for calcium, sodium, phosphorus, and carbonate. In acidosis bone CO3/Ca decreased 9.5% and bone Na/Ca decreased 6.3%. In alkalosis bone CO3/Ca increased 3.1% and bone Na/Ca increased 3.0%. Previous attempts to account for changes in net acid balance by summation of extra- and intracellular acid-base changes have uniformly resulted in about 40-60% of acid gained or lost being “unaccounted for.” If it is assumed that changes in tibial cortex reflect changes in the entire skeletal system, changes in bone CO3= are sufficiently large to account for the “unaccounted for” acid change without postulating changes in cellular metabolic acid production. PMID:5540172

  19. Effects of hypoxia, hyperkalemia, and metabolic acidosis on canine subendocardial action potential conduction.

    PubMed

    Veenstra, R D; Joyner, R W; Wiedmann, R T; Young, M L; Tan, R C

    1987-01-01

    We have studied the individual and combined effects of elevated external potassium concentration (8 mM [K+], metabolic acidosis (pH = 6.8), and hypoxia at different stimulation 400 milliseconds) on Purkinje (P) and ventricular (V) conduction velocities and on Purkinje-ventricular junctional conduction delay (PVJ delay) in in vitro preparations from canine ventricles. Elevated [K+] had opposite effects on P and V velocities, increasing V velocity by 8% while reducing P velocity by 7%. Acidosis reduced P velocity by 9% while reducing V velocity by only 4%. Hypoxia and rapid stimulation rates had no significant effect on either P or V velocities. All test solutions (except hypoxia alone) significantly increased the PVJ delay. The magnitude of the increase in PVJ delay was much greater than the effects on either P or V velocity. In addition, hypoxia and rapid stimulation augmented the increase in PVJ delay in the presence of elevated [K+] and/or acidosis. The special features of conduction at the PV junctional sites may produce altered pathways of excitation of the ventricles during myocardial ischemia. PMID:3568289

  20. Lanthanum carbonate versus sevelamer hydrochloride: improvement of metabolic acidosis and hyperkalemia in hemodialysis patients.

    PubMed

    Filiopoulos, Vassilis; Koutis, Ioannis; Trompouki, Sofia; Hadjiyannakos, Dimitrios; Lazarou, Dimitrios; Vlassopoulos, Dimosthenis

    2011-02-01

    Sevelamer hydrochloride (SH) has been reported to aggravate metabolic acidosis and hyperkalemia. This study was performed to evaluate acid-base status and serum potassium changes after replacing SH with lanthanum carbonate (LC) in hemodialysis patients. SH was prescribed for 24 weeks in 14 stable hemodialysis patients and replaced by LC in a similar treatment schedule. Laboratory tests, including indices of acid-base status, nutrition, bone/mineral metabolism, and dialysis adequacy, were performed monthly during the study. Dialysate bicarbonate, potassium and calcium concentrations remained constant. Serum bicarbonate and pH rose, and serum potassium dropped significantly under LC. Alkaline phosphatase also decreased significantly under LC. No significant differences were observed in the other studied parameters between the two treatment periods. Control of serum phosphate was similar under both phosphate-binders and no differences were observed in calcium, Ca × P product, CRP, or lipid levels. Dialysis adequacy was constantly kept within K/DOQI target-range. Although full compliance to treatment was reported, three patients on LC complained of gastrointestinal upset and/or a metallic taste, and four had difficulty chewing the LC tablet. LC improves metabolic acidosis and hyperkalemia in hemodialysis patients previously under SH. Although both medications are well-tolerated, the gastrointestinal side-effects appear to occur more frequently with LC; a fact that, together with difficulties in chewing the tablet, may result in decreased compliance. PMID:21272248

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

    PubMed Central

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

    2013-01-01

    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

  2. [Hyperthermia and metabolic acidosis during subtotal thyroidectomy for a patient with Basedow's disease].

    PubMed

    Mizuno, Ju; Yonenaga, Kazumichi; Mimura, Yoshikazu; Arita, Hideko; Hanaoka, Kazuo

    2008-07-01

    A 32-year-old man underwent subtotal thyroidectomy for Basedow's disease under general anesthesia. Preoperatively, the free thyroxine (fT4) and free triiodothyronine (fT3) levels were suppressed and thyroid stimulating hormone level was elevated with administration of iodine and propylthiouracil. Heart rate was 52 beats x min(-1) in sinus rhythm. General anesthesia was induced with fentanyl, propofol and vecuronium, and maintained with nitrous oxide, oxygen and sevoflurane. Systolic blood pressure was controlled within 100 and 130 mmHg. Rectal temperature was 36.5 degrees C after anesthesia induction, gradually rising at a range of 0.4 and 0.7 degrees C per hour, up to 38.6 degrees C four hours after the operation. Arterial blood gas showed bicarbonate 17.1 mEq x l(-1) and base excess -8.1 mmol x l(-1). The metabolic acidosis with normal anion gap lasted during and after the operation. We cooled his body with cold acetyl linger fluid and cooling mattress, and administered sodium bicarbonate. Heart rate increased to 96 beats x min(-1) before the end of operation. Subtotal thyroidectomy was finished in 5 hours 16 minutes. The amount of blood loss was 950 ml. Postoperatively, the serum fT4 and fT3 were suppressed. The serum creatine kinase and lactate dehydrogenase levels increased slightly. He did not show muscle rigidity and neurological disorders. We suspect that he has developed thyroid storm-like symptoms such as hyperthermia and tachycardia induced by subtotal thyroidectomy. Metabolic acidosis might be the result of distal tubular acidosis, which rarely accompanies Basedow's disease. Arterial blood gas analysis and urinalysis should be performed, preoperatively. PMID:18649649

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

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2015-01-01

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

  5. Reversal of severe lactic acidosis with thiamine in a renal allograft recipient

    PubMed Central

    Kumar, K. Nanda; Shah, Veena R.; Parikh, Beena K.; Sonde, Sumedha

    2015-01-01

    A 48-year-old female patient with end-stage renal failure developed unexplained severe lactic acidosis (LA) associated with hyperglycemia during robotic-assisted laparoscopic renal transplantation. Initial treatment with sodium bicarbonate and insulin infusion were ineffective in treating acidemia. Postoperatively, intravenous administration of thiamine resulted in rapid improvement of LA and blood sugar levels. Uremia and chronic hemodialysis might be the causes behind the quantitative/qualitative deficiency of thiamine unmasked during the surgical stress. Though a rare entity, acute thiamine deficiency should be considered in the differential diagnosis of unexplained severe LA in patients with chronic kidney disease and hemodialysis who undergo major surgery or admitted to critical illness care units.

  6. Reversal of severe lactic acidosis with thiamine in a renal allograft recipient.

    PubMed

    Kumar, K Nanda; Shah, Veena R; Parikh, Beena K; Sonde, Sumedha

    2015-07-01

    A 48-year-old female patient with end-stage renal failure developed unexplained severe lactic acidosis (LA) associated with hyperglycemia during robotic-assisted laparoscopic renal transplantation. Initial treatment with sodium bicarbonate and insulin infusion were ineffective in treating acidemia. Postoperatively, intravenous administration of thiamine resulted in rapid improvement of LA and blood sugar levels. Uremia and chronic hemodialysis might be the causes behind the quantitative/qualitative deficiency of thiamine unmasked during the surgical stress. Though a rare entity, acute thiamine deficiency should be considered in the differential diagnosis of unexplained severe LA in patients with chronic kidney disease and hemodialysis who undergo major surgery or admitted to critical illness care units. PMID:26180438

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

    PubMed

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

    1985-03-01

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

  8. Effects of NH4Cl-induced systemic metabolic acidosis on kidney mitochondrial coupling and calcium transport in rats

    Microsoft Academic Search

    Leda Marcia; A. Bento; Marcia M. Fagian; Anibal Eugenio Vercesi; JoseAntonio Rocha Gontijo

    Background. We have previously shown that chronic metabolic acidosis, induced in rats by NH4Cl feeding, leads to nephron hypertrophy and to a decreased water-salt reabsorption by the kidneys. Since mito- chondria are the main source of metabolic energy that drives ion transport in kidney tubules, we examined energy-linked functions (respiration, electrochemical membrane potential and coupling between respiration and ADP phosphorylation)

  9. Effect of intercalated cell-specific Rh C glycoprotein deletion on basal and metabolic acidosis-stimulated renal ammonia excretion.

    PubMed

    Lee, Hyun-Wook; Verlander, Jill W; Bishop, Jesse M; Nelson, Raoul D; Handlogten, Mary E; Weiner, I David

    2010-08-01

    Rh C glycoprotein (Rhcg) is an NH(3)-specific transporter expressed in both intercalated cells (IC) and principal cells (PC) in the renal collecting duct. Recent studies show that deletion of Rhcg from both intercalated and principal cells inhibits both basal and acidosis-stimulated renal ammonia excretion. The purpose of the current studies was to better understand the specific role of Rhcg expression in intercalated cells in basal and metabolic acidosis-stimulated renal ammonia excretion. We generated mice with intercalated cell-specific Rhcg deletion (IC-Rhcg-KO) using Cre-loxP techniques; control (C) mice were floxed Rhcg but Cre negative. Under basal conditions, IC-Rhcg-KO and C mice excreted urine with similar ammonia content and pH. Mice were then acid loaded by adding HCl to their diet. Ammonia excretion after acid loading increased similarly in IC-Rhcg-KO and C mice during the first 2 days of acid loading but on day 3 was significantly less in IC-Rhcg-KO than in C mice. During the first 2 days of acid loading, urine was significantly more acidic in IC-Rhcg-KO mice than in C mice; there was no difference on day 3. In IC-Rhcg-KO mice, acid loading increased principal cell Rhcg expression in both the cortex and outer medulla as well as expression of another ammonia transporter, Rh glycoprotein B (Rhbg), in principal cells in the outer medulla. We conclude that 1) Rhcg expression in intercalated cells is necessary for the normal renal response to metabolic acidosis; 2) principal cell Rhcg contributes to both basal and acidosis-stimulated ammonia excretion; and 3) adaptations in Rhbg expression occur in response to acid-loading. PMID:20462967

  10. Consequences and therapy of the metabolic acidosis of chronic kidney disease

    PubMed Central

    Kraut, Jeffrey A.

    2010-01-01

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

  11. The effect of sodium bicarbonate on cytokine secretion in CKD patients with metabolic acidosis.

    PubMed

    Ori, Yaacov; Zingerman, Boris; Bergman, Michael; Bessler, Hanna; Salman, Hertzel

    2015-04-01

    The incidence of acidosis increases with the progression of chronic kidney disease (CKD). Correction of acidosis by sodium bicarbonate may slow CKD deterioration. Inflammation, which is common in CKD, may be related to acidosis. Whether the slower rate of GFR decline following the correction of acidosis is related to changes in inflammatory markers is unknown. The current study examined whether correcting CKD-acidosis affected inflammatory cytokines secretion. Thirteen patients with CKD 4-5 and acidosis were tested for cytokines secretion from peripheral-blood mononuclear cells at baseline and after one month of oral sodium bicarbonate. Following treatment with sodium bicarbonate there was no change in weight, blood pressure, serum creatinine, albumin, sodium, calcium, phosphate, PTH, hemoglobin and CRP. Serum urea decreased (134±10-116±8mg/dl, P=0.002), potassium decreased (5.1±0.4-4.8±0.1mequiv./l, P=0.064), pH increased (7.29±0.01-7.33±0.01, P=0.008), and serum bicarbonate increased (18.6±0.4mequiv./l to 21.3±0.3mequiv./l, P=0.001). The secretion of the anti-inflammatory cytokine IL-10 decreased (2.75±0.25ng/ml to 2.29±0.21ng/ml, P=0.041). There was no significant change in the secretion of the other pro-inflammatory and anti-inflammatory cytokines, including IL-1?, IL-2, IL-6, TNF?, IFN?, IL-1ra. Thus, correcting acidosis in CKD with bicarbonate decreases IL-10 secretion. Its significance needs to be further investigated. PMID:25960222

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

    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.

  13. Lactic acidosis due to pyruvate carboxylase deficiency

    Microsoft Academic Search

    J. C. Haworth; B. H. Robinson; T. L. Perry

    1981-01-01

    Two unrelated Canadian Indian infants presented with metabolic acidosis. Lactate, pyruvate, glutamic acid, proline and alanine were greatly elevated in plasma. Urinary excretion of -ketoglutarate and pyruvate was increased. Pyruvate carboxylase activity was very low in skin fibroblasts and liver. Phosphoenolpyruvate carboxykinase was low in liver. Both infants were unresponsive to several enzyme cofactors, including biotin. Both survive at age

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

    PubMed

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

    2014-07-01

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

  15. Effect of dietary-induced metabolic acidosis and ovariectomy on bone mineral density and markers of bone turnover.

    PubMed

    Macleay, Jennifer M; Olson, Jerry D; Turner, A Simon

    2004-01-01

    Dietary-induced metabolic acidosis (DIMA) has been implicated as a significant confounder in the development of osteoporosis. Twenty-four mature ewes were randomly assigned to four groups of six sheep. Group 1 consumed a control diet (ND); group 2 consumed a normal diet (ND) and had ovariectomy (OVX), group 3 consumed a diet that induced metabolic acidosis (MA), without OVX, and group 4 consumed a diet that induced MA, with OVX. The study was conducted over 180 days and the sheep were maintained on the assigned diet throughout. Sheep were weighed and bone mineral density (BMD) was measured, using dual-energy X-ray absorptiometry (DEXA), on days 0 and 180. Serum bone alkaline phosphatase (BAP), urine deoxypyridinoline (DPD), and fractional excretions (FE) of Ca and P were determined on days 0, 90, and 180. Arterial blood pH was determined on day 180. Analysis consisted of a two-way analysis of variance for repeated measures with significance set at P < or = 0.05. Body weights, serum BAP, and urine DPD were not influenced by either diet or OVX status. DIMA did significantly increase urinary FE of Ca and P and significantly decreased lumbar BMD and arterial pH. Arterial pH remained within physiologic normal limits. DIMA was a more potent cause of calcium wasting than OVX over the time frame of this study. Sheep appear to be sensitive to DIMA and will therefore be a useful animal model to study the influence of diet on the development of osteoporosis. The specific mechanisms through which DIMA exerts its influence are still unknown and are the subject of ongoing studies. PMID:15490266

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

    PubMed Central

    Walmsley, Scott J.; Freund, Dana M.

    2012-01-01

    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

  17. [Kidney transplants from donors burdened metabolic acidosis in the course of poisoning with methanol and carbon monoxide].

    PubMed

    Ko?aci?ski, Zbigniew; Skrzypek-Mikulska, Agnieszka; Pitrus, Ewelina; Matych, Józef; Winnicka, Renata; Czyzewska, Sylwia; Krakowiak, Anna

    2013-01-01

    The question of obtaining organs from donors who died of methanol poisoning has been discussed in the medical literature for many years. The results of such transplants published so far are very optimistic. However, the possibility of permanent and significant injury to transplanted organs caused by poisons or its metabolites raises serious concerns regarding the procedure. The long-term effects of intensive treatment of poisoning need to be considered as well. Metabolic acidosis and high blood osmolality are agents with recognized damaging potential impairing organ function at cellular level. The study traced the fate of kidney transplants from 13 donors who died of methanol poisoning and one isoned with carbon monoxide. The donors group consisted of 12 men and 2 women, of mean age 49 years (SD +/- 7.93). The kidneys were transplanted 20 men and 8 women. The mean age of recipients was 50.29 years (SD +/- 12.9). At the time of admission to the Department of Toxicology all donors presented with profound metabolic acidosis and high plasma osmolality (mean 434.71 mOsm/kg H2O (SD +/- 73.29). Metabolic acidosis was treated high doses of sodium bicarbonate (mean infusion volume of was 409 ml) before the HD procedure. Blood methanol levels were between 125 and 470 mg% (mean 317.23 SD +/- 136.83). The carboxyhaemoglobin concentration of in the donor poisoned with carbon monoxide was 47.2%. Transplantation was performed after confirmation of the brain death, the period of cold ischemia (CIT) ranged from 6 to 22 hours (mean 16.06 hours; SD +/- 3.99). Kidneys have taken function immediately after transplantation in 21 recipients. In seven cases, patients required two or three HD procedures. A total of 16 dialysis were performed post-transplants. In the group of patients, the mean glomerular filtration rate (GFR) at 3 months after transplantation was 46.71 ml/min/1.73m2 (SD +/- 10.89). During the 18 months follow-up a constant upward trend to the mean GFR 50.55 was noticed. In the group of donors, the mean blood urea concentration (BUN) 3 months after transplantation was 61.43 mg/dL, including 7 patients with BUN within the range of 80-100 mg/dL. At 18 months post transplant, the average concentration was 42.36 mg/dL, with no cases exceeding 55 mg/dL. Similarly, serum creatinine level normalized with the mean value of 3.01 mg/dL at 3 months and 1.68 mg/dL at 18 months post the procedure. There was no case exceeding 2 mg/dL. One recipient died of a heart attack after a period of more than 18 months after transplantation. However, the transplant was efficiently active at all times (GFR 56-60 ml). PMID:24466684

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

    Microsoft Academic Search

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

    2002-01-01

    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

  19. Respiratory acidosis

    MedlinePLUS

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

  20. Metabolic Response to Severe Surgical Illness: Overview

    Microsoft Academic Search

    Douglas W. Wilmore

    2000-01-01

    .   Severe surgical illness results in metabolic responses that mobilize substrate (amino acids and fatty acids) from body stores\\u000a to support vital organs, enhance resistance to infection, and ensure wound healing. Central to this process is the redistribution\\u000a of body protein, which moves from skeletal muscle to support the central viscera. If unsupported, this protein-wasting state\\u000a could result in prolonged

  1. [Gastric emptying and metabolic acidosis. II. Study, in an experimental model in rats, of gastric retention of a sodium bicarbonate solution].

    PubMed

    Belangero, V M; Collares, E F

    1992-01-01

    The gastric emptying of a 0.25 M sodium bicarbonate solution was studied in rats with metabolic acidosis induced by a previous (6 hours) orogastric infusion of a 0.5 M ammonium chloride solution. Two control groups were used: one previously infused with 0.5 M sodium chloride and the other with water, in the same volume that further solutions. Every animal was fed with 2 ml/100 g of its weight of these solutions. The test meal (bicarbonate solution) was utilized containing 6 mg% red fenol as a marker. The gastric retentions were determined 6 hours after those first meals at 5, 10, 20 and 30 minutes. The results demonstrated that the gastric retentions of the bicarbonate solution were significantly lower in the acidotic group than that one of water group (at 20 minutes) and that one of the sodium chloride (at 10, 20 and 30 minutes). The data here presented suggest that metabolic acidosis accelerates the gastric emptying of a sodium bicarbonate solution. PMID:1339142

  2. Severe Hyperosmolar Metabolic Acidosis Due to a Large Dose of Intravenous Lorazepam

    E-print Network

    Barnes, Brian Joseph

    2002-04-18

    Anabolic Steroids To the Editor: The popliteal-artery entrapment syndrome is a potentially serious but rare cause of ischemia of the legs.1 It occurs predominantly in young persons and is due to an abnormal anatomical relation between the popliteal artery... syndrome who abused anabolic steroids. A 31-year-old male bodybuilder was referred to our emer- gency department with a three-day history of claudication and paresthesias of the left foot. Clinical examination re- vealed symmetric muscular hypertrophy...

  3. L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome

    PubMed Central

    Rodan, Lance H.; Wells, Greg D.; Banks, Laura; Thompson, Sara; Schneiderman, Jane E.; Tein, Ingrid

    2015-01-01

    Objective To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. Methods We performed a case control study in 3 MELAS siblings (m.3243A>G tRNAleu(UUR) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO2peak) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. Results At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 31P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg2+ (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO2peak. On 31P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. Significance These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Classification of Evidence Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. Trial Registration ClinicalTrials.gov NCT01603446. PMID:25993630

  4. A Homozygous Mutation in LYRM7/MZM1L Associated with Early Onset Encephalopathy, Lactic Acidosis, and Severe Reduction of Mitochondrial Complex III Activity

    PubMed Central

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

    2013-01-01

    Mutations in nuclear genes associated with defective complex III (cIII) of the mitochondrial respiratory chain are rare, having been found in only two cIII assembly factors and, as private changes in single families, three cIII structural subunits. Recently, human LYRM7/MZM1L, the ortholog of yeast MZM1, has been identified as a new assembly factor for cIII. In a baby patient with early onset, severe encephalopathy, lactic acidosis and profound, isolated cIII deficiency in skeletal muscle, we identified a disease-segregating homozygous mutation (c.73G>A) in LYRM7/MZM1L, predicting a drastic change in a highly conserved amino-acid residue (p.Asp25Asn). In a mzm1? yeast strain, the expression of a mzm1D25N mutant allele caused temperature-sensitive respiratory growth defect, decreased oxygen consumption, impaired maturation/stabilization of the Rieske Fe–S protein, and reduced complex III activity and amount. LYRM7/MZM1L is a novel disease gene, causing cIII-defective, early onset, severe mitochondrial encephalopathy. PMID:24014394

  5. Liver Pathology and the Metabolic Syndrome X in Severe Obesity

    Microsoft Academic Search

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

    1999-01-01

    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

  6. Protein metabolism in severe childhood malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The major clinical syndromes of severe childhood malnutrition (SCM) are marasmus (non-oedematous SCM), kwashiorkor and marasmic-kwashiorkor (oedematous SCM). Whereas treatment of marasmus is straightforward and the associated mortality is low, kwashiorkor and marasmic-kwashiorkor are difficult to tr...

  7. Polyuria, acidosis, and coma following massive ibuprofen ingestion.

    PubMed

    Levine, Michael; Khurana, Amandeep; Ruha, Anne-Michelle

    2010-09-01

    Ibuprofen was the first over-the-counter nonsteroidal anti-inflammatory drug available in the United States. Despite being a common agent of ingestion, significant toxicity in overdose is rare. We report a case of a massive ibuprofen ingestion who developed polyuria, acidosis, and coma but survived, despite having a serum ibuprofen concentration greater than previous fatal cases. A 19-year-old man ingested 90 g (1,200 mg/kg) ibuprofen. He was initially awake and alert, but his level of consciousness deteriorated over several hours. Seven hours following the ingestion, he was intubated and mechanically ventilated secondary to loss of airway reflexes. He developed a lactic acidosis and polyuria, which lasted for nearly 24 h. His serum creatinine peaked at 1.12 mg/dL. An ibuprofen level drawn 7 h postingestion was 739.2 mg/L (therapeutic 5-49 mg/L). We describe a case of a massive ibuprofen overdose characterized by metabolic acidosis, coma, and a state of high urine output who survived with aggressive supportive care. This case is unique in several ways. First, ibuprofen levels this high have only rarely been described. Second, polyuria is very poorly described following ibuprofen ingestions. PMID:20419362

  8. Positive Correlation between Severity of Blepharospasm and Thalamic Glucose Metabolism

    PubMed Central

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

    2011-01-01

    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

  9. Mitochondrial DNA depletion, near-fatal metabolic acidosis, and liver failure in an HIV-infected child treated with combination antiretroviral therapy

    Microsoft Academic Search

    Joseph A. Church; Wendy G. Mitchell; Ignacio Gonzalez-Gomez; Jim Christensen; Tuan H. Vu; Salvatore Dimauro; Richard G. Boles

    2001-01-01

    A child with controlled human immunodeficiency virus infection presented with neurologic deterioration, lactic acidosis, and organic aciduria. Muscle biopsy revealed abnormal mitochondrial (mt) morphology, reduced mt enzyme activities, and mtDNA depletion. After adjustment of antiretroviral therapy to a regimen free of nucleoside analogs, marked improvement was seen in clinical status and mt abnormalities. (J Pediatr 2001;138:748-51)

  10. The metabolic syndrome and severity of diabetic retinopathy

    PubMed Central

    Chen, John J; Wendel, Lucas J; Birkholz, Emily S; Vallone, John G; Coleman, Anne L; Yu, Fei; Mahajan, Vinit B

    2015-01-01

    Background While metabolic syndrome has been strongly implicated as a risk factor for macrovascular diseases, such as stroke and cardiovascular disease, its relationship with microvascular diseases, including diabetic retinopathy, has been less defined. The purpose of this pilot study was to investigate the association between metabolic syndrome and the presence and severity of diabetic retinopathy. Methods A retrospective case–control chart review at the University of Iowa ophthalmology and primary care clinics included 100 patients with proliferative diabetic retinopathy (PDR), 100 patients with nonproliferative diabetic retinopathy (NPDR), 100 diabetic patients without diabetic retinopathy, and 100 nondiabetic patients who were randomly selected. Using the International Diabetes Foundation definition, the prevalence of metabolic syndrome and the number of components of metabolic syndrome were compared among these groups. Results The prevalence of metabolic syndrome in patients with diabetes was 69.3%, which was significantly higher than that in patients without diabetes (27%; P<0.0001) (odds ratio [OR] =6.28; 95% confidence interval [CI]: 3.76–10.49; P=0.0004). However, there was no significant difference in the prevalence of metabolic syndrome between diabetics with and without diabetic retinopathy, with rates of 67.5% and 73%, respectively (P=0.36) (OR =0.77; 95% CI: 0.45–1.32; P=0.34). In addition, there was no significant difference between the PDR and NPDR groups, with rates of 63% and 72%, respectively (P=0.23) (OR =0.70; 95% CI: 0.38–1.30; P=0.26). Conclusion The metabolic syndrome was highly prevalent in patients with diabetes, but it was not associated with the presence or severity of retinopathy. PMID:25995613

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

    PubMed Central

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

    2014-01-01

    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

  12. Homozygous and compound heterozygous mutations in the ATP6V1B1 gene in patients with renal tubular acidosis and sensorineural hearing loss.

    PubMed

    Mohebbi, N; Vargas-Poussou, R; Hegemann, S C A; Schuknecht, B; Kistler, A D; Wüthrich, R P; Wagner, C A

    2013-03-01

    Distal renal tubular acidosis (dRTA) is characterized by the inability to excrete acid in the renal collecting ducts resulting in inappropriately alkaline urine and hyperchloremic (normal anion gap) metabolic acidosis in the context of a normal (or near-normal) glomerular filtration rate. Inborn dRTA can be due to autosomal dominant or recessive gene defects. Clinical symptoms vary from mild acidosis, incidental detection of kidney stones or renal tract calcification to severe findings such as failure to thrive, severe metabolic acidosis, and nephrocalcinosis. The majority of patients with recessive dRTA present with sensorineural hearing loss (SNHL). Few cases with abnormal widening of the vestibular aqueduct have been described with dRTA. Mutations in three different genes have been identified, namely SLC4A1, ATP6V1B1, and ATP6V0A4. Patients with mutations in the ATP6V1B1 proton pump subunit develop dRTA and in most of the cases sensorineural hearing loss early in childhood. We present two patients from two different and non-consanguineous families with dRTA and SNHL. Direct sequencing of the ATP6V1B1 gene revealed that one patient harbors two homozygous mutations and the other one is a compound heterozygous. To our knowledge, this is the first case in the literature describing homozygosity in the same dRTA gene on both alleles. PMID:22509993

  13. Haploinsufficiency of the Ammonia Transporter Rhcg Predisposes to Chronic Acidosis

    PubMed Central

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

    2013-01-01

    Ammonia secretion by the collecting duct (CD) is critical for acid-base homeostasis and, when defective, causes distal renal tubular acidosis (dRTA). The Rhesus protein RhCG mediates NH3 transport as evident from cell-free and cellular models as well as from Rhcg-null mice. Here, we investigated in a Rhcg mouse model the metabolic effects of Rhcg haploinsufficiency, the role of Rhcg in basolateral NH3 transport, and the mechanisms of adaptation to the lack of Rhcg. Both Rhcg+/+ and Rhcg+/? mice were able to handle an acute acid load, whereas Rhcg?/? mice developed severe metabolic acidosis with reduced ammonuria and high mortality. However, chronic acid loading revealed that Rhcg+/? mice did not fully recover, showing lower blood HCO3? concentration and more alkaline urine. Microperfusion studies demonstrated that transepithelial NH3 permeability was reduced by 80 and 40%, respectively, in CDs from Rhcg?/? and Rhcg+/? mice compared with controls. Basolateral membrane permeability to NH3 was reduced in CDs from Rhcg?/? mice consistent with basolateral Rhcg localization. Rhcg?/? responded to acid loading with normal expression of enzymes and transporters involved in proximal tubular ammoniagenesis but reduced abundance of the NKCC2 transporter responsible for medullary accumulation of ammonium. Consequently, tissue ammonium content was decreased. These data demonstrate a role for apical and basolateral Rhcg in transepithelial NH3 transport and uncover an incomplete dRTA phenotype in Rhcg+/? mice. Haploinsufficiency or reduced expression of RhCG may underlie human forms of (in)complete dRTA. PMID:23281477

  14. On the Severity of Carpal Tunnel Syndrome: Diabetes or Metabolic Syndrome

    PubMed Central

    Bodur, Hatice; Öztop Çakmak, Özgür; Ate?, Can; Sivas, Filiz; Eser, Filiz; Y?lmaz Ta?delen, Özlem

    2015-01-01

    Background and Purpose Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy. Although its etiology is unknown, certain conditions are commonly associated with CTS, such as obesity, arthritis, hypothyroidism, diabetes mellitus, trauma, mass lesions, amyloidosis, and sarcoidosis. We aimed to determine the association between metabolic syndrome and CTS, and we compared the severity of CTS between patients with diabetes (and no concomitant metabolic syndrome) and patients with metabolic syndrome. Methods Two hundred patients with a clinically and electrophysiological confirmed diagnosis of CTS were included in the study. Their demographic characteristics and severity of CTS were analyzed according to the presence or the absence of metabolic syndrome. Differences in the electrophysiological findings were evaluated between the following four groups: 1) metabolic syndrome alone (n=52), 2) diabetes alone (n=20), 3) combined metabolic syndrome and diabetes (n=44), and 4) no metabolic syndrome or diabetes (n=84). Results CTS was more severe in the patients with metabolic syndrome than those without this syndrome. The electrophysiological findings were worse in patients with metabolic syndrome alone than in those with diabetes alone and those without diabetes and metabolic syndrome. Conclusions CTS appears to be more severe in patients with metabolic syndrome than patients with diabetes. Diabetes is one of the well-known risk factors for CTS, but other components of metabolic syndrome may have a greater effect on the severity of CTS. PMID:26174786

  15. Metformin-associated lactic acidosis.

    PubMed

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

    2015-03-01

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

  16. Combined renal tubular acidosis and diabetes insipidus in hematological disease

    Microsoft Academic Search

    Robert Zietse; Ewout J Hoorn

    2007-01-01

    Background A 39-year-old male with multiple myeloma was admitted for treatment with melphalan and autologous stem cell reinfusion. He presented with hypokalemia and hyperchloremic non-anion-gap metabolic acidosis with a high urinary pH. He also had hypomagnesemia, hypophosphatemia, hypouricemia, proteinuria and glucosuria. The patient subsequently developed polyuria with a low urine osmolality, hypernatremia and, finally, acute renal failure.Investigations Physical examination, blood

  17. Comparison of the measurement of total carbon dioxide and strong ion difference for the evaluation of metabolic acidosis in diarrhoeic calves.

    PubMed

    Grove-White, D H; Michell, A R

    2001-03-24

    Eighty-four calves with diarrhoea were treated with fluids and 13 apparently healthy calves of similar ages were sampled as controls. Their total blood carbon dioxide (TCO2) was measured with a Harleco apparatus and 31 of the calves were treated with oral fluids and 53 with parenteral fluids. The oral fluid contained 118 mmol/litre Na+, 25 mmol/litre K+, 110 mmol/litre glucose, 108 mmol/litre bicarbonate (HCO3- as citrate), 43 mmol/litre Cl-, 4 mmol/litre Ca++, 4 mmol/litre Mg++ and 20 mmol/litre glycine, and the parenteral fluid contained 144 mmol/litre Na+, 4 mmol/litre K+, 35 mmol/litre HCO3- and 113 mmol/litre Cl-. Both treatments resulted in significant improvements in acid-base status as demonstrated by an increase in TCO2, and the treatment was successful in 27 of the 31 calves receiving oral fluids and in 45 of the 53 calves receiving parenteral fluids. Thirty-seven of the calves treated parenterally were very severely acidotic (TCO2 <8 mmol/litre) initially and they received an additional 400 mmol HCO3- added to the first 5 litres of infusion. Treatment was successful in 33 of these calves. The decision to administer additional bicarbonate was made on the basis of their acid-base status as measured with a Harleco apparatus. The strong ion difference (Na++K+-Cl-) (SID) of the calves was calculated retrospectively. There was a significant correlation between the SID and TCO2 of the calves treated with oral fluids but not among the control calves or the calves treated parenterally. Furthermore, measurements of the change in SID during therapy gave little indication of the change in acid-base status as measured by the Harleco apparatus, with the SID decreasing (suggesting a worsening of acid-base status) in 16 calves in which the TCO2 increased (suggesting an improvement in acid-base status). There was a significant correlation between the change in SID and the change in TCO2 during treatment in the calves receiving oral fluids but not in the calves treated parenterally. PMID:11321551

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

    PubMed Central

    2013-01-01

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

  19. Collecting duct-specific Rh C glycoprotein deletion alters basal and acidosis-stimulated renal ammonia excretion.

    PubMed

    Lee, Hyun-Wook; Verlander, Jill W; Bishop, Jesse M; Igarashi, Peter; Handlogten, Mary E; Weiner, I David

    2009-06-01

    NH3 movement across plasma membranes has traditionally been ascribed to passive, lipid-phase diffusion. However, ammonia-specific transporters, Mep/Amt proteins, are present in primitive organisms and mammals express orthologs of Mep/Amt proteins, the Rh glycoproteins. These findings suggest that the mechanisms of NH3 movement in mammalian tissues should be reexamined. Rh C glycoprotein (Rhcg) is expressed in the collecting duct, where NH3 secretion is necessary for both basal and acidosis-stimulated ammonia transport. To determine whether the collecting duct secretes NH3 via Rhcg or via lipid-phase diffusion, we generated mice with collecting duct-specific Rhcg deletion (CD-KO). CD-KO mice had loxP sites flanking exons 5 and 9 of the Rhcg gene (Rhcg(fl/fl)) and expressed Cre-recombinase under control of the Ksp-cadherin promoter (Ksp-Cre). Control (C) mice were Rhcg(fl/fl) but Ksp-Cre negative. We confirmed kidney-specific genomic recombination using PCR analysis and collecting duct-specific Rhcg deletion using immunohistochemistry. Under basal conditions, urinary ammonia excretion was less in KO vs. C mice; urine pH was unchanged. After acid-loading for 7 days, CD-KO mice developed more severe metabolic acidosis than did C mice. Urinary ammonia excretion did not increase significantly on the first day of acidosis in CD-KO mice, despite an intact ability to increase urine acidification, whereas it increased significantly in C mice. On subsequent days, urinary ammonia excretion slowly increased in CD-KO mice, but was always significantly less than in C mice. We conclude that collecting duct Rhcg expression contributes to both basal and acidosis-stimulated renal ammonia excretion, indicating that collecting duct ammonia secretion is, at least in part, mediated by Rhcg and not solely by lipid diffusion. PMID:19321595

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

    Microsoft Academic Search

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

    2007-01-01

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

  1. Renal tubular acidosis and nerve deafness.

    PubMed Central

    Dunger, D B; Brenton, D P; Cain, A R

    1980-01-01

    Two brothers are described with renal tubular acidosis and nerve deafness: the elder also had rickets and hypokalaemia. The parents were unaffected. Studies of urinary acidification and bicarbonate excretion were consistent with a distal tubular abnormality. This report strengthens the view previously proposed in similar cases that nerve deafness and renal tubular acidosis constitute a genetic entity. Examination for nerve deafness is indicated in any child with renal tubular acidosis. Images Fig. 2 PMID:7387165

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

    PubMed

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

    2014-09-01

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

  3. Management of Moderate to Severe Psoriasis in Patients with Metabolic Comorbidities

    PubMed Central

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

    2015-01-01

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

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

    Microsoft Academic Search

    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

    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.

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

    Microsoft Academic Search

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

    2001-01-01

    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.

  6. Metabolic dysfunction associated with adiponectin deficiency enhances kainic acid-induced seizure severity.

    PubMed

    Lee, Edward B; Warmann, Genevieve; Dhir, Ravindra; Ahima, Rexford S

    2011-10-01

    Metabolic syndrome has deleterious effects on the CNS, and recent evidence suggests that obesity rates are higher at presentation in children who develop epilepsy. Adiponectin is secreted by adipose tissue and acts in the brain and peripheral organs to regulate glucose and lipid metabolism. Adiponectin deficiency predisposes toward metabolic syndrome, characterized by obesity, insulin resistance, impaired glucose tolerance, hyperlipidemia, and cardiovascular morbidity. To investigate the relationship between metabolic syndrome and seizures, wild-type C57BL/6J and adiponectin knock-out mice were fed a high-fat diet, followed by treatment with low doses of kainic acid to induce seizures. Adiponectin deficiency in mice fed a high-fat diet resulted in greater fat accumulation, impaired glucose tolerance, hyperlipidemia, increased seizure severity, and increased hippocampal pathology. In contrast, there were no adverse effects of adiponectin deficiency on metabolic phenotype or seizure activity in mice fed a normal (low-fat) chow diet. These findings demonstrate that metabolic syndrome modulates the outcome of seizures and brain injury. PMID:21976521

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    2013-01-01

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

  9. [Adenosine deaminase 1 deficiency, an inborn error of metabolism underlying a severe form of combined immunodeficiency].

    PubMed

    Giraud, A; Lavocat, M-P; Cremillieux, C; Patural, H; Thouvenin, S; David, A; Perignon, J-L; Stephan, J-L

    2015-06-01

    Severe combined immune deficiencies (SCIDs) are a heterogeneous group of severe cellular immunodeficiencies. Early diagnosis is essential to allow adapted care before life-threatening systemic infections or complications associated with live vaccines. Adenosine deaminase 1 deficiency (ADA1) is an inborn error of metabolism leading to severe lymphopenia and characteristic bone lesions. Herein, we present the typical case of a child in whom ADA SCID was diagnosed at 2months of life, revealed by lung involvement and extreme lymphopenia. Immune restoration in terms of peripheral lymphocyte count with enzyme replacement therapy, namely pegylated bovine ADA, is satisfactory so far. The search for a compatible donor is underway. Correcting the genetic defect by gene transfer is also being considered. The phenotype of this very rare condition is described. A severe peripheral lymphopenia in a young child is a finding of utmost importance for the diagnosis of a primary cellular immunodeficiency. PMID:25842197

  10. Changes in energy metabolism after induction therapy in patients with severe or moderate ulcerative colitis

    PubMed Central

    Inoue, Mai; Sasaki, Masaya; Takaoka, Azusa; Kurihara, Mika; Iwakawa, Hiromi; Bamba, Shigeki; Ban, Hiromitsu; Andoh, Akira

    2015-01-01

    We investigated the changes in energy expenditure during induction therapy in patients with severe or moderate ulcerative colitis. Thirteen patients (10 men, 3 women; mean age, 36.5 years) with ulcerative colitis admitted to the Shiga University Hospital were enrolled in this study. We measured the resting energy expenditure and respiratory quotients of these patients before and after induction therapy with indirect calorimetry. We analyzed the changes of nutritional status and serum inflammatory cytokine levels and also evaluated the relationship between energy metabolism and disease activity by using the Seo index and Lichtiger index. The resting energy expenditure was 26.3 ± 3.8 kcal/kg/day in the active stage and significantly decreased to 23.5 ± 2.4 kcal/kg/day after induction therapy (p<0.01). The resting energy expenditure changed in parallel with the disease activity index and C-reactive protein and inflammatory cytokine levels. The respiratory quotient significantly increased after induction therapy. Thus, moderate to severe ulcerative colitis patients had a hyper-metabolic status, and the energy metabolism of these patients significantly changed after induction therapy. Therefore, we recommend that nutritional management with 30–34 kcal/kg/day (calculated as measured resting energy expenditure × activity factor, 1.3) may be optimal for hospitalized ulcerative colitis patients. PMID:26060352

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

    PubMed

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

    2014-08-01

    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

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

    SciTech Connect

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

    1985-08-01

    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.

  13. The metabolic effects of moderately severe upper gastrointestinal haemorrhage in man.

    PubMed Central

    Foster, K. J.; Alberti, K. G.; Binder, C.; Holdstock, G.; Karran, S. J.; Smith, C. L.; Talbot, S.; Turnell, D. C.

    1982-01-01

    The metabolic effects of moderately severe gastrointestinal haemorrhage were investigated in man. Before resuscitation, patients had raised circulating concentrations of glucose, lactate, alanine, glycerol and cortisol. After urgent operation for haemorrhage, metabolite concentrations were similar to those of control patients having elective abdominal surgery, but insulin concentrations were higher and cortisol lower in haemorrhage patients. There were no significant differences in nitrogen excretion between haemorrhage patients and their controls, but urinary 3-methyl-histidine excretion by haemorrhage patients was lower indicating decreased muscle protein breakdown. Decreased amino acid release from muscle might account for previously reported imparied wound healing after haemorrhage. PMID:7045838

  14. The effect of LLLT on bone metabolism in children with severe cerebral palsy (a secondary publication)

    PubMed Central

    2014-01-01

    Background and aims: It is said that the average frequency of bone fracture in hospitalized children with severe cerebral palsy (unable to remain seated) is 1% (0.2 to 2.0%). Cerebral palsy patients' bones are known to be vulnerable to fracture, and refractory bone atrophy may be observed. However, the effect of low level laser therapy (LLLT) on bone density or bone metabolism has not been fully investigated. In recent years, tests for bone density or bone metabolism markers have become available. Material and methods: In this study, we evaluated changes in bone density and bone metabolism markers in 4 children with severe cerebral palsy who underwent LLLT for an average of 22 days. Results: B-ALP, a marker of ossification, increased 1 month after the start of irradiation in 3 of the 4 subjects and returned to a level close to the pre-irradiation level 2 months after the start of irradiation. In the remaining subjects in whom B-ALP failed to increase, B-ALP had been low before irradiation. Urinary N-terminal telopeptide (NTx) levels, a marker of bone resorption, decreased in 3 of the 4 subjects after the start of irradiation and remained low even 10 months later. Serum NTx levels tended to decrease in 3 of the 4 subjects. The levels of serum NTx/Crea, Deoxy-Pyridinoline (DPd) and DPd/Crea (DPd/Crea) also decreased in 3 of the 4 subjects. Transient decreases in intact parathyroid hormone (PTH) levels were observed in all 4 cases. Changes were particularly apparent in 2 cases: one with high NTx levels, which showed enhanced bone resorption, and one with high PTH levels, probably due to a vitamin D (VitD) deficiency. Although the metacarpal bone density measured by DIP was found to be lower than in normal children, there were no changes due to LLLT. Conclusion: These results suggest that LLLT has a positive influence on bone metabolism in that it temporarily increases bone formation and suppresses bone resorption while also tending to improve secondary hyperparathyroidism caused by VitD deficiency. Enhanced bone resorption in the case with high NTx levels was noteworthy, together with marked changes in the case with high PTH levels due to VitD deficiency. These positive influences on bone metabolism merit attention as potential new indications of LLLT. PMID:25705079

  15. Relative risk of diabetes, dyslipidaemia, hypertension and the metabolic syndrome in people with severe mental illnesses: Systematic review and metaanalysis

    Microsoft Academic Search

    David PJ Osborn; Christine A Wright; Gus Levy; Michael B King; Raman Deo; Irwin Nazareth

    2008-01-01

    BACKGROUND: Severe mental illnesses (SMI) may be independently associated with cardiovascular risk factors and the metabolic syndrome. We aimed to systematically assess studies that compared diabetes, dyslipidaemia, hypertension and metabolic syndrome in people with and without SMI. METHODS: We systematically searched MEDLINE, EMBASE, CINAHL & PsycINFO. We hand searched reference lists of key articles. We employed three search main themes:

  16. [The effect of subclinical and acute ante partum acidosis in cows on the course of pregnancy with regard to the steroid hormone profile].

    PubMed

    Ra?, A; Janowski, T; Zdu?czyk, S

    1996-08-01

    Experiment 1: In a field experiment in 19 of 87 cows being in day 260-265 of pregnancy subclinical metabolic acidosis was found. The control group included 10 healthy cows in the same stage of pregnancy. Blood samples from cows of both groups were collected once daily until day 2 post partum for determination of oestrogens, progesterone and cortisol. Dystocia was found in four and retained placenta in three cows having acidosis. These cows had lower oestrogens and markedly higher cortisol and progesterone concentrations during parturition. Course of pregnancy and delivery in control cows an without any difficulties and hormonal profiles in these cows were typical. Experiment 2: On day 265 of pregnancy experimental acute acidosis was evoked in five cows and five other cows served as control. Sampling of blood was the same as in experiment 1. Acidosis caused on day 269 in two cows premature birth with retained placenta. Moreover concentrations of studied steroids were atypical. In three other cows with acidosis course of pregnancy and delivery was without any trouble. Only cortisol was increased while progesterone and oestrogen values were in agreement with concentrations of control cows. Data suggest that metabolic acidosis can cause dystocia, premature birth and retained placenta. Furthermore, acidosis clearly affects the profile of steroid hormones. PMID:9012018

  17. The effect of fetal hypoxia and acidosis on the changes in fetal electroencephalogram during labor.

    PubMed

    Djelmis, J; Drazanci?, A; Dürrigl, V; Djelmis, J; Ivanseni?, M

    1988-04-01

    As artefact-free recordings of the fetal brain bioelectric potentials can only be obtained by specially designed electrodes, an electrode for taking electroencephalogram (EEG) and cardiotocogram (CTG), according to the principle of vacuum electrode developed by Rosen and Scibetta, has been designed. The polygraphic technique was used to examine a total of 65 deliveries, divided into two groups. The first group (n = 33) consisted of newborns free of any signs of hypoxia and acidosis, whereas the second group (n = 32) was comprised of newborns with evident clinical and biochemical signs of hypoxia and acidosis. Fetal hypoxia and acidosis were observed to entail some characteristic changes in EEG, that is, a decrease in the frequency and wave amplitude through the appearance of the isoelectric line (ISO) featuring in severe cases of fetal hypoxia and acidosis. The following changes were found to occur during the development of hypoxia and acidosis:hypoxia, a decrease in the EEG frequency and amplitude, preacidosis with the appearance of both early and late decelerations coupled with a significant drop in the oscillation and, eventually, severe variable decelerations accompanied by terminal bradycardia. The time interval between the manifestation of initial signs of a decreasing central nervous system (CNS) activity and changes in the fetal heart rate was found to be about 10 minutes. PMID:3348865

  18. [Lowering the cesarean section rate by exclusion of cardiotocographically suspected acidosis using fetal blood gas analysis].

    PubMed

    Köppel, R; Benz, J

    1984-09-01

    In 871 deliveries out of a total of 3980 effected during 1980-1982 at the Winterthur Gynaecological Hospital, we found it necessary to perform one or several microanalyses of blood (blood gas analyses) sub partu. Among these, we found retrospectively that in 22 cases the microanalysis of the blood gas had prevented us from performing caesarean section which would have seemed necessary if we had relied on the cardiotocographical findings alone. Micro-analysis of blood gas made it possible to exclude the presence of pre-acidosis or acidosis which would have made Caesarean section imperative; in all these cases, normal delivery via the vagina was achieved, and in no case did this result in severe acidosis. All newborn had a 5-minute Apgar score of 7 and higher. We can conclude from these results, therefore, that the indication for an immediate termination of delivery via Caesarean section should not depend solely on a pathological cardiotocogram; the final decision should be arrived at only after micro-analyses of blood gas have confirmed the presence of foetal pre-acidosis or acidosis. PMID:6567560

  19. Metabolism

    MedlinePLUS

    ... For Kids For Parents MORE ON THIS TOPIC Metabolic Syndrome Blood Test: Basic Metabolic Panel (BMP) Your Child's ... System Thyroid Disorders Diabetes Center Movie: Endocrine System Metabolic Syndrome Blood Test: Basic Metabolic Panel Blood Test: Comprehensive ...

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

    PubMed Central

    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

    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

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

    PubMed

    Samuelov, Liat; Sarig, Ofer; Harmon, Robert M; 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

    2013-10-01

    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 have a crucial role in maintaining epidermal integrity and barrier function. Mutations causing SAM syndrome 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. Our deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect. PMID:23974871

  2. Crassulacean acid metabolism under severe light limitation: a matter of plasticity in the shadows?

    PubMed

    Ceusters, Johan; Borland, Anne M; Godts, Christof; Londers, Elsje; Croonenborghs, Sarah; Van Goethem, Davina; De Proft, Maurice P

    2011-01-01

    Despite the increased energetic costs of CAM compared with C(3) photosynthesis, it is hypothesized that the inherent photosynthetic plasticity of CAM allows successful acclimation to light-limiting conditions. The present work sought to determine if CAM presented any constraints to short and longer term acclimation to light limitation and to establish if and how metabolic and photosynthetic plasticity in the deployment of the four phases of CAM might facilitate acclimation to conditions of deep shade. Measurements of leaf gas exchange, organic acids, starch and soluble sugar (glucose, fructose, and sucrose) contents were made in the leaves of the constitutive CAM bromeliad Aechmea 'Maya' over a three month period under severe light limitation. A. 'Maya' was not particularly tolerant of severe light limitation in the short term. A complete absence of net CO(2) uptake and fluctuations in key metabolites (i.e. malate, starch or soluble sugars) indicated a dampened metabolism whilst cell death in the most photosynthetically active leaves was attributed to an over-acidification of the cytoplasm. However, in the longer term, plasticity in the use of the different phases of gas exchange and different storage carbohydrate pools, i.e. a switch from starch to sucrose as the major carbohydrate source, ensured a positive carbon balance for this CAM species under extremely low levels of irradiance. As such, co-ordinated plasticity in the use of C(3) and C(4) carboxylases and different carbohydrate pools together with an increase in the abundance of light-harvesting complexes, appear to underpin the adaptive radiation of the energetically costly CAM pathway within light-limiting environments such as wet cloud forests and shaded understoreys of tropical forests. PMID:20861137

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

    PubMed Central

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

    2009-01-01

    Introduction Maintaining arterial blood glucose within tight limits is beneficial in critically ill patients. Upper and lower limits of detrimental blood glucose levels must be determined. Methods In 69 patients with severe traumatic brain injury (TBI), cerebral metabolism was monitored by assessing changes in arterial and jugular venous blood at normocarbia (partial arterial pressure of carbon dioxide (paCO2) 4.4 to 5.6 kPa), normoxia (partial arterial pressure of oxygen (paO2) 9 to 20 kPa), stable haematocrit (27 to 36%), brain temperature 35 to 38°C, and cerebral perfusion pressure (CPP) 70 to 90 mmHg. This resulted in a total of 43,896 values for glucose uptake, lactate release, oxygen extraction ratio (OER), carbon dioxide (CO2) and bicarbonate (HCO3) production, jugular venous oxygen saturation (SjvO2), oxygen-glucose index (OGI), lactate-glucose index (LGI) and lactate-oxygen index (LOI). Arterial blood glucose concentration-dependent influence was determined retrospectively by assessing changes in these parameters within pre-defined blood glucose clusters, ranging from less than 4 to more than 9 mmol/l. Results Arterial blood glucose significantly influenced signs of cerebral metabolism reflected by increased cerebral glucose uptake, decreased cerebral lactate production, reduced oxygen consumption, negative LGI and decreased cerebral CO2/HCO3 production at arterial blood glucose levels above 6 to 7 mmol/l compared with lower arterial blood glucose concentrations. At blood glucose levels more than 8 mmol/l signs of increased anaerobic glycolysis (OGI less than 6) supervened. Conclusions Maintaining arterial blood glucose levels between 6 and 8 mmol/l appears superior compared with lower and higher blood glucose concentrations in terms of stabilised cerebral metabolism. It appears that arterial blood glucose values below 6 and above 8 mmol/l should be avoided. Prospective analysis is required to determine the optimal arterial blood glucose target in patients suffering from severe TBI. PMID:19196488

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

    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

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

    Microsoft Academic Search

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

    2005-01-01

    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)

  7. Severe Uncompensated Metabolic Alkalosis due to Plasma Exchange in a Patient with Pulmonary-Renal Syndrome: A Clinician's Challenge

    PubMed Central

    Ijaz, Mohsin; Abbas, Naeem; Lvovsky, Dmitry

    2015-01-01

    Metabolic alkalosis secondary to citrate toxicity from plasma exchange is very uncommon in patients with normal renal function. In patients with advanced renal disease this can be a fatal event. We describe a case of middle-aged woman with Goodpasture's syndrome treated with plasma exchange who developed severe metabolic alkalosis. High citrate load in plasma exchange fluid is the underlying etiology. Citrate metabolism generates bicarbonate and once its level exceeds the excretory capacity of kidneys, the severe metabolic alkalosis ensues. Our patient presented with generalized weakness, fever, and oliguria and developed rapidly progressive renal failure. Patient had positive serology for antineutrophilic cytoplasmic antibodies myeloperoxidase (ANCA-MPO) and anti-glomerular basement membrane antibodies (anti-GBM). Renal biopsy showed diffuse necrotizing and crescentic glomerulonephritis with linear glomerular basement membrane staining. Patient did not respond to intravenous steroids. Plasma exchange was started with fresh frozen plasma but patient developed severe metabolic alkalosis. This metabolic alkalosis normalized with cessation of plasma exchange and initiation of low bicarbonate hemodialysis. ANCA-MPO and anti-GBM antibodies levels normalized within 2 weeks and remained undetectable at 3 months. Patient still required maintenance hemodialysis.

  8. Altered lipid metabolism in Hfe-knockout mice promotes severe NAFLD and early fibrosis.

    PubMed

    Tan, Terrence C H; Crawford, Darrell H G; Jaskowski, Lesley A; Murphy, Therese M; Heritage, Mandy L; Subramaniam, V Nathan; Clouston, Andrew D; Anderson, Gregory J; Fletcher, Linda M

    2011-11-01

    The HFE protein plays a crucial role in the control of cellular iron homeostasis. Steatosis is commonly observed in HFE-related iron-overload disorders, and current evidence suggests a causal link between iron and steatosis. Here, we investigated the potential contribution of HFE mutations to hepatic lipid metabolism and its role in the pathogenesis of nonalcoholic fatty liver disease. Wild-type (WT) and Hfe knockout mice (Hfe(-/-)) were fed either standard chow, a monounsaturated low fat, or a high-fat, high-carbohydrate diet (HFD) and assessed for liver injury, body iron status, and markers of lipid metabolism. Despite hepatic iron concentrations and body weights similar to WT controls, Hfe(-/-) mice fed the HFD developed severe hypoxia-related steatohepatitis, Tnf-? activation, and mitochondrial respiratory complex and antioxidant dysfunction with early fibrogenesis. These features were associated with an upregulation in the expression of genes involved in intracellular lipid synthesis and trafficking, while transcripts for mitochondrial fatty acid ?-oxidation and adiponectin signaling-related genes were significantly attenuated. In contrast, HFD-fed WT mice developed bland steatosis only, with no inflammation or fibrosis and no upregulation of lipogenesis-related genes. A HFD led to reduced hepatic iron in Hfe(-/-) mice compared with chow-fed mice, despite higher serum iron, decreased hepcidin expression, and increased duodenal ferroportin mRNA. In conclusion, our results demonstrate that Hfe(-/-) mice show defective hepatic-intestinal iron and lipid signaling, which predispose them toward diet-induced hepatic lipotoxicity, accompanied by an accelerated progression of injury to fibrosis. PMID:21817060

  9. Genetic Variation Throughout the Folate Metabolic Pathway Influences Negative Symptom Severity in Schizophrenia

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-03-01

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

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

    PubMed

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

    2015-03-01

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

  12. Dissociation between lactate accumulation and acidosis in middle cerebral artery-occluded rats assessed by 31P and 1H NMR metabolic images under A 2-T magnetic field

    Microsoft Academic Search

    Shigehiro Morikawa; Toshiro Inubushi; Kan Takahashi; Hisanari Ishii; Shino Shigemori

    1996-01-01

    The relationships among tissue edema, lactate accumulation, and intracellular pH in middle cerebral artery (MCA)-occluded rats were investigated with multiecho 1H magnetic resonance imaging and spatially resolved metabolic images constructed by 1H and 31P nuclear magnetic resonance (NMR) chemical shift imaging (CSI). For the effective and sensitive detection of NMR signals from the brain, outer volume suppression (OVS), reduced k-space

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

    PubMed Central

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

    2014-01-01

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

  14. Hyperhomocysteinemia as a metabolic disorder parameter is independently associated with the severity of coronary heart disease

    PubMed Central

    Liu, Chenggui; Yang, Yinzhong; Peng, Duanliang; Chen, Linong; Luo, Jun

    2015-01-01

    Objectives: To study the associations between hyperhomocysteinemia (HHcy) and the severity of coronary heart disease (CHD). Methods: We retrospectively analyzed metabolic parameters, anthropometric variables, and life style habits in 292 CHD patients of different categories, and 100 controlled non-CHD patients with chest pain symptoms who were hospitalized in the Department of Cardiovascular Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, China between October 2013 and September 2014. Results: The prevalence of HHcy in CHD patients was 79.1%, while only 5% of non-CHD patients had elevated serum homocysteine (Hcy) concentrations. The prevalence of HHcy significantly increased from 5% in non-CHD controls to 66% in the stable angina pectoris (SAP) group, to 81.9% in the unstable angina pectoris group, and to 93.15% in the acute myocardial infarction (AMI) group (p<0.001). After adjusting for confounding factors, multivariate logistic regression analysis showed that HHcy was independently associated with CHD category (AMI versus SAP, odds ratio [6.38], 95% confidence interval; 1.18-34.46). The Hcy was negatively correlated with folic acid (r=-0.67, p<0.001) and vitamin B12 (r=-0.56, p<0.001). Of the CHD patients with HHcy, 51.1% had low folic acid and 42% had low vitamin B12, 7 or 5 times higher than that of CHD patients with normal-low Hcy concentrations (p<0.001). Conclusion: Hyperhomocysteinemia is independently associated with the severity of CHD, and significantly correlated with low status of folic acid and vitamin B12 in CHD patients. PMID:26108589

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

    E-print Network

    Abry, Patrice

    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

  16. Distal renal tubular acidosis with hereditary spherocytosis.

    PubMed

    Sinha, Rajiv; Agarwal, Indira; Bawazir, Waleed M; Bruce, Lesley J

    2013-07-01

    Hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA), although distinct entities, share the same protein i.e. the anion exchanger1 (AE1) protein. Despite this, their coexistence has been rarely reported. We hereby describe the largest family to date with co-existence of dRTA and HS and discuss the molecular basis for the co-inheritance of these conditions. PMID:23942433

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

    PubMed Central

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

    2004-01-01

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

  18. Oviposition in land snails requires the successful completion of several metabolically costly processes, including oogenesis,

    E-print Network

    Chase, Ronald

    the optimized conditions of a breeding farm, only 13% of snails Helix aspersa oviposit more than once every of Biologists Ltd doi:10.1242/jeb.00625 Because oviposition in the land snail Helix aspersa is a metabolically). Clutch sizes in H. aspersa vary considerably between populations and under different conditions

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

    Microsoft Academic Search

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

    2004-01-01

    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

  20. MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis

    ClinicalTrials.gov

    2015-06-19

    Mucopolysaccharidosis I; Mucopolysaccharidosis II; Mucopolysaccharidosis VI; Mucopolysaccharidosis VII; Hurler Syndrome; Hunter Syndrome; Maroteaux Lamy Syndrome; Sly Syndrome; Glycoprotein Metabolic Disorders; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Adrenoleukodystrophy; Peroxisomal Disorders; Osteopetrosis; Sphingolipidosis; Gangliosidosis; Globoid Cell Leukodystrophy; Metachromatic Leukodystrophy; Niemann Pick B; Niemann Pick C Subtype 2; I-cell Disease

  1. DIAGNOSING & MANAGING SUBCLINICAL RUMEN ACIDOSIS IN DAIRY CATTLE.

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. Contribution of respiratory acidosis to diaphragmatic fatigue at exercise

    Microsoft Academic Search

    S. Jonville; N. Delpech; A. Denjean

    2002-01-01

    Contribution of respiratory acidosis to diaphragmatic fatigue at exercise. S. Jonville, N. Delpech, A. Denjean. #ERS Journals Ltd 2002. ABSTRACT: The factors that may modulate ventilatory muscle fatigue during exercise are controversial. In this study the contribution of acidosis to exercise-induced diaphragmatic fatigue was investigated, using measurements of the twitch mouth pressure response (tw,Pmo) to cervical magnetic stimulation. After learning

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

    NASA Astrophysics Data System (ADS)

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

    1985-02-01

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

  4. Bone and metabolic complications of urinary diversions.

    PubMed

    Cano Megías, Marta; Muñoz Delgado, Eva Golmayo

    2015-02-01

    Hyperchloremic metabolic acidosis is a complication of urinary diversion using ileum or colon. Its prevalence ranges from 25% and 46% depending on the procedure used and renal function of the patient. It is a consequence of intestinal fluid and electrolyte exchange between intestinal mucosa and urine. The main mechanism is absorption of ammonium and chloride from urine. Long-term chronic metabolic acidosis in these patients may lead to impaired bone metabolism and osteomalacia. Regular monitoring of pH, chlorine, bicarbonate, and calcium-phosphorus metabolism is therefore essential for early diagnosis and treatment. PMID:25481805

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

    PubMed Central

    2011-01-01

    Background The relationship between relative metabolic disturbances and developmental disorders is an emerging research focus. This study compares the nutritional and metabolic status of children with autism with that of neurotypical children and investigates the possible association of autism severity with biomarkers. Method Participants were children ages 5-16 years in Arizona with Autistic Spectrum Disorder (n = 55) compared with non-sibling, neurotypical controls (n = 44) of similar age, gender and geographical distribution. Neither group had taken any vitamin/mineral supplements in the two months prior to sample collection. Autism severity was assessed using the Pervasive Development Disorder Behavior Inventory (PDD-BI), Autism Treatment Evaluation Checklist (ATEC), and Severity of Autism Scale (SAS). Study measurements included: vitamins, biomarkers of vitamin status, minerals, plasma amino acids, plasma glutathione, and biomarkers of oxidative stress, methylation, sulfation and energy production. Results Biomarkers of children with autism compared to those of controls using a t-test or Wilcoxon test found the following statistically significant differences (p < 0.001): Low levels of biotin, plasma glutathione, RBC SAM, plasma uridine, plasma ATP, RBC NADH, RBC NADPH, plasma sulfate (free and total), and plasma tryptophan; also high levels of oxidative stress markers and plasma glutamate. Levels of biomarkers for the neurotypical controls were in good agreement with accessed published reference ranges. In the Autism group, mean levels of vitamins, minerals, and most amino acids commonly measured in clinical care were within published reference ranges. A stepwise, multiple linear regression analysis demonstrated significant associations between several groups of biomarkers with all three autism severity scales, including vitamins (adjusted R2 of 0.25-0.57), minerals (adj. R2 of 0.22-0.38), and plasma amino acids (adj. R2 of 0.22-0.39). Conclusion The autism group had many statistically significant differences in their nutritional and metabolic status, including biomarkers indicative of vitamin insufficiency, increased oxidative stress, reduced capacity for energy transport, sulfation and detoxification. Several of the biomarker groups were significantly associated with variations in the severity of autism. These nutritional and metabolic differences are generally in agreement with other published results and are likely amenable to nutritional supplementation. Research investigating treatment and its relationship to the co-morbidities and etiology of autism is warranted. PMID:21651783

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

    PubMed

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

    2015-03-01

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

  7. The prevalence of metabolic syndrome amongst patients with severe mental illness in the community in Hong Kong – a cross sectional study

    PubMed Central

    2013-01-01

    Background Patients with severe mental illness are at increased risk of developing metabolic disorders. The risk of metabolic syndrome in the Hong Kong general population is lower than that observed in western countries; however the prevalence of metabolic syndrome in patients with severe mental illness in Hong Kong is unknown. Method This cross-sectional study aimed to estimate the prevalence of metabolic syndrome in patients with severe mental illness in Hong Kong and to identify the relationships between metabolic syndrome and socio-demographic, clinical and lifestyle factors. Results A total of 139 patients with a diagnosis of severe mental illness participated in the study. The unadjusted prevalence of metabolic syndrome was 35%. The relative risk of metabolic syndrome in comparison with the general Hong Kong population was 2.008 (95% CI 1.59-2.53, p?metabolic syndrome is highly prevalent and that physical health inequalities in patients with severe mental illness in Hong Kong are similar to those observed in western countries. The results provide sufficient evidence to support the need for intervention studies in this setting and reinforce the requirement to conduct regular physical health checks for all patients with severe mental illness. PMID:23506322

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

    PubMed

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

    2013-02-22

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

  9. Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome.

    PubMed

    Kim, Hae Rim; Lee, Young Sun; Yim, Hyung Joon; Lee, Hyun Joo; Ryu, Ja Young; Lee, Hyun Jung; Yoon, Eileen L; Lee, Sun Jae; Hyun, Jong Jin; Jung, Sung Woo; Koo, Ja Seol; Choung, Rok Sun; Lee, Sang Woo; Choi, Jai Hyun

    2013-12-01

    Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin. PMID:24459647

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

    PubMed

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

    2013-11-12

    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

  11. 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 ...

  12. Hyperalaninemia, hyperpyruvicemia and lactic acidosis due to pyruvate carboxylase deficiency of the liver; Treatment with thiamine and lipoic acid

    Microsoft Academic Search

    Hatae Maesaka; Kazuhiko Komiya; Kazuaki Misugi; Keiya Tada

    1976-01-01

    A 16-month-old female infant with severe mental and motor retardation, clinically diagnosed as Leigh's encephalomyelopathy, forms the basis of this study. This infant was found to have lactic acidosis, low cerebrospinal fluid glucose, hyperalaninemia, and increased levels of urine lactate, pyruvate and alanine. These laboratory studies suggested an inborn error in gluconeogenesis. Further investigation revealed a low level of hepatic

  13. Effect of ginkgolide B on brain metabolism and tissue oxygenation in severe haemorrhagic stroke

    PubMed Central

    Chi, Chun-Ling; Shen, Dong-Fang; Wang, Peng-Jun; Li, Hu-Lun; Zhang, Li

    2015-01-01

    Ginkgolide B, a diterpene, is an herbal constituent isolated from the leaves of Ginkgo biloba tree. The present study demonstrates the effect of ginkgolide B in osmotherapy on brain metabolism and tissue oxygenation. Multimodality monitoring including intracranial pressure (ICP), cerebral perfusion pressure (CPP), partial pressure of brain tissue oxygen (PbtO2), lactate/pyruvate ratio (LPR) and microdialysis were employed to study the effect of ginkgolide B osmotherapy. The results demonstrated that administration of 15% solution of ginkgolide B to the comatose patients with raised ICP (> 20 mm Hg) and resistant to standard therapy led to a significant decrease in ICP. The cerebral microdialysis was used to compare mean arterial blood pressure (MAP), ICP, CPP, PbtO2, brain lactate, pyruvate and glucose level after hourly intervals starting 3 h before and up to 4 h after hyperosmolar therapy. There was a decrease in ICP in 45 min from 23 ± 14 mm Hg (P < 0.001) to 18 ± 24 mm Hg and increase in CPP after 1 h of gingkolide B infusion from 74 ± 18 to 85 ± 22 mm Hg (P < 0.002). However there was no significant effect on MAP but PbtO2 was maintained in the range of 22-26. The peak lactate/pyruvate ratio was recorded at the time of initiation of osmotherapy (44 ± 20) with an 18% decrease over 2 h following gingkolide B therapy. Also the brain glucose remained unaffected.

  14. Increased blood flow prevents intramucosal acidosis in sheep endotoxemia: a controlled study

    PubMed Central

    Dubin, Arnaldo; Murias, Gastón; Maskin, Bernardo; Pozo, Mario O; Sottile, Juan P; Barán, Marcelo; Edul, Vanina S Kanoore; Canales, Héctor S; Badie, Julio C; Etcheverry, Graciela; Estenssoro, Elisa

    2005-01-01

    Introduction Increased intramucosal–arterial carbon dioxide tension (PCO2) difference (?PCO2) is common in experimental endotoxemia. However, its meaning remains controversial because it has been ascribed to hypoperfusion of intestinal villi or to cytopathic hypoxia. Our hypothesis was that increased blood flow could prevent the increase in ?PCO2. Methods In 19 anesthetized and mechanically ventilated sheep, we measured cardiac output, superior mesenteric blood flow, lactate, gases, hemoglobin and oxygen saturations in arterial, mixed venous and mesenteric venous blood, and ileal intramucosal PCO2 by saline tonometry. Intestinal oxygen transport and consumption were calculated. After basal measurements, sheep were assigned to the following groups, for 120 min: (1) sham (n = 6), (2) normal blood flow (n = 7) and (3) increased blood flow (n = 6). Escherichia coli lipopolysaccharide (5 ?g/kg) was injected in the last two groups. Saline solution was used to maintain blood flood at basal levels in the sham and normal blood flow groups, or to increase it to about 50% of basal in the increased blood flow group. Results In the normal blood flow group, systemic and intestinal oxygen transport and consumption were preserved, but ?PCO2 increased (basal versus 120 min endotoxemia, 7 ± 4 versus 19 ± 4 mmHg; P < 0.001) and metabolic acidosis with a high anion gap ensued (arterial pH 7.39 versus 7.35; anion gap 15 ± 3 versus 18 ± 2 mmol/l; P < 0.001 for both). Increased blood flow prevented the elevation in ?PCO2 (5 ± 7 versus 9 ± 6 mmHg; P = not significant). However, anion-gap metabolic acidosis was deeper (7.42 versus 7.25; 16 ± 3 versus 22 ± 3 mmol/l; P < 0.001 for both). Conclusions In this model of endotoxemia, intramucosal acidosis was corrected by increased blood flow and so might follow tissue hypoperfusion. In contrast, anion-gap metabolic acidosis was left uncorrected and even worsened with aggressive volume expansion. These results point to different mechanisms generating both alterations. PMID:15774052

  15. Unique metabolic characteristics of the major syndromes of severe childhood malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2014-10-27

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

  17. Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer.

    PubMed

    Gatenby, R A; Smallbone, K; Maini, P K; Rose, F; Averill, J; Nagle, R B; Worrall, L; Gillies, R J

    2007-09-01

    Conceptual models of carcinogenesis typically consist of an evolutionary sequence of heritable changes in genes controlling proliferation, apoptosis, and senescence. We propose that these steps are necessary but not sufficient to produce invasive breast cancer because intraductal tumour growth is also constrained by hypoxia and acidosis that develop as cells proliferate into the lumen and away from the underlying vessels. This requires evolution of glycolytic and acid-resistant phenotypes that, we hypothesise, is critical for emergence of invasive cancer. Mathematical models demonstrate severe hypoxia and acidosis in regions of intraductal tumours more than 100 microm from the basement membrane. Subsequent evolution of glycolytic and acid-resistant phenotypes leads to invasive proliferation. Multicellular spheroids recapitulating ductal carcinoma in situ (DCIS) microenvironmental conditions demonstrate upregulated glucose transporter 1 (GLUT1) as adaptation to hypoxia followed by growth into normoxic regions in qualitative agreement with model predictions. Clinical specimens of DCIS exhibit periluminal distribution of GLUT-1 and Na(+)/H(+) exchanger (NHE) indicating transcriptional activation by hypoxia and clusters of the same phenotype in the peripheral, presumably normoxic regions similar to the pattern predicted by the models and observed in spheroids. Upregulated GLUT-1 and NHE-1 were observed in microinvasive foci and adjacent intraductal cells. Adaptation to hypoxia and acidosis may represent key events in transition from in situ to invasive cancer. PMID:17687336

  18. Differential impacts of elevated CO2 and acidosis on the energy budget of gill and liver cells from Atlantic cod, Gadus morhua.

    PubMed

    Stapp, L S; Kreiss, C M; Pörtner, H O; Lannig, G

    2015-09-01

    Ocean acidification impacts fish and other marine species through increased seawater PCO2 levels (hypercapnia). Knowledge of the physiological mechanisms mediating effects in various tissues of fish is incomplete. Here we tested the effects of extracellular hypercapnia and acidosis on energy metabolism of gill and liver cells of Atlantic cod. Exposure media mimicked blood conditions in vivo, either during normo- or hypercapnia and at control or acidic extracellular pH (pHe). We determined metabolic rate and energy expenditure for protein biosynthesis, Na(+)/K(+)-ATPase and H(+)-ATPase and considered nutrition status by measurements of metabolic rate and protein biosynthesis in media with and without free amino acids (FAA). Addition of FAA stimulated hepatic but not branchial oxygen consumption. Normo- and hypercapnic acidosis as well as hypercapnia at control pHe depressed metabolic stimulation of hepatocytes. In gill cells, acidosis depressed respiration independent of PCO2 and FAA levels. For both cell types, depressed respiration was not correlated with the same reduction in energy allocated to protein biosynthesis or Na(+)/K(+)-ATPase. Hepatic energy expenditure for protein synthesis and Na(+)/K(+)-ATPase was even elevated at acidic compared to control pHe suggesting increased costs for ion regulation and cellular reorganization. Hypercapnia at control pHe strongly reduced oxygen demand of branchial Na(+)/K(+)-ATPase with a similar trend for H(+)-ATPase. We conclude that extracellular acidosis triggers metabolic depression in gill and metabolically stimulated liver cells. Additionally, hypercapnia itself seems to limit capacities for metabolic usage of amino acids in liver cells while it decreases the use and costs of ion regulatory ATPases in gill cells. PMID:26005104

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

    SciTech Connect

    Swenson, E.R.

    1986-06-01

    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.

  20. Severe Acute Malnutrition in Childhood: Hormonal and Metabolic Status at Presentation, Response to Treatment, and Predictors of Mortality

    PubMed Central

    Bartz, Sarah; Mody, Aaloke; Hornik, Christoph; Bain, James; Muehlbauer, Michael; Kiyimba, Tonny; Kiboneka, Elizabeth; Stevens, Robert; Bartlett, John; St Peter, John V.; Newgard, Christopher B.

    2014-01-01

    Objective: Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict complications prior to and during treatment. Methods: We used targeted and nontargeted metabolomic analysis to characterize changes in a broad array of hormones, cytokines, growth factors, and metabolites during treatment of severe childhood malnutrition. Children aged 6 months to 5 years were studied at presentation to Mulago Hospital and during inpatient therapy with milk-based formulas and outpatient supplementation with ready-to-use food. We assessed the relationship between baseline hormone and metabolite levels and subsequent mortality. Results: Seventy-seven patients were enrolled in the study; a subset was followed up from inpatient treatment to the outpatient clinic. Inpatient and outpatient therapies increased weight/height z scores and induced striking changes in the levels of fatty acids, amino acids, acylcarnitines, inflammatory cytokines, and various hormones including leptin, insulin, GH, ghrelin, cortisol, IGF-I, glucagon-like peptide-1, and peptide YY. A total of 12.2% of the patients died during hospitalization; the major biochemical factor predicting mortality was a low level of leptin (P = .0002), a marker of adipose tissue reserve and a critical modulator of immune function. Conclusions: We have used metabolomic analysis to provide a comprehensive hormonal and metabolic profile of severely malnourished children at presentation and during nutritional rehabilitation. Our findings suggest that fatty acid metabolism plays a central role in the adaptation to acute malnutrition and that low levels of the adipose tissue hormone leptin associate with, and may predict, mortality prior to and during treatment. PMID:24606092

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

    PubMed

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

    2014-02-15

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

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

    PubMed Central

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

    2013-01-01

    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

  3. Effects of ulinastatin on cerebral oxygen metabolism and CRP levels in patients with severe traumatic brain injury.

    PubMed

    Hui, Lei; Shen, Fazheng; Chang, Haigang; Li, Xiangsheng; Gao, Guojun; Ma, Jiwei

    2014-06-01

    The aim of the present study was to investigate the effects of ulinastatin on cerebral oxygen metabolism and C-reactive protein (CRP) levels in patients with severe traumatic brain injury (sTBI). A total of 92 patients with sTBI, admitted to the First Affiliated Hospital of Xinxiang Medical University (Xinxiang, China), were randomly divided into control and observation groups. The control group received conventional therapy plus a placebo (0.9% sodium chloride), while the observation group were administered conventional therapy plus 200,000 units ulinastatin via intravenous injection twice a day for seven days. Arterial and jugular venous blood was collected for blood gas analysis. The jugular venous blood lactate (JVBL), jugular venous bulb oxygen saturation (SjvO2), arteriovenous oxygen content difference (AVDO2) and cerebral extraction of oxygen (CEO2) levels were measured on day 1, 3, 5 and 7, as well as the level of CRP in the peripheral blood. In the control group, the level of JVBL decreased as compared with the level at day 1, however, no statistically significant differences were observed (P>0.05). By contrast, the observation group exhibited a significant reduction in the level of JVBL (P<0.05), which was also significantly lower compared with the control group (P<0.05). Statistically significant differences were observed between the two groups with regard to SjvO2, AVDO2 and CEO2 on day 3, 5 and 7. The CRP levels in the two groups increased and peaked on day 3. However, the CRP level in the observation group significantly decreased on day 5 (35.27±15.18 mg/l) and day 7 (22.65±10.48 mg/l), which was lower compared with the control group (56.19±13.24 mg/l and 47.36±15.73 mg/l, respectively); statistically significant differences were observed (P<0.05). Therefore, ulinastatin effectively improved cerebral oxygen metabolism and reduced the CRP level in patients with sTBI. PMID:24926366

  4. Effects of ulinastatin on cerebral oxygen metabolism and CRP levels in patients with severe traumatic brain injury

    PubMed Central

    HUI, LEI; SHEN, FAZHENG; CHANG, HAIGANG; LI, XIANGSHENG; GAO, GUOJUN; MA, JIWEI

    2014-01-01

    The aim of the present study was to investigate the effects of ulinastatin on cerebral oxygen metabolism and C-reactive protein (CRP) levels in patients with severe traumatic brain injury (sTBI). A total of 92 patients with sTBI, admitted to the First Affiliated Hospital of Xinxiang Medical University (Xinxiang, China), were randomly divided into control and observation groups. The control group received conventional therapy plus a placebo (0.9% sodium chloride), while the observation group were administered conventional therapy plus 200,000 units ulinastatin via intravenous injection twice a day for seven days. Arterial and jugular venous blood was collected for blood gas analysis. The jugular venous blood lactate (JVBL), jugular venous bulb oxygen saturation (SjvO2), arteriovenous oxygen content difference (AVDO2) and cerebral extraction of oxygen (CEO2) levels were measured on day 1, 3, 5 and 7, as well as the level of CRP in the peripheral blood. In the control group, the level of JVBL decreased as compared with the level at day 1, however, no statistically significant differences were observed (P>0.05). By contrast, the observation group exhibited a significant reduction in the level of JVBL (P<0.05), which was also significantly lower compared with the control group (P<0.05). Statistically significant differences were observed between the two groups with regard to SjvO2, AVDO2 and CEO2 on day 3, 5 and 7. The CRP levels in the two groups increased and peaked on day 3. However, the CRP level in the observation group significantly decreased on day 5 (35.27±15.18 mg/l) and day 7 (22.65±10.48 mg/l), which was lower compared with the control group (56.19±13.24 mg/l and 47.36±15.73 mg/l, respectively); statistically significant differences were observed (P<0.05). Therefore, ulinastatin effectively improved cerebral oxygen metabolism and reduced the CRP level in patients with sTBI. PMID:24926366

  5. Deficiency of the ? and ? subunits of pyruvate dehydrogenase in a patient with lactic acidosis and unexpected sudden death

    Microsoft Academic Search

    W. Sperl; W. Ruitenbeek; C. M. C. Kerkhof; R. C. A. Sengers; J. M. F. Trijbels; J. P. Guggenbichler; A. J. M. Janssen; J. A. J. M. Bakkeren

    1990-01-01

    An infant with moderate muscular hypotonia and congenital lactic acidosis died suddenly at the age of 3 months. Autopsy revealed no abnormalities responsible for this unexpected death. Measurement of mitochondrial enzymes involved in energy production indicated a severely decreased total pyruvate dehydrogenase complex (PDHC) activity in muscle tissue (0.23 nmoles · min?1 · mg protein?1, control range 2.8–8.7) and moderately

  6. Sodium Bicarbonate for the Treatment of Lactic Acidosis

    Microsoft Academic Search

    Sean M. Forsythe; Gregory A. Schmidt

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

  7. How well does reflectance pulse oximetry reflect intrapartum fetal acidosis?

    Microsoft Academic Search

    Ruth Stiller; Ruth von Mering; Volker König; Albert Huch; Renate Huch

    2002-01-01

    Objective: The purpose of this study was to determine the sensitivity and specificity for acidosis of intrapartum fetal oxygen saturation measured by reflectance pulse oximetry. Study Design: Intrapartum fetal oxygen saturation values per labor stage were correlated with umbilical artery pH, base excess and PCO2 by regression analysis. Receiver operating characteristic curve analysis was performed with the use of historic

  8. Metabolic studies of transient tyrosinemia in premature infants

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

    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.

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

    Microsoft Academic Search

    Christoph Wittmann; Elmar Heinzle

    2002-01-01

    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.

  10. Effects of methionine sulphoximine treatment on renal amino acid and ammonia metabolism in rats

    Microsoft Academic Search

    Sylvia Heeneman; Cornelis H. C. Dejong; Nicolaas E. P. Deutz

    1994-01-01

    Renal glutamine metabolism in relation to ammoniagenesis has been extensively studied during chronic metabolic acidosis, when arterial glutamine levels are reduced. However, little is known about the effects of reduced glutamine delivery on renal glutamine and ammonia metabolism at physiological systemic pH values. Therefore, a model of decreased arterial glutamine concentrations at normal pH values was developed using methionine sulphoximine

  11. Modeling and simulation of the main metabolism in Escherichia coli and its several single-gene knockout mutants with experimental verification

    PubMed Central

    2010-01-01

    Background It is quite important to simulate the metabolic changes of a cell in response to the change in culture environment and/or specific gene knockouts particularly for the purpose of application in industry. If this could be done, the cell design can be made without conducting exhaustive experiments, and one can screen out the promising candidates, proceeded by experimental verification of a select few of particular interest. Although several models have so far been proposed, most of them focus on the specific metabolic pathways. It is preferred to model the whole of the main metabolic pathways in Escherichia coli, allowing for the estimation of energy generation and cell synthesis, based on intracellular fluxes and that may be used to characterize phenotypic growth. Results In the present study, we considered the simulation of the main metabolic pathways such as glycolysis, TCA cycle, pentose phosphate (PP) pathway, and the anapleorotic pathways using enzymatic reaction models of E. coli. Once intracellular fluxes were computed by this model, the specific ATP production rate, the specific CO2 production rate, and the specific NADPH production rate could be estimated. The specific ATP production rate thus computed was used for the estimation of the specific growth rate. The CO2 production rate could be used to estimate cell yield, and the specific NADPH production rate could be used to determine the flux of the oxidative PP pathway. The batch and continuous cultivations were simulated where the changing patterns of extracellular and intra-cellular metabolite concentrations were compared with experimental data. Moreover, the effects of the knockout of such pathways as Ppc, Pck and Pyk on the metabolism were simulated. It was shown to be difficult for the cell to grow in Ppc mutant due to low concentration of OAA, while Pck mutant does not necessarily show this phenomenon. The slower growth rate of the Ppc mutant was properly estimated by taking into account the lower specific ATP production rate. In the case of Pyk mutant, the enzyme level regulation was made clear such that Pyk knockout caused PEP concentration to be up-regulated and activated Ppc, which caused the increase in MAL concentration and backed up reduced PYR through Mez, resulting in the phenotypic growth characteristics similar to the wild type. Conclusions It was shown to be useful to simulate the main metabolism of E. coli for understanding metabolic changes inside the cell in response to specific pathway gene knockouts, considering the whole main metabolic pathways. The comparison of the simulation result with the experimental data indicates that the present model could simulate the effect of the specific gene knockouts to the changes in the metabolisms to some extent. PMID:21092096

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

    PubMed

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

    2014-01-01

    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

  13. 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

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

    2014-01-01

    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

  14. Ruminal acidosis in a 21-month-old Holstein heifer.

    PubMed

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

    2014-06-01

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

  15. Ruminal acidosis in a 21-month-old Holstein heifer

    PubMed Central

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

    2014-01-01

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

  16. Metformin-Associated Lactic Acidosis: Predisposing Factors and Outcome

    PubMed Central

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

    2015-01-01

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

  17. Beyond Warburg effect – dual metabolic nature of cancer cells

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-04-01

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

  19. Hereditary myopathy with lactic acidosis, succinate dehydrogenase and aconitase deficiency in northern Sweden: a genealogical study.

    PubMed Central

    Drugge, U; Holmberg, M; Holmgren, G; Almay, B G; Linderholm, H

    1995-01-01

    A hereditary myopathy with lactic acidosis during physical exercise, low physical work capacity, and paroxysmal myoglobinuria (HML), called "Myopathy with deficiency of succinate dehydrogenase and aconitase" (McKusick 255125) has been described in 19 members of nine families who lived in two geographically separate areas in northern Sweden. By using the unique Swedish historical archives, including Catechetical Meeting Records from a number of northern Swedish parishes, it has been possible to trace ancestors of the nine families including all known 19 cases back in time to some key couples, who lived up to 300 years ago (that is seven to ten generations). No common single couple or common links between families in the past was found in these registers as a support for a single or several mutations that had developed far back in time. The mode of inheritance in this family is most likely autosomal recessive. This material will be used for the chromosomal localisation of the gene. Images PMID:7616539

  20. Changes in activities of several enzymes involved in carbohydrate metabolism during the cell cycle of Saccharomyces cerevisiae.

    PubMed Central

    Van Doorn, J; Valkenburg, J A; Scholte, M E; Oehlen, L J; Van Driel, R; Postma, P W; Nanninga, N; Van Dam, K

    1988-01-01

    Activity changes of a number of enzymes involved in carbohydrate metabolism were determined in cell extracts of fractionated exponential-phase populations of Saccharomyces cerevisiae grown under excess glucose. Cell-size fractionation was achieved by an improved centrifugal elutriation procedure. Evidence that the yeast populations had been fractionated according to age in the cell cycle was obtained by examining the various cell fractions for their volume distribution and their microscopic appearance and by flow cytometric analysis of the distribution patterns of cellular DNA and protein contents. Trehalase, hexokinase, pyruvate kinase, phosphofructokinase 1, and fructose-1,6-diphosphatase showed changes in specific activities throughout the cell cycle, whereas the specific activities of alcohol dehydrogenase and glucose-6-phosphate dehydrogenase remained constant. The basal trehalase activity increased substantially (about 20-fold) with bud emergence and decreased again in binucleated cells. However, when the enzyme was activated by pretreatment of the cell extracts with cyclic AMP-dependent protein kinase, no significant fluctuations in activity were seen. These observations strongly favor posttranslational modification through phosphorylation-dephosphorylation as the mechanism underlying the periodic changes in trehalase activity during the cell cycle. As observed for trehalase, the specific activities of hexokinase and phosphofructokinase 1 rose from the beginning of bud formation onward, finally leading to more than eightfold higher values at the end of the S phase. Subsequently, the enzyme activities dropped markedly at later stages of the cycle. Pyruvate kinase activity was relatively low during the G1 phase and the S phase, but increased dramatically (more than 50-fold) during G2. In contrast to the three glycolytic enzymes investigated, the highest specific activity of the gluconeogenic enzyme fructose-1, 6-diphosphatase 1 was found in fractions enriched in either unbudded cells with a single nucleus or binucleated cells. The observed changes in enzyme activities most likely underlie pronounced alterations in carbohydrate metabolism during the cell cycle. PMID:2844728

  1. Acidosis slows electrical conduction through the atrio-ventricular node

    PubMed Central

    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

    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

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

    SciTech Connect

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

    1989-12-01

    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).

  3. Nephrocalcinosis in glucose-galactose malabsorption, association with renal tubular acidosis

    Microsoft Academic Search

    Walid El-Naggar; J. Williamson Balfe; Maha Barbar; Doris Taha

    2005-01-01

    We report an association of renal tubular acidosis (RTA) in two children with glucose-galactose malabsorption (GGM), who were found to have nephrocalcinosis. Although GGM has been reported previously with nephrocalcinosis, this report is the first to show that renal tubular acidosis could explain the coexistence of nephrocalcinosis in patients with glucose galactose malabsorption.

  4. Nephrocalcinosis in glucose-galactose malabsorption, association with renal tubular acidosis.

    PubMed

    El-Naggar, Walid; Balfe, J Williamson; Barbar, Maha; Taha, Doris

    2005-09-01

    We report an association of renal tubular acidosis (RTA) in two children with glucose-galactose malabsorption (GGM), who were found to have nephrocalcinosis. Although GGM has been reported previously with nephrocalcinosis, this report is the first to show that renal tubular acidosis could explain the coexistence of nephrocalcinosis in patients with glucose galactose malabsorption. PMID:16010597

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

    SciTech Connect

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

    1990-12-01

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

  6. [Brachial artery endothelial function in teenagers with obesity depending on severity of clinical, trophological and metabolic disorders].

    PubMed

    Maskova, G S; Chernaia, N L; Nagornova, E Iu; Fomina, O V; Byteva, T A

    2014-01-01

    We carried out complex examination of 68 adolescents aged 11-17 years with primary obesity which in addition to assessment of clinical-anamnestic, laboratory data and functional parameters of cardiovascular system included registration of reaction of brachial artery endothelium to reactive hyperemia. Vascular endothelial dysfunction (VED) was found in 66% of obese teenagers. Obesity in adolescents with VED was characterized by aggravated course with higher fat mass index (36.8 +/- 4.39%) and prevalence of hypothalamic (42%) and metabolic (8.8%) syndromes. Stable arterial hypertension (AH) found in 37% of examined adolescents was 1.5 times more often registered in those with VED. We distinguished 4 groups of adolescents with various degree of risk of development of cardiovascular disorders: with stable AH and VED (group I), with stable AH and normal function of vascular endothelium (group II), with normal or labile arterial pressure with VED (group III), with normal or labile arterial pressure with normal function of vascular endothelium. It is expedient to supplement examination of obese adolescents with assessment of the state of vascular endothelium aiming at determination of degree of risk of development of atherosclerosis and/or stable AH. PMID:24888198

  7. Antioxidant and metabolic impairment result in DNA damage in arsenic-exposed individuals with severe dermatological manifestations in Eastern India.

    PubMed

    Maiti, Smarajit; Chattopadhyay, Sandip; Deb, Bimal; Samanta, Tanmoy; Maji, Gurupada; Pan, Bappaditya; Ghosh, Amar; Ghosh, Debidas

    2012-05-01

    Arsenic is an environmental toxicant, free-radical generator, carcinogenic agent, and aging promoter. Recently, blood samples were analyzed from individuals (control- male 12, female 13; arsenic-exposed- male 16, female 14; and exposed to ?100 ?g/L As, ?10 y) with dermatological symptoms in few affected villages in Eastern India to unravel their hematopoietic, metabolic, and antioxidant profiles. White blood cells recovered from buffy coat were used for DNA fragmentation test. Present observation suggests that significant number of individuals developed pigmentation and palmoplantar hyperkeratosis with black-brownish patch on their body and many of those developed carcinomas. Hematopoietic data show a significant increase in eosinophil and decrease in monocyte count in either sex. Though insignificant, an increase in neutrophil in female and lymphocyte count in male arsenic-exposed individuals are supported by the earlier report on sex dimorphic immune sensitization. Significant increase in serum alanine transaminase in both sexes and bilirubin only in male suggests the eventuality of hepatic disintegration. Arsenic exposure significantly decreased serum amylase in female. A significant decrease in antioxidant components like catalase, soluble thiol, and recently recognized uric acid worsened the situation by generating free radicals as observed in significant rise in malondialdehyde level, which finally increased DNA fragmentation and arsenic-associated mutagenesis and carcinogenesis. This could attribute to lowering in immune competence and related necrotic and/or apoptotic manifestations. PMID:20925122

  8. SLO2, a mitochondrial pentatricopeptide repeat protein affecting several RNA editing sites, is required for energy metabolism.

    PubMed

    Zhu, Qiang; Dugardeyn, Jasper; Zhang, Chunyi; Takenaka, Mizuki; Kühn, Kristina; Craddock, Christian; Smalle, Jan; Karampelias, Michael; Denecke, Jurgen; Peters, Janny; Gerats, Tom; Brennicke, Axel; Eastmond, Peter; Meyer, Etienne H; Van Der Straeten, Dominique

    2012-09-01

    Pentatricopeptide repeat (PPR) proteins belong to a family of approximately 450 members in Arabidopsis, of which few have been characterized. We identified loss of function alleles of SLO2, defective in a PPR protein belonging to the E+ subclass of the P-L-S subfamily. slo2 mutants are characterized by retarded leaf emergence, restricted root growth, and late flowering. This phenotype is enhanced in the absence of sucrose, suggesting a defect in energy metabolism. The slo2 growth retardation phenotypes are largely suppressed by supplying sugars or increasing light dosage or the concentration of CO?. The SLO2 protein is localized in mitochondria. We identified four RNA editing defects and reduced editing at three sites in slo2 mutants. The resulting amino acid changes occur in four mitochondrial proteins belonging to complex I of the electron transport chain. Both the abundance and activity of complex I are highly reduced in the slo2 mutants, as well as the abundance of complexes III and IV. Moreover, ATP, NAD+, and sugar contents were much lower in the mutants. In contrast, the abundance of alternative oxidase was significantly enhanced. We propose that SLO2 is required for carbon energy balance in Arabidopsis by maintaining the abundance and/or activity of complexes I, III, and IV of the mitochondrial electron transport chain. PMID:22540321

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

    PubMed

    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

    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

  10. Hashimoto thyroiditis, distal renal tubular acidosis, pernicious anaemia and encephalopathy: A rare combination of auto-immune disorders in a 12-year-old girl

    Microsoft Academic Search

    N. Suzuki; R. Mitamura; H. Ohmi; Y. Itoh; K. Yano; A. Okuno; M. Tateno; T. Itoh

    1994-01-01

    A case of a 12-year-old girl with a multiple auto-immune disorder is reported. She showed Hashimoto thyroiditis which subsequently developed to hashitoxicosis and distal renal tubular acidosis at 5 years of age, pernicious anaemia at the age of 9 and severe encephalopathy at the age of 12. Laboratory studies revealed very high titres of anti-microsomal and anti-thyroglobulin antibodies and positive

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

    PubMed Central

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

    2014-01-01

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

  12. Metabolic Heterogeneity in Human Calf Muscle During Maximal Exercise

    Microsoft Academic Search

    K. Vandenborne; K. McCully; H. Kakihira; M. Prammer; L. Bolinger; J. A. Detre; K. de Meirleir; G. Walter; B. Chance; J. S. Leigh

    1991-01-01

    Human skeletal muscle is composed of various muscle fiber types. We hypothesized that differences in metabolism between fiber types could be detected noninvasively with ^31P nuclear magnetic resonance spectroscopy during maximal exercise. This assumes that during maximal exercise all fiber types are recruited and all vary in the amount of acidosis. The calf muscles of seven subjects were studied. Two

  13. Expression of cell wall invertase and several other genes of sugar metabolism in relation to seed development in sorghum (Sorghum bicolor).

    PubMed

    Jain, Mukesh; Chourey, Prem S; Li, Qin-Bao; Pring, Daryl R

    2008-01-01

    We report expression profiles of several genes of carbohydrate metabolism, cell wall invertase (CWI) in particular, to better understand sugar transport and its utilization in developing caryopses of grain sorghum [Sorghum bicolor (L.) Moench]. Gene expression analyses for CWI using RNA gel blot and real-time quantitative PCR approaches on developing caryopses, including the glumes (maternal tissue appended to the seeds), showed expression of SbIncw (ZmIncw2 ortholog) primarily in the basal sugar unloading zone of endosperm. The expression of ZmIncw1 ortholog was significantly less abundant and restricted to the glumes. The protein and enzyme activity data corroborated the temporal transcript expression profile that showed maximal CWI protein (INCW) expression preceding the starch-filling phase of endosperm development, i.e. 6-12d-after-pollination (DAP). Protein gel blot analysis using polyclonal maize INCW1 antibodies showed a single polypeptide of 72kDa. The highest level of enzyme activity was unique to the basal part of the endosperm, in particular the basal endosperm transfer cell (BETC) layer and the maternal pedicel region that were highly enriched for the INCW protein, as seen by immunolocalization. High hexose-to-sucrose ratio in 6-12 DAP seeds, and negligible starch deposition in glumes corroborated the CWI activity data. Additionally, we report transcription profiles of several other genes related to sugar-to-starch metabolism in developing sorghum endosperm. As in maize, the INCW-mediated apoplastic cleavage of sucrose in the BETC and pedicel during the early developmental stages of caryopses is essential for the normal development of filial tissues. The unique cell-specificity of the INCW protein to both proximal and distal ends of placental sac shown here for the first time is likely to greatly increase uptakes of both hexose sugars and water through turgor sensing into developing seed. This trait is unique to sorghum among cereals and may facilitate its survival in drought environment. PMID:17293002

  14. [Deep lactic acidosis after valproate self-poisoning].

    PubMed

    Blayac, D; Roch, A; Michelet, P; De Francheschi, E; Auffray, J-P

    2004-10-01

    A sixty-year-old woman was admitted in the ICU after Depamide (Valpromide) self-poisoning (430 mg/kg). Four hours after the ingestion, the patient presented coma (Glagow coma score of 3) with bilateral mydriasis requiring tracheal intubation and mechanical ventilation, hypotension requiring epinephrine infusion (0.9 microg/kg per minute), acidosis and hyperlactatemia (29.7 mmol/l at 12 hours) without any kidney or liver failure. The maximal serum valproic acid concentration measured was 342 mg/l after twelve hours (therapeutic rate: 35-85 mg/l). A continuous infusion of sodium bicarbonate was associated with continuous venovenous haemodiafiltration. Progressive haemodynamic improvement and neurologic recovery leaded to extubation at 36 hours. PMID:15501631

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

    Microsoft Academic Search

    Markus Rehm; Udilo Finsterer

    2003-01-01

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

  16. Expression of Glutamine Transporter Slc38a3 (SNAT3) During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression

    PubMed Central

    Balkrishna, Sarojini; Bröer, Angelika; Welford, Scott M.; Hatzoglou, Maria; Bröer, Stefan

    2015-01-01

    Background Despite homeostatic pH regulation, systemic and cellular pH changes take place and strongly influence metabolic processes. Transcription of the glutamine transporter SNAT3 (Slc38a3) for instance is highly up-regulated in the kidney during metabolic acidosis to provide glutamine for ammonia production. Methods Slc38a3 promoter activity and messenger RNA stability were measured in cultured cells in response to different extracellular pH values. Results Up-regulation of SNAT3 mRNA was mediated both by the stabilization of its mRNA and by the up-regulation of gene transcription. Stabilisation of the mRNA involved a pH-response element, while enhanced transcription made use of a second pH-sensitive Sp1 binding site in addition to a constitutive Sp1 binding site. Transcriptional regulation dominated the early response to acidosis, while mRNA stability was more important for chronic adaptation. Tissue-specific expression of SNAT3, by contrast, appeared to be controlled by promoter methylation and histone modifications. Conclusions Regulation of SNAT3 gene expression by extracellular pH involves post-transcriptional and transcriptional mechanisms, the latter being distinct from the mechanisms that control the tissue-specific expression of the gene. PMID:24854847

  17. [Non-fatal hyperkalemia in lactic acidosis due to metformin overdose. Report of one case].

    PubMed

    Díaz, Rienzi; Vega, Jorge; Goecke, Helmuth

    2015-03-01

    We report a 74-year-old man with diabetes mellitus type 2 and hypertension, who recently underwent coronary bypass surgery due to severe triple vessel disease receiving cardiological and combined antidiabetic therapy, including metformin 4 g/day. He was admitted with abdominal pain, nausea, vomiting, diarrhea and loss of consciousness. At admission, he was disoriented and agitated with signs of poor perfusion. His blood pressure was 80/70 mmHg, pulse rate 40 beats/min, respiratory rate 20-breaths/min, and axillary temperature 35°C. Biochemical profile revealed an extreme hyperkalemia of 15.4 mEq/L (double checked), elevated creatinine, uremia and brain natriuretic peptide; hypoglycemia (blood glucose 68 mg/dl) and normal C Reactive Protein. Arterial blood gases revealed severe lactic acidemia. The electrocardiogram showed sinus bradycardia, simple AV block, widened QRS with prominent T wave and prolonged QT. He was admitted to the Intensive Care Unit (ICU) with the suspicion of lactic acidosis associated with metformin, receiving fluid management, intravenous hypertonic glucose plus insulin and sodium bicarbonate, mechanical ventilation, vasopressor therapy, a temporary pacemaker lead, in addition to continuous venovenous hemodiafiltration. Two days later, the patient experienced a significant clinical improvement with normalization of the acid-base status, plasma lactate and potassium levels. On day 9, diuresis was recovered, creatinine and uremia returned to normal levels and the patient was discharged from the ICU. PMID:26005828

  18. Metabolic changes after urinary diversion.

    PubMed

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

    2011-01-01

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

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

    PubMed

    Herrero, Óscar; Planelló, Rosario; Morcillo, Gloria

    2015-06-01

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

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

    PubMed

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

    2011-10-01

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

  1. A Dynamic Model of Excitation-Contraction Coupling during Acidosis in Cardiac Ventricular Myocytes

    PubMed Central

    Crampin, Edmund J.; Smith, Nicolas P.

    2006-01-01

    Acidosis in cardiac myocytes is a major factor in the reduced inotropy that occurs in the ischemic heart. During acidosis, diastolic calcium concentration and the amplitude of the calcium transient increase, while the strength of contraction decreases. This has been attributed to the inhibition by protons of calcium uptake and release by the sarcoplasmic reticulum, to a rise of intracellular sodium caused by activation of sodium-hydrogen exchange, decreased calcium binding affinity to Troponin-C, and direct effects on the contractile machinery. The relative contributions and concerted action of these effects are, however, difficult to establish experimentally. We have developed a mathematical model to examine altered calcium-handling mechanisms during acidosis. Each of the alterations was incorporated into a dynamical model of pH regulation and excitation-contraction coupling to predict the time courses of key ionic species during acidosis, in particular intracellular pH, sodium and the calcium transient, and contraction. This modeling study suggests that the most significant effects are elevated sodium, inhibition of sodium-calcium exchange, and the direct interaction of protons with the contractile machinery; and shows how the experimental data on these contributions can be reconciled to understand the overall effects of acidosis in the beating heart. PMID:16473911

  2. “Damage Control” in Severely Injured Patients

    Microsoft Academic Search

    Marius Keel; Ludwig Labler; Otmar Trentz

    2005-01-01

    The concept of “damage control” is established in the\\u000amanagement of severely injured patients. This strategy\\u000asaves life by deferring repair of anatomic lesions and\\u000afocusing on restoring the physiology. The “lethal triad”\\u000ahypothermia, coagulopathy, and acidosis are physiological\\u000acriteria in the selection of injured patients for\\u000a”damage control”. Other criteria, such as scoring of injury\\u000aseverity or the time

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

    PubMed Central

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

    2012-01-01

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

  4. Severe hyperkalemia requiring hospitalization: predictors of mortality

    PubMed Central

    2012-01-01

    Introduction Severe hyperkalemia, with potassium (K+) levels ? 6.5 mEq/L, is a potentially life-threatening electrolyte imbalance. For prompt and effective treatment, it is important to know its risk factors, clinical manifestations, and predictors of mortality. Methods An observational cohort study was performed at 2 medical centers. A total of 923 consecutive Korean patients were analyzed. All were 19 years of age or older and were hospitalized with severe hyperkalemia between August 2007 and July 2010; the diagnosis of severe hyperkalemia was made either at the time of admission to the hospital or during the period of hospitalization. Demographic and baseline clinical characteristics at the time of hyperkalemia diagnosis were assessed, and clinical outcomes such as in-hospital mortality were reviewed, using the institutions' electronic medical record systems. Results Chronic kidney disease (CKD) was the most common underlying medical condition, and the most common precipitating factor of hyperkalemia was metabolic acidosis. Emergent admission was indicated in 68.6% of patients, 36.7% had electrocardiogram findings typical of hyperkalemia, 24.5% had multi-organ failure (MOF) at the time of hyperkalemia diagnosis, and 20.3% were diagnosed with severe hyperkalemia at the time of cardiac arrest. The in-hospital mortality rate was 30.7%; the rate was strongly correlated with the difference between serum K+ levels at admission and at their highest point, and with severe medical conditions such as malignancy, infection, and bleeding. Furthermore, a higher in-hospital mortality rate was significantly associated with the presence of cardiac arrest and/or MOF at the time of diagnosis, emergent admission, and intensive care unit treatment during hospitalization. More importantly, acute kidney injury (AKI) in patients with normal baseline renal function was a strong predictor of mortality, compared with AKI superimposed on CKD. Conclusions Severe hyperkalemia occurs in various medical conditions; the precipitating factors are similarly diverse. The mortality rate is especially high in patients with severe underlying disease, coexisting medical conditions, and those with normal baseline renal function. PMID:23171442

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

    E-print Network

    Vyduna, Jennifer Lynn

    2012-12-31

    , and BMI. Patient characteristics collected included gender, age, cause of renal failure, BMI class, months on hemodialysis, and subjective nutrition status. The variable of race/ethnic group was originally requested, however was excluded from analysis... to total sample size due to missing values 2 Race/ethnic group not included due to more than 50% missing data from the database 3 Percents do not always add up to 100 due to rounding 4 Subcategories based on Form CMS-2728-U3: List of Primary Causes of ESRD...

  6. 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

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

    2007-01-01

    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

  7. Ultrastructural study of the childhood mitochondrial myopathic syndrome associated with lactic acidosis

    Microsoft Academic Search

    Y. Kobayashi; S. Miyabayashi; G. Takada; K. Narisawa; K. Tada; T. Y. Yamamoto

    1982-01-01

    The quadriceps femoris muscle and the muscularis mucosae of the rectum from two children with mitochondrial myopathic syndrome associated with lactic acidosis were studied by electron microscopy. Striking morphological abnormalities of mitochondria were noted not only in the skeletal but also in the smooth muscle cells. Endothelial cells of blood capillaries distributed in these affected muscles were so greatly swollen

  8. Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer

    E-print Network

    Maini, Philip K.

    (DCIS) microenvironmental conditions demonstrate upregulated glucose transporter 1 (GLUT1) as adaptationCellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer RA Gatenby but not sufficient to produce invasive breast cancer because intraductal tumour growth is also constrained by hypoxia

  9. Nutritional Approaches to Minimize Subacute Ruminal Acidosis and Laminitis in Dairy Cattle

    Microsoft Academic Search

    W. C. Stone

    2004-01-01

    Lameness and subacute ruminal acidosis (SARA) both appear to be very prevalent throughout the US dairy industry. Reduced ruminal efficiency, liver and lung abscesses, and laminitis are all thought to be re- lated to SARA. Both the nutritionist and dairy manag- ers are responsible for the delivery and consumption of a ration that is likely to produce a ruminally healthy

  10. Basic research: Salt wasting in distal renal tubular acidosis-new look, old problem.

    PubMed

    Al-Awqati, Qais

    2013-12-01

    Acidosis affects sodium and potassium excretion, likely via the pH sensitivity of ion transporters. A recent paper shows that ?-intercalated cells with deleted H(+)-ATPase release ATP into urine, which induces the production of prostaglandin E2 (PGE2). PGE2 then reduces sodium absorption in the principal cells of the cortical collecting tubule and increases potassium secretion. PMID:24189652

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

    PubMed Central

    Stacy, B. D.; Wilson, B. W.

    1970-01-01

    1. Observations were made on the excretion of calcium and magnesium by the sheep's kidney following manipulation of the acid—base status. 2. Intravascular administration of a synthetic solution resembling saliva abolished the naturally occurring acidosis in sheep during feeding, and it also prevented the normal onset of post-prandial hypercalciuria and hypermagnesiuria. 3. Non-respiratory acidosis (induced by infusion of hydrochloric acid) and respiratory acidosis arising from inhalation of 6% (v/v) CO2 in air both caused an acute increase in calcium excretion. 4. Measurement of filtered loads showed that feeding exerted an effect on the functional characteristics of the sheep's kidney. The renal clearances of calcium and magnesium increased, whereas sodium clearance decreased. 5. Experimental conditions were arranged so that variations in acid—base status could be imposed at a time when the filtered load of calcium was declining. 6. With hydrochloric acid-acidosis the renal excretion of calcium increased, despite a steady fall in the filtered load. With sodium bicarbonate alkalosis, the filtered load and the renal excretion of calcium decreased in unison. 7. These variations in calcium excretion were not accompanied by corresponding changes in the excretion of sodium. 8. It is concluded that the renal tubules in the sheep are sensitive to acid—base status and that they respond to a lowering of the blood pH by decreasing the tubular reabsorption of filtered calcium. PMID:5499811

  12. The role of chemokines in severe malaria: more than meets the eye.

    PubMed

    Ioannidis, Lisa J; Nie, Catherine Q; Hansen, Diana S

    2014-04-01

    Plasmodium falciparum malaria is responsible for over 250 million clinical cases every year worldwide. Severe malaria cases might present with a range of disease syndromes including acute respiratory distress, metabolic acidosis, hypoglycaemia, renal failure, anaemia, pulmonary oedema, cerebral malaria (CM) and placental malaria (PM) in pregnant women. Two main determinants of severe malaria have been identified: sequestration of parasitized red blood cells and strong pro-inflammatory responses. Increasing evidence from human studies and malaria infection animal models revealed the presence of host leucocytes at the site of parasite sequestration in brain blood vessels as well as placental tissue in complicated malaria cases. These observations suggested that apart from secreting cytokines, leucocytes might also contribute to disease by migrating to the site of parasite sequestration thereby exacerbating organ-specific inflammation. This evidence attracted substantial interest in identifying trafficking pathways by which inflammatory leucocytes are recruited to target organs during severe malaria syndromes. Chemo-attractant cytokines or chemokines are the key regulators of leucocyte trafficking and their potential contribution to disease has recently received considerable attention. This review summarizes the main findings to date, investigating the role of chemokines in severe malaria and the implication of these responses for the induction of pathogenesis and immunity to infection. PMID:24476686

  13. Outcomes of Extremely Low Birth Weight Infants with Acidosis at Birth

    PubMed Central

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

    2014-01-01

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

  14. Transcriptional analysis of hnRNPA0, A1, A2, B1, and A3 in lung cancer cell lines in response to acidosis, hypoxia, and serum deprivation conditions.

    PubMed

    Romero-Garcia, Susana; Prado-Garcia, Heriberto; Lopez-Gonzalez, Jose Sullivan

    2014-02-01

    The ribonucleoproteins (hnRNPs) have important roles in multiple aspects of nucleic acid metabolism and in the regulation of different cellular processes. Abnormal expression of hnRNPs has been reported in several types of cancer including lung, pancreatic, and gastric carcinomas. Heterogenous tumor cell populations generate a tumor microenvironment that can present normoxic, hypoxic, or acidic regions. The analysis of hnRNP transcriptional responses considering the changing nature of the tumor microenvironment is important to understand tumor cell survival under stress conditions. We analyzed the transcriptional response of hnRNPA0, A1, A2, B1, and A3 in lung tumor cell lines under acidosis, hypoxia, and serum deprivation conditions. We used qRT-PCR to obtain a relative quantification of the hnRNPA/B transcript levels. We found that the hnRNPA2 transcript was the most abundant, followed by B1, A0, and A1. Expression of hnRNPA3 was the lowest, although its transcript levels were the most constant. hnRNPA/B transcript levels in lung tumor cell lines responded to changes in the microenvironment; however, hnRNPB1 transcript levels relative to hnRNPA2 expression did no change in all tested stress conditions, indicating that the alternative splicing between these isoforms was constant. hnRNPA1, A2, and B1 transcript levels were upregulated under serum deprivation conditions; possibly to promote a migration phenotype. Our data provide new insights into the transcriptional responses of ribonucleoproteins that might favor tumor cell survival and migration. PMID:24246049

  15. Metabolic Syndrome

    MedlinePLUS

    ... applies to a condition known as metabolic syndrome. Metabolic Syndrome Is an Early Warning Sign Metabolic syndrome isn' ... 2 diabetes down the road. What Exactly Is Metabolic Syndrome? Metabolic syndrome is a collection of problems that ...

  16. Risk Factors for Acute Kidney Injury in Severe Rhabdomyolysis

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    2012-01-01

    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

  18. Quiescence as a mechanism for cyclical hypoxia and acidosis.

    PubMed

    Smallbone, Kieran; Gavaghan, David J; Maini, Philip K; Brady, J Michael

    2007-11-01

    Tumour tissue characteristically experiences fluctuations in substrate supply. This unstable microenvironment drives constitutive metabolic changes within cellular populations and, ultimately, leads to a more aggressive phenotype. Previously, variations in substrate levels were assumed to occur through oscillations in the haemodynamics of nearby and distant blood vessels. In this paper we examine an alternative hypothesis, that cycles of metabolite concentrations are also driven by cycles of cellular quiescence and proliferation. Using a mathematical modelling approach, we show that the interdependence between cell cycle and the microenvironment will induce typical cycles with the period of order hours in tumour acidity and oxygenation. As a corollary, this means that the standard assumption of metabolites entering diffusive equilibrium around the tumour is not valid; instead temporal dynamics must be considered. PMID:17609956

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

    PubMed

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

    2008-08-01

    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

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

    PubMed

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

    2015-04-01

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

  1. Effects of the ionophores monensin and tetronasin on simulated development of ruminal lactic acidosis in vitro.

    PubMed Central

    Newbold, C J; Wallace, R J

    1988-01-01

    A continuous coculture of four ruminal bacteria, Megasphaera elsdenii, Selenomonas ruminantium, Streptococcus bovis, and Lactobacillus sp. strain LB17, was used to study the effects of the ionophores monensin and tetronasin on the changes in ruminal microbial ecology that occur during the onset of lactic acidosis. In control incubations, the system simulated the development of lactic acidosis in vivo, with an initial overgrowth of S. bovis when an excess of glucose was added to the fermentor. Lactobacillus sp. strain LB17 subsequently became dominant as pH fell and lactate concentration rose. Both ionophores were able to prevent the accumulation of lactic acid and maintain a healthy non-lactate-producing bacterial population when added at the same time as an excess of glucose. Tetronasin was more potent in this respect than monensin. When tetronasin was added to the culture 24 h after glucose, the proliferation of lactobacilli was reversed and a non-lactate-producing bacterial population developed, with an associated drop in lactate concentration in the fermentor. Rises in culture pH and volatile fatty acid concentrations accompanied these changes. Monensin was unable to suppress the growth of lactobacilli; therefore, in contrast to tetronasin, monensin added 24 h after the addition of glucose failed to reverse the acidosis. Numbers of lactobacilli and lactate concentrations remained high, whereas pH and volatile fatty acid concentrations were low. PMID:3223764

  2. Glycogen Storage Disease Type Ia: Linkage of Glucose, Glycogen, Lactic Acid, Triglyceride, and Uric Acid Metabolism

    PubMed Central

    Sever, Sakine; Weinstein, David A.; Wolfsdorf, Joseph I.; Gedik, Reyhan; Schaefer, Ernst J.

    2013-01-01

    Case Summary A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides > 5,000 mg/dl. The diagnosis of type 1A glycogen storage disease (GSD) was made by liver biopsy that showed increased glycogen and absent glucose-6-phosphatase enzyme activity. She was treated with dextrose feeding, which was replaced by frequent cornstarch feeding, with improvement of her metabolic parameters. At age 18 years she had marked hypertriglyceridemia (3,860 mg/dl) and eruptive xanthomas, and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels > 75 mg/dl and lactate levels < 2 mmol/L. After 15 months on this regimen, her lipids levels (measured in mg/dl) off all medications were: total cholesterol 222, triglycerides 179, high density lipoprotein cholesterol 32, and calculated low density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m2. Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels > 75 mg/dl is critical in the management of this disease. PMID:23312056

  3. Comparison of Malated Ringer's with Two Other Balanced Crystalloid Solutions in Resuscitation of Both Severe and Moderate Hemorrhagic Shock in Rats

    PubMed Central

    Keitel, Judith; Lendemans, Sven; de Groot, Herbert; Rohrig, Ricarda

    2015-01-01

    In preclinical treatment of polytraumatized patients crystalloids are preferentially used. To avoid metabolic acidosis, metabolizable anions like lactate or acetate are used to replace chloride in these solutions. We here studied the effects of malated Ringer's in resuscitation of both shock severities in comparison to lactated and acetated Ringer's. Male Wistar rats underwent severe (mean arterial blood pressure (MAP) of 25–30?mmHg) or moderate (MAP 40–45?mmHg) hemorrhagic shock. Adjacent to the shock period animals were resuscitated with acetated (AR), lactated (LR), or malated Ringer's (MR) and observed for 150?min. MR improved survival compared with LR and AR in severe hemorrhagic shock whereas it was equally effective to LR and superior to AR in moderate hemorrhagic shock. In all other parameters tested, MR was also effective similar to the other solutions under these conditions. We conclude that MR is preferable to AR and LR in resuscitation of hemorrhagic shock independent of shock depth. The positive effects of MR may stem from the absence of any adverse impact on energy metabolism under both conditions.

  4. Metabolic Syndrome

    MedlinePLUS

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

  5. The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism.

    PubMed

    Conde, Vanessa R; Oliveira, Pedro F; Nunes, Ana R; Rocha, Cátia S; Ramalhosa, Elsa; Pereira, José A; Alves, Marco G; Silva, Branca M

    2015-07-01

    Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. PMID:25907297

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

    PubMed

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

    2013-06-01

    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

  7. Mutations in GTPBP3 Cause a Mitochondrial Translation Defect Associated with Hypertrophic Cardiomyopathy, Lactic Acidosis, and Encephalopathy

    PubMed Central

    Kopajtich, Robert; Nicholls, Thomas J.; Rorbach, Joanna; Metodiev, Metodi D.; Freisinger, Peter; Mandel, Hanna; Vanlander, Arnaud; Ghezzi, Daniele; Carrozzo, Rosalba; Taylor, Robert W.; Marquard, Klaus; Murayama, Kei; Wieland, Thomas; Schwarzmayr, Thomas; Mayr, Johannes A.; Pearce, Sarah F.; Powell, Christopher A.; Saada, Ann; Ohtake, Akira; Invernizzi, Federica; Lamantea, Eleonora; Sommerville, Ewen W.; Pyle, Angela; Chinnery, Patrick F.; Crushell, Ellen; Okazaki, Yasushi; Kohda, Masakazu; Kishita, Yoshihito; Tokuzawa, Yoshimi; Assouline, Zahra; Rio, Marlène; Feillet, François; Mousson de Camaret, Bénédict; Chretien, Dominique; Munnich, Arnold; Menten, Björn; Sante, Tom; Smet, Joél; Régal, Luc; Lorber, Abraham; Khoury, Asaad; Zeviani, Massimo; Strom, Tim M.; Meitinger, Thomas; Bertini, Enrico S.; Van Coster, Rudy; Klopstock, Thomas; Rötig, Agnès; Haack, Tobias B.; Minczuk, Michal; Prokisch, Holger

    2014-01-01

    Respiratory chain deficiencies exhibit a wide variety of clinical phenotypes resulting from defective mitochondrial energy production through oxidative phosphorylation. These defects can be caused by either mutations in the mtDNA or mutations in nuclear genes coding for mitochondrial proteins. The underlying pathomechanisms can affect numerous pathways involved in mitochondrial physiology. By whole-exome and candidate gene sequencing, we identified 11 individuals from 9 families carrying compound heterozygous or homozygous mutations in GTPBP3, encoding the mitochondrial GTP-binding protein 3. Affected individuals from eight out of nine families presented with combined respiratory chain complex deficiencies in skeletal muscle. Mutations in GTPBP3 are associated with a severe mitochondrial translation defect, consistent with the predicted function of the protein in catalyzing the formation of 5-taurinomethyluridine (?m5U) in the anticodon wobble position of five mitochondrial tRNAs. All case subjects presented with lactic acidosis and nine developed hypertrophic cardiomyopathy. In contrast to individuals with mutations in MTO1, the protein product of which is predicted to participate in the generation of the same modification, most individuals with GTPBP3 mutations developed neurological symptoms and MRI involvement of thalamus, putamen, and brainstem resembling Leigh syndrome. Our study of a mitochondrial translation disorder points toward the importance of posttranscriptional modification of mitochondrial tRNAs for proper mitochondrial function. PMID:25434004

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

    PubMed

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

    2014-04-01

    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

  9. Effects of a reduced calcium, phosphorus and protein intake and of benzoic acid on calcium and phosphorus metabolism of growing pigs

    Microsoft Academic Search

    A. Gutzwiller; H. D. Hess; A. Adam; D. Guggisberg; A. Liesegang; P. Stoll

    2011-01-01

    In order to minimise environmental pollution, many pig feeds contain low phosphorus and protein concentrations as well as benzoic acid (BA), an additive which reduces ammonia formation in the slurry. Since both a low P intake and metabolic acidosis compromise bone mineralisation, the effect of a diet with a low concentration of calcium (Ca), phosphorus (P) and crude protein (CP)

  10. Severe exacerbations of chronic obstructive pulmonary disease: management with noninvasive ventilation on a general medicine ward

    Microsoft Academic Search

    Sirio Fiorino; Eugenio Detotto; Michele Battilana; Letizia Bacchi-Reggiani; Renzo Moretti; Furio Benfenati; Adriana Caselli; Serena Marchi; Maria R. Testi; Claudio G. Gallo; Andrea Cuppini; Giuseppe Kindt; Maurizio Moretti

    2010-01-01

    IntroductionRecent evidence suggests that, with a well-trained staff, severe exacerbations of chronic obstructive pulmonary disease (COPD) with moderate respiratory acidosis (pH > 7.3) can be successfully treated with noninvasive mechanical ventilation (NIMV) on a general respiratory care ward. We conducted an open prospective study to evaluate the efficacy of this approach on a general medicine ward.

  11. Concentrations of indoleamine metabolic intermediates in the ventricular cerebrospinal fluid of advanced Parkinson's patients with severe postural instability and gait disorders

    Microsoft Academic Search

    R. P. Iacono; S. M. Kuniyoshi; J. R. Ahlman; G. J. Zimmerman; G. Maeda; R. D. Pearlstein

    1997-01-01

    Summary Postural instability and gait disorders (PIGD) are the primary causes of disability in many but not all advanced Parkinson's disease (PD) patients. We have measured the concentrations of serotonin, 5-hydroxytryptophan (5-HTP), 5-hydroxy-3-indoleacetic acid (5-HIAA), and homovanillic acid (HVA) in samples of ventricular cerebrospinal fluid from ten PD patients with severe disability from PIGD and from ten PD patients with

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

    PubMed

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

    2014-04-15

    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

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

    PubMed Central

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

    2013-01-01

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

  14. Treatment of severe malaria.

    PubMed Central

    Warrell, D A

    1989-01-01

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

  15. Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment

    PubMed Central

    Justus, Calvin R.; Sanderlin, Edward J.; Yang, Li V.

    2015-01-01

    Cancer cells preferentially utilize glycolysis, instead of oxidative phosphorylation, for metabolism even in the presence of oxygen. This phenomenon of aerobic glycolysis, referred to as the “Warburg effect”, commonly exists in a variety of tumors. Recent studies further demonstrate that both genetic factors such as oncogenes and tumor suppressors and microenvironmental factors such as spatial hypoxia and acidosis can regulate the glycolytic metabolism of cancer cells. Reciprocally, altered cancer cell metabolism can modulate the tumor microenvironment which plays important roles in cancer cell somatic evolution, metastasis, and therapeutic response. In this article, we review the progression of current understandings on the molecular interaction between cancer cell metabolism and the tumor microenvironment. In addition, we discuss the implications of these interactions in cancer therapy and chemoprevention. PMID:25988385

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

    PubMed

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

    2015-01-01

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

  17. Metabolic neuropathies

    MedlinePLUS

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

  18. Metabolic Fluxes and Metabolic Engineering

    Microsoft Academic Search

    Gregory Stephanopoulos

    1999-01-01

    Metabolic engineering is the directed improvement of cellular properties through the modification of specific biochemical reactions or the introduction of new ones, with the use of recombinant DNA technology. As such, metabolic engineering emphasizes metabolic pathway integration and relies on metabolic fluxes as determinants of cell physiology and measures of metabolic control. The combination of analytical methods to quantify fluxes

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

    PubMed

    Santin, J M; Hartzler, L K

    2013-02-01

    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

  20. Dynorphin opioid peptides enhance acid sensing ion channel 1a activity and acidosis induced neuronal death

    PubMed Central

    Sherwood, Thomas W.; Askwith, Candice C

    2009-01-01

    Acid sensing ion channel 1a (ASIC1a) promotes neuronal damage during pathological acidosis. ASIC1a undergoes a process called steady-state desensitization in which incremental pH reductions desensitize the channel and prevent activation when the threshold for acid-dependent activation is reached. We find that Dynorphin A and Big Dynorphin limit steady-state desensitization of ASIC1a and acid-activated currents in cortical neurons. Dynorphin potentiation of ASIC1a activity is independent of opioid or bradykinin receptor activation but is prevented in the presence of PcTx1, a peptide which is known to bind the extracellular domain of ASIC1a. This suggests that dynorphins interact directly with ASIC1a to enhance channel activity. Inducing steady-state desensitization prevents ASIC1a-mediated cell death during prolonged acidosis. This neuroprotection is abolished in the presence of dynorphins. Together, these results define ASIC1a as a new, non-opioid, target for dynorphin action and suggest that dynorphins enhance neuronal damage following ischemia by preventing steady-state desensitization of ASIC1a. PMID:19906984

  1. D-Lactic Acidosis: An Underrecognized Complication of Short Bowel Syndrome

    PubMed Central

    Kowlgi, N. Gurukripa; Chhabra, Lovely

    2015-01-01

    D-lactic acidosis or D-lactate encephalopathy is a rare condition that occurs primarily in individuals who have a history of short bowel syndrome. The unabsorbed carbohydrates act as a substrate for colonic bacteria to form D-lactic acid among other organic acids. The acidic pH generated as a result of D-lactate production further propagates production of D-lactic acid, hence giving rise to a vicious cycle. D-lactic acid accumulation in the blood can cause neurologic symptoms such as delirium, ataxia, and slurred speech. Diagnosis is made by a combination of clinical and laboratory data including special assays for D-lactate. Treatment includes correcting the acidosis and decreasing substrate for D-lactate such as carbohydrates in meals. In addition, antibiotics can be used to clear colonic flora. Although newer techniques for diagnosis and treatment are being developed, clinical diagnosis still holds paramount importance, as there can be many confounders in the diagnosis as will be discussed subsequently. PMID:25977687

  2. Metabolism at Evolutionary Optimal States

    PubMed Central

    Rabbers, Iraes; van Heerden, Johan H.; Nordholt, Niclas; Bachmann, Herwig; Teusink, Bas; Bruggeman, Frank J.

    2015-01-01

    Metabolism is generally required for cellular maintenance and for the generation of offspring under conditions that support growth. The rates, yields (efficiencies), adaptation time and robustness of metabolism are therefore key determinants of cellular fitness. For biotechnological applications and our understanding of the evolution of metabolism, it is necessary to figure out how the functional system properties of metabolism can be optimized, via adjustments of the kinetics and expression of enzymes, and by rewiring metabolism. The trade-offs that can occur during such optimizations then indicate fundamental limits to evolutionary innovations and bioengineering. In this paper, we review several theoretical and experimental findings about mechanisms for metabolic optimization. PMID:26042723

  3. Metabolism at evolutionary optimal States.

    PubMed

    Rabbers, Iraes; van Heerden, Johan H; Nordholt, Niclas; Bachmann, Herwig; Teusink, Bas; Bruggeman, Frank J

    2015-01-01

    Metabolism is generally required for cellular maintenance and for the generation of offspring under conditions that support growth. The rates, yields (efficiencies), adaptation time and robustness of metabolism are therefore key determinants of cellular fitness. For biotechnological applications and our understanding of the evolution of metabolism, it is necessary to figure out how the functional system properties of metabolism can be optimized, via adjustments of the kinetics and expression of enzymes, and by rewiring metabolism. The trade-offs that can occur during such optimizations then indicate fundamental limits to evolutionary innovations and bioengineering. In this paper, we review several theoretical and experimental findings about mechanisms for metabolic optimization. PMID:26042723

  4. Amino acid profile in pyruvate carboxylase deficiency: Comparison with some other metabolic disorders

    Microsoft Academic Search

    C. Charpentier; J. M. Tetau; H. Ogier; J. M. Saudubray; F. X. Coude; A. Lemonnier

    1982-01-01

    Blood amino-acid patterns can be very similar in several disorders diagnosed in the neonatal period. In patients with lactic acidosis, we found abnormal profiles in two enzymopathies, pyruvate carboxylase (PC) and dihydrolipoyldehydrogenase deficiencies. The PC deficiency produced the most striking profile with citrulline and other amino acids increased. We have compared these results with urea cycle enzymopathies, glutaric aciduria type

  5. Zonation of gluconeogenesis, ketogenesis and intracellular pH in livers from normal and diabetic ketoacidotic rats: evidence for intralobular redistribution of metabolic events in ketoacidosis.

    PubMed Central

    Burns, S P; Cohen, R D; Iles, R A; Bailey, R A; Desai, M; Germain, J P; Going, T C

    1999-01-01

    The intralobular distribution of metabolism was examined in the livers from rats with severe diabetic ketoacidosis (DKA), perfused at pH 6.8, and compared with that in livers from normal starved animals perfused at either pH 7.4 or 6.8. With lactate and palmitate as substrates, the perivenous uptake of periportally synthesized glucose seen in normal livers at pH 7.4 was abolished during DKA; indeed, gluconeogenesis was most active in the perivenous region. Whereas in normal livers perfused at pH 7.4 the periportal region showed a markedly elevated intracellular pH (pH(i)) compared with the perivenous zone, this distribution of pH(i) was reversed in DKA, with an intermediate distribution in normal livers perfused at pH 6. 8. 3-Hydroxybutyrate was generated throughout the lobule. Some acetoacetate generated periportally was converted to 3-hydroxybutyrate more perivenously. A steep gradient of oxygen uptake along the radius of the lobule was apparent in all three groups; oxygen uptake was greatly decreased perivenously despite adequate oxygen supply. These findings are consistent with our previous observations of the lobular co-location of high pH(i) and gluconeogenesis, and might offer an explanation of how high gluconeogenic rates can continue in spite of severe systemic acidosis in DKA. The findings provide direct evidence for a marked redistribution of intralobular metabolism in DKA. PMID:10493939

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

    PubMed Central

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

    1998-01-01

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

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

    Microsoft Academic Search

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

    2006-01-01

    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

  8. Clinical features and risk factors of lactic acidosis following long-term antiretroviral therapy: 4 fatal cases.

    PubMed

    ter Hofstede, H J; de Marie, S; Foudraine, N A; Danner, S A; Brinkman, K

    2000-09-01

    Our objective was to describe clinical features and predisposing factors attributed to lactic acidosis in 4 HIV-infected patients on long-term nucleoside reverse transcriptase inhibitor (NRTI) therapy. All patients had received at least 6-20 months of NRTI-containing antiretroviral therapy: all used stavudine (d4T), in one combined with lamivudine (3TC), in the other 3 with didanosine (ddI); in one hydroxyurea was added. In all, the initial symptoms were gastrointestinal (nausea and vomiting), followed by tachypnoea preceding the lactic acidosis; death followed 6-22 days after admission (liver failure and uncontrollable arrhythmias). Treatment with riboflavin was unsuccessful in one patient. The only definite risk factor in all cases was NRTI-induced mitochondrial toxicity; one patient was concomitantly treated for Kaposi's sarcoma (with bleomycin and vinblastine) and one just recovered from pneumococcal sepsis. None of the patients had a history of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. In all patients, some sort of toxicity to other previously used NRTIs had occurred earlier. Lactic acidosis occurred after months of NRTI therapy in patients who had already suffered other forms of NRTI toxicity. Concomitant diseases or comedication might have aggravated the mitochondrial toxicity of the NRTIs. Screening methods to detect mitochondrial toxicity are necessary, since lactic acidosis occurs rather unexpectedly, with a rapid, fatal course. PMID:10997508

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. The definition of acidosis in dairy herds predominantly fed on pasture and concentrates.

    PubMed

    Bramley, E; Lean, I J; Fulkerson, W J; Stevenson, M A; Rabiee, A R; Costa, N D

    2008-01-01

    This cross-sectional survey examined the prevalence of ruminal acidosis and the effects of acidosis on the production of dairy cattle. Eight fresh cows, 3 primiparous and 5 multiparous (< 100 d in milk), were selected randomly from each of 100 dairy herds in 5 regions of Australia. Rumen fluid was obtained from each cow by rumenocentesis and a stomach tube, and samples were tested for pH. Stomach tube rumen fluid samples were analyzed for volatile fatty acid, ammonia, and D-lactate concentrations. On the basis of the results of all assays, cows were categorized into 3 distinct categories (categories 1, 2, and 3) by cluster analysis. The percentages of cattle in categories 1, 2, and 3 were 10.2, 29.9, and 59.9%, respectively. Mean rumen pH for categories 1, 2, and 3 were 5.74 +/- 0.47, 6.18 +/- 0.44, and 6.33 +/- 0.43, respectively. Biochemically, categories 1, 2, and 3 were characterized, respectively, as follows: mean total VFA concentration (mM), 100.74 +/- 23.22, 94.79 +/- 18.13, and 62.81 +/- 15.65; mean ammonia concentration (mM), 2.46 +/- 2.02, 7.79 +/- 3.75, and 3.64 +/- 2.03; and mean D-lactate concentration (mM), 0.34 +/- 0.86, 0.28 +/- 0.97, and 0.12 +/- 0.51. Category 1 cows had higher propionate, valerate, isovalerate, and caproate concentrations and were of lower parity than cows in other categories. Cows in category 1 had higher milk production but lower milk fat content than category 2 cows. Herds were assigned to 1 of 3 groups according to the numbers of cows assigned to each category. Herds with > or = 3 of the 8 cows in category 1 were classified as acidotic. Herds with > or = 3 of the 8 cows in category 2 were classified as having suboptimal rumen function, and herds with > or = 3 of the 8 cows in category 3 were classified as normal. Herds that had 3 or more of the 8 cows in category 1 (acidotic herds) had diets with higher energy and nonfiber carbohydrate contents and a lower neutral detergent fiber content than herds with a high prevalence of category 2 or 3 cows. The lack of significance of a herd effect in the statistical models developed suggests that the categories were robust across production systems, in which diets varied from all pasture to total mixed rations. A point prevalence of 10% (95% credible interval, 8 to 12%) of cows with an acidotic profile indicates a high risk for acidosis in the cattle sampled. The higher nonfiber carbohydrate and lower neutral detergent fiber contents of diets for herds with a high prevalence of category 1 cows (acidotic herds) indicates that there may be opportunities to reduce the risk of acidosis by dietary manipulation. PMID:18096953

  11. Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise

    Microsoft Academic Search

    Hyerang Kim; Saningun Lee; Ryowon Choue

    2011-01-01

    Background  High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen\\u000a and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle\\u000a mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Eight elite Korean bodybuilders within the age from

  12. Evolution of Metabolism

    NASA Astrophysics Data System (ADS)

    Nealson, K. H.; Rye, R.

    2003-12-01

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

  13. Predicting the risk of metabolic acidosis for newborns based on fetal heart rate signal classification using support vector machines

    Microsoft Academic Search

    George Georgoulas; D. Stylios; Peter P. Groumpos

    2006-01-01

    Cardiotocography is the main method used for fetal assessment in everyday clinical practice for the last 30 years. Many attempts have been made to increase the effectiveness of the evaluation of cardiotocographic recordings and minimize the variations of their interpretation utilizing technological advances. This research work proposes and focuses on an advanced method able to identify fetuses compromised and suspicious

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

    SciTech Connect

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

    1992-12-31

    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.

  15. Epigenetics and metabolism.

    PubMed

    Keating, Samuel T; El-Osta, Assam

    2015-02-13

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

  16. Dysregulated lipid metabolism in cancer

    PubMed Central

    Zhang, Feng; Du, Guangwei

    2012-01-01

    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

  17. Metabolic syndrome

    MedlinePLUS

    Metabolic syndrome is a name for a group of risk factors that occur together and increase the chance ... Metabolic syndrome is becoming very common in the United States. Doctors are not sure whether the syndrome is ...

  18. Metabolic Syndrome

    MedlinePLUS

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These ... doctors agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

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

    PubMed Central

    2013-01-01

    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

  20. Mechanism of oxidative stress-induced intracellular acidosis in rat cerebellar astrocytes and C6 glioma cells.

    PubMed Central

    Tsai, K L; Wang, S M; Chen, C C; Fong, T H; Wu, M L

    1997-01-01

    1. Following ischaemic reperfusion, large amounts of superoxide anion (.O2-), hydroxyl radical (.OH) and H2O2 are produced, resulting in brain oedema and changes in cerebral vascular permeability. We have found that H2O2 (100 microM) induces a significant intracellular acidosis in both cultured rat cerebellar astrocytes (0.37 +/- 0.04 pH units) and C6 glioma cells (0.33 +/- 0.07 pH units). 2. Two membrane-crossing ferrous iron chelators, phenanthroline and deferoxamine, almost completely inhibited H2O2-induced intracellular acidosis, while the non-membrane-crossing iron chelator apo-transferrin had no effect. Furthermore, the acidosis was completely inhibited by two potent membrane-crossing .OH scavengers, N-(2-mercaptopropionyl)-glycine (N-MPG) and dimethyl thiourea (DMTU). Since .OH can be produced during iron-catalysed H2O2 breakdown (Fenton reaction), we have shown that a large reduction in pH1 in glial cells can result from the production of intracellular .OH via H2O2 oxidation. 3. We have ruled out the possible involvement of: (i) an increase in intracellular Ca2+ levels; and (ii) inhibition of oxidative phosphorylation. 4. Our results suggest that .OH inhibits glycolysis, leading to ATP hydrolysis and intracellular acidosis. This conclusion is based on the following observations: (i) in glucose-free medium, or in the presence of iodoacetate or 2-deoxy-D-glucose, H2O2-induced acidosis is completely suppressed; (ii) H2O2 and iodoacetate both produce an increase in levels of intracellular free Mg2+, an indicator of ATP breakdown; and (iii) direct measurement of intracellular ATP levels and lactate production show 50 and 55% reductions in ATP content and lactate production, respectively, following treatment with 100 microM H2O2. 5. Inhibition of the pH1 regulators (i.e. the Na(+)-H+ exchange and possibly the Na(+)-HCO3(-)-dependent pH1 transporters) resulting from H2O2-induced intracellular ATP reduction may also be involved in the H2O2-evoked intracellular acidosis in glial cells. PMID:9234204

  1. Metabolic Syndrome

    MedlinePLUS

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

  2. Psoriasis and Metabolic Syndrome

    PubMed Central

    Malkic Salihbegovic, Eldina; Hadzigrahic, Nermina; Cickusic, Amra Jakubovic

    2015-01-01

    Introduction: Psoriasis is a chronic skin ailment which can be connected with an increased occurrence of other illnesses, including the metabolic syndrome. Examinees and methods: A prospective study has been conducted which included 70 patients affected by psoriasis, both genders, older than 18 years. Average age being 47,14 (SD=±15,41) years, from that there were 36 men or 51,43 and 34 women or 48,57%. The average duration of psoriasis was 15,52 (SD= ±12,54) years. For purposes of diagnosing the metabolic syndrome, the criteria of National Cholesterol Education Program Adult Treatment Panel III, (NCEP ATP III) were used. For purposes of detecting the severity and spread of psoriasis, Psoriasis Area and Severity Index (PASI) was used. Results: The incidence of metabolic syndrome in patients with psoriasis was 38,57%. Average values of PASI score were 16,65. The increase in values of PASI score and metabolic syndrome were statistically highly connected. (r=0,3, p=0,0001). Conclusion: Psoriasis is connected with metabolic syndrome, there is a positive correlation between the severity of psoriasis and frequency of metabolic syndrome. PMID:26005254

  3. Effects of sodium bicarbonate on striated muscle metabolism and intracellular pH during endotoxic shock.

    PubMed

    Bollaert, P E; Robin-Lherbier, B; Mallie, J P; Nace, L; Escanye, J M; Larcan, A

    1994-03-01

    The effects of HCO3Na load on acid-base balance and muscle intracellular bioenergetics have been investigated using 31P-magnetic resonance spectroscopy in an experimental model of endotoxinic shock. Anesthetized, mechanically ventilated, and paralyzed rats (n = 16) were given an intravenous bolus of Escherichia coli lipopolysaccharide (15 mg/kg). When shock was established they were randomly assigned to receive either HCO3Na intravenously (2 mmol/kg in 2 min) or an equimolar saline injection. Lipopolysaccharide induced a significant decrease in the levels of mean arterial pressure (58 +/- 6 vs. 120 +/- 8 mmHg), arterial pH (7.20 +/- .03 vs. 7.35 +/- .01), intracellular pH (6.86 +/- .04 vs. 7.08 +/- .01), a marked hyperlactatemia (7 +/- 3 vs. 1.2 +/- .2 mmol/L) and a drop in the phosphocreatine-inorganic phosphate ratio. In the bicarbonate-loaded rats, mean arterial pressure further decreased whereas it remained unchanged in the saline group. Bicarbonate increased arterial pH and PaCO2 transiently. In the saline group, arterial pH decreased and PaCO2 remained stable. In both groups, intracellular pH and high energy phosphates had a similar evolution. In this model of septic shock, partial correction of arterial pH using HCO3Na did not reduce the metabolic cellular injury in skeletal muscle. Based on these results, HCO3Na may be of limited therapeutic value in severe septic metabolic acidosis. PMID:7735951

  4. Anaerobic Metabolism 1 ANAEROBIC METABOLISM

    E-print Network

    Prestwich, Ken

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

  5. Effect of acidosis on IL8 and MCP-1 during hypoxia and reoxygenation in human NT2-N neurons

    Microsoft Academic Search

    Elisabeth Frøyland; Elena Didenko Pedersen; Anne-Katrine Kvissel; Runar Almaas; Anne Pharo; Bjørn Steen Skålhegg; Tom Eirik Mollnes; Terje Rootwelt

    2006-01-01

    Inflammation probably plays a significant role in perinatal brain injury. To study the contribution of locally produced cytokines, the effect on cell death of addition of IL-8 and MCP-1 or antibodies to these, and the impact of acidosis, human postmitotic NT2-N neurons were exposed to 3 h of hypoxia and glucose deprivation and reoxygenated for 21 h. After 3 h of hypoxia with

  6. Alternate-Sided Homonymous Hemianopia as the Solitary Presentation of Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-Like Episodes Syndrome

    Microsoft Academic Search

    Wan-Ya Su; Ling-Yuh Kao; Sien-Tsong Chen

    Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome has various presentations. We report on a case of MELAS in which alternate-sided homonymous hemianopia was the main symptom of recurrent neurological defects. A 19- year-old woman suffered from blurred vision, headaches, vomiting, and fever that subsided within days. The ophthalmic examination demonstrated right homonymous hemianopia. One month later a similar

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

    PubMed Central

    2010-01-01

    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

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

    PubMed Central

    2014-01-01

    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

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

    PubMed

    Raithatha, Ajay H; Bryden, Daniele C

    2012-01-01

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

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

    PubMed Central

    Raithatha, Ajay H.; Bryden, Daniele C.

    2012-01-01

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

  11. Acidosis or inorganic phosphate enhances the length dependence of tension in rat skinned cardiac muscle

    PubMed Central

    Fukuda, Norio; O-Uchi, Jin; Sasaki, Daisuke; Kajiwara, Hidetoshi; Ishiwata, Shin'ichi; Kurihara, Satoshi

    2001-01-01

    We investigated the effect of acidosis on the sarcomere length (SL) dependence of tension generation, in comparison with the effect of inorganic phosphate (Pi), in rat skinned ventricular trabeculae. The shift of the mid-point of the pCa-tension relationship associated with an increase in SL from 1.9 to 2.3 ?m (?pCa50) was studied.Decreasing pH from 7.0 to 6.2 lowered maximal and submaximal Ca2+-activated tension and increased ?pCa50 in a pH-dependent manner (from 0.21 ± 0.01 to 0.30 ± 0.01 pCa units). The addition of Pi (20 mm) decreased maximal tension and enhanced the SL dependence, both to a similar degree as observed when decreasing pH to 6.2 (?pCa50 increased from 0.20 ± 0.01 to 0.29 ± 0.01 pCa units).Further experiments were performed using 6 % (w/v) Dextran T-500 (molecular weight ?500 000) to osmotically reduce interfilament lattice spacing (SL, 1.9 ?m). Compared with that at pH 7.0, in the absence of Pi the increase in the Ca2+ sensitivity of tension induced by osmotic compression was enhanced at pH 6.2 (0.18 ± 0.01 vs. 0.25 ± 0.01 pCa units) or in the presence of 20 mm Pi (0.17 ± 0.01 vs. 0.24 ± 0.01 pCa units).H+, as well as Pi, has been reported to decrease the number of strongly binding cross-bridges, which reduces the co-operative activation of the thin filament and increases the pool of detached cross-bridges available for interaction with actin. It is therefore considered that during acidosis, the degree of increase in the number of force-generating cross-bridges upon reduction of interfilament lattice spacing is enhanced, resulting in greater SL dependence of tension generation.Our results suggest that the Frank-Starling mechanism may be enhanced when tension development is suppressed due to increased H+ and/or Pi under conditions of myocardial ischaemia or hypoxia. PMID:11579165

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

    PubMed Central

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

    2014-01-01

    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

  13. Metabolic cutis laxa syndromes.

    PubMed

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

    2011-08-01

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

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

    PubMed Central

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

    2012-01-01

    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

  15. Short communication: Effect of subacute ruminal acidosis on in situ fiber digestion in lactating dairy cows.

    PubMed

    Krajcarski-Hunt, H; Plaizier, J C; Walton, J P; Spratt, R; McBride, B W

    2002-03-01

    Subacute ruminal acidosis (SARA) was induced by replacing 25% of the total mixed ration intake [dry matter (DM) basis] with pellets consisting of 50% wheat and 50% barley. This reduced dietary forage content (DM basis) from 39.7 to 29.8% and increased the dietary concentrate content from 60.3 to 70.2%. Induction of SARA reduced the 24- and 48-h in situ neutral detergent fiber (NDF) degradabilities of grass hay numerically from 31.5% to 24.6% (P = 0.29) and from 51.3% to 36.9% (P < 0.05), respectively. The 24- and 48-h in situ NDF degradabilities of legume hay were reduced from 35.3 to 26.3% (P < 0.05) and from 49.0 to 35.8% (P < 0.05), respectively. The 24- and 48-h in situ NDF degradabilities of corn silage were reduced from 44.0 to 37.2% (P < 0.05) and from 56.1 to 44.8% (P < 0.05), respectively. This study suggests that induction of SARA by excess feeding of wheat/barley pellets reduces the rumen digestion of NDF from grass hay, legume hay, and corn silage. PMID:11949861

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

    PubMed Central

    Yoshida, S.

    1994-01-01

    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

  17. Metabolic syndrome.

    PubMed

    Cho, L W

    2011-11-01

    Metabolic syndrome is a clustering of different risk factors that collectively increases the risk of developing cardiovascular disease and type 2 diabetes mellitus. The syndrome itself is associated with various metabolic abnormalities, including insulin resistance, non-alcoholic fatty liver disease, obstructive sleep apnoea, male hypogonadism and polycystic ovary syndrome. This review aims to discuss recent developments related to the syndrome, including the associated metabolic complications and goals for therapeutic strategies. PMID:22173246

  18. Metabolic myopathies

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

    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.

  19. Structural control of metabolic flux.

    PubMed

    Sajitz-Hermstein, Max; Nikoloski, Zoran

    2013-01-01

    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

  20. Impaired trafficking of human kidney anion exchanger (kAE1) caused by hetero-oligomer formation with a truncated mutant associated with distal renal tubular acidosis.

    PubMed Central

    Quilty, Janne A; Cordat, Emmanuelle; Reithmeier, Reinhart A F

    2002-01-01

    Autosomal dominant distal renal tubular acidosis (dRTA) has been associated with several mutations in the anion exchanger AE1 gene. The effect of an 11-amino-acid C-terminal dRTA truncation mutation (901 stop) on the expression of kidney AE1 (kAE1) and erythroid AE1 was examined in transiently transfected HEK-293 cells. Unlike the wild-type proteins, kAE1 901 stop and AE1 901 stop mutants exhibited impaired trafficking from the endoplasmic reticulum to the plasma membrane as determined by immunolocalization, cell-surface biotinylation, oligosaccharide processing and pulse-chase experiments. The 901 stop mutants were able to bind to an inhibitor affinity resin, suggesting that these mutant membrane proteins were not grossly misfolded. Co-expression of wild-type and mutant kAE1 or AE1 resulted in intracellular retention of the wild-type proteins in a pre-medial Golgi compartment. This dominant negative effect was due to hetero-oligomer formation of the mutant and wild-type proteins. Intracellular retention of kAE1 in the alpha-intercalated cells of the kidney would account for the impaired acid secretion into the urine characteristic of dRTA. PMID:12227829

  1. Genetic investigation of autosomal recessive distal renal tubular acidosis: evidence for early sensorineural hearing loss associated with mutations in the ATP6V0A4 gene.

    PubMed

    Vargas-Poussou, Rosa; Houillier, Pascal; Le Pottier, Nelly; Strompf, Laurence; Loirat, Chantal; Baudouin, Véronique; Macher, Marie-Alice; Déchaux, Michèle; Ulinski, Tim; Nobili, François; Eckart, Philippe; Novo, Robert; Cailliez, Mathilde; Salomon, Rémi; Nivet, Hubert; Cochat, Pierre; Tack, Ivan; Fargeot, Anne; Bouissou, François; Kesler, Gwenaelle Roussey; Lorotte, Stéphanie; Godefroid, Nathalie; Layet, Valérie; Morin, Gilles; Jeunemaître, Xavier; Blanchard, Anne

    2006-05-01

    Mutations in the ATP6V1B1 and ATP6V0A4 genes, encoding subunits B1 and 4 of apical H(+) ATPase, cause recessive forms of distal renal tubular acidosis (dRTA). ATP6V1B mutations have been associated with early sensorineural hearing loss (SNHL), whereas ATP6V0A4 mutations are classically associated with either late-onset SNHL or normal hearing. The phenotype and genotype of 39 new kindreds with recessive dRTA, 18 of whom were consanguineous, were assessed. Novel and known loss-of-function mutations were identified in 31 kindreds. Fourteen new and five recurrent mutations of the ATP6V0A4 gene were identified in 21 families. For the ATP6V1B1 gene, two new and two previously described mutations were identified in 10 families. Surprisingly, seven probands with ATP6V0A4 gene mutations developed severe early SNHL between the ages of 2 mo and 10 yr. No mutation was detected in eight families. These data extend the spectrum of disease-causing mutations and provide evidence for genetic heterogeneity in SNHL. The data also demonstrate that mutations in either of these genes may cause early deafness, and they highlight the importance of genetic screening for recessive forms of dRTA independent of hearing status. PMID:16611712

  2. Peracute onset of severe tumor lysis syndrome immediately after 4 Gy fractionated TBI as part of reduced intensity preparative regimen in a patient with T-ALL with high tumor burden.

    PubMed

    Linck, D; Basara, N; Tran, V; Vucinic, V; Hermann, S; Hoelzer, D; Fauser, A A

    2003-05-01

    We report a 30-year-old patient with therapy-refractory T-ALL undergoing unrelated allogeneic PBSCT. He developed severe tumor lysis syndrome (TLS) with extreme biochemical changes, cardiac and neurological symptoms and dialysis-dependent acute renal failure after TBI (4 Gy) on the first day of reduced intensity conditioning (RIC) for unrelated allogeneic PBSCT. The patient's clinical condition was stabilized after beginning daily hemodialysis and treatment for disturbed electrolytes, metabolic acidosis and plasma coagulation, as well as reduction of uric acid by rasburicase. The conditioning therapy and the allogenic PBSCT were scheduled according to the preparative regimen. According to our knowledge, severe TLS induced by 4 Gy TBI has not been reported so far. Regimen-related toxicity using RIC regimen was mild, allowing 30-50% of the patients to have an entirely outpatient transplantation. However, we would like to point out that severe TLS could also complicate PBSCT using RIC regimens in patients with relatively radiation-sensitive malignancies and high tumor burden. PMID:12748673

  3. Nutritional Management of Metabolic Disorders

    Microsoft Academic Search

    JOE D. PAGAN

    2009-01-01

    I N T R O D U C T I O N Several metabolic disorders are common in modern breeds of horses. Many of these disorders such as equine Cushing's disease (ECD), equine metabolic syndrome (EMS), osteochondritis dissecans (OCD), recur- rent equine rhabdomyolysis (RER), and polysaccharide storage myopathy (PSSM) can be managed nutritionally by careful regulation of caloric intake with

  4. Gut Microbiota and Metabolic Disorders

    PubMed Central

    Hur, Kyu Yeon

    2015-01-01

    Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders.

  5. Metabolic engineering

    Microsoft Academic Search

    J. Nielsen

    2001-01-01

    Metabolic engineering has developed as a very powerful approach to optimising industrial fermentation processes through the introduction of directed genetic changes using recombinant DNA technology. Successful metabolic engineering starts with a careful analysis of cellular function; based on the results of this analysis, an improved strain is designed and subsequently constructed by genetic engineering. In recent years some very powerful

  6. Severe Weather

    NSDL National Science Digital Library

    National Science Teachers Association (NSTA)

    2005-04-01

    Meteorologists disagree as to what constitutes severe weather. However, most concur that thunderstorms, tornadoes, and hurricanes, all considered to be "convective" weather, fit the definition of severe weather, which is a weather condition likely to cause hardship. This science guide will explore each of the three weather phenomena. By virtue of their locations, most students are familiar with at least one of the three severe weather events. Students who tour the web sites will have an opportunity to make connections between the familiar and the perhaps less understood weather events.

  7. Oxygen-deficient metabolism and corneal edema

    PubMed Central

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

    2014-01-01

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

  8. Severe Storms

    NSDL National Science Digital Library

    2010-01-01

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

  9. Sever's Disease

    MedlinePLUS

    ... pretty frightening, Sever's disease is really a common heel injury that occurs in kids. It can be ... inflammation (swelling) of the growth plate in the heel. A growth plate, also called an epiphyseal plate, ...

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

    PubMed

    Katnik, Christopher; Cuevas, Javier

    2014-01-01

    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

  11. Kidney stone inhibitors in patients with renal stones and endemic renal tubular acidosis in northeast Thailand.

    PubMed

    Nakagawa, Yasushi; Carvalho, Mauricio; Malasit, Prida; Nimmannit, Sumalee; Sritippaywan, Suchai; Vasuvattakul, Somkiat; Chutipongtanate, Somchai; Chaowagul, Vipada; Nilwarangkur, Sanga

    2004-05-01

    Distal renal tubular acidosis (dRTA) is generally associated with hypercalciuria, hypocitraturia, and nephrolithiasis. Our intention was to study glycosaminoglycans (GAGS) and nephrocalcin (NC), two well-known crystal growth inhibitors, in a population with endemic dRTA and nephrolithiasis in northeast (NE) Thailand. We studied 13 patients, six with dRTA and seven with nephrolithiasis with normal or undefined acidification function. Six healthy adults living in the same area as the patients and another six from the Bangkok (BKK) area were used as controls. We measured urinary pH, ammonia, calcium, citrate, magnesium, oxalate, potassium, sodium and uric acid. GAGS were determined by an Alcian blue precipitation method and were qualitated by agarose gel electrophoresis after being isolated using 5% cetyltrimethylammonium bromide at pH 6.0. NC isoforms were isolated as previously described by Nakagawa et al. Citrate was higher in BKK controls ( p<0.04). There was a striking difference among GAGS from BKK when compared with other groups (103.85+/-10.70 vs. 23.52+/-8.11 for dRTA, 22.36+/-14.98 for kidney stone patients and 14.73+/-2.87 mg/ml in controls from the NE region, ( p<0.0001). dRTA and stone-forming patients excrete proportionally more (C+D) than (A+B) NC isoforms ( p<0.05). Also, their NC showed a 100-fold weaker binding capacity of calcium oxalate monohydrate crystals. The ratio of chondroitin sulfate/heparin sulfate in GAGS was approximately 9/1. In addition to the traditional risk factors for nephrolithiasis in dRTA, GAGS and NC might play an important role in the pathogenesis of stone formation in this population. PMID:14758448

  12. Risk factors for mortality in children with diabetic keto acidosis from developing countries

    PubMed Central

    Poovazhagi, Varadarajan

    2014-01-01

    Diabetic keto acidosis (DKA) is the major cause for mortality in children with Diabetes mellitus (DM). With increasing incidence of type 1 DM worldwide, there is an absolute increase of DM among children between 0-14 year age group and overall incidence among less than 30 years remain the same. This shift towards younger age group is more of concern especially in developing countries where mortality in DKA is alarmingly high. Prior to the era of insulin, DKA was associated with 100% mortality and subsequently mortality rates have come down and is now, 0.15%-0.31% in developed countries. However the scenario in developing countries like India, Pakistan, and Bangladesh are very different and mortality is still high in children with DKA. Prospective studies on DKA in children are lacking in developing countries. Literature on DKA related mortality are based on retrospective studies and are very recent from countries like India, Pakistan and Bangladesh. There exists an urgent need to understand the differences between developed and developing countries with respect to mortality rates and factors associated with increased mortality in children with DKA. Higher mortality rates, increased incidence of cerebral edema, sepsis, shock and renal failure have been identified among DKA in children from developing countries. Root cause for all these complications and increased mortality in DKA could be delayed diagnosis in children from developing countries. This necessitates creating awareness among parents, public and physicians by health education to identify symptoms of DM/DKA in children, in order to decrease mortality in DKA. Based on past experience in Parma, Italy it is possible to prevent occurrence of DKA both in new onset DM and in children with established DM, by simple interventions to increase awareness among public and physicians. PMID:25512799

  13. Early hemorrhage triggers metabolic responses that build up during prolonged shock.

    PubMed

    D'Alessandro, Angelo; Moore, Hunter B; Moore, Ernest E; Wither, Matthew; Nemkov, Travis; Gonzalez, Eduardo; Slaughter, Anne; Fragoso, Miguel; Hansen, Kirk C; Silliman, Christopher C; Banerjee, Anirban

    2015-06-15

    Metabolic staging after trauma/hemorrhagic shock is a key driver of acidosis and directly relates to hypothermia and coagulopathy. Metabolic responses to trauma/hemorrhagic shock have been assayed through classic biochemical approaches or NMR, thereby lacking a comprehensive overview of the dynamic metabolic changes occurring after shock. Sprague-Dawley rats underwent progressive hemorrhage and shock. Baseline and postshock blood was collected, and late hyperfibrinolysis was assessed (LY30 >3%) in all of the tested rats. Extreme and intermediate time points were collected to assay the dynamic changes of the plasma metabolome via ultra-high performance liquid chromatography-mass spectrometry. Sham controls were used to determine whether metabolic changes could be primarily attributable to anesthesia and supine positioning. Early hemorrhage-triggered metabolic changes that built up progressively and became significant during sustained hemorrhagic shock. Metabolic phenotypes either resulted in immediate hypercatabolism, or late hypercatabolism, preceded by metabolic deregulation during early hemorrhage in a subset of rats. Hemorrhagic shock consistently promoted hyperglycemia, glycolysis, Krebs cycle, fatty acid, amino acid, and nitrogen metabolism (urate and polyamines), and impaired redox homeostasis. Early dynamic changes of the plasma metabolome are triggered by hemorrhage in rats. Future studies will determine whether metabolic subphenotypes observed in rats might be consistently observed in humans and pave the way for tailored resuscitative strategies. PMID:25876652

  14. The acidosis-induced right shift of the HbO2 dissociation curve is maintained during erythrocyte storage

    PubMed Central

    Opdahl, Helge; Strømme, Tæwje A; Jørgensen, Lise; Bajelan, Livia; Heier, Hans E

    2011-01-01

    Background and objectives. In fresh blood, tissue hypoxia increases microcirculatory acidosis, which enhances erythrocyte O2 unloading and increases the amount of available O2. Storage of eryfhrocytes increases the HbO2 affinity and reduces O2 unloading. We examined the development of the affinity change during a period of 5 weeks of storage by present blood bank standards, and investigated to what extent acidosis offsets the affinity change. Materials and methods. Blood from volunteer donors was processed and stored as erythrocyte concentrates (EC). At 2–5 day intervals, EC were drawn from the bags and suspended in plasma and crystalloids to an Hb ? 10 g/dL. The suspensions were adjusted to give a pH of 7.40, 7.10, 6.80 or 6.30 and equilibrated with different gas mixtures to SO2 0, 25, 50, 75 and 100%. Measurements of the PO2/SO2 pairs at each pH were used to calculate the position of the HbO2 curve and its P50 value. Results. A significant leftward shift in the HbO2 curve was established after 1 week of storage; after 2.5 weeks only minor further changes were observed. Acidification right-shifted the HbO2 curve, after 2.5 weeks of storage the curve at pH 7.10 was similar to that for fresh blood at pH 7.40. Calculations of extractable O2 showed that the left-shifted HbO2 curve of stored EC could be advantageous at a low arterial PO2. Conclusions. The rightward shift of the HbO2 curve due to acidosis is well maintained in stored eryfhrocytes, a moderate pH decrease offsets the storage-induced increased HbO2 affinity. PMID:21476827

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2008-01-01

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

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

    PubMed Central

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

    2014-01-01

    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

  18. Imaging metabolic syndrome

    PubMed Central

    Han, Weiping; Chuang, Kai-Hsiang; Chang, Young-Tae; Olivo, Malini; Velan, S Sendhil; Bhakoo, Kishore; Townsend, David; Radda, George K

    2010-01-01

    Metabolic syndrome is a fast growing public health burden for almost all the developed countries and many developing nations. Despite intense efforts from both biomedical and clinical scientists, many fundamental questions regarding its aetiology and development remain unclear, partly due to the lack of suitable imaging technologies to visualize lipid composition and distribution, insulin secretion, ?-cell mass and functions in vivo. Such technologies would not only impact on our understanding of the complexity of metabolic disorders such as obesity and diabetes, but also aid in their diagnosis, drug development and assessment of treatment efficacy. In this article we discuss and propose several strategies for visualization of physiological and pathological changes that affect pancreas and adipose tissue as a result of the development of metabolic diseases. PMID:20533426

  19. Coagulopathy after severe pediatric trauma: A review

    PubMed Central

    Russell, Robert T.; Lisco, Steven J.; Kerby, Jeffrey D.; Pittet, Jean-François

    2014-01-01

    Trauma remains the leading cause of morbidity and mortality in the United States among children from the age 1 year to 21 years old. The most common cause of lethality in pediatric trauma is traumatic brain injury (TBI). Early coagulopathy has been commonly observed after severe trauma and is usually associated with severe hemorrhage and/or traumatic brain injury. In contrast to adult patients, massive bleeding is less common after pediatric trauma. The classical drivers of trauma-induced coagulopathy (TIC) include hypothermia, acidosis, hemodilution and consumption of coagulation factors secondary to local activation of the coagulation system following severe traumatic injury. Furthermore, there is also recent evidence for a distinct mechanism of TIC that involves the activation of the anticoagulant protein C pathway. Whether this new mechanism of posttraumatic coagulopathy plays a role in children is still unknown. The goal of this review is to summarize the current knowledge on the incidence and potential mechanisms of coagulopathy after pediatric trauma and the role of rapid diagnostic tests for early identification of coagulopathy. Finally, we discuss different options for treating coagulopathy after severe pediatric trauma. PMID:24569507

  20. Iodine-based radiographic contrast medium may precipitate metformin-associated lactic acidosis in diabetic patients. A case report, literature review and practical approach.

    PubMed

    Tonolini, M

    2012-01-01

    Lactic acidosis in diabetic patients undergoing metformin therapy is a widely recognized, rare but usually serious adverse event, particularly in presence of comorbidities such as cardiorespiratory disease, sepsis and renal failure. As demonstrated by the case of an elderly woman presented, administration of radiographic iodine-based contrast agents may precipitate lactic acidosis through worsening of renal function. Awareness of this condition, identification of at-risk patients, adequate prevention following published guidelines, early diagnosis and treatment including hemodialysis are necessary to avoid a fatal outcome. PMID:22362235

  1. Dynorphin opioid peptides enhance acid-sensing ion channel 1a activity and acidosis-induced neuronal death.

    PubMed

    Sherwood, Thomas W; Askwith, Candice C

    2009-11-11

    Acid-sensing ion channel 1a (ASIC1a) promotes neuronal damage during pathological acidosis. ASIC1a undergoes a process called steady-state desensitization in which incremental pH reductions desensitize the channel and prevent activation when the threshold for acid-dependent activation is reached. We find that dynorphin A and big dynorphin limit steady-state desensitization of ASIC1a and acid-activated currents in cortical neurons. Dynorphin potentiation of ASIC1a activity is independent of opioid or bradykinin receptor activation but is prevented in the presence of PcTx1, a peptide which is known to bind the extracellular domain of ASIC1a. This suggests that dynorphins interact directly with ASIC1a to enhance channel activity. Inducing steady-state desensitization prevents ASIC1a-mediated cell death during prolonged acidosis. This neuroprotection is abolished in the presence of dynorphins. Together, these results define ASIC1a as a new nonopioid target for dynorphin action and suggest that dynorphins enhance neuronal damage following ischemia by preventing steady-state desensitization of ASIC1a. PMID:19906984

  2. [Hypovitaminosis D and metabolic syndrome].

    PubMed

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

    2014-12-23

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

  3. Lipid Chaperones and Metabolic Inflammation

    PubMed Central

    Furuhashi, Masato; Ishimura, Shutaro; Ota, Hideki; Miura, Tetsuji

    2011-01-01

    Over the past decade, a large body of evidence has emerged demonstrating an integration of metabolic and immune response pathways. It is now clear that obesity and associated disorders such as insulin resistance and type 2 diabetes are associated with a metabolically driven, low-grade, chronic inflammatory state, referred to as “metaflammation.” Several inflammatory cytokines as well as lipids and metabolic stress pathways can activate metaflammation, which targets metabolically critical organs and tissues including adipocytes and macrophages to adversely affect systemic homeostasis. On the other hand, inside the cell, fatty acid-binding proteins (FABPs), a family of lipid chaperones, as well as endoplasmic reticulum (ER) stress, and reactive oxygen species derived from mitochondria play significant roles in promotion of metabolically triggered inflammation. Here, we discuss the molecular and cellular basis of the roles of FABPs, especially FABP4 and FABP5, in metaflammation and related diseases including obesity, diabetes, and atherosclerosis. PMID:22121495

  4. Masquerading acidosis after cardiopulmonary bypass: a case of propionic acidemia and congenital heart disease.

    PubMed

    Palermo, Robert A; Monge, Michael C; Charrow, Joel; Costello, John M; Epting, Conrad L

    2015-04-01

    We report the case of a child with both propionic acidemia and cyanotic congenital heart disease. The presence of an underlying inborn error of metabolism confounded the management of this patient in the postoperative period, resulting in therapeutic misdirection until the true etiology of hyperlactemia was recognized. PMID:25870350

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

    PubMed Central

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

    2014-01-01

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

  6. Heme Oxygenase1 Does Not Mediate the Effects of Extracellular Acidosis on Vascular Smooth Muscle Cell Proliferation, Migration, and Susceptibility to Apoptosis

    Microsoft Academic Search

    Lineke Brenninkmeijer; Constantin Kuehl; Adriana Miele Geldart; Elena Arons; Helen Christou

    2011-01-01

    Background: Unbalanced vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis contribute to vascular disorders such as atherosclerosis, restenosis, and pulmonary hypertension. The effect of extracellular acidosis (EA) on VSMC homeostasis is incompletely understood but we previously reported that EA increases heme oxygenase-1 (HO-1) expression in VSMCs. Since HO-1 regulates VSMC proliferation and apoptosis we sought to define the role

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

    PubMed Central

    Salter, Mark D.

    2013-01-01

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

  8. Changes in the profile of liver enzymes in newborn calves induced by experimental, subclinical acidosis in pregnant cows and osmotic diarrhoea

    Microsoft Academic Search

    R. Lechowski

    1996-01-01

    Experimental, subclinical acidosis was induced by oral administration of sacharose during the last 2 months of pregnancy in 15 cows. Seven cows and their newborn calves were used as a control group. The liver enzyme activities in the serum and the blood acid-base status were determined in the 15 calves from the cows in the experimental group. Mannitol was administered

  9. Ontogeny and sorafenib metabolism

    PubMed Central

    Zimmerman, Eric I.; Roberts, Justin L.; Li, Lie; Finkelstein, David; Gibson, Alice; Chaudhry, Amarjit S.; Schuetz, Erin G.; Rubnitz, Jeffrey E.; Inaba, Hiroto; Baker, Sharyn D.

    2012-01-01

    Purpose To investigate the role of ontogeny in sorafenib metabolism to the equipotent active metabolite sorafenib N-oxide. Experimental Design Steady-state pharmacokinetic studies of sorafenib and metabolites were performed in thirty children and young adults (17 males; median age, 9.5 years) receiving sorafenib 150 mg/m2 or 200 mg/m2 twice daily. Sorafenib metabolism was evaluated in vitro at 10 µM using a panel of purified human cytochrome P450 (CYP) enzymes. Sorafenib metabolism and CYP3A4 expression was evaluated in 52 human liver samples from donors ? 20 years old. The drug-drug interaction potential between sorafenib and azole antifungal agents was evaluated in vitro and in vivo. Results No age-related differences in sorafenib apparent oral clearance were observed. Mean sorafenib N-oxide metabolite ratio was 0.27±0.14. In children ? 10 years of age, boys had approximately 2-fold higher N-oxide ratios than girls (0.40±0.15 versus 0.22±0.12, P = 0.026). Of the CYPs evaluated, sorafenib was exclusively metabolized to sorafenib N-oxide by CYP3A4. A trend for increased N-oxide formation in boys was observed in liver samples, which correlated with CYP3A4 mRNA expression. Posaconazole and voriconazole potently inhibited sorafenib N-oxide formation in vitro, and reduced sorafenib N-oxide formation in 3 children given sorafenib concurrent with azoles. Conclusion We have identified several factors affecting inter-patient variability in sorafenib metabolism to the active N-oxide metabolite including age, sex, and concurrent treatment with azole antifungals. This knowledge may provide important considerations for the clinical use of sorafenib in children and possibly other kinase inhibitors undergoing CYP3A4-mediated metabolism. PMID:22927483

  10. Tissue-Specific Metabolic Responses of Cyprinus flammans to Copper.

    PubMed

    Hu, Ming-Yan; Ye, Yang-Fang; Xue, Liang-Yi; Tang, Ze-Yuan

    2015-07-01

    Copper (Cu) contamination is serious in China, with ?2.76 mg/L in some waters. Exposure to Cu causes a high toxicity to the aquatic organisms and subsequent ecological risk. To understand fish responses to Cu exposure, we analyzed the metabonomic changes in multiple tissues (gill, liver, and muscle) of Cyprinus flammans using an nuclear magnetic resonance-based metabonomic technique. Our results showed that metabolic alterations are dose-dependent. No significant metabolic alterations in three tissues of fish are caused by 0.25 mg/L Cu. However, 1.53 mg/L Cu caused changes of energy-related metabolites and amino acids, which we suggest are due to enhanced metabolic acidosis in gill and muscle, decreased tricarboxylic acid cycle activity in muscle, increased gluconeogenesis from amino acids in liver, and improved glycogenesis in liver and muscle. The Cori cycle between liver and muscle is concurrently triggered. Furthermore, high concentration of Cu resulted in the alteration of choline metabolism such that we hypothesize that Cu induces membrane damage and detoxification of CuSO4 in gill as well as altered osmoregulation in all three tissues. Choline-O-sulfate in gill may be used as a biomarker to provide an early warning of Cu exposure in C. flammans. Moreover, Cu exposure caused alterations of nucleoside and nucleotide metabolism in both gill and muscle. These findings provide a new insight into the metabolic effects of Cu exposure on C. flammans and highlight the value of metabonomics in the study of metabolic metal disturbance in fish. PMID:25827945

  11. Hepatic manifestations of metabolic syndrome.

    PubMed

    Medina-Santillán, Roberto; López-Velázquez, Jorge A; Chávez-Tapia, Norberto; Torres-Villalobos, Gonzalo; Uribe, Misael; Méndez-Sánchez, Nahum

    2013-03-01

    The prevalence of metabolic syndrome is growing around the world at an alarming rate. Obesity involves a plethora of molecules that predispose individuals to an inflammatory state and various metabolic complications. Dysregulation of nutrient metabolism is a key step during the progression of chronic liver disease that induces an inflammatory state, cellular damage, and impaired hepatic insulin signaling, which leads to insulin resistance. Insulin resistance arises from multiple defects in the liver, adipose tissues, and muscle signaling, which leads to a failure to suppress hepatic gluconeogenesis and glycogenolysis, thereby enhancing fat accumulation in the hepatocytes via increased lipolysis and increased hepatic synthesis of triglycerides. This metabolic condition also increases the frequency of other comorbidities such as liver and biliary diseases. Nonalcoholic fatty liver disease is the hepatic expression of metabolic syndrome, which comprises a spectrum of clinical and histological events ranging from simple and benign fatty liver to steatohepatitis, which is characterized by the abnormal activation of pathways leading to an aggressive inflammatory condition. This pathological state may progress to more severe damage known as cirrhosis, which endangers the anatomy and function of liver tissue. In addition, a small group of patients with end-stage liver disease may develop hepatocellular carcinoma and finally death. By contrast, cholesterol gallstone disease is a common metabolic disease, and is considered to be the main biliary indicator of metabolic syndrome. This review provides a detailed summary of the hepatic manifestations associated with metabolic syndrome. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23471889

  12. Association of lipid metabolism with ovarian cancer

    PubMed Central

    Tania, M.; Khan, M.A.; Song, Y.

    2010-01-01

    Defects in lipid metabolism have been found to be linked to several diseases, among which atherosclerosis, hypertension, obesity, and diabetes are the most important. Although cancer is chiefly a genetic disease, dietary lipid intake and metabolism are related to some cancer risks, including the risk for ovarian cancer. Higher intake of dietary lipids, systemic lipid metabolism malfunction, and abnormal serum lipid levels are somehow related to ovarian cancer. Overexpression of some lipid metabolic enzymes are also found in ovarian cancer. In this review article, we summarize the relationships between lipid intake, lipid metabolism, and ovarian cancer. PMID:20975872

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

    PubMed

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

    2011-10-01

    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

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

    PubMed

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

    1997-11-01

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

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

    PubMed

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

    2014-08-01

    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

  16. Metabolic Syndrome (For Parents)

    MedlinePLUS

    ... this is a condition called metabolic syndrome . About Metabolic Syndrome Not to be confused with metabolic disease (which ... chemicals in the body fail to interact properly), metabolic syndrome describes a cluster of risk factors that put ...

  17. Children with severe asthma have unique oxidative stress-associated metabolomic profiles

    PubMed Central

    Fitzpatrick, Anne M.; Park, Youngja; Brown, Lou Ann; Jones, Dean P.

    2014-01-01

    Summary Children with severe asthma have unique metabolic derangements associated with oxidative stress-related pathways. These metabolic differences may contribute to corticosteroid insensitivity in severe asthma and may be novel targets for further study and therapeutic intervention. PMID:24369802

  18. Myocardial fatty acid metabolism and cardiac performance in heart failure

    Microsoft Academic Search

    Helena Tuunanen; Heikki Ukkonen; Juhani Knuuti

    2008-01-01

    It is well established that cardiac metabolism is abnormal in heart failure (HF). Experimental studies suggest that in severe\\u000a HF, cardiac metabolism reverts to a more fetal-like substrate use characterized by enhanced glucose and downregulated free\\u000a fatty acid (FFA) metabolism. Correspondingly, in humans, when FFA levels are similar, myocardial glucose metabolism is increased,\\u000a and FFA metabolism is decreased. However, depression

  19. Sternal recumbency or suspension by the hind legs immediately after delivery improves respiratory and metabolic adaptation to extra uterine life in newborn calves delivered by caesarean section.

    PubMed

    Uystepruyst, Christophe; Coghe, Joost; Dorts, Thierry; Harmegnies, Natacha; Delsemme, Marie-Hélène; Art, Tatiana; Lekeux, Pierre

    2002-01-01

    The aim of this study was to evaluate the effect of body positioning immediately after delivery on respiratory and metabolic adaptation to extra-uterine life in newborn calves. One hundred and one Belgian White and Blue calves were delivered at term by an elective caesarean section and were assigned into three categories according to the body position imposed immediately after umbilical cord rupture: 71 calves were placed in lateral recumbency; 16 calves were placed in sternal recumbency and 14 calves were suspended by the hind legs for less than 90 seconds (75 +/- 5 s). Following this initial body position, the calves were allowed to move without restraint. They were examined at birth, 5, 15, 30, 45 and 60 minutes, and 2, 3, 6, 12 and 24 hours after birth by the following measurements: physical examination, heart rate, arterial blood gas analysis, pulmonary function tests using the esophageal balloon catheter technique, arterial and venous blood acid-base balance analysis, rectal temperature, jugular venous blood sampling for the determination of blood glucose, plasma lactate and serum cortisol concentrations, haematologic variables and passive immune transfer variables. Body positioning immediately after delivery clearly influenced respiratory and metabolic adaptation to extra-uterine life in term calves delivered by an elective caesarean section. Systematic sternal recumbency and suspension by the hind legs for less than 90 seconds immediately after umbilical cord rupture had a positive functional impact on postnatal pulmonary mechanics and gas exchange and on postnatal correction of mixed acidosis present at birth, contributing in turn to an enhanced passive immune transfer. These two body positions should be encouraged to improve adaptation at birth in healthy term calves delivered by an elective caesarean section. Evaluation of possible side-effects is required before application in severely asphyxiated calves. PMID:12498571

  20. Metabolic Downregulation

    PubMed Central

    Yenari, Midori; Kitagawa, Kazuo; Lyden, Patrick; Perez-Pinzon, Miguel

    2008-01-01

    Background and Purpose The search for effective neuroprotectants remains frustrating, particularly with regard to specific pharmaceuticals. However, laboratory studies have consistently shown remarkable neuroprotection with 2 nonpharmacological strategies—therapeutic hypothermia and ischemic preconditioning. Recent studies have shown that the mechanism of protection underlying both of these treatments is correlated to downregulation of cellular and tissue metabolism. Thus, understanding the mechanisms underlying such robust protective effects could lead to appropriate translation at the clinical level. In fact, hypothermia is already being used at many centers to improve neurological outcome from cardiac arrest. Methods A systematic review of both topics is presented in terms of underlying pathophysiological mechanisms and application at the clinical level. Results Although the mechanisms of protection for both therapeutic strategies are multifold, both share features of downregulating metabolism. Both therapeutic strategies are robust neuroprotectants, but translating them to the clinical arena is challenging, though not impossible, and clinical studies have shown or suggest benefits of both treatments. Conclusions The strategy of metabolic downregulation should be further explored to identify effective neuroprotectants that can be easily applied clinically. PMID:18658035

  1. Lipid metabolism in prostate cancer

    PubMed Central

    Wu, Xinyu; Daniels, Garrett; Lee, Peng; Monaco, Marie E

    2014-01-01

    The malignant transformation of cells requires adaptations across multiple metabolic processes to satisfy the energy required for their increased rate of proliferation. Dysregulation of lipid metabolism has been a hallmark of the malignant phenotype; increased lipid accumulation secondary to changes in the levels of a variety of lipid metabolic enzymes has been documented in a variety of tumors, including prostate. Alterations in prostate lipid metabolism include upregulation of several lipogenic enzymes as well as of enzymes that function to oxidize fatty acids as an energy source. Cholesterol metabolism and phospholipid metabolism are also affected. With respect to lipogenesis, most studies have concentrated on increased expression and activity ofthe de novo fatty acid synthesis enzyme, fatty acid synthase (FASN), with suggestions that FASN might function as an oncogene. A central role for fatty acid oxidation in supplying energy to the prostate cancer cell is supported by the observation that the peroxisomal enzyme, ?-methylacyl-CoA racemase (AMACR), which facilitates the transformation of branched chain fatty acids to a form suitable for ?-oxidation, is highly overexpressed in prostate cancer compared with normal prostate. Exploitation of the alterations in lipid metabolic pathways in prostate cancer could result in the development of new therapeutic modalities as well as provide candidates for new prognostic and predictive biomarkers. AMACR has already proven to be a valuable biomarker in distinguishing normal from malignant prostate tissue, and is used routinely in clinical practice. PMID:25374912

  2. Organelle pathology in metabolic neuromuscular disease: an overview.

    PubMed Central

    Becker, L E

    1990-01-01

    The spectrum of metabolic neuromuscular disorders is wide. Most inherited metabolic diseases are related to enzyme defects within lysosomes but recent advances emphasize abnormalities of mitochondria, peroxisomes and intermediate filaments. In this overview, organelle pathology is described in the context of both the clinical manifestations and the biochemical and/or molecular aspects of the disease. Among the many clinical presentations of mitochondrial disorders three emerge as distinctive entities: mitochondrial encephalopathy with lactic acidosis and stroke-like symptoms, mitochondrial encephalopathy with ragged-red fibers, and Kearns-Sayre syndrome. Peroxisomal disorders are associated with numerous biochemical defects, the most frequent of which are Zellweger's syndrome, neonatal adrenoleukodystrophy, and infantile Refsum's disease. Disorders of cytoskeletal proteins are associated with distinctive pathological accumulation of intermediate filaments but are without confirmed evidence of a biochemical defect. Understanding the role that organelle pathology plays in the pathogenesis of cellular disturbance or demise is essential to the elucidation of the pathogenesis of metabolic disorders. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. PMID:2407327

  3. Combined in situ analysis of metabolic and myoelectrical changes associated with electrically induced fatigue.

    PubMed

    Darques, J L; Bendahan, D; Roussel, M; Giannesini, B; Tagliarini, F; Le Fur, Y; Cozzone, P J; Jammes, Y

    2003-10-01

    Electrical muscle stimulation (Mstim) at a low or high frequency is associated with failure of force production, but the exact mechanisms leading to fatigue in this model are still poorly understood. Using 31P magnetic resonance spectroscopy (31PMRS), we investigated the metabolic changes in rabbit tibialis anterior muscle associated with the force decline during Mstim at low (10 Hz) and high (100 Hz) frequency. We also simultaneously recorded the compound muscle mass action potential (M-wave) evoked by direct muscle stimulation, and we analyzed its post-Mstim variations. The 100-Hz Mstim elicited marked M-wave alterations and induced mild metabolic changes at the onset of stimulation followed by a paradoxical recovery of phosphocreatine (PCr) and pH during the stimulation period. On the contrary, the 10-Hz Mstim produced significant PCr consumption and intracellular acidosis with no paradoxical recovery phenomenon and no significant changes in M-wave characteristics. In addition, the force depression was linearly linked to the stimulation-induced acidosis and PCr breakdown. These results led us to conclude that force failure during 100-Hz Mstim only results from an impaired propagation of muscle action potentials with no metabolic involvement. On the contrary, fatigue induced by 10-Hz Mstim is closely associated with metabolic changes with no alteration of the membrane excitability, thereby underlining the central role of muscle energetics in force depression when muscle is stimulated at low frequency. Finally, our results further indicate a reduction of energy cost of contraction when stimulation frequency is increased from 10 to 100 Hz. PMID:12819224

  4. Why Metabolic Syndrome Matters

    MedlinePLUS

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

  5. Cerebral energy metabolism in isovaleric acidaemia.

    PubMed Central

    Lorek, A. K.; Penrice, J. M.; Cady, E. B.; Leonard, J. V.; Wyatt, J. S.; Iles, R. A.; Burns, S. P.; Reynolds, E. O.

    1996-01-01

    A newborn infant with an acute metabolic encephalopathy caused by isovaleric acidaemia had severe impairment of cerebral energy metabolism. This was detected by phosphorus and proton magnetic resonance spectroscopy. After treatment she made excellent clinical recovery, her spectroscopic abnormalities resolved, and she was neurologically normal at the age of 1 year. PMID:8777688

  6. An Advance Organizer for Teaching Bacterial Metabolism

    ERIC Educational Resources Information Center

    Barbosa, Heloiza R.; Marques, Marilis V.; Torres, Bayardo B.

    2005-01-01

    The metabolic versatility of bacteria is a source of learning difficulty for students in classical microbiology courses. To facilitate the learning process, the authors developed an advance organizer. It consists of a set of six diagrams of metabolic pathways describing the basic living requirements of several types of bacteria: energy, carbon…

  7. 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

    Niazi, Masooma

    2014-01-01

    A 66-year-old male with newly diagnosed untreated acquired immunodeficiency syndrome (AIDS) presented with chronic nonspecific complaints of weakness, fatigue, myalgia, and weight loss. His initial EKG showed complete heart block necessitating temporary pacemaker placement. He had no previous history of cardiac disease. He was also found to have a persistent lactic acidosis and imaging studies showed abdominal lymphadenopathy. The patient underwent biopsy of these lymph nodes and was found to have diffuse large B-cell lymphoma. The hospital course was complicated by respiratory failure requiring mechanical ventilator support and cardiac arrest. Patient remained critically ill; he was not a candidate for chemotherapy and, after a month of hospitalization, he died. Lactic acidosis and heart block as an initial presentation of non-Hodgkin lymphoma in an AIDS patient are an unusual and unique presentation. PMID:25431684

  8. Application of research findings and summary of research needs: Bud Britton Memorial Symposium on Metabolic Disorders of Feedlot Cattle.

    PubMed

    Galyean, M L; Eng, K S

    1998-01-01

    Updated research findings with acidosis, feedlot bloat, liver abscesses, and sudden death syndromes were presented at the Bud Britton Memorial Symposium on Metabolic Disorders of Feedlot Cattle. Possible industry applications include the need to establish guidelines for use of clostridial vaccines in feedlot cattle, further assessment of the relationship between acidosis and polioencephalomalacia, examination of the effects of various ionophores on the incidence of metabolic disorders, and evaluation of the effects of feed bunk management and limit- and restricted-feeding programs on the incidence of metabolic disorders. A multidisciplinary approach among researchers, consulting nutritionists and veterinarians, and feedlot managers will be required for effective progress in research and in the application of research findings. Areas suggested for further research include 1) assessment of feed consumption patterns and social behavior of cattle in large-pen, feedlot settings; 2) evaluation of the relationship between feed intake management systems (feed bunk management programs, limit- and programmed-feeding) and the incidence of metabolic disorders, including delineation of the role of variability in feed intake in the etiology of such disorders; 3) efforts to improve antemortem and postmortem diagnosis, and to establish standardized regional or national epidemiological databases for various metabolic disorders; 4) ascertaining the accuracy of diagnosis of metabolic disorders and determining the relationship of previous health history of animals to the incidence of metabolic disorders; 5) further defining ruminal and intestinal microbiology as it relates to metabolic disorders and deeper evaluation of metabolic changes that occur with such disorders; 6) continued appraisal of the effects of grain processing and specific feed ingredients and nutrients on metabolic disorders, and development of new feed additives to control or prevent these disorders; and 7) application of biotechnology to develop grain varieties with altered nutrient degradation profiles that decrease the propensity for disastrous acid loads in the rumen, feed-grade enzymes and probiotics that modify nutrient digestion or microbial profiles in the rumen and intestine, and specific strains of ruminal bacteria and protozoa that alter ruminal and metabolic conditions that may precipitate metabolic disorders. PMID:9464915

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

    PubMed

    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

    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

  10. Correction of Pancreatic ?-Cell Dysfunction with Coenzyme Q10 in a Patient with Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes Syndrome and Diabetes mellitus

    Microsoft Academic Search

    Chia-Wei Liou; Chin-Chang Huang; Tsu-Kung Lin; Jin-Lian Tsai; Yau-Huei Wei

    2000-01-01

    Most patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome have a A3243G mutation in the tRNALeu(UUR) gene of mtDNA [1, 2]. Moreover, this mutation was found in MELAS patients with diabetes mellitus (DM) [3]and in patients with maternally inherited non-insulin-dependent DM [4]. Previous studies have demonstrated that mutation of mtDNA may cause defects in mitochondrial respiratory enzymes

  11. Acidosis decreases low Ca2+ -induced neuronal excitation by inhibiting the activity of calcium-sensing cation channels in cultured mouse hippocampal neurons

    PubMed Central

    Chu, Xiang-Ping; Zhu, Xiao-Man; Wei, Wen-Li; Li, Guo-Hua; Simon, Roger P; MacDonald, John F; Xiong, Zhi-Gang

    2003-01-01

    The effects of extracellular pH (pHo) on calcium-sensing non-selective cation (csNSC) channels in cultured mouse hippocampal neurons were investigated using whole-cell voltage-clamp and current-clamp recordings. Decreasing extracellular Ca2+ concentrations ([Ca2+]o) activated slow and sustained inward currents through the csNSC channels. Decreasing pHo activated amiloride-sensitive transient proton-gated currents which decayed to baseline in several seconds. With proton-gated channels inactivated by pre-perfusion with low pH solution or blocked by amiloride, decreasing pHo to 6.5 inhibited the csNSC currents with a leftward shift of the Ca2+ dose–inhibition curve. Increasing pH to 8.5, on the other hand, caused a rightward shift of the Ca2+ dose–inhibition curve and potentiated the csNSC currents. Intracellular alkalinization following bath perfusion of quinine mimicked the potentiation of the csNSC currents by increasing pHo, while intracellular acidification by addition and subsequent withdrawal of NH4Cl mimicked the inhibition of the csNSC currents by decreasing pHo. Intracellular pH (pHi) imaging demonstrated that decreasing pHo induced a corresponding decrease in pHi. Including 30 mM Hepes in the pipette solution eliminated the effects of quinine and NH4Cl on the csNSC currents, but only partially reduced the effect of lowering pHo. In current-clamp recordings, decreasing [Ca2+]o induced sustained membrane depolarization and excitation of hippocampal neurons. Decreasing pHo to 6.5 inhibited the low [Ca2+]o-induced csNSC channel-mediated membrane depolarization and the excitation of neurons. Our results indicate that acidosis may inhibit low [Ca2+]o-induced neuronal excitation by inhibiting the activity of the csNSC channels. Both the extracellular and the intracellular sites are involved in the proton modulation of the csNSC channels. PMID:12777448

  12. Phthalate Exposure Changes the Metabolic Profile of Cardiac Muscle Cells

    PubMed Central

    Swift, Luther M.; Kay, Matthew W.; Lee, Norman H.; Sarvazyan, Narine

    2012-01-01

    Background: Phthalates are common plasticizers present in medical-grade plastics and other everyday products. They can also act as endocrine-disrupting chemicals and have been linked to the rise in metabolic disorders. However, the effect of phthalates on cardiac metabolism remains largely unknown. Objectives: We examined the effect of di(2-ethylhexyl)phthalate (DEHP) on the metabolic profile of cardiomyocytes because alterations in metabolic processes can lead to cell dysfunction. Methods: Neonatal rat cardiomyocytes were treated with DEHP at a concentration and duration comparable to clinical exposure (50–100 ?g/mL, 72 hr). We assessed the effect of DEHP on gene expression using microarray analysis. Physiological responses were examined via fatty acid utilization, oxygen consumption, mitochondrial mass, and Western blot analysis. Results: Exposure to DEHP led to up-regulation of genes associated with fatty acid transport, esterification, mitochondrial import, and ?-oxidation. The functional outcome was an increase in myocyte fatty acid–substrate utilization, oxygen consumption, mitochondrial mass, PPAR? (peroxisome proliferator-activated receptor ?) protein expression, and extracellular acidosis. Treatment with a PPAR? agonist (Wy-14643) only partially mimicked the effects observed in DEHP-treated cells. Conclusions: Data suggest that DEHP exposure results in metabolic remodeling of cardiomyocytes, whereby cardiac cells increase their dependence on fatty acids for energy production. This fuel switch may be regulated at both the gene expression and posttranscription levels. Our findings have important clinical implications because chronic dependence on fatty acids is associated with an accumulation in lipid intermediates, lactate, protons, and reactive oxygen species. This dependence can sensitize the heart to ischemic injury and ventricular dysfunction. PMID:22672789

  13. Basic metabolic panel

    MedlinePLUS

    The basic metabolic panel is a group of blood tests that provides information about your body's metabolism . ... SMAC7; Sequential multi-channel analysis with computer-7; SMA7; Metabolic panel 7; CHEM-7

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

    PubMed

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

    2014-09-01

    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

  15. Rationale for, and design of, a clinical trial targeting polyamine metabolism for colon cancer chemoprevention.

    E-print Network

    Gerner, E W; Meyskens, F L Jr; Goldschmid, S; Lance, P; Pelot, D

    2007-01-01

    the polyamine metabolic pathway in epithelial cancermetabolic genes are downstream targets of several genes commonly mutated in colon adenomas and cancers.cancer (excepting adequately treated non-melanomatous skin can- cer) within five years of study entry, severe metabolic

  16. A Diagnostic Algorithm for Metabolic Myopathies

    PubMed Central

    Berardo, Andres; DiMauro, Salvatore

    2010-01-01

    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

  17. Jaws: The Inside Story. The Metabolism of Elasmobranch Fishes

    Microsoft Academic Search

    James S Ballantyne

    1997-01-01

    Elasmobranchs are of metabolic interest for several reasons, including their primitive evolutionary position, their osmotic strategy and their low incidence of neoplasia. Some aspects of the metabolism of elasmobranch fishes are unique when compared with those of the other vertebrates. Although many features of their metabolism can be attributed to their primitive evolutionary position (e.g., fewer isoforms of enzymes and

  18. Cold adaptation and oxidative metabolism of Antarctic fish

    Microsoft Academic Search

    Annalisa Colella; Maria Patamia; Antonio Galtieri; Bruno Giardina

    2000-01-01

    A well known characteristic of the oxidative metabolism of Antarctic fishes is their preferential utilization of the lipid metabolic pathway. Since oxidative metabolism may lead to a significant production of oxygen?derived free radicals, which may have several harmful effects on biological structures, it seemed worthwhile to investigate the presence, in various tissues from different Antarctic fishes, of those ions and

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

    PubMed Central

    Kurtz, Ira; Zhu, Quansheng

    2013-01-01

    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

  20. [Metabolic neuropathies: overview in 2011].

    PubMed

    Franques, J; Verschueren, A

    2012-12-01

    Metabolic diseases constitute a frequent etiologic group of axonal and small-fiber neuropathies. Recent works in this field are dominated by diabetic neuropathy (clinical presentation, prognostic factors) because of its prevalence. Vitamin B12 deficiency aroused several studies in 2011. This renewed interest for this well known entity ensues from the lack of sensibility of its biological markers underestimating its prevalence, its clinical spectrum and therefore, access to its therapy. Finally, 2011 highlighted the growing interest of the measure of the intra-epidermic nerve fibers density by skin biopsy for some metabolic disorders such as infra-clinical hypothyroïdism, chronic renal failure or Fabry disease. PMID:23107883

  1. Mitochondrial T9098C sequence change in the MTATP6 gene and development of severe mitochondrial disease after in utero antiretroviral prophylaxis.

    PubMed

    Velinov, Milen; Dolzhanskaya, Natalia; Mendez, Hermann

    2009-12-01

    Mitochondrial toxicity is a well-recognized adverse effect of nucleoside reverse transcriptase inhibitor therapy for human immunodeficiency virus (HIV) infection. Transient lactic acidosis is often observed in children born after in utero antiretroviral prophylaxis against mother-to-child transmission of HIV. However, the extent and the mechanism of in utero adverse effects are largely unknown. We describe a 4-year-old girl who presented with manifestations of severe mitochondrial disease, specifically, developmental and growth delay, hypotonia, lactic acidosis, congenital cataracts, and pancreatitis. Her HIV-positive mother was receiving lamivudine, zidovudine, and nelfinavir mesylate during her pregnancy. The child tested HIV negative after birth. She was found to have a homoplastic T9098C sequence change in the mitochondrial gene coding for adenosine 5'-triphosphate synthase 6 (MTATP6) that was previously reported as a mitochondrial polymorphism. This polymorphism is in the MTATP6 gene-coding sequence and leads to the replacement of a nonpolar amino acid with a polar amino acid. Because of the typical clinical manifestations of mitochondrial disorder and because of the nature of the mitochondrial sequence change, the observed polymorphism likely predisposed this patient to develop severe antiretroviral-associated mitochondrial disease. Mitochondrial sequence alterations may be important factors in mitochondrial toxicity associated with antiretroviral treatment. Mitochondrial sequencing may be warranted in cases of persistent lactic acidosis after antiretroviral prophylaxis to further study this association. PMID:19947808

  2. Metabolic responses to high protein diet in Korean elite bodybuilders with high-intensity resistance exercise

    PubMed Central

    2011-01-01

    Background High protein diet has been known to cause metabolic acidosis, which is manifested by increased urinary excretion of nitrogen and calcium. Bodybuilders habitually consumed excessive dietary protein over the amounts recommended for them to promote muscle mass accretion. This study investigated the metabolic response to high protein consumption in the elite bodybuilders. Methods Eight elite Korean bodybuilders within the age from 18 to 25, mean age 21.5 ± 2.6. For data collection, anthropometry, blood and urinary analysis, and dietary assessment were conducted. Results They consumed large amounts of protein (4.3 ± 1.2 g/kg BW/day) and calories (5,621.7 ± 1,354.7 kcal/day), as well as more than the recommended amounts of vitamins and minerals, including potassium and calcium. Serum creatinine (1.3 ± 0.1 mg/dl) and potassium (5.9 ± 0.8 mmol/L), and urinary urea nitrogen (24.7 ± 9.5 mg/dl) and creatinine (2.3 ± 0.7 mg/dl) were observed to be higher than the normal reference ranges. Urinary calcium (0.3 ± 0.1 mg/dl), and phosphorus (1.3 ± 0.4 mg/dl) were on the border of upper limit of the reference range and the urine pH was in normal range. Conclusions Increased urinary excretion of urea nitrogen and creatinine might be due to the high rates of protein metabolism that follow high protein intake and muscle turnover. The obvious evidence of metabolic acidosis in response to high protein diet in the subjects with high potassium intake and intensive resistance exercise were not shown in this study results. However, this study implied that resistance exercise with adequate mineral supplementation, such as potassium and calcium, could reduce or offset the negative effects of protein-generated metabolic changes. This study provides preliminary information of metabolic response to high protein intake in bodybuilders who engaged in high-intensity resistance exercise. Further studies will be needed to determine the effects of the intensity of exercise and the level of mineral intakes, especially potassium and calcium, which have a role to maintain acid-base homeostasis, on protein metabolism in large population of bodybuilders. PMID:21722409

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

    Microsoft Academic Search

    Li-Jun Yao; Michael Leitges; Volker Vallon

    2006-01-01

    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

  4. Differing effects of 2 active dried yeast (Saccharomyces cerevisiae) strains on ruminal acidosis and methane production in nonlactating dairy cows.

    PubMed

    Chung, Y-H; Walker, N D; McGinn, S M; Beauchemin, K A

    2011-05-01

    Fifteen ruminally cannulated, nonlactating Holstein cows were used to measure the effects of 2 strains of Saccharomyces cerevisiae, fed as active dried yeasts, on ruminal pH and fermentation and enteric methane (CH(4)) emissions. Nonlactating cows were blocked by total duration (h) that their ruminal pH was below 5.8 during a 6-d pre-experimental period. Within each block, cows were randomly assigned to control (no yeast), yeast strain 1 (Levucell SC), or yeast strain 2 (a novel strain selected for enhanced in vitro fiber degradation), with both strains (Lallemand Animal Nutrition, Montréal, QC, Canada) providing 1 × 10(10) cfu/head per day. Cows were fed once daily a total mixed ration consisting of a 50:50 forage to concentrate ratio (dry matter basis). The yeast strains were dosed via the rumen cannula daily at the time of feeding. During the 35-d experiment, ruminal pH was measured continuously for 7 d (d 22 to 28) by using an indwelling system, and CH(4) gas was measured for 4 d (d 32 to 35) using the sulfur hexafluoride tracer gas technique (with halters and yokes). Rumen contents were sampled on 2 d (d 22 and 26) at 0, 3, and 6h after feeding. Dry matter intake, body weight, and apparent total-tract digestibility of nutrients were not affected by yeast feeding. Strain 2 decreased the average daily minimum (5.35 vs. 5.65 or 5.66), mean (5.98 vs. 6.24 or 6.34), and maximum ruminal pH (6.71 vs. 6.86 or 6.86), and prolonged the time that ruminal pH was below 5.8 (7.5 vs. 3.3 or 1.0 h/d) compared with the control or strain 1, respectively. The molar percentage of acetate was lower and that of propionate was greater in the ruminal fluid of cows receiving strain 2 compared with cows receiving no yeast or strain 1. Enteric CH(4) production adjusted for intake of dry matter or gross energy, however, did not differ between either yeast strain compared with the control but it tended to be reduced by 10% when strain 2 was compared with strain 1. The study shows that different strains of S. cerevisiae fed as active dried yeasts vary in their ability to modify the rumen fermentative pattern in nonlactating dairy cows. Because strain 2 tended (when compared with strain 1) to lower CH(4) emissions but increase the risk of acidosis, it may be prudent to further evaluate this strain in cattle fed high-forage diets, for which the risk of acidosis is low but CH(4) emissions are high. PMID:21524535

  5. Automated Microbial Metabolism Laboratory

    NASA Technical Reports Server (NTRS)

    1971-01-01

    The effect of several environmental parameters on previously developed life detection systems is explored. Initial attempts were made to conduct all the experiments in a moist mode (high soil volume to water volume ratio). However, only labeled release and measurement of ATP were found to be feasible under conditions of low moisture. Therefore, these two life detection experiments were used for most of the environmental effects studies. Three soils, Mojave (California desert), Wyaconda (Maryland, sandy loam) and Victoria Valley (Antarctic desert) were generally used throughout. The environmental conditions studied included: incubation temperature 3 C to 80 C, ultraviolet irradiation of soils, variations in soil/liquid ratio, specific atmospheric gases, various antimetabolites, specific substrates, and variation in pH. An experiment designed to monitor nitrogen metabolism was also investigated.

  6. Modeling cancer metabolism on a genome scale

    PubMed Central

    Yizhak, Keren; Chaneton, Barbara; Gottlieb, Eyal; Ruppin, Eytan

    2015-01-01

    Cancer cells have fundamentally altered cellular metabolism that is associated with their tumorigenicity and malignancy. In addition to the widely studied Warburg effect, several new key metabolic alterations in cancer have been established over the last decade, leading to the recognition that altered tumor metabolism is one of the hallmarks of cancer. Deciphering the full scope and functional implications of the dysregulated metabolism in cancer requires both the advancement of a variety of omics measurements and the advancement of computational approaches for the analysis and contextualization of the accumulated data. Encouragingly, while the metabolic network is highly interconnected and complex, it is at the same time probably the best characterized cellular network. Following, this review discusses the challenges that genome-scale modeling of cancer metabolism has been facing. We survey several recent studies demonstrating the first strides that have been done, testifying to the value of this approach in portraying a network-level view of the cancer metabolism and in identifying novel drug targets and biomarkers. Finally, we outline a few new steps that may further advance this field. PMID:26130389

  7. Metabolic characteristics of cortical malformations causing epilepsy

    PubMed Central

    Mueller, Susanne G.; Barakos, Jerome A.; Cashdollar, Nathan; Flenniken, Derek L.; Vermathen, Peter; Matson, Gerald B.; Weiner, Michael W.

    2009-01-01

    Purpose Cortical malformations (CMs) are increasingly recognized as the epileptogenic substrate in patients with medically refractory neocortical epilepsy (NE). The aim of this study was to test the hypotheses that: 1. CMs are metabolically heterogeneous. 2. The structurally normal appearing perilesional zone is characterized by similar metabolic abnormalities as the CM. Methods Magnetic resonance spectroscopic imaging (MRSI) in combination with tissue segmentation was performed on eight patients with NE and CMs and 19 age-matched controls. In controls, NAA, Cr, Cho, NAA/Cr and NAA/Cho of all voxels of a given lobe were expressed as a function of white matter content and thresholds for pathological values determined by calculating the 95% prediction intervals. These thresholds were used to identify metabolically abnormal voxels within the CM and in the perilesional zone. Results 30% of all voxels in the CMs were abnormal, most frequently because of decreases of NAA or increases of Cho. Abnormal voxels tended to form metabolically heterogeneous clusters interspersed in metabolically normal regions. Furthermore, 15% of all voxels in the perilesional zone were abnormal, the most frequent being decreases of NAA and Cr. Conclusion In CMs metabolically normal regions are interspersed with metabolically heterogeneous abnormal regions. Metabolic abnormalities in the perilesional zone share several characteristics of CMs and might therefore represent areas with microscopic malformations and/or intrinsic epileptogenicity. PMID:15868069

  8. Metabolic syndrome: from epidemiology to systems biology

    Microsoft Academic Search

    Alan D. Attie; Karen Reue; Aldons J. Lusis

    2008-01-01

    Metabolic syndrome (MetSyn) is a group of metabolic conditions that occur together and promote the development of cardiovascular disease (CVD) and diabetes. Recent genome-wide association studies have identified several novel susceptibility genes for MetSyn traits, and studies in rodent models have provided important molecular insights. However, as yet, only a small fraction of the genetic component is known. Systems-based approaches

  9. Legal pre-event nutritional supplements to assist energy metabolism.

    PubMed

    Spriet, Lawrence L; Perry, Christopher G R; Talanian, Jason L

    2008-01-01

    Physical training and proper nutrition are paramount for success in sport. A key tissue is skeletal muscle, as the metabolic pathways that produce energy or ATP allow the muscles to complete the many activities critical to success in sport. The energy-producing pathways must rapidly respond to the need for ATP during sport and produce energy at a faster rate or for a longer duration through training and proper nutrition which should translate into improved performance in sport activities. There is also continual interest in the possibility that nutritional supplements could further improve muscle metabolism and the provision of energy during sport. Most legal sports supplements do not improve performance following oral ingestion. However, three legal supplements that have received significant attention over the years include creatine, carnitine and sodium bicarbonate. The ingestion of large amounts of creatine for 4-6 days increases skeletal muscle creatine and phosphocreatine contents. The majority of the experimental evidence suggests that creatine supplementation can improve short-term exercise performance, especially in sports that require repeated short-term sprints. It may also augment the accretion of skeletal muscle when taken in combination with a resistance-exercise training programme. Supplementary carnitine has been touted to increase the uptake and oxidation of fat in the mitochondria. However, muscle carnitine levels are not augmented following oral carnitine supplementation and the majority of well-controlled studies have reported no effect of carnitine on enhancing fat oxidation, Vo(2max) or prolonged endurance exercise performance. The ingestion of sodium bicarbonate before intense exercise decreases the blood [H+] to potentially assist the efflux of H+ from the muscle and temper the metabolic acidosis associated with intense exercise. Many studies have reported performance increases in laboratory-based cycling tests and simulated running races in the field following sodium bicarbonate ingestion where the need for ATP from substrate phosphorylation is high. However, other studies have reported no benefit and the incidence of negative side effects is high. PMID:18384281

  10. Inflammation and metabolic disorders

    Microsoft Academic Search

    Gökhan S. Hotamisligil

    2006-01-01

    Metabolic and immune systems are among the most fundamental requirements for survival. Many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily conserved throughout species. As a result, immune response and metabolic regulation are highly integrated and the proper function of each is dependent on the other. This interface can be viewed as a central homeostatic

  11. Equine Metabolic Syndrome

    Microsoft Academic Search

    Nicholas Frank

    2009-01-01

    Equine metabolic syndrome (EMS) is important because of its association with laminitis. Obesity and insulin resistance are two important components of EMS, and the underlying cause of this syndrome is likely to be enhanced metabolic efficiency. Affected horses are often referred to as “easy keepers” because they require fewer calories to maintain body condition, and enhanced metabolic efficiency is an

  12. CYTOKININ METABOLISM AND ACTION

    Microsoft Academic Search

    David WS Mok; Machteld C Mok

    2001-01-01

    ? Abstract Cytokinins are structurally diverse and biologically versatile. The chem- istry and physiology of cytokinin have been studied extensively, but the regulation of cytokinin biosynthesis, metabolism, and signal transduction is still largely undefined. Recent advances in cloning metabolic genes and identifying putative receptors por- tend more rapid progress based on molecular techniques. This review centers on cytokinin metabolism with

  13. Protective Effect of Hypercapnic Acidosis in Ischemia-Reperfusion Lung Injury Is Attributable to Upregulation of Heme Oxygenase-1

    PubMed Central

    Wu, Shu-Yu; Li, Min-Hui; Ko, Fu-Chang; Wu, Geng-Chin

    2013-01-01

    Hypercapnic acidosis (HCA) has protective effects in animal models of acute lung injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that protects tissue from inflammation injury. We investigated whether HO-1 contributes to the protective effects of HCA in ischemia-reperfusion (IR)-induced lung injury. Typical acute lung injury in rats was successfully induced by 40 min of ischemia and 90 min of reperfusion in an isolated perfused lung model. The rat lungs were randomly assigned to the control group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP), an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. In in vitro experiments, HO-1 siRNA transfected A549 cells were exposed to a normoxic or hypoxia-reoxygenation (H/R) environment in the presence or absence of HCA. IR caused significant increases in the pulmonary arterial pressure, lung weight to body weight and wet/dry ratios, lung weight gain, capillary filtration coefficient, lung injury scores, neutrophil infiltration, and concentrations of protein and TNF-? in the BALF. IR also induced degradation of inhibitor of nuclear factor (NF)-?B-?, increased I?B kinase (IKK)-? phosphorylation and nuclear translocation of NF-?B, and up-regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein expression and increased the number of active caspase-3 stained cells. HCA treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF-?B signaling, inhibited apoptosis, and significantly attenuated IR-induced changes. Treatment with ZnPP partially blocked the protective effect of HCA. In addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-?B signaling in A549 cells subjected to H/R. In conclusion, the protective effect of HCA in IR lung injury in rats was mediated in part by the anti-inflammatory and anti-apoptotic action of HO-1. PMID:24040332

  14. Structure and Dynamics of the Acidosis-Resistant A162H Mutant of the Switch Region of Troponin I Bound to the Regulatory Domain of Troponin C.

    PubMed

    Pineda-Sanabria, Sandra E; Robertson, Ian M; Sykes, Brian D

    2015-06-16

    Intracellular acidosis lowers the Ca(2+) sensitivity of cardiac muscle, which results in decreased force generation, decreased cardiac output, and, eventually, heart failure. The A162H mutant of cardiac troponin I in the thin filament turns the heart acidosis-resistant. Physiological and structural studies have provided insights into the mechanism of protection by the A162H substitution; however, the effect of other native residues of cardiac troponin I is not fully understood. In this study, we determined the structure of the A162H mutant of the switch region of cardiac troponin I bound to the regulatory domain of troponin C at pH 6.1, and the dynamics as a function of pH, by NMR spectroscopy to evaluate the changes induced by protonation of A162H. The results indicate that A162H induces a transitory curved conformation on troponin I that promotes contraction, but it is countered by residue E164 to ensure proper relaxation. Our model explains the absence of diastolic impairment in the gain-of-function phenotype induced by the A162H substitution as well as the effects of a variety of mutants studied previously. The description of this mechanism underlines the fine quality of regulation on cardiac muscle contraction and anticipates pharmacological agents that induce modest changes in the contraction-relaxation equilibrium to produce marked effects in cardiac performance. PMID:25996354

  15. [The effect of metabolic alkalosis on colostrum and milk quality of cows and on the health status of their newborns].

    PubMed

    Nicpo?, J; Hej?asz, Z

    1991-06-01

    The investigation was carried out on 12 cows and their calves. At the time of 3 months before parturition and 7 days after parturition metabolic alkalosis one provoked with the high protein feed. The laboratory investigations dependent of determinations on the rumen content the pH, NH3, volatile fatty, acids, the protozoa, bacteria, total gas CO2 and CH4. On the arterial and venous blood on determination the pH, BE, sO2, pO2, HCO3 and coefficient of consumption of the oxygen, and on the venous blood the levels of Na, K, Mg, Ca, P, total proteins, albumins and globulins, cholesterol, glucose, bilirubin, alkaline phosphatase and urea. In the colostrum and in milk one determined the pH, potential acidosis--degree SH, proper weight, proteins, dried mas of milk, time of coagulation in the presence of rennin, Na, K, Ca, Cl, total fats and their composition with different fatty acids. No existed truly changes of clinical signs, only feces was sickly. The metabolic alkalosis of cows decreased the consumption of oxygen across the tissue, deficient of the energy, disorders of water-electrolyte and acid-base balances. The calves form cows with metabolic alkalosis delivered also with metabolic alkalosis, with the symptoms of achondroplasia and degeneration of the liver and other organs. Metabolic alkalosis of cows influenced on the quality of colostrum and milk. The colostrum gained from cows with alkalosis caused of disturbance of gastrointestinal tract and diarrhea presence. PMID:1889361

  16. Acid-base disorders in ICU patients.

    PubMed

    Oh, Yun Kyu

    2010-12-01

    Metabolic acid-base disorders are comnom clinical problems in ICU patients. Arterial blood gas analysis and anion gap (AG) are important laboratory data in approaching acid-base interpretation. When measuring the AG, several factors such as albumin have influence on unmeasured anions and unmeasured cations. If a patient has hypoalbuminemia, the AG should be adjusted according to the albumin level. High AG metabolic acidoses including lactic acidosis, ketoacidosis, and ingestion of toxic alcohols are common in ICU patients. The treatment target of lactic acidosis and ketoacidosis is not the acidosis, but the underlying condition causing acidosis. Gastric acid loss, diuretics, volume depletion, renal compensation for respiratory acidosis, hypokalemia, and mineralocorticoid excess are common causes of metaboic alkalosis. In chloride responsive metaboic alkalosis, volume and potassium repletion are mandatory. PMID:21468199

  17. Abdominal Compartment Syndrome in Severe Acute Pancreatitis Treated with Percutaneous Catheter Drainage

    PubMed Central

    Park, Soonyoung; Lee, Seungho; Lee, Hyo Deok; Kim, Min; Kim, Kyeongmin; Jeong, Yusook

    2014-01-01

    Acute pancreatitis is one of the main causes of intra-abdominal hypertension (IAH). IAH contributes to multiple physiologic alterations and leads to the development of abdominal compartment syndrome (ACS) that induces multiorgan failure. We report a case of ACS in a patient with severe acute pancreatitis. A 44-year-old man who was admitted in a drunk state was found to have severe acute pancreatitis. During management with fluid resuscitation in an intensive care unit, drowsy mentality, respiratory acidosis, shock requiring inotropes, and oliguria developed in the patient, with his abdomen tensely distended. With a presumptive diagnosis of ACS, abdominal decompression through percutaneous catheter drainage was performed immediately. The intraperitoneal pressure measured with a drainage catheter was 31 mm Hg. After abdominal decompression, the multiorgan failure was reversed. We present a case of ACS managed with percutaneous catheter decompression. PMID:25325011

  18. Deep body composition phenotyping during weight cycling: relevance to metabolic efficiency and metabolic risk.

    PubMed

    Bosy-Westphal, A; Kahlhöfer, J; Lagerpusch, M; Skurk, T; Müller, M J

    2015-02-01

    Weight cycling may lead to adverse effects on metabolic efficiency (i.e. adaptive thermogenesis or 'metabolic slowing') and metabolic risks (e.g. increased risk for insulin resistance and the metabolic syndrome). In order to investigate these topics, the partitioning of fat and lean mass (i.e. the change in the proportion of both compartments) needs to be extended to the organ and tissue level because metabolic risk differs between adipose tissue depots and lean mass is metabolically heterogeneous being composed of organs and tissues differing in metabolic rate. Contrary to data obtained with severe weight loss and regain in lean people, weight cycling most likely has no adverse effects on fat distribution and metabolic risk in obese patients. There is even evidence for an increased ability of fat storage in subcutaneous fat depots (at the trunk in men and at the limbs in women) with weight cycling that may provide a certain protection from ectopic lipid deposition and thus explain the preservation of a favourable metabolic profile despite weight regain. On the other hand, the mass-specific metabolic rate of lean mass may increase with weight gain and decrease with weight loss mainly because of an increase and respective decrease in the proportion (and/or activity) of metabolically active organ mass. Obese people could therefore have a higher slope of the regression line between resting energy expenditure (REE) and fat-free mass that leads to an overestimation of metabolic efficiency when applied to normalize REE data after weight loss. Furthermore, in addressing the impact of macronutrient composition of the diet on partitioning of lean and fat mass, and the old controversy about whether a calorie is a calorie, we discuss recent evidence in support of a low glycaemic weight maintenance diet in countering weight regain and challenge this concept for weight loss by proposing the opposite. PMID:25614202

  19. Aerobic and Anaerobic Metabolism Aerobic = oxidative metabolism

    E-print Network

    Jodice, Patrick

    and lizards · Anaerobic metabolism may supply 50-90% of energy during activity · As with many other processes flight is positively related to drag and velocity #12;Laysan Albatross Horned Puffin AspectRatio Red

  20. Distal renal tubular acidosis

    MedlinePLUS

    ... that may be prescribed include potassium citrate and sodium bicarbonate. These are alkaline medicines that help correct the acidic condition of the body. Sodium bicarbonate may correct the loss of potassium and calcium.

  1. Renal Tubular Acidosis

    MedlinePLUS

    ... blood calcium, sickle cell disease , autoimmune disorders like lupus and Sjogren syndrome, or the use of certain ... Diseases in Childhood Nephrotic Syndrome Glomerulonephritis Living With Lupus Vesicoureteral Reflux (VUR) Do You Know About Sickle ...

  2. Renal Tubular Acidosis

    MedlinePLUS

    ... disturb many bodily functions. Healthy kidneys help maintain acid-base balance by excreting acids into the urine and ... RTA diagnosed? To diagnose RTA, doctors check the acid-base balance in blood and urine samples. If the ...

  3. Proximal renal tubular acidosis

    MedlinePLUS

    The doctor will perform a physical exam and ask about the symptoms. Tests that may be ordered include: Arterial blood gas Blood chemistry Other tests that may be done include: Blood pH level Urine pH Urinalysis

  4. Energy metabolism and regeneration are impaired by seawater acidification in the infaunal brittlestar Amphiura filiformis.

    PubMed

    Hu, Marian Y; Casties, Isabel; Stumpp, Meike; Ortega-Martinez, Olga; Dupont, Sam

    2014-07-01

    Seawater acidification due to anthropogenic release of CO2 as well as the potential leakage of pure CO2 from sub-seabed carbon capture storage (CCS) sites may impose a serious threat to marine organisms. Although infaunal organisms can be expected to be particularly impacted by decreases in seawater pH, as a result of naturally acidified conditions in benthic habitats, information regarding physiological and behavioral responses is still scarce. Determination of PO2 and P(CO2) gradients within burrows of the brittlestar Amphiura filiformis during environmental hypercapnia demonstrated that besides hypoxic conditions, increases of environmental P(CO2) are additive to the already high P(CO2) (up to 0.08 kPa) within the burrows. In response to up to 4 weeks exposure to pH 7.3 (0.3 kPa P(CO2)) and pH 7.0 (0.6 kPa P(CO2)), metabolic rates of A. filiformis were significantly reduced in pH 7.0 treatments, accompanied by increased ammonium excretion rates. Gene expression analyses demonstrated significant reductions of acid-base (NBCe and AQP9) and metabolic (G6PDH, LDH) genes. Determination of extracellular acid-base status indicated an uncompensated acidosis in CO2-treated animals, which could explain the depressed metabolic rates. Metabolic depression is associated with a retraction of filter feeding arms into sediment burrows. Regeneration of lost arm tissues following traumatic amputation is associated with significant increases in metabolic rate, and hypercapnic conditions (pH 7.0, 0.6 kPa) dramatically reduce the metabolic scope for regeneration, reflected in an 80% reduction in regeneration rate. Thus, the present work demonstrates that elevated seawater P(CO2) significantly affects the environment and the physiology of infaunal organisms like A. filiformis. PMID:24737772

  5. Association of cancer metabolism-related proteins with oral carcinogenesis – indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

    PubMed Central

    2014-01-01

    Background Tumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Methods Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n?=?5), oral precursor lesions (simple hyperplasia, n?=?11; squamous intraepithelial neoplasia, SIN I-III, n?=?35), and OSCC specimen (n?=?42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines. Results Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay). Conclusions This study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC. PMID:25048361

  6. The metabolic response to skin temperature.

    PubMed

    Kuhnen, G; Jessen, C

    1988-09-01

    Experiments were done to assess that fraction of the metabolic response to external cold exposure, which is attributable to skin temperature. In 5 conscious and closely clipped goats the metabolic rate was determined at various stable levels of skin temperature in the range from 13 to 41 degrees C, while core temperature was kept constant at 38.8 degrees C. Skin temperature was manipulated by a rapidly circulating shower bath, while core temperature was controlled by means of heat exchangers acting on arterial blood temperature in a chronic arteriovenous shunt. The metabolic response to skin temperature fell into two clearly discernible sections: a first zone with skin temperatures above 25-30 degrees C, within which the metabolic rate rose at a rate of -0.34 +/- 0.07 W/kg.degrees C with decreasing skin temperature, and a second zone with skin temperatures below 25-30 degrees C, within which the metabolic rate either plateaued or even grew smaller with further decreasing skin temperature. It is concluded that the relationship between skin temperature and metabolic rate does not directly reproduce the temperature-response curve of cutaneous cold receptors but also reflects a complex interaction of several factors, including an unspecific temperature effect on muscle metabolism. PMID:3174397

  7. Metabolic Engineering of Saccharomyces cerevisiae

    PubMed Central

    Ostergaard, Simon; Olsson, Lisbeth; Nielsen, Jens

    2000-01-01

    Comprehensive knowledge regarding Saccharomyces cerevisiae has accumulated over time, and today S. cerevisiae serves as a widley used biotechnological production organism as well as a eukaryotic model system. The high transformation efficiency, in addition to the availability of the complete yeast genome sequence, has facilitated genetic manipulation of this microorganism, and new approaches are constantly being taken to metabolicially engineer this organism in order to suit specific needs. In this paper, strategies and concepts for metabolic engineering are discussed and several examples based upon selected studies involving S. cerevisiae are reviewed. The many different studies of metabolic engineering using this organism illustrate all the categories of this multidisciplinary field: extension of substrate range, improvements of producitivity and yield, elimination of byproduct formation, improvement of process performance, improvements of cellular properties, and extension of product range including heterologous protein production. PMID:10704473

  8. MP-Align: alignment of metabolic pathways

    PubMed Central

    2014-01-01

    Background Comparing the metabolic pathways of different species is useful for understanding metabolic functions and can help in studying diseases and engineering drugs. Several comparison techniques for metabolic pathways have been introduced in the literature as a first attempt in this direction. The approaches are based on some simplified representation of metabolic pathways and on a related definition of a similarity score (or distance measure) between two pathways. More recent comparative research focuses on alignment techniques that can identify similar parts between pathways. Results We propose a methodology for the pairwise comparison and alignment of metabolic pathways that aims at providing the largest conserved substructure of the pathways under consideration. The proposed methodology has been implemented in a tool called MP-Align, which has been used to perform several validation tests. The results showed that our similarity score makes it possible to discriminate between different domains and to reconstruct a meaningful phylogeny from metabolic data. The results further demonstrate that our alignment algorithm correctly identifies subpathways sharing a common biological function. Conclusion The results of the validation tests performed with MP-Align are encouraging. A comparison with another proposal in the literature showed that our alignment algorithm is particularly well-suited to finding the largest conserved subpathway of the pathways under examination. PMID:24886436

  9. Evolution of metabolic networks: a computational frame-work

    Microsoft Academic Search

    Christoph Flamm; Alexander Ullrich; Heinz Ekker; Martin Mann; Daniel Högerl; Markus Rohrschneider; Sebastian Sauer; Gerik Scheuermann; Konstantin Klemm; Ivo L Hofacker; Peter F Stadler

    2010-01-01

    Background  The metabolic architectures of extant organisms share many key pathways such as the citric acid cycle, glycolysis, or the\\u000a biosynthesis of most amino acids. Several competing hypotheses for the evolutionary mechanisms that shape metabolic networks\\u000a have been discussed in the literature, each of which finds support from comparative analysis of extant genomes. Alternatively,\\u000a the principles of metabolic evolution can be

  10. Metabolic recovery from exhaustive exercise in rainbow trout

    Microsoft Academic Search

    C. Louise Milligan

    1996-01-01

    Exercise to exhaustion results in severe metabolic, acid-base, and endocrine disturbances to fish. Recovery metabolism from this type of activity may place limits on performance, since the time requirements for restoration of high energy stores (e.g. glycogen, high energy phosphates) will ultimately determine the frequency of maximal performance. This article reviews the types of metabolic, acid-base, and endocrine disturbances associated

  11. Exercise Intensity Modulation of Hepatic Lipid Metabolism

    PubMed Central

    Lira, Fábio S.; Carnevali, Luiz C.; Zanchi, Nelo E.; Santos, Ronaldo VT.; Lavoie, Jean Marc; Seelaender, Marília

    2012-01-01

    Lipid metabolism in the liver is complex and involves the synthesis and secretion of very low density lipoproteins (VLDL), ketone bodies, and high rates of fatty acid oxidation, synthesis, and esterification. Exercise training induces several changes in lipid metabolism in the liver and affects VLDL secretion and fatty acid oxidation. These alterations are even more conspicuous in disease, as in obesity, and cancer cachexia. Our understanding of the mechanisms leading to metabolic adaptations in the liver as induced by exercise training has advanced considerably in the recent years, but much remains to be addressed. More recently, the adoption of high intensity exercise training has been put forward as a means of modulating hepatic metabolism. The purpose of the present paper is to summarise and discuss the merit of such new knowledge. PMID:22545209

  12. Exercise intensity modulation of hepatic lipid metabolism.

    PubMed

    Lira, Fábio S; Carnevali, Luiz C; Zanchi, Nelo E; Santos, Ronaldo Vt; Lavoie, Jean Marc; Seelaender, Marília

    2012-01-01

    Lipid metabolism in the liver is complex and involves the synthesis and secretion of very low density lipoproteins (VLDL), ketone bodies, and high rates of fatty acid oxidation, synthesis, and esterification. Exercise training induces several changes in lipid metabolism in the liver and affects VLDL secretion and fatty acid oxidation. These alterations are even more conspicuous in disease, as in obesity, and cancer cachexia. Our understanding of the mechanisms leading to metabolic adaptations in the liver as induced by exercise training has advanced considerably in the recent years, but much remains to be addressed. More recently, the adoption of high intensity exercise training has been put forward as a means of modulating hepatic metabolism. The purpose of the present paper is to summarise and discuss the merit of such new knowledge. PMID:22545209

  13. Effects of biguanides on the intermediate metabolism of glucose in normal and portal-strictured rats.

    PubMed

    Schlienger, J L; Frick, A; Marbach, J; Freund, H; Imler, M

    1979-03-01

    Phenformin and metformin treatments may be complicated by lactic adidosis. This metabolic complication seems favoured by preexistent hepatic disease. We have therefore compared the metabolic effects of phenformin and metformin on non fasting normal and portal-strictured rats. The latter group is characterized by impaired hepatic passage of these drugs without hepatocellular lesions. Given orally to normal rats over 5 days, phenformin (20 mg/kg/24 h) and metformin (150 mg/kg/24 h) decreased blood glucose levels and increased blood urea and the substrates of gluconeogenesis (alanine, glutamine, lactic and pyruvic acids), effects more apparent with phenformin than metformin. In non-treated portal strictured rats, blood glucose levels were lower and the intermediate metabolites were higher than in noraml rats, suggesting a modification of gluconeogenesis. Treatment of the portal strictured group by phenformin or metformin induced no changes in the studied parameters. This absence of effect of the biguanides in portal strictured rats supports the postulate that, in normal rats, biguanides act principally on hepatic metabolism by reducing gluconeogenesis and that, in the absence of other hepatic damage, the presence of a peri-hepatic shunt, which, by itself, modifies gluconeogenesis, does not further predispose to lactic acidosis during short term administration of biguanides. PMID:446834

  14. The metabolic syndrome and neuropathy: therapeutic challenges and opportunities.

    PubMed

    Callaghan, Brian; Feldman, Eva

    2013-09-01

    The metabolic syndrome and neuropathy are common conditions, especially in the elderly, that are associated with significant morbidity. Furthermore, the metabolic syndrome is reaching epidemic proportions across the world. Current evidence supports the association of the metabolic syndrome and its individual components with neuropathy. Several clinical trials have demonstrated that treating hyperglycemia, a component of the metabolic syndrome, has a significant effect on reducing the incidence of neuropathy in those with type 1 diabetes. However, glucose control has only a marginal effect on preventing neuropathy in those with type 2 diabetes, suggesting that other factors may be driving nerve injury in these patients. Emerging evidence supports the metabolic syndrome as including risk factors for neuropathy. Interventions exist for treatment of all of the metabolic syndrome components, but only glucose control has strong evidence to support its use and is widely employed. Our understanding of the biology of metabolic nerve injury has rapidly expanded over the past several years. Mechanisms of injury include fatty deposition in nerves, extracellular protein glycation, mitochondrial dysfunction, and oxidative stress. Additionally, the activation of counter-regulatory signaling pathways leads to chronic metabolic inflammation. Medications that target these signaling pathways are being used for a variety of diseases and are intriguing therapeutic agents for future neuropathy clinical trials. As we move forward, we need to expand our understanding of the association between the metabolic syndrome and neuropathy by addressing limitations of previous studies. Just as importantly, we must continue to investigate the pathophysiology of metabolically induced nerve injury. PMID:23929529

  15. Metabolic profiling in nutrition and metabolic disorders.

    PubMed

    LeMieux, Monique; Al-Jawadi, Arwa; Wang, Shu; Moustaid-Moussa, Naima

    2013-01-01

    Nutrients exert potent effects on metabolism through a variety of regulatory mechanisms, resulting in local and systemic changes in metabolite levels. Numerous studies have focused on mechanisms by which nutrients and disease states regulate metabolism at the gene or protein levels using genomic and proteomic approaches, respectively. However, few studies have investigated nutritional regulation of the whole metabolome. Thus, metabolomic approaches have recently emerged to complement the genomics and proteomics research and to help identify biologically meaningful metabolites and metabolic networks that control cellular responses to genetic and environmental factors, including diet, and to identify metabolic diseases that are influenced by genetic and dietary factors. These large-scale studies expedite our ability to develop targeted treatments. The goal of this symposium was to provide a forum to introduce the metabolomics field to nutrition researchers. An overview of the state-of-the-art metabolomic technologies used was provided. The impact of some specific nutrients, disease states, or genetic variations and their interaction with the metabolome was discussed by the speakers. Our objectives were as follows: 1) to educate the audience about the use of metabolomics as an innovative tool for linking changes in cell metabolites and genetic variations to nutrient metabolism, energy balance, and the overlying effects on health and disease; 2) to understand the concept of metabolomics and describe the analytical tools and resources available in this area; 3) to introduce the potential application of metabolomics in the field of nutrition research; and 4) to provide specific nutrition-relevant metabolomics study examples in investigating regulation of the metabolic network or metabolic changes resulting from disease states by dietary factors. PMID:24038253

  16. Respiratory manifestations in patients with inherited metabolic diseases.

    PubMed

    Santamaria, Francesca; Montella, Silvia; Mirra, Virginia; De Stefano, Sara; Andria, Generoso; Parenti, Giancarlo

    2013-12-01

    Growing evidence indicates that inherited metabolic diseases are increasingly being recognised. Life expectancy for many patients is progressively improving because new therapeutic strategies are available. Because most inherited metabolic diseases are systemic disorders, virtually all organs may be involved. Respiratory disease complicates the management of several inherited metabolic diseases, either at presentation or as late-onset features. This review will describe the most exemplary respiratory manifestations of inherited metabolic diseases in childhood and adulthood. Since airways disease worsens the morbidity of many inherited metabolic disorders, leading to increased hospitalisations, mortality and overall healthcare costs, respiratory manifestations of inherited metabolic diseases need to be carefully recognised and treated. All patients with inherited metabolic disease and suspected airway disease should undergo a detailed diagnostic work-up. Current treatments for several inherited metabolic diseases (including enzyme replacement therapy, substrate reduction, bone marrow transplantation, or even more innovative strategies such as pharmacological chaperone or gene therapies) may provide significant benefits for associated respiratory disease. The integration of several specialists dedicated to airway disease management in a multidisciplinary team is essential to provide the most appropriate care to children and adults with inherited metabolic disease. PMID:24293461

  17. Metabolic Adaptation and Protein Complexes in Prokaryotes

    PubMed Central

    Krüger, Beate; Liang, Chunguang; Prell, Florian; Fieselmann, Astrid; Moya, Andres; Schuster, Stefan; Völker, Uwe; Dandekar, Thomas

    2012-01-01

    Protein complexes are classified and have been charted in several large-scale screening studies in prokaryotes. These complexes are organized in a factory-like fashion to optimize protein production and metabolism. Central components are conserved between different prokaryotes; major complexes involve carbohydrate, amino acid, fatty acid and nucleotide metabolism. Metabolic adaptation changes protein complexes according to environmental conditions. Protein modification depends on specific modifying enzymes. Proteins such as trigger enzymes display condition-dependent adaptation to different functions by participating in several complexes. Several bacterial pathogens adapt rapidly to intracellular survival with concomitant changes in protein complexes in central metabolism and optimize utilization of their favorite available nutrient source. Regulation optimizes protein costs. Master regulators lead to up- and downregulation in specific subnetworks and all involved complexes. Long protein half-life and low level expression detaches protein levels from gene expression levels. However, under optimal growth conditions, metabolite fluxes through central carbohydrate pathways correlate well with gene expression. In a system-wide view, major metabolic changes lead to rapid adaptation of complexes and feedback or feedforward regulation. Finally, prokaryotic enzyme complexes are involved in crowding and substrate channeling. This depends on detailed structural interactions and is verified for specific effects by experiments and simulations. PMID:24957769

  18. The Metabolic Syndrome

    Microsoft Academic Search

    Aoife M. Brennan; Laura Sweeney; Christos S. Mantzoros

    The metabolic syndrome refers to the clustering of metabolic abnormalities more frequently than would be expected by chance\\u000a alone. These metabolic abnormalities are all risk factors for cardiovascular disease (CVD), and the epidemiological association\\u000a between these multiple risk factors points to the possibility of a unifying underlying pathophysiology. Obesity, in particular\\u000a visceral adiposity, insulin resistance, and some degree of abnormal

  19. Metabolic activity, experiment M171. [space flight effects on human metabolism

    NASA Technical Reports Server (NTRS)

    Michel, E. L.; Rummel, J. A.

    1973-01-01

    The Skylab metabolic activity experiment determines if man's metabolic effectiveness in doing mechanical work is progressively altered by a simulated Skylab environment, including environmental factors such as slightly increased pCO2. This test identified several hardware/procedural anomalies. The most important of these were: (1) the metabolic analyzer measured carbon dioxide production and expired water too high; (2) the ergometer load module failed under continuous high workload conditions; (3) a higher than desirable number of erroneous blood pressure measurements were recorded; (4) vital capacity measurements were unreliable; and (5) anticipated crew personal exercise needs to be more structured.

  20. [Metabolic functions and sport].

    PubMed

    Riviere, Daniel

    2004-01-01

    Current epidemiological studies emphasize the increased of metabolic diseases of the adults, such as obesity, type-2 diabetes and metabolic syndromes. Even more worrying is the rising prevalence of obesity in children. It is due more to sedentariness, caused more by inactivity (television, video, games, etc.) than by overeating. Many studies have shown that regular physical activities benefit various bodily functions including metabolism. After dealing with the major benefits of physical exercise on some adult metabolic disorders, we focus on the prime role played by physical activity in combating the public health problem of childhood obesity. PMID:15651421

  1. Mevalonate metabolism in cancer.

    PubMed

    Gruenbacher, Georg; Thurnher, Martin

    2015-01-28

    Cancer cells are characterized by sustained proliferative signaling, insensitivity to growth suppressors and resistance to apoptosis as well as by replicative immortality, the capacity to induce angiogenesis and to perform invasive growth. Additional hallmarks of cancer cells include the reprogramming of energy metabolism as well as the ability to evade immune surveillance. The current review focuses on the metabolic reprogramming of cancer cells and on the immune system's capacity to detect such changes in cancer cell metabolism. Specifically, we focus on mevalonate metabolism, which is a target for drug and immune based cancer treatment. PMID:24467965

  2. Eicosanoids in Metabolic Syndrome

    PubMed Central

    Hardwick, James P.; Eckman, Katie; Lee, Yoon Kwang; Abdelmegeed, Mohamed A.; Esterle, Andrew; Chilian, William M.; Chiang, John Y.; Song, Byoung-Joon

    2013-01-01

    Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism.The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS. PMID:23433458

  3. Regulation of pyruvate metabolism in metabolic-related diseases.

    PubMed

    Jeoung, Nam Ho; Harris, Chris R; Harris, Robert A

    2014-03-01

    Pyruvate is an obligatory intermediate in the oxidative disposal of glucose and a major precursor for the synthesis of glucose, glycerol, fatty acids, and non-essential amino acids. Stringent control of the fate of pyruvate is critically important for cellular homeostasis. The regulatory mechanisms for its metabolism are therefore of great interest. Recent advances include the findings that (a) the mitochondrial pyruvate carrier is sensitive to inhibition by thiazolidinediones; (b) pyruvate dehydrogenase kinases induce the Warburg effect in many disease states; and (c) pyruvate carboxylase is an important determinate of the rates of gluconeogenesis in humans with type 2 diabetes. These enzymes are potential therapeutic targets for several diseases. PMID:24214243

  4. [Porphyrin metabolism in women with metabolic syndrome].

    PubMed

    Krivosheev, A B; Kuimov, A D; Kondratova, M A; Tuguleva, T A

    2014-01-01

    A total of 47 women with metabolic syndrome (MS) were examined with the fractional determination of porphyrins in urine (uroporphyrin and coproporphyrin) and feces (coproporphyrin and protoporphyrin) as well as their precursors (5-aminolevulinic acid and porphobilinogen). Disorders of porphyrin metabolism were documented in 29 (61.7%) women All patients had elevated levels of porphyrin precursors. Five women exhibited qualitative changes in the form of abnormal ratios of different porphyrin fractions(coproporphyrin/uroporphyrin < 1--0.8 ± 0.1 vs normal ratio 3.6 ± 0.4). 21 patients suffered quantitative changes in porphyrin metabolism in the form of manifold increase of porphyrin levels in urine and/or feces and formation of biochemical syndromes of secondary coproporphyrinuiria, symptomatic rise in porphyrin content in feces, and chronic latent hepatic porfiria. Disorders of porphyrin metabolism were associated with insulin resistance. Changes of porphyrin metabolism in MS extend the spectrum of concomitant disturbances and can be regarded as an additional criterion. PMID:25980299

  5. Metabolic adaptations supporting anoxia tolerance in reptiles: Recent advances

    Microsoft Academic Search

    Kenneth B. Storey

    1996-01-01

    Animal survival during severe hypoxia and\\/or anoxia is enhanced by a variety of biochemical adaptations including adaptations of fermentative pathways of energy production and, most importantly, the ability to sharply reduce metabolic rate by 5–20 fold and enter a hypometabolic state. The biochemical regulation of metabolic arrest is proving to have common molecular principles that extend across phylogenetic lines and

  6. Actions of juglone on energy metabolism in the rat liver

    Microsoft Academic Search

    Simoni Cristina Saling; Jurandir Fernando Comar; Márcio Shigueaki Mito; Rosane Marina Peralta; Adelar Bracht

    Juglone is a phenolic compound used in popular medicine as a phytotherapic to treat inflammatory and infectious diseases. However, it also acts as an uncoupler of oxidative phosphorylation in isolated liver mitochondria and, thus, may interfere with the hepatic energy metabolism. The purpose of this work was to evaluate the effect of juglone on several metabolic parameters in the isolated

  7. Carboxylate metabolism in sugar beet plants grown with excess Zn

    Microsoft Academic Search

    R. Sagardoy; F. Morales; R. Rellán-Álvarez; A. Abadía; J. Abadía; A. F. López-Millán

    2011-01-01

    The effects of Zn excess on carboxylate metabolism were investigated in sugar beet (Beta vulgaris L.) plants grown hydroponically in a growth chamber. Root extracts of plants grown with 50 or 100?M Zn in the nutrient solution showed increases in several enzymatic activities related to organic acid metabolism, including citrate synthase and phosphoenolpyruvate carboxylase, when compared to activities in control

  8. POSTER PRESENTATION Open Access Disturbance of HDL apolipoprotein AI metabolism

    E-print Network

    Paris-Sud XI, Université de

    POSTER PRESENTATION Open Access Disturbance of HDL apolipoprotein AI metabolism in severe the metabolic abnormalities resulting in low HDL apolipoprotein AI (HDL-AI) levels in lipodystrophy HIV infected are on protease inhibitors since at least six months. Patients were underwent in vivo kinetics of HDL-AI using

  9. Acyl-Lipid Metabolism

    PubMed Central

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2013-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:23505340

  10. Nitrogen metabolism meets phytopathology.

    PubMed

    Fagard, Mathilde; Launay, Alban; Clément, Gilles; Courtial, Julia; Dellagi, Alia; Farjad, Mahsa; Krapp, Anne; Soulié, Marie-Christine; Masclaux-Daubresse, Céline

    2014-10-01

    Nitrogen (N) is essential for life and is a major limiting factor of plant growth. Because soils frequently lack sufficient N, large quantities of inorganic N fertilizers are added to soils for crop production. However, nitrate, urea, and ammonium are a major source of global pollution, because much of the N that is not taken up by plants enters streams, groundwater, and lakes, where it affects algal production and causes an imbalance in aquatic food webs. Many agronomical data indicate that the higher use of N fertilizers during the green revolution had an impact on the incidence of crop diseases. In contrast, examples in which a decrease in N fertilization increases disease severity are also reported, indicating that there is a complex relationship linking N uptake and metabolism and the disease infection processes. Thus, although it is clear that N availability affects disease, the underlying mechanisms remain unclear. The aim of this review is to describe current knowledge of the mechanisms that link plant N status to the plant's response to pathogen infection and to the virulence and nutritional status of phytopathogens. PMID:25080088

  11. Acyl-Lipid Metabolism

    PubMed Central

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2010-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:22303259

  12. Molecular mechanism of constitutive endocytosis of Acid-sensing ion channel 1a and its protective function in acidosis-induced neuronal death.

    PubMed

    Zeng, Wei-Zheng; Liu, Di-Shi; Duan, Bo; Song, Xing-Lei; Wang, Xiang; Wei, Dong; Jiang, Wen; Zhu, Michael X; Li, Yong; Xu, Tian-Le

    2013-04-17

    Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the peripheral and CNSs, which critically contribute to a variety of pathophysiological conditions that involve tissue acidosis, such as ischemic stroke and epileptic seizures. However, the trafficking mechanisms of ASICs and the related proteins remain largely unknown. Here, we demonstrate that ASIC1a, the main ASIC subunit in the brain, undergoes constitutive endocytosis in a clathrin- and dynamin-dependent manner in both mouse cortical neurons and heterologous cell cultures. The endocytosis of ASIC1a was inhibited by either the small molecular inhibitor tyrphostin A23 or knockdown of the core subunit of adaptor protein 2 (AP2) ?2 using RNA interference, supporting a clathrin-dependent endocytosis of ASIC1a. In addition, the internalization of ASIC1a was blocked by dominant-negative dynamin1 mutation K44A and the small molecular inhibitor dynasore, suggesting that it is also dynamin-dependent. We show that the membrane-proximal residues (465)LCRRG(469) at the cytoplasmic C terminus of ASIC1a are critical for interaction with the endogenous adaptor protein complex and inhibition of ASIC1a internalization strongly exacerbated acidosis-induced death of cortical neurons from wild-type but not ASIC1a knock-out mice. Together, these results reveal the molecular mechanism of ASIC1a internalization and suggest the importance of endocytic pathway in functional regulation of ASIC1a channels as well as neuronal damages mediated by these channels during neurodegeneration. PMID:23595764

  13. Multifunctional albumin-MnO? nanoparticles modulate solid tumor microenvironment by attenuating hypoxia, acidosis, vascular endothelial growth factor and enhance radiation response.

    PubMed

    Prasad, Preethy; Gordijo, Claudia R; Abbasi, Azhar Z; Maeda, Azusa; Ip, Angela; Rauth, Andrew Michael; DaCosta, Ralph S; Wu, Xiao Yu

    2014-04-22

    Insufficient oxygenation (hypoxia), acidic pH (acidosis), and elevated levels of reactive oxygen species (ROS), such as H2O2, are characteristic abnormalities of the tumor microenvironment (TME). These abnormalities promote tumor aggressiveness, metastasis, and resistance to therapies. To date, there is no treatment available for comprehensive modulation of the TME. Approaches so far have been limited to regulating hypoxia, acidosis, or ROS individually, without accounting for their interdependent effects on tumor progression and response to treatments. Hence we have engineered multifunctional and colloidally stable bioinorganic nanoparticles composed of polyelectrolyte-albumin complex and MnO2 nanoparticles (A-MnO2 NPs) and utilized the reactivity of MnO2 toward peroxides for regulation of the TME with simultaneous oxygen generation and pH increase. In vitro studies showed that these NPs can generate oxygen by reacting with H2O2 produced by cancer cells under hypoxic conditions. A-MnO2 NPs simultaneously increased tumor oxygenation by 45% while increasing tumor pH from pH 6.7 to pH 7.2 by reacting with endogenous H2O2 produced within the tumor in a murine breast tumor model. Intratumoral treatment with NPs also led to the downregulation of two major regulators in tumor progression and aggressiveness, that is, hypoxia-inducible factor-1 alpha and vascular endothelial growth factor in the tumor. Combination treatment of the tumors with NPs and ionizing radiation significantly inhibited breast tumor growth, increased DNA double strand breaks and cancer cell death as compared to radiation therapy alone. These results suggest great potential of A-MnO2 NPs for modulation of the TME and enhancement of radiation response in the treatment of cancer. PMID:24702320

  14. Acidosis increases MHC class II-restricted presentation of a protein endowed with a pH-dependent heparan sulfate-binding ability.

    PubMed

    Knittel, Delphine; Savatier, Alexandra; Upert, Grégory; Lortat-Jacob, Hugues; Léonetti, Michel

    2015-04-15

    Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed molecules that participate in numerous biological processes. We previously showed that HSPGs expressed on the surface of APCs can serve as receptors for a hybrid protein containing an HS ligand and an Ag, which leads to more efficient stimulation of Th cells. To investigate whether such behavior is shared by proteins with inherent HS-binding ability, we looked for proteins endowed with this characteristic. We found that diphtheria toxin and its nontoxic mutant, called CRM197, can interact with HS. However, we observed that their binding ability is higher at pH 6 than at pH 7.4. Therefore, as extracellular acidosis occurs during infection by various micro-organisms, we assessed whether HS-binding capacity affects MHC class II-restricted presentation at different pHs. We first observed that pH decrease allows CRM197 binding to HSPG-expressing cells, including APCs. Then, we showed that this interaction enhances Ag uptake and presentation to Th cells. Lastly, we observed that pH decrease does not affect processing and presentation abilities of the APCs. Our findings show that acidic pH causes an HSPG-mediated uptake and an enhancement of T cell stimulation of Ags with the inherent ability to bind HSPGs pH-dependently. Furthermore, they suggest that proteins from micro-organisms with this binding characteristic might be supported more efficiently by the adaptive immune system when acidosis is triggered during infection. PMID:25754736

  15. Effects of maturation and acidosis on the chaos-like complexity of the neural respiratory output in the isolated brainstem of the tadpole, Rana esculenta.

    PubMed

    Straus, Christian; Samara, Ziyad; Fiamma, Marie-Noëlle; Bautin, Nathalie; Ranohavimparany, Anja; Le Coz, Patrick; Golmard, Jean-Louis; Darré, Pierre; Zelter, Marc; Poon, Chi-Sang; Similowski, Thomas

    2011-05-01

    Human ventilation at rest exhibits mathematical chaos-like complexity that can be described as long-term unpredictability mediated (in whole or in part) by some low-dimensional nonlinear deterministic process. Although various physiological and pathological situations can affect respiratory complexity, the underlying mechanisms remain incompletely elucidated. If such chaos-like complexity is an intrinsic property of central respiratory generators, it should appear or increase when these structures mature or are stimulated. To test this hypothesis, we employed the isolated tadpole brainstem model [Rana (Pelophylax) esculenta] and recorded the neural respiratory output (buccal and lung rhythms) of pre- (n = 8) and postmetamorphic tadpoles (n = 8), at physiologic (7.8) and acidic pH (7.4). We analyzed the root mean square of the cranial nerve V or VII neurograms. Development and acidosis had no effect on buccal period. Lung frequency increased with development (P < 0.0001). It also increased with acidosis, but in postmetamorphic tadpoles only (P < 0.05). The noise-titration technique evidenced low-dimensional nonlinearities in all the postmetamorphic brainstems, at both pH. Chaos-like complexity, assessed through the noise limit, increased from pH 7.8 to pH 7.4 (P < 0.01). In contrast, linear models best fitted the ventilatory rhythm in all but one of the premetamorphic preparations at pH 7.8 (P < 0.005 vs. postmetamorphic) and in four at pH 7.4 (not significant vs. postmetamorphic). Therefore, in a lower vertebrate model, the brainstem respiratory central rhythm generator accounts for ventilatory chaos-like complexity, especially in the postmetamorphic stage and at low pH. According to the ventilatory generators homology theory, this may also be the case in mammals. PMID:21325645

  16. Attractor Metabolic Networks

    PubMed Central

    De la Fuente, Ildefonso M.; Cortes, Jesus M.; Pelta, David A.; Veguillas, Juan

    2013-01-01

    Background The experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a Systemic Metabolic Structure in the cell, characterized by a set of different enzymatic reactions always locked into active states (metabolic core) while the rest of the catalytic processes are only intermittently active. This global metabolic structure was verified for Escherichia coli, Helicobacter pylori and Saccharomyces cerevisiae, and it seems to be a common key feature to all cellular organisms. In concordance with these observations, the cell can be considered a complex metabolic network which mainly integrates a large ensemble of self-organized multienzymatic complexes interconnected by substrate fluxes and regulatory signals, where multiple autonomous oscillatory and quasi-stationary catalytic patterns simultaneously emerge. The network adjusts the internal metabolic activities to the external change by means of flux plasticity and structural plasticity. Methodology/Principal Findings In order to research the systemic mechanisms involved in the regulation of the cellular enzymatic activity we have studied different catalytic activities of a dissipative metabolic network under different external stimuli. The emergent biochemical data have been analysed using statistical mechanic tools, studying some macroscopic properties such as the global information and the energy of the system. We have also obtained an equivalent Hopfield network using a Boltzmann machine. Our main result shows that the dissipative metabolic network can behave as an attractor metabolic network. Conclusions/Significance We have found that the systemic enzymatic activities are governed by attractors with capacity to store functional metabolic patterns which can be correctly recovered from specific input stimuli. The network attractors regulate the catalytic patterns, modify the efficiency in the connection between the multienzymatic complexes, and stably retain these modifications. Here for the first time, we have introduced the general concept of attractor metabolic network, in which this dynamic behavior is observed. PMID:23554883

  17. Severe Aplastic Anemia (SAA)

    MedlinePLUS

    ... Email this page Print this page Severe aplastic anemia (SAA) Severe aplastic anemia (SAA) is a disease in which the bone ... make enough blood cells for the body. Aplastic anemia is rare and occurs more frequently in eastern ...

  18. Metabolic status and respiratory physiology of Gecarcoidea natalis, the Christmas Island red crab, during the annual breeding migration.

    PubMed

    Adamczewsk, A M; Morris, S

    2001-06-01

    With the arrival of the monsoonal rains and after months of inactivity during the dry season, the terrestrial crab Gecarcoidea natalis embarks on its annual breeding migration to the coast. The physiological demands of the migration were assessed by determining respiratory gases in the hemolymph, key metabolites, and energy stores in G. natalis during two migratory seasons. At the end of each day of migration the pulmonary hemolymph PO2 decreased by 1-2.5 kPa, but the hemocyanin remained saturated with O2 and the venous reserve was largely unchanged (O2 > 0.4 mmol x l(-1)). The breeding migration of red crabs was accomplished without recourse to anaerobiosis, even though at times walking speeds (up to 6.2 +/- 0.5 m x min(-1)) exceeded those that promoted anaerobiosis in non-migrating crabs and in crabs exercised in the laboratory. In contrast to all previous studies, at the end of each day of migrating, red crabs experienced an alkalosis (up to 0.1 pH units) rather than any acidosis. This alkalosis was removed overnight when the crabs were inactive. Although there were seasonal fluctuations in the glycogen, glucose, and triglyceride stores, crabs engaging in the migration did not draw on these stores and must have fed along the way. In contrast, crabs returning from breeding activities on the shore terraces had significantly depleted glycogen stores. Additionally, in 1993, the male crabs returning from the breeding activities on the terraces were dehydrated and experienced a decrease in muscle tissue water of 11%. In contrast to the breeding migration per se, fighting for burrows in which breeding occurs produced severe anaerobiosis in males, especially the victors: after 135 s of combat, the maximum L-lactate concentration in the hemolymph was 35 mmol x l(-1). It appears that burrowing, courtship, and mating are more demanding than the migration itself. Furthermore, the data provide evidence that the metabolic responses of migrating individuals of G. natalis might be different from those at other times of the year. PMID:11441974

  19. Novel Adipokines and Bone Metabolism

    PubMed Central

    Liu, Yuan; Song, Cheng-Yuan; Wu, Shan-Shan; Liang, Qiu-Hua; Yuan, Ling-Qing; Liao, Er-Yuan

    2013-01-01

    Osteoporosis is a serious social issue nowadays. Both the high morbidity and its common complication osteoporotic fracture load a heavy burden on the whole society. The adipose tissue is the biggest endocrinology organ that has a different function on the bone. The adipocytes are differentiated from the same cell lineage with osteoblast, and they can secrete multiple adipokines with various functions on bone remolding. Recently, several novel adipokines have been identified and investigated thoroughly. In this paper, we would like to highlight the complicated relation between the bone metabolism and the novel adipokines, and it may provide us with a new target for prediction and treatment of osteoporosis. PMID:23431296

  20. Metabolic pathways of ochratoxin A.

    PubMed

    Wu, Qinghua; Dohnal, Vlastimil; Huang, Lingli; Ku?a, Kamil; Wang, Xu; Chen, Guyue; Yuan, Zonghui

    2011-01-01

    Ochratoxin A (OTA) as a carcinogenic of group 2B to humans is produced by various fungi strains as Aspergillus and Penicillium. It is one of the most common contaminant in foodstuff. OTA is nephrotoxic, hepatotoxic, teratogenic, and immunotoxic and is assumed to cause Balkan Endemic Nephropathy (BEN), a chronic kidney disease in humans when it is digested in combination with mycotoxin citrinin. The metabolism affects greatly the fates and the toxicity of a mycotoxins in humans, animals, and plants. The understanding of the metabolism of mycotoxins by the organism as fungi, yeast, bacteria and enzymes would be very helpful for the control of the contamination by the mycotoxins in foods and feeds, and understanding of the biotransformation of the mycotoxin in the body of humans, animals, plants, microorganisms would be beneficial to the risk assessment of food safety. In animals and humans, OTA can be metabolized in the kidney, liver and intestines. Hydrolysis, hydroxylation, lactone-opening and conjugation are the major metabolic pathways. OTalpha (OT?) formed by the cleavage of the peptidic bond in OTA is a major metabolite not only in animals and humans, but also in microorganisms and enzyme systems. It is considered as a nontoxic product. However, the lactone-opened product (OP-OTA), found in rodents, is higher toxic than its parent, OTA.. (4R)-4-OH-OTA is the major hydroxy product in rodents, whereas the 4S isomer is the major in pigs. 10-OH-OTA is currently found only in rabbits. Furthermore, OTA can lose the chlorine on C-5 to produce ochratoxin B (OTB), and OTB is further to 4-OH-OTB and ochratoxin ? (OT?). Ochratoxin quinine/hydroquinone (OTQ/OTHQ) is the metabolite of OTA in animals. In addition, the conjugates of OTA such as hexose and pentose conjugates can be found in animals. Such more polar metabolites make OTA to eliminate faster. Currently, a debate exits on the formation of OTA-DNA adducts. Plants can metabolize OTA as well. OH-OTA methyl ester and OH-OTA-?-glucoside are formed in many plants besides OT? and OH-OTA. OTA can be biotransformed into OT? by some yeast strains. Fungi can produce some of the same metabolites as animals. OT?, OT?, 4-R-OH-OTA, 4-R-OH-OTB, and 10-OH-OTA are the metabolites in fungi. Several commercial enzymes are able to biodegrade OTA into the nontoxic OT? efficiently. This review on the metabolism of OTA helps to well understand the fate of OTA in different organisms, as well as provides very crucial information for toxicology and food safety assessments on human health. PMID:21222585

  1. Mitochondrial 2-hydroxyglutarate metabolism.

    PubMed

    Engqvist, Martin K M; Eßer, Christian; Maier, Alexander; Lercher, Martin J; Maurino, Veronica G

    2014-11-01

    2-Hydroxyglutarate (2-HG) is a five-carbon dicarboxylic acid with a hydroxyl group at the alpha position, which forms a stereocenter in this molecule. Although the existence of mitochondrial D- and L-2HG metabolisms has long been known in different eukaryotes, the biosynthetic pathways, especially in plants, have not been completely elucidated. While D-2HG is involved in intermediary metabolism, L-2HG may not have a cellular function but it needs to be recycled through a metabolic repair reaction. Independent of their metabolic origin, D- and L-2HG are oxidized in plant mitochondria to 2-ketoglutarate through the action of two stereospecific enzymes, D- and L-2-hydroxyacid dehydrogenases. While plants are to a large extent unaffected by high cellular concentrations of D-2HG, deficiencies in the metabolism of D- and L-2HG result in fatal disorders in humans. We present current data gathered on plant D- and L-2HG metabolisms and relate it to existing knowledge on 2HG metabolism in other organisms. We focus on the metabolic origin of these compounds, the mitochondrial catabolic steps catalyzed by the stereospecific dehydrogenases, and phylogenetic relationships between different studied 2-hydroxyacid dehydrogenases. PMID:24561575

  2. Metabolic rate measurement system

    NASA Technical Reports Server (NTRS)

    Koester, K.; Crosier, W.

    1980-01-01

    The Metabolic Rate Measurement System (MRMS) is an uncomplicated and accurate apparatus for measuring oxygen consumption and carbon dioxide production of a test subject. From this one can determine the subject's metabolic rate for a variety of conditions, such as resting or light exercise. MRMS utilizes an LSI/11-03 microcomputer to monitor and control the experimental apparatus.

  3. Oncogenic alterations of metabolism

    Microsoft Academic Search

    Chi V. Dang; Gregg L. Semenza

    1999-01-01

    Over seven decades ago, classical biochemical studies showed that tumors have altered metabolic profiles and display high rates of glucose uptake and glycolysis. Although these metabolic changes are not the fundamental defects that cause cancer, they might confer a common advantage on many different types of cancers, which allows the cells to survive and invade. Recent molecular studies have revealed

  4. The metabolic syndrome

    Microsoft Academic Search

    Robert H Eckel; Scott M Grundy; Paul Z Zimmet

    2005-01-01

    This constellation of metabolic disturbances, all risk factors for cardiovascular disease, was first described in the 1920s by Kylin, a Swedish physician, as the clustering of hypertension, hyperglycaemia, and gout. 2 Later, in 1947, Vague drew attention to upper body adiposity (android or male-type obesity) as the obesity phenotype that was commonly associated with metabolic abnormalities associated with type 2

  5. The duration of time that beef cattle are fed a high-grain diet affects the recovery from a bout of ruminal acidosis: dry matter intake and ruminal fermentation.

    PubMed

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

    2013-12-01

    This study was conducted to determine if the duration of time cattle are fed a high-grain diet affects their susceptibility to and recovery from ruminal acidosis. Sixteen Angus heifers (BW ± SEM, 261 ± 6.1 kg) were assigned to 1 of 4 blocks and fed a backgrounding diet consisting of 60% barley silage, 30% barley grain, and 10% supplement (DM basis). Within block, cattle were randomly assigned to 1 of 2 treatments differing in the number of days they were fed the high-grain diet before an acidosis challenge: 34 d for long adapted (LA) and 8 d for short adapted (SA). All heifers were exposed to the same 20 d dietary transition to a high-grain diet containing 9% barley silage, 81% barley grain, and 10% supplement (DM basis). Ruminal acidosis was induced by restricting feed to 50% of DMI:BW for 24 h followed by an intraruminal infusion of ground barley at 10% DMI:BW. Heifers were then given their regular diet allocation 1 h after the intraruminal infusion. Data were collected during an 8-d baseline period (BASE), on the day of the acidosis challenge (CHAL), and during 2 consecutive 8-d recovery periods (REC1 and REC2). Acidosis induction increased daily duration (531 to 1,020 min/d; P < 0.001) and area (176 to 595 (min × pH)/d; P < 0.001) that ruminal pH was <5.5 relative to BASE. Relative to BASE, inducing acidosis also increased the daily mean (0.3 to 11.4 mM; P = 0.013) and maximum (1.3 to 29.3 mM; P = 0.008) ruminal fluid lactate concentrations. There was no effect of dietary treatment on ruminal pH, lactate, or short-chain fatty acid (SCFA) concentrations (P > 0.050). However, during BASE and CHAL, SA heifers experienced greater linear (P = 0.031), quadratic (P = 0.016), and cubic (P = 0.008) coefficients for the duration of time that pH was <5.5. In addition, a treatment × day interaction for the duration that pH was <5.5 during REC1 suggested that LA cattle tended to recover from the challenge more rapidly than SA cattle (P = 0.085). Regression analysis confirmed that the LA heifers experienced a quicker linear (P = 0.019) recovery from induced acidosis over time. These results indicate adaptation of the ruminal epithelium continues with advancing time as evidenced by more stable ruminal pH both before and after an induced bout of acute ruminal acidosis but does not affect susceptibility of cattle to ruminal acidosis. PMID:24158369

  6. DIABETES, OBESITY AND METABOLISM INSTITUTE

    E-print Network

    Engman, David M.

    DIABETES, OBESITY AND METABOLISM INSTITUTE AT NORTHWESTERN MEDICINE THE INSTITUTES AT NORTHWESTERN MEDICINE #12;THE INSTITUTES AT NORTHWESTERN MEDICINE DIABETES, OBESITY AND METABOLISM INSTITUTE AT NORTHWESTERN MEDICINE "As we launch the Diabetes, Obesity and Metabolism Institute at Northwestern Medicine, I

  7. Nitrogen metabolism in cyanobacteria under osmotic stress

    Microsoft Academic Search

    ARAN INCHAROENSAKDI

    Osmotic stress can interfere with the metabolism of inorganic and organic nitrogen compounds. Osmotic stress mostly in the form of high salinity affects several points of inorganic nitrogen assimilation pathway. The uptake of nitrate by cyanobacteria under salt stress can be increased or decreased depending on the species. One transport system for nitrate with either low or high affinity can

  8. Metabolic and endocrine effects of sedative agents

    Microsoft Academic Search

    Giovanni Mistraletti; Francesco Donatelli; Franco Carli

    2005-01-01

    Summary Metabolically critical illness can be divided in two phases, and acute and a prolonged one. Whereas the acute or hypermetabolic phase is characterized by elevated circulating concentration of catabolic hormones and substrate utilization to provide energy to vital organs, the prolonged or catabolic phase of critical illness is marked by reduced endocrine stimulation and severe loss of body cell

  9. Cell Metabolism The Unfolded Protein Response

    E-print Network

    Campbell, Kevin P.

    Cell Metabolism Article The Unfolded Protein Response Mediates Adaptation to Exercise in Skeletal that maintains ER homeostasis upon luminal stress, is activated in skeletal muscle during exercise and adapts skeletal muscle to exercise training. The transcriptional coac- tivator PGC-1a, which regulates several

  10. Metabolism and cancer: the circadian clock connection

    Microsoft Academic Search

    Saurabh Sahar; Paolo Sassone-Corsi

    2009-01-01

    Circadian rhythms govern a remarkable variety of metabolic and physiological functions. Accumulating epidemiological and genetic evidence indicates that the disruption of circadian rhythms might be directly linked to cancer. Intriguingly, several molecular gears constituting the clock machinery have been found to establish functional interplays with regulators of the cell cycle, and alterations in clock function could lead to aberrant cellular

  11. Metabolic Engineering VII Conference

    SciTech Connect

    Kevin Korpics

    2012-12-04

    The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

  12. Metabolic Syndrome and Cancer

    PubMed Central

    Pothiwala, Pooja; Jain, Sushil K.

    2009-01-01

    Abstract Since its first description by Reavan in 1988, accepted criteria for clinical identification of the components of metabolic syndrome have been promulgated by the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) and the World Health Organization (WHO) as well as the International Diabetes Federation (IDF), and the American Association of Clinical Endocrinologists (AACE). Insulin resistance is a common metabolic abnormality underlying type 2 diabetes mellitus and is also an independent risk factor for cardiovascular disease. Although ATP III identified cardiovascular disease (CVD) as the primary clinical outcome of the metabolic syndrome, we now have evidence that metabolic syndrome is associated with type 2 diabetes mellitus, polycystic ovarian disease, nonalcoholic fatty liver disease, and possibly some cancers. This review summarizes evidence in support of the relationship between metabolic syndrome and various cancers and possible underlying mechanisms and therapeutic interventions. PMID:19284314

  13. Metabolism of halophilic archaea

    PubMed Central

    Falb, Michaela; Müller, Kerstin; Königsmaier, Lisa; Oberwinkler, Tanja; Horn, Patrick; von Gronau, Susanne; Gonzalez, Orland; Pfeiffer, Friedhelm; Bornberg-Bauer, Erich

    2008-01-01

    In spite of their common hypersaline environment, halophilic archaea are surprisingly different in their nutritional demands and metabolic pathways. The metabolic diversity of halophilic archaea was investigated at the genomic level through systematic metabolic reconstruction and comparative analysis of four completely sequenced species: Halobacterium salinarum, Haloarcula marismortui, Haloquadratum walsbyi, and the haloalkaliphile Natronomonas pharaonis. The comparative study reveals different sets of enzyme genes amongst halophilic archaea, e.g. in glycerol degradation, pentose metabolism, and folate synthesis. The carefully assessed metabolic data represent a reliable resource for future system biology approaches as it also links to current experimental data on (halo)archaea from the literature. Electronic supplementary material The online version of this article (doi:10.1007/s00792-008-0138-x) contains supplementary material, which is available to authorized users. PMID:18278431

  14. Renal Ammonia Metabolism and Transport

    PubMed Central

    Weiner, I. David; Verlander, Jill W.

    2015-01-01

    Renal ammonia metabolism and transport mediates a central role in acid-base homeostasis. In contrast to most renal solutes, the majority of renal ammonia excretion derives from intrarenal production, not from glomerular filtration. Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH4+ and 2 HCO3? for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO3?-consuming process, resulting in no net benefit to acid-base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH3 diffusion, protonation in the lumen and NH4+ trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH3 permeability in combination with the presence of specific NH3-transporting and NH4+-transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K+, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid-base homeostasis. PMID:23720285

  15. Dynamic interplay between metabolic syndrome and immunity.

    PubMed

    Paragh, György; Seres, Ildikó; Harangi, Mariann; Fülöp, Péter

    2014-01-01

    Obesity and its co-morbidities as metabolic syndrome, type 2 diabetes mellitus and cardiovascular diseases are major health problems worldwide. Several reports indicated that nutrient excess and metabolic syndrome are linked with altered immune response. Indeed, metabolic syndrome is characterized by insulin resistance and chronic low-grade inflammation, which conditions are the consequences of the complex interaction between adipocytes and immune cells. Enlarged white adipose tissue is infiltrated by immune cells and secretes various bioactive substances, like adipokines, cytokines and other inflammatory mediators. Due to its special architecture in which metabolic and immune cells are in intimate proximity, metabolic and immunologic pathways are closely integrated in adipose tissue. With the contribution of altered gut microbiota, adipokines and cytokines modulate insulin signaling and immune response leading to adipose tissue inflammation and systemic insulin resistance. In this chapter, we focus on the cellular and molecular mechanisms that lead to impaired insulin sensitivity and chronic low-grade inflammation in obesity. We also detail the potential role of adipokines and immune cells in this deleterious process, and the concerns of vaccination in metabolic syndrome. Finally, we address the links between obesity and gut microbiota as an emerging new field of interest, and scratch the surface of potential therapeutic opportunities. PMID:25039000

  16. Effects of conjugated linoleic acid on cholesterol metabolism in swine

    E-print Network

    Koteras, Theresa Ann

    2000-01-01

    products and meats. This "all-natural" supplement is gaining notoriety for its beneficial health claims, including weight reduction and prevention of cancer and atherosclerosis. Several studies have explored the impact of CLA on lipid metabolism...

  17. The Implausibility of Metabolic Cycles on the Prebiotic Earth

    Microsoft Academic Search

    Leslie E. Orgel

    2008-01-01

    It has been suggested that complex reaction cycles, analogous to metabolic cycles, operated on the primitive Earth prior to the origin of genetic systems, but severe difficulties arise when these proposals are scrutinized from the standpoint of chemical plausibility.

  18. Metabolism of dopamine by the nasal mucosa.

    PubMed

    Chemuturi, Nagendra V; Donovan, Maureen D

    2006-11-01

    The nasal route of administration offers several advantages over oral and intravenous administration, including the ability to avoid hepatic first pass metabolism. Dopamine deficiency has been associated with several neurological disorders; it has been shown to have good systemic bioavailability and significant uptake into the CNS following intranasal administration. The purpose of these studies was to investigate the limiting role of mucosal metabolism of dopamine during nasal absorption. In vitro transport and initial rate studies were carried out using nasal mucosal explants to study dopamine permeability and metabolism. Dihydroxyphenylacetic acid (DOPAC) was the only metabolite detected. Monoamine oxidase (MAO), the enzyme responsible for DOPAC formation, was localized to the submucosal region of the nasal explants. The amount of DOPAC formed during the transport studies was less than 0.5% of the initial amount of dopamine placed into the system. Iproniazid, an MAO inhibitor, blocked DOPAC formation but had no effect on dopamine transport. The limited extent of dopamine metabolism compared to its mucosal transport demonstrates that nasal dopamine transport is not significantly reduced by mucosal metabolism and suggests that the nasal route may be promising for the efficient delivery of dopamine to the CNS. PMID:16917843

  19. Identifying Branched Metabolic Pathways by Merging Linear Metabolic Pathways

    NASA Astrophysics Data System (ADS)

    Heath, Allison P.; Bennett, George N.; Kavraki, Lydia E.

    This paper presents a graph-based algorithm for identifying complex metabolic pathways in multi-genome scale metabolic data. These complex pathways are called branched pathways because they can arrive at a target compound through combinations of pathways that split compounds into smaller ones, work in parallel with many compounds, and join compounds into larger ones. While most previous work has focused on identifying linear metabolic pathways, branched metabolic pathways predominate in metabolic networks. Automatic identification of branched pathways has a number of important applications in areas that require deeper understanding of metabolism, such as metabolic engineering and drug target identification. Our algorithm utilizes explicit atom tracking to identify linear metabolic pathways and then merges them together into branched metabolic pathways. We provide results on two well-characterized metabolic pathways that demonstrate that this new merging approach can efficiently find biologically relevant branched metabolic pathways with complex structures.

  20. Influence of metabolism in skin on dosimetry after topical exposure.

    PubMed Central

    Bronaugh, R L; Collier, S W; Macpherson, S E; Kraeling, M E

    1994-01-01

    Metabolism of chemicals occurs in skin and therefore should be taken into account when one determines topical exposure dose. Skin metabolism is difficult to measure in vivo because biological specimens may also contain metabolites from other tissues. Metabolism in skin during percutaneous absorption can be studied with viable skin in flow-through diffusion cells. Several compounds metabolized by microsomal enzymes in skin (benzo[a]pyrene and 7-ethoxycoumarin) penetrated human and hairless guinea pig skin predominantly unmetabolized. However, compounds containing a primary amino group (p-aminobenzoic acid, benzocaine, and azo color reduction products) were substrates for acetyltransferase activity in skin and were substantially metabolized during absorption. A physiologically based pharmacokinetic model has been developed with an input equation, allowing modeling after topical exposure. Plasma concentrations in the hairless guinea pig were accurately predicted for the model compound, benzoic acid, from in vitro absorption, metabolism, and other pharmacokinetic parameters. PMID:7737045

  1. Dietary fiber is related to metabolic risk factors in the Framingham Offspring Cohort

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic and epidemiological evidence suggests that high fiber diets improve glucose and lipid metabolism. We examined the association between energy-adjusted dietary fiber intake and several metabolic markers of disease risk in X men and Y women in the Framingham Offspring Cohort. Dietary fiber ...

  2. Metabolic Alterations and Systemic Inflammation in Obstructive Sleep Apnea among Nonobese and Obese Prepubertal Children

    Microsoft Academic Search

    David Gozal; Oscar Sans Capdevila; Leila Kheirandish-Gozal

    2008-01-01

    Rationale : Obstructive sleep apnea (OSA) has been associated with a higher prevalence and severity of the metabolic syndrome in adult patients, even after controlling for obesity. In contrast, OSA in prepubertal children does not appear to correlate with the magni- tude of such metabolic derangements. Objectives: To further establish the potential mechanistic role of OSA in metabolic regulation in

  3. Oxidative stress in inborn errors of metabolism: Lessons from glutathione deficiency

    Microsoft Academic Search

    E. Ristoff; A. Larsson

    2002-01-01

    Oxidative stress has been thought to be involved in the pathogenesis of several inborn errors of metabolism, such as mitochondrial enzyme deficiencies, G6PD deficiency, methylmalonic acidaemia and PKU. The possible role of oxidative stress in the pathogenesis of inborn errors of metabolism is discussed in the light of inborn errors in the metabolism of glutathione.

  4. The metabolic organization of a primitive air-breathing fish, the Florida gar (lepisosteus platyrhincus)

    Microsoft Academic Search

    Natasha Therese Frick; Jason Scott Bystriansky; James Stuart Ballantyne

    2007-01-01

    The metabolic organization of the air-breathing Florida gar, Lepisosteus platyrhincus, was assessed by measuring the maximal activities of key enzymes in several metabolic pathways in selected tissues, concentrations of plasma metabolites including nonesterified fatty acids (NEFA), free amino acids (FAA) and glucose as well as tissue FAA levels. In general, L. platyrhincus has an enhanced capacity for carbohydrate metabolism as

  5. Autophagy: a targetable linchpin of cancer cell metabolism

    PubMed Central

    Leone, Robert D.; Amaravadi, Ravi K.

    2014-01-01

    Cancer cells display several features of aberrant cellular metabolism. Two consequences of this dysregulated metabolism are rapid depletion of intracellular nutrients and a buildup of aggregated proteins and damaged organelles. Autophagy provides a mechanism for recycling proteins, lipids, and organelles. In cancer cells, oncogenes and conditions of severe stress drive profound upregulation of autophagy. In this setting, autophagy ameliorates the ill effects of dysregulated cellular metabolism, allowing a steady supply of nutrients and removal of damaged organelles. Although therapeutic strategies targeting cancer cell metabolism and autophagy are already entering clinical trials, further study of the precise mechanisms of interplay between oncogenic signaling, cellular metabolism, and autophagy will provide more effective strategies in the future. PMID:23474062

  6. Rhinosinusitis in severe asthma

    Microsoft Academic Search

    Megon Bresciani; Louis Paradis; Anne Des Roches; Hélène Vernhet; Isabelle Vachier; Philippe Godard; Jean Bousquet; Pascal Chanez

    2001-01-01

    Background: Chronic rhinosinusitis is a common comorbidity of asthma. However, sinonasal involvement in severe steroid-dependent asthma is still undefined. Objective: The aim of the study was to evaluate chronic rhinosinusitis in 35 patients with severe steroid-dependent asthma by using a clinical score and coronal computed tomography (CT) scanning. Methods: Thirty-five subjects (16 female subjects) with severe asthma requiring daily doses

  7. Physiology of iron metabolism.

    PubMed

    Waldvogel-Abramowski, Sophie; Waeber, Gérard; Gassner, Christoph; Buser, Andreas; Frey, Beat M; Favrat, Bernard; Tissot, Jean-Daniel

    2014-06-01

    A revolution occurred during the last decade in the comprehension of the physiology as well as in the physiopathology of iron metabolism. The purpose of this review is to summarize the recent knowledge that has accumulated, allowing a better comprehension of the mechanisms implicated in iron homeostasis. Iron metabolism is very fine tuned. The free molecule is very toxic; therefore, complex regulatory mechanisms have been developed in mammalian to insure adequate intestinal absorption, transportation, utilization, and elimination. 'Ironomics' certainly will be the future of the understanding of genes as well as of the protein-protein interactions involved in iron metabolism. PMID:25053935

  8. Cellular and metabolic engineering

    Microsoft Academic Search

    Douglas C. Cameron; I-Teh Tong

    1993-01-01

    Metabolic engineering is defined as the purposeful modification of intermediary metabolism using recombinant DNA techniques.\\u000a Cellular engineering, a more inclusive term, is defined as the purposeful modification of cell properties using the same techniques.\\u000a Examples of cellular and metabolic engineering are divided into five categories:\\u000a \\u000a \\u000a 1. \\u000a \\u000a Improved production of chemicals already produced by the host organism;\\u000a \\u000a \\u000a \\u000a \\u000a 2. \\u000a \\u000a Extended substrate range

  9. A Systems Biology Approach to Iron Metabolism

    PubMed Central

    Chifman, J.; Laubenbacher, R.; Torti, S.V.

    2015-01-01

    Iron is critical to the survival of almost all living organisms. However, inappropriately low or high levels of iron are detrimental and contribute to a wide range of diseases. Recent advances in the study of iron metabolism have revealed multiple intricate pathways that are essential to the maintenance of iron homeostasis. Further, iron regulation involves processes at several scales, ranging from the subcellular to the organismal. This complexity makes a systems biology approach crucial, with its enabling technology of computational models based on a mathematical description of regulatory systems. Systems biology may represent a new strategy for understanding imbalances in iron metabolism and their underlying causes. PMID:25480643

  10. The new metabolic treatments for sarcopenia.

    PubMed

    Barillaro, Christian; Liperoti, Rosa; Martone, Anna Maria; Onder, Graziano; Landi, Francesco

    2013-05-01

    In terms of managing sarcopenia, many studies have shown that physical activity (in particular resistance exercise) and specific nutrition interventions such as protein and amino acids supplementation can improve muscle mass and strength in older adults. Moreover, several drugs have been suggested to have an impact on muscle outcomes, with various levels of scientific evidence. In the present paper we have reviewed the evidence regarding the effect of some new metabolic agents (vitamin D, leucine, ?-hydroxy ?-methylbutyrate, citrulline malate, ornithine, isoflavones) on sarcopenia and muscular outcomes in older adults. For each metabolic agent, we have also discussed the biological plausibility of the described effect. PMID:23739896

  11. Identifying Branched Metabolic Pathways by Merging Linear Metabolic Pathways

    E-print Network

    Kavraki, Lydia E.

    applications in fields such as metabolic engineering, which focuses on discovering and implementing newIdentifying Branched Metabolic Pathways by Merging Linear Metabolic Pathways Allison P. Heath1 presents a graph-based algorithm for identify- ing complex metabolic pathways in multi-genome scale

  12. Severity of Bulimia Nervosa

    Microsoft Academic Search

    A. Hartmann; A. Zeeck; A. J. van der Kooij

    2009-01-01

    Aims: In order to identify the most important components of the severity of bulimia nervosa (as well as identifying clinical cases), we explored the relation between dimensional and categorical assessment. This was achieved by studying the performance of variables from standard instruments (measuring specific and general psychopathology) in predicting an expert rating of overall syndrome severity. Method: In total, 213

  13. Currency flaw severity. [Banknotes

    SciTech Connect

    Johnson, C.; Burnett, M.; Goodman, C.; Sherrod, R.; Schmoyer, R.; Harrison, C.; Uppuluri, R.

    1986-01-01

    A survey of currency flaw severity was carried out using 300 banknotes and 37 judges. Each judge assigned each note to one of five flaw severity categories. These categories correspond to severity grades of 1 to 5 with 1 equivalent to ''always accepted'' and 5 ''never accepted.'' An average flaw severity grade for each note was obtained by taking the mean of the severity grades assigned to that note by the 37 judges. Thus, each note has a single numerical real-number flaw grade between 1 and 5. Mathematical modeling of the currency flaw survey results is continuing with some very promising initial results. Our present model handles common excess ink and missing ink flaw types quite well. We plan to extend the model to ink level, mash, setoff and blanket impression flaw types.

  14. Monte-Carlo Modeling of the Central Carbon Metabolism of Lactococcus lactis: Insights into Metabolic Regulation

    PubMed Central

    Murabito, Ettore; Verma, Malkhey; Bekker, Martijn; Bellomo, Domenico; Westerhoff, Hans V.; Teusink, Bas; Steuer, Ralf

    2014-01-01

    Metabolic pathways are complex dynamic systems whose response to perturbations and environmental challenges are governed by multiple interdependencies between enzyme properties, reactions rates, and substrate levels. Understanding the dynamics arising from such a network can be greatly enhanced by the construction of a computational model that embodies the properties of the respective system. Such models aim to incorporate mechanistic details of cellular interactions to mimic the temporal behavior of the biochemical reaction system and usually require substantial knowledge of kinetic parameters to allow meaningful conclusions. Several approaches have been suggested to overcome the severe data requirements of kinetic modeling, including the use of approximative kinetics and Monte-Carlo sampling of reaction parameters. In this work, we employ a probabilistic approach to study the response of a complex metabolic system, the central metabolism of the lactic acid bacterium Lactococcus lactis, subject to perturbations and brief periods of starvation. Supplementing existing methodologies, we show that it is possible to acquire a detailed understanding of the control properties of a corresponding metabolic pathway model that is directly based on experimental observations. In particular, we delineate the role of enzymatic regulation to maintain metabolic stability and metabolic recovery after periods of starvation. It is shown that the feedforward activation of the pyruvate kinase by fructose-1,6-bisphosphate qualitatively alters the bifurcation structure of the corresponding pathway model, indicating a crucial role of enzymatic regulation to prevent metabolic collapse for low external concentrations of glucose. We argue that similar probabilistic methodologies will help our understanding of dynamic properties of small-, medium- and large-scale metabolic networks models. PMID:25268481

  15. MEASURING AND MODELLING METABOLISM

    EPA Science Inventory

    The use of QSAR with potential metabolism (bioactivation or deactivation) is an experimental approach for exploring toxicity pathways and estimating the relative toxicity of chemicals within a pathway. This conference will hear and discuss the potential and limitations of these ...

  16. Engineering of metabolic control

    DOEpatents

    Liao, James C.

    2004-03-16

    The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

  17. Engineering of metabolic control

    DOEpatents

    Liao, James C.

    2006-10-17

    The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

  18. Abdominal obesity and metabolic syndrome

    Microsoft Academic Search

    Jean-Pierre Després; Isabelle Lemieux

    2006-01-01

    Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease

  19. Exercise testing in metabolic myopathies.

    PubMed

    Tarnopolsky, Mark

    2012-02-01

    Metabolic myopathies are a group of genetic disorders specifically affecting glucose/glycogen, lipid, and mitochondrial metabolism. The main metabolic myopathies that are evaluated in this article are the mitochondrial myopathies, fatty acid oxidation defects, and glycogen storage disease. This article focuses on the usefulness of exercise in the evaluation of genetic metabolic myopathies. PMID:22239882

  20. Diphosphoinositol Polyphosphates: Metabolic Messengers?

    PubMed Central

    Shears, Stephen B.

    2009-01-01

    The diphosphoinositol polyphosphates (“inositol pyrophosphates”) are a specialized subgroup of the inositol phosphate signaling family. This review proposes that many of the current data concerning the metabolic turnover and biological effects of the diphosphoinositol polyphosphates are linked by a common theme: these polyphosphates act as metabolic messengers. This review will also discuss the latest proposals concerning possible molecular mechanisms of action of this intriguing class of molecules. PMID:19439500

  1. Interactions between negative energy balance, metabolic diseases, uterine health and immune response in transition dairy cows.

    PubMed

    Esposito, Giulia; Irons, Pete C; Webb, Edward C; Chapwanya, Aspinas

    2014-01-30

    The biological cycles of milk production and reproduction determine dairying profitability thus making management decisions dynamic and time-dependent. Diseases also negatively impact on net earnings of a dairy enterprise. Transition cows in particular face the challenge of negative energy balance (NEB) and/or disproportional energy metabolism (fatty liver, ketosis, subacute, acute ruminal acidosis); disturbed mineral utilization (milk fever, sub-clinical hypocalcemia); and perturbed immune function (retained placenta, metritis, mastitis). Consequently NEB and reduced dry matter intake are aggravated. The combined effects of all these challenges are reduced fertility and milk production resulting in diminishing profits. Risk factors such as NEB, inflammation and impairment of the immune response are highly cause-and-effect related. Thus, managing cows during the transition period should be geared toward reducing NEB or feeding specially formulated diets to improve immunity. Given that all cows experience a reduced feed intake and body condition, infection and inflammation of the uterus after calving, there is a need for further research on the immunology of transition dairy cows. Integrative approaches at the molecular, cellular and animal level may unravel the complex interactions between disturbed metabolism and immune function that predispose cows to periparturient diseases. PMID:24378117

  2. Role of Epidermal Growth Factor Receptor (EGFR)Signaling Versus Cellular Acidosis Via Na+\\/H+ Exchanger1(NHE1)Inhibition in Troglitazone-Induced Growth Arrest of Breast Cancer-Derived Cells MCF7

    Microsoft Academic Search

    Ellen Friday; Robert Oliver III; Tomas Welbourne; Francesco Turturro

    2007-01-01

    Purpose:We previously showed that troglitazone (TRO) induces a profound cellular acidosis in MCF-7 cells as a result of inhibiting Na+\\/H+ exchanger (NHE)1-mediated acid extrusion and this was associated with a marked reduction in cellular proliferation. The present study focuses on TRO-activated signaling pathways versus TRO-mediated NHE1-inhibition in reducing DNA synthesis. Experimental Design: TRO activation of the signaling pathway involving epidermal

  3. Metabolic disturbances connecting obesity and depression

    PubMed Central

    Hryhorczuk, Cecile; Sharma, Sandeep; Fulton, Stephanie E.

    2013-01-01

    Obesity markedly increases the odds of developing depression. Depressed mood not only impairs motivation, quality of life and overall functioning but also increases the risks of obesity complications. Abdominal obesity is a better predictor of depression and anxiety risk than overall adipose mass. A growing amount of research suggests that metabolic abnormalities stemming from central obesity that lead to metabolic disease may also be responsible for the increased incidence of depression in obesity. As reviewed here, a higher mass of dysfunctional adipose tissue is associated with several metabolic disturbances that are either directly or indirectly implicated in the control of emotions and mood. To better comprehend the development of depression in obesity, this review pulls together select findings addressing the link between adiposity, diet and negative emotional states and discusses the evidence that alterations in glucocorticoids, adipose-derived hormones, insulin and inflammatory signaling that are characteristic of central obesity may be involved. PMID:24109426

  4. Integrating transcriptomics with metabolic modeling predicts biomarkers and drug targets for Alzheimer's disease.

    PubMed

    Stempler, Shiri; Yizhak, Keren; Ruppin, Eytan

    2014-01-01

    Accumulating evidence links numerous abnormalities in cerebral metabolism with the progression of Alzheimer's disease (AD), beginning in its early stages. Here, we integrate transcriptomic data from AD patients with a genome-scale computational human metabolic model to characterize the altered metabolism in AD, and employ state-of-the-art metabolic modelling methods to predict metabolic biomarkers and drug targets in AD. The metabolic descriptions derived are first tested and validated on a large scale versus existing AD proteomics and metabolomics data. Our analysis shows a significant decrease in the activity of several key metabolic pathways, including the carnitine shuttle, folate metabolism and mitochondrial transport. We predict several metabolic biomarkers of AD progression in the blood and the CSF, including succinate and prostaglandin D2. Vitamin D and steroid metabolism pathways are enriched with predicted drug targets that could mitigate the metabolic alterations observed. Taken together, this study provides the first network wide view of the metabolic alterations associated with AD progression. Most importantly, it offers a cohort of new metabolic leads for the diagnosis of AD and its treatment. PMID:25127241

  5. Dengue and Severe Dengue

    MedlinePLUS

    ... dengue is a potentially deadly complication due to plasma leaking, fluid accumulation, respiratory distress, severe bleeding, or ... removing artificial man-made habitats; covering, emptying and cleaning of domestic water storage containers on a weekly ...

  6. Several notes on physics

    NASA Astrophysics Data System (ADS)

    Chen, Xiao-Fan

    2015-03-01

    Several notes on physics are presented, which include our views of quantum mechanics, general relativity, special relativity, electric charge, nonlinear electrodynamic, general transformation in hyperspace, solutions to equations of operators, superstring, shapes of particles and statistical mechanics.

  7. Management of severe acne.

    PubMed

    Zouboulis, C C; Bettoli, V

    2015-07-01

    Acne is the most common skin disease, affecting up to 95% of adolescents. Severe episodes of acne can cause considerable physical and psychological scarring, and overexpression of transforming growth factor-? can lead to formation of hypertrophic scars and keloids. The severity of acne in adolescence is associated with a positive history of severe acne in first-degree relatives, especially the mother. In most cases acne is a chronic disease, and it is often a component of systemic diseases or syndromes. All forms of severe acne require systemic treatment. The available options include oral antibiotics, hormonal antiandrogens for female patients and oral isotretinoin, as well as other combination treatments. Oral isotretinoin is the only drug available that affects all four pathogenic factors of acne. However, due to possible serious side-effects, a European directive states that oral isotretinoin should be used only as a second-line therapy in cases of severe, nodular and conglobate acne. The pharmaceutical quality of generic isotretinoin products and the obtainability of isotretinoin through e-pharmacies without prescription raise new therapeutic problems. New anti-inflammatory compounds, such as the 5-lipoxygenase inhibitor zileuton, may replace systemic antibiotics in the future, especially under the scope of antibiotic resistance prevention. This review looks into the various options and latest approaches, and factors to consider, when combating severe acne. PMID:25597508

  8. What is the relationship between exercise and metabolic abnormalities? A review of the metabolic syndrome.

    PubMed

    Carroll, Sean; Dudfield, Mike

    2004-01-01

    Prevention of the metabolic syndrome and treatment of its main characteristics are now considered of utmost importance in order to combat the epidemic of type 2 diabetes mellitus and to reduce the increased risk of cardiovascular disease and all-cause mortality. Insulin resistance/hyperinsulinaemia are consistently linked with a clustering of multiple clinical and subclinical metabolic risk factors. It is now widely recognised that obesity (especially abdominal fat accumulation), hyperglycaemia, dyslipidaemia and hypertension are common metabolic traits that, concurrently, constitute the distinctive insulin resistance or metabolic syndrome. Cross-sectional and prospective data provide an emerging picture of associations of both physical activity habits and cardiorespiratory fitness with the metabolic syndrome. The metabolic syndrome, is a disorder that requires aggressive multi-factorial intervention. Recent treatment guidelines have emphasised the clinical utility of diagnosis and an important treatment role for 'therapeutic lifestyle change', incorporating moderate physical activity. Several previous narrative reviews have considered exercise training as an effective treatment for insulin resistance and other components of the syndrome. However, the evidence cited has been less consistent for exercise training effects on several metabolic syndrome variables, unless combined with appropriate dietary modifications to achieve weight loss. Recently published randomised controlled trial data concerning the effects of exercise training on separate metabolic syndrome traits are evaluated within this review. Novel systematic review and meta-analysis evidence is presented indicating that supervised, long-term, moderate to moderately vigorous intensity exercise training, in the absence of therapeutic weight loss, improves the dyslipidaemic profile by raising high density lipoprotein-cholesterol and lowering triglycerides in overweight and obese adults with characteristics of the metabolic syndrome. Lifestyle interventions, including exercise and dietary-induced weight loss may improve insulin resistance and glucose tolerance in obesity states and are highly effective in preventing or delaying the onset of type 2 diabetes in individuals with impaired glucose regulation. Randomised controlled trial evidence also indicates that exercise training decreases blood pressure in overweight/obese individuals with high normal blood pressure and hypertension. These evidence-based findings continue to support recommendations that supervised or partially supervised exercise training is an important initial adjunctive step in the treatment of individuals with the metabolic syndrome. Exercise training should be considered an essential part of 'therapeutic lifestyle change' and may concurrently improve insulin resistance and the entire cluster of metabolic risk factors. PMID:15157122

  9. MRS: a noninvasive window into cardiac metabolism.

    PubMed

    van Ewijk, Petronella A; Schrauwen-Hinderling, Vera B; Bekkers, Sebastiaan C A M; Glatz, Jan F C; Wildberger, Joachim E; Kooi, M Eline

    2015-07-01

    A well-functioning heart requires a constant supply of a balanced mixture of nutrients to be used for the production of adequate amounts of adenosine triphosphate, which is the main energy source for most cellular functions. Defects in cardiac energy metabolism are linked to several myocardial disorders. MRS can be used to study in vivo changes in cardiac metabolism noninvasively. MR techniques allow repeated measurements, so that disease progression and the response to treatment or to a lifestyle intervention can be monitored. It has also been shown that MRS can predict clinical heart failure and death. This article focuses on in vivo MRS to assess cardiac metabolism in humans and experimental animals, as experimental animals are often used to investigate the mechanisms underlying the development of metabolic diseases. Various MR techniques, such as cardiac (31) P-MRS, (1) H-MRS, hyperpolarized (13) C-MRS and Dixon MRI, are described. A short overview of current and emerging applications is given. Cardiac MRS is a promising technique for the investigation of the relationship between cardiac metabolism and cardiac disease. However, further optimization of scan time and signal-to-noise ratio is required before broad clinical application. In this respect, the ongoing development of advanced shimming algorithms, radiofrequency pulses, pulse sequences, (multichannel) detection coils, the use of hyperpolarized nuclei and scanning at higher magnetic field strengths offer future perspective for clinical applications of MRS. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26010681

  10. Protein lysine acylation and cysteine succination by intermediates of energy metabolism

    PubMed Central

    Su, Xiaoyang; He, Bin

    2012-01-01

    In the last few years, several new protein post-translational modifications that use intermediates in metabolism have been discovered. These include various acyl lysine modifications (formylation, propionylation, butyrylation, crotonylation, malonylation, succinylation, myristoylation) and cysteine succination. Here, we review the discovery and the current understanding of these modifications. Several of these modifications are regulated by the deacylases, sirtuins, which use nicotinamide adenine dinucleotide (NAD), an important metabolic small molecule. Interestingly, several of these modifications in turn regulate the activity of metabolic enzymes. These new modifications reveal interesting connections between metabolism and protein post-translational modifications and raise many questions for future investigations. PMID:22571489

  11. Metabolic engineering of propanediol pathways.

    PubMed

    Cameron, D C; Altaras, N E; Hoffman, M L; Shaw, A J

    1998-01-01

    Microbial fermentation is an important technology for the conversion of renewable resources to chemicals. In this paper, we describe the application of metabolic engineering for the development of two new fermentation processes: the microbial conversion of sugars to 1,3-propanediol (1,3-PD) and 1,2-propanediol (1,2-PD). A variety of naturally occurring organisms ferment glycerol to 1,3-PD, but no natural organisms ferment sugars directly to 1,3-PD. We first describe the fed-batch fermentation of glycerol to 1,3-PD by Klebsiella pneumoniae. We then present various approaches for the conversion of sugars to 1,3-PD, including mixed-culture fermentation, cofermentation of glycerol and glucose, and metabolic engineering of a "sugars to 1,3-PD" pathway in a single organism. Initial results are reported for the expression of genes from the K. pneumoniae 1,3-PD pathway in Saccharomyces cerevisiae. The best naturally occurring organism for the fermentation of sugars to 1,2-PD is Thermoanaerobacterium thermosaccharolyticum. We describe the fermentation of several different sugars to 1,2-PD by this organism in batch and continuous culture. We report that Escherichia coli strains engineered to express either aldose reductase or glycerol dehydrogenase convert glucose to (R)-1,2-PD. We then analyze the ultimate potential of fermentation processes for the production of propanediols. Linear optimization studies indicate that, under aerobic conditions, propanediol yields that approach the theoretical maximum are possible and CO2 is the primary coproduct. Without the need to produce acetate, final product titers in the range of 100 g/L should be possible; the high titers and low coproduct levels should make product recovery and purification straightforward. The examples given in this paper illustrate the importance of metabolic engineering for fermentation process development in general. PMID:9496676

  12. Comparative genome-scale metabolic modeling of actinomycetes: The topology of essential core metabolism

    Microsoft Academic Search

    Mohammad Tauqeer Alam; Marnix H. Medema; Eriko Takano; Rainer Breitling

    2011-01-01

    Actinomycetes are highly important bacteria. On one hand, some of them cause severe human and plant diseases, on the other hand, many species are known for their ability to produce antibiotics. Here we report the results of a comparative analysis of genome-scale metabolic models of 37 species of actinomycetes. Based on in silico knockouts we generated topological and genomic maps

  13. Severe propylene glycol toxicity secondary to use of anti-epileptics.

    PubMed

    Pillai, Unnikrishnan; Hothi, Jatinder C; Bhat, Zeenat Y

    2014-01-01

    Propylene glycol toxicity presenting as high anion gap metabolic acidosis and osmolar gap has been extensively reported in literature, and most of them are secondary to intravenous lorazepam infusion. However, propylene glycol is used as a solvent in a number of medications that are frequently utilized in critical care setting, and hence one should be aware that the toxicity is possible from a variety of medication. Phenobarbital and phenytoin are one of those, and we hereby report a novel case of propylene glycol toxicity secondary to phenobarbital and phenytoin infusion in a patient with refractory status epilepticus. Furthermore, our patient had end-stage renal disease, which we think could have been an important precipitating factor for the toxicity. Because most of the symptoms from propylene glycol toxicity can mimic sepsis-which is very common in critical care unit patients-this life threatening scenario could be easily missed. Regular monitoring of osmolar gap is an easily available intervention in the at risk patients. PMID:22926232

  14. Severe Accidental Hypothermia Center.

    PubMed

    Darocha, Tomasz; Kosi?ski, Sylweriusz; Jarosz, Anna; Ga??zkowski, Robert; Sadowski, Jerzy; Drwi?a, Rafa?

    2015-08-01

    Hypothermic patients may be rewarmed using passive or active techniques. In case of severe accidental hypothermia (temperature<28°C) and stage III/IV according to the Swiss Staging System, standard methods might not be effective and aggressive treatment is needed. Extracorporeal membrane oxygenation (ECMO) has proved to be both effective and safe in such cases. The Department of Anesthesiology and Intensive Care, John Paul II Hospital, Cracow, Poland, established the Severe Accidental Hypothermia Center, which provides 24?h on-call to consult and accept patients who need ECMO implantation for profound hypothermia rewarming. Our center is so far the only one in Poland and can accept patients from south-east Poland. Most importantly, it collaborates with all prehospital medical services, namely, with 115 Ambulances, Polish Medical Air Rescue, Mountain Rescue Services, and all 28 Emergency Departments in the area. Severe Accidental Hypothermia Center is a solution for advanced treatment of patients with accidental hypothermia requiring ECMO implantation. PMID:25304125

  15. Severe acute asthma.

    PubMed

    Racusin, Diana Alex; Fox, Karin Anneliese; Ramin, Susan Marie

    2013-08-01

    Asthma is common among women of reproductive age and affects between 4% and 8% of pregnant women. Pregnancy outcomes are correlated to the degree of asthma severity and control. Approximately one-third of pregnant women with asthma remain stable, a third will have improvement of their asthma, and a third will have worsening of the disease. Pregnant women with severe asthma are at markedly increased risk of maternal and perinatal morbidity and mortality, preeclampsia, low-birth weight infants, and preterm delivery. A severe asthma exacerbation in a pregnant woman may be clinically daunting, however immediate intervention with appropriate supplemental oxygenation, medical therapy, and intubation if necessary can be life-saving. A focus on maternal well-being and pulmonary function in a pregnant asthmatic is essential to ensure optimal outcomes for both mother and her fetus. This article will provide an overview of asthma management, particularly in the acute care setting. PMID:23916022

  16. A workflow for mathematical modeling of subcellular metabolic pathways in leaf metabolism of Arabidopsis thaliana

    PubMed Central

    Nägele, Thomas; Weckwerth, Wolfram

    2013-01-01

    During the last decade genome sequencing has experienced a rapid technological development resulting in numerous sequencing projects and applications in life science. In plant molecular biology, the availability of sequence data on whole genomes has enabled the reconstruction of metabolic networks. Enzymatic reactions are predicted by the sequence information. Pathways arise due to the participation of chemical compounds as substrates and products in these reactions. Although several of these comprehensive networks have been reconstructed for the genetic model plant Arabidopsis thaliana, the integration of experimental data is still challenging. Particularly the analysis of subcellular organization of plant cells limits the understanding of regulatory instances in these metabolic networks in vivo. In this study, we develop an approach for the functional integration of experimental high-throughput data into such large-scale networks. We present a subcellular metabolic network model comprising 524 metabolic intermediates and 548 metabolic interactions derived from a total of 2769 reactions. We demonstrate how to link the metabolite covariance matrix of different Arabidopsis thaliana accessions with the subcellular metabolic network model for the inverse calculation of the biochemical Jacobian, finally resulting in the calculation of a matrix which satisfies a Lyaponov equation. In this way, different strategies of metabolite compartmentation and involved reactions were identified in the accessions when exposed to low temperature. PMID:24400018

  17. Duration of time that beef cattle are fed a high-grain diet affects the recovery from a bout of ruminal acidosis: short-chain fatty acid and lactate absorption, saliva production, and blood metabolites.

    PubMed

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

    2013-12-01

    This study was conducted to determine if the duration of time that beef cattle are fed a high-grain diet affects short-chain fatty acid (SCFA) absorption, saliva production, and blood metabolites before, during, and following an induced bout of ruminal acidosis. Sixteen Angus heifers were assigned to 1 of 4 blocks and within block to 1 of 2 treatments designated as long adapted (LA) or short adapted (SA). Long adapted and SA heifers were fed a backgrounding diet [forage:concentrate (F:C) = 60:40] for 33 and 7 d, respectively, and then transitioned over 20 d to a high-grain diet (F:C = 9:91) with the timing of dietary transition staggered such that the LA and SA heifers were fed the high-grain diet for 34 and 8 d, respectively, before inducing ruminal acidosis. Ruminal acidosis was induced by restricting feed to 50% of DMI:BW for 24 h followed by an intraruminal infusion of ground barley at 10% DMI:BW. Heifers were then given their regular diet allocation 1 h after the intraruminal infusion. Data were collected during an 8 d baseline period (BASE), on the day of the acidosis challenge (CHAL), and during 2 consecutive 8 d recovery periods (REC1 and REC2). When pooled across periods, the fractional rates of propionate (42 vs. 34%/h; P = 0.045) and butyrate (45 vs. 36%/h; P = 0.019) absorption, measured using the isolated and washed reticulorumen technique, were greater for LA than SA heifers. Moreover, overall, LA heifers tended to have greater absolute rates of butyrate absorption (94 vs. 79 mmol/h; P = 0.087) and fractional rates of total SCFA absorption (37 vs. 32%/h; P = 0.100). Treatment × period interactions for lactate absorption (P = 0.024) and serum D-lactate concentration (P = 0.003) were detected with LA heifers having greater D-lactate concentrations during CHAL and greater fractional rates of lactate absorption during REC1 than SA. The absolute and fractional absorption of acetate, propionate, and butyrate increased between REC1 and REC2, with intermediate values for BASE (P ? 0.05). Although fractional rates of SCFA absorption were low during REC1, saliva production (P = 0.018) increased between BASE and REC1, with intermediate values for REC2. These results suggest that the duration of time that animals are fed a high-grain diet may increase propionate, butyrate, and lactate absorption, and that cattle may decrease SCFA absorption and increase saliva production shortly after an acute bout of ruminal acidosis. PMID:24158368

  18. Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) plus associated with a novel de novo mutation (m.8969G>A) in the mitochondrial encoded ATP6 gene.

    PubMed

    Burrage, Lindsay C; Tang, Sha; Wang, Jing; Donti, Taraka R; Walkiewicz, Magdalena; Luchak, J Michael; Chen, Li-Chieh; Schmitt, Eric S; Niu, Zhiyv; Erana, Rodrigo; Hunter, Jill V; Graham, Brett H; Wong, Lee-Jun; Scaglia, Fernando

    2014-11-01

    Mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) is a rare mitochondrial disorder that has previously been associated with mutations in PUS1 and YARS2. In the present report, we describe a 6-year old male with an MLASA plus phenotype. This patient had features of MLASA in the setting of developmental delay, sensorineural hearing loss, epilepsy, agenesis of the corpus callosum, failure to thrive, and stroke-like episodes. Sequencing of the mitochondrial genome identified a novel de novo, heteroplasmic mutation in the mitochondrial DNA (mtDNA) encoded ATP6 gene (m.8969G>A, p.S148N). Whole exome sequencing did not identify mutations or variants in PUS1 or YARS2 or any known nuclear genes that could affect mitochondrial function and explain this phenotype. Studies of fibroblasts derived from the patient revealed a decrease in oligomycin-sensitive respiration, a finding which is consistent with a complex V defect. Thus, this mutation in MT-ATP6 may represent the first mtDNA point mutation associated with the MLASA phenotype. PMID:25037980

  19. A new disease-related mutation for mitochondrial encephalopathy lactic acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit of the respiratory complex I

    SciTech Connect

    Lertrit, P.; Noer, A.S.; Kapsa, R.; Marzuki, S. (Monash Univ., Clayton, Victoria (Australia)); Jean-Francois, M.J.B.; Thyagarajan, D.; Byrne, E. (St. Vincent's Hospital, Fitzroy, Victoria (Australia)); Dennett, X. (Univ. of Melbourne, Parkville, Victoria (Australia)); Lethlean, K. (Prince Henry Hospital, Sydney (Australia))

    1992-09-01

    The molecular lesions in two patients exhibiting classical clinical manifestations of MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome have been investigated. A recently reported disease-related A[yields]G base substitution at nt 3243 of the mtDNA, in the DHU loop of tRNA[sup Leu], was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA of one patient but was not observed, by either restriction-enzyme analysis or nucleotide sequencing, in the other. To define the molecular lesion in the patient who does not have the A[yields]G base substitution at nt 3243, the total mitochondrial genome of the patient has been sequenced. An A[yields]G base substitution at nt 11084, leading to a Thr-to-Ala amino acid replacement in the ND4 subunit of the respiratory complex I, is suggested to be a disease-related mutation. 49 refs., 7 figs., 1 tab.

  20. Starch Metabolism in Arabidopsis

    PubMed Central

    Streb, Sebastian; Zeeman, Samuel C.

    2012-01-01

    Starch is the major non-structural carbohydrate in plants. It serves as an important store of carbon that fuels plant metabolism and growth when they are unable to photosynthesise. This storage can be in leaves and other green tissues, where it is degraded during the night, or in heterotrophic tissues such as roots, seeds and tubers, where it is stored over longer time periods. Arabidopsis accumulates starch in many of its tissues, but mostly in its leaves during the day. It has proven to be a powerful genetic system for discovering how starch is synthesised and degraded, and new proteins and processes have been discovered. Such work has major significance for our starch crops, whose yield and quality could be improved by the application of this knowledge. Research into Arabidopsis starch metabolism has begun to reveal how its daily turnover is integrated into the rest of metabolism and adapted to the environmental conditions. Furthermore, Arabidopsis mutant lines deficient in starch metabolism have been employed as tools to study other biological processes ranging from sugar sensing to gravitropism and flowering time control. This review gives a detailed account of the use of Arabidopsis to study starch metabolism. It describes the major discoveries made and presents an overview of our understanding today, together with some as-yet unresolved questions. PMID:23393426

  1. Metabolic Dysfunction in Diabetic Cardiomyopathy

    PubMed Central

    Isfort, Michael; Stevens, Sarah C.W.; Schaffer, Stephen; Jong, Chian Ju; Wold, Loren E.

    2013-01-01

    Diabetic cardiomyopathy (DCM) is defined as cardiac disease independent of vascular complications during diabetes. The number of new cases of DCM is rising at epidemic rates in proportion to newly diagnosed cases of diabetes mellitus (DM) throughout the world. DCM is a heart failure syndrome found in diabetic patients that is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction, occurring in the absence of hypertension and coronary artery disease. DCM and other diabetic complications are caused in part by elevations in blood glucose and lipids, characteristic of DM. Although there are pathological consequences to hyperglycemia and hyperlipidemia, the combination of the two metabolic abnormalities potentiates the severity of diabetic complications. A natural competition exists between glucose and fatty acid metabolism in the heart that is regulated by allosteric and feedback control and transcriptional modulation of key limiting enzymes. Inhibition of these glycolytic enzymes not only controls flux of substrate through the glycolytic pathway, but also leads to the diversion of glycolytic intermediate substrate through pathological pathways, which mediate the onset of diabetic complications. The present review describes the limiting steps involved in the development of these pathological pathways and the factors involved in the regulation of these limiting steps. Additionally, therapeutic options with demonstrated or postulated effects on DCM are described. PMID:23443849

  2. Representations of metabolic knowledge: Pathways

    SciTech Connect

    Karp, P.D.; Paley, S.M. [SRI International, Menlo Park, CA (United States)

    1994-12-31

    The automatic generation of drawings of metabolic pathways is a challenging problem that depends intimately on exactly what information has been recorded for each pathway, and on how that information is encoded. The chief contributions of the paper are a minimized representation for biochemical pathways called the predecessor list, and inference procedures for converting the predecessor list into a pathway-graph representation that can serve as input to a pathway-drawing algorithm. The predecessor list has several advantages over the pathway graph, including its compactness and its lack of redundancy. The conversion between the two representations can be formulated as both a constraint-satisfaction problem and a logical inference problem, whose goal is to assign directions to reactions, and to determine which are the main chemical compounds in the reaction. We describe a set of production rules that solves this inference problem. We also present heuristics for inferring whether the exterior compounds that are substrates of reactions at the periphery of a pathway are side or main compounds. These techniques were evaluated on 18 metabolic pathways from the EcoCyc knowledge base.

  3. Benzodiazepine metabolism: an analytical perspective.

    PubMed

    Mandrioli, Roberto; Mercolini, Laura; Raggi, Maria Augusta

    2008-10-01

    Benzodiazepines are currently among the most frequently prescribed drugs all over the world. They act as anxiolytics, sedatives, hypnotics, amnesics, antiepileptics and muscle relaxants. Despite their common chemical scaffold, these drugs differ in their pharmacokinetic and metabolic properties. In particular, they are biotransformed by different cytochrome P450 isoforms and also by different UDP-glucuronosyltransferase subtypes. The most important studies on the metabolic characteristics of several 1,4-benzodiazepines, carried out from 1998 onwards, are reported and briefly discussed in this review. Moreover, the analytical methods related to these studies are also described and commented upon and their most important characteristics are highlighted. Most methods are based on liquid chromatography, which provides wide applicability and good analytical performance granting high precision, accuracy and feasibility. Mass spectrometry is gaining widespread acceptance, particularly if the matrix is very complex and variable, such as human or animal blood. However, spectrophotometric detection is still used for this purpose and can grant sufficient selectivity and sensitivity when coupled to suitable sample pre-treatment procedures. A monograph is included for each of the following benzodiazepines: alprazolam, bromazepam, brotizolam, clotiazepam, diazepam, etizolam, flunitrazepam, lorazepam, midazolam, oxazepam and triazolam. PMID:18855614

  4. Serotonin metabolism in cystic fibrosis.

    PubMed Central

    Partington, M W; Ferguson, A C

    1977-01-01

    The average blood serotonin level of 67 children with cystic fibrosis was found to be about twice that of age-matched normal children. There was no corresponding increase in the urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). Children with cystic fibrosis were well able to metabolize serotonin taken by mouth. No significant correlations were found between the blood serotonin level and the platelet count, height, weight, skinfold thickness, and pulmonary function test, 5 out of 44 patients had raised serum IgE levels, and their mean blood serotonin was higher than in those with normal IgE levels. No explanation for this emerged. Comparable findings (raised blood serotonin normal platelet count, normal urinary 5-HIAA) have been reported only in severe mental retardation. Further study of this phenomenon is warranted because (a) a raised blood serotonin level is sufficiently characteristic of cystic fibrosis to explore its use in diagnosis, and (b) it may help to explain the pathogenesis of cystic fibrosis and (c) the metabolism and function of serotonin. PMID:869568

  5. Representations of metabolic knowledge: pathways.

    PubMed

    Karp, P D; Paley, S M

    1994-01-01

    The automatic generation of drawings of metabolic pathways is a challenging problem that depends intimately on exactly what information has been recorded for each pathway, and on how that information is encoded. The chief contributions of the paper are a minimized representation for biochemical pathways called the predecessor list, and inference procedures for converting the predecessor list into a pathway-graph representation that can serve as input to a pathway-drawing algorithm. The predecessor list has several advantages over the pathway graph, including its compactness and its lack of redundancy. The conversion between the two representations can be formulated as both a constraint-satisfaction problem and a logical inference problem, whose goal is to assign directions to reactions, and to determine which are the main chemical compounds in the reaction. We describe a set of production rules that solves this inference problem. We also present heuristics for inferring whether the exterior compounds that are substrates of reactions at the periphery of a pathway are side or main compounds. These techniques were evaluated on 18 metabolic pathways from the EcoCyc knowledge base. PMID:7584392

  6. Diagnostics of Severe PCVAD

    Technology Transfer Automated Retrieval System (TEKTRAN)

    About 2 years ago case reports in Eastern Canada described a syndrome of an acute onset of high mortality in finishing age pigs. Within a year this syndrome had spread westward in Canada and was reported in several states in the U.S. Although diagnostic investigations into these cases have detecte...

  7. Severe acute respiratory syndrome

    Microsoft Academic Search

    Y Guan; K Y Yuen; J S M Peiris

    2004-01-01

    Severe acute respiratory syndrome (SARS) was caused by a previously unrecognized animal coronavirus that exploited opportunities provided by 'wet markets' in southern China to adapt to become a virus readily transmissible between humans. Hospitals and international travel proved to be 'amplifiers' that permitted a local outbreak to achieve global dimensions. In this review we will discuss the substantial scientific progress

  8. Ecophysiology. Climate change tightens a metabolic constraint on marine habitats.

    PubMed

    Deutsch, Curtis; Ferrel, Aaron; Seibel, Brad; Pörtner, Hans-Otto; Huey, Raymond B

    2015-06-01

    Warming of the oceans and consequent loss of dissolved oxygen (O2) will alter marine ecosystems, but a mechanistic framework to predict the impact of multiple stressors on viable habitat is lacking. Here, we integrate physiological, climatic, and biogeographic data to calibrate and then map a key metabolic index-the ratio of O2 supply to resting metabolic O2 demand-across geographic ranges of several marine ectotherms. These species differ in thermal and hypoxic tolerances, but their contemporary distributions are all bounded at the equatorward edge by a minimum metabolic index of ~2 to 5, indicative of a critical energetic requirement for organismal activity. The combined effects of warming and O2 loss this century are projected to reduce the upper ocean's metabolic index by ~20% globally and by ~50% in northern high-latitude regions, forcing poleward and vertical contraction of metabolically viable habitats and species ranges. PMID:26045435

  9. Metabolism of phencyclidine

    SciTech Connect

    Hoag, M.K.P.

    1987-01-01

    Phencyclidine (PCP) is a drug of abuse which may produce, in some users, a persistent schizophreniform psychosis. The possibility that long term effects of PCP are mediated by metabolic activation of the parent compound to reactive species is consistent with the demonstration of metabolism-dependent covalent binding of radiolabeled PCP in vivo and in vitro to macromolecules in rodent lung, liver, and kidney. Formation of the electrophilic iminium ion metabolite of PCP is believed to be critical for covalent binding since binding was inhibited by cyanide ion at concentrations which did not inhibit metabolism of PCP but did trap the iminium ion to form the corresponding alpha-aminonitrile. The present studies were designed to characterize further the biological fate of PCP by identifying possible macromolecular targets of the reactive metabolite(s).

  10. FGFs and metabolism.

    PubMed

    Kharitonenkov, Alexei

    2009-12-01

    Although the first fibroblast growth factor (FGF) was discovered as a mitogen on 3T3 fibroblasts [Gospodarowicz D: Localization of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth. Nature 1974, 249:123-127], this name is functionally misleading. This group of secreted proteins consisting now of 22 members was composed based on common structural characteristics rather than on functional similarity. Thus, only a few members of the human FGF family promote growth and strictly act on fibroblasts. While the research in the last century firmly established FGFs as key players in development, morphogenesis, angiogenesis, hematopoiesis, and survival, this decade provided clues on FGF roles in metabolism. In particular, 'hormone-like' FGF19, FGF21, and FGF23, were shown to be involved in glucose, lipid, bile acid, phosphate, and vitamin D metabolism but the mechanisms underlying their functions as metabolic regulators are still being defined. PMID:19683963

  11. Nitrile Metabolizing Yeasts

    NASA Astrophysics Data System (ADS)

    Bhalla, Tek Chand; Sharma, Monica; Sharma, Nitya Nand

    Nitriles and amides are widely distributed in the biotic and abiotic components of our ecosystem. Nitrile form an important group of organic compounds which find their applications in the synthesis of a large number of compounds used as/in pharmaceutical, cosmetics, plastics, dyes, etc>. Nitriles are mainly hydro-lyzed to corresponding amide/acid in organic chemistry. Industrial and agricultural activities have also lead to release of nitriles and amides into the environment and some of them pose threat to human health. Biocatalysis and biotransformations are increasingly replacing chemical routes of synthesis in organic chemistry as a part of ‘green chemistry’. Nitrile metabolizing organisms or enzymes thus has assumed greater significance in all these years to convert nitriles to amides/ acids. The nitrile metabolizing enzymes are widely present in bacteria, fungi and yeasts. Yeasts metabolize nitriles through nitrilase and/or nitrile hydratase and amidase enzymes. Only few yeasts have been reported to possess aldoxime dehydratase. More than sixty nitrile metabolizing yeast strains have been hither to isolated from cyanide treatment bioreactor, fermented foods and soil. Most of the yeasts contain nitrile hydratase-amidase system for metabolizing nitriles. Transformations of nitriles to amides/acids have been carried out with free and immobilized yeast cells. The nitrilases of Torulopsis candida>and Exophiala oligosperma>R1 are enantioselec-tive and regiospecific respectively. Geotrichum>sp. JR1 grows in the presence of 2M acetonitrile and may have potential for application in bioremediation of nitrile contaminated soil/water. The nitrilase of E. oligosperma>R1 being active at low pH (3-6) has shown promise for the hydroxy acids. Immobilized yeast cells hydrolyze some additional nitriles in comparison to free cells. It is expected that more focus in future will be on purification, characterization, cloning, expression and immobilization of nitrile metabolizing enzymes of yeasts.

  12. Artemether for severe malaria

    PubMed Central

    Esu, Ekpereonne; Effa, Emmanuel E; Opie, Oko N; Uwaoma, Amirahobu; Meremikwu, Martin M

    2014-01-01

    Background In 2011 the World Health Organization (WHO) recommended parenteral artesunate in preference to quinine as first-line treatment for people with severe malaria. Prior to this recommendation, many countries, particularly in Africa, had begun to use artemether, an alternative artemisinin derivative. This review evaluates intramuscular artemether compared with both quinine and artesunate. Objectives To assess the efficacy and safety of intramuscular artemether versus any other parenteral medication in treating severe malaria in adults and children. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE and LILACS, ISI Web of Science, conference proceedings and reference lists of articles. We also searched the WHO clinical trial registry platform, ClinicalTrials.gov and the metaRegister of Controlled Trials (mRCT) for ongoing trials up to 9 April 2014. Selection criteria Randomized controlled trials (RCTs) comparing intramuscular artemether with intravenous or intramuscular antimalarial for treating severe malaria. Data collection and analysis The primary outcome was all-cause death.Two authors independently assessed trial eligibility, risk of bias and extracted data. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD), and presented both measures with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses and assessed the quality of the evidence using the GRADE approach. Main results We included 18 RCTs, enrolling 2662 adults and children with severe malaria, carried out in Africa (11) and in Asia (7). Artemether versus quinine For children in Africa, there is probably little or no difference in the risk of death between intramuscular artemether and quinine (RR 0.96, 95% CI 0.76 to 1.20; 12 trials, 1447 participants, moderate quality evidence). Coma recovery may be about five hours shorter with artemether (MD -5.45, 95% CI -7.90 to -3.00; six trials, 358 participants, low quality evidence), and artemether may result in fewer neurological sequelae, but larger trials would be needed to confirm this (RR 0.84, 95% CI 0.66 to 1.07; seven trials, 968 participants, low quality evidence). Artemether probably shortens the parasite clearance time by about nine hours (MD -9.03, 95% CI -11.43 to -6.63; seven trials, 420 participants, moderate quality evidence), and may shorten the fever clearance time by about three hours (MD -3.73, 95% CI -6.55 to -0.92; eight trials, 457 participants, low quality evidence). For adults in Asia, treatment with intramuscular artemether probably results in fewer deaths than treatment with quinine (RR 0.59, 95% CI 0.42 to 0.83; four trials, 716 participants, moderate quality evidence). Artemether versus artesunate Artemether and artesunate have not been directly compared in randomized trials in African children. For adults in Asia, mortality is probably higher with intramuscular artemether (RR 1.80, 95% CI 1.09 to 2.97, two trials,494 participants, moderate quality evidence). Authors' conclusions Although there is a lack of direct evidence comparing artemether with artesunate, artemether is probably less effective than artesunate at preventing deaths from severe malaria. In circumstances where artesunate is not available, artemether is an alternative to quinine. PLAIN LANGUAGE SUMMARY Artemether injection for treating people with severe malaria In this review, researchers from The Cochrane Collaboration examined the effects of treating people that have severe malaria with artemether injected intramuscularly, and compared it to treatment with other antimalarial drugs given intramuscularly or intravenously. After searching for relevant trials up to 9 April 2014, we included 18 randomized controlled trials that recruited 2662 adults and children and were conducted mainly in Africa and Asia. What is severe malaria and how might artemether injection reduce deaths Severe malaria is caused by infection with the Plasmodium parasite, which

  13. Equine metabolic syndrome.

    PubMed

    Frank, Nicholas

    2011-04-01

    The concept of an equine metabolic syndrome (EMS) was first proposed in 2002. This concept has developed over time, and EMS was recently described in a consensus statement released by the American College of Veterinary Internal Medicine. In human medicine, metabolic syndrome (MetS) refers to a set of risk factors that predict the risk of cardiovascular disease, including obesity, glucose intolerance and insulin resistance (IR), dyslipidemia, microalbuminuria, and hypertension. EMS shares some of the features of MetS, including increased adiposity, hyperinsulinemia, IR, but differs in that laminitis is the primary disease of interest. PMID:21392655

  14. Drug metabolism and ageing

    PubMed Central

    Kinirons, M T; O'Mahony, M S

    2004-01-01

    Important changes in drug metabolism occur with ageing. Age-associated reductions in function of some but not all cytochrome P450 enzymes (CYPs) have been described. Induction and inhibition of CYPs needs to be revisited in light of recent advances. The function and pharmacology of transporters have not yet been examined for an age-related effect. Finally, the concept of frailty is being underpinned by studies documenting a decline in drug metabolism and changes in disposition in frail older people compared with either healthy elderly or the young. PMID:15089805

  15. Jejunal versus gastric feeding in patients with severe head trauma

    Microsoft Academic Search

    I. GRECU; M. NICOLAU; D. OLOGOIU; A. CONSTANTINESCU

    Introduction: Head trauma patients are highly catabolic and therefore require early and adequate nutritional support in order to sustain this metabolic reaction and prevent severe de- pletion of the body reserves. Although we have now an important body of evidence regarding the benefits of early enteral nutrition in these patients, there are still controversies regarding the method of nutrition delivery:

  16. Modelling runway incursion severity.

    PubMed

    Wilke, Sabine; Majumdar, Arnab; Ochieng, Washington Y

    2015-06-01

    Analysis of the causes underlying runway incursions is fundamental for the development of effective mitigation measures. However, there are significant weaknesses in the current methods to model these factors. This paper proposes a structured framework for modelling causal factors and their relationship to severity, which includes a description of the airport surface system architecture, establishment of terminological definitions, the determination and collection of appropriate data, the analysis of occurrences for severity and causes, and the execution of a statistical analysis framework. It is implemented in the context of U.S. airports, enabling the identification of a number of priority interventions, including the need for better investigation and causal factor capture, recommendations for airfield design, operating scenarios and technologies, and better training for human operators in the system. The framework is recommended for the analysis of runway incursions to support safety improvements and the methodology is transferable to other areas of aviation safety risk analysis. PMID:25819211

  17. Severe Snowstorm in Lesotho

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Some snow isn't an unexpected occurrence in the mountainous terrain of the small country of Lesotho, a small, roughly circular country located between Free State Province and Eastern Cape Province in the Republic of South Africa. But over the weekend of July 20, 2002, a severe snow storm dumped several feet of snow in the Drakensbueg Mountains, and turned many parts of the country into disaster areas. According to news reports, at least 22 people died and many more were stranded in mountain towns and camping areas, often without fuel or electricity, or food and water. This image was acquired by the Moderate Resolution Imaging Spectroradiometer (MODIS) on July 25, 2002. Credits: Image by Jesse Allen, based on data from the MODIS Rapid Response Team, NASA-GSFC

  18. Genetic determinants of the metabolic syndrome

    Microsoft Academic Search

    Michèle M. Sale; Jonathan Woods; Barry I. Freedman

    2006-01-01

    Complex interactions between inherited factors and the environment determine an individual’s susceptibility to type 2 diabetes\\u000a mellitus and related syndromes. Insulin resistance, obesity, hypertension, and hyperlipidemia frequently precede the development\\u000a of frank diabetes and aggregate in families. Several genome-wide scans have recently been performed in families with this\\u000a constellation of findings, called the “metabolic syndrome.” These analyses strongly support an

  19. Normal roles for dietary fructose in carbohydrate metabolism.

    PubMed

    Laughlin, Maren R

    2014-08-01

    Although there are many well-documented metabolic effects linked to the fructose component of a very high sugar diet, a healthy diet is also likely to contain appreciable fructose, even if confined to that found in fruits and vegetables. These normal levels of fructose are metabolized in specialized pathways that synergize with glucose at several metabolic steps. Glucose potentiates fructose absorption from the gut, while fructose catalyzes glucose uptake and storage in the liver. Fructose accelerates carbohydrate oxidation after a meal. In addition, emerging evidence suggests that fructose may also play a role in the secretion of insulin and GLP-1, and in the maturation of preadipocytes to increase fat storage capacity. Therefore, fructose undergoing its normal metabolism has the interesting property of potentiating the disposal of a dietary carbohydrate load through several routes. PMID:25100436

  20. Normal Roles for Dietary Fructose in Carbohydrate Metabolism

    PubMed Central

    Laughlin, Maren R.

    2014-01-01

    Although there are many well-documented metabolic effects linked to the fructose component of a very high sugar diet, a healthy diet is also likely to contain appreciable fructose, even if confined to that found in fruits and vegetables. These normal levels of fructose are metabolized in specialized pathways that synergize with glucose at several metabolic steps. Glucose potentiates fructose absorption from the gut, while fructose catalyzes glucose uptake and storage in the liver. Fructose accelerates carbohydrate oxidation after a meal. In addition, emerging evidence suggests that fructose may also play a role in the secretion of insulin and GLP-1, and in the maturation of preadipocytes to increase fat storage capacity. Therefore, fructose undergoing its normal metabolism has the interesting property of potentiating the disposal of a dietary carbohydrate load through several routes. PMID:25100436

  1. Tropical Severe Local Storms

    NSDL National Science Digital Library

    2014-09-14

    The module provides a brief overview of severe local storms in the tropics. Basic ingredients for thunderstorms and assessment of thunderstorm potential from soundings are described. Then properties and hazards of ordinary thunderstorms, multicellular thunderstorms, supercells are reviewed. Conditions conducive to supercell formation in the tropics are examined along with methods of identifying them in radar and satellite images. Supercell and non-supercell tornado properties and formation are described. Finally, tornadoes, waterspouts, and dust devils properties are compared.

  2. Management of severe hypospadias

    PubMed Central

    Catti, Massimo; Demède, Delphine; Valmalle, Anne-Frédérique; Mure, Pierre-Yves; Hameury, Frédéric; Mouriquand, Pierre

    2008-01-01

    Many classifications of hypospadias have been published, mainly based on the position of the ectopic meatus, which is an insufficient criterion to define the severity of this malformation. What really marks the proximal landmark of this malformation is the level of division of the corpus spongiosum, which is always proximal to the ectopic meatus. In this article, we will focus on the most severe forms of hypospadias which include those with a proximal division of corpus spongiosum (below the midshaft), important chordee and a poor development of the ventral radius, reflecting a marked hypovirilization of the genital tubercle, and cripple hypospadias resulting from several previous failed surgical procedures. The principle of hypospadias surgery will be reviewed together with the outcome of the current surgical techniques. Furthermore, common complications will be outlined. There is no minor or major hypospadias and all forms require a solid experience of the surgeon, as minor looking hypospadias may turn out to be far more complex to repair than they appear once the ventral radius of the penis has been dissected. PMID:19468403

  3. Bariatric metabolic surgery.

    PubMed

    Scopinaro, N

    2014-08-01

    According to the WHO, the worldwide prevalence of obesity body mass index (BMI) 30 kg/m² nearly doubled between 1980 and 2008, with 10% of men and 14% of women and a total of more than half a billion adults (aged >20 years old) being classed as obese. At least 2.8 million people die each year worldwide as a result of being overweight or obese, usually from the inevitable related comorbidities. It has been reported that approximately 65% of the worlds population inhabits countries where overweight and obesity are responsible for higher mortality than underweight. The recently published Interdisciplinary European Guidelines on Metabolic and Bariatric Surgery note that despite the WHO stating that excess weight is considered the fifth leading risk for deaths worldwide, it has not yet been possible to successfully curb the obesity epidemic. Moreover, severe obesity (BMI>35 kg/m²) represents a rapidly growing segment of the epidemic in which the negative effects on health and disability are especially marked. Excess weight drastically elevates a persons risk of developing a number of non-communicable diseases, such as diabetes, hypertension, stroke, dyslipidaemia, sleep apnoea, cancer, non-alcoholic steatohepatitis, and other serious comorbidities. The WHO emphasises that 44% of type 2 diabetes mellitus, 23% of ischaemic heart disease and around 741% of certain cancers are attributable to overweight and obesity. In the majority of European countries, overweight and obesity are responsible for about 80% of cases of type 2 diabetes, 35% of cases of ischaemic heart disease and 55% of cases of hypertensive disease among adults. Additionally, a range of debilitating conditions such as osteoarthritis, respiratory difficulties, gallbladder disease, infertility, and psychosocial problems, among others, which lead to reduced life expectancy, quality of life and disability, are extremely costly in terms of both absence from work and use of health resources. Noteworthy, the lifespan of severely obese individuals is decreased by an estimated 5-20 years depending on gender, age, and race. Weight loss and maintenance are the obvious aims of bariatric surgery. The ideal bariatric operation should be easy and quick to perform, with minimal perioperative and long-term complications. It should result in excellent weight loss and indefinite weight maintenance in the vast majority of operated patients, necessitating minimal follow-up care, and be equally suitable for all patients, independent of individual characteristics such as compliance, age, and different degrees of overweight. It is immediately apparent that such a surgical procedure does not exist, and therefore we must carefully evaluate all the different features and characteristics of each operation and of each patient to try to select the procedure that provides the greatest probability of long-term success for a particular patient, with the best cost/benefit ratio. Bariatric surgery has proven to be the most effective mode of treatment for morbidly obese patients, with recent long-term studies providing evidence of a substantial reduction of mortality in bariatric surgery patients, as well as a decreased risk of developing new health-related comorbidities. Furthermore, a reduction in the use of healthcare services and therefore a reduction in direct healthcare costs was also observed. Bariatric surgery is an established and integral part of the comprehensive management of morbidly obese patients. PMID:25230385

  4. Branched Tricarboxylic Acid Metabolism in Plasmodium falciparum

    PubMed Central

    Olszewski, Kellen L.; Mather, Michael W.; Morrisey, Joanne M.; Garcia, Benjamin A.; Vaidya, Akhil B.; Rabinowitz, Joshua D.; Llinás, Manuel

    2010-01-01

    A central hub of carbon metabolism is the tricarboxylic acid (TCA) cycle1, which serves to connect the processes of glycolysis, gluconeogenesis, respiration, amino acid synthesis and other biosynthetic pathways. The protozoan intracellular malaria parasites (Plasmodium spp.), however, have long been suspected of possessing a significantly streamlined carbon metabolic network in which TCA metabolism plays a minor role2. Blood-stage Plasmodium parasites rely almost entirely on glucose fermentation for energy and consume minimal amounts of oxygen3, yet the parasite genome encodes all of the enzymes necessary for a complete TCA cycle4. By tracing 13C-labeled compounds using mass spectrometry5 we show that TCA metabolism in the human malaria parasite P. falciparum is largely disconnected from glycolysis and is organized along a fundamentally different architecture than the canonical textbook pathway. We find that this pathway is not cyclic but rather a branched structure in which the major carbon sources are the amino acids glutamate and glutamine. As a consequence of this branched architecture, several reactions must run in the reverse of the standard direction thereby generating two-carbon units in the form of acetyl-coenzyme A (acetyl-CoA). We further show that glutamine-derived acetyl-CoA is used for histone acetylation while glucose-derived acetyl-CoA is used to acetylate aminosugars. Thus the parasite has evolved two independent acetyl-CoA-production mechanisms with different biological functions. These results significantly clarify our understanding of the Plasmodium metabolic network and highlight the ability of altered variants of central carbon metabolism to arise in response to unique environments. PMID:20686576

  5. Arsenic Toxicity: The Effects on Plant Metabolism

    PubMed Central

    Finnegan, Patrick M.; Chen, Weihua

    2012-01-01

    The two forms of inorganic arsenic, arsenate (AsV) and arsenite (AsIII), are easily taken up by the cells of the plant root. Once in the cell, AsV can be readily converted to AsIII, the more toxic of the two forms. AsV and AsIII both disrupt plant metabolism, but through distinct mechanisms. AsV is a chemical analog of phosphate that can disrupt at least some phosphate-dependent aspects of metabolism. AsV can be translocated across cellular membranes by phosphate transport proteins, leading to imbalances in phosphate supply. It can compete with phosphate during phosphorylation reactions, leading to the formation of AsV adducts that are often unstable and short-lived. As an example, the formation and rapid autohydrolysis of AsV-ADP sets in place a futile cycle that uncouples photophosphorylation and oxidative phosphorylation, decreasing the ability of cells to produce ATP and carry out normal metabolism. AsIII is a dithiol reactive compound that binds to and potentially inactivates enzymes containing closely spaced cysteine residues or dithiol co-factors. Arsenic exposure generally induces the production of reactive oxygen species that can lead to the production of antioxidant metabolites and numerous enzymes involved in antioxidant defense. Oxidative carbon metabolism, amino acid and protein relationships, and nitrogen and sulfur assimilation pathways are also impacted by As exposure. Readjustment of several metabolic pathways, such as glutathione production, has been shown to lead to increased arsenic tolerance in plants. Species- and cultivar-dependent variation in arsenic sensitivity and the remodeling of metabolite pools that occurs in response to As exposure gives hope that additional metabolic pathways associated with As tolerance will be identified. PMID:22685440

  6. Metabolic Interdependence of Obligate Intracellular Bacteria and Their Insect Hosts†

    PubMed Central

    Zientz, Evelyn; Dandekar, Thomas; Gross, Roy

    2004-01-01

    Mutualistic associations of obligate intracellular bacteria and insects have attracted much interest in the past few years due to the evolutionary consequences for their genome structure. However, much less attention has been paid to the metabolic ramifications for these endosymbiotic microorganisms, which have to compete with but also to adapt to another metabolism—that of the host cell. This review attempts to provide insights into the complex physiological interactions and the evolution of metabolic pathways of several mutualistic bacteria of aphids, ants, and tsetse flies and their insect hosts. PMID:15590782

  7. Inflammasomes and Metabolic Disorders: Old Genes in Modern Diseases

    PubMed Central

    Robbins, Gregory R.; Wen, Haitao; Ting, Jenny P.-Y.

    2014-01-01

    Summary Modern medical and hygienic practices have greatly improved human health and longevity; however, increased human lifespan occurs concomitantly with the emergence of metabolic and age-related diseases. Studies over the past decade have strongly linked host inflammatory responses to the etiology of several metabolic diseases including atherosclerosis, type 2 diabetes (T2D), obesity and gout. A common immunological factor to these diseases is the activation of the inflammasome and release of pro-inflammatory cytokines that promote disease progression. Here we review the molecular mechanism(s) of inflammasome activation in response to metabolic damage associated molecular patterns (DAMPs) and discuss potential targets for therapeutic intervention. PMID:24766894

  8. Cardiac Metabolism in Heart Failure - Implications beyond ATP production

    PubMed Central

    Doenst, Torsten; Nguyen, T. Dung; Abel, E. Dale

    2013-01-01

    The heart has a high rate of ATP production and turnover which is required to maintain its continuous mechanical work. Perturbations in ATP generating processes may therefore affect contractile function directly. Characterizing cardiac metabolism in heart failure revealed several metabolic alterations termed metabolic remodeling, ranging from changes in substrate utilization to mitochondrial dysfunction, ultimately resulting in ATP deficiency and impaired contractility. However, ATP depletion is not the only relevant consequence of metabolic remodeling during heart failure. By providing cellular building blocks and signaling molecules, metabolic pathways control essential processes such as cell growth and regeneration. Thus, alterations in cardiac metabolism may also affect the progression to heart failure by mechanisms beyond ATP supply. Our aim is therefore to highlight that metabolic remodeling in heart failure not only results in impaired cardiac energetics, but also induces other processes implicated in the development of heart failure such as structural remodeling and oxidative stress. Accordingly, modulating cardiac metabolism in heart failure may have significant therapeutic relevance that goes beyond the energetic aspect. PMID:23989714

  9. Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency

    Microsoft Academic Search

    Leo AJ Kluijtmans; Udo Wendel; Erik MB Stevens; Lambert PWJ van den Heuvel; Frans JM Trijbels; Henk J Blom

    1998-01-01

    Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is an inborn error of folate metabolism, and is inherited as an autosomal recessive trait. MTHFR is a key enzyme in folate-dependent remethylation of homocysteine, and reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Patients with this severe enzymatic deficiency are biochemically characterised by homocystinuria and hypomethioninaemia, and may suffer from neurological abnormalities, mental retardation and premature vascular disease.

  10. Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia

    SciTech Connect

    Volkow, N.D.; Wolf, A.P.; Van Gelder, P.; Brodie, J.D.; Overall, J.E.; Cancro, R.; Gomez-Mont, F.

    1987-02-01

    Using (11C)-deoxy-D-glucose and positron emission tomography (PET), the authors measured brain metabolism in 18 patients with chronic schizophrenia to assess which of the metabolic measures from two test conditions was more closely related to the patients' differing clinical characteristics. The two conditions were resting and activation, and an eye tracking task was used. Patients with more negative symptoms showed lower global metabolic rates and more severe hypofrontality than did the patients with fewer negative symptoms. Differences among the patients were distinguished by the task: sicker patients failed to show a metabolic activation response. These findings suggest that cerebral metabolic patterns reflect clinical characteristics of schizophrenic patients.

  11. How Is Metabolic Syndrome Treated?

    MedlinePLUS

    ... page from the NHLBI on Twitter. How Is Metabolic Syndrome Treated? Healthy lifestyle changes are the first line of treatment for metabolic syndrome. Lifestyle changes include losing weight, being physically active, ...

  12. Speech-induced cerebral metabolic activation reflects recovery from aphasia

    Microsoft Academic Search

    Wolf-Dieter Heiss; Hans Karbe; Gerald Weber-Luxenburger; Karl Herholz; Josef Kessler; Uwe Pietrzyk; Gunter Pawlik

    1997-01-01

    Six stroke patients with clinically significant aphasia were studied 4 weeks and again 12–18 months after their first left hemispheric ictus. The regional cerebral metabolic rate of glucose (rCMRglc) was measured repeatedly by PET at rest and during word repetition, and severity of speech impairment was assessed by a neuropsychologic test battery. The patterns of speech-associated activation of glucose metabolism

  13. Lipidomics as a Tool for the Study of Lipoprotein Metabolism

    Microsoft Academic Search

    Anatol Kontush; M. John Chapman

    2010-01-01

    Although technologies for lipidomic and proteomic investigations have developed very recently, lipidomic and proteomic studies\\u000a of plasma lipoproteins have already provided several impressive examples of detailed characterization of distinct metabolic\\u000a pathways potentially involved in lipoprotein metabolism in both health and disease states (obesity, insulin resistance, fatty\\u000a liver disease) as well as under lifestyle and dietary modification (fish consumption, carbohydrates, probiotics)

  14. The link between abdominal obesity and the metabolic syndrome

    Microsoft Academic Search

    Liza K. Phillips; Johannes B. Prins

    2008-01-01

    The clustering of cardiovascular risk factors associated with abdominal obesity is well established. Although currently lacking\\u000a a universal definition, the metabolic syndrome describes a constellation of metabolic abnormalities, including abdominal obesity,\\u000a and was originally introduced to characterize a population at high cardiovascular risk. Adipose tissue is a dynamic endocrine\\u000a organ that secretes several inflammatory and immune mediators known as adipokines.

  15. A Simple and Inexpensive Apparatus for Measuring Fish Metabolism

    NSDL National Science Digital Library

    Dr. Martin Bolduc (Universite´ du Que´bec a` Rimouski De´partement de Biologie, de Chimie et des Sciences de la Sante´)

    2002-06-01

    A simple, noninvasive, and economical home-made respirometer has been used to determine the standard metabolism of goldfish. The apparatus has been tested on several fishes and has proved its accuracy in determining a mass effect on standard metabolism. The apparatus can be made easily by middle school, high school, and undergraduate students and can be used to introduce them to basic concepts in animal physiology and in biological statistics.

  16. Cell Metabolism Short Article

    E-print Network

    Chanfreau, Guillaume

    sphingolipid synthesis and signaling is sufficient to allow yeast cells to grow in otherwise toxic ironCell Metabolism Short Article Sphingolipid Signaling Mediates Iron Toxicity Yueh-Jung Lee,1 Xinhe: guillom@chem.ucla.edu http://dx.doi.org/10.1016/j.cmet.2012.06.004 SUMMARY Iron constitutes a major source

  17. [Metabolic and mitochondrial myopathies].

    PubMed

    Vorgerd, M; Deschauer, M

    2013-04-01

    Metabolic myopathies include a broad group of diseases involving inherited enzyme defects in the various metabolic pathways and skeletal musculature. They show an extensive phenotypic variability of symptoms and different ages of manifestation. Symptoms often included intolerance to duress or permanent paresis. Some forms of metabolic myopathy, in particular mitochondriopathy, are associated with multsystemic organ participation. The diagnostics must be adjusted to individual cases and carried out in stages. Primary investigations should include blood parameters (e.g. creatine kinase measurement, muscle load tests and determination of the acylcarnitine spectrum) and a second step includes muscle biopsy for histological and enzyme investigations and special molecular genetic tests although the causative enzyme defect cannot be clarified in every case. On the other hand by means of a thorough investigation it is particularly important in patients with load intolerance to differentiate between other causes, in particular psychosomatic diseases. If this is not done there is a danger of classifying the symptoms of a metabolic myopathy as a somatoform disorder. Therapy is mostly symptom-oriented as Pompe disease is the only one which can be treated with enzyme replacement therapy. PMID:23553022

  18. Secondary metabolism in tobacco

    Microsoft Academic Search

    Laurentius H. Nugroho; Robert Verpoorte

    2002-01-01

    Tobacco has been quite well studied phytochemically, more than 2500 compounds have been identified. Here, the secondary metabolism in tobacco will be reviewed in a biosynthetic perspective. Major groups of compounds which have extensively been studied are the isoprenoids, alkaloids, cinnamoylputrescines, flavonoids, and anthocyanins. Their biosynthetic pathways and its regulation, and their occurrence in cell cultures and in intact plants

  19. Disorders of Calcium Metabolism

    Microsoft Academic Search

    John F. O’Toole

    2011-01-01

    The genetic contribution to calcium metabolism is well recognized. Many of the proteins that contribute to calcium homeostasis through intestinal absorption, bone deposition and resorption, renal reabsorption and the molecules regulating these processes have been identified. Mutations in many of the genes coding for these proteins have been identified and often have clear clinical phenotypes. These mutations are generally rare

  20. Glyphosate metabolism in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many soil microbes and plant species metabolically degrade the herbicide glyphosate. The primary degradation routes are by a glyphosate oxidoreductase (GOX) to form aminomethylphosphonic acid (AMPA) as the distinctive metabolite and by a C-P lyase that forms sarcosine as a main metabolite. AMPA app...

  1. Anaerobic Amino Acid Metabolism

    Microsoft Academic Search

    R. Reggiani; A. Bertani

    2003-01-01

    Anoxic stress induces a strong change in sugar, protein, and amino acid metabolism in higher plants. Sugars are rapidly consumed through the anaerobic glycolysis to sustain energy production. Protein degradation under anoxia is a mechanism to release free amino acids contributing in this way to maintaining the osmotic potential of the tissue under stress. Among free amino acids, a particular

  2. Lipoprotein(a) metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein. The metabolism of this lipoprotein is still not well understood. It has long been known that the plasma concentration of Lp(a) is highly heritable, with its genetic determinants located in the apo(a) locus and regulating the rate of hepatic apo(a...

  3. Metabolic breath analyzer

    NASA Technical Reports Server (NTRS)

    Perry, C. L.

    1971-01-01

    Instrument measures metabolic breathing rate and dynamics of human beings in atmospheres ranging from normal air to 100 percent oxygen at ambient pressures from 14.7 to 3.0 psia. Measurements are made at rest or performing tasks up to maximum physical capacity under either zero or normal gravity.

  4. [Regulation of terpene metabolism

    Microsoft Academic Search

    Croteau

    1989-01-01

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C[sub 10]) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites

  5. Metabolism of trichloroethylene.

    PubMed Central

    Lash, L H; Fisher, J W; Lipscomb, J C; Parker, J C

    2000-01-01

    A major focus in the study of metabolism and disposition of trichloroethylene (TCE) is to identify metabolites that can be used reliably to assess flux through the various pathways of TCE metabolism and to identify those metabolites that are causally associated with toxic responses. Another important issue involves delineation of sex- and species-dependent differences in biotransformation pathways. Defining these differences can play an important role in the utility of laboratory animal data for understanding the pharmacokinetics and pharmacodynamics of TCE in humans. Sex-, species-, and strain-dependent differences in absorption and distribution of TCE may play some role in explaining differences in metabolism and susceptibility to toxicity from TCE exposure. The majority of differences in susceptibility, however, are likely due to sex-, species-, and strain-dependent differences in activities of the various enzymes that can metabolize TCE and its subsequent metabolites. An additional factor that plays a role in human health risk assessment for TCE is the high degree of variability in the activity of certain enzymes. TCE undergoes metabolism by two major pathways, cytochrome P450 (P450)-dependent oxidation and conjugation with glutathione (GSH). Key P450-derived metabolites of TCE that have been associated with specific target organs, such as the liver and lungs, include chloral hydrate, trichloroacetate, and dichloroacetate. Metabolites derived from the GSH conjugate of TCE, in contrast, have been associated with the kidney as a target organ. Specifically, metabolism of the cysteine conjugate of TCE by the cysteine conjugate ss-lyase generates a reactive metabolite that is nephrotoxic and may be nephrocarcinogenic. Although the P450 pathway is a higher activity and higher affinity pathway than the GSH conjugation pathway, one should not automatically conclude that the latter pathway is only important at very high doses. A synthesis of this information is then presented to assess how experimental data, from either animals or from (italic)in vitro (/italic)studies, can be extrapolated to humans for risk assessment. (italic)Key words(/italic): conjugate beta-lyase, cysteine glutathione, cytochrome P450, glutathione (italic)S(/italic)-transferases, metabolism, sex dependence, species dependence, tissue dependence, trichloroethylene. Images Figure 2 Figure 3 PMID:10807551

  6. Symptoms and Diagnosis of Metabolic Syndrome

    MedlinePLUS

    ... Tools & Resources Stroke More Symptoms and Diagnosis of Metabolic Syndrome Updated:Nov 20,2014 What are the symptoms ... content was last reviewed on 05/14/2014. Metabolic Syndrome • Home • About Metabolic Syndrome • Why Metabolic Syndrome Matters • ...

  7. Redundancy in Metabolic Networks

    NASA Astrophysics Data System (ADS)

    Domach, Michael M.

    2009-09-01

    Metabolic networks possess redundant functionalities and thus they can behave as highly resilient systems. One practical consequence is many seemingly obvious mutations fail to work as intended when metabolic engineering is attempted. Alternately, mutations distal from where an effect on metabolism is sought prove to be effective. The existence of viable and alternate flux solutions can also confound the interpretation of 13C NMR experiments. Unless 13C label design for a precursor such as glucose is correctly done, wrong answers can be obtained concerning the effect of a mutation when one goes numerically from NMR data to the values of the metabolic fluxes. From the practical stand point, such incorrect answers can then (i) cause one to reject a mutation strategy that is actually successful or (ii) lead to formulating incorrect next steps for the round(s) of mutation. After summarizing different ways to analyze metabolic networks (e.g. mixed integer programming), this presentation will first present examples of how a non-obvious mutation proved to be the winner. Both modeling and experimental results will be shown. Abolishing pyruvate kinase activity (rPyk) will be shown to increase folic acid synthesis in B. subtilis by 700% Interesting the same mutation in a different organism, E. coli, significantly increases the yield of therapeutic DNA as shown below. This presentation will close with a case study that shows how different NMR-based flux distributions were reported in the literature for the same E. coli mutant. Through network analysis and NMR simulation it will be shown that one answer is incorrect and it arose due to network redundancy and low-contrast label design.

  8. Evolution of metabolic network organization

    Microsoft Academic Search

    Aurélien Mazurie; Danail Bonchev; Benno Schwikowski; Gregory A Buck

    2010-01-01

    BACKGROUND: Comparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks. By selecting taxa representative of different lineages or lifestyles and using a comprehensive set of descriptors of the structure and complexity of their metabolic networks, one can highlight both qualitative and quantitative differences in the metabolic organization of species subject to distinct

  9. 13C Metabolic Flux Analysis

    Microsoft Academic Search

    Wolfgang Wiechert

    2001-01-01

    Metabolic flux analysis using 13C-labeled substrates has become an important tool in metabolic engineering. It allows the detailed quantification of all intracellular fluxes in the central metabolism of a microorganism. The method has strongly evolved in recent years by the introduction of new experimental procedures, measurement techniques, and mathematical data evaluation methods. Many of these improvements require advanced skills in

  10. Metabolic syndrome and localization of white matter hyperintensities in the elderly Florence Portet1,2,3

    E-print Network

    Paris-Sud XI, Université de

    1 Metabolic syndrome and localization of white matter hyperintensities in the elderly Florence; inserm-00715982,version1-9Jul2012 #12;3 ABSTRACT Background: Metabolic syndrome (MetS) is defined. INTRODUCTION Several epidemiological studies have investigated the association between metabolic syndrome (Met

  11. Pulmonary metabolism of foreign compounds: its role in metabolic activation.

    PubMed Central

    Cohen, G M

    1990-01-01

    The lung has the potential of metabolizing many foreign chemicals to a vast array of metabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity of many pulmonary toxins. Environmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity. PMID:2200668

  12. Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome

    PubMed Central

    2012-01-01

    Background MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. Case presentation We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Conclusions Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves. PMID:22353239

  13. Severe Staphylococcus lugdunensis keratitis.

    PubMed

    Inada, N; Harada, N; Nakashima, M; Shoji, J

    2015-02-01

    We report a severe case of Staphylococcus lugdunensis (S. lugdunensis) keratitis presenting as suppurative keratitis in a 77-year-old woman. The patient's chief complaint was eye pain and decreased visual acuity in her right eye. Suppurative keratitis with a severe corneal abscess was diagnosed by a slit-lamp ophthalmic examination. The causative organism was identified as S. lugdunensis by bacterial culture, using a corneal abrasion specimen. She was treated with an intravenous drip infusion of ceftazidime and instillation of gentamicin sulfate ophthalmic solution (six times daily) and ofloxacin ophthalmic ointment (once daily before bedtime) as empiric therapy. Her hospital course was complicated by a corneal perforation of her right eye. The antibiotic susceptibility for S. lugdunensis was sensitive, but with a slightly high MIC for antibiotics used in empiric therapy. The therapeutic drug was changed to levofloxacin ophthalmic solution. The corneal abscess left a scar after healing. Representative causative organisms of suppurative keratitis include Pseudomonas aeruginosa and Streptococcus pneumoniae, but care must be taken in cases involving rare causative organisms. Empiric therapy is necessary for rapidly progressing suppurative keratitis, but a detailed examination of the causative organism is important for therapeutic planning before empiric therapy. PMID:25082203

  14. Gas biology: tiny molecules controlling metabolic systems.

    PubMed

    Kajimura, Mayumi; Nakanishi, Tsuyoshi; Takenouchi, Toshiki; Morikawa, Takayuki; Hishiki, Takako; Yukutake, Yoshinori; Suematsu, Makoto

    2012-11-15

    It has been recognized that gaseous molecules and their signaling cascades play a vital role in alterations of metabolic systems in physiologic and pathologic conditions. Contrary to this awareness, detailed mechanisms whereby gases exert their actions, in particular in vivo, have been unclear because of several reasons. Gaseous signaling involves diverse reactions with metal centers of metalloproteins and thiol modification of cysteine residues of proteins. Both the multiplicity of gas targets and the technical limitations in accessing local gas concentrations make dissection of exact actions of any gas mediator a challenge. However, a series of advanced technologies now offer ways to explore gas-responsive regulatory processes in vivo. Imaging mass spectrometry combined with quantitative metabolomics by capillary-electrophoresis/mass spectrometry reveals spatio-temporal profiles of many metabolites. Comparing the metabolic footprinting of murine samples with a targeted deletion of a specific gas-producing enzyme makes it possible to determine sites of actions of the gas. In this review, we intend to elaborate on the ideas how small gaseous molecules interact with metabolic systems to control organ functions such as cerebral vascular tone and energy metabolism in vivo. PMID:22516267

  15. Metabolism of hop-derived bitter acids.

    PubMed

    Cattoor, Ko; Dresel, Michael; De Bock, Lies; Boussery, Koen; Van Bocxlaer, Jan; Remon, Jean-Paul; De Keukeleire, Denis; Deforce, Dieter; Hofmann, Thomas; Heyerick, Arne

    2013-08-21

    In this study, in vitro metabolism of hop-derived bitter acids was investigated. Besides their well-known use as bitter compounds in beer, in several studies, bioactive properties have been related to these types of molecules. However, scientific data on the absorption, distribution, metabolism, and excretion aspects of these compounds are limited. More specific, in this study, ?-acids, ?-acids, and iso-?-acids were incubated with rabbit microsomes, and fractions were subjected to LC-MS/MS analysis for identification of oxidative biotransformation products. Metabolism of ?-acids was mainly characterized by conversion into hulupones and the formation of a series of tricyclic oxygenated products. The most important metabolites of ?-acids were identified as humulinones and hulupones. Iso-?-acids were found to be primarly metabolized into cis- and trans-humulinic acids, next to oxidized alloiso-?-acids. Interestingly, the phase I metabolites were highly similar to the oxidative degradation products in beer. These findings show a first insight into the metabolites of hop-derived bitter acids and could have important practical implications in the bioavailability aspects of these compounds, following ingestion of hop-based food products and nutraceuticals. PMID:23898921

  16. Measurement by phase severance

    SciTech Connect

    Noyes, H.P.

    1987-03-01

    It is claimed that the measurement process is more accurately described by ''quasi-local phase severance'' than by ''wave function collapse''. The approach starts from the observation that the usual route to quantum mechanics starting from the Hamilton-Jacobi equations throws away half the degrees of freedom, namely, the classical initial state parameters. To overcome this difficulty, the full set of Hamilton-Jacobi equations is interpreted as operator equations acting on a state vector. The measurement theory presented is based on the conventional S-matrix boundary condition of N/sub A/ free particles in the distant past and N/sub B/ free particles in the distant future and taking the usual free particle wave functions, multiplied by phase factors.

  17. Flux Balance Analysis of Cyanobacterial Metabolism: The Metabolic Network of Synechocystis sp. PCC 6803

    PubMed Central

    Knoop, Henning; Gründel, Marianne; Zilliges, Yvonne; Lehmann, Robert; Hoffmann, Sabrina; Lockau, Wolfgang; Steuer, Ralf

    2013-01-01

    Cyanobacteria are versatile unicellular phototrophic microorganisms that are highly abundant in many environments. Owing to their capability to utilize solar energy and atmospheric carbon dioxide for growth, cyanobacteria are increasingly recognized as a prolific resource for the synthesis of valuable chemicals and various biofuels. To fully harness the metabolic capabilities of cyanobacteria necessitates an in-depth understanding of the metabolic interconversions taking place during phototrophic growth, as provided by genome-scale reconstructions of microbial organisms. Here we present an extended reconstruction and analysis of the metabolic network of the unicellular cyanobacterium Synechocystis sp. PCC 6803. Building upon several recent reconstructions of cyanobacterial metabolism, unclear reaction steps are experimentally validated and the functional consequences of unknown or dissenting pathway topologies are discussed. The updated model integrates novel results with respect to the cyanobacterial TCA cycle, an alleged glyoxylate shunt, and the role of photorespiration in cellular growth. Going beyond conventional flux-balance analysis, we extend the computational analysis to diurnal light/dark cycles of cyanobacterial metabolism. PMID:23843751

  18. Modeling metabolic homeostasis and nutrient sensing in Drosophila: implications for aging and metabolic diseases

    PubMed Central

    Owusu-Ansah, Edward; Perrimon, Norbert

    2014-01-01

    Over the past decade, numerous reports have underscored the similarities between the metabolism of Drosophila and vertebrates, with the identification of evolutionarily conserved enzymes and analogous organs that regulate carbohydrate and lipid metabolism. It is now well established that the major metabolic, energy-sensing and endocrine signaling networks of vertebrate systems are also conserved in flies. Accordingly, studies in Drosophila are beginning to unravel how perturbed energy balance impinges on lifespan and on the ensuing diseases when energy homeostasis goes awry. Here, we highlight several emerging concepts that are at the nexus between obesity, nutrient sensing, metabolic homeostasis and aging. Specifically, we summarize the endocrine mechanisms that regulate carbohydrate and lipid metabolism, and provide an overview of the neuropeptides that regulate feeding behavior. We further describe the various efforts at modeling the effects of high-fat or -sugar diets in Drosophila and the signaling mechanisms involved in integrating organ function. Finally, we draw attention to some of the cardinal discoveries made with these disease models and how these could spur new research questions in vertebrate systems. PMID:24609035

  19. Is Cancer a Metabolic Disease?

    PubMed Central

    Coller, Hilary A.

    2015-01-01

    Although cancer has historically been viewed as a disorder of proliferation, recent evidence has suggested that it should also be considered a metabolic disease. Growing tumors rewire their metabolic programs to meet and even exceed the bioenergetic and biosynthetic demands of continuous cell growth. The metabolic profile observed in cancer cells often includes increased consumption of glucose and glutamine, increased glycolysis, changes in the use of metabolic enzyme isoforms, and increased secretion of lactate. Oncogenes and tumor suppressors have been discovered to have roles in cancer-associated changes in metabolism as well. The metabolic profile of tumor cells has been suggested to reflect the rapid proliferative rate. Cancer-associated metabolic changes may also reveal the importance of protection against reactive oxygen species or a role for secreted lactate in the tumor microenvironment. This article reviews recent research in the field of cancer metabolism, raising the following questions: Why do cancer cells shift their metabolism in this way? Are the changes in metabolism in cancer cells a consequence of the changes in proliferation or a driver of cancer progression? Can cancer metabolism be targeted to benefit patients? PMID:24139946

  20. Metabolic Studies in Familial Hypercholesterolemia

    PubMed Central

    Bilheimer, David W.; Stone, Neil J.; Grundy, Scott M.

    1979-01-01

    To investigate the gene-dosage effect in familial hypercholesterolemia (FH), metabolic studies were conducted in a group of well-characterized patients with either heterozygous (n = 7) or homozygous (n = 7) FH and the results were compared to those obtained in normal subjects (n = 6). The turnover of 125I-labeled low-density lipoprotein (LDL) was measured in all of the normals, all but one of the FH heterozygotes, and in all of the homozygotes. Chemical cholesterol balance was performed simultaneously with the 125I-LDL turnover in all seven of the homozygotes. With regard to 125I-LDL turnover, FH homozygotes, who possess two doses of the mutant FH gene, exhibited a threefold increase in the rate of apoLDL synthesis while the fractional catabolic rate (FCR) for the apoprotein was only about one-third of normal. Heterozygotes, who have only one dose of the mutant FH gene, exhibited intermediate values for both parameters; that is, the FCR was two-thirds of normal and the apoLDL synthetic rate was 1.7-fold greater than normal. The data indicate that the single gene defect in FH produces two distinct abnormalities of LDL metabolism: (a) an increase in the synthetic rate for apoLDL and (b) a decrease in the efficiency of apoLDL catabolism. Both defects are more severe in FH homozygotes than in heterozygotes. The FCR for apoLDL in the homozygotes appeared to be fixed at ? 17%/d whereas the plasma LDL level varied about twofold. These findings suggest that the twofold variation in plasma LDL levels observed in these seven patients is caused by variation in the plasma apoLDL synthetic rates. Consistent with this conclusion was the finding that the correlation between the plasma LDL level and the apoLDL synthetic rates in the seven FH homozygotes was 0.943. The rate of total body cholesterol synthesis determined by chemical cholesterol balance did not appear to clearly differ between normals and patients with either one or two mutant FH genes. Two of the youngest FH homozygotes exhibited cholesterol overproduction but the other five did not. No consistent abnormality of bile acid metabolism was observed in these patients. Because the daily plasma flux of cholesterol on LDL is about threefold greater than the amount of cholesterol produced per day, a significant amount of the cholesterol liberated from LDL degradation must be reused. PMID:222811