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Sample records for severe metabolic acidosis

  1. Severe metabolic acidosis following assault chemical burn.

    PubMed

    Roock, Sophie D; Deleuze, Jean-Paul; Rose, Thomas; Jennes, Serge; Hantson, Philippe

    2012-04-01

    Assault chemical burns are uncommon in northern Europe. Besides local toxicity, systemic manifestations are possible after strong acid exposure. A 40-year-old woman was admitted 1 h after a criminal assault with sulfuric acid. The total burned surface area was 35%, third degree. Injury was due to sulfuric acid (measured pH 0.9) obtained from a car battery. Immediate complications were obstructive dyspnea and metabolic acidosis. The admission arterial pH was 6.92, with total bicarbonate 8.6 mEq/l and base deficit 23.4 mEq/l. The correction of metabolic acidosis was achieved after several hours by the administration of bicarbonate and lactate buffers. The patient developed several burns-related complications (sepsis and acute renal failure). Cutaneous projections of strong acids may cause severe metabolic acidosis, particularly when copious irrigation and clothes removal cannot be immediately performed at the scene. PMID:22787349

  2. Safe delivery of two parturient women in severe metabolic acidosis

    PubMed Central

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

    2014-01-01

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

  3. An unusual case of severe high anion gap metabolic acidosis

    PubMed Central

    Bavakunji, Riaz V.; Turner, Jake D.; Jujjavarapu, Sagar; Taal, Maarten W.; Fluck, Richard J.; Leung, Janson C.; Kolhe, Nitin V.

    2011-01-01

    We present a case of high anion gap metabolic acidosis with an unusual aetiology in a 75-year-old lady with hypoglycaemia, encephalopathy and relatively preserved renal function. Full toxicology and biochemical analysis suggested that she had an inborn error of metabolism, riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency that can predispose to severe acidosis in situations where calorific intake is reduced. We believe this to be one of the few published cases and is remarkable for the presentation in late adulthood in addition to the requirement for emergency haemodialysis due to the severity of the metabolic disturbance. PMID:25984120

  4. 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 ...

  5. Severe metabolic acidosis and "muti" (traditional herbal medicine) ingestion in young children.

    PubMed

    Nkrumah, F K; Nathoo, K J; Gomo, Z A; Pirie, D J

    1990-01-01

    Twenty infants and young children admitted with severe metabolic acidosis and a positive history of 'muti' ingestion were investigated. All had accompanying gastroenteritis and significant dehydration. Biochemical data was diagnostic of high anion/gap metabolic acidosis in the majority (70 per cent). Further biochemical data indicated that lactic acidosis and pre-renal azotaemia resulting from severe hypovolaemia were likely causes of the high anion GAP metabolic acidosis. There was no evidence to suggest that the ingested muti per se was associated directly with the acidosis or acute renal failure seen in these children. PMID:2397494

  6. Metabolic acidosis

    MedlinePlus

    ... diarrhea. Lactic acidosis results from a buildup of lactic acid. It can be caused by: Alcohol Cancer Exercising ... functions) Urine pH Urine ketones or blood ketones Lactic acid test Arterial blood gas analysis Other tests may ...

  7. Drug-Induced Metabolic Acidosis

    PubMed Central

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W.

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics. PMID:26918138

  8. Drug-Induced Metabolic Acidosis.

    PubMed

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs' characteristics. PMID:26918138

  9. Severe hypernatremic dehydration and metabolic acidosis due to neonatal intestinal microvillus inclusion disease.

    PubMed

    Shahid, Shaneela; Fraser, Douglas D; Driman, David K; Bax, Kevin C

    2012-01-01

    Neonatal microvillus inclusion disease (MID) is a congenital secretory diarrhea diagnosed by morphological enterocyte abnormalities on histology. The secretory diarrhea associated with MID occurs within the first few hours of birth and is exacerbated by enteral feeding. Affected newborns will die of dehydration and acid-base disturbances if MID is not rapidly recognized and treated with massive intravenous fluid replacement and gut rest. We report a case of a 4-day-old neonate presenting with 18% weight loss, hypernatremic dehydration and metabolic acidosis. Despite aggressive fluid resuscitation (206 ml/kg for the first 24 h), the dehydration and metabolic acidosis were only minimally improved. The diapers were found soaked with clear, non-odorous fluid on repeated examinations. Persistent secretory diarrhea was suspected. Stool electrolytes analyses showed a high NaCl content typical of secretory diarrhea and intestinal biopsy with electron microscopy was diagnostic of MID. PMID:21968248

  10. Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study

    PubMed Central

    2011-01-01

    Background There is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory) versus normocapnic (metabolic) acidosis in an ex vivo model of ventilator-induced lung injury (VILI). Methods Sixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA), metabolic acidosis (MA) and normocapnic-normoxic (Control - C) groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain), changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations. Results HPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024), while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276) and 40 min (P = 0.0012) compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p < 0.001). Conclusions In our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation. PMID:21486492

  11. Metabolic acidosis: neo-considerations for general surgeons.

    PubMed

    Martin, L C E; Abah, U; Bean, E; Gupta, S

    2012-11-01

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

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

    PubMed

    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. PMID:26113997

  13. Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis

    PubMed Central

    Bulathsinghala, Marie; Keefer, Kimberly; Van de Louw, Andry

    2016-01-01

    Abstract Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG. A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid–base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity. Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX. PMID:27124045

  14. Acidosis

    MedlinePlus

    ... Severe dehydration Lactic acidosis is a buildup of lactic acid . Lactic acid is mainly produced in muscle cells and red ... prevented, including diabetic ketoacidosis and some causes of lactic ... with healthy kidneys and lungs do not have serious acidosis.

  15. 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

  16. 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

  17. 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

  18. Metabolic Acidosis of CKD: An Update.

    PubMed

    Kraut, Jeffrey A; Madias, Nicolaos E

    2016-02-01

    The kidney has the principal role in the maintenance of acid-base balance. Therefore, a decrease in renal ammonium excretion and a positive acid balance often leading to a reduction in serum bicarbonate concentration are observed in the course of chronic kidney disease (CKD). The decrease in serum bicarbonate concentration is usually absent until glomerular filtration rate decreases to <20 to 25mL/min/1.73 m(2), although it can develop with lesser degrees of decreased kidney function. Non-anion gap acidosis, high-anion gap acidosis, or both can be found at all stages of CKD. The acidosis can be associated with muscle wasting, bone disease, hypoalbuminemia, inflammation, progression of CKD, and increased mortality. Administration of base may decrease muscle wasting, improve bone disease, and slow the progression of CKD. Base is suggested when serum bicarbonate concentration is <22 mEq/L, but the target serum bicarbonate concentration is unclear. Evidence that increments in serum bicarbonate concentration > 24 mEq/L might be associated with worsening of cardiovascular disease adds complexity to treatment decisions. Further study of the mechanisms through which metabolic acidosis contributes to the progression of CKD, as well as the pathways involved in mediating the benefits and complications of base therapy, is warranted. PMID:26477665

  19. Approach to the Treatment of Chronic Metabolic Acidosis in CKD.

    PubMed

    Raphael, Kalani L

    2016-04-01

    Chronic metabolic acidosis is not uncommon in patients with chronic kidney disease (CKD). Clinical practice guidelines suggest that clinicians administer alkali to maintain serum bicarbonate level at a minimum of 22 mEq/L to prevent the effects of acidosis on bone demineralization and protein catabolism. Small interventional studies support the notion that correcting acidosis slows CKD progression as well. Furthermore, alkaline therapy in persons with CKD and normal bicarbonate levels may also preserve kidney function. Observational studies suggest that targeting a serum bicarbonate level near 28 mEq/L may improve clinical outcomes above and beyond targeting a value ≥ 22 mEq/L, yet values > 26 mEq/L have been reported to be associated with incident heart failure and mortality in the CRIC (Chronic Renal Insufficiency Cohort) Study. Furthermore, correcting acidosis may provoke vascular calcification. This teaching case discusses several uncertainties regarding the management of acidosis in CKD, such as when to initiate alkali treatment, potential side effects of alkali, and the optimum serum bicarbonate level based on current evidence in CKD. Suggestions regarding the maximum sodium bicarbonate dose to administer to patients with CKD to achieve the target serum bicarbonate concentration are offered. PMID:26776539

  20. Metabolic acidosis during parenteral nutrition: Pathophysiological mechanisms

    PubMed Central

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

    2015-01-01

    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

  1. Late Metabolic Acidosis Caused by Renal Tubular Acidosis in Acute Salicylate Poisoning.

    PubMed

    Sakai, Norihiro; Hirose, Yasuo; Sato, Nobuhiro; Kondo, Daisuke; Shimada, Yuko; Hori, Yasushi

    2016-01-01

    A 16-year-old man was transferred to our emergency department seven hours after ingesting 486 aspirin tablets. His blood salicylate level was 83.7 mg/dL. He was treated with fluid resuscitation and sodium bicarbonate infusion, and his condition gradually improved, with a decline in the blood salicylate level. However, eight days after admission, he again reported nausea, a venous blood gas revealed metabolic acidosis with a normal anion gap. The blood salicylate level was undetectable, and a urinalysis showed glycosuria, proteinuria and elevated beta-2 microglobulin and n-acetyl glucosamine levels, with a normal urinary pH despite the acidosis. We diagnosed him with relapse of metabolic acidosis caused by renal tubular acidosis. PMID:27181539

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-09-01

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

  4. Acidosis

    MedlinePlus

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

  5. Severe lactic acidosis in a diabetic patient after ethanol abuse and floor cleaner intake.

    PubMed

    Hendrikx, Jeroen J M A; Lagas, Jurjen S; Daling, Ratana; Hooijberg, Jan Hendrik; Schellens, Jan H M; Beijnen, Jos H; Brandjes, Desiderius P M; Huitema, Alwin D R

    2014-11-01

    An intoxication with drugs, ethanol or cleaning solvents may cause a complex clinical scenario if multiple agents have been ingested simultaneously. The situation can become even more complex in patients with (multiple) co-morbidities. A 59-year-old man with type 2 diabetes mellitus (without treatment two weeks before the intoxication) intentionally ingested a substantial amount of ethanol along with ~750 mL of laminate floor cleaner containing citric acid. The patient was admitted with severe metabolic acidosis (both ketoacidosis and lactic acidosis, with serum lactate levels of 22 mM). He was treated with sodium bicarbonate, insulin and thiamine after which he recovered within two days. Diabetic ketoacidosis and lactic acidosis aggravated due to ethanol intoxication, thiamine deficiency and citrate. The high lactate levels were explained by excessive lactate formation caused by the combination of untreated diabetes mellitus, thiamine deficiency and ethanol abuse. Metabolic acidosis in diabetes is multi-factorial, and the clinical situation may be further complicated, when ingestion of ethanol and toxic agents are involved. Here, we reported a patient in whom diabetic ketoacidosis was accompanied by severe lactic acidosis as a result of citric acid and mainly ethanol ingestion and a possible thiamine deficiency. In the presence of lactic acidosis in diabetic ketoacidosis, physicians need to consider thiamine deficiency and ingestion of ethanol or other toxins. PMID:24717115

  6. Metabolic acidosis in an infant associated with permethrin toxicity.

    PubMed

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

    2015-01-01

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

  7. Metabolic Acidosis with Ophthalmic Dorzolamide in a Neonate

    PubMed Central

    Capino, Amanda C.; Dannaway, Douglas C.

    2016-01-01

    Carbonic anhydrase inhibitors are a common cause of normal anion gap metabolic acidosis; however, development is less commonly associated with ophthalmic administration of these agents. We report a case of a premature neonate who was being treated at our institution with betaxolol, dorzolamide, and latanoprost ophthalmic products for suspected bilateral congenital glaucoma. In addition, the patient was also receiving caffeine, ursodiol, and acidified liquid human milk fortifier. The patient developed a normal anion gap metabolic acidosis, and both dorzolamide ophthalmic solution and the acidified human milk fortifier were considered potential causes. Upon discontinuation of the dorzolamide ophthalmic solution and the switching of liquid human milk fortifiers, the normal anion gap metabolic acidosis gradually resolved. As a result of the pH and acidity, the acidified liquid human milk fortifier is thought to be associated with an anion gap acidosis; therefore, dorzolamide is suspected to be the primary cause of a normal gap acidosis. This case demonstrates that systemic effects can occur with ophthalmic administration of dorzolamide in a premature neonate. Ophthalmic agents should not be overlooked as a potential cause of systemic toxicity. PMID:27453705

  8. Metabolic Acidosis with Ophthalmic Dorzolamide in a Neonate.

    PubMed

    Capino, Amanda C; Dannaway, Douglas C; Miller, Jamie L

    2016-01-01

    Carbonic anhydrase inhibitors are a common cause of normal anion gap metabolic acidosis; however, development is less commonly associated with ophthalmic administration of these agents. We report a case of a premature neonate who was being treated at our institution with betaxolol, dorzolamide, and latanoprost ophthalmic products for suspected bilateral congenital glaucoma. In addition, the patient was also receiving caffeine, ursodiol, and acidified liquid human milk fortifier. The patient developed a normal anion gap metabolic acidosis, and both dorzolamide ophthalmic solution and the acidified human milk fortifier were considered potential causes. Upon discontinuation of the dorzolamide ophthalmic solution and the switching of liquid human milk fortifiers, the normal anion gap metabolic acidosis gradually resolved. As a result of the pH and acidity, the acidified liquid human milk fortifier is thought to be associated with an anion gap acidosis; therefore, dorzolamide is suspected to be the primary cause of a normal gap acidosis. This case demonstrates that systemic effects can occur with ophthalmic administration of dorzolamide in a premature neonate. Ophthalmic agents should not be overlooked as a potential cause of systemic toxicity. PMID:27453705

  9. Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis: A Case Report and Review of the Literature.

    PubMed

    Bulathsinghala, Marie; Keefer, Kimberly; Van de Louw, Andry

    2016-04-01

    Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid-base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity.Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX. PMID:27124045

  10. 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

  11. Chronic metabolic acidosis increases the serum concentration of 1,25-dihydroxyvitamin D in humans by stimulating its production rate. Critical role of acidosis-induced renal hypophosphatemia.

    PubMed Central

    Krapf, R; Vetsch, R; Vetsch, W; Hulter, H N

    1992-01-01

    Chronic metabolic acidosis results in metabolic bone disease, calcium nephrolithiasis, and growth retardation. The pathogenesis of each of these sequelae is poorly understood in humans. We therefore investigated the effects of chronic extrarenal metabolic acidosis on the regulation of 1,25-(OH)2D, parathyroid hormone, calcium, and phosphate metabolism in normal humans. Chronic extrarenal metabolic acidosis was induced by administering two different doses of NH4Cl [2.1 (low dose) and 4.2 (high dose) mmol/kg body wt per d, respectively] to four male volunteers each during metabolic balance conditions. Plasma [HCO3-] decreased by 4.5 +/- 0.4 mmol/liter in the low dose and by 9.1 +/- 0.3 mmol/liter (P < 0.001) in the high dose group. Metabolic acidosis induced renal hypophosphatemia, which strongly correlated with the severity of acidosis (Plasma [PO4] on plasma [HCO3-]; r = 0.721, P < 0.001). Both metabolic clearance and production rates of 1,25-(OH)2D increased in both groups. In the high dose group, the percentage increase in production rate was much greater than the percentage increase in metabolic clearance rate, resulting in a significantly increased serum 1,25-(OH)2D concentration. A strong inverse correlation was observed for serum 1,25-(OH)2D concentration on both plasma [PO4] (r = -0.711, P < 0.001) and plasma [HCO3-] (r = -0.725, P < 0.001). Plasma ionized calcium concentration did not change in either group whereas intact serum parathyroid hormone concentration decreased significantly in the high dose group. In conclusion, metabolic acidosis results in graded increases in serum 1,25-(OH)2D concentration by stimulating its production rate in humans. The increased production rate is explained by acidosis-induced hypophosphatemia/cellular phosphate depletion resulting at least in part from decreased renal tubular phosphate reabsorption. The decreased serum intact parathyroid hormone levels in more severe acidosis may be the consequence of hypophosphatemia and

  12. Propylene Glycol Poisoning From Excess Whiskey Ingestion: A Case of High Osmolal Gap Metabolic Acidosis.

    PubMed

    Cunningham, Courtney A; Ku, Kevin; Sue, Gloria R

    2015-01-01

    In this report, we describe a case of high anion gap metabolic acidosis with a significant osmolal gap attributed to the ingestion of liquor containing propylene glycol. Recently, several reports have characterized severe lactic acidosis occurring in the setting of iatrogenic unintentional overdosing of medications that use propylene glycol as a diluent, including lorazepam and diazepam. To date, no studies have explored potential effects of excess propylene glycol in the setting of alcohol intoxication. Our patient endorsed drinking large volumes of cinnamon flavored whiskey, which was likely Fireball Cinnamon Whisky. To our knowledge, this is the first case of propylene glycol toxicity from an intentional ingestion of liquor containing propylene glycol. PMID:26904700

  13. Metabolic Acidosis Without Clinical Signs of Dehydration in Young Calves

    PubMed Central

    Kasari, T. R.; Naylor, J. M.

    1984-01-01

    Metabolic acidosis without clinical signs of dehydration was diagnosed in four calves between nine and 21 days of age. In each calf either coma or depression with weakness and ataxia was observed. Two calves had slow deep respirations. Treatment with intravenous administration of solutions of sodium bicarbonate was accompanied by a rise in blood pH and a return to normal demeanor, ambulation and appetites, allowing these calves to return to their respective herds. ImagesFigure 1. PMID:17422463

  14. Regulation of renal amino acid transporters during metabolic acidosis.

    PubMed

    Moret, Caroline; Dave, Mital H; Schulz, Nicole; Jiang, Jean X; Verrey, Francois; Wagner, Carsten A

    2007-02-01

    The kidney plays a major role in acid-base homeostasis by adapting the excretion of acid equivalents to dietary intake and metabolism. Urinary acid excretion is mediated by the secretion of protons and titratable acids, particularly ammonia. NH(3) is synthesized in proximal tubule cells from glutamine taken up via specific amino acid transporters. We tested whether kidney amino acid transporters are regulated in mice in which metabolic acidosis was induced with NH(4)Cl. Blood gas and urine analysis confirmed metabolic acidosis. Real-time RT-PCR was performed to quantify the mRNAs of 16 amino acid transporters. The mRNA of phosphoenolpyruvate carboxykinase (PEPCK) was quantified as positive control for the regulation and that of GAPDH, as internal standard. In acidosis, the mRNA of kidney system N amino acid transporter SNAT3 (SLC38A3/SN1) showed a strong induction similar to that of PEPCK, whereas all other tested mRNAs encoding glutamine or glutamate transporters were unchanged or reduced in abundance. At the protein level, Western blotting and immunohistochemistry demonstrated an increased abundance of SNAT3 and reduced expression of the basolateral cationic amino acid/neutral amino acid exchanger subunit y(+)-LAT1 (SLC7A7). SNAT3 was localized to the basolateral membrane of the late proximal tubule S3 segment in control animals, whereas its expression was extended to the earlier S2 segment of the proximal tubule during acidosis. Our results suggest that the selective regulation of SNAT3 and y(+)LAT1 expression may serve a major role in the renal adaptation to acid secretion and thus for systemic acid-base balance. PMID:17003226

  15. Outcome of severe lactic acidosis associated with metformin accumulation

    PubMed Central

    2010-01-01

    Introduction Metformin associated lactic acidosis (MALA) may complicate metformin therapy, particularly if metformin accumulates due to renal dysfunction. Profound lactic acidosis (LA) generally predicts poor outcome. We aimed to determine if MALA differs in outcome from LA of other origin (LAOO). Methods We conducted a retrospective analysis of all patients admitted with LA to our medical ICU of a tertiary referral center during a 5-year period. MALA patients and LAOO patients were compared with respect to parameters of acid-base balance, serum creatinine, hospital outcome, Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) score, using Pearson's Chi-square or the Mann-Whitney U-test. Results Of 197 patients admitted with LA, 10 had been diagnosed with MALA. With MALA, median arterial blood pH was significantly lower (6.78 [range 6.5 to 6.94]) and serum lactate significantly higher (18.7 ± 5.3 mmol/L) than with LAOO (pH 7.20 [range 6.46 to 7.35], mean serum lactate 11.2 ± 6.1 mmol/L). Overall mortality, however, was comparable (MALA 50%, LAOO 74%). Furthermore, survival of patients with arterial blood pH < 7.00 (N = 41) was significantly better (50% vs. 0%) if MALA (N = 10) was the underlying condition compared to LAOO (N = 31). Conclusions Compared to similarly severe lactic acidosis of other origin, the prognosis of MALA is significantly better. MALA should be considered in metformin-treated patients presenting with lactic acidosis. PMID:21171991

  16. Risk Factors for Developing Metabolic Acidosis after Radical Cystectomy and Ileal Neobladder

    PubMed Central

    Yoon, Hyun Suk; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Ryu, Dong-Ryeol; Lee, Dong Hyeon

    2016-01-01

    Purpose To investigate the serial changes of metabolic acidosis and identify associated risk factors in patients who underwent radical cystectomy and ileal neobladder. Material and Methods From January 2010 to August 2014, 123 patients who underwent radical cystectomy and ileal neobladder reconstruction for bladder cancer were included in this study. Metabolic acidosis was defined as a serum bicarbonate level less than 22 mEq/L and impaired renal function was defined as a GFR <50ml/min. The presence of metabolic acidosis was evaluated at 1 month, 1 year, and 2 years after surgery. Multivariate logistic regression analysis was conducted to identify risk factors associated with development of metabolic acidosis. Results Metabolic acidosis was observed in 52%, 19.5%, and 7.3% of patients at 1 month, 1 year, and 2 years after surgery, respectively. At 1 month after surgery, impaired renal function was the only independent risk factor associated with metabolic acidosis (OR 3.87, P = 0.046). At 1 year after surgery, diabetes was the only independent risk factor associated with metabolic acidosis (OR 5.68, P = 0.002). At 2 years post-surgery, both age and diabetes were significant risk factors associated with metabolic acidosis. Conclusion Approximately, half of patients experienced metabolic acidosis one month after ileal neobladder reconstruction. Preoperative impaired renal function was the most significant risk factor for developing metabolic acidosis in the early postoperative period. However, the incidence of metabolic acidosis decreased to less than 20% 1 year after surgery, and diabetes was an independent risk factor during this period. PMID:27384686

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2014-06-01

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

  19. Lentiform Fork Sign: a Magnetic Resonance Finding in a Case of Acute Metabolic Acidosis

    PubMed Central

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

    2014-01-01

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

  20. Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis.

    PubMed

    Kraut, Jeffrey A; Xing, Shelly Xiaolei

    2011-09-01

    An increase in serum osmolality and serum osmolal gap with or without high-anion-gap metabolic acidosis is an important clue to exposure to one of the toxic alcohols, which include methanol, ethylene glycol, diethylene glycol, propylene glycol, or isopropanol. However, the increase in serum osmolal gap and metabolic acidosis can occur either together or alone depending on several factors, including baseline serum osmolal gap, molecular weight of the alcohol, and stage of metabolism of the alcohol. In addition, other disorders, including diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis, can cause high-anion-gap metabolic acidosis associated with an increased serum osmolal gap and therefore should be explored in the differential diagnosis. It is essential for clinicians to understand the value and limitations of osmolal gap to assist in reaching the correct diagnosis and initiating appropriate treatment. In this teaching case, we present a systematic approach to diagnosing high serum osmolality and increased serum osmolal gap with or without high-anion-gap metabolic acidosis. PMID:21794966

  1. [5-0xoproline (pyroglutamic acid) acidosis and acetaminophen- a differential diagnosis in high anion gap metabolic acidosis].

    PubMed

    Weiler, Stefan; Bellmann, Romuald; Kullak-Ublick, Gerd A

    2015-12-01

    Rare cases of high anion gap metabolic acidosis during long-term paracetamol administration in therapeutic doses with causative 5-oxoproline (pyroglutamic acid} accumulation have been reported. Other concomitant risk factors such as malnutrition, alcohol abuse, renal or hepatic dysfunction, comedication with flue/oxacillin, vigabatrin, netilmicin or sepsis have been described. The etiology seems to be a drug-induced reversible inhibition of glutathione synthetase or 5-oxoprolinase leading to elevated serum and urine levels of 5-oxoproline. Other more frequent differential diagnoses, such as intoxications, ketoacidosis or lactic acidosis should be excluded. Causative substances should be stopped. 5-oxoproline concentrations in urine can be quantified to establish the diagnosis. Adverse drug reactions, which are not listed or insufficiently described in the respective Swiss product information, should be reported to the regional pharmacovigilance centres for early signal detection. 5-0 xoproline acidosis will be integrated as a potential adverse drug reaction in the Swiss product information for paracetamol. PMID:26654818

  2. Abnormalities of acid-base balance and predisposition to metabolic acidosis in Metachromatic Leukodystrophy patients.

    PubMed

    Lorioli, L; Cicalese, M P; Silvani, P; Assanelli, A; Salvo, I; Mandelli, A; Fumagalli, F; Fiori, R; Ciceri, F; Aiuti, A; Sessa, M; Roncarolo, M G; Lanzani, C; Biffi, A

    2015-05-01

    Metachromatic Leukodystrophy (MLD; MIM# 250100) is a rare inherited lysosomal storage disorder caused by the deficiency of Arylsulfatase A (ARSA). The enzymatic defect results in the accumulation of the ARSA substrate that is particularly relevant in myelin forming cells and leads to progressive dysmyelination and dysfunction of the central and peripheral nervous system. Sulfatide accumulation has also been reported in various visceral organs, although little is known about the potential clinical consequences of such accumulation. Different forms of MLD-associated gallbladder disease have been described, and there is one reported case of an MLD patient presenting with functional consequences of sulfatide accumulation in the kidney. Here we describe a wide cohort of MLD patients in whom a tendency to sub-clinical metabolic acidosis was observed. Furthermore in some of them we report episodes of metabolic acidosis of different grades of severity developed in acute clinical conditions of various origin. Importantly, we finally show how a careful acid-base balance monitoring and prompt correction of imbalances might prevent severe consequences of acidosis. PMID:25796965

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

    PubMed

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

    2012-09-01

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

  4. 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. PMID:26131288

  5. Prevalence of Metformin Use and the Associated Risk of Metabolic Acidosis in US Diabetic Adults With CKD

    PubMed Central

    Kuo, Chin-Chi; Yeh, Hung-Chieh; Chen, Bradley; Tsai, Ching-Wei; Lin, Yu-Sheng; Huang, Chiu-Ching

    2015-01-01

    Abstract The use of metformin in chronic kidney disease (CKD) population has been intensely debated with conflicting evidence. Large population studies are needed to inform risk assessment and therapeutic decision-making. We evaluated the associations among metformin, metabolic acidosis, and CKD in a 10-year nationally representative noninstitutionalized civilian population in the United States. In this cross-sectional study, a total of 2279 diabetic adults aged 20 years or older in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2012 were included and had measurements of serum bicarbonate, sodium, potassium, and chloride. The exposure was metformin use. The outcome was subclinical and severe metabolic acidosis defined by serum bicarbonate <23 mEq/L and anion gap > 16mEq/L and by serum bicarbonate < 20 mEq/L, respectively. The prevalence of metformin use decreased from 67.2% among CKD-1 and -2, 40.6% among CKD-3, to 1.3% among advanced CKD-4 and -5. Across CKD stages up to CKD-3b, we observed a tendency of lower levels of serum bicarbonate that was significant in metformin users with CKD-2 and CKD-3a and marginally significant with CKD-3b compared to nonmetformin users. The corresponding tendency of higher anion gap in metformin users with the estimated glomerular filtration rate >60 mL/min/1.73 m2 was also observed. In multiple linear regression analysis, metformin was significantly associated with decreased serum bicarbonate levels (β = −0.45, 95% CI: −0.73, −0.17) and increased serum anion gap levels (β = 0.40, 95% CI: 0.19, 0.61). The adjusted odds ratio of subclinical high anion gap and severe metabolic acidosis for metformin users was 1.68 (95% CI: 1.11, 2.55) and 1.31 (0.49, 3.47), respectively. The association between metformin and serum bicarbonate was significantly modified by CKD status. No interaction was found between metformin and CKD stages for serum anion gap and acidosis. Metformin is associated

  6. Ionized alkaline water: new strategy for management of metabolic acidosis in experimental animals.

    PubMed

    Abol-Enein, Hassan; Gheith, Osama A; Barakat, Nashwa; Nour, Eman; Sharaf, Abd-Elhameed

    2009-06-01

    Metabolic acidosis can occur as a result of either the accumulation of endogenous acids or loss of bicarbonate from the gastrointestinal tract or the kidney, which represent common causes of metabolic acidosis. The appropriate treatment of acute metabolic acidosis has been very controversial. Ionized alkaline water was not evaluated in such groups of patients in spite of its safety and reported benefits. So, we aimed to assess its efficacy in the management of metabolic acidosis in animal models. Two models of metabolic acidosis were created in dogs and rats. The first model of renal failure was induced by ligation of both ureters; and the second model was induced by urinary diversion to gut (gastrointestinal bicarbonate loss model). Both models were subjected to ionized alkaline water (orally and by hemodialysis). Dogs with renal failure were assigned to two groups according to the type of dialysate utilized during hemodialysis sessions, the first was utilizing alkaline water and the second was utilizing conventional water. Another two groups of animals with urinary diversion were arranged to receive oral alkaline water and tap water. In renal failure animal models, acid-base parameters improved significantly after hemodialysis with ionized alkaline water compared with the conventional water treated with reverse osmosis (RO). Similar results were observed in urinary diversion models as there was significant improvement of both the partial pressure of carbon dioxide and serum bicarbonate (P = 0.007 and 0.001 respectively) after utilizing alkaline water orally. Alkaline ionized water can be considered as a major safe strategy in the management of metabolic acidosis secondary to renal failure or dialysis or urinary diversion. Human studies are indicated in the near future to confirm this issue in humans. PMID:19527469

  7. Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis.

    PubMed

    Kim, Se Young

    2015-12-01

    It is important to fast diagnosis and management of the pediatric patients of the endocrine metabolic emergencies because the signs and symptoms of these disorders are nonspecific. Delayed diagnosis and treatment may lead to serious consequences of the pediatric patients, for example, cerebral dysfunction leading to coma or death of the patients with hypoglycemia, hypocalcemia, adrenal insufficiency, or diabetic ketoacidosis. The index of suspicion of the endocrine metabolic emergencies should be preceded prior to the starting nonspecific treatment. Importantly, proper diagnosis depends on the collection of blood and urine specimen before nonspecific therapy (intravenous hydration, electrolytes, glucose or calcium injection). At the same time, the taking of precise history and searching for pathognomonic physical findings should be performed. This review was described for fast diagnosis and proper management of hypoglycemic emergencies, hypocalcemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis. PMID:26817004

  8. Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis

    PubMed Central

    2015-01-01

    It is important to fast diagnosis and management of the pediatric patients of the endocrine metabolic emergencies because the signs and symptoms of these disorders are nonspecific. Delayed diagnosis and treatment may lead to serious consequences of the pediatric patients, for example, cerebral dysfunction leading to coma or death of the patients with hypoglycemia, hypocalcemia, adrenal insufficiency, or diabetic ketoacidosis. The index of suspicion of the endocrine metabolic emergencies should be preceded prior to the starting nonspecific treatment. Importantly, proper diagnosis depends on the collection of blood and urine specimen before nonspecific therapy (intravenous hydration, electrolytes, glucose or calcium injection). At the same time, the taking of precise history and searching for pathognomonic physical findings should be performed. This review was described for fast diagnosis and proper management of hypoglycemic emergencies, hypocalcemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis. PMID:26817004

  9. Severity and Nature of Acidosis in Diarrheic Calves Over and Under One Week of Age

    PubMed Central

    Naylor, Jonathan M.

    1987-01-01

    A prospective study of the severity of dehydration and acidosis was carried out in 42 calves under 35 days of age presented for treatment of neonatal diarrhea. Clinically the mean level of dehydration was 8 to 10%. The plasma volume was 65% of that in the hydrated calf but the calves only gained 6.5% in weight during therapy. Calves under eight days of age often had a lactic acidosis. Blood pH was 7.118±0.026 (mean ± 1 standard error), bicarbonate concentration 18.8±1.3 mmol/L, base deficit 11.4±1.7 mmol/L and lactate of 3.6± 0.06 mmol/L. Calves over eight days usually had a nonlactic acidosis. Blood pH was 7.042±0.021, bicarbonate 10.8±1.0 mmol/L, base deficit 19.5±1.2 mmol/L and lactate 1.2±0.3 mmol/L. These values were all significantly different from those in younger calves. Over all calves there was a poor correlation between the severity of acidosis and dehydration(r=0.05). The severity of lactic acidosis was related to the severity of dehydration. Mean bicarbonate requirements to correct acidosis were calculated to be 200 mmol(17 g of sodium bicarbonate)and 450 mmol(37 g of sodium bicarbonate)in calves under and over eight days of age respectively. Both groups of calves required a mean volume of 4L of fluid to correct dehydration. PMID:17422754

  10. [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

  11. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells

    PubMed Central

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N8-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  12. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells.

    PubMed

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N(8)-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  13. Chronic metabolic acidosis reduces urinary oxalate excretion and promotes intestinal oxalate secretion in the rat.

    PubMed

    Whittamore, Jonathan M; Hatch, Marguerite

    2015-11-01

    Urinary oxalate excretion is reduced in rats during a chronic metabolic acidosis, but how this is achieved is not clear. In this report, we re-examine our prior work on the effects of a metabolic acidosis on urinary oxalate handling [Green et al., Am J Physiol Ren Physiol 289(3):F536-F543, 2005], offering a more detailed analysis and interpretation of the data, together with new, previously unpublished observations revealing a marked impact on intestinal oxalate transport. Sprague-Dawley rats were provided with 0.28 M ammonium chloride in their drinking water for either 4 or 14 days followed by 24 h urine collections, blood-gas and serum ion analysis, and measurements of (14)C-oxalate fluxes across isolated segments of the distal colon. Urinary oxalate excretion was significantly reduced by 75% after just 4 days compared to control rats, and this was similarly sustained at 14 days. Oxalate:creatinine clearance ratios indicated enhanced net re-absorption of oxalate by the kidney during a metabolic acidosis, but this was not associated with any substantive changes to serum oxalate levels. In the distal colon, oxalate transport was dramatically altered from net absorption in controls (6.20 ± 0.63 pmol cm(-2) h(-1)), to net secretion in rats with a metabolic acidosis (-5.19 ± 1.18 and -2.07 ± 1.05 pmol cm(-2) h(-1) at 4 and 14 days, respectively). Although we cannot rule out modifications to bi-directional oxalate movements along the proximal tubule, these findings support a gut-kidney axis in the management of oxalate homeostasis, where this shift in renal handling during a metabolic acidosis is associated with compensatory adaptations by the intestine. PMID:26162424

  14. Differential effects of acidosis, high potassium concentrations, and metabolic inhibition on noradrenaline release and its presynaptic muscarinic regulation.

    PubMed

    Haunstetter, Armin; Schulze Icking, Babette; Backs, Johannes; Krüger, Carsten; Haass, Markus

    2002-03-01

    It was the aim of the present study to characterize the effect of single components of ischaemia, such as inhibition of aerobic and anaerobic energy production by combined anoxic and glucose-free perfusion (metabolic inhibition), high extracellular potassium concentrations (hyperkalaemia), and acidosis, on (1). the stimulated release of noradrenaline from the in situ perfused guinea-pig heart and (2). its presynaptic modulation by the muscarinic agonist carbachol. The release of endogenous noradrenaline from efferent cardiac sympathetic nerve endings was induced by electrical stimulation of the left stellate ganglion (1 min, 5 V, 12 Hz) and quantified in the coronary venous effluent by high-performance liquid chromatography. Under control conditions, two consecutive electrical stimulations (S1, S2) elicited a similar noradrenaline overflow (S2/S1: 0.98 plus minus 0.05). After 10 min of global myocardial ischaemia overflow of endogenous noradrenaline was significantly reduced (S2/S1: 0.18 plus minus 0.03; P< 0.05). When studied separately, metabolic inhibition, hyperkalaemia (16 mM), and acidosis (pH 6.0) each markedly attenuated stimulated noradrenaline overflow (S2/S1: 0.65 plus minus 0.05, 0.43 plus minus 0.14, and 0.37 plus minus 0.09, respectively; P< 0.05). The muscarinic agonist carbachol (10 microM) inhibited stimulated noradrenaline release under normoxic conditions (S2/S1: 0.41 plus minus 0.07; P< 0.05). However, after 10 min of global myocardial ischaemia the inhibitory effect of carbachol on noradrenaline overflow was completely lost. Single components of ischaemia had a differential effect on presynaptic muscarinic modulation. Whereas hyperkalaemia (8-16 mM) did not affect muscarinic inhibition of noradrenaline release, carbachol lost its inhibitory effect during acidosis and metabolic inhibition. In conclusion, hyperkalaemia, metabolic inhibition, and severe acidosis each contribute to reduced overflow of noradrenaline after 10 min of myocardial

  15. An autopsy case of death due to metabolic acidosis after citric acid ingestion.

    PubMed

    Ikeda, Tomoya; Usui, Akihito; Matsumura, Takashi; Aramaki, Tomomi; Hosoya, Tadashi; Igari, Yui; Ohuchi, Tsukasa; Hayashizaki, Yoshie; Usui, Kiyotaka; Funayama, Masato

    2015-11-01

    A man in his 40s was found unconscious on a sofa in a communal residence for people with various disabilities. He appeared to have drunk 800 ml of undiluted citric acid from a commercial plastic bottle. The instructions on the label of the beverage specified that the beverage be diluted 20- to 30-fold before consumption. The patient was admitted to an emergency hospital with severe metabolic acidosis (pH, 6.70; HCO3(-), 3.6 mEq/L) and a low ionized calcium level (0.73 mmol/L). Although ionized calcium and catecholamines were continuously administered intravenously to correct the acidosis, the state of acidemia and low blood pressure did not improve, and he died 20 h later. Citric acid concentrations in the patient's serum drawn shortly after treatment in the hospital and from the heart at autopsy were 80.6 mg/ml and 39.8 mg/dl, respectively (normal range: 1.3-2.6 mg/dl). Autopsy revealed black discoloration of the mucosal surface of the esophagus. Microscopically, degenerated epithelium and neutrophilic infiltration in the muscle layer were observed. In daily life, drinking a large amount of concentrated citric acid beverage is rare as a cause of lethal poisoning. However, persons with mental disorders such as dementia may mistakenly drink detergent or concentrated fluids, as in our case. Family members or facility staff in the home or nursing facility must bear in mind that they should not leave such bottles in places where they are easily accessible to mentally handicapped persons. PMID:26594004

  16. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    SciTech Connect

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-06-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH/sub 4/Cl x 100 g body wt/sup -1/ x day/sup -1/. Epitrochlearis muscles were incubated with L-(1-/sup 14/C)-valine and L-(1-/sup 14/C)leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain ..cap alpha..-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain ..cap alpha..-keto acid dehydrogenase.

  17. Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism.

    PubMed

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Lamers, Wouter H; Chaudhry, Farrukh A; Verlander, Jill W; Weiner, I David

    2016-06-01

    Glutamine synthetase (GS) catalyzes the recycling of NH4 (+) with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na(+)-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression. PMID:27009341

  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. Hyperchloremic Metabolic Acidosis due to Cholestyramine: A Case Report and Literature Review

    PubMed Central

    Kamar, Fareed B.; McQuillan, Rory F.

    2015-01-01

    Cholestyramine is a bile acid sequestrant that has been used in the treatment of hypercholesterolemia, pruritus due to elevated bile acid levels, and diarrhea due to bile acid malabsorption. This medication can rarely cause hyperchloremic nonanion gap metabolic acidosis, a complication featured in this report of an adult male with concomitant acute kidney injury. This case emphasizes the caution that must be taken in prescribing cholestyramine to patients who may also be volume depleted, in renal failure, or taking spironolactone. PMID:26425378

  20. Hyperchloremic Metabolic Acidosis due to Cholestyramine: A Case Report and Literature Review.

    PubMed

    Kamar, Fareed B; McQuillan, Rory F

    2015-01-01

    Cholestyramine is a bile acid sequestrant that has been used in the treatment of hypercholesterolemia, pruritus due to elevated bile acid levels, and diarrhea due to bile acid malabsorption. This medication can rarely cause hyperchloremic nonanion gap metabolic acidosis, a complication featured in this report of an adult male with concomitant acute kidney injury. This case emphasizes the caution that must be taken in prescribing cholestyramine to patients who may also be volume depleted, in renal failure, or taking spironolactone. PMID:26425378

  1. Baking soda induced severe metabolic alkalosis in a haemodialysis patient.

    PubMed

    Solak, Yalcin; Turkmen, Kultigin; Atalay, Huseyin; Turk, Suleyman

    2009-08-01

    Metabolic alkalosis is a rare occurence in hemodialysis population compared to metabolic acidosis unless some precipitating factors such as nasogastric suction, vomiting and alkali ingestion or infusion are present. When metabolic alkalosis develops, it may cause serious clinical consequences among them are sleep apnea, resistent hypertension, dysrhythmia and seizures. Here, we present a 54-year-old female hemodialysis patient who developed a severe metabolic alkalosis due to baking soda ingestion to relieve dyspepsia. She had sleep apnea, volume overload and uncontrolled hypertension due to metabolic alkalosis. Metabolic alkalosis was corrected and the patient's clinical condition was relieved with negative-bicarbonate hemodialysis. PMID:25984015

  2. [Hypokalemic pareses secondary to renal tubular acidosis].

    PubMed

    Gøransson, L G; Apeland, T; Omdal, R

    2000-01-30

    A 24 year old woman presented with flaccid paralysis, severe hypokalaemia and hyperchloremia, metabolic acidosis. Immunological tests and labial glandular biopsy indicated primary Sjögren's syndrome as the underlying cause of her distal renal tubular acidosis. The patient recovered after alkali and potassium substitution and was put on oral treatment with potassium citrate. PMID:10827521

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

    PubMed Central

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

    2012-01-01

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

  4. Prevalence of Metformin Use and the Associated Risk of Metabolic Acidosis in US Diabetic Adults With CKD: A National Cross-Sectional Study.

    PubMed

    Kuo, Chin-Chi; Yeh, Hung-Chieh; Chen, Bradley; Tsai, Ching-Wei; Lin, Yu-Sheng; Huang, Chiu-Ching

    2015-12-01

    The use of metformin in chronic kidney disease (CKD) population has been intensely debated with conflicting evidence. Large population studies are needed to inform risk assessment and therapeutic decision-making. We evaluated the associations among metformin, metabolic acidosis, and CKD in a 10-year nationally representative noninstitutionalized civilian population in the United States.In this cross-sectional study, a total of 2279 diabetic adults aged 20 years or older in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2012 were included and had measurements of serum bicarbonate, sodium, potassium, and chloride. The exposure was metformin use. The outcome was subclinical and severe metabolic acidosis defined by serum bicarbonate <23 mEq/L and anion gap > 16mEq/L and by serum bicarbonate < 20 mEq/L, respectively.The prevalence of metformin use decreased from 67.2% among CKD-1 and -2, 40.6% among CKD-3, to 1.3% among advanced CKD-4 and -5. Across CKD stages up to CKD-3b, we observed a tendency of lower levels of serum bicarbonate that was significant in metformin users with CKD-2 and CKD-3a and marginally significant with CKD-3b compared to nonmetformin users. The corresponding tendency of higher anion gap in metformin users with the estimated glomerular filtration rate >60 mL/min/1.73 m was also observed. In multiple linear regression analysis, metformin was significantly associated with decreased serum bicarbonate levels (β = -0.45, 95% CI: -0.73, -0.17) and increased serum anion gap levels (β = 0.40, 95% CI: 0.19, 0.61). The adjusted odds ratio of subclinical high anion gap and severe metabolic acidosis for metformin users was 1.68 (95% CI: 1.11, 2.55) and 1.31 (0.49, 3.47), respectively. The association between metformin and serum bicarbonate was significantly modified by CKD status. No interaction was found between metformin and CKD stages for serum anion gap and acidosis.Metformin is associated with subclinical

  5. Multiplexed Microneedle-based Biosensor Array for Characterization of Metabolic Acidosis

    PubMed Central

    Miller, Philip R.; Skoog, Shelby A.; Edwards, Thayne L.; Lopez, Deanna M.; Wheeler, David R.; Arango, Dulce C.; Xiao, Xiaoyin; Brozik, Susan M.; Wang, Joseph; Polsky, Ronen; Narayan, Roger J.

    2011-01-01

    The development of a microneedle-based biosensor array for multiplexed in situ detection of exercise-induced metabolic acidosis, tumor microenvironment, and other variations in tissue chemistry is described. Simultaneous and selective amperometric detection of pH, glucose, and lactate over a range of physiologically-relevant concentrations in complex media is demonstrated. Furthermore, materials modified with a cell-resistant (Lipidure®) coating were shown to inhibit macrophage adhesion; no signs of coating delamination were noted over a 48-hour period. PMID:22265568

  6. Multiplexed microneedle-based biosensor array for characterization of metabolic acidosis.

    PubMed

    Miller, Philip R; Skoog, Shelby A; Edwards, Thayne L; Lopez, Deanna M; Wheeler, David R; Arango, Dulce C; Xiao, Xiaoyin; Brozik, Susan M; Wang, Joseph; Polsky, Ronen; Narayan, Roger J

    2012-01-15

    The development of a microneedle-based biosensor array for multiplexed in situ detection of exercise-induced metabolic acidosis, tumor microenvironment, and other variations in tissue chemistry is described. Simultaneous and selective amperometric detection of pH, glucose, and lactate over a range of physiologically relevant concentrations in complex media is demonstrated. Furthermore, materials modified with a cell-resistant (Lipidure(®)) coating were shown to inhibit macrophage adhesion; no signs of coating delamination were noted over a 48-h period. PMID:22265568

  7. Role of proton receptor OGR1 in bone response to metabolic acidosis?

    PubMed

    Jorgetti, Vanda; Drüeke, Tilman B; Ott, Susan M

    2016-03-01

    Chronic metabolic acidosis stimulates bone resorption, resulting in loss of calcium and bicarbonate from bone. Both osteoblasts and osteoclasts sense extracellular H(+) by the G-protein coupled receptor, OGR1, whose activation leads to increased bone resorption as well as decreased bone formation. Krieger et al. examined the effect of OGR1 knockout in mice. They found an unexpected increase in bone resorption, but nevertheless an increase in bone volume linked to enhanced bone formation. This discovery opens a window of opportunity to explore potential new anabolic treatments for patients with low bone mass. PMID:26880446

  8. 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

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

    PubMed

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

    2013-12-15

    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), α-hydroxybutyric acid (aHBA), β-hydroxybutyric acid (bHBA), p-hydroxyphenyllactic acid (pHPLA), malonic acid (MA), methylmalonic acid (MMA), ethylmalonic acid (EMA) and α-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: 2.5-2500μg/mL for LA, 0.125-125μg/mL for aHBA, 7.5-375μg/mL for bHBA, 0.1-100μg/mL for pHPLA, 1-1000μg/mL for MA, 0.25-250μg/mL for MMA, 0.25-100μg/mL for EMA, and 30-1500μg/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=177-1169μg/mL, aHBA=4.70-38.4μg/mL, bHBA=7.70-38.0μg/mL, pHPLA=0.900-4.30

  10. 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), α-hydroxybutyric acid (aHBA), β-hydroxybutyric acid (bHBA), p-hydroxyphenyllactic acid (pHPLA), malonic acid (MA), methylmalonic acid (MMA), ethylmalonic acid (EMA) and α-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 μg/mL for LA, 0.125–125 μg/mL for aHBA, 7.5–375 μg/mL for bHBA, 0.1–100 μg/mL for pHPLA, 1–1000 μg/mL for MA, 0.25–250 μg/mL for MMA, 0.25–100 μg/mL for EMA, and 30–1500 μg/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 μg/mL, aHBA = 4.70–38.4

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

    PubMed

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

    2014-03-01

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

  12. Metabolic acidosis in a patient with type 1 diabetes mellitus complicated by methanol and amitriptyline intoxication.

    PubMed

    Celik, Umit; Celik, Tamer; Avci, Akkan; Annagur, Ali; Yilmaz, Hayri Levent; Kucukosmanoglu, Osman; Topaloglu, Ali Kemal; Daglioglu, Nebile

    2009-02-01

    Diabetic ketoacidosis (DKA) is a widely known acute metabolic complication of diabetes mellitus (DM), which can be potentially fatal. It is not difficult to diagnose when a patient with DM comes with symptoms such as coma, fruity breath, hyperglycemia, acidosis, and tachypnea. If the patient has not been diagnosed with DM before, then other sicknesses characterized by an increased anion gap should be considered. A 12-year-old boy with type 1 DM and repeated earlier admissions for DKA was admitted to the emergency department in another apparent case of DKA with coma, hyperglycemia, and profound metabolic acidosis. When his condition did not improve with initial treatment, intoxication was suspected as an alternate cause of his condition. Further laboratory tests detected methanol and amitriptyline. The patient underwent hemodialysis and recovered completely. This case illustrates that a seemingly obvious medical condition can mask serious intoxication. This report is the only publication on two different entities characterized by an increased anion gap and at the end the patient has been cured completely without any complications. PMID:19106720

  13. A Rare Cause of Metabolic Acidosis: Fatal Transdermal Methanol Intoxication in an Infant.

    PubMed

    Sahbudak Bal, Zumrut; Can, Fulya Kamit; Anil, Ayse Berna; Bal, Alkan; Anil, Murat; Gokalp, Gamze; Yavascan, Onder; Aksu, Nejat

    2016-08-01

    Oral methanol intoxication is common, but dermal intoxication is rare. We report a previously healthy 19-month-old female infant admitted to the emergency department (ED) with vomiting and tonic-clonic seizure. On physical examination, she was comatose and presented signs of decompensated shock with Kussmaul breathing. Her left thigh was edematous, with purple coloration. Methanol intoxication was suspected due to high anion gap metabolic acidosis (pH, 6.89; HCO3, <3 meq/L) and exposure to spirit-soaked bandages (%96 methanol) for 24 hours and 3 days. The patient's serum methanol level was 20.4 mg/dL. She was treated with fomepizole and continuous venovenous hemodialysis (CVVHD) in the pediatric intensive care unit, and methanol levels decreased to 0 mg/dL after 12 hours. During follow-up, massive edema and subarachnoid hemorrhage in the occipital lobe were detected by computed tomography of the brain. The patient died after 7 days.Although methanol intoxication occurs predominantly in adults, it must be considered in children with high-anion gap metabolic acidosis. This case report demonstrates that fatal transdermal methanol intoxication can occur in children, and it is the second report in the English literature of transdermal methanol intoxication in an infant. PMID:26196361

  14. Fructose 1,6 biphosphate administration to rats prevents metabolic acidosis and oxidative stress induced by deep hypothermia and rewarming.

    PubMed

    Alva, Norma; Carbonell, Teresa; Roig, Teresa; Bermúdez, Jordi; Palomeque, Jesús

    2011-06-01

    Fructose 1,6 biphosphate (F1,6BP) exerts a protective effect in several in vitro models of induced injury and in isolated organs; however, few studies have been performed using in vivo hypothermia. Here we studied the effects of deep hypothermia (21ºC) and rewarming in anaesthetised rats after F1,6BP administration (2 g/kg body weight). Acid-base and oxidative stress parameters (plasma malondialdehyde and glutathione, and erythrocyte antioxidant enzymes) were evaluated. Erythrocyte and leukocyte numbers in blood and plasma nitric oxide were also measured 3 h after F1,6BP administration in normothermia animals. In the absence of F1,6BP metabolic acidosis developed after rewarming. Oxidative stress was also evident after rewarming, as shown by a decrease in thiol groups and in erythrocyte superoxide dismutase, catalase and GSH-peroxidase, which corresponded to an increase in AST in rewarmed animals. These effects were reverted in rats treated with F1,6BP. Blood samples of F1,6BP-treated animals showed a significant increase in plasma nitric oxide 3 h after administration, coinciding with a significant rise in leukocyte number. F1,6BP protection may be due to the decrease in oxidative stress and to the preservation of the antioxidant pool. In addition, we propose that the reduction in extracellular acidosis may be due to improved tissue perfusion during rewarming and that nitric oxide may play a central role. PMID:21463624

  15. 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. PMID:26180438

  16. Insulin sensitivity of muscle protein metabolism is altered in patients with chronic kidney disease and metabolic acidosis

    PubMed Central

    Garibotto, Giacomo; Sofia, Antonella; Russo, Rodolfo; Paoletti, Ernesto; Bonanni, Alice; Parodi, Emanuele L; Viazzi, Francesca; Verzola, Daniela

    2015-01-01

    An emergent hypothesis is that a resistance to the anabolic drive by insulin may contribute to loss of strength and muscle mass in patients with chronic kidney disease (CKD). We tested whether insulin resistance extends to protein metabolism using the forearm perfusion method with arterial insulin infusion in 7 patients with CKD and metabolic acidosis (bicarbonate 19 mmol/l) and 7 control individuals. Forearm glucose balance and protein turnover (2H-phenylalanine kinetics) were measured basally and in response to insulin infused at different rates for 2 h to increase local forearm plasma insulin concentration by approximately 20 and 50 μU/ml. In response to insulin, forearm glucose uptake was significantly increased to a lesser extent (−40%) in patients with CKD than controls. In addition, whereas in the controls net muscle protein balance and protein degradation were decreased by both insulin infusion rates, in patients with CKD net protein balance and protein degradation were sensitive to the high (0.035 mU/kg per min) but not the low (0.01 mU/kg per min) insulin infusion. Besides blunting muscle glucose uptake, CKD and acidosis interfere with the normal suppression of protein degradation in response to a moderate rise in plasma insulin. Thus, alteration of protein metabolism by insulin may lead to changes in body tissue composition which may become clinically evident in conditions characterized by low insulinemia. PMID:26308671

  17. 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

  18. Sodium bicarbonate use and the risk of hypernatremia in thoracic aortic surgical patients with metabolic acidosis following deep hypothermic circulatory arrest

    PubMed Central

    Ghadimi, Kamrouz; Gutsche, Jacob T.; Ramakrishna, Harish; Setegne, Samuel L.; Jackson, Kirk R.; Augoustides, John G.; Ochroch, E. Andrew; Weiss, Stuart J.; Bavaria, Joseph E.; Cheung, Albert T.

    2016-01-01

    Objective: Metabolic acidosis after deep hypothermic circulatory arrest (DHCA) for thoracic aortic operations is commonly managed with sodium bicarbonate (NaHCO3). The purpose of this study was to determine the relationships between total NaHCO3 dose and the severity of metabolic acidosis, duration of mechanical ventilation, duration of vasoactive infusions, and Intensive Care Unit (ICU) or hospital length of stay (LOS). Methods: In a single center, retrospective study, 87 consecutive elective thoracic aortic operations utilizing DHCA, were studied. Linear regression analysis was used to test for the relationships between the total NaHCO3 dose administered through postoperative day 2, clinical variables, arterial blood gas values, and short-term clinical outcomes. Results: Seventy-five patients (86%) received NaHCO3. Total NaHCO3 dose averaged 136 ± 112 mEq (range: 0.0–535 mEq) per patient. Total NaHCO3 dose correlated with minimum pH (r = 0.41, P < 0.0001), minimum serum bicarbonate (r = −0.40, P < 0.001), maximum serum lactate (r = 0.46, P = 0.007), duration of metabolic acidosis (r = 0.33, P = 0.002), and maximum serum sodium concentrations (r = 0.29, P = 0.007). Postoperative hypernatremia was present in 67% of patients and peaked at 12 h following DHCA. Eight percent of patients had a serum sodium ≥ 150 mEq/L. Total NaHCO3 dose did not correlate with anion gap, serum chloride, not the duration of mechanical ventilator support, vasoactive infusions, ICU or hospital LOS. Conclusion: Routine administration of NaHCO3 was common for the management of metabolic acidosis after DHCA. Total dose of NaHCO3 was a function of the severity and duration of metabolic acidosis. NaHCO3 administration contributed to postoperative hypernatremia that was often severe. The total NaHCO3 dose administered was unrelated to short-term clinical outcomes. PMID:27397449

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

    PubMed

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

    2013-08-01

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

  20. Gene expression profile of duodenal epithelial cells in response to chronic metabolic acidosis.

    PubMed

    Wongdee, Kannikar; Teerapornpuntakit, Jarinthorn; Riengrojpitak, Suda; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2009-01-01

    Chronic metabolic acidosis (CMA) affects ion transport, permeability, and metabolism of the intestinal absorptive cells. Most effects of CMA on the intestine are long-term adaptations at genomic level. To identify the CMA-regulated genes, the Illumina's microarray featuring high-performance BeadArray technology was performed on RNA samples from the rat duodenal epithelial cells exposed to long-standing acidemia. After 21 days of CMA, we found 423 transcripts upregulated and 261 transcripts downregulated. Gene ontology analysis suggested effects of CMA on cellular processes, such as cell adhesion, proliferation, fuel metabolism, and biotransformation. Interestingly, 27 upregulated transcripts (e.g., Aqp1, Cacnb1, Atp1a2, Kcnab2, and Slc2a1) and 13 downregulated transcripts (e.g., Slc17a7, Slc9a4, and Slc30a3) are involved in the absorption of water, ions, and nutrients. Some upregulated genes, such as Slc38a5 and Slc1a7 encoding glutamine transporters, may be parts of the total body adaptation to alleviate negative nitrogen balance. Therefore, the present results provided a novel genome-wide information for further investigations of the mechanism of CMA effect on the intestine. PMID:18979233

  1. Respiratory acidosis

    MedlinePlus

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

  2. Intra-operative correction of acidosis, coagulopathy and hypothermia in combat casualties with severe haemorrhagic shock.

    PubMed

    Morrison, J J; Ross, J D; Poon, H; Midwinter, M J; Jansen, J O

    2013-08-01

    We assessed acidosis, coagulopathy and hypothermia, before and after surgery in 51 combat troops operated on for severe blast injury. Patients were transfused a median (IQR [range]) of 27 (17-38 [5-84]) units of red cell concentrate, 27 (16-38 [4-83]) units of plasma, 2.0 (0.5-3.5 [0-13.0]) units of cryoprecipitate and 4 (2-6 [0-17]) pools of platelets. The pH, base excess, prothrombin time and temperature increased: from 7.19 (7.10-7.29 [6.50-7.49]) to 7.45 (7.40-7.51 [7.15-7.62]); from -9.0 (-13.5 to -4.5 [-28 to -2]) mmol.l⁻¹ to 4.5 (1.0-8.0 [-7 to +11]) mmol.l⁻¹; from 18 (15-21 [9-24]) s to 14 (11-18 [9-21]) s; and from 36.1 (35.1-37.1 [33.0-38.1]) °C to 37.4 (37.0-37.9 [36.0-38.0]) °C, respectively. Contemporary intra-operative resuscitation strategies can normalise the physiological derangements caused by haemorrhagic shock. PMID:23724784

  3. Recent Advances in Targeting Tumor Energy Metabolism with Tumor Acidosis as a Biomarker of Drug Efficacy

    PubMed Central

    Akhenblit, Paul J; Pagel, Mark D

    2016-01-01

    Cancer cells employ a deregulated cellular metabolism to leverage survival and growth advantages. The unique tumor energy metabolism presents itself as a promising target for chemotherapy. A pool of tumor energy metabolism targeting agents has been developed after several decades of efforts. This review will cover glucose and fatty acid metabolism, PI3K/AKT/mTOR, HIF-1 and glutamine pathways in tumor energy metabolism, and how they are being exploited for treatments and therapies by promising pre-clinical or clinical drugs being developed or investigated. Additionally, acidification of the tumor extracellular microenvironment is hypothesized to be the result of active tumor metabolism. This implies that tumor extracellular pH (pHe) can be a biomarker for assessing the efficacy of therapies that target tumor metabolism. Several translational molecular imaging methods (PET, MRI) for interrogating tumor acidification and its suppression are discussed as well. PMID:26962408

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

    PubMed Central

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

    2011-01-01

    The pathogenesis of cerebral malaria (CM) remains largely unknown. There is growing evidence that combination of both parasite and host factors could be involved in blood–brain barrier (BBB) breakdown. However, lack of adequate in vitro model of human BBB so far hampered molecular studies. In this article, we propose the use of hCMEC/D3 cells, a well-established human cerebral microvascular endothelial cell (EC) line, to study BBB breakdown induced by Plasmodium falciparum-parasitized red blood cells and environmental conditions. We show that coculture of parasitized erythrocytes with hCMEC/D3 cells induces cell adhesion and paracellular permeability increase, which correlates with disorganization of zonula occludens protein 1 expression pattern. Permeability increase and modification of tight junction proteins distribution are cytoadhesion independent. Finally, we show that permeability of hCMEC/D3 cell monolayers is mediated through parasite induced metabolic acidosis, which in turns correlates with apoptosis of parasitized erythrocytes. This new coculture model represents a very useful tool, which will improve the knowledge of BBB breakdown and the development of adjuvant therapies, together with antiparasitic drugs. PMID:20683453

  5. Acidosis Drives the Reprogramming of Fatty Acid Metabolism in Cancer Cells through Changes in Mitochondrial and Histone Acetylation.

    PubMed

    Corbet, Cyril; Pinto, Adán; Martherus, Ruben; Santiago de Jesus, João Pedro; Polet, Florence; Feron, Olivier

    2016-08-01

    Bioenergetic preferences of cancer cells foster tumor acidosis that in turn leads to dramatic reduction in glycolysis and glucose-derived acetyl-coenzyme A (acetyl-CoA). Here, we show that the main source of this critical two-carbon intermediate becomes fatty acid (FA) oxidation in acidic pH-adapted cancer cells. FA-derived acetyl-CoA not only fuels the tricarboxylic acid (TCA) cycle and supports tumor cell respiration under acidosis, but also contributes to non-enzymatic mitochondrial protein hyperacetylation, thereby restraining complex I activity and ROS production. Also, while oxidative metabolism of glutamine supports the canonical TCA cycle in acidic conditions, reductive carboxylation of glutamine-derived α-ketoglutarate sustains FA synthesis. Concomitance of FA oxidation and synthesis is enabled upon sirtuin-mediated histone deacetylation and consecutive downregulation of acetyl-CoA carboxylase ACC2 making mitochondrial fatty acyl-CoA degradation compatible with cytosolic lipogenesis. Perturbations of these regulatory processes lead to tumor growth inhibitory effects further identifying FA metabolism as a critical determinant of tumor cell proliferation under acidosis. PMID:27508876

  6. Perinatal inflammation/infection and its association with correction of metabolic acidosis in hypoxic-ischemic encephalopathy

    PubMed Central

    Johnson, CT; Burd, I; Raghunathan, R; Northington, FJ; Graham, EM

    2016-01-01

    OBJECTIVE To investigate the decreased response to hypothermia in neonates with hypoxic-ischemic encephalopathy (HIE) and infection, we sought to determine the association of fetal inflammation/infection with perinatal metabolic acidosis. STUDY DESIGN We performed a retrospective cohort study of neonates with suspected HIE started on whole-body hypothermia within 6 h of birth that had a cord gas at delivery and placental pathology performed. Neonates were compared based on the presence of clinical and histologic chorioamnionitis. The cord gas at delivery was compared with the initial arterial gas after birth. RESULTS In all, 50 out of 67 (74.6%) neonates admitted for therapeutic hypothermia met inclusion criteria. Chorioamnionitis did not affect the cord gas at delivery, but both clinical and histologic chorioamnionitis were associated with a significantly increased metabolic acidosis on the initial neonatal arterial gas. CONCLUSION Chorioamnionitis, diagnosed both clinically and histologically, is associated with a persistent state of acidosis in neonates with HIE that may contribute to worse neurologic outcomes. PMID:26796123

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

    PubMed Central

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

    2010-01-01

    Rh C glycoprotein (Rhcg) is an NH3-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

  8. Severe lactic acidosis and multiorgan failure due to thiamine deficiency during total parenteral nutrition

    PubMed Central

    Ramsi, Musaab; Mowbray, Claire; Hartman, Gary; Pageler, Natalie

    2014-01-01

    A 16-year-old perioperative paediatric patient presented with refractory lactic acidosis and multiorgan failure due to thiamine-deficient total parenteral nutrition during a recent national multivitamin shortage. Urgent empiric administration of intravenous thiamine resulted in prompt recovery from this life-threatening condition. Despite readily available treatment, a high index of suspicion is required to prevent cardiovascular collapse and mortality. PMID:24895398

  9. Lactic acidosis

    MedlinePlus

    Lactic acidosis is when lactic acid builds up in the bloodstream faster than it can be removed. Lactic acid ... The most common cause of lactic acidosis is intense exercise. ... as: AIDS Cancer Kidney failure Respiratory failure Sepsis A ...

  10. 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.

  11. Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect.

    PubMed

    Celotto, A C; Ferreira, L G; Capellini, V K; Albuquerque, A A S; Rodrigues, A J; Evora, P R B

    2016-02-01

    Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control. PMID:26648089

  12. Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

    PubMed Central

    Celotto, A.C.; Ferreira, L.G.; Capellini, V.K.; Albuquerque, A.A.S.; Rodrigues, A.J.; Evora, P.R.B.

    2015-01-01

    Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control. PMID:26648089

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

    PubMed Central

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

    2013-01-01

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

  14. Dichloroacetate attenuates myocardial acidosis and metabolic changes induced by partial occlusion of the coronary artery in dogs.

    PubMed

    Sakai, K; Ichihara, K; Nasa, Y; Kamigaki, M; Abiko, Y

    1990-01-01

    The present study was undertaken to examine whether dichloroacetate, which inhibits pyruvate dehydrogenase kinase and, therefore, increases the activity of pyruvate dehydrogenase, attenuates myocardial acidosis and metabolic changes induced by coronary occlusion. In dogs anesthetized with pentobarbital, the left anterior descending coronary artery was incompletely occluded to reduce the left anterior descending flow to a half to one third of the original flow (partial occlusion) to produce myocardial (regional) ischemia. Partial occlusion was continued for 90 min, and a bolus injection of saline or dichloroacetate was made intravenously 30 min after the onset of occlusion. Partial occlusion decreased myocardial pH significantly. An injection of dichloroacetate (150 mg/kg) increased myocardial pH that had been lowered by partial occlusion. Myocardial metabolites were measured in other dogs. Partial occlusion decreased the myocardial levels of adenosine triphosphate, creatine phosphate and energy charge potential, and increased that of lactate significantly, without affecting the myocardial levels of pyruvate and nonesterified fatty acids. Dichloroacetate attenuated the ischemia-induced changes in the myocardial levels of adenosine triphosphate, creatine phosphate, energy charge potential and lactate. These results indicate that dichloroacetate attenuates the myocardial acidosis and metabolic changes during coronary partial occlusion. PMID:2095718

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

    PubMed

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

    2014-01-01

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

  16. Atypical distal renal tubular acidosis confirmed by mutation analysis.

    PubMed

    Weber, S; Soergel, M; Jeck, N; Konrad, M

    2000-12-01

    In autosomal dominant distal renal tubular acidosis type I (dRTA) impaired hydrogen ion secretion is associated with metabolic acidosis, hyperchloremic hypokalemia, hypercalciuria, nephrocalcinosis, and/or nephrolithiasis. A retardation of growth is commonly observed. In this report we present a family with autosomal dominant dRTA with an atypical and discordant clinical picture. The father presented with severe nephrocalcinosis, nephrolithiasis, and isosthenuria but metabolic acidosis was absent. His 6-year-old daughter, however, suffered from metabolic acidosis, hypokalemia, and hypercalciuria. In addition, sonography revealed multiple bilateral renal cysts but no nephrocalcinosis. Mutation analysis of the AE1 gene coding for the renal Cl-/HCO3(-)-exchanger AE1 displayed a heterozygous Arg589Cys exchange in both patients but not in the healthy family members. This point mutation is frequently associated with autosomal dominant dRTA. Diagnosis of autosomal dominant dRTA is supported in this family by results of AE1 mutation analysis. PMID:11149111

  17. Extracorporeal treatment with high-volume continuous venovenous hemodiafiltration and charcoal-based sorbent hemoperfusion for severe metformin-associated lactic acidosis

    PubMed Central

    Garg, Suneel Kumar; Singh, Omender; Deepak, Desh; Singh, Akhilesh; Yadav, Rohit; Vashist, Kirti

    2016-01-01

    We present a case of a 49-year-old female with an alleged history of ingestion of approximately 100 tablets of metformin (850 mg each). Investigations revealed severe lactic acidosis with lactate levels of 13.5 mmol/L and pH of 7.17. This indicates severe toxicity and is associated with a high mortality. Charcoal-based sorbent hemoperfusion was done as a desperate effort, as patient continued to deteriorate despite supportive care and high-volume continuous venovenous hemodiafiltration. The patient survived despite metformin-associated lactic acidosis related to severe metformin toxicity. PMID:27275079

  18. Extracorporeal treatment with high-volume continuous venovenous hemodiafiltration and charcoal-based sorbent hemoperfusion for severe metformin-associated lactic acidosis.

    PubMed

    Garg, Suneel Kumar; Singh, Omender; Deepak, Desh; Singh, Akhilesh; Yadav, Rohit; Vashist, Kirti

    2016-05-01

    We present a case of a 49-year-old female with an alleged history of ingestion of approximately 100 tablets of metformin (850 mg each). Investigations revealed severe lactic acidosis with lactate levels of 13.5 mmol/L and pH of 7.17. This indicates severe toxicity and is associated with a high mortality. Charcoal-based sorbent hemoperfusion was done as a desperate effort, as patient continued to deteriorate despite supportive care and high-volume continuous venovenous hemodiafiltration. The patient survived despite metformin-associated lactic acidosis related to severe metformin toxicity. PMID:27275079

  19. Lactic acidosis associated with cerebellar vermal atrophy and cardiomyopathy.

    PubMed

    Challa, V R; Markesbery, W R; Baumann, R J; Noonan, J A

    1978-08-01

    The association of fluctuating neurological signs and congestive cardiomyopathy with chronic lactic acidosis is described in a 5 1/2 year-old-boy who ultimately succumbed to congestive heart failure. The autopsy findings included severe atrophy of the anterior cerebellar vermis and a hypertrophied heart with left sided endocardial fibroelastosis. Skeletal and cardial muscle calcification was prominent and probably due to the effect of intracellular metabolic alterations associated with lactic acidosis. A review of the literature shows that the combination of cardiomyopathy, isolated atrophy of cerebellar vermis and muscle fiber calcification have not been reported in association with idiopathic lactic acidosis previously. PMID:152418

  20. Glucocorticoid activity and metabolism with NaCl-induced low-grade metabolic acidosis and oral alkalization: results of two randomized controlled trials.

    PubMed

    Buehlmeier, Judith; Remer, Thomas; Frings-Meuthen, Petra; Maser-Gluth, Christiane; Heer, Martina

    2016-04-01

    Low-grade metabolic acidosis (LGMA), as induced by high dietary acid load or sodium chloride (NaCl) intake, has been shown to increase bone and protein catabolism. Underlying mechanisms are not fully understood, but from clinical metabolic acidosis interactions of acid-base balance with glucocorticoid (GC) metabolism are known. We aimed to investigate GC activity/metabolism under alkaline supplementation and NaCl-induced LGMA. Eight young, healthy, normal-weight men participated in two crossover designed interventional studies. In Study A, two 10-day high NaCl diet (32 g/d) periods were conducted, one supplemented with 90 mmol KHCO3/day. In Study B, participants received a high and a low NaCl diet (31 vs. 3 g/day), each for 14 days. During low NaCl, the diet was moderately acidified by replacement of a bicarbonate-rich mineral water (consumed during high NaCl) with a non-alkalizing drinking water. In repeatedly collected 24-h urine samples, potentially bioactive-free GCs (urinary-free cortisol + free cortisone) were analyzed, as well as tetrahydrocortisol (THF), 5α-THF, and tetrahydrocortisone (THE). With supplementation of 90 mmol KHCO3, the marker of total adrenal GC secretion (THF + 5α-THF + THE) dropped (p = 0.047) and potentially bioactive-free GCs were reduced (p = 0.003). In Study B, however, GC secretion and potentially bioactive-free GCs did not exhibit the expected fall with NaCl-reduction as net acid excretion was raised by 30 mEq/d. Diet-induced acidification/alkalization affects GC activity and metabolism, which in case of long-term ingestion of habitually acidifying western diets may constitute an independent risk factor for bone degradation and cardiometabolic diseases. PMID:26349936

  1. Respiratory acidosis

    MedlinePlus

    ... when the lungs cannot remove all of the carbon dioxide the body produces. This causes body fluids, especially ... Acute respiratory acidosis is a condition in which carbon dioxide builds up very quickly, before the kidneys can ...

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

    PubMed Central

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

    2001-01-01

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

  3. Rumen microbial abundance and fermentation profile during severe subacute ruminal acidosis and its modulation by plant derived alkaloids in vitro.

    PubMed

    Mickdam, Elsayed; Khiaosa-Ard, Ratchaneewan; Metzler-Zebeli, Barbara U; Klevenhusen, Fenja; Chizzola, Remigius; Zebeli, Qendrim

    2016-06-01

    Rumen microbiota have important metabolic functions for the host animal. This study aimed at characterizing changes in rumen microbial abundances and fermentation profiles using a severe subacute ruminal acidosis (SARA) in vitro model, and to evaluate a potential modulatory role of plant derived alkaloids (PDA), containing quaternary benzophenanthridine and protopine alkaloids, of which sanguinarine and chelerythrine were the major bioactive compounds. Induction of severe SARA strongly affected the rumen microbial composition and fermentation variables without suppressing the abundance of total bacteria. Protozoa and fungi were more sensitive to the low ruminal pH condition than bacteria. Induction of severe SARA clearly depressed degradation of fiber (P < 0.001), which came along with a decreased relative abundance of fibrolytic Ruminococcus albus and Fibrobacter succinogenes (P < 0.001). Under severe SARA conditions, the genus Prevotella, Lactobacillus group, Megasphaera elsdenii, and Entodinium spp. (P < 0.001) were more abundant, whereas Ruminobacter amylophilus was less abundant. SARA largely suppressed methane formation (-70%, P < 0.001), although total methanogenic 16S rRNA gene abundance was not affected. According to principal component analysis, Methanobrevibacter spp. correlated to methane concentration. Addition of PDA modulated ruminal fermentation under normal conditions such as enhanced (P < 0.05) concentration of total SCFA, propionate and valerate, and increased (P < 0.05) degradation of crude protein compared with the unsupplemented control diet. Our results indicate strong shifts in the microbial community during severe SARA compared to normal conditions. Supplementation of PDA positively modulates ruminal fermentation under normal ruminal pH conditions. PMID:26868619

  4. Tonometry revisited: perfusion-related, metabolic, and respiratory components of gastric mucosal acidosis in acute cardiorespiratory failure.

    PubMed

    Jakob, Stephan M; Parviainen, Ilkka; Ruokonen, Esko; Kogan, Alexander; Takala, Jukka

    2008-05-01

    Mucosal pH (pHi) is influenced by local perfusion and metabolism (mucosal-arterial pCO2 gradient, DeltapCO2), systemic metabolic acidosis (arterial bicarbonate), and respiration (arterial pCO2). We determined these components of pHi and their relation to outcome during the first 24 h of intensive care. We studied 103 patients with acute respiratory or circulatory failure (age, 63+/-2 [mean+/-SEM]; Acute Physiology and Chronic Health Evaluation II score, 20+/-1; Sequential Organ Failure Assessment score, 8+/-0). pHi, and the effects of bicarbonate and arterial and mucosal pCO2 on pHi, were assessed at admission, 6, and 24 h. pHi was reduced (at admission, 7.27+/-0.01) due to low arterial bicarbonate and increased DeltapCO2. Low pHi (<7.32) at admission (n=58; mortality, 29% vs. 13% in those with pHi>or=7.32 at admission; P=0.061) was associated with an increased DeltapCO2 in 59% of patients (mortality, 47% vs. 4% for patients with low pHi and normal DeltapCO2; P=0.0003). An increased versus normal DeltapCO2, regardless of pHi, was associated with increased mortality at admission (51% vs. 5%; P<0.0001; n=39) and at 6 h (34% vs. 13%; P=0.016; n=45). A delayed normalization or persistently low pHi (n=47) or high DeltapCO2 (n=25) was associated with high mortality (low pHi [34%] vs. high DeltapCO2 [60%]; P=0.046). In nonsurvivors, hypocapnia increased pHi at baseline, 6, and 24 h (all Pacidosis. Inadequate tissue perfusion may persist despite stable hemodynamics and contributes to poor outcome. PMID:18004228

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

    PubMed Central

    2012-01-01

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

  6. Metabolic multianalyte microphysiometry reveals extracellular acidosis is an essential mediator of neuronal preconditioning.

    PubMed

    McKenzie, Jennifer R; Palubinsky, Amy M; Brown, Jacquelynn E; McLaughlin, Bethann; Cliffel, David E

    2012-07-18

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

  7. Lactate Clearance and Vasopressor Seem to Be Predictors for Mortality in Severe Sepsis Patients with Lactic Acidosis Supplementing Sodium Bicarbonate: A Retrospective Analysis

    PubMed Central

    Kim, Eun Bin; Jeong, Hyo Jin; Son, Young Ki; An, Won Suk

    2015-01-01

    Introduction Initial lactate level, lactate clearance, C-reactive protein, and procalcitonin in critically ill patients with sepsis are associated with hospital mortality. However, no study has yet discovered which factor is most important for mortality in severe sepsis patients with lactic acidosis. We sought to clarify this issue in patients with lactic acidosis who were supplementing with sodium bicarbonate. Materials and Methods Data were collected from a single center between May 2011 and April 2014. One hundred nine patients with severe sepsis and lactic acidosis who were supplementing with sodium bicarbonate were included. Results The 7-day mortality rate was 71.6%. The survivors had higher albumin levels and lower SOFA, APACHE II scores, vasopressor use, and follow-up lactate levels at an elapsed time after their initial lactate levels were checked. In particular, a decrement in lactate clearance of at least 10% for the first 6 hours, 24 hours, and 48 hours of treatment was more dominant among survivors than non-survivors. Although the patients who were treated with broad-spectrum antibiotics showed higher illness severity than those who received conventional antibiotics, there was no significant mortality difference. 6-hour, 24-hour, and 48-hour lactate clearance (HR: 4.000, 95% CI: 1.309–12.219, P = 0.015) and vasopressor use (HR: 4.156, 95% CI: 1.461–11.824, P = 0.008) were significantly associated with mortality after adjusting for confounding variables. Conclusions Lactate clearance at a discrete time point seems to be a more reliable prognostic index than initial lactate value in severe sepsis patients with lactic acidosis who were supplementing with sodium bicarbonate. Careful consideration of vasopressor use and the initial application of broad-spectrum antibiotics within the first 48 hours may be helpful for improving survival, and further study is warranted. PMID:26692209

  8. Anorexia nervosa, laxative abuse, hypopotassemia and distal renal tubular acidosis.

    PubMed

    Pines, A; Kaplinsky, N; Olchovsky, D; Frankl, O; Goldfarb, D; Iaina, A

    1985-01-01

    A case of anorexia nervosa in a 28-year-old woman with laxative abuse, hypopotassemia and severe metabolic acidosis, is described. The diagnosis of classical renal tubular acidosis, Type I, was confirmed by our inability to decrease urinary pH beyond 5.5 and to increase ammonia excretion during an ammonium chloride loading test. A bicarbonate loading test and normal plasma aldosterone with high renin activity excluded proximal renal tubular acidosis, hyporeninemic-hypoaldosteronemic renal tubular acidosis and Bartter's syndrome. The inability to increase ammonium excretion during severe metabolic acidosis following ammonium chloride loading did not favor the possibility of a transient physiological adaptation of ammoniagenesis at the tubular cell level, related to potassium depletion. Although mental disorder, laxative abuse, abstinence from food intake and severe potassium depletion intermingled in a vicious cycle, we assume that one of the following possibilities may explain the clinical presentation in our patient: either two separated and unrelated disorders, or laxative abuse as the cause of renal tubular acidification impairment. PMID:3972559

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

    PubMed

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

    2014-12-01

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

  10. [An autopsy case of neonatal lactic acidosis].

    PubMed

    Giordano, G; Corradi, D; D'Adda, T; Melissari, M

    2001-02-01

    Defects in mitochondrial enzymes, such as pyruvate dehydrogenase and cytochrome oxidase, cause hereditary disorders which lead to modifications in cellular pH due to the accumulation of pyruvate and lactic acid. Mitochondrial diseases include severe neonatal diseases and less severe forms of adult diseases. We report the case of lactic acidosis in a newborn girl who was delivered at 36 weeks of gestation and who died 3 months after birth. Her family history revealed a relative with tetraparesis and mental retardation. Her clinical findings, such as tonic-clonic convulsions and accumulation of pyruvate and lactic acid in blood, urine and cerebrospinal fluid, were refractory to treatment and developed soon after birth. Ultrasound scans of the brain some days before death revealed cerebral atrophy with ventricular dilatation and thinning of the corpus callosum and septum pellucidum. The clinical diagnosis of metabolic lactic acidosis was confirmed by macroscopic, microscopic and ultrastructural findings seen at autopsy. On macroscopic examination, the heart was hypertrophic, and the brain was atrophic with ventricular dilatation and thinning of corpus callosum. Small cystic lesions were present in the basal ganglia. On microscopic examination, the latter were characterized by loss of neurons, gliosis and capillary proliferation. Ultrastructural examination of the heart and skeletal muscle showed lysis of myofibrils, mitochondrial pleomorphism and hyperplasia, and crystalline inclusion in mitochondria and in the matrix compartment. In reporting this case, we emphasize the importance of accurate postmortem examination and clinical data for the diagnosis of metabolic lactic acidosis. PMID:11294018

  11. Proximal renal tubular acidosis

    MedlinePlus

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  12. Transient feeding of a concentrate-rich diet increases the severity of subacute ruminal acidosis in dairy cattle.

    PubMed

    Pourazad, P; Khiaosa-Ard, R; Qumar, M; Wetzels, S U; Klevenhusen, F; Metzler-Zebeli, B U; Zebeli, Q

    2016-02-01

    The objective of this study was to investigate the effect of the pattern of concentrate-rich feeding on subacute ruminal acidosis (SARA), its severity, and the corresponding changes in VFA concentration. Eight rumen-cannulated Holstein cows were assigned to a 2 × 2 crossover design with 2 SARA challenge models and 2 experimental runs ( = 8 per treatment). Each run lasted for 40 d, consisting of a 6-d baseline, a 6-d gradual grain adaptation, and a 28-d SARA challenge period. The 2 SARA challenge models were transient (TRA) and persistent (PER) SARA. Initially, all cows were subjected to a forage-only diet (baseline) and gradually switched to 60% concentrate (DM basis). Then, cows in the PER model were continuously challenged for 28 d, whereas cows in the TRA model had a 7-d break from the SARA diet and were fed the forage-only diet after the first 7 d of SARA challenge. Thereafter, the TRA cows were rechallenged with the SARA diet. Wireless ruminal pH sensors were used to obtain ruminal pH profiles and temperature over the experimental period. For the determination of VFA, free ruminal liquid (FRL) and particle-associated ruminal liquid (PARL) were collected once for the baseline and twice (d 20 and 40 for the PER model) or 3 times (d 13, 30, and 40 for the TRA model) during SARA, each time at 0, 4, and 8 h after the morning feeding. Cows in both models experienced SARA albeit with day-to-day variation. From the start until the first 7-d SARA, cows of both models had similar pH profiles, but during the rechallenge, SARA was more severe in the TRA model than in the PER model based on lower daily mean ruminal pH (5.93 vs. 6.15; SEM 0.058) and double the amount of time at pH < 5.8 (497 vs. 278 min; SEM 68.61, < 0.05). Mean ruminal temperature was raised during SARA compared with the baseline (38.9 vs. 38.7°C; SEM 0.057, < 0.001). Concentrations of VFA increased with increasing time after feeding ( < 0.001). In general, SARA challenge (d 40 vs. the baseline), but not

  13. Lactic acidosis induced by metformin: incidence, management and prevention.

    PubMed

    Lalau, Jean-Daniel

    2010-09-01

    Lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. First, this potential event still influences treatment strategies in type 2 diabetes mellitus, particularly in the many patients at risk of kidney failure, in those presenting contraindications to metformin and in the elderly. Second, the relationship between metformin and lactic acidosis is complex, since use of the drug may be causal, co-responsible or coincidental. The present review is divided into three parts, dealing with the incidence, management and prevention of lactic acidosis occurring during metformin treatment. In terms of incidence, the objective of this article is to counter the conventional view of the link between metformin and lactic acidosis, according to which metformin-associated lactic acidosis is rare but is still associated with a high rate of mortality. In fact, the direct metformin-related mortality is close to zero and metformin may even be protective in cases of very severe lactic acidosis unrelated to the drug. Metformin has also inherited a negative class effect, since the early biguanide, phenformin, was associated with more frequent and sometimes fatal lactic acidosis. In the second part of this review, the objective is to identify the most efficient patient management methods based on our knowledge of how metformin acts on glucose/lactate metabolism and how lactic acidosis may occur (at the organ and cellular levels) during metformin treatment. The liver appears to be a key organ for both the antidiabetic effect of metformin and the development of lactic acidosis; the latter is attributed to mitochondrial impairment and subsequent adenosine triphosphate depletion, acceleration of the glycolytic flux, increased glucose uptake and the generation of lactate, which effluxes into the circulation rather than being oxidized further. Haemodialysis should systematically be performed in severe forms of lactic

  14. (Uncommon) Mechanisms of Branchial Ammonia Excretion in the Common Carp (Cyprinus carpio) in Response to Environmentally Induced Metabolic Acidosis.

    PubMed

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

    2016-01-01

    Freshwater fishes generally increase ammonia excretion in acidic waters. The new model of ammonia transport in freshwater fish involves an association between the Rhesus (Rh) protein Rhcg-b, the Na(+)/H(+) exchanger (NHE), and a suite of other membrane transporters. We tested the hypothesis that Rhcg-b and NHE3 together play a critical role in branchial ammonia excretion in common carp (Cyprinus carpio) chronically exposed to a low-pH environment. Carp were exposed to three sequential environmental treatments-control pH 7.6 water (24 h), pH 4.0 water (72 h), and recovery pH 7.6 water (24 h)-or in a separate series were simply exposed to either control (72 h) or pH 4.0 (72 h) water. Branchial ammonia excretion was increased by ∼2.5-fold in the acid compared with the control period, despite the absence of an increase in the plasma-to-water partial pressure NH3 gradient. Alanine aminotransferase activity was higher in the gills of fish exposed to pH 4 versus control water, suggesting that ammonia may be generated in gill tissue. Gill Rhcg-b and NHE3b messenger RNA levels were significantly elevated in acid-treated relative to control fish, but at the protein level Rhcg-b decreased (30%) and NHE3b increased (2-fold) in response to water of pH 4.0. Using immunofluorescence microscopy, NHE3b and Rhcg-b were found to be colocalized to ionocytes along the interlamellar space of the filament of control fish. After 72 h of acid exposure, Rhcg-b staining almost disappeared from this region, and NHE3b was more prominent along the lamellae. We propose that ammoniagenesis within the gill tissue itself is responsible for the higher rates of branchial ammonia excretion during chronic metabolic acidosis. Unexpectedly, gill Rhcg-b does not appear to be important in gill ammonia transport in low-pH water, but the strong induction of NHE3b suggests that some NH4(+) may be eliminated directly in exchange for Na(+). These findings contrast with previous studies in larval zebrafish

  15. Endolymphatic sac enlargement in a girl with a novel mutation for distal renal tubular acidosis and severe deafness.

    PubMed

    Nikki, Rink; Martin, Bitzan; Gus, O'Gorman; Mato, Nagel; Elena, Torban; Paul, Goodyer

    2012-01-01

    Hereditary distal renal tubular acidosis (dRTA) is caused by mutations of genes encoding subunits of the H(+)-ATPase (ATP6V0A4 and ATP6V1B1) expressed in α-intercalated cells of the distal renal tubule and in the cochlea. We report on a 2-year-old girl with distal RTA and profound speech delay which was initially misdiagnosed as autism. Genetic analysis showed compound heterozygous mutations with one known and one novel mutation of the ATP6V1B1 gene; cerebral magnetic resonance imaging (MRI) revealed bilateral enlargement of the endolymphatic sacs of the inner ear. With improved cooperation, audiometric testing showed that hearing loss was most profound on the right, where endolymphatic sac enlargement was greatest, demonstrating a clear link between the degree of deafness and the degree of inner ear abnormality. This case indicates the value of MRI for diagnosis of inner ear involvement in very young children with distal RTA. Although citrate therapy quickly corrects the acidosis and restores growth, early diagnosis of deafness is crucial so that hearing aids can be used to assist acquisition of speech and to provide enough auditory nerve stimulation to assure the affected infants remain candidates for cochlear implantation. PMID:22966473

  16. Atypical presentation of distal renal tubular acidosis in two siblings.

    PubMed

    Tasic, Velibor; Korneti, Petar; Gucev, Zoran; Hoppe, Bernd; Blau, Nenad; Cheong, Hae Il

    2008-07-01

    Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH <5.50 during systemic acidosis. We report two male siblings who presented with severe hyperchloremic metabolic acidosis, high urinary pH, nephrocalcinosis, growth retardation, sensorineural hearing loss, and hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy. PMID:18386070

  17. Bone Density Is Directly Associated With Glomerular Filtration and Metabolic Acidosis but Do Not Predict Fragility Fractures in Men With Moderate Chronic Kidney Disease.

    PubMed

    Lima, Guilherme Alcantara Cunha; de Paula Paranhos-Neto, Francisco; Silva, Luciana Colonese; de Mendonça, Laura Maria Carvalho; Delgado, Alvimar Gonçalves; Leite, Maurilo; Gomes, Carlos Perez; Farias, Maria Lucia Fleiuss

    2016-01-01

    Hyperparathyroidism, vitamin D deficiency, increased fibroblast growth factor-23 (FGF-23), and metabolic acidosis promote bone fragility in chronic kidney disease (CKD). Although useful in predicting fracture risk in the general population, the role of dual-energy X-ray absorptiometry (DXA) in CKD remains uncertain. This cross-sectional study included 51 men aged 50-75 yr with moderate CKD. The stage 4 CKD patients had higher levels of parathyroid hormone (p<0.001), FGF-23 (p=0.029), and lowest 25-hydroxyvitamin D (p=0.016), bicarbonate (p<0.001), total femur (p=0.003), and femoral neck (p=0.011) T-scores compared with stage 3 CKD patients. Total femur and femoral neck T-scores were directly correlated with serum bicarbonate (p=0.003, r=0.447 and p=0.005, r=0.427, respectively) and estimated glomerular filtration rate (p=0.024, r=0.325 and p=0.003, r=0.313, respectively) but were not significantly associated with parathyroid hormone, 25-hydroxyvitamin D, or FGF-23. Only 3.9% of the participants had osteoporosis on DXA scan, whereas 31.4% reported a low-impact fracture. Our data point to a pivotal role of metabolic acidosis for bone impairment and to the inadequacy of DXA to evaluate bone fragility in CKD patients. PMID:24709549

  18. [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

  19. The Association Between Admission Magnesium Concentrations and Lactic Acidosis in Critical Illness

    PubMed Central

    Moskowitz, Ari; Lee, Joon; Donnino, Michael W.; Mark, Roger; Celi, Leo Anthony; Danziger, John

    2016-01-01

    Introduction Although magnesium plays an important role in aerobic metabolism and magnesium deficiency is a common phenomenon in critical illness, the association between magnesium deficiency and lactic acidosis in the intensive care unit (ICU) has not been defined. Methods This was a retrospective, cross-sectional study conducted at a 77 ICU bed tertiary medical center. Data pertaining to the first unique admission of any ICU patient between 2001 and 2008 were extracted from the Multiparameter Intelligent Monitoring in Intensive Care database. Hypomagnesemia was defined as serum magnesium <1.6 mg/dL. Mild and severe lactic acidosis were defined as lactate concentrations of >2 and > 4 mmol/L, respectively. Multivariate modeling was used to explore the association between magnesium and lactate concentrations. Results Of 8922 critically ill patients, 22.6% were hypomagnesemic. Hypomagnesemia was associated with an increased adjusted risk of mild lactic acidosis (odds ratio [OR] 1.71, 95% confidence interval [95%CI] 1.51–1.94, P < .001) and severe lactic acidosis (OR 1.56, 95%CI 1.32–1.84, P < .001) than the reference quartile. The association between hypomagnesemia and mild lactic acidosis was stronger in those at risk of magnesium deficiency, including diabetics (OR 2.02, 95%CI 1.51–2.72, P < .001) and alcoholics (OR 1.92, 95%CI 1.16–3.19, P = .01). As an internal model control, hypokalemia was not associated with an increased risk of lactic acidosis. Conclusions Magnesium deficiency is a common finding in patients admitted to the ICU and is associated with lactic acidosis. Our findings support the biologic role of magnesium in metabolism and raise the possibility that hypomagnesemia is a correctable risk factor for lactic acidosis in critical illness. PMID:24733810

  20. Phenylbutyrate Therapy for Pyruvate Dehydrogenase Complex Deficiency and Lactic Acidosis

    PubMed Central

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

    2014-01-01

    Lactic acidosis is a build-up of lactic acid in the blood and tissues, which can be due to several inborn errors of metabolism as well as nongenetic conditions. Deficiency of pyruvate dehydrogenase complex (PDHC) is the most common genetic disorder leading to lactic acidosis. Phosphorylation of specific serine residues of the E1α subunit of PDHC by pyruvate dehydrogenase kinase (PDK) inactivates the enzyme, whereas dephosphorylation restores PDHC activity. We found that phenylbutyrate enhances PDHC enzymatic activity in vitro and in vivo by increasing the proportion of unphosphorylated enzyme through inhibition of PDK. Phenylbutyrate given to C57B6/L wild-type mice results in a significant increase in PDHC enzyme activity and a reduction of phosphorylated E1α in brain, muscle, and liver compared to saline-treated mice. By means of recombinant enzymes, we showed that phenylbutyrate prevents phosphorylation of E1α through binding and inhibition of PDK, providing a molecular explanation for the effect of phenylbutyrate on PDHC activity. Phenylbutyrate increases PDHC activity in fibroblasts from PDHC-deficient patients harboring various molecular defects and corrects the morphological, locomotor, and biochemical abnormalities in the noam631 zebrafish model of PDHC deficiency. In mice, phenylbutyrate prevents systemic lactic acidosis induced by partial hepatectomy. Because phenylbutyrate is already approved for human use in other diseases, the findings of this study have the potential to be rapidly translated for treatment of patients with PDHC deficiency and other forms of primary and secondary lactic acidosis. PMID:23467562

  1. 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 mzm1Δ 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

  2. The Use of Sodium Bicarbonate in the Treatment of Acidosis in Sepsis: A Literature Update on a Long Term Debate

    PubMed Central

    Velissaris, Dimitrios; Karamouzos, Vasilios; Ktenopoulos, Nikolaos; Pierrakos, Charalampos; Karanikolas, Menelaos

    2015-01-01

    Introduction. Sepsis and its consequences such as metabolic acidosis are resulting in increased mortality. Although correction of metabolic acidosis with sodium bicarbonate seems a reasonable approach, there is ongoing debate regarding the role of bicarbonates as a therapeutic option. Methods. We conducted a PubMed literature search in order to identify published literature related to the effects of sodium bicarbonate treatment on metabolic acidosis due to sepsis. The search included all articles published in English in the last 35 years. Results. There is ongoing debate regarding the use of bicarbonates for the treatment of acidosis in sepsis, but there is a trend towards not using bicarbonate in sepsis patients with arterial blood gas pH > 7.15. Conclusions. Routine use of bicarbonate for treatment of severe acidemia and lactic acidosis due to sepsis is subject of controversy, and current opinion does not favor routine use of bicarbonates. However, available evidence is inconclusive, and more studies are required to determine the potential benefit, if any, of bicarbonate therapy in the sepsis patient with acidosis. PMID:26294968

  3. Fuel metabolism during severe rowing exercise

    SciTech Connect

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

    1986-03-01

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

  4. Hypokalemic periodic paralysis in Sjogren's syndrome secondary to distal renal tubular acidosis.

    PubMed

    Yılmaz, Hakkı; Kaya, Mustafa; Özbek, Mustafa; ÜUreten, Kemal; Safa Yıldırım, İ

    2013-07-01

    We report a 53-year-old Turkish female presented with progressive weakness and mild dyspnea. Laboratory results demonstrated severe hypokalemia with hyperchloremic metabolic acidosis. The urinary anion gap was positive in the presence of acidemia, thus she was diagnosed with hypokalemic paralysis from a severe distal renal tubular acidosis (RTA). Immunologic work-up showed a strongly positive ANA of 1:3,200 and positive antibodies to SSA and SSB. Schirmer's test was abnormal. Autoimmune and other tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede sicca complaints. The pathology in most cases is a tubulointerstitial nephritis causing among other things, distal RTA, and, rarely, hypokalemic paralysis. Treatment consists of potassium repletion, alkali therapy, and corticosteroids. Primary SS could be a differential in women with acute weakness and hypokalemia. PMID:22212410

  5. Lactate clearance and metabolic aspects of continuous high-volume hemofiltration

    PubMed Central

    Cheungpasitporn, Wisit; Zand, Ladan; Dillon, John J.; Qian, Qi; Leung, Nelson

    2015-01-01

    Lactic acidosis is associated with high morbidity and mortality in hospitalized patients. Treatment of lactic acidosis is targeted on correcting the underlying causes and optimizing adequate oxygen delivery to the tissues. Even though evidence is lacking, continuous renal replacement therapy (CRRT) and dialysis have been advocated as treatments for lactic acidosis. We report a 28-year-old Caucasian male with a history of hemophagocytic lymphohistiocytosis who presented with septic shock, severe lactic acidosis and multiple organ failure. Metabolic acidosis was corrected after bicarbonate therapy and CRRT with a hemofiltration rate of 7 L/h (58 mL/kg/h). Lactate clearance was calculated to be 79 mL/min. Compared with reported rates of lactate overproduction in septic shock, the rate of lactate clearance is quite small. Our case suggests that CRRT with high-volume hemofiltration is not effective for severe lactic acidosis. Lactic acidosis alone should not be considered as a nonrenal indication for CRRT. PMID:26251702

  6. Renal tubular acidosis due to the milk-alkali syndrome.

    PubMed

    Rochman, J; Better, O S; Winaver, J; Chaimowitz, C; Barzilai, A; Jacobs, R

    1977-06-01

    A 60-year-old man with a history of excessive ingestion of calcium carbonate presented with azotemia, hypercalcemia and hyperphosphatemia. His acid-base status was initially normal. Following the cessation of calcium carbonate treatment, the hypercalcemia and azotemia disappeared, and the patient was found to be in metabolic acidosis with blunted acid excretion and a urine pH of 6.1. Kidney biopsy showed focal tubular calcification; the tubular damage was apparently caused by hypercalcemia and had resulted in renal tubular acidosis. During the three months of observation since that time there has been a tendecy for spontaneous remission of the renal tubular acidosis. Impaired renal hydrogen ion excretion prevented the development of metabolic alkalosis despite ingestion of alkali initially, and was later responsible for the metabolic acidosis. Renal tubular acidosis occurring as a sequel to the milk-alkali syndrome may aggravate the danger of nephrocalcinosis in this syndrome. PMID:885714

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

    PubMed

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

    2003-08-01

    This study compared the metabolic-ventilatory responses and the glycemic threshold identified during lactate minimum (LM) and individual anaerobic threshold (IAT) tests. In addition, the ability to determine the anaerobic power, aerobic-anaerobic transition (Trans) (e.g. ventilatory threshold; VT) and the maximal oxygen consumption (VO(2max)) all within a single incremental treadmill test (IT) was investigated. Fifteen physically fit men [25.9 (5.5) years; 77.4 (6.5) kg] performed the following: test 1, IT for IAT; and test 2, LM: 30-s Wingate test followed by 8 min rest and then an IT that was the same as test 1. Blood lactate concentration [lac], glucose concentration [gluc], pH, PO(2), PCO(2), base excess (BE) and ventilatory variables were measured. At the beginning of the IT for LM, the ventilation, PO(2) and VO(2) were higher and the pH, BE and PCO(2) were lower in relation to IAT ( P<0.05), while no differences were observed after reaching LM intensity during IT. Moreover, the Trans could be identified by [lac] (IAT, LM), minute ventilation [V(E;) VT identified during IAT protocol (VT-IAT) and VT identified during LM protocol (VT-LM)], and [gluc] (IGT, GM) during the IT for IAT and LM. The velocities (kilometers per hour) corresponding to IAT (12.6+/-1.6), VT-IAT (12.5+/-1.7), IGT (12.6+/-1.6), LM (12.5+/-1.5), VT-LM (12.3+/-1.5), and GM (12.6+/-1.9) were not different from each other and the LM and IAT protocols resulted in the similar VO(2max). We concluded that: (1) after reaching the LM the metabolic responses during IT are similar to IAT; (2) performing a Wingate test prior to an IT does not interfere with the Trans and VO(2max) attainment; (3) and the IGT and GM can predict the Trans. PMID:12759761

  8. The use of dichloroacetate in the treatment of overwhelming hypoxic acidosis.

    PubMed

    Wahr, J A; Ullrich, K; Bolling, S F

    1994-02-01

    Overwhelming hypoxic acidosis due to poor tissue oxygen delivery from low cardiac output, pulmonary failure, and other causes has devastating effects postoperatively on patient outcome. Whereas conventional therapeutics often can not reverse the downward spiral of these patients, dichloroacetate (DCA) has been shown to be beneficial. This study investigated the metabolic and hemodynamic effects of DCA given after the onset of overwhelming hypoxic acidosis in a canine model. A hypoxically ventilated canine model of severe induced acidosis was established and dogs surviving the development of acidosis were randomized to receive DCA or sodium chloride (NaCl) treatment. Dogs receiving DCA after development of hypoxic lactic acidosis showed no further change in metabolic parameters during the 90-minute treatment period (pH, 7.24 to 7.23; HCO3, 17.7 to 18 mmol/L; lactate, 2.04 to 1.05 mM/L); whereas animals receiving an equivalent sodium load showed progressive, significant deterioration in all parameters (pH, 7.24 to 7.12; HCO3, 16.8 to 13.2 mM/L; lactate, 2.05 to 3.55 mM/L). Myocardial blood flow was significantly increased by hypoxia in all dogs. Finally, cardiac output and stroke volume were significantly increased at 90 minutes by DCA versus control. Myocardial oxygen utilization efficiency (LV work/M VO2) was improved during DCA treatment. DCA, a carboxylic acid, increases pyruvate dehydrogenase activity, thereby enhancing lactate use a metabolic substrate. DCA had an ameliorative metabolic effect, and benefitted myocardial performance without a direct inotropic effect. DCA treatment appears to enhance myocardial performance on a metabolic and not primarily inotropic basis, does not increase the "cost" of myocardial work, and warrants further study. PMID:8167289

  9. 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...

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

    PubMed

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

    2013-11-01

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

  11. Metabolic syndrome in patients with severe mental illness in Gorgan

    PubMed Central

    Kamkar, Mohammad Zaman; Sanagoo, Akram; Zargarani, Fatemeh; Jouybari, Leila; Marjani, Abdoljalal

    2016-01-01

    Background: Metabolic syndrome is commonly associated with cardiovascular diseases and psychiatric mental illness. Hence, we aimed to assess the metabolic syndrome among severe mental illness (SMI). Materials and Methods: The study included 267 patients who were referred to the psychiatric unit at 5th Azar Education Hospital of Golestan University of Medical Sciences in Gorgan, Iran. Results: The mean waist circumference, systolic and diastolic blood pressure, triglyceride and fasting blood glucose levels were significantly higher in the SMI with metabolic syndrome, but the high density lipoprotein (HDL)-cholesterol was significantly lower. The prevalence of metabolic syndrome in SMI patients was 20.60%. There were significant differences in the mean of waist circumference, systolic (except for women) and diastolic blood pressure, triglyceride, HDL-cholesterol and fasting blood glucose in men and women with metabolic syndrome when compared with subjects without metabolic syndrome. The prevalence of metabolic syndrome in SMI women was higher than men. The most age distribution was in range of 30-39 years old. The most prevalence of metabolic syndrome was in age groups 50-59 years old. The prevalence of metabolic syndrome was increased from 30 to 59 years old. Conclusion: The prevalence of metabolic syndrome in patients with SMI in Gorgan is almost similar to those observed in Asian countries. The prevalence of metabolic syndrome was lower than western countries. These observations may be due to cultural differences in the region. It should be mention that the families of mental illness subjects in our country believe that their patients must be cared better than people without mental illness. These findings of this study suggest that mental illness patients are at risk of metabolic syndrome. According to our results, risk factors such as age and gender differences may play an important role in the presence of metabolic syndrome. In our country, women do less

  12. Thiamine Deficiency in a Developed Country: Acute Lactic Acidosis in Two Neonates Due to Unsupplemented Parenteral Nutrition.

    PubMed

    Salvatori, Guglielmo; Mondì, Vito; Piersigilli, Fiammetta; Capolupo, Irma; Pannone, Veronica; Vici, Carlo Dionisi; Rizzo, Cristiano; Dotta, Andrea

    2016-08-01

    Thiamine is a water-soluble vitamin implicated in several metabolic processes. Its deficiency, due to prolonged parenteral nutrition without adequate vitamin supplementation, can lead to multiorgan failure characterized by cardiovascular impairment and metabolic acidosis refractory to bicarbonate administration. Only thiamine administration allows the remission of symptoms. We report 2 preterm infants with acute thiamine deficiency due to prolonged parenteral nutrition without adequate vitamin supplementation. PMID:25591974

  13. SDF1 induction by acidosis from principal cells regulates intercalated cell subtype distribution

    PubMed Central

    Schwartz, George J.; Gao, XiaoBo; Tsuruoka, Shuichi; Purkerson, Jeffrey M.; Peng, Hu; D’Agati, Vivette; Picard, Nicolas; Eladari, Dominique; Al-Awqati, Qais

    2015-01-01

    The nephron cortical collecting duct (CCD) is composed of principal cells, which mediate Na, K, and water transport, and intercalated cells (ICs), which are specialized for acid-base transport. There are two canonical IC forms: acid-secreting α-ICs and HCO3-secreting β-ICs. Chronic acidosis increases α-ICs at the expense of β-ICs, thereby increasing net acid secretion by the CCD. We found by growth factor quantitative PCR array that acidosis increases expression of mRNA encoding SDF1 (or CXCL12) in kidney cortex and isolated CCDs from mouse and rabbit kidney cortex. Exogenous SDF1 or pH 6.8 media increased H+ secretion and decreased HCO3 secretion in isolated perfused rabbit CCDs. Acid-dependent changes in H+ and HCO3 secretion were largely blunted by AMD3100, which selectively blocks the SDF1 receptor CXCR4. In mice, diet-induced chronic acidosis increased α-ICs and decreased β-ICs. Additionally, IC-specific Cxcr4 deletion prevented IC subtype alterations and magnified metabolic acidosis. SDF1 was transcriptionally regulated and a target of the hypoxia-sensing transcription factor HIF1α. IC-specific deletion of Hif1a produced no effect on mice fed an acid diet, as α-ICs increased and β-ICs decreased similarly to that observed in WT littermates. However, Hif1a deletion in all CCD cells prevented acidosis-induced IC subtype distribution, resulting in more severe acidosis. Cultured principal cells exhibited an HIF1α-dependent increase of Sdf1 transcription in response to media acidification. Thus, our results indicate that principal cells respond to acid by producing SDF1, which then acts on adjacent ICs. PMID:26517693

  14. [Primary distal renal tubular acidosis: a case report].

    PubMed

    Abdallah, Jihene Ben; Charfeddine, Bassem; Braham, Imen; Neffati, Souhir; Othmen, Leila Ben; Letaief, Affef; Smach, Mohamed Ali; Bourfifa, Zoheier; Dridi, Hedi; Limem, Khalifa

    2011-01-01

    The primary distal renal tubular acidosis is characterized biochemically by the inability of the kidney to produce appropriately acid urine in the presence of systemic metabolic acidosis or after acid loading (e.g. ammonium chloride). It is secondary to defective excretion of H(+) by the cells of the collecting duct. We report the observation of the child MC, 4-year-old, for whom the association of polyuria-polydipsia syndrome, a failure to thrive, nephrolithiasis, hypercalciuria, and especially a high urine pH in the presence of metabolic acidosis did evoke diagnosis of distal renal tubular acidosis. An urine acidification test with ammonium chloride was performed, the urinary pH was always higher than 5.5, thus confirming the diagnosis. PMID:21464016

  15. Acquired distal renal tubular acidosis in man.

    PubMed

    Better, O S

    1982-10-01

    Distal renal tubular acidosis (dRTA) may complicate renal transplantation, liver cirrhosis, and obstructive uropathy. Indeed, its occurrence may be an early clue to an episode of rejection of the graft or to obstructive uropathy. The mechanism in most patients with dRTA is impaired distal secretion of protons. In some patients, however, back leak of protons from tubular lumen to blood may abolish distal tubular ability to maintain urine to blood proton gradients. In patients with obstructive uropathy the spectrum of tubular acidosis is widened by the occurrence of additional defects in tubular secretion of potassium and impairment of hydrogen ion secretion secondary to hypoaldosteronism. Hyperkalemia is also seen in "voltage dependent" states such as following the administration of lithium and amiloride. Hyperkalemia per se is conducive to acidosis by a combination of extrarenal and several intrarenal mechanisms. PMID:6755051

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

    PubMed

    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

  17. 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

  18. Trauma triggering thyrotoxic crisis with lactic acidosis

    PubMed Central

    Prosser, Jennifer S.; Quan, Dan K.

    2015-01-01

    Thyrotoxic crisis (TC) is defined as a life-threatening exacerbation of the hyperthyroid state that causes multiple autonomic and metabolic disturbances. It is considered to be an endocrine emergency that must be urgently diagnosed and treated. We describe a case of TC precipitated by trauma with a resultant lactic acidosis. The patient is a 24-year-old male with a history of hyperthyroidism who presented to the emergency department following a motor vehicle accident. The patient was initially tachycardic and hypertensive, however, was afebrile. Initial laboratory analysis showed an anion gap of 26, lactic acid 7.6, free T4 5.61 and thyroid stimulating hormone < 0.015. A diagnosis of TC was made, and he was treated with intravenous fluids, propranolol, and methimazole with improvement of tachycardia and lactic acidosis. We discuss the features of this case, which reviews the presentations of TC as well as its metabolic sequelae. PMID:26604530

  19. Absence of acidosis in the initial presentation of propionic acidaemia.

    PubMed

    Walter, J H; Wraith, J E; Cleary, M A

    1995-05-01

    The clinical presentation and results of the initial biochemical and haematological investigations in 11 newborn term infants with propionic acidaemia are described. All patients had neurological symptoms. Only four had clinically important acidosis, but all had a raised blood ammonia. A diagnosis of propionic acidaemia should be considered in all newborn infants with unexplained neurological deterioration even in the absence of a metabolic acidosis. PMID:7796239

  20. [Ischemic myocardial metabolism and antianginal drugs].

    PubMed

    Ichihara, K

    1986-12-01

    The effect of several kinds of antianginal drugs: nitrates, coronary vasodilators, beta-adrenergic blocking agents and calcium entry blocking agents on the myocardial metabolism and myocardial acidosis during ischemia was studied in the dog heart in vivo. Ischemia was induced by ligating the left anterior descending coronary artery. Ischemia accelerated anaerobic metabolism in the myocardium, in which glycogen breakdown, accumulation of glycolytic intermediates, loss of high energy phosphate and tissue acidosis occurred. Nitroglycerin, beta-adrenergic blocking agents such as propranolol, and some calcium entry blocking agents such as diltiazem and flunarizine prevented the myocardial metabolism from shifting to an anaerobic metabolism in spite of ischemia. However, coronary vasodilators and the dihydropyridine type of calcium entry blocking agents were not capable of reducing changes in the myocardial metabolism and myocardial acidosis during ischemia. The author makes a point in the present review that all the drugs which dilate coronary artery are not always effective on the ischemic myocardium. PMID:3549484

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

    PubMed

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

    2010-02-01

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

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

    PubMed

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

    1976-12-20

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

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

    PubMed

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

    1976-10-18

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

  4. Lactic Acidosis: Current Treatments and Future Directions.

    PubMed

    Kraut, Jeffrey A; Madias, Nicolaos E

    2016-09-01

    Mortality rates associated with severe lactic acidosis (blood pH<7.2) due to sepsis or low-flow states are high. Eliminating the triggering conditions remains the most effective therapy. Although recommended by some, administration of sodium bicarbonate does not improve cardiovascular function or reduce mortality. This failure has been attributed to both reduction in serum calcium concentration and generation of excess carbon dioxide with intracellular acidification. In animal studies, hyperventilation and infusion of calcium during sodium bicarbonate administration improves cardiovascular function, suggesting that this approach could allow expression of the positive aspects of sodium bicarbonate. Other buffers, such as THAM or Carbicarb, or dialysis might also provide base with fewer untoward effects. Examination of these therapies in humans is warranted. The cellular injury associated with lactic acidosis is partly due to activation of NHE1, a cell-membrane Na(+)/H(+) exchanger. In animal studies, selective NHE1 inhibitors improve cardiovascular function, ameliorate lactic acidosis, and reduce mortality, supporting future research into their possible use in humans. Two main mechanisms contribute to lactic acid accumulation in sepsis and low-flow states: tissue hypoxia and epinephrine-induced stimulation of aerobic glycolysis. Targeting these mechanisms could allow for more specific therapy. This Acid-Base and Electrolyte Teaching Case presents a patient with acute lactic acidosis and describes current and future approaches to treatment. PMID:27291485

  5. D-lactic acidosis: an unusual cause of encephalopathy in a patient with short bowel syndrome.

    PubMed

    Dahlqvist, G; Guillen-Anaya, M A; Vincent, M F; Thissen, J P; Hainaut, P

    2013-01-01

    A 24-year-old woman with a short bowel syndrome following post-ischemic small bowel resection, developed several episodes of lethargy, echolalia and ataxia. D-lactic acidosis was identified as the cause of neurological disturbances. This infrequent disorder can be precipitated by intake of a large amount of sugars, in patients with short bowel syndrome. It should be suspected in the presence of metabolic acidosis with increased anion gap and a normal level of L-lactic acid. The diagnosis relies on the specific dosage of D-lactic stereoisomer. Proper management involves rehydration, diet adaptation and oral administration of poorly absorbed antibiotics in order to modify the colonic flora responsible for D-lactic production. PMID:24156228

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

    PubMed Central

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

    1977-01-01

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

  7. Phaeochromocytoma presenting with pseudo-intestinal obstruction and lactic acidosis

    PubMed Central

    Kek, Peng Chin; Ho, Emily Tse Lin; Loh, Lih Ming

    2015-01-01

    Phaeochromocytomas are rare neuroendocrine tumours with variable clinical signs and symptoms. Hypertension, tachycardia, sweating and headaches are cardinal manifestations. Although nausea and abdominal pain are the more common gastrointestinal features, rare gastrointestinal spectrums have been reported that can mimic abdominal emergencies. Metabolic effects of hypercatecholaminaemia are vast and one such rare presentation is lactic acidosis. We describe a case of phaeochromocytoma presenting with both intestinal pseudo-obstruction as well as lactic acidosis. This case report highlights the importance of having a high index of suspicion for and early recognition of the gastrointestinal and metabolic manifestations of phaeochromocytomas. PMID:26311913

  8. Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring.

    PubMed

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

    2015-04-01

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

  9. The dental management of troublesome twos: renal tubular acidosis and rampant caries

    PubMed Central

    B, Sandhyarani; Huddar, Dayanand; Patil, Anil; Sankeshwari, Banashree

    2013-01-01

    Renal tubular acidosis is a group of disorders in which there is metabolic acidosis due to defect in renal tubular acidification mechanism to maintain normal plasma bicarbonate and blood pH. Irrespective of organ system involved, oral cavity often reflects the disease occurring anywhere in the body. Thus congenital chronic renal diseases, causing acid–base disturbances affects development and structure of the teeth. Chronic renal tubular acidosis causes enamel defects, dental caries, oral candidiasis, angular cheilitis, etc. We hereby present an unusual case report of a 4-year-old boy suffering from renal tubular acidosis associated with rampant caries, whose full mouth rehabilitation has been done. PMID:23667245

  10. A metabolic syndrome severity score: A tool to quantify cardio-metabolic risk factors.

    PubMed

    Wiley, Joshua F; Carrington, Melinda J

    2016-07-01

    Metabolic syndrome is a cluster of cardio-metabolic risk factors and is associated with increased mortality. There is no standard, validated way to assess the severity of aggregated metabolic syndrome risk factors. Cardiovascular and diabetes risk factor data came from two studies conducted in Australia from 2006 to 2010 in adults aged 18 or above. In medication free adults, sex-specific clinical thresholds and Principal Component Analysis were used to develop a formula to calculate a metabolic syndrome severity score (MetSSS). These scores were compared to scores derived using the same process in subgroups by sex, age, medication status, and time. We also examined the MetSSS in relation to other known risk factors. In 2125 adults (57.6±14.7years of age), the MetSSS ranged from 0 to 8.7 with a mean of 2.6. There were strong correlations (.95-.99) between the MetSSS in medication free adults and the MetSSS calculated from subgroups. MetSSS predicted medication initiation for hypertension, hyperlipidemia and hyperglycemia over six months (OR=1.31, 95% CI [1.00-1.70], per MetSSS unit, p=.043). Lower education, medication prescription, history of smoking and age were associated with higher MetSSS (all p<.05). Higher physical but not mental health quality of life was associated with lower MetSSS (p<.001). A standardized formula to measure cardio-metabolic risk factor severity was constructed and demonstrated expected relations with known risk factors. The use of the MetSSS is recommended as a measure of change within individuals in cardio-metabolic risk factors and to guide treatment and management. PMID:27095322

  11. 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

  12. Type 4 renal tubular acidosis in a kidney transplant recipient.

    PubMed

    Kulkarni, Manjunath

    2016-02-01

    We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim - sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment. PMID:27105603

  13. Acidosis Promotes Bcl-2 Family-mediated Evasion of Apoptosis

    PubMed Central

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

    2012-01-01

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

  14. Neurological damage arising from intrapartum hypoxia/acidosis.

    PubMed

    Rei, M; Ayres-de-Campos, D; Bernardes, J

    2016-01-01

    Complications occurring at any level of foetal oxygen supply will result in hypoxaemia, and this may ultimately lead to hypoxia/acidosis and neurological damage. Hypoxic-ischaemic encephalopathy (HIE) is the short-term neurological dysfunction caused by intrapartum hypoxia/acidosis, and this diagnosis requires the presence of a number of findings, including the confirmation of newborn metabolic acidosis, low Apgar scores, early imaging evidence of cerebral oedema and the appearance of clinical signs of neurological dysfunction in the first 48 h of life. Cerebral palsy (CP) consists of a heterogeneous group of nonprogressive movement and posture disorders, frequently accompanied by cognitive and sensory impairments, epilepsy, nutritional deficiencies and secondary musculoskeletal lesions. Although CP is the most common long-term neurological complication associated with intrapartum hypoxia/acidosis, >80% of cases are caused by other phenomena. Data on minor long-term neurological deficits are scarce, but they suggest that less serious intellectual and motor impairments may result from intrapartum hypoxia/acidosis. This chapter focuses on the existing evidence of neurological damage associated with poor foetal oxygenation during labour. PMID:26148854

  15. Oxidative stress in a novel model of chronic acidosis in LLC-PK1 cells.

    PubMed

    Rustom, Rana; Wang, Bohan; McArdle, Frank; Shalamanova, Liliana; Alexander, John; McArdle, Anne; Thomas, Carol E; Bone, J Michael; Shenkin, Alan; Jackson, Malcolm J

    2003-01-01

    Chronic metabolic acidosis occurs commonly in chronic renal failure (CRF). The proximal renal tubular cell is the site in the kidney of high oxidative metabolic activity and in CRF is associated with adaptive hypertrophy and hypermetabolism. We hypothesised that chronic acidosis may lead to increased generation of reactive oxygen species due to increased oxidative activity. We developed a novel model of chronic acidosis in LLC-PK1 cells and measured markers of oxidative stress and metabolism. Acidosis led to a reduction in cellular total glutathione and protein thiol content and an increase in glutathione peroxidase activity and NH3 generation. The expression of constitutively expressed heat stress protein (HSP) HSC70 and HSP60 increased at pH 7.0. PMID:14520010

  16. Plasma First Resuscitation Reduces Lactate Acidosis, Enhances Redox Homeostasis, Amino Acid and Purine Catabolism in a Rat Model of Profound Hemorrhagic Shock.

    PubMed

    D'Alessandro, Angelo; Moore, Hunter B; Moore, Ernest E; Wither, Matthew J; Nemkov, Travis; Morton, Alexander P; Gonzalez, Eduardo; Chapman, Michael P; Fragoso, Miguel; Slaughter, Anne; Sauaia, Angela; Silliman, Christopher C; Hansen, Kirk C; Banerjee, Anirban

    2016-08-01

    The use of aggressive crystalloid resuscitation to treat hypoxemia, hypovolemia, and nutrient deprivation promoted by massive blood loss may lead to the development of the blood vicious cycle of acidosis, hypothermia, and coagulopathy and, utterly, death. Metabolic acidosis is one of the many metabolic derangements triggered by severe trauma/hemorrhagic shock, also including enhanced proteolysis, lipid mobilization, as well as traumatic diabetes. Appreciation of the metabolic benefit of plasma first resuscitation is an important concept. Plasma resuscitation has been shown to correct hyperfibrinolysis secondary to severe hemorrhage better than normal saline. Here, we hypothesize that plasma first resuscitation corrects metabolic derangements promoted by severe hemorrhage better than resuscitation with normal saline. Ultra-high-performance liquid chromatography-mass spectrometry-based metabolomics analyses were performed to screen plasma metabolic profiles upon shock and resuscitation with either platelet-free plasma or normal saline in a rat model of severe hemorrhage. Of the 251 metabolites that were monitored, 101 were significantly different in plasma versus normal saline resuscitated rats. Plasma resuscitation corrected lactate acidosis by promoting glutamine/amino acid catabolism and purine salvage reactions. Plasma first resuscitation may benefit critically injured trauma patients by relieving the lactate burden and promoting other non-clinically measured metabolic changes. In the light of our results, we propose that plasma resuscitation may promote fueling of mitochondrial metabolism, through the enhancement of glutaminolysis/amino acid catabolism and purine salvage reactions. The treatment of trauma patients in hemorrhagic shock with plasma first resuscitation is likely not only to improve coagulation, but also to promote substrate-specific metabolic corrections. PMID:26863033

  17. Type B Lactic Acidosis Associated With Venlafaxine Overdose.

    PubMed

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

    2016-01-01

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

  18. Cadmium induces acidosis in maize root cells.

    PubMed

    Nocito, Fabio Francesco; Espen, Luca; Crema, Barbara; Cocucci, Maurizio; Sacchi, Gian Attilio

    2008-01-01

    * Cadmium (Cd) stress increases cell metabolic demand for sulfur, reducing equivalents, and carbon skeletons, to sustain phytochelatin biosynthesis for Cd detoxification. In this condition the induction of potentially acidifying anaplerotic metabolism in root tissues may be expected. For these reasons the effects of Cd accumulation on anaplerotic metabolism, glycolysis, and cell pH control mechanisms were investigated in maize (Zea mays) roots. * The study compared root apical segments, excised from plants grown for 24 h in a nutrient solution supplemented, or not, with 10 microM CdCl(2), using physiological, biochemical and (31)P-nuclear magnetic resonance (NMR) approaches. * Cadmium exposure resulted in a significant decrease in both cytosolic and vacuolar pH of root cells and in a concomitant increase in the carbon fluxes through anaplerotic metabolism leading to malate biosynthesis, as suggested by changes in dark CO2 fixation, metabolite levels and enzyme activities along glycolysis, and mitochondrial alternative respiration capacity. This scenario was accompanied by a decrease in the net H(+) efflux from the roots, probably related to changes in plasma membrane permeability. * It is concluded that anaplerotic metabolism triggered by Cd detoxification processes might lead to an imbalance in H(+) production and consumption, and then to cell acidosis. PMID:18537888

  19. [Traumatic disease and metabolism].

    PubMed

    Deriabin, I I; Nasonkin, O S; Nemchenko, N S; Gol'm, N P; Zimina, Z P

    1984-06-01

    The authors have established that the traumatic disease is accompanied by phasic nonspecific changes of metabolism correlating with the trauma severity as well as with its specific features and outcomes. Within the first 3-7 days catabolic processes are found to prevail and metabolic acidosis develop. Later, anabolic processes become activated in the non-complicated course of the disease. Normalization of most biochemical processes is accomplished within 15-21 days. More pronounced and prolonged disturbances of metabolism are observed in complications and lethal outcomes. PMID:6474706

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

    PubMed Central

    2014-01-01

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

  1. A patient with foot ulcer and severe metabolic alkalosis.

    PubMed

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

    2012-01-01

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

  2. Treatment of lactic acidosis with dichloroacetate in dogs.

    PubMed

    Park, R; Arieff, A I

    1982-10-01

    Lactic acidosis is a clinical condition due to accumulation of H(+) ions from lactic acid, characterized by blood lactate levels >5 mM and arterial pH <7.25. In addition to supportive care, treatment usually consists of intravenous NaHCO(3), with a resultant mortality >60%. Dichloroacetate (DCA) is a compound that lowers blood lactate levels under various conditions in both man and laboratory animals. It acts to increase pyruvate oxidation by activation of pyruvate dehydrogenase. We evaluated the effects of DCA in the treatment of two different models of type B experimental lactic acidosis in diabetic dogs: hepatectomy-lactic acidosis and phenformin-lactic acidosis. The metabolic and systemic effects examined included arterial blood pH and levels of bicarbonate and lactate; the intracellular pH (pHi) in liver and skeletal muscle; cardiac index, arterial blood pressure and liver blood flow; liver lactate uptake and extrahepatic splanchnic (gut) lactate production; and mortality. Effects of DCA were compared with those of either NaCl or NaHCO(3). The infusion of DCA and NaHCO(3), delivered equal amounts of volume and sodium, although the quantity of NaHCO(3) infused (2.5 meq/kg per h) was insufficient to normalize arterial pH. In phenformin-lactic acidosis, DCA-treated animals had a mortality of 22%, vs. 89% in those treated with NaHCO(3). DCA therapy increased arterial pH and bicarbonate, liver pHi and cardiac index, with increased liver lactate uptake and a fall in blood lactate. With NaHCO(3) therapy, there were decrements of cardiac index and liver pHi, with an increase in venous pCO(2) and gut production of lactate. Dogs with hepatectomy-lactic acidosis were either treated or pretreated with DCA. Treatment with DCA resulted in stabilization of cardiac index, a fall in blood lactate, and 17% mortality. NaHCO(3) was associated with a continuous decline of cardiac index, rise in blood lactate, and 67% mortality. In dogs pretreated with NaCl, mortality was 33%, but

  3. Development of diabetes-induced acidosis in the rat retina.

    PubMed

    Dmitriev, Andrey V; Henderson, Desmond; Linsenmeier, Robert A

    2016-08-01

    We hypothesized that the retina of diabetic animals would be unusually acidic due to increased glycolytic metabolism. Acidosis in tumors and isolated retina has been shown to lead to increased VEGF. To test the hypothesis we have measured the transretinal distribution of extracellular H(+) concentration (H(+)-profiles) in retinae of control and diabetic dark-adapted intact Long-Evans rats with ion-selective electrodes. Diabetes was induced by intraperitoneal injection of streptozotocin. Intact rat retinae are normally more acidic than blood with a peak of [H(+)]o in the outer nuclear layer (ONL) that averages 30 nM higher than H(+) in the choroid. Profiles in diabetic animals were similar in shape, but diabetic retinae began to be considerably more acidic after 5 weeks of diabetes. In retinae of 1-3 month diabetics the difference between the ONL and choroid was almost twice as great as in controls. At later times, up to 6 months, some diabetics still demonstrated abnormally high levels of [H(+)]o, but others were even less acidic than controls, so that the average level of acidosis was not different. Greater variability in H(+)-profiles (both between animals and between profiles recorded in one animal) distinguished the diabetic retinae from controls. Within animals, this variability was not random, but exhibited regions of higher and lower H(+). We conclude that retinal acidosis begins to develop at an early stage of diabetes (1-3 months) in rats. However, it does not progress, and the acidity of diabetic rat retina was diminished at later stages (3-6 months). Also the diabetes-induced acidosis has a strongly expressed local character. As result, the diabetic retinas show much wider variability in [H(+)] distribution than controls. pH influences metabolic and neural processes, and these results suggest that local acidosis could play a role in the pathogenesis of diabetic retinopathy. PMID:27262608

  4. Changes in intermediary metabolism in severe surgical illness.

    PubMed

    Wolfe, R R; Martini, W Z

    2000-06-01

    Under normal circumstances there is a reciprocal relation between the availability of free fatty acids (FFAs) and glucose in plasma. In the fasted state, FFAs predominate in both availability and the relative contribution to energy production, whereas the same is true for glucose in the fed state. The extent of glucose oxidation is directly determined by its availability, whereas FFAs are normally available well in excess of their rate of oxidation. The rate of FFA oxidation is determined by the rate of transfer into the mitochondria via the carnitine palmitoyltransferase (CPT) enzyme system, which in turn is regulated by the metabolism of glucose. With critical illness the stress response involves mobilization of both plasma glucose and FFAs simultaneously in both the fed and fasted states. In the situation of excess availability of substrates, the metabolism of glucose limits the oxidation of FFAs, thereby channeling those fatty acids into triglyceride (TG) stores in the muscle and the liver. The high FFA concentrations and increased tissue TG stores can limit glucose clearance from the blood, thereby contributing to the development of hyperglycemia. Also, the excessive metabolism of glucose can result in lacticacidemia and can contribute to the depletion of muscle glutamine. The nutritional treatment of such patients must account for these underlying metabolic responses to avoid amplifying potentially detrimental responses to the excess availability of substrates already present in the fasting state. PMID:10773115

  5. Clinical profile of distal renal tubular acidosis.

    PubMed

    Jha, Ratan; Muthukrishnan, J; Shiradhonkar, Shekhar; Patro, Kiran; Harikumar, Kvs; Modi, K D

    2011-03-01

    To determine the clinical profile and progression of renal dysfunction in distal renal tubular acidosis (dRTA), we retrospectively studied 96 consecutive cases of dRTA diagnosed at our center. Patients with unexplained metabolic bone disease, short stature, hypokalemia, re-current renal stones, chronic obstructive uropathy or any primary autoimmune condition known to cause dRTA were screened. Distal RTA was diagnosed on the basis of systemic metabolic acidosis with urine pH >5.5 and positive urine anion gap. In those patients who had fasting urine pH >5.5 with normal baseline systemic pH and bicarbonate levels (incomplete RTA), acid load test with ammonium chloride was done. A cause of dRTA could be established in 53 (54%) patients. Urological defect in children (22/44) and autoimmune disease in adults (11/52) were the commonest causes. Hypokalemic paralysis, proximal muscle weakness and voiding difficulty were the common modes of presentation. Doubling of serum creatinine during the study period was noted in 13 out of 27 patients who had GFR <60 mL/min at presentation whereas in only one of the 70 with initial GFR >60 mL/min (P <0.005). In conclusion, urological disorders were the commonest cause of dRTA in children while autoimmune disorders were the commonest asso-ciation in adults. Worse baseline renal function, longer duration of disease and greater frequency of nephrolithiasis/nephrocalcinosis and urological disorders were noted in those who had wor-sening of renal dysfunction during the study period. PMID:21422623

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

    PubMed

    Musoke, Philippa M; Fergusson, Pamela

    2011-12-01

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

  7. [The role of lactate besides the lactic acidosis].

    PubMed

    Brucculeri, S; Urso, C; Caimi, G

    2013-01-01

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

  8. Fatal Tenofovir-Associateacd Lactic Acidosis: A Case Report

    PubMed Central

    Hashim, Hasriza; Sahari, Narisa Sulaiman; Sazlly Lim, Sazlyna Mohd; Hoo, Fan Kee

    2015-01-01

    Introduction: The introduction of highly active antiretroviral therapy (HAART), in 1996, has resulted in marked reductions in the rate of illness and death, due to HIV infection. The HAART has transformed HIV infection into a manageable chronic disease. However, although many regimens lower plasma viral load, to below the limit of detection, in most patients, maintaining viral load suppression remains challenging, because of adverse effects and toxicity in the long term, which can lead to non-adherence, virologic failure and drug resistance. Although rare, lactic acidosis often develops fatal complications, as reported in several human immunodeficiency virus infected patients treated with nucleoside reverse transcriptase inhibitors (NRTIs). The purpose of this paper is to report a case of tenofovir induced lactic acidosis and review the literature. Case Presentation: A 52-year-old Malay gentleman, with hepatitis C virus and HIV infection was admitted to the intensive care unit for severe lactic acidosis, with concurrent Escherichia coli bacteremia with multiorgan dysfunction. The patient was started on highly active antiretroviral therapy, which included tenofovir, 5 weeks before presentation. Antimicrobial therapy, continuous veno-venous hemofiltration, and other supportive treatments were instituted. However, the patient eventually succumbed to his illness. Conclusions: It is essential for clinicians to be able to recognize the signs and symptoms of lactic acidosis in NRTIs treated HIV patients, as an early diagnosis is important to institute treatment. PMID:26568856

  9. Metformin-induced lactic acidosis: a case series

    PubMed Central

    Silvestre, Joana; Carvalho, Susana; Mendes, Vitor; Coelho, Luis; Tapadinhas, Camila; Ferreira, Pedro; Povoa, Pedro; Ceia, Fatima

    2007-01-01

    Introduction Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin. Case presentation We present two case reports of metformin-associated lactic acidosis. The first case is a 77 year old female with a past medical history of hypertension and type 2 diabetes mellitus who had recently been prescribed metformin (3 g/day), perindopril and acetylsalicylic acid. She was admitted to the emergency department two weeks later with abdominal pain and psychomotor agitation. Physical examination revealed only signs of poor perfusion. Laboratory evaluation revealed hyperkalemia, elevated creatinine and blood urea nitrogen and mild leukocytosis. Arterial blood gases showed severe lactic acidemia. She was admitted to the intensive care unit. Vasopressor and ventilatory support was initiated and continuous venovenous hemodiafiltration was instituted. Twenty-four hours later, full clinical recovery was observed, with return to a normal serum lactate level. The patient was discharged from the intensive care unit on the sixth day. The second patient is a 69 year old male with a past medical history of hypertension, type 2 diabetes mellitus and ischemic heart disease who was on metformin (4 g/day), glycazide, acetylsalicylic acid and isosorbide dinitrate. He was admitted to the emergency department in shock with extreme bradycardia. Initial evaluation revealed severe lactic acidosis and elevated creatinine and urea. The patient was admitted to the Intensive Care Unit and commenced on continuous venovenous hemodiafiltration in addition to other supportive measures. A progressive recovery was observed

  10. Severe cow's milk protein allergy in a Chinese neonate.

    PubMed

    Siu, L Y; Tse, K; Lui, Y S

    2001-12-01

    Cow's milk protein allergy is a growing problem in developed countries. We report the case of a Chinese infant, born at term, who presented on day 28 with severe growth failure, chronic diarrhoea, and metabolic acidosis. Investigations supported a diagnosis of cow's milk protein allergy. This was confirmed by withdrawing and reintroducing the relevant infant formula under controlled clinical conditions. Both acidosis and diarrhoea were seen to resolve, and 'catch-up' growth was evident after introduction of an elemental infant formula. Early recognition of this problem leads to a rapid 'cure', as seen in this case. However, later presentation with other atopic conditions has been reported. PMID:11773683

  11. Metformin associated lactic acidosis in Auckland City Hospital 2005 to 2009

    PubMed Central

    Haloob, Imad; de Zoysa, Janak R

    2016-01-01

    AIM: To determine the incidence, clinical characteristics and outcomes of patients with metformin associated lactic acidosis (MALA). METHODS: Auckland City Hospital drains a population of just over 400000 people. All cases presenting with metabolic acidosis between July 2005 and July 2009 were identified using clinical coding. A retrospective case notes review identified patients with MALA. Prescribing data for metformin was obtained from the national pharmaceutical prescribing scheme. RESULTS: There were 42 cases of metabolic lactic acidosis over 1718000 patient years. There were 51000 patient years of metformin prescribed to patients over the study period. There were thirty two cases of lactic acidosis due to sepsis, seven in patients treated with metformin. Ten cases of MALA were identified. The incidence of MALA was estimated at 19.46 per 100000 patient year exposure to metformin. The relative risk of lactic acidosis in patients on metformin was 13.53 (95%CI: 7.88-21.66) compared to the general population. The mean age of patients with MALA was 63 years, range 40-83 years. A baseline estimated glomerular filtration rate was obtained in all patients and ranged from 23-130 mL/min per 1.73 m2. Only two patients had chronic kidney disease G4. Three patients required treatment with haemodialysis. Two patients died. CONCLUSION: Lactic acidosis is an uncommon but significant complication of use of metformin which carries a high risk of morbidity. PMID:27458565

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

    PubMed

    Song, Rongrong; Zhang, Liming; Yang, Zichao; Tian, Xiaoyan

    2011-05-15

    Acidosis and alkalosis, associated with metabolic disorders, lead to the pathological changes of cognition and behaviors in clinical practices of neurology and psychology. Cellular mechanisms for these functional disorders in the central nervous system remain unclear. We have investigated the influences of acidosis and alkalosis on the functions of cortical GABAergic neurons. Both acidosis and alkalosis impair the ability of encoding sequential spikes at these GABAergic neurons. The impairments of their spiking are associated with the increases of refractory periods, threshold potential and afterhyperpolarization. Our studies reveal that acidosis and alkalosis impair cortical GABAergic neurons and in turn deteriorate brain functions, in which their final targets may be voltage-gated channels of sodium and potassium. PMID:21353681

  13. Seizure Termination by Acidosis Depends on ASIC1a

    PubMed Central

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

    2008-01-01

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

  14. Lipoyltransferase 1 Gene Defect Resulting in Fatal Lactic Acidosis in Two Siblings

    PubMed Central

    Taché, Véronique; Bivina, Liga; White, Sophie; Gregg, Jeffrey; Deignan, Joshua; Boyadjievd, Simeon A.; Poulain, Francis R.

    2016-01-01

    A term male neonate developed severe intractable lactic acidosis on day of life 1 and died the same day at our institution. The family previously lost another term, female newborn on day of life 1 from suspected sepsis at an outside hospital. After performing an autopsy on the neonate who died at our institution, extensive and lengthy neonatal and parental genetic testing, as well as biochemical analyses, and whole exome sequencing analysis identified compound heterozygous mutations in the lipoyltransferase 1 (LIPT1) gene responsible for the lipoylation of the 2-keto dehydrogenase complexes in the proband. These mutations were also identified in the deceased sibling. The clinical manifestations of these two siblings are consistent with those recently described in two unrelated families with lactic acidosis due to LIPT1 mutations, an underrecognized and underreported cause of neonatal death. Conclusions. Our observations contribute to the delineation of a new autosomal recessive metabolic disorder, leading to neonatal death. Our case report also highlights the importance of an interdisciplinary team in solving challenging cases. PMID:27247813

  15. Lipoyltransferase 1 Gene Defect Resulting in Fatal Lactic Acidosis in Two Siblings.

    PubMed

    Taché, Véronique; Bivina, Liga; White, Sophie; Gregg, Jeffrey; Deignan, Joshua; Boyadjievd, Simeon A; Poulain, Francis R

    2016-01-01

    A term male neonate developed severe intractable lactic acidosis on day of life 1 and died the same day at our institution. The family previously lost another term, female newborn on day of life 1 from suspected sepsis at an outside hospital. After performing an autopsy on the neonate who died at our institution, extensive and lengthy neonatal and parental genetic testing, as well as biochemical analyses, and whole exome sequencing analysis identified compound heterozygous mutations in the lipoyltransferase 1 (LIPT1) gene responsible for the lipoylation of the 2-keto dehydrogenase complexes in the proband. These mutations were also identified in the deceased sibling. The clinical manifestations of these two siblings are consistent with those recently described in two unrelated families with lactic acidosis due to LIPT1 mutations, an underrecognized and underreported cause of neonatal death. Conclusions. Our observations contribute to the delineation of a new autosomal recessive metabolic disorder, leading to neonatal death. Our case report also highlights the importance of an interdisciplinary team in solving challenging cases. PMID:27247813

  16. 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

  17. The Roles of Acidosis in Osteoclast Biology

    PubMed Central

    Yuan, Feng-Lai; Xu, Ming-Hui; Li, Xia; Xinlong, He; Fang, Wei; Dong, Jian

    2016-01-01

    The adverse effect of acidosis on the skeletal system has been recognized for almost a century. Although the underlying mechanism has not been fully elucidated, it appears that acidosis acts as a general stimulator of osteoclasts derived from bone marrow precursors cells and enhances osteoclastic resorption. Prior work suggests that acidosis plays a significant role in osteoclasts formation and activation via up-regulating various genes responsible for its adhesion, migration, survival and bone matrix degradation. Understanding the role of acidosis in osteoclast biology may lead to development of novel therapeutic approaches for the treatment of diseases related to low bone mass. In this review, we aim to discuss the recent investigations into the effects of acidosis in osteoclast biology and the acid-sensing molecular mechanism. PMID:27445831

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

    PubMed

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

    2011-08-01

    The ischemic tissue becomes acidic after initiation of anaerobic respiration, which may result in impaired tissue metabolism and, ultimately, in severe tissue damage. Although changes in the major cerebral metabolites can be studied using magnetic resonance (MR) spectroscopy (MRS)-based techniques, their spatiotemporal resolution is often not sufficient for routine examination of fast-evolving and heterogeneous acute stroke lesions. Recently, pH-weighted MR imaging (MRI) has been proposed as a means to assess tissue acidosis by probing the pH-dependent chemical exchange of amide protons from endogenous proteins and peptides. In this study, we characterized acute ischemic tissue damage using localized proton MRS and multiparametric imaging techniques that included perfusion, diffusion, pH, and relaxation MRI. Our study showed that pH-weighted MRI can detect ischemic lesions and strongly correlates with tissue lactate content measured by (1)H MRS, indicating lactic acidosis. Our results also confirmed the correlation between apparent diffusion coefficient and lactate; however, no significant relationship was found for perfusion, T(1), and T(2). In summary, our study showed that optimized endogenous pH-weighted MRI, by sensitizing to local tissue pH, remains a promising tool for providing a surrogate imaging marker of lactic acidosis and altered tissue metabolism, and augments conventional techniques for stroke diagnosis. PMID:21386856

  19. Early and Sustained Changes in Bone Metabolism After Severe Burn Injury.

    PubMed

    Muschitz, Gabriela Katharina; Schwabegger, Elisabeth; Kocijan, Roland; Baierl, Andreas; Moussalli, Hervé; Fochtmann, Alexandra; Nickl, Stefanie; Tinhofer, Ines; Haschka, Judith; Resch, Heinrich; Rath, Thomas; Pietschmann, Peter; Muschitz, Christian

    2016-04-01

    This study investigated serum burnover marker in male patients after severe burn injury. Ongoing changes suggest alterations in bone metabolism with a likely adverse influence on bone quality and structure. PMID:26789778

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  1. [Dose dependent effects of dichloroacetate on lactic acidosis in dogs].

    PubMed

    Fujita, Y; Fukui, A; Yoshida, H; Ohsumi, A; Sakai, T; Takaori, M

    1989-08-01

    Dose dependent effects of DCA (dichloroacetate) on lactic acidosis were studied in 30 mongrel dogs under pentobarbital anesthesia. Lactic acidosis was induced by infusion of either lactate (n = 15) or pyruvate (n = 15) for 20 min. In each dog, saline or DCA (100 mg.kg-1 or 300 mg.kg-1) was given for ten min iv. at ten min after the beginning of lactate or pyruvate infusions. Reduction in serum pyruvate levels was more prominent than that in lactate levels in both the lactate and pyruvate infusion groups. DCA in a dose of 100 mg.kg-1 was more effective to reduce serum pyruvate levels and arterial pH than 300 mg.kg-1 of DCA. There were no differences between saline and DCA (100 mg.kg-1 or 300 mg.kg-1) administrations in mean arterial pressure and cardiac index. This study confirmed the hypothesis that DCA reduces serum lactate levels via acceleration of pyruvate metabolism. It was concluded that the ability of DCA to reduce serum lactate levels is dose-dependent and a large dose of DCA (300 mg.kg-1) would not be necessary for lactic acidosis. PMID:2810694

  2. Distal renal tubular acidosis associated with concurrent leptospirosis in a dog.

    PubMed

    Martinez, Stephen A; Hostutler, Roger A

    2014-01-01

    A 9 yr old spayed female boxer was presented for evaluation of vomiting, lethargy, anorexia, and weight loss. Initial laboratory evaluation revealed a hyperchloremic normal anion gap metabolic acidosis with alkaline urine that was consistent with a diagnosis of distal renal tubular acidosis (RTA). Targeted therapy was initiated with Na bicarbonate (HCO3) and potassium (K) gluconate. Leptospirosis was subsequently diagnosed with paired microagglutination testing (MAT), and doxycycline was added to the other treatments. Clinical signs resolved, and 6 mo after diagnosis, although the dog remained on alkali therapy (i.e., NaHCO3 and K gluconate) and a mild metabolic acidosis persisted, the dog remained otherwise healthy with a good quality of life. To the authors' knowledge, this is the first report to describe the concomitant association of those two disorders. Leptospirosis should be considered for any case of RTA in dogs. PMID:24659721

  3. Citric acid as the last therapeutic approach in an acute life-threatening metabolic decompensation of propionic acidaemia.

    PubMed

    Siekmeyer, Manuela; Petzold-Quinque, Stefanie; Terpe, Friederike; Beblo, Skadi; Gebhardt, Rolf; Schlensog-Schuster, Franziska; Kiess, Wieland; Siekmeyer, Werner

    2013-01-01

    The tricarboxylic acid (TCA) cycle represents the key enzymatic steps in cellular energy metabolism. Once the TCA cycle is impaired in case of inherited metabolic disorders, life-threatening episodes of metabolic decompensation and severe organ failure can arise. We present the case of a 6 ½-year-old girl with propionic acidaemia during an episode of acute life-threatening metabolic decompensation and severe lactic acidosis. Citric acid given as an oral formulation showed the potential to sustain the TCA cycle flux. This therapeutic approach may become a treatment option in a situation of acute metabolic crisis, possibly preventing severe disturbance of energy metabolism. PMID:23412866

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

    PubMed

    Forslid, A; Augustinsson, O

    1988-02-01

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

  5. Severe metabolic alkalosis due to pyloric obstruction: case presentation, evaluation, and management.

    PubMed

    McCauley, Meredith; Gunawardane, Manjula; Cowan, Mark J

    2006-12-01

    A 46-year-old man presented to the emergency room with severe metabolic alkalosis, hypokalemia, and respiratory failure requiring intubation and mechanical ventilation. The cause of his acid-base disorder was initially unclear. Although alkalosis is common in the intensive care unit, metabolic alkalosis of this severity is unusual, carries a very high mortality rate, and requires careful attention to the pathophysiology and differential diagnosis to effectively evaluate and treat the patient. A central concept in the diagnosis of metabolic alkalosis is distinguishing chloride responsive and chloride nonresponsive states. Further studies are then guided by the history and physical examination in most cases. By using a systematic approach to the differential diagnosis, we were able to determine that a high-grade gastric outlet obstruction was the cause of the patients' alkalosis and to offer effective therapy for his condition. A literature review and algorithm for the diagnosis and management of metabolic alkalosis are also presented. PMID:17170625

  6. [Keto acidosis and coma in 44-years old man with diabetes t1 in Internal Diseases Department in Dabrowa Tarnowska].

    PubMed

    Jasiński, Marcin; Radziszewski, Andrzej

    2015-01-01

    Diabetic ketoacidosis (DKA) is an acute complication metabolic occur- ring in patients with diabetes type-1 and much less likely to type 2 diabetes. This article shows clinical manifesta- tion, biochemical criteria and algorithm for the immediate assessment and management of diabetic acidosis in a 44 years old men. This specification describes a rare case of keto acidosis and coma therapy and the challenges that these disorders carry. PMID:27012135

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

    PubMed

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

    2009-11-01

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

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

    PubMed

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

    2014-01-01

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

  9. Distal renal tubular acidosis and hypokalemic paralysis in a patient with hypothyroidism.

    PubMed

    Koul, Parvaiz Ahmad; Wahid, A

    2011-09-01

    A 43- year- old woman on treatment for primary hypothyroidism presented with 1- day progressive weakness of all her limbs and history of similar episodes in the past. Clinical examination revealed grade 2 hyporeflexive weakness. Investigations revealed features of hypokalemia, metabolic acidosis, alkaline urine, and a fractional bicarbonate excretion of 3.5%, consistent with distal renal tubular acidosis. Antithyroid peroxidase and antithroglobulin antibodies were positive, suggesting an autoimmune basis for the pathogenesis of the functional tubular defect. Bicarbonate therapy resulted in a sustained clinical recovery. PMID:21912036

  10. [Regional vasoactive and metabolic therapy of patients with severe cranio-cerebral traumas].

    PubMed

    Lapshin, V N; Shakh, B N; Teplov, V M; Smirnov, D B

    2012-01-01

    In patients with severe cranio-cerebral traumas an investigation was performed of the efficiency of using vasoactive therapy in complex treatment directed to earlier recovery of the microcirculatory blood flow and aerobic metabolism in ischemic parts of the brain. PMID:22880433

  11. Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson's Disease.

    PubMed

    Xu, Yunqi; Wei, Xiaobo; Liu, Xu; Liao, Jinchi; Lin, Jiaping; Zhu, Cansheng; Meng, Xiaochun; Xie, Dongsi; Chao, Dongman; Fenoy, Albert J; Cheng, Muhua; Tang, Beisha; Zhang, Zhuohua; Xia, Ying; Wang, Qing

    2015-11-01

    This study explored the association between cerebral metabolic rates of glucose (CMRGlc) and the severity of Vascular Parkinsonism (VP) and Parkinson's disease (PD). A cross-sectional study was performed to compare CMRGlc in normal subjects vs. VP and PD patients. Twelve normal subjects, 22 VP, and 11 PD patients were evaluated with the H&Y and MMSE, and underwent 18F-FDG measurements. Pearson's correlations were used to identify potential associations between the severity of VP/PD and CMRGlc. A pronounced reduction of CMRGlc in the frontal lobe and caudate putamen was detected in patients with VP and PD when compared with normal subjects. The VP patients displayed a slight CMRGlc decrease in the caudate putamen and frontal lobe in comparison with PD patients. These decreases in CMRGlc in the frontal lobe and caudate putamen were significantly correlated with the VP patients' H&Y, UPDRS II, UPDRS III, MMSE, cardiovascular, and attention/memory scores. Similarly, significant correlations were observed in patients with PD. This is the first clinical study finding strong evidence for an association between low cerebral glucose metabolism and the severity of VP and PD. Our findings suggest that these changes in glucose metabolism in the frontal lobe and caudate putamen may underlie the pathophysiological mechanisms of VP and PD. As the scramble to find imaging biomarkers or predictors of the disease intensifies, a better understanding of the roles of cerebral glucose metabolism may give us insight into the pathogenesis of VP and PD. PMID:26618044

  12. The Severity of Fatty Liver Disease Relating to Metabolic Abnormalities Independently Predicts Coronary Calcification

    PubMed Central

    Lee, Ying-Hsiang; Wu, Yih-Jer; Liu, Chuan-Chuan; Hou, Charles Jia-Yin; Yeh, Hung-I.; Tsai, Cheng-Ho; Shih, Shou-Chuan; Hung, Chung-Lieh

    2011-01-01

    Background. Nonalcoholic fatty liver disease (NAFLD) is one of the metabolic disorders presented in liver. The relationship between severity of NAFLD and coronary atherosclerotic burden remains largely unknown. Methods and Materials. We analyzed subjects undergoing coronary calcium score evaluation by computed tomography (MDCT) and fatty liver assessment using abdominal ultrasonography. Framingham risk score (FRS) and metabolic risk score (MRS) were obtained in all subjects. A graded, semiquantitative score was established to quantify the severity of NAFLD. Multivariate logistic regression analysis was used to depict the association between NAFLD and calcium score. Results. Of all, 342 participants (female: 22.5%, mean age: 48.7 ± 7.0 years) met the sufficient information rendering detailed analysis. The severity of NAFLD was positively associated with MRS (X2 = 6.12, trend P < 0.001) and FRS (X2 = 5.88, trend P < 0.001). After multivariable adjustment for clinical variables and life styles, the existence of moderate to severe NAFLD was independently associated with abnormal calcium score (P < 0.05). Conclusion. The severity of NAFLD correlated well with metabolic abnormality and was independently predict coronary calcification beyond clinical factors. Our data suggests that NAFLD based on ultrasonogram could positively reflect the burden of coronary calcification. PMID:22254139

  13. [The characteristics of changes in lipid metabolism indices of patients with severe mechanical trauma].

    PubMed

    Moroz, V V; Bessekeev, A A; Molchanova, L V; Shcherbakova, L N

    2003-01-01

    The paper contains the study results of some lipid-metabolism indices in patients with severe mechanical injury. Changing concentrations of total cholesterol, triglycerides and of different lipoprotein fractions in blood plasma are demonstrated. It was established that the investigated lipid-metabolism indices reflect a degree of liver malfunction in severely impaired homeostasis. It can be stated on the basis of comparing the study results with the clinical outcome that the dynamic concentration of total cholesterol in blood plasma is an important prognostication factor. Changing ratios of high-density lipoproteins, low-density lipoproteins and extra-low-density lipoproteins were observed in survivors yet by day 15, which is indicative of a commencing dislipidemia. PMID:14991968

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

    PubMed

    Fitzgibbons, L J; Snoey, E R

    1999-01-01

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

  15. Ruminal Acidosis in Feedlot: From Aetiology to Prevention

    PubMed Central

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

    2014-01-01

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

  16. Metformin-Associated Lactic Acidosis in a Patient with Normal Renal Function.

    PubMed

    Omar, Ahmed; Ellen, Ruth; Sorisky, Alexander

    2016-08-01

    We report a case of metformin-associated lactic acidosis (MALA) in the setting of normal renal function and review the relevant medical literature. A 77-year-old female diagnosed with type 2 diabetes mellitus previously treated with insulin and gliclazide MR was started on metformin. A few weeks later, she was found to have lactic acidosis. Renal function was normal, and no severe underlying illness was identified. Metformin was discontinued, and lactate levels normalized within 4 days, suggesting metformin was a reversible precipitant of the lactic acidosis. MALA can occur in the absence of renal impairment, systemic hypoperfusion or severe liver disease. A possible mechanism is a genetically determined alteration in metformin pharmacokinetics. Metformin is beneficial and safe in patients with normal renal function, but the development of MALA, although rare, should be kept in mind to prevent potentially life-threatening toxicity. PMID:27197687

  17. Metabolite mapping reveals severe widespread perturbation of multiple metabolic processes in Huntington's disease human brain.

    PubMed

    Patassini, Stefano; Begley, Paul; Xu, Jingshu; Church, Stephanie J; Reid, Suzanne J; Kim, Eric H; Curtis, Maurice A; Dragunow, Mike; Waldvogel, Henry J; Snell, Russell G; Unwin, Richard D; Faull, Richard L M; Cooper, Garth J S

    2016-09-01

    Huntington's disease (HD) is a genetically-mediated neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein (Htt) through lengthening of its polyglutamine tract, thus initiating a cascade that ultimately leads to premature death. However, neurodegeneration typically manifests in HD only in middle age, and mechanisms linking the causative mutation to brain disease are poorly understood. Brain metabolism is severely perturbed in HD, and some studies have indicated a potential role for mutant Htt as a driver of these metabolic aberrations. Here, our objective was to determine the effects of HD on brain metabolism by measuring levels of polar metabolites in regions known to undergo varying degrees of damage. We performed gas-chromatography/mass spectrometry-based metabolomic analyses in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine matched controls. In each patient, we measured metabolite content in representative tissue-samples from eleven brain regions that display varying degrees of damage in HD, thus identifying the presence and abundance of 63 different metabolites from several molecular classes, including carbohydrates, amino acids, nucleosides, and neurotransmitters. Robust alterations in regional brain-metabolite abundances were observed in HD patients: these included changes in levels of small molecules that play important roles as intermediates in the tricarboxylic-acid and urea cycles, and amino-acid metabolism. Our findings point to widespread disruption of brain metabolism and indicate a complex phenotype beyond the gradient of neuropathologic damage observed in HD brain. PMID:27267344

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Raś, A; Janowski, T; Zduńczyk, 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

  20. Maple Bark Biochar Affects Rhizoctonia solani Metabolism and Increases Damping-Off Severity.

    PubMed

    Copley, Tanya R; Aliferis, Konstantinos A; Jabaji, Suha

    2015-10-01

    Many studies have investigated the effect of biochar on plant yield, nutrient uptake, and soil microbial populations; however, little work has been done on its effect on soilborne plant diseases. To determine the effect of maple bark biochar on Rhizoctonia damping-off, 11 plant species were grown in a soilless potting substrate amended with different concentrations of biochar and inoculated or not with Rhizoctonia solani anastomosis group 4. Additionally, the effect of biochar amendment on R. solani growth and metabolism in vitro was evaluated. Increasing concentrations of maple bark biochar increased Rhizoctonia damping-off of all 11 plant species. Using multivariate analyses, we observed positive correlations between biochar amendments, disease severity and incidence, abundance of culturable bacterial communities, and physicochemical parameters. Additionally, biochar amendment significantly increased R. solani growth and hyphal extension in vitro, and altered its primary metabolism, notably the mannitol and tricarboxylic acid cycles and the glycolysis pathway. One or several organic compounds present in the biochar, as identified by gas chromatography-mass spectrometry analysis, may be metabolized by R. solani. Taken together, these results indicate that future studies on biochar should focus on the effect of its use as an amendment on soilborne plant pathogens before applying it to soils. PMID:25938176

  1. Renal tubular acidosis complicated with hypokalemic periodic paralysis.

    PubMed

    Chang, Y C; Huang, C C; Chiou, Y Y; Yu, C Y

    1995-07-01

    Three Chinese girls with hypokalemic periodic paralysis secondary to different types of renal tubular acidosis are presented. One girl has primary distal renal tubular acidosis complicated with nephrocalcinosis. Another has primary Sjögren syndrome with distal renal tubular acidosis, which occurs rarely with hypokalemic periodic paralysis in children. The third has an isolated proximal renal tubular acidosis complicated with multiple organ abnormalities, unilateral carotid artery stenosis, respiratory failure, and consciousness disturbance. The diagnostic evaluation and emergent and prophylactic treatment for these three types of renal tubular acidosis are discussed. PMID:7575850

  2. 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 β-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, β-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

  3. Genetic background of uric acid metabolism in a patient with severe chronic tophaceous gout.

    PubMed

    Petru, Lenka; Pavelcova, Katerina; Sebesta, Ivan; Stiburkova, Blanka

    2016-09-01

    Hyperuricemia depends on the balance of endogenous production and renal excretion of uric acid. Transporters for urate are located in the proximal tubule where uric acid is secreted and extensively reabsorbed: secretion is principally ensured by the highly variable ABCG2 gene. Enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) plays a central role in purine metabolism and its deficiency is an X-linked inherited metabolic disorder associated with clinical manifestations of purine overproduction. Here we report the case of a middle-aged man with severe chronic tophaceous gout with a poor response to allopurinol and requiring repeated surgical intervention. We identified the causal mutations in the HPRT1 gene, variant c.481G>T (p.A161S), and in the crucial urate transporter ABCG2, a heterozygous variant c.421C>A (p.Q141K). This case shows the value of an analysis of the genetic background of serum uric acid. PMID:27288985

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

    PubMed

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

    2014-11-01

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

  5. Morning cortisol levels and glucose metabolism parameters in moderate and severe obstructive sleep apnea patients.

    PubMed

    Bozic, Josko; Galic, Tea; Supe-Domic, Daniela; Ivkovic, Natalija; Ticinovic Kurir, Tina; Valic, Zoran; Lesko, Josip; Dogas, Zoran

    2016-09-01

    Obstructive sleep apnea (OSA) has been associated with dysregulation of the hypothalamic-pituitary-adrenal axis and alterations in glucose metabolism with increased risk for type 2 diabetes. The aim of the current study was to compare morning plasma cortisol levels and glucose metabolism parameters between moderate (apnea-hypopnea index (AHI): 15-30 events/h) and severe OSA patients (AHI >30 events/h), with respective controls. A total of 56 male OSA patients, 24 moderate (AHI = 21.1 ± 5.3) and 32 severe (AHI = 49.7 ± 18.1), underwent a full-night polysomnography, oral glucose tolerance test (OGTT), and measurement of morning plasma cortisol levels. These groups were compared to 20 matched subjects in a control group. Morning plasma cortisol levels were statistically lower in severe OSA group than in moderate OSA and control groups (303.7 ± 93.5 vs. 423.9 ± 145.1 vs. 417.5 ± 99.8 pmol/L, P < 0.001). Significant negative correlations were found between morning plasma cortisol levels and AHI (r = -0.444, P = 0.002), as well as oxygen desaturation index (r = -0.381, P = 0.011). Fasting plasma glucose (5.0 ± 0.5 vs. 5.4 ± 0.7 vs. 4.9 ± 0.6 mmol/L, P = 0.009) was higher in the severe OSA group compared to moderate OSA and controls. Homeostasis model assessment insulin resistance (HOMA-IR) was higher in the severe OSA group compared to moderate OSA and controls (4.6 ± 3.7 vs. 2.7 ± 2.0 and 2.2 ± 1.8, respectively, P = 0.006). In conclusion, our study showed that morning plasma cortisol levels measured at 8 a.m. were significantly lower in severe OSA patients than those in moderate OSA group and controls. Morning plasma cortisol levels showed a negative correlation with AHI and oxygen desaturation index. Additionally, this study confirmed the evidence of glucose metabolism impairment in moderate and severe OSA patients, with more pronounced effect in the severe OSA patients group. PMID:27000083

  6. Neonatal onset propionic acidemia without acidosis: a case report.

    PubMed

    Akman, Ipek; Imamoğlu, Sebahat; Demirkol, Mübeccel; Alpay, Harika; Ozek, Eren

    2002-01-01

    Propionic acidemia is an inherited disorder of organic acid metabolism characterized by a spectrum of clinical and biochemical findings. The usual presentation is life-threatening ketoacidosis and hyperammonemia. In this report we present a neonate with propionic acidemia presenting with prominent neurologic problems without ketoacidosis. The patient had a serum ammonia level of 3,500 microg/dl which was effectively lowered to normal values in 48 hours by peritoneal dialysis, with remarkable improvement in neurologic status. However, she developed Candida albicans peritonitis, and sepsis and died of cardiorespiratory failure. Infants who have an early onset propionic acidemia have a high mortality and morbidity rate. In conclusion, propionic acidemia should be in the differential diagnosis of patients with neurologic symptoms and hyperammonemia with or without acidosis. PMID:12458812

  7. Severe Obesity Shifts Metabolic Thresholds but Does Not Attenuate Aerobic Training Adaptations in Zucker Rats

    PubMed Central

    Rosa, Thiago S.; Simões, Herbert G.; Rogero, Marcelo M.; Moraes, Milton R.; Denadai, Benedito S.; Arida, Ricardo M.; Andrade, Marília S.; Silva, Bruno M.

    2016-01-01

    Severe obesity affects metabolism with potential to influence the lactate and glycemic response to different exercise intensities in untrained and trained rats. Here we evaluated metabolic thresholds and maximal aerobic capacity in rats with severe obesity and lean counterparts at pre- and post-training. Zucker rats (obese: n = 10, lean: n = 10) were submitted to constant treadmill bouts, to determine the maximal lactate steady state, and an incremental treadmill test, to determine the lactate threshold, glycemic threshold and maximal velocity at pre and post 8 weeks of treadmill training. Velocities of the lactate threshold and glycemic threshold agreed with the maximal lactate steady state velocity on most comparisons. The maximal lactate steady state velocity occurred at higher percentage of the maximal velocity in Zucker rats at pre-training than the percentage commonly reported and used for training prescription for other rat strains (i.e., 60%) (obese = 78 ± 9% and lean = 68 ± 5%, P < 0.05 vs. 60%). The maximal lactate steady state velocity and maximal velocity were lower in the obese group at pre-training (P < 0.05 vs. lean), increased in both groups at post-training (P < 0.05 vs. pre), but were still lower in the obese group at post-training (P < 0.05 vs. lean). Training-induced increase in maximal lactate steady state, lactate threshold and glycemic threshold velocities was similar between groups (P > 0.05), whereas increase in maximal velocity was greater in the obese group (P < 0.05 vs. lean). In conclusion, lactate threshold, glycemic threshold and maximal lactate steady state occurred at similar exercise intensity in Zucker rats at pre- and post-training. Severe obesity shifted metabolic thresholds to higher exercise intensity at pre-training, but did not attenuate submaximal and maximal aerobic training adaptations. PMID:27148063

  8. 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.

  9. 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

  10. Lactic acidosis following intentional overdose by inhalation of salmeterol and fluticasone.

    PubMed

    Manara, Alessandro; Hantson, Philippe; Vanpee, Dominique; Thys, Frédéric

    2012-11-01

    Salmeterol, a long-acting β2-adrenergic receptor agonist used for the treatment of asthma and chronic obstructive pulmonary disease, has an adverse effects profile that is similar to that of salbutamol and other β2-agonists. We report a sympathomimetic syndrome with metabolic acidosis and hyperlactatemia after intentional inhalation of salmeterol in a suicide attempt. A 16-year-old female patient was admitted to the emergency department approximately 2 hours after having inhaled 60 puffs of a combination of salmeterol xinafoate 25 μg and fluticasone propionate 50 μg. She presented in an anxious state with complaints of palpitations and chest pain. The electrocardiogram demonstrated sinus tachycardia and ST-segment depression in the inferior and anterolateral leads. Laboratory findings showed hypokalemia, hypophosphatemia, and lactic acidosis. Cardiac troponin I and creatine kinase MB remained within the normal range. Treatment was supportive and included intravenous fluids and cautious potassium supplementation. The next day, electrocardiographic and laboratory findings returned to normal. We hypothesize that stimulation of β2-adrenergic receptors by inhalation of salmeterol caused this patient's lactic acidosis. This observation is consistent with the hypothesis that the hyperlactatemia observed during asthma attacks is due in part to the administration of high doses of β2-agonists. Salmeterol overdose by inhalation appears to be sufficient to cause lactic acidosis. PMID:23131487

  11. 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

  12. Dietary management of D-lactic acidosis in short bowel syndrome.

    PubMed Central

    Mayne, A J; Handy, D J; Preece, M A; George, R H; Booth, I W

    1990-01-01

    Manipulation of carbohydrate intake was used to treat severe, recurrent D-lactic acidosis in a patient with short bowel syndrome. Dietary carbohydrate composition was determined after assessment of D-lactic acid production from various carbohydrate substrates by faecal flora in vitro. This approach may be preferable to repeated courses of antibiotics. PMID:2317072

  13. Treatment of Severe Metabolic Alkalosis with Continuous Renal Replacement Therapy: Bicarbonate Kinetic Equations of Clinical Value.

    PubMed

    Yessayan, Lenar; Yee, Jerry; Frinak, Stan; Kwon, David; Szamosfalvi, Balazs

    2015-01-01

    Concomitant severe metabolic alkalosis, hypernatremia, and kidney failure pose a therapeutic challenge. Hemodialysis to correct azotemia and abnormal electrolytes results in rapid correction of serum sodium, bicarbonate, and urea but presents a risk for dialysis disequilibrium and brain edema. We describe a patient with Zollinger-Ellison syndrome with persistent encephalopathy, severe metabolic alkalosis (highest bicarbonate 81 mEq/L), hypernatremia (sodium 157 mEq/L), and kidney failure despite 30 hours of intravenous crystalloids and proton pump inhibitor. We used continuous renal replacement therapy (RRT) with delivered hourly urea clearance of ~3 L/hour (24 hour sustained low efficiency dialysis with regional citrate anticoagulation protocol at blood flow rate 60 ml/min and dialysate flow rate 400 ml/min). To mitigate a pronounced decrease in plasma osmolality while removing urea from this hypernatremic patient, dialysate sodium was set to start at 155 mEq/L then at 150 mEq/L after 6 hours. Serum bicarbonate, urea, and sodium were slowly corrected over 26 hours. This case demonstrates how to regulate and predict the systemic bicarbonate level using single pool kinetic modeling during convective or diffusive RRT. Kinetic modeling provides a valuable tool for systemic blood pH control in future combined use of extracorporeal CO2 removal and continuous RRT systems. PMID:25794247

  14. Glycolysis in energy metabolism during seizures.

    PubMed

    Yang, Heng; Wu, Jiongxing; Guo, Ren; Peng, Yufen; Zheng, Wen; Liu, Ding; Song, Zhi

    2013-05-15

    Studies have shown that glycolysis increases during seizures, and that the glycolytic metabolite lactic acid can be used as an energy source. However, how lactic acid provides energy for seizures and how it can participate in the termination of seizures remains unclear. We reviewed possible mechanisms of glycolysis involved in seizure onset. Results showed that lactic acid was involved in seizure onset and provided energy at early stages. As seizures progress, lactic acid reduces the pH of tissue and induces metabolic acidosis, which terminates the seizure. The specific mechanism of lactic acid-induced acidosis involves several aspects, which include lactic acid-induced inhibition of the glycolytic enzyme 6-diphosphate kinase-1, inhibition of the N-methyl-D-aspartate receptor, activation of the acid-sensitive 1A ion channel, strengthening of the receptive mechanism of the inhibitory neurotransmitter γ-minobutyric acid, and changes in the intra- and extracellular environment. PMID:25206426

  15. 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

  16. Association of the ADRA1A gene and the severity of metabolic abnormalities in patients with schizophrenia.

    PubMed

    Cheng, Chin; Chiu, Hsien-Jane; Loh, El-Wui; Chan, Chin-Hong; Hwu, Tzong-Ming; Liu, Yun-Ru; Lan, Tsuo-Hung

    2012-01-10

    Patients with schizophrenia have a higher risk of developing metabolic abnormalities and their associated diseases. Some studies found that the accumulative number of metabolic syndrome components was associated with the severity of metabolic abnormalities. The purpose of this study was to examine the roles of the ADRA1A, ADRA2A, ADRB3, and 5HT2A genes in the risk of having more severe metabolic abnormalities among patients with schizophrenia. We studied a sample of 232 chronic inpatients with schizophrenia (120 males and 112 females) to explore the associations between the four candidate genes and the severity of metabolic syndrome by accumulative number of the components. Four single nucleotide polymorphisms in the candidate genes were genotyped, including the Arg347Cys in ADRA1A, the C1291G in ADRA2A, the Try64Arg in ADRB3, and the T102C in 5HT2A. An association between the accumulative number of metabolic syndrome components and the ADRA1A gene was found after adjusting age, sex, and other related variables (p-value=0.036). Presence of the Arg347 allele in the ADRA1A gene is a risk factor for having more severe metabolic abnormalities. These findings suggest a medical attention of closely monitoring metabolic risks for schizophrenia patients with high-risk genotypes. PMID:22037178

  17. Lactic Acidosis Induced by Linezolid Mimics Symptoms of an Acute Intracranial Bleed: A Case Report and Literature Review

    PubMed Central

    Zuccarini, Nichole Suzzanne; Yousuf, Tariq; Wozniczka, Daniel; Rauf, Anis Abdul

    2016-01-01

    Lactic acidosis is common and most often associated with disturbed acid-base balance. Rarely, it can be a life-threatening medication side effect. Hence, determining the etiology of lactic acidosis early in patients is paramount in choosing the correct therapeutic intervention. Although lactic acidosis as an adverse drug reaction of linezolid is a well-recognized and documented clinical entity, the occurrence of such mimicking an acute intracranial bleed has not been reported to our knowledge. The following case is presented as an example of such an occurrence. A 67-year-old woman presented to the emergency department for lethargy, nausea and syncope. The head CT did not demonstrate any bleeding or mass effect, but lab results were significant for elevated lactic acid. The patient recently underwent left total hip replacement surgery, which was complicated by a methicillin-resistant Staphylococcus aureus (MRSA) infection. She received 6 weeks of oral linezolid therapy. And upon learning that key part of her history, the linezolid was discontinued. Her lactic acid rapidly normalized and she was discharged home. Several publications demonstrate that linezolid induces lactic acidosis by disrupting crucial mitochondrial functions. It is essential that clinicians are aware that linezolid can cause lactic acidosis. And, the important reminder is that adverse drug reactions can often mimic common diseases. If it is not recognized early, ominous clinical consequences may occur. In conclusion, linezolid should be suspected and included in the differential diagnosis if lactic acidosis exists with an uncommon clinical picture.

  18. ASAS Centennial Paper: contributions in the Journal of Animal Science to understanding cattle metabolic and digestive disorders.

    PubMed

    Vasconcelos, J T; Galyean, M L

    2008-07-01

    Acute and subacute ruminal acidosis, bloat, liver abscesses, and polioencephalomalacia (PEM) were reviewed with respect to contributions published in the Journal of Animal Science (JAS) regarding these metabolic and digestive disorders in beef cattle. Increased grain feeding and expansion of the feedlot industry in the 1960s led to considerable research on acidosis, and early publications defined ruminal changes with acute acidosis. The concept of subacute acidosis was developed in the 1970s. Significant research was published during the 1980s and 1990s on adaptation to high-grain diets, effects of ionophores, and the development of model systems to study ruminal and metabolic changes in acidosis. Since 2000, JAS publications on acidosis have largely focused on individual animal variability in response to acid loads and the role of management strategies in controlling acidosis. Increased grain feeding also was associated with an increase in the incidence of liver abscesses, which were quickly linked to insults to the ruminal epithelium associated with acidosis. The role of antibiotics, particularly tylosin, in decreasing the incidence and severity of liver abscesses was a significant contribution of JAS publications during the 1970s and 1980s. Papers on bloat were among the earliest published in JAS related to metabolic and digestive disorders in cattle. Noteworthy accomplishments in bloat research chronicled in JAS include the nature of ruminal contents in legume and feedlot bloat, the role of plant fractions and microbial populations in the development of bloat, and the efficacy of poloxalene, ionophores, and, more recently, condensed tannins in decreasing the incidence and severity of bloat. Although less research has been published on PEM in JAS, early publications highlighting the association between PEM and ruminal acidity and the role of thiaminase in certain forms of the disorder, as well as more recent publications related to the role of sulfur in the

  19. A Heterozygous ZMPSTE24 Mutation Associated with Severe Metabolic Syndrome, Ectopic Fat Accumulation, and Dilated Cardiomyopathy

    PubMed Central

    Galant, Damien; Gaborit, Bénédicte; Desgrouas, Camille; Abdesselam, Ines; Bernard, Monique; Levy, Nicolas; Merono, Françoise; Coirault, Catherine; Roll, Patrice; Lagarde, Arnaud; Bonello-Palot, Nathalie; Bourgeois, Patrice; Dutour, Anne; Badens, Catherine

    2016-01-01

    ZMPSTE24 encodes the only metalloprotease, which transforms prelamin into mature lamin A. Up to now, mutations in ZMPSTE24 have been linked to Restrictive Dermopathy (RD), Progeria or Mandibulo-Acral Dysplasia (MAD). We report here the phenotype of a patient referred for severe metabolic syndrome and cardiomyopathy, carrying a mutation in ZMPSTE24. The patient presented with a partial lipodystrophic syndrome associating hypertriglyceridemia, early onset type 2 diabetes, and android obesity with truncal and abdominal fat accumulation but without subcutaneous lipoatrophy. Other clinical features included acanthosis nigricans, liver steatosis, dilated cardiomyopathy, and high myocardial and hepatic triglycerides content. Mutated fibroblasts from the patient showed increased nuclear shape abnormalities and premature senescence as demonstrated by a decreased Population Doubling Level, an increased beta-galactosidase activity and a decreased BrdU incorporation rate. Reduced prelamin A expression by siRNA targeted toward LMNA transcripts resulted in decreased nuclear anomalies. We show here that a central obesity without subcutaneous lipoatrophy is associated with a laminopathy due to a heterozygous missense mutation in ZMPSTE24. Given the high prevalence of metabolic syndrome and android obesity in the general population, and in the absence of familial study, the causative link between mutation and phenotype cannot be formally established. Nevertheless, altered lamina architecture observed in mutated fibroblasts are responsible for premature cellular senescence and could contribute to the phenotype observed in this patient. PMID:27120622

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

    PubMed Central

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

    2009-01-01

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

  1. A Heterozygous ZMPSTE24 Mutation Associated with Severe Metabolic Syndrome, Ectopic Fat Accumulation, and Dilated Cardiomyopathy.

    PubMed

    Galant, Damien; Gaborit, Bénédicte; Desgrouas, Camille; Abdesselam, Ines; Bernard, Monique; Levy, Nicolas; Merono, Françoise; Coirault, Catherine; Roll, Patrice; Lagarde, Arnaud; Bonello-Palot, Nathalie; Bourgeois, Patrice; Dutour, Anne; Badens, Catherine

    2016-01-01

    ZMPSTE24 encodes the only metalloprotease, which transforms prelamin into mature lamin A. Up to now, mutations in ZMPSTE24 have been linked to Restrictive Dermopathy (RD), Progeria or Mandibulo-Acral Dysplasia (MAD). We report here the phenotype of a patient referred for severe metabolic syndrome and cardiomyopathy, carrying a mutation in ZMPSTE24. The patient presented with a partial lipodystrophic syndrome associating hypertriglyceridemia, early onset type 2 diabetes, and android obesity with truncal and abdominal fat accumulation but without subcutaneous lipoatrophy. Other clinical features included acanthosis nigricans, liver steatosis, dilated cardiomyopathy, and high myocardial and hepatic triglycerides content. Mutated fibroblasts from the patient showed increased nuclear shape abnormalities and premature senescence as demonstrated by a decreased Population Doubling Level, an increased beta-galactosidase activity and a decreased BrdU incorporation rate. Reduced prelamin A expression by siRNA targeted toward LMNA transcripts resulted in decreased nuclear anomalies. We show here that a central obesity without subcutaneous lipoatrophy is associated with a laminopathy due to a heterozygous missense mutation in ZMPSTE24. Given the high prevalence of metabolic syndrome and android obesity in the general population, and in the absence of familial study, the causative link between mutation and phenotype cannot be formally established. Nevertheless, altered lamina architecture observed in mutated fibroblasts are responsible for premature cellular senescence and could contribute to the phenotype observed in this patient. PMID:27120622

  2. New insights into the metabolic and nutritional determinants of severe combined immunodeficiency

    PubMed Central

    Field, Martha S; Kamynina, Elena; Watkins, David; Rosenblatt, David S; Stover, Patrick J

    2015-01-01

    Human mutations in MTHFD1 have recently been identified in patients with severe combined immunodeficiency (SCID). SCID results from inborn errors of metabolism that cause impaired T- and B-cell proliferation and function. One of the most common causes of SCID is adenosine deaminase (ADA) deficiency, which ultimately inhibits DNA synthesis and cell division. MTHFD1 has been shown to translocate to the nucleus during S-phase of the cell cycle; this localization is critical for synthesis of thymidyate (dTMP or the “T” base in DNA) and subsequent progression through the cell cycle and cell proliferation. Identification of MTHFD1 mutations that are associated with SCID highlights the potential importance of adequate dTMP synthesis in the etiology of SCID. PMID:27123375

  3. 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

  4. Acidosis: A potential explanation for adverse fetal outcome in intrahepatic cholestasis of pregnancy. A case report

    PubMed Central

    Visser, W; Smit, LS; Cornette, J

    2014-01-01

    Background Intrahepatic cholestasis of pregnancy is a cholestatic disorder with an increased risk for adverse perinatal outcome. The mechanism underlying intrauterine demise is poorly understood. Case A nulliparous woman with gestational age of 36 plus 6 weeks presented with suspected intrahepatic cholestasis. Continuous CTG monitoring evolved from a normal pattern towards a non-reassuring pattern. A male neonate was delivered by caesarean section. Apgar scores 0, 1 and 4 at 1, 5 and 10 min. Fetal cord gas analysis showed pH 6.98, base deficit –15 mmol/L. Blood results showed maternal serum bile acid concentration of 220 µmol/L. Conclusion Our case suggests gradual evolution towards hypoxia and acidosis. It is unknown whether certain components in the bile acid concentrations might contribute to a fetal metabolic component of the acidosis.

  5. [Type B lactic acidosis associated with marginal lymphoma of the spleen: report of one case].

    PubMed

    Vega, Jorge; Rodríguez, María de los Ángeles; Peña, Armando; Vásquez, Alejadro

    2012-02-01

    Lactic acidosis in the absence of hypoxia or tissue hypoperfusion (type B) is very rare and is associated with the use of some drugs or malignancy. We report a 79-year-old woman, with a marginal non-Hodgkin's lymphoma of the spleen that was subjected to a splenectomy one year ago. She presented with unexplained tachypnea associated with pancytopenia and elevation of IgM to 10 times over the higher normal limit. Laboratory tests showed the presence of metabolic acidosis and high lactic acid levels in the absence of infection, tissue hypoxia or hypoperfusion. She was treated with sodium bicarbonate and steroids without obtaining a reduction in lactate levels. Twelve days after admission, a single dose of Rituximab quickly normalized lactate concentrations and platelet count. After the fourth dose of Rituximab, pancytopenia disappeared and IgM fell to 25% of its baseline concentration. PMID:22739955

  6. Distal Renal Tubular Acidosis and Calcium Nephrolithiasis

    NASA Astrophysics Data System (ADS)

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

    2008-09-01

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

  7. Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9.

    PubMed

    Danhauser, Katharina; Herebian, Diran; Haack, Tobias B; Rodenburg, Richard J; Strom, Tim M; Meitinger, Thomas; Klee, Dirk; Mayatepek, Ertan; Prokisch, Holger; Distelmaier, Felix

    2016-03-01

    Coenzyme Q10 (CoQ10) has an important role in mitochondrial energy metabolism by way of its functioning as an electron carrier in the respiratory chain. Genetic defects disrupting the endogenous biosynthesis pathway of CoQ10 may lead to severe metabolic disorders with onset in early childhood. Using exome sequencing in a child with fatal neonatal lactic acidosis and encephalopathy, we identified a homozygous loss-of-function variant in COQ9. Functional studies in patient fibroblasts showed that the absence of the COQ9 protein was concomitant with a strong reduction of COQ7, leading to a significant accumulation of the substrate of COQ7, 6-demethoxy ubiquinone10. At the same time, the total amount of CoQ10 was severely reduced, which was reflected in a significant decrease of mitochondrial respiratory chain succinate-cytochrome c oxidoreductase (complex II/III) activity. Lentiviral expression of COQ9 restored all these parameters, confirming the causal role of the variant. Our report on the second COQ9 patient expands the clinical spectrum associated with COQ9 variants, indicating the importance of COQ9 already during prenatal development. Moreover, the rescue of cellular CoQ10 levels and respiratory chain complex activities by CoQ10 supplementation points to the importance of an early diagnosis and immediate treatment. PMID:26081641

  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-α 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 β-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. Interrelation between compensation of carbohydrate metabolism and severity of manifestations of oxidative stress in type II diabetes mellitus.

    PubMed

    Nedosugova, L V; Lankin, V Z; Balabolkin, M I; Konovalova, G G; Lisina, M O; Antonova, K V; Tikhaze, A K; Belenkov, Yu N

    2003-08-01

    Glycosylation end-products formed during diabetes mellitus promoted atherogenic oxidative modification of low-density lipoproteins. We evaluated the effects of compensation of carbohydrate metabolism and therapy with antioxidant probucol on parameters of free radical oxidation in patients with type II diabetes mellitus. Compensation of carbohydrate metabolism reduced manifestations of oxidative stress, which was manifested in accelerated enzymatic utilization of reactive oxygen species and lipid peroxides and decreased content of free radical oxidation products in low-density lipoproteins. In patients with type II diabetes mellitus combination therapy with antioxidant probucol decreased the severity of oxidative stress and stabilized carbohydrate metabolism without increasing the dose of hypoglycemic preparations. PMID:14631491

  11. 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

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

    PubMed

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

    2014-04-29

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

  13. 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. PMID:26167308

  14. Purine nucleoside metabolism in the erythrocytes of patients with adenosine deaminase deficiency and severe combined immunodeficiency.

    PubMed Central

    Agarwal, R P; Crabtree, G W; Parks, R E; Nelson, J A; Keightley, R; Parkman, R; Rosen, F S; Stern, R C; Polmar, S H

    1976-01-01

    Deficiency of erythrocytic and lymphocytic adenosine deaminase (ADA) occurs in some patients with severe combined immunodeficiency disease (SCID). SCID with ADA deficiency is inherited as an autosomal recessive trait. ADA is markedly reduced or undetectable in affected patients (homozygotes), and approximately one-half normal levels are found in individuals heterozygous for ADA deficiency. The metabolism of purine nucleosides was studied in erythrocytes from normal individuals, four ADA-deficiency patients, and two heterozygous individuals. ADA deficiency in intake erythrocytes was confirmed by a very sensitive ammonia-liberation technique. Erythrocytic ADA activity in three heterozygous individuals (0.07,0.08, and 0.14 mumolar units/ml of packed cells) was between that of the four normal controls (0.20-0.37 mumol/ml) and the ADA-deficient patients (no activity). In vitro, adenosine was incorporated principally into IMP in the heterozygous and normal individuals but into the adenosine nucleotides in the ADa-deficient patients. Coformycin (3-beta-D-ribofuranosyl-6,7,8-trihydroimidazo[4,5-4] [1,3] diazepin-8 (R)-ol), a potent inhibitor of ADA, made possible incorporation of adenosine nucleotides in the ADA-deficient patients... PMID:947948

  15. 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.

  16. Effects of dichloroacetate in the treatment of hypoxic lactic acidosis in dogs.

    PubMed

    Graf, H; Leach, W; Arieff, A I

    1985-09-01

    The metabolic and systemic effects of dichloroacetate (DCA) in the treatment of hypoxic lactic acidosis were evaluated in the dog and compared with the infusion of equal quantities of volume and sodium. Hypoxic lactic acidosis was induced by ventilating dogs with an hypoxic gas mixture of 8% oxygen and 92% nitrogen, resulting in arterial PO2 of less than 30 mmHg, pH below 7.20, bicarbonate less than 15 mM, and lactate greater than 7 mM. After, the development of hypoxic lactic acidosis dogs were treated for 60 min with either DCA as sodium salt or NaCl at equal infusions of volume and sodium. Dogs treated with DCA showed a significant increase of arterial blood pH and bicarbonate, and steady levels of lactate, whereas NaCl resulted in further declines of blood pH and bicarbonate, and rising blood lactate levels. Overall lactate production decreased during therapy with either regimen, but hepatic lactate extraction increased significantly with DCA, while it remained unchanged with NaCl. Tissue lactate levels in liver and skeletal muscle decreased significantly with DCA treatment but were unchanged with NaCl. Additionally, an increase in muscle intracellular pH was observed only in DCA treated dogs. A possible mechanism for the observed actions of DCA might be related to a significant increase in oxygen delivery to tissues. Such an effect was found with DCA administration, but was not observed with NaCl therapy. In conclusion, DCA therapy in hypoxic lactic acidosis has beneficial systemic effects compared with therapy with NaCl. DCA administration is accompanied by increases of blood pH and bicarbonate, a decrease in lactate production, and enhanced liver lactate extraction, and a lowering of tissue lactate levels. PMID:4044835

  17. Severe hypoglycemic encephalopathy due to hypoallergenic formula in an infant.

    PubMed

    Ogawa, Erika; Ishige, Mika; Takahashi, Yuno; Kodama, Hiroko; Fuchigami, Tatsuo; Takahashi, Shori

    2016-08-01

    A 7-month-old girl was brought to hospital due to vomiting. Upon admission, she was in a convulsive state and stupor with extremely low blood glucose. Head computed tomography showed brain edema, and comprehensive treatment for acute encephalopathy was initiated immediately. Severe hypoglycemia, metabolic acidosis, elevation of ammonia and serum transaminases and creatine kinase suggested metabolic decompensation. Infusion of a high-glucose solution containing vitamins, biotin, and l-carnitine resolved the metabolic crisis quickly, but brain damage was irreversible. She was found to have been fed exclusively on a hypoallergenic formula (HF) for 7 months, although she was found later to be non-allergic. Evidence of inborn metabolic diseases was absent, therefore biotin deficiency and carnitine deficiency were concluded to be a consequence of reliance on a HF for a prolonged period. Health-care professionals should warn parents of the consequences of using HF. PMID:27324861

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

    PubMed

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

    2014-12-01

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

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

    PubMed

    Soliz, Jose; Lim, Jeffrey; Zheng, Gang

    2014-01-01

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

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

    PubMed Central

    Lim, Jeffrey

    2014-01-01

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

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

    PubMed Central

    Morvan, Daniel

    2013-01-01

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

  2. Influence of 72% injury in one kidney on several organs involved in guanidino compound metabolism: a time course study.

    PubMed

    Levillain, O; Marescau, B; Possemiers, I; Al Banchaabouchi, M; De Deyn, P P

    2001-07-01

    Arginine (Arg) produced from citrulline originates mostly from kidneys. Arg is involved in guanidino compound biosynthesis, which requires interorgan co-operation. In renal insufficiency, citrulline accumulates in the plasma in proportion to renal damage. Thus, disturbances in Arg and guanidino compound metabolism are expected in several tissues. An original use of the model of nephrectomy based on ligating branches of the renal artery allowed us to investigate Arg and guanidino compound metabolism simultaneously in injured (left) and healthy (right) kidneys. The left kidney of adult rats was subjected to 72% nephrectomy. Non-operated, sham-operated and nephrectomized rats were studied for a period of 21 days. Constant renal growth was observed only in the healthy kidneys. Guanidino compound levels were modified transiently during the first 48 h. The metabolism and/or tissue content of several guanidino compounds were disturbed throughout the experimental period. Arg synthesis was greatly reduced in the injured kidney, while it increased in the healthy kidney. The renal production of guanidinoacetic acid decreased in the injured kidney and its urinary excretion was reduced. The experimentally proven toxins alpha-keto-delta-guanidinovaleric acid and guanidinosuccinic acid (GSA) accumulated only in the injured kidney. The urinary excretion of GSA and methylguanidine increased in nephrectomized rats. When the injured kidney grew again, the level of some guanidino compounds tended to normalize. Nephrectomy affected the guanidino compound levels and metabolism in muscles and liver. In conclusion, the specific accumulation of toxic guanidino compounds in the injured kidney reflects disturbances in renal metabolism and function. The healthy kidney compensates for the injured kidney's loss of metabolic functions (e.g. Arg: production). This model is excellent for investigating renal metabolism when a disease destroys a limited area in one kidney, as is observed in patients

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

    PubMed

    Arveladze, G A; Geladze, N M; Sanikidze, T B; Khachapuridze, N S; Bakhtadze, S Z

    2015-02-01

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

  4. Normal liver enzymes are correlated with severity of metabolic syndrome in a large population based cohort

    PubMed Central

    Kälsch, Julia; Bechmann, Lars P.; Heider, Dominik; Best, Jan; Manka, Paul; Kälsch, Hagen; Sowa, Jan-Peter; Moebus, Susanne; Slomiany, Uta; Jöckel, Karl-Heinz; Erbel, Raimund; Gerken, Guido; Canbay, Ali

    2015-01-01

    Key features of the metabolic syndrome are insulin resistance and diabetes. The liver as central metabolic organ is not only affected by the metabolic syndrome as non-alcoholic fatty liver disease (NAFLD), but may contribute to insulin resistance and metabolic alterations. We aimed to identify potential associations between liver injury markers and diabetes in the population-based Heinz Nixdorf RECALL Study. Demographic and laboratory data were analyzed in participants (n = 4814, age 45 to 75y). ALT and AST values were significantly higher in males than in females. Mean BMI was 27.9 kg/m2 and type-2-diabetes (known and unkown) was present in 656 participants (13.7%). Adiponectin and vitamin D both correlated inversely with BMI. ALT, AST, and GGT correlated with BMI, CRP and HbA1c and inversely correlated with adiponectin levels. Logistic regression models using HbA1c and adiponectin or HbA1c and BMI were able to predict diabetes with high accuracy. Transaminase levels within normal ranges were closely associated with the BMI and diabetes risk. Transaminase levels and adiponectin were inversely associated. Re-assessment of current normal range limits should be considered, to provide a more exact indicator for chronic metabolic liver injury, in particular to reflect the situation in diabetic or obese individuals. PMID:26269425

  5. Normal liver enzymes are correlated with severity of metabolic syndrome in a large population based cohort.

    PubMed

    Kälsch, Julia; Bechmann, Lars P; Heider, Dominik; Best, Jan; Manka, Paul; Kälsch, Hagen; Sowa, Jan-Peter; Moebus, Susanne; Slomiany, Uta; Jöckel, Karl-Heinz; Erbel, Raimund; Gerken, Guido; Canbay, Ali

    2015-01-01

    Key features of the metabolic syndrome are insulin resistance and diabetes. The liver as central metabolic organ is not only affected by the metabolic syndrome as non-alcoholic fatty liver disease (NAFLD), but may contribute to insulin resistance and metabolic alterations. We aimed to identify potential associations between liver injury markers and diabetes in the population-based Heinz Nixdorf RECALL Study. Demographic and laboratory data were analyzed in participants (n = 4814, age 45 to 75 y). ALT and AST values were significantly higher in males than in females. Mean BMI was 27.9 kg/m(2) and type-2-diabetes (known and unkown) was present in 656 participants (13.7%). Adiponectin and vitamin D both correlated inversely with BMI. ALT, AST, and GGT correlated with BMI, CRP and HbA1c and inversely correlated with adiponectin levels. Logistic regression models using HbA1c and adiponectin or HbA1c and BMI were able to predict diabetes with high accuracy. Transaminase levels within normal ranges were closely associated with the BMI and diabetes risk. Transaminase levels and adiponectin were inversely associated. Re-assessment of current normal range limits should be considered, to provide a more exact indicator for chronic metabolic liver injury, in particular to reflect the situation in diabetic or obese individuals. PMID:26269425

  6. Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern.

    PubMed

    Gelaye, Alehegn; Haidar, Abdallah; Kassab, Christina; Kazmi, Syed; Sinha, Prabhat

    2016-01-01

    Canagliflozin (Invokana) is a selective sodium glucose cotransporter-2 (SGLT-2) inhibitor that was first introduced in 2013 for the treatment of type 2 diabetes mellitus (DM). Though not FDA approved yet, its use in type 1 DM has been justified by the fact that its mechanism of action is independent of insulin secretion or action. However, some serious side effects, including severe anion gap metabolic acidosis and euglycemic diabetic ketoacidosis (DKA), have been reported. Prompt identification of the causal association and initiation of appropriate therapy should be instituted for this life threatening condition. PMID:27088018

  7. Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern

    PubMed Central

    Gelaye, Alehegn; Haidar, Abdallah; Kassab, Christina; Kazmi, Syed; Sinha, Prabhat

    2016-01-01

    Canagliflozin (Invokana) is a selective sodium glucose cotransporter-2 (SGLT-2) inhibitor that was first introduced in 2013 for the treatment of type 2 diabetes mellitus (DM). Though not FDA approved yet, its use in type 1 DM has been justified by the fact that its mechanism of action is independent of insulin secretion or action. However, some serious side effects, including severe anion gap metabolic acidosis and euglycemic diabetic ketoacidosis (DKA), have been reported. Prompt identification of the causal association and initiation of appropriate therapy should be instituted for this life threatening condition. PMID:27088018

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

    PubMed

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

    2014-02-01

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

  9. Complex III deficiency due to an in-frame MT-CYB deletion presenting as ketotic hypoglycemia and lactic acidosis.

    PubMed

    Mori, Mari; Goldstein, Jennifer; Young, Sarah P; Bossen, Edward H; Shoffner, John; Koeberl, Dwight D

    2015-09-01

    Complex III deficiency due to a MT-CYB mutation has been reported in patients with myopathy. Here, we describe a 15-year-old boy who presented with metabolic acidosis, ketotic hypoglycemia and carnitine deficiency. Electron transport chain analysis and mitochondrial DNA sequencing on muscle tissue lead to the eventual diagnosis of complex III deficiency. This case demonstrates the critical role of muscle biopsies in a myopathy work-up, and the clinical efficacy of supplement therapy. PMID:26937408

  10. Genetics Home Reference: renal tubular acidosis with deafness

    MedlinePlus

    ... a disorder characterized by kidney (renal) problems and hearing loss. The kidneys normally filter fluid and waste products ... In people with renal tubular acidosis with deafness , hearing loss caused by changes in the inner ear (sensorineural ...

  11. Side Effects of HIV Medicines: HIV and Lactic Acidosis

    MedlinePlus

    ... HIV medicines. All HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class may cause lactic acidosis, but ... some HIV medicines. HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class can cause the body to ...

  12. Distal Renal Tubular Acidosis in Infancy: A Bicarbonate Wasting State

    ERIC Educational Resources Information Center

    Rodriguez-Soriano, J.; And Others

    1975-01-01

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

  13. Drug-induced haemolysis, renal failure, thrombocytopenia and lactic acidosis in patients with HIV and cryptococcal meningitis: a diagnostic challenge.

    PubMed

    Camara-Lemarroy, Carlos R; Flores-Cantu, Hazael; Calderon-Hernandez, Hector J; Diaz-Torres, Marco A; Villareal-Velazquez, Hector J

    2015-12-01

    Patients with HIV are at risk of both primary and secondary haematological disorders. We report two cases of patients with HIV and cryptococcal meningitis who developed severe haemolytic anaemia, thrombocytopenia, renal failure and lactic acidosis while on treatment with amphotericin B and co-trimoxazole. PMID:25614519

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

    ClinicalTrials.gov

    2016-08-15

    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

  15. The effect of occlusive dressings on the energy metabolism of severely burned children.

    PubMed

    Caldwell, F T; Bowser, B H; Crabtree, J H

    1981-05-01

    Metabolic studies were performed on 23 burned children. They were studied sequentially until their burn wounds were healed. A metabolic study lasted 20 minutes, during which continuous measurements were made of O2 consumption and CO2 production rates, rectal temperature, average surface temperatures (dressings, skin and wound), body heat content, and rate of body weight loss using a bed scale. These measurements allowed solution of the heat balance equation for each study period. After 24 hours in a constant temperature room kept at 28 C and 40% relative humidity, metabolic studies were initiated when blood was drawn for catecholamine assay, followed by a metabolic analysis, after which dressings were removed and fresh silvadene applied to the wounds. No dressings were applied. Metabolic analyses were repeated after two and four hours of exposure, after which blood for catecholamine analysis was drawn and the study terminated. Without dressings in a thermally neutral environment, burn patients demonstrated an increased rate of heat loss of 27 watts/square meter body surface area (W/M2), compared with the predicted normal. The major portion of this increment is by evaporation, which increased 300%. The rate of heat production equals heat loss, and is increased 50% above the predicted normal. Occlusive dressings result in a 15 W/M2 decrease in the rate of heat loss, about evenly divided between evaporative and dry routes, with a corresponding 15 W/M2 decrease in the rate of heat production. Plasma catecholamine levels of bandaged burn patients are not significantly different from values for healed burn patients, and do not correlate with the rate of heat production. The increased heat production of burn patients is a response to an increased rate of heat loss, not vice versa. The use of occlusive dressings substantially reduces the energy requirements to manageable levels, even in patients with very large burns. PMID:7235763

  16. Effect of dichloroacetate in the treatment of anoxic lactic acidosis in dogs.

    PubMed

    Sheikh, A; Fleisher, G; Delgado Paredes, C; Caputo, G; Schaible, D; Egler, J; Swedlow, D

    1986-11-01

    Lactic acidosis is seen frequently after severe anoxia and circulatory failure. Because dichloroacetate (DCA) has been shown to be effective in the treatment of lactic acidosis, we studied its effect on lactate levels and pH in arterial and sagittal sinus blood specimens in a pediatric canine model of anoxic cardiac arrest followed by CPR. Lactate levels rose steadily in all puppies receiving DCA alone (group 1), DCA plus bicarbonate (group 2), bicarbonate alone (group 3), or neither drug (group 4). Arterial and sagittal-sinus lactate levels were in the range of 2 mmol/L during the baseline period, 6 mmol/L after anoxic arrest, and 10 mmol/L after 20 min of CPR. Bicarbonate, but not DCA, significantly raised arterial pH. Neither drug reversed the progression of acidosis in the sagittal sinus; mean pH ranged from 6.85 to 6.92 among the four groups after 20 min of CPR. We speculate that DCA did not decrease lactate levels or raise the pH in either the peripheral circulation or the CNS (sagittal sinus) because of poor perfusion achieved during closed-chest cardiac compression. PMID:3021391

  17. Protein and acidosis alter calcium-binding and fluorescence spectra of the calcium indicator indo-1.

    PubMed Central

    Baker, A J; Brandes, R; Schreur, J H; Camacho, S A; Weiner, M W

    1994-01-01

    The fluorescent indicator indo-1 is widely used to monitor intracellular calcium concentration. However, quantitation is limited by uncertain effects of the intracellular environment on indicator properties. The goal of this study was to determine the effects of protein and acidosis on the fluorescence spectra and calcium dissociation constant (Kd) of indo-1. With 350 nm excitation light, the ratio of indo-1 fluorescence in the absence versus the presence of saturating Ca2+ at wavelength lambda (S lambda) and Kd increased with [protein]. At pH 7.3, Kd, S400, and S470, which were 210 nM, 0.033, and 1.433 in the absence of protein, increased to 808 nM, 0.161, and 2.641, respectively, by adding proteins from frog muscle and to 638 nM, 0.304, and 3.039, respectively, by adding proteins from rat heart. Effects of protein on indo-1 fluorescence were reduced at higher [indo-1]. Acidosis (pH 6.3) had separate effects, which were additive to those of protein: in the absence of protein, acidosis increased Kd to 640 nM; frog muscle proteins further increased Kd to 1700 nM. Acidosis also changed S lambda slightly. In summary, interaction with protein or protons alters indo-1 calcium-binding and fluorescence. These findings are consistent with several previous studies and suggest that indo-1 calibration constants need to be derived in the presence of appropriate types of protein, ratio of [indo-1]/[protein], and pH. PMID:7819496

  18. Acidosis promotes Bcl-2 family-mediated evasion of apoptosis: involvement of acid-sensing G protein-coupled receptor Gpr65 signaling to Mek/Erk.

    PubMed

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

    2012-08-10

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

  19. Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson’s Disease

    PubMed Central

    Xu, Yunqi; Wei, Xiaobo; Liu, Xu; Liao, Jinchi; Lin, Jiaping; Zhu, Cansheng; Meng, Xiaochun; Xie, Dongsi; Chao, Dongman; Fenoy, Albert J; Cheng, Muhua; Tang, Beisha; Zhang, Zhuohua; Xia, Ying; Wang, Qing

    2015-01-01

    This study explored the association between cerebral metabolic rates of glucose (CMRGlc) and the severity of Vascular Parkinsonism (VP) and Parkinson’s disease (PD). A cross-sectional study was performed to compare CMRGlc in normal subjects vs. VP and PD patients. Twelve normal subjects, 22 VP, and 11 PD patients were evaluated with the H&Y and MMSE, and underwent 18F-FDG measurements. Pearson’s correlations were used to identify potential associations between the severity of VP/PD and CMRGlc. A pronounced reduction of CMRGlc in the frontal lobe and caudate putamen was detected in patients with VP and PD when compared with normal subjects. The VP patients displayed a slight CMRGlc decrease in the caudate putamen and frontal lobe in comparison with PD patients. These decreases in CMRGlc in the frontal lobe and caudate putamen were significantly correlated with the VP patients’ H&Y, UPDRS II, UPDRS III, MMSE, cardiovascular, and attention/memory scores. Similarly, significant correlations were observed in patients with PD. This is the first clinical study finding strong evidence for an association between low cerebral glucose metabolism and the severity of VP and PD. Our findings suggest that these changes in glucose metabolism in the frontal lobe and caudate putamen may underlie the pathophysiological mechanisms of VP and PD. As the scramble to find imaging biomarkers or predictors of the disease intensifies, a better understanding of the roles of cerebral glucose metabolism may give us insight into the pathogenesis of VP and PD. PMID:26618044

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

    PubMed

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

    2015-04-01

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

  1. 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

  2. [POSSIBILITY OF CORRECTION OF METABOLIC DISORDERS WITH REAMBERIN IN ACUTE PERIOD OF TRAUMATIC INJURY].

    PubMed

    Gerasimov, L V; Marchenkov, Yu V; Volkov, D P; Rodionov, E P; Izmajlov, V V

    2015-01-01

    56 patients at the age of 18-60 years with severe trauma were examined. Influence of the polyelectrolytic (Reamberin)solution on an acid-base state, osmolarity and electrolytic composition of plasma in the acute posttraumatic period was evaluated. It was found that patients, who was treated by isotonic sodium chloride solution and Ringer's solution, had metabolic acidosis and hyperchloremia. In contrast, in the reamberin group 82% of patients had lower concentrations of chloride and had nothing acid-base disturbances on the second day after trauma. Reamberin didn't influence on plasma osmolarity and the rate of metabolic alkalosis during the acute period of a trauma. PMID:27025136

  3. [Severe accidental hypothermia in an elderly woman].

    PubMed

    Knobel, B; Mikhlin, A

    2001-11-01

    Profound hypothermia (core temperature of less than 28 degrees C) is a life threatening state and a medical emergency associated with a high mortality rate. The prognosis depends on underlying diseases, advanced or very early age, the duration prior to treatment, the degree of hemodynamic deterioration, and especially, the methods of treatment, including active external or internal rewarming. This is a case study of an 80-year-old female patient with severe accidental hypothermia (core temperature 27 degrees C). She was found in her home lying immobile on the cold floor after a fall. The patient was in a profound coma with cardiocirculatory collapse, and the medical staff treating her was inclined to pronounce her deceased. On her arrival at the hospital, she was resuscitated, put on a respirator and actively warmed. Very severe metabolic disorders were found, including a marked metabolic acidosis composed of diabetic ketoacidosis (she had suffered from insulin treated type 2 diabetes mellitus) and lactic acidosis with a very high anion gap (42) and a hyperosmotic state (blood glucose 1202 mg/dl). There were pathognomonic electrocardiographic abnormalities, J-wave of Osborn and prolonged repolarization. Slow atrial fibrillation with a ventricular response of 30 bpm followed by a nodal rhythm of 12 bpm and reversible cardiac arrest were recorded. The pulse and blood pressure were unobtainable. Despite the successful resuscitation and hemodynamic and cognitive improvement, rhabdomyolysis (CKP 6580 u/L), renal failure and hepatic damage developed. She was extubated and treated with intravenous fluids containing dopamine, bicarbonate, insulin and antibiotics. Her medical condition gradually improved, and she was discharged clear minded, functioning very well and independent. Renal and liver tests returned eventually to normal limits. Progressive bradycardia, hypotension and death due to ventricular fibrillation or asystole commonly occur during severe hypothermia

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

    PubMed Central

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

    1985-01-01

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

  5. Loss of inherited genomic imprints in mice leads to severe disruption in placental lipid metabolism

    PubMed Central

    Himes, K. P.; Young, A.; Koppes, E.; Stolz, D.; Barak, Y.; Sadovsky, Y.; Chaillet, J.R.

    2015-01-01

    Introduction Monoallelic expression of imprinted genes is necessary for placental development and normal fetal growth. Differentially methylated domains (DMDs) largely determine the parental-specific monoallelic expression of imprinted genes. Maternally derived DNA (cytosine-5-) -methyltransferase 1o (DNMT1o) maintains DMDs during the eight-cell stage of development. DNMT1o-deficient mouse placentas have a generalized disruption of genomic imprints. Previous studies have demonstrated that DNMT1o deficiency alters placental morphology and broadens the embryonic weight distribution in late gestation. Lipids are critical for fetal growth. Thus, we assessed the impact of disrupted imprinting on placental lipids. Methods Lipids were quantified from DNMT1o-deficient mouse placentas and embryos at E17.5 using a modified Folch method. Expression of select genes critical for lipid metabolism was quantified with RT-qPCR. Mitochondrial morphology was assessed by TEM and mitochondrial aconitase and cytoplasmic citrate concentrations quantified. DMD methylation was determined by EpiTYPER. Results We found that DNMT1o deficiency is associated with increased placental triacylglycerol levels. Neither fetal triacylglycerol concentrations nor expression of select genes that mediate placental lipid transport were different from wild type. Placental triacylglycerol accumulation was associated with impaired beta-oxidation and abnormal citrate metabolism with decreased mitochondrial aconitase activity and increased cytoplasmic citrate concentrations. Loss of methylation at the MEST DMD was strongly associated with placental triacylglycerol accumulation. Discussion A generalized disruption of genomic imprints leads to triacylglycerol accumulation and abnormal mitochondrial function. This could stem directly from a loss of methylation at a given DMD, such as MEST, or represent a consequence of abnormal placental development. PMID:25662615

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

    PubMed Central

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

    2014-01-01

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

  7. Metabolism

    MedlinePlus

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

  8. 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

  9. Mechanistic Modeling of the Effects of Acidosis on Thrombin Generation

    PubMed Central

    Mitrophanov, Alexander Y.; Rosendaal, Frits R.

    2015-01-01

    BACKGROUND: Acidosis, a frequent complication of trauma and complex surgery, results from tissue hypoperfusion and IV resuscitation with acidic fluids. While acidosis is known to inhibit the function of distinct enzymatic reactions, its cumulative effect on the blood coagulation system is not fully understood. Here, we use computational modeling to test the hypothesis that acidosis delays and reduces the amount of thrombin generation in human blood plasma. Moreover, we investigate the sensitivity of different thrombin generation parameters to acidosis, both at the individual and population level. METHODS: We used a kinetic model to simulate and analyze the generation of thrombin and thrombin–antithrombin complexes (TAT), which were the end points of this study. Large groups of temporal thrombin and TAT trajectories were simulated and used to calculate quantitative parameters, such as clotting time (CT), thrombin peak time, maximum slope of the thrombin curve, thrombin peak height, area under the thrombin trajectory (AUC), and prothrombin time. The resulting samples of parameter values at different pH levels were compared to assess the acidosis-induced effects. To investigate intersubject variability, we parameterized the computational model using the data on clotting factor composition for 472 subjects from the Leiden Thrombophilia Study. To compare acidosis-induced relative parameter changes in individual (“virtual”) subjects, we estimated the probabilities of relative change patterns by counting the pattern occurrences in our virtual subjects. Distribution overlaps for thrombin generation parameters at distinct pH levels were quantified using the Bhattacharyya coefficient. RESULTS: Acidosis in the range of pH 6.9 to 7.3 progressively increased CT, thrombin peak time, AUC, and prothrombin time, while decreasing maximum slope of the thrombin curve and thrombin peak height (P < 10–5). Acidosis delayed the onset and decreased the amount of TAT generation (P

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

    SciTech Connect

    Roubin, G.S.; Anderson, S.D.; Shen, W.F.; Choong, C.Y.; Alwyn, M.; Hillery, S.; Harris, P.J.; Kelly, D.T. )

    1990-04-01

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

  11. 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. PMID:26064244

  12. 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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. Intracellular Acidosis Enhances the Excitability of Working Muscle

    NASA Astrophysics Data System (ADS)

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

    2004-08-01

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

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

    SciTech Connect

    Peek, K.E.H.

    1988-01-01

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

  16. Oxidative damage in muscular dystrophy correlates with the severity of the pathology: role of glutathione metabolism.

    PubMed

    Renjini, R; Gayathri, N; Nalini, A; Srinivas Bharath, M M

    2012-04-01

    Muscular dystrophies (MDs) such as Duchenne muscular dystrophy (DMD), sarcoglycanopathy (Sgpy) and dysferlinopathy (Dysfy) are recessive genetic neuromuscular diseases that display muscle degeneration. Although these MDs have comparable endpoints of muscle pathology, the onset, severity and the course of these diseases are diverse. Different mechanisms downstream of genetic mutations might underlie the disparity in these pathologies. We surmised that oxidative damage and altered antioxidant function might contribute to these differences. The oxidant and antioxidant markers in the muscle biopsies from patients with DMD (n = 15), Sgpy (n = 15) and Dysfy (n = 15) were compared to controls (n = 10). Protein oxidation and lipid peroxidation was evident in all MDs and correlated with the severity of pathology, with DMD, the most severe dystrophic condition showing maximum damage, followed by Sgpy and Dysfy. Oxidative damage in DMD and Sgpy was attributed to the depletion of glutathione (GSH) and lowered antioxidant activities while loss of GSH peroxidase and GSH-S-transferase activities was observed in Dysfy. Lower GSH level in DMD was due to lowered activity of gamma-glutamyl cysteine ligase, the rate limiting enzyme in GSH synthesis. Similar analysis in cardiotoxin (CTX) mouse model of MD showed that the dystrophic muscle pathology correlated with GSH depletion and lipid peroxidation. Depletion of GSH prior to CTX exposure in C2C12 myoblasts exacerbated oxidative damage and myotoxicity. We deduce that the pro and anti-oxidant mechanisms could be correlated to the severity of MD and might influence the dystrophic pathology to a different extent in various MDs. On a therapeutic note, this could help in evolving novel therapies that offer myoprotection in MD. PMID:22219131

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

    PubMed Central

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

    1979-01-01

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

  18. Metabolic and Hormonal Changes of Severely Burned Children Receiving Long-Term Oxandrolone Treatment

    PubMed Central

    Przkora, Rene; Jeschke, Marc G.; Barrow, Robert E.; Suman, Oscar E.; Meyer, Walter J.; Finnerty, Celeste C.; Sanford, Arthur P.; Lee, Jong; Chinkes, David L.; Mlcak, Ronald P.; Herndon, David N.

    2005-01-01

    Objective: When given to children for 1 year after a severe burn, oxandrolone significantly improves lean body mass, bone mineral content, and muscle strength. The beneficial effects of oxandrolone on height and weight were observed 1 year after treatment was discontinued. To study the efficacy of oxandrolone in severely burned children for 12 months after burn and 12 months after the drug was discontinued. Summary Background Data: Oxandrolone attenuates body catabolism during the acute phase after burn. It is unclear whether oxandrolone would have any beneficial effects during long-term treatment or if there were any effects after the drug was stopped. Methods: Sixty-one children with 40% total body surface area burns were enrolled in this study. Patients were randomized into those to receive oxandrolone (n = 30) or placebo (n = 31) for the first 12 months. Treatment was discontinued after 12 months, and the patients were studied without the drug for the following 12 months. At discharge and 6, 12, 18, and 24 months after burn, height, weight, body composition, resting energy expenditure, muscle strength, and serum human growth hormone, insulin-like growth factor-I (IGF-1), IGF binding protein-3, insulin, cortisol, parathyroid hormone, tri-iodothyronine uptake (T3 uptake), and free thyroxine index (FTI) were measured. Statistical analysis used Tukey multiple comparison test. Significance was accepted at P < 0.05. Results: Oxandrolone improved lean body mass, bone mineral content and muscle strength compared with controls during treatment, P < 0.05. Serum IGF-1, T3 uptake, and FTI were significantly higher during drug treatment compared with controls, P < 0.05. Significant increases in height and weight with oxandrolone were observed after the end of treatment. Conclusions: Oxandrolone improved body composition and strength in severely burned children during the 12 months of treatment. Its effect on height and weight continued after treatment was discontinued. PMID

  19. An XRCC4 Splice Mutation Associated With Severe Short Stature, Gonadal Failure, and Early-Onset Metabolic Syndrome

    PubMed Central

    de Bruin, Christiaan; Mericq, Verónica; Andrew, Shayne F.; van Duyvenvoorde, Hermine A.; Verkaik, Nicole S.; Losekoot, Monique; Porollo, Aleksey; Garcia, Hernán; Kuang, Yi; Hanson, Dan; Clayton, Peter; van Gent, Dik C.; Wit, Jan M.; Hwa, Vivian

    2015-01-01

    Context: Severe short stature can be caused by defects in numerous biological processes including defects in IGF-1 signaling, centromere function, cell cycle control, and DNA damage repair. Many syndromic causes of short stature are associated with medical comorbidities including hypogonadism and microcephaly. Objective: To identify an underlying genetic etiology in two siblings with severe short stature and gonadal failure. Design: Clinical phenotyping, genetic analysis, complemented by in vitro functional studies of the candidate gene. Setting: An academic pediatric endocrinology clinic. Patients or Other Participants: Two adult siblings (male patient [P1] and female patient 2 [P2]) presented with a history of severe postnatal growth failure (adult heights: P1, −6.8 SD score; P2, −4 SD score), microcephaly, primary gonadal failure, and early-onset metabolic syndrome in late adolescence. In addition, P2 developed a malignant gastrointestinal stromal tumor at age 28. Intervention(s): Single nucleotide polymorphism microarray and exome sequencing. Results: Combined microarray analysis and whole exome sequencing of the two affected siblings and one unaffected sister identified a homozygous variant in XRCC4 as the probable candidate variant. Sanger sequencing and mRNA studies revealed a splice variant resulting in an in-frame deletion of 23 amino acids. Primary fibroblasts (P1) showed a DNA damage repair defect. Conclusions: In this study we have identified a novel pathogenic variant in XRCC4, a gene that plays a critical role in non-homologous end-joining DNA repair. This finding expands the spectrum of DNA damage repair syndromes to include XRCC4 deficiency causing severe postnatal growth failure, microcephaly, gonadal failure, metabolic syndrome, and possibly tumor predisposition. PMID:25742519

  20. Cerebral blood flow and metabolism in children with severe head injuries. Part 2: Cerebrovascular resistance and its determinants.

    PubMed Central

    Sharples, P M; Matthews, D S; Eyre, J A

    1995-01-01

    It has been proposed that in children with severe head injuries the cerebral circulation does not respond appropriately to normal physiological control mechanisms, making children more susceptible than adults to low cerebrovascular resistance, increased cerebral blood flow (cerebral hyperaemia), and raised intracranial pressure. To investigate this issue, 122 serial measurements of cerebrovascular resistance in 17 children with severe head injuries have been performed and related to cerebral perfusion pressure, arterial CO2 (PaCO2), arterial oxygen content (AO2), and the cerebral metabolic rate of oxygen (CMRO2). Cerebrovascular resistance values (mean (SD) 1.54 (0.61) mm Hg.ml-1.100 g.min) were normal or raised in most cases; 71 values (58%) were within the normal range, 39 (32%) above the upper limit, and only 12 (10%) below the lower limit. There was a significant correlation between cerebral perfusion pressure and cerebrovascular resistance (r = 0.32, p = 0.0003), suggesting preservation of pressure autoregulation. This correlation was absent in four of the five children who died or survived with severe handicap. Analysis by multilevel modelling indicated that, as in normal subjects, CMRO2, CPP, AO2, PaCO2, and cerebrovenous pH were important independent determinants of cerebrovascular resistance. The results indicate that normal cerebrovascular reactivity is often preserved in children with severe head injuries but may be impaired in the most severely injured patients. PMID:7876844

  1. Acidosis, magnesium and acetylsalicylic acid: Effects on thrombin

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  2. Acidosis Blocks CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP)- and c-Jun-Mediated Induction of p53-Upregulated Mediator of Apoptosis (PUMA) during Amino Acid Starvation

    PubMed Central

    Ryder, Christopher B.; McColl, Karen; Distelhorst, Clark W.

    2012-01-01

    Cancer cells must avoid succumbing to a variety of noxious conditions within their surroundings. Acidosis is one such prominent feature of the tumor microenvironment that surprisingly promotes tumor survival and progression. We recently reported that acidosis prevents apoptosis of starved or stressed lymphoma cells through regulation of several Bcl-2 family members (Ryder et al., JBC, 2012). Mechanistic studies in that work focused on the acid-mediated upregulation of anti-apoptotic Bcl-2 and Bcl-xL, while additionally showing inhibition of glutamine starvation-induced expression of pro-apoptotic PUMA by acidosis. Herein we report that amino acid (AA) starvation elevates PUMA, an effect that is blocked by extracellular acidity. Knockdown studies confirm that PUMA induction during AA starvation requires expression of both CHOP and c-Jun. Interestingly, acidosis strongly attenuates AA starvation-mediated c-Jun expression, which correlates with PUMA repression. As c-Jun exerts a tumor suppressive function in this and other contexts, its inhibition by acidosis has broader implications for survival of cancer cells in the acidic tumor milieu. PMID:23261451

  3. 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-α and -β, 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

  4. Hypokalemic paralysis and osteomalacia secondary to renal tubular acidosis in a case with primary Sjögren's syndrome.

    PubMed

    Kawashima, Masanori; Amano, Tetsuki; Morita, Yoshitaka; Yamamura, Masahiro; Makino, Hirofumi

    2006-01-01

    A 39-year-old Japanese woman was admitted to our hospital for severe weakness owing to potassium deficiency caused by type 1 renal tubular acidosis (RTA1). Sicca complex, serological tests, and lip biopsy revealed that she had Sjögren's syndrome (SS). Acidosis was corrected by alkali supplement treatment. She also had an impaired renal function with proteinuria, and high absorbance on Ga scintigram was recognized in both kidneys. She was taking warfarin potassium after aortic valve substitution due to aortic regurgitation, therefore renal biopsy was not performed. Prednisone (20 mg/day) was administered for renal inflammation. One month later, she suffered severe chest wall pains with some local tender points over the costae of both sides, which was presumed to be due to pseudo-fractures based on osteomalacia. Hypokalemic paralysis and osteomalacia should be taken into consideration in the diagnosis of SS with RTA1. PMID:16622725

  5. 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

  6. Changes in the rumen epimural bacterial diversity of beef cattle as affected by diet and induced ruminal acidosis.

    PubMed

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

    2013-06-01

    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

  7. 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.

  8. The effect of cyclical and severe heat stress on growth performance and metabolism in Afshari lambs.

    PubMed

    Mahjoubi, E; Yazdi, M Hossein; Aghaziarati, N; Noori, G R; Afsarian, O; Baumgard, L H

    2015-04-01

    lambs' ADG was more than 2-fold greater than the PFTN controls. These results indicate that HS markedly alters the energetics of weight gain during growth and that the effects of HS are dependent on the severity of the heat load. PMID:26020185

  9. Metabolic Syndrome in South African Patients with Severe Mental Illness: Prevalence and Associated Risk Factors

    PubMed Central

    Saloojee, Shamima; Burns, Jonathan K; Motala, Ayesha A

    2016-01-01

    Background There is a surge of cardiovascular disease (CVD) in Africa. CVD is the leading cause of mortality among patients with severe mental illness (SMI) in developed countries, with little evidence from the African context. Objective To determine the prevalence and risk factors for MetS among South African patients with SMI. Method In a cross sectional study, individuals with SMI treated with antipsychotics and a control group without a mental illness, matched for age, gender and ethnicity were evaluated for MetS using the 2009 Joint Interim statement (JIS) criteria. Results Of the 276 study group subjects, 65.9% were male, 84.1% black African, 9.1% white, 5.4% of Indian descent and 1.5% coloured (mixed race) with a mean age of 34.7 years (±12.5). Schizophrenia was the most common diagnosis (73.2%) and 40% were taking first generation antipsychotics. The prevalence of MetS was 23.2% (M: 15.4%, F: 38.3%) in the study group and 19.9% (M: 11.9%, F: 36.3%) in the control group (p = 0.4). MetS prevalence was significantly higher in study subjects over 55 years compared to controls (p = 0.03). Increased waist circumference (p< 0.001) and low high density lipoprotein (HDL) cholesterol (p = 0.003) were significantly more prevalent in study subjects compared to controls. In study subjects, risk factors associated with MetS included age (OR: 1.09, 95% CI 1.06–1.12, p < 0.001), female gender (OR: 2.19, 95% CI 1.06–4.55, p = 0.035) and Indian descent (OR: 5.84, 95% CI 1.66–20.52, p = 0.006) but not class of antipsychotic (p = 0.26). Conclusion The overall MetS prevalence was not increased in patients with SMI compared to controls; however, the higher prevalence of the individual components (HDL cholesterol and waist circumference) suggests an increased risk for CVD, especially in patients over 55 years. PMID:26882230

  10. 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

  11. CD64-Neutrophil expression and stress metabolic patterns in early sepsis and severe traumatic brain injury in children

    PubMed Central

    2013-01-01

    Background Critical illness constitutes a serious derangement of metabolism. The aim of our study was to compare acute phase metabolic patterns in children with sepsis (S) or severe sepsis/septic shock (SS) to those with severe traumatic brain injury (TBI) and healthy controls (C) and to evaluate their relations to neutrophil, lymphocyte and monocyte expressions of CD64 and CD11b. Methods Sixty children were enrolled in the study. Forty-five children with systemic inflammatory response syndrome (SIRS) were classified into three groups: TBI (n = 15), S (n = 15), and SS (n = 15). C consisted of 15 non- SIRS patients undergoing screening tests for minor elective surgery. Blood samples were collected within 6 hours after admission for flow cytometry of neutrophil, lymphocyte and monocyte expression of CD64 and CD11b (n = 60). Procalcitonin (PCT), C-reactive protein (CRP), glucose, triglycerides (TG), total cholesterol (TC), high (HDL) or low-density-lipoproteins (LDL) were also determined in all groups, and repeated on day 2 and 3 in the 3 SIRS groups (n = 150). Results CRP, PCT and TG (p < 0.01) were significantly increased in S and SS compared to TBI and C; glucose did not differ among critically ill groups. Significantly lower were the levels of TC, LDL, and HDL in septic groups compared to C and to moderate changes in TBI (p < 0.0001) but only LDL differed between S and SS (p < 0.02). Among septic patients, PCT levels declined significantly (p < 0.02) with time, followed by parallel decrease of HDL (p < 0.03) and increase of TG (p < 0.02) in the SS group. Neutrophil CD64 (nCD64) expression was higher in patients with SS (81.2%) and S (78.8%) as compared to those with TBI (5.5%) or C (0.9%, p < 0.0001). nCD64 was positively related with CRP, PCT, glucose, and TG (p < 0.01) and negatively with TC, LDL, and HDL (p < 0.0001), but not with severity of illness, hematologic indices, length of stay or mechanical

  12. Successful management of drug-induced hypercapnic acidosis with naloxone and noninvasive positive pressure ventilation.

    PubMed

    Agrafiotis, Michalis; Tryfon, Stavros; Siopi, Demetra; Chassapidou, Georgia; Galanou, Artemis; Tsara, Venetia

    2015-02-01

    A 74-year-old man was referred to our hospital due to deteriorating level of consciousness and desaturation. His Glasgow Coma Scale was 6, and his pupils were constricted but responded to light. Chest radiograph was negative for significant findings. Arterial blood gas evaluation on supplemental oxygen revealed severe acute on chronic respiratory acidosis: pH 7.15; PCO2, 133 mm Hg; PO2,64 mm Hg; and HCO3, 31 mmol/L. He regained full consciousness (Glasgow Coma Scale, 15) after receiving a 0.4 mg dose of naloxone, but because of persistent severe respiratory acidosis (pH 7.21; PCO2, 105 mm Hg), he was immediately commenced on noninvasive positive pressure ventilation (NIV) displaying a remarkable improvement in arterial blood gas values within the next few hours. However, in the days that followed, he remained dependent on NIV, and he was finally discharged on a home mechanical ventilation prescription. In cases of drug-induced respiratory depression, NIV should be regarded as an acceptable treatment, as it can provide ventilatory support without the increased risks associated with invasive mechanical ventilation. PMID:25176564

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

    PubMed Central

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

    1998-01-01

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

  14. [Multiple calcium oxalate stone formation in a patient with glycogen storage disease type I (von Gierke's disease) and renal tubular acidosis type I: a case report].

    PubMed

    Kanematsu, A; Segawa, T; Kakehi, Y; Takeuchi, H

    1993-07-01

    A case of multiple urinary stones in a patient with glycogen storage disease type 1 (GSD-1) is reported. In spite of the presence of hyperuricemia, these stones did not consist of uric acid, but mainly of calcium oxalate. Laboratory studies revealed distal renal tubular acidosis and hypocitraturia, but no significant abnormality in calcium metabolism. We discussed the mechanism of calcium stone formation in our case, and its prophylactic treatment by oral administration of citrate compound. PMID:8362684

  15. Metabolism of platelet activating factor (PAF) and lyso-PAF in polymorphonuclear granulocytes from severely burned patients.

    PubMed

    Schönfeld, W; Kasimir, S; Köller, M; Erbs, G; Müller, F E; König, W

    1990-12-01

    We studied the metabolism of 3H-platelet activating factor (PAF) and lyso-PAF in human polymorphonuclear granulocytes (PMN) from severely burned patients (n = 6) on days 1, 5, 9, 15, and 25 post-trauma. All patients suffered from a severe burn trauma of more than 30% total body surface area. Stimulation of PMN in healthy donors (n = 10) with the Ca-ionophore resulted in the conversion of 3H-lyso-PAF into PAF (18 +/- 2% of total radioactivity) and alkyl-acyl-glycero-phosphorylcholine (alkyl-acyl-GPC, 50 +/- 6%). In burned patients a significantly reduced formation of 3H-PAF was observed between days 1 and 15 post-trauma (day 9: 1 +/- 1%, p less than 0.0001). This pattern was normalized again in patients (n = 5) who survived the trauma after septic periods and was observed during the second week post-trauma. In one patient who succumbed to his injuries a sustained inhibition of PAF formation was observed up to his death. The decreased formation of PAF correlated weakly with the appearance of immature granulocytes within the analyzed cell fraction (ratio of immature cells versus PAF-formation, r = -0.55, p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2258972

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

    PubMed

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

    2010-03-01

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

  17. Cellular acidosis inhibits assembly, disassembly, and motility of stress granules.

    PubMed

    Chudinova, E M; Nadezhdina, E S; Ivanov, P A

    2012-11-01

    Stress granules (SGs) are large ribonucleoprotein (RNP)-containing particles that form in cytoplasm in response to a variety of acute changes in the cellular environment. One of the general parameters of the cell environment is pH. In some diseases, as well as in muscle fatigue, tissue acidosis occurs, leading to decrease in intracellular pH. Here we studied whether decrease in pH causes the formation of SGs in cultured animal cells, whether it affects the formation of the SGs under the action of arsenite and, if such effects occur, what are the mechanisms of the influence of acidosis. Acidosis was simulated by decreasing the pH of the culture medium, which acidified the cytoplasm. We found that medium acidification to pH 6.0 in itself did not cause formation of SGs in cells. Moreover, acidification prevented the formation of SGs under treatment with sodium arsenite or sodium arsenite together with the proteasome inhibitor MG132, and it inhibited the dissociation of preformed SGs under the influence of cycloheximide. We established that pH decrease did not affect the phosphorylation of eIF2α that occurs under the action of sodium arsenite, and even caused such phosphorylation by itself. We also found that the velocity of SG motion in cytoplasm at acidic pH was very low, and the mobile fraction of SG-incorporated PABP protein revealed by FRAP was decreased. We suppose that acidic pH impairs biochemical processes favoring assembly of RNPs in stress conditions and RNP dissociation on the termination of stress. Thus, in acidosis the reaction of the cellular translation apparatus to stress is modified. PMID:23240565

  18. 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

  19. 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

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

    PubMed

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

    2013-09-01

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

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

    PubMed Central

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

    2013-01-01

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

  2. Human anion exchanger1 mutations and distal renal tubular acidosis.

    PubMed

    Yenchitsomanus, Pa-thai

    2003-09-01

    The human anion exchanger 1 (AE1 or SLC4A1) gene encodes anion exchanger 1 (or band 3) protein in erythrocytes and in alpha-intercalated cells of the kidney. Thus, AE1 mutations show pleiotrophic effects resulting in two distinct and seemingly unrelated defects, an erythrocyte abnormality and distal renal tubular acidosis (dRTA). Southeast Asian ovalocytosis (SAO), a well-known red blood cell (RBC) defect, which is widespread in Southeast Asian regions, is caused by AE1 mutation due to a deletion of 27 base pairs in codons 400-408 (delta400-408) leading to an in-frame 9 amino-acid loss in the protein. Co-existence of SAO and dRTA is usually not seen in the same individual. However, the two conditions can co-exist as the result of compound heterozygosities between delta400-408 and other mutations. The reported genotypes include delta400-408/G701D, delta400-408/R602H, delta400-408/deltaV850, and delta400-408/A858D. The presence of dRTA, with or without RBC abnormalities, may occur from homozygous or compound heterozygous conditions of recessive AE1 mutations (eg G701D/G701D, V488M/V488M, deltaV850/deltaV850, deltaV850/A858D, G701D/S773P) or heterozygous dominant AE1 mutations (eg R598H, R589C, R589S, S613F, R901X). Codon 589 of this gene seems to be a 'mutational hot-spot' since repeated mutations at this codon occurring in different ethnic groups and at least two de novo (R589H and R589C) mutations have been observed. Therefore, AE1 mutations can result in both recessive and dominant dRTA, possibly depending on the position of the amino acid change in the protein. As several mutant AE1 proteins still maintain a significant anion transport function but are defective in targeting to the cell surface, impaired intracellular trafficking of the mutant AE1 is an important molecular mechanism involved in the pathogenesis of dRTA associated with AE1 mutations. PMID:15115146

  3. Fetal acidosis and hypotension during repeated umbilical cord occlusions are associated with enhanced chemoreflex responses in near-term fetal sheep.

    PubMed

    Bennet, Laura; Westgate, Jenny A; Liu, Yung-Chi Jack; Wassink, Guido; Gunn, Alistair J

    2005-10-01

    This study examined the hypothesis that repeated episodes of brief but severe hypoxia would not attenuate the chemoreflex-mediated rapid initial fall in fetal heart rate (FHR) and, further, that greater hypoxic stress, as shown by hypotension and metabolic acidosis, would be associated with an enhanced chemoreflex response. Chronically instrumented, near-term fetal sheep received 1 min total umbilical cord occlusion either every 5 min for 4 h (1:5 group; n = 8) or every 2.5 min (1:2.5 group; n = 8) until mean arterial blood pressure fell to <20 mmHg on two successive occlusions. Umbilical cord occlusion caused variable decelerations, with sustained hypertension in the 1:5 group and little change in acid-base status (pH 7.34 +/- 0.03 after 4 h). In contrast, the 1:2.5 group showed progressive hypotension and metabolic acidemia (pH 6.92 +/- 0.04 after the last occlusion). The 1:2.5 group showed a significant increase in the rate of initial fall in FHR during the occlusion series, which was greater than the 1:5 group in the last 30 min of the occlusion series (9.4 +/- 1.4 vs. 3.5 +/- 0.3 beats.min(-1).s(-1); P < 0.01), with a greater fall in FHR (71.9 +/- 6.5 vs. 47.0 +/- 8.7 beats/min; P < 0.05). In summary, this study demonstrated that repetitive laborlike cord occlusions, which led to severe fetal compromise, were associated with an increase in the slope and magnitude of the initial FHR deceleration. These findings support the concept of the chemoreflex as a central, robust component of fetal adaptation to severe hypoxia. PMID:15976361

  4. More sensitivity of cortical GABAergic neurons than glutamatergic neurons in response to acidosis.

    PubMed

    Liu, Hua; Li, Fang; Wang, Chunyan; Su, Zhiqiang

    2016-05-25

    Acidosis impairs brain functions. Neuron-specific mechanisms underlying acidosis-induced brain dysfunction remain elusive. We studied the sensitivity of cortical GABAergic neurons and glutamatergic neurons to acidosis by whole-cell recording in brain slices. The acidification to the neurons was induced by perfusing artificial cerebral spinal fluid with lower pH. This acidification impairs excitability and synaptic transmission in the glutamatergic and GABAergic neurons. Acidosis impairs spiking capacity in the GABAergic neurons more than in the glutamatergic neurons. Acidosis also strengthens glutamatergic synaptic transmission and attenuates GABAergic synaptic transmission on the GABAergic neurons more than the glutamatergic neurons, which results in the functional impairment of these GABAergic neurons. This acidosis-induced dysfunction predominantly in the cortical GABAergic neurons drives the homeostasis of neuronal networks toward overexcitation and exacerbates neuronal impairment. PMID:27116702

  5. EARS2 mutations cause fatal neonatal lactic acidosis, recurrent hypoglycemia and agenesis of corpus callosum.

    PubMed

    Danhauser, Katharina; Haack, Tobias B; Alhaddad, Bader; Melcher, Marlen; Seibt, Annette; Strom, Tim M; Meitinger, Thomas; Klee, Dirk; Mayatepek, Ertan; Prokisch, Holger; Distelmaier, Felix

    2016-06-01

    Mitochondrial aminoacyl tRNA synthetases are essential for organelle protein synthesis. Genetic defects affecting the function of these enzymes may cause pediatric mitochondrial disease. Here, we report on a child with fatal neonatal lactic acidosis and recurrent hypoglycemia caused by mutations in EARS2, encoding mitochondrial glutamyl-tRNA synthetase 2. Brain ultrasound revealed agenesis of corpus callosum. Studies on patient-derived skin fibroblasts showed severely decreased EARS2 protein levels, elevated reactive oxygen species (ROS) production, and altered mitochondrial morphology. Our report further illustrates the clinical spectrum of the severe neonatal-onset form of EARS2 mutations. Moreover, in this case the live-cell parameters appeared to be more sensitive to mitochondrial dysfunction compared to standard diagnostics, which indicates the potential relevance of fibroblast studies in children with mitochondrial diseases. PMID:26780086

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

    PubMed Central

    Rixen, Dieter; Siegel, John H

    2005-01-01

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

  7. Ibuprofen-related renal tubular acidosis in pregnancy

    PubMed Central

    Mallett, Andrew; Lynch, Matthew; John, George T; Healy, Helen; Lust, Karin

    2011-01-01

    Ibuprofen-related renal tubular acidosis (RTA) has not been previously described in pregnancy but its occurrence outside of pregnancy is being increasingly described. In this case, a 34-year-old woman presented in the third trimester of pregnancy with Type 1 or distal RTA related to ibuprofen and codeine abuse. It was complicated by acute on chronic renal dysfunction and hypokalemia. Delivery at 37 weeks gestation due to concerns of evolving preeclampsia resulted in the birth of a healthy neonate. RTA and hypokalemia were remediated and ibuprofen and codeine abuse ceased. Some renal dysfunction however continued. Thorough and repeated history taking as well as vigilance for this condition is suggested.

  8. Type-B lactic acidosis associated with progressive multiple myeloma

    PubMed Central

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

    2015-01-01

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

  9. 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.

  10. Pre-treatment evaluation of 5-fluorouracil degradation rate: association of poor and ultra-rapid metabolism with severe toxicity in a colorectal cancer patients cohort

    PubMed Central

    Mazzuca, Federica; Borro, Marina; Botticelli, Andrea; Mazzotti, Eva; Marchetti, Luca; Gentile, Giovanna; La Torre, Marco; Lionetto, Luana; Simmaco, Maurizio; Marchetti, Paolo

    2016-01-01

    Despite the wide use of 5-fluorouracil-based chemotherapy, development of severe toxicity that follow the treatment is not a rare event. The efforts to establish pretreatment tools for toxicity prediction, led to the development of various pharmacogenetic and biochemical assays, mainly targeted to assess the activity level of dihydropyrimidine dehydrogenase (DPD), the main metabolizing enzyme for 5-fluorouracil. Using peripheral blood mononuclear cells, we developed a biochemical assay, that is not limited to the evaluation of DPD activity, but determines the net result of all the enzymatic transformation of 5FU, in terms of the amount of drug consumed by the cells in a time unit. This parameter, named 5-fluorauracil degradation rate, presents a normal distribution inside the population and highlight the presence of an ultra-rapid metabolizers class of subjects, besides the expected poor metabolizers class. Here we will show that, in a colorectal cancer patient cohort, both poor and ultra-rapid metabolizers have significantly increased the risk of developing severe toxicity (grade3–4). Patient stratification depending on the individual 5-fluorouracil degradation rate allows to identify a 10% of the overall population at high risk of developing severe toxicity, compared to the 1.3% (as assessed in the Italian population) identified by the most commonly employed pharmacogenetic test, including the DPD polymorphism IVS14+1G>A. PMID:26967565

  11. A fatal adverse effect of cefazolin administration: severe brain edema in a patient with multiple meningiomas

    PubMed Central

    Tribuddharat, Sirirat; Sathitkarnmanee, Thepakorn; Kitkhuandee, Amnat; Theerapongpakdee, Sunchai; Ngamsaengsirisup, Kriangsak; Chanthawong, Sarinya

    2016-01-01

    Cefazolin is commonly administered before surgery as a prophylactic antibiotic. Hypersensitivity to cefazolin is not uncommon, and the symptoms mostly include urticaria, skin reaction, diarrhea, vomiting, and transient neutropenia, which are rarely life threatening. We present a rare case of fatal cefazolin hypersensitivity in a female who was diagnosed with multiple meningiomas and scheduled for craniotomy and tumor removal. Immediately after cefazolin IV administration, the patient developed acute hypertensive crisis, which resolved within 10 minutes after the treatment. This was followed by unexplained metabolic acidosis. The patient then developed severe brain edema 100 minutes later. The patient had facial edema when her face was exposed for the next 30 minutes. A computed tomography scan revealed global brain edema with herniation. She was admitted to the intensive care unit for symptomatic treatment and died 10 days after surgery from multiorgan failure. The serum IgE level was very high (734 IU/mL). Single-dose administration of cefazolin for surgical prophylaxis may lead to rare, fatal adverse reaction. The warning signs are sudden, unexplained metabolic acidosis, hypertensive crisis, tachycardia, and facial angioedema predominating with or without cutaneous symptoms like urticaria. PMID:26929668

  12. 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. )

    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).

  13. Nineteen-year follow-up of a patient with severe glutathione synthetase deficiency.

    PubMed

    Atwal, Paldeep S; Medina, Casey R; Burrage, Lindsay C; Sutton, V Reid

    2016-07-01

    Glutathione synthetase deficiency is a rare autosomal recessive disorder resulting in low levels of glutathione and an increased susceptibility to oxidative stress. Patients with glutathione synthetase deficiency typically present in the neonatal period with hemolytic anemia, metabolic acidosis and neurological impairment. Lifelong treatment with antioxidants has been recommended in an attempt to prevent morbidity and mortality associated with the disorder. Here, we present a 19-year-old female who was diagnosed with glutathione synthetase deficiency shortly after birth and who has been closely followed in our metabolic clinic. Despite an initial severe presentation, she has had normal intellectual development and few complications of her disorder with a treatment regimen that includes polycitra (citric acid, potassium citrate and sodium citrate), vitamin C, vitamin E and selenium. PMID:26984560

  14. A fatal outcome of complicated severe diabetic ketoacidosis in a 11-year-old girl.

    PubMed

    Severinski, Srećko; Butorac Ahel, Ivona; Ovuka, Aleksandar; Verbić, Arijan

    2016-08-01

    Diabetic ketoacidosis (DKA) is a complex metabolic state characterized by hyperglycemia, metabolic acidosis and ketonuria. Cerebral edema is the most common rare complication of DKA in children. The objective of the study was to emphasize the importance of careful evaluation and monitoring for signs and symptoms of cerebral edema in all children undergoing treatment for DKA. We present a case of 11-year-old girl with a history of diabetes mellitus type I (T1DM) who presented with severe DKA complicated by hypovolemic shock, cerebral edema and hematemesis. Considering the fact that complications of DKA are rare and require a high index of clinical suspicion, early recognition and treatment are crucial for avoiding permanent damage. PMID:27226096

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

    SciTech Connect

    Leitz, T.

    1987-07-01

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

  16. 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

  17. Retransfusion acidosis after brief haemorrhagic hypotension in the dog.

    PubMed

    Takács, L; Szántó, G; Vándor, E

    1976-01-01

    Dogs under chloralose anasthesia were bled at a rate of 50 ml/min to a total of 25 ml/kg body weight and 2 minutes later a quick reinfusion of adequate volumes of blood, dextran, or Locke's solution was done. Within 2 minutes after reinfusion, the pH of arterial blood fell by 0.074--0.127; concurrently, PaCO2 rose by 9.2-12.9 mm Hg. A close correlation was demonstrated between these changes. After retransfusion, PaO2 and the arterial lactic acid level did not change significantly. Thus retransfusion acidosis in the dog appears after a brief hypotensive period, too, but cannot be attributed to a "washout" of lactate from the tissues. PMID:11626

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

    PubMed

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

    2009-04-01

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

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

    PubMed Central

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

    1996-01-01

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

  20. Lactic acidosis and diastolic hypotension after intermittent albuterol nebulization in a pediatric patient

    PubMed Central

    Saadia, Tehila A.; George, Mathew; Lee, Haesoon

    2015-01-01

    We describe a case of 13-year-old female with intermittent asthma who developed lactic acidosis and diastolic hypotension after receiving intermittent albuterol nebulizer treatment. She presented to the emergency department (ED) with sudden onset of shortness of breath and chest pain. She received two albuterol nebulizer treatments at home without symptomatic relief. She was treated in the ED with intermittent albuterol nebulization for a total of 22.5 mg over the next 5 hours. A decrease in diastolic blood pressure from 60 mmHg to 40 mmHg was noted after the treatment. Blood lactate level was 5.9 mmol/L. She recovered from it and was discharged to home but she had recurrence of shortness of breath and presented to the ED two days later. She was treated with albuterol nebulization for a total of 17.5 mg over the next two and half hours and developed diastolic hypotension again, as low as 30 mm Hg. After discontinuation of albuterol nebulization, her BP normalized. Cardiopulmonary and metabolic side effects of continuous albuterol therapy have been reported in the recent medical literature. Our patient, however, developed these adverse effects on intermittent albuterol nebulizer treatment. It is important for the pediatrician to recognize the adverse effects of β2-agonist therapy to avoid carrying out extensive workup for hypotension and hyperlactatemia prolonging hospital stay. PMID:26744665

  1. Identification of elevated urea as a severe, ubiquitous metabolic defect in the brain of patients with Huntington's disease.

    PubMed

    Patassini, Stefano; Begley, Paul; Reid, Suzanne J; Xu, Jingshu; Church, Stephanie J; Curtis, Maurice; Dragunow, Mike; Waldvogel, Henry J; Unwin, Richard D; Snell, Russell G; Faull, Richard L M; Cooper, Garth J S

    Huntington's disease (HD) is a neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein through the lengthening of a polyglutamine tract and initiates a cascade that ultimately leads to dementia and premature death. However, neurodegeneration typically manifests in HD only in middle age, and processes linking the causative mutation to brain disease are poorly understood. Here, our objective was to elucidate further the processes that cause neurodegeneration in HD, by measuring levels of metabolites in brain regions known to undergo varying degrees of damage. We applied gas-chromatography/mass spectrometry-based metabolomics in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine controls. Unexpectedly, a single major abnormality was evident in all eleven brain regions studied across the forebrain, midbrain and hindbrain, namely marked elevation of urea, a metabolite formed in the urea cycle by arginase-mediated cleavage of arginine. Urea cycle activity localizes primarily in the liver, where it functions to incorporate protein-derived amine-nitrogen into urea for recycling or urinary excretion. It also occurs in other cell-types, but systemic over-production of urea is not known in HD. These findings are consistent with impaired local urea regulation in brain, by up-regulation of synthesis and/or defective clearance. We hypothesize that defective brain urea metabolism could play a substantive role in the pathogenesis of neurodegeneration, perhaps via defects in osmoregulation or nitrogen metabolism. Brain urea metabolism is therefore a target for generating novel monitoring/imaging strategies and/or therapeutic interventions aimed at ameliorating the impact of HD in patients. PMID:26522227

  2. Markers of acidosis and stress in a sprint versus a conducted electrical weapon.

    PubMed

    Ho, Jeffrey D; Dawes, Donald M; Nystrom, Paul C; Collins, Donal P; Nelson, Rebecca S; Moore, Johanna C; Miner, James R

    2013-12-10

    Both profound acidosis and catecholamine excess have been proposed as underlying physiologic derangements in subjects at high risk for arrest related death (ARD). In this study, the objective was to determine a level of physical exertion that is "equivalent" in terms of levels of acidosis and catecholamines to a "standard" TASER X26 exposure. Data were collected on subjects who underwent a 5-s TASER X26 exposure or a sprint of variable distances during a law enforcement training exercise. Our results show that levels of acidosis and catecholamines are less among subjects exposed to the TASER X26 than among subjects who sprinted 20 yards or more. PMID:24314505

  3. Assimilation, Accumulation, and Metabolism of Dinophysistoxins (DTXs) and Pectenotoxins (PTXs) in the Several Tissues of Japanese Scallop Patinopecten yessoensis

    PubMed Central

    Matsushima, Ryoji; Uchida, Hajime; Nagai, Satoshi; Watanabe, Ryuichi; Kamio, Michiya; Nagai, Hiroshi; Kaneniwa, Masaki; Suzuki, Toshiyuki

    2015-01-01

    Japanese scallops, Patinopecten yessoensis, were fed with the toxic dinoflagellate Dinophysis fortii to elucidate the relative magnitude of assimilation, accumulation, and metabolism of diarrhetic shellfish toxins (DSTs) and pectenotoxins (PTXs). Three individual scallops were separately exposed to cultured D. fortii for four days. The average cell number of D. fortii assimilated by each individual scallop was 7.7 × 105. Dinophysistoxin-1 (DTX1), pectenotoxin-2 (PTX2) and their metabolites were analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS) and the toxin content in individual tissues (digestive gland, adductor muscle, gill, gonad, mantle, and the others), feces and the seawater medium were quantified. Toxins were almost exclusively accumulated in the digestive gland with only low levels being detected in the gills, mantles, gonads, and adductor muscles. DTX1 and PTX2 were the dominant toxins in the D. fortii cells fed to the scallops, whereas the dominant toxins detected in the digestive gland of scallops were PTX6 and esterified acyl-O-DTX1 (DTX3). In other tissues PTX2 was the dominant toxin observed. The ratio of accumulated to assimilated toxins was 21%–39% and 7%–23% for PTXs and DTXs respectively. Approximately 54%–75% of PTX2 and 52%–70% of DTX1 assimilated by the scallops was directly excreted into the seawater mainly without metabolic transformation. PMID:26633503

  4. Perinatal risk factors for severe injury in neonates treated with whole-body hypothermia for encephalopathy

    PubMed Central

    Wayock, Christopher P.; Meserole, Rachel L.; Saria, Suchi; Jennings, Jacky M.; Huisman, Thierry A. G. M.; Northington, Frances J.; Graham, Ernest M.

    2016-01-01

    Objective Our objective was to identify perinatal risk factors that are available within 1 hour of birth that are associated with severe brain injury after hypothermia treatment for suspected hypoxic-ischemic encephalopathy. Study Design One hundred nine neonates at ≥35 weeks' gestation who were admitted from January 2007 to September 2012 with suspected hypoxic-ischemic encephalopathy were treated with whole-body hypothermia; 98 of them (90%) underwent brain magnetic resonance imaging (MRI) at 7-10 days of life. Eight neonates died before brain imaging. Neonates who had severe brain injury, which was defined as death or abnormal MRI results (cases), were compared with surviving neonates with normal MRI (control subjects). Logistic regression models were used to identify risk factors that were predictive of severe injury. Results Cases and control subjects did not differ with regard to gestational age, birthweight, mode of delivery, or diagnosis of non-reassuring fetal heart rate before delivery. Cases were significantly (P ≤ .05) more likely to have had an abruption, a cord and neonatal arterial gas level that showed metabolic acidosis, lower platelet counts, lower glucose level, longer time to spontaneous respirations, intubation, chest compressions in the delivery room, and seizures. In multivariable logistic regression, lower initial neonatal arterial pH (P = .004), spontaneous respiration at >30 minutes of life (P = .002), and absence of exposure to oxytocin (P = .033) were associated independently with severe injury with 74.3% sensitivity and 74.4% specificity. Conclusion Worsening metabolic acidosis at birth, longer time to spontaneous respirations, and lack of exposure to oxytocin correlated with severe brain injury in neonates who were treated with whole-body hypothermia. These risk factors may help quickly identify neonatal candidates for time-sensitive investigational therapies for brain neuroprotection. PMID:24657795

  5. Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study

    PubMed Central

    Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Bardhan, Pradip Kumar; Faruque, Abu S. G.; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Das, Sumon Kumar; Hossain, Md Iqbal; Ahmed, Tahmeed

    2015-01-01

    Background In developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM) children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children. Methods In this retrospective case-control study SAM children aged 0–59 months, admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50) with those without severe sepsis (controls = 354). Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline. Results The case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons). Conclusion and Significance We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case

  6. Inducing subacute ruminal acidosis in lactating dairy cows.

    PubMed

    Krause, K M; Oetzel, G R

    2005-10-01

    Data from experiments in which subacute ruminal acidosis (SARA) was induced in lactating dairy cows (days in milk = 154 +/- 118) were evaluated to investigate the effectiveness of the induction protocol and its effect on production outcomes. For 13 cows in 3 trials, ruminal pH was measured continuously and recorded each minute; dry matter intake and milk yield were recorded daily. Milk composition data were obtained from 9 cows in 2 of these trials. The SARA induction protocol included 4 separate periods: 4 d of baseline [normal total mixed ration (TMR)], 1 d of 50% restricted feeding, 1 or 2 d of challenge feeding [addition of 3.5 or 4.6 kg of wheat-barley pellet (dry matter basis) to normal TMR], and 2 d of recovery measurements when feeding normal TMR. The SARA induction protocol lowered mean ruminal pH from 6.31 during the baseline period to 5.85 during the challenge period; pH remained below baseline level during the recovery period (6.16). Mean ruminal pH was highest (6.59) during the day of restricted feeding. Nadir ruminal pH decreased from baseline to challenge period (5.76 vs. 5.13). Hours below pH 5.6 increased from 1.10 to 8.26/d from baseline to challenge period and area below 5.6 (pH x min/d) increased from 15.0 to 190.3. Dry matter intake was not affected by SARA induction. Milk yield dropped from 35.2 kg/d during baseline to 31.7 k/d during the challenge period and did not return to baseline level during the recovery period (31.3 kg/d). No depression in milk fat percentage was observed when SARA was induced. Yield of fat was highest during the restricted feeding period (1.47 kg/d) and was lower during the recovery period than during the baseline period (1.12 vs. 1.31 kg/d). The protocol successfully induced SARA (low ruminal pH without signs of acute ruminal acidosis) on the challenge day. Milk yield was substantially reduced and did not recover within 2 d after the challenge. PMID:16162537

  7. Localization of a Gene for Autosomal Recessive Distal Renal Tubular Acidosis with Normal Hearing (rdRTA2) to 7q33-34

    PubMed Central

    Karet, Fiona E.; Finberg, Karin E.; Nayir, Ahmet; Bakkaloglu, Aysin; Ozen, Seza; Hulton, Sally A.; Sanjad, Sami A.; Al-Sabban, Essam A.; Medina, Juan F.; Lifton, Richard P.

    1999-01-01

    Summary Failure of distal nephrons to excrete excess acid results in the “distal renal tubular acidoses” (dRTA). Early childhood features of autosomal recessive dRTA include severe metabolic acidosis with inappropriately alkaline urine, poor growth, rickets, and renal calcification. Progressive bilateral sensorineural hearing loss (SNHL) is evident in approximately one-third of patients. We have recently identified mutations in ATP6B1, encoding the B-subunit of the collecting-duct apical proton pump, as a cause of recessive dRTA with SNHL. We now report the results of genetic analysis of 13 kindreds with recessive dRTA and normal hearing. Analysis of linkage and molecular examination of ATP6B1 indicated that mutation in ATP6B1 rarely, if ever, accounts for this phenotype, prompting a genomewide linkage search for loci underlying this trait. The results strongly supported linkage with locus heterogeneity to a segment of 7q33-34, yielding a maximum multipoint LOD score of 8.84 with 68% of kindreds linked. The LOD-3 support interval defines a 14-cM region flanked by D7S500 and D7S688. That 4 of these 13 kindreds do not support linkage to rdRTA2 and ATP6B1 implies the existence of at least one additional dRTA locus. These findings establish that genes causing recessive dRTA with normal and impaired hearing are different, and they identify, at 7q33-34, a new locus, rdRTA2, for recessive dRTA with normal hearing. PMID:10577919

  8. [Combined exchange transfusion and peritoneal dialysis treatment in a neonatal case of methylmalonic acidemia with severe hyperammonemia].

    PubMed

    Sanjurjo, P; Jaquotot, C; Vallo, A; Uriarte, R; Prats, J M; Ugarte, M; Rodríguez Soriano, J

    1982-10-01

    A case of methyl-malonic acidemia with severe neonatal hyperammoniemia is presented. Treatment during the first days of live with exchange-transfusion, with protein-free blood and peritoneal dialysis induced a decrease of blood ammonia values from 1360 to 270 micrograms/dl and the correction of systemic metabolic acidosis. Continuation of treatment by dietary means was followed by normalization of clinical status and almost total correction of the urinary excretion of methyl-malonic and propionic acids, but the patient died at 33 days of life due to an intercurrent infection. This case, together with a case previously reported of propionic acidemia with neonatal hyperammoniemia and prolonged survival, demonstrates that complementary treatment by means of exchange transfusion and peritoneal dialysis is mandatory in all cases of neonatal hyperammoniemia of metabolic origin, since survival without irreversible neurological damage is possible. PMID:6818879

  9. A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia.

    PubMed

    Kaneko, Kazuhiro; Yonemitsu, Yoshikazu; Fujii, Takaaki; Onimaru, Mitsuho; Jin, Chen-Hao; Inoue, Makoto; Hasegawa, Mamoru; Onohara, Toshihiro; Maehara, Yoshihiko; Sueishi, Katsuo

    2006-04-01

    The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed. PMID:16301206

  10. Energy metabolic disorder is a major risk factor in severe influenza virus infection: Proposals for new therapeutic options based on animal model experiments.

    PubMed

    Kido, Hiroshi; Indalao, Irene L; Kim, Hyejin; Kimoto, Takashi; Sakai, Satoko; Takahashi, Etsuhisa

    2016-09-01

    Severe influenza is characterized by cytokine storm and multiorgan failure. Influenza patients with underlying diseases show a rapid progression in disease severity. The major mechanism that underlies multiorgan failure during the progressive stage of infection, particularly in patients with underlying risk factors, is mitochondrial energy crisis. The relationship between the factors that determine infection severity, such as influenza virus, cytokines, cellular trypsin as a hemagglutinin processing protease for viral multiplication, accumulation of metabolic intermediates and ATP crisis in mitochondria, is termed the "influenza virus-cytokine-trypsin" cycle. This occurs during the initial stages of infection, and is interconnected with the "metabolic disorders-cytokine" cycle in the middle to late phase of infection. Experiments using animal models have highlighted the complex relationship between these two cycles. New treatment options have been proposed that target the ATP crisis and multiorgan failure during the late phase of infection, rather than antiviral treatments with neuraminidase inhibitors that work during the initial phase. These options are (i) restoration of glucose oxidation in mitochondria by diisopropylamine dichloroacetate, which inhibits infection-induced pyruvate dehydrogenase kinase 4 activity, and (ii) restoration of long-chain fatty acid oxidation in mitochondria by l-carnitine and bezafibrate, an agonist of peroxisome proliferation-activated receptors-β/δ, which transcriptionally upregulates carnitine palmitoyltransferase II. The latter is particularly effective in patients with influenza-associated encephalopathy who have thermolabile and short half-life compound variants of carnitine palmitoyltransferase II. PMID:27566378

  11. Medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome

    PubMed Central

    2012-01-01

    Background Medullary nephrocalcinosis and distal renal tubular acidosis are closely associated and each can lead to the other. These clinical entities are rare in patients with nephrotic syndrome and polycythaemia is an unusual finding in such patients. We describe the presence of medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome due to minimal change disease. Proposed mechanisms of polycythaemia in patients with nephrotic syndrome and distal renal tubular acidosis include, increased erythropoietin production and secretion of interleukin 8 which in turn stimulate erythropoiesis. Case presentation A 22 year old Sri Lankan Sinhala male with nephrotic syndrome due to minimal change disease was investigated for incidentally detected polycythaemia. Investigations revealed the presence of renal tubular acidosis type I and medullary nephrocalcinosis. Despite extensive investigation, a definite cause for polycythaemia was not found in this patient. Treatment with potassium and bicarbonate supplementation with potassium citrate led to correction of acidosis thereby avoiding the progression of nephrocalcinosis and harmful effects of chronic acidosis. Conclusion The constellation of clinical and biochemical findings in this patient is unique but the pathogenesis of erythrocytosis is not clearly explained. The proposed mechanisms for erythrocytosis in other patients with proteinuria include increased erythropoietin secretion due to renal hypoxia and increased secretion of interleukin 8 from the kidney. This case illustrates that there may exist hitherto unknown connections between tubular and glomerular dysfunction in patients with nephrotic syndrome. PMID:22834973

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

    PubMed Central

    Krapf, R

    1989-01-01

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

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

    PubMed

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

    2008-10-01

    The present study was performed to determine the prevalence of metabolic syndrome (MS) and its risk factors in obese children and adolescents. The study included 352 obese children and adolescents (body mass index [BMI] > or = 95th percentile) aged between 2 and 19 years. The diagnosis of MS was made according to the criteria adapted from the World Health Organization (WHO) and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines. BMI z-scores were calculated to assess the degree of obesity. The prevalence of MS and risk factors were determined. Determinants of MS were examined using regression analysis. The prevalence of MS was 41.8%. The age at onset of obesity, sedentary life-span, fasting blood levels of glucose, insulin, triglyceride, very-low-density lipoprotein (VLDL) cholesterol, and alanine aminotransferase (ALT) were higher, while levels of high-density lipoprotein (HDL) cholesterol and the number of actively spent hours were lower in cases with MS (p < 0.05). The most important determinant of MS was BMI z-score (r = 0.31, p < 0.0001). A one-point increase in BMI z-score yielded a 2-fold increase in the prevalence of MS. The prevalence of MS increased from 27.6% to 60.7% when the BMI z-score increased from 2.3 to 3.3. The risk of developing MS was 2.6-fold higher in cases with BMI z-score > 3 when compared to those with z-scores between 2 and 3. The results from this study indicate that, although the correlation between MS and the BMI z-score was weak, the BMI z-score may be an effective parameter in identifying obese children and adolescents at risk for MS. Screening the cases with BMI z-scores > or = 2 for MS is important for establishing an early diagnosis. PMID:18205011

  14. 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

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

    PubMed

    Kato, Kohtaro; Morita, Ikuo

    2011-08-01

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

  16. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children.

    PubMed

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-08-01

    Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05).Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern. PMID:27583886

  17. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children

    PubMed Central

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-01-01

    Abstract Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness. A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression. HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05). Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern. PMID:27583886

  18. Reversible lactic acidosis in a newborn with thiamine transporter-2 deficiency.

    PubMed

    Pérez-Dueñas, Belén; Serrano, Mercedes; Rebollo, Mónica; Muchart, Jordi; Gargallo, Eva; Dupuits, Celine; Artuch, Rafael

    2013-05-01

    Thiamine transporter-2 deficiency is a recessive disease caused by mutations in the SLC19A3 gene. Patients manifest acute episodes of encephalopathy; symmetric lesions in the cortex, basal ganglia, thalami or periaqueductal gray matter, and a dramatic response to biotin or thiamine. We report a 30-day-old patient with mutations in the SLC19A3 gene who presented with acute encephalopathy and increased level of lactate in the blood (8.6 mmol/L) and cerebrospinal fluid (7.12 mmol/L), a high excretion of α-ketoglutarate in the urine, and increased concentrations of the branched-chain amino acids leucine and isoleucine in the plasma. MRI detected bilateral and symmetric cortico-subcortical lesions involving the perirolandic area, bilateral putamina, and medial thalami. Some lesions showed low apparent diffusion coefficient values suggesting an acute evolution; others had high values likely to be subacute or chronic, most likely related to the perinatal period. After treatment with thiamine and biotin, irritability and opisthotonus disappeared, and the patient recovered consciousness. Biochemical disturbances also disappeared within 48 hours. After discontinuing biotin, the patient remained stable for 6 months on thiamine supplementation (20 mg/kg/day). The examination revealed subtle signs of neurologic sequelae, and MRI showed necrotic changes and volume loss in some affected areas. Our observations suggest that patients with thiamine transporter 2 deficiency may be vulnerable to metabolic decompensation during the perinatal period, when energy demands are high. Thiamine defects should be excluded in newborns and infants with lactic acidosis because prognosis largely depends on the time from diagnosis to thiamine supplementation. PMID:23589815

  19. Pathogenesis of sudden unexplained nocturnal death (lai tai) and endemic distal renal tubular acidosis.

    PubMed

    Nimmannit, S; Malasit, P; Chaovakul, V; Susaengrat, W; Vasuvattakul, S; Nilwarangkur, S

    1991-10-12

    Sudden unexplained nocturnal death (SUND), a disorder of unknown cause that occurs in otherwise healthy young adults, mostly male, during their sleep, is prevalent in the north-east region of Thailand, where it has been known for generations as lai tai. It occurs in the same population and area where hypokalaemic periodic paralysis (HPP), endemic distal renal tubular acidosis (EdRTA), and renal stones are also endemic. SUND has occurred in families of patients with EdRTA, and HPP can present as sudden onset of muscle parlysis with potentially lethal cardiac arrhythmias and respiratory failure from severe hypokalaemia occurring in the middle of the night. Surveys in which serum and urinary potassium have been measured indicate a deficiency of the electrolyte in the population. Potassium deficiency is probably the prime factor responsible for SUND and HPP. Low urinary citrate concentrations and the high prevalence of acidification defects in the population indicate that potassium deficiency is also responsible for the prevalence of EdRTA and for renal stones. PMID:1681278

  20. Contribution of nitric oxide to coronary vasodilation during hypercapnic acidosis.

    PubMed

    Gurevicius, J; Salem, M R; Metwally, A A; Silver, J M; Crystal, G J

    1995-01-01

    The present study was performed to evaluate the role of nitric oxide (NO) in coronary vasodilation during hypercapnic acidosis (HC). The left anterior descending coronary arteries of 17 anesthetized, open-chest dogs were perfused with normal arterial blood or with arterial blood equilibrated in an extracorporeal circuit with 90% O2-10% CO2 [arterial carbon dioxide tension (PaCO2) 72 +/- 3 mmHg, arterial pH 7.16 +/- 0.02]. Coronary perfusion pressure (CPP) was initially set at 100 mmHg. Coronary blood flow (CBF) was measured with a Doppler transducer. Studies were conducted under constant-pressure (variable CBF; n = 13) and constant-flow (variable CPP) conditions (n = 4). Steady-state changes in CBF (or CPP) during HC and during intracoronary infusions of acetylcholine (ACh, 20 micrograms/min), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP, 80 micrograms/min), an endothelium-independent vasodilator, were compared before and after intracoronary infusion of a NO synthase inhibitor, either NG-nitro-L-arginine methyl ester (L-NAME, 4.5 mg) or NG-monomethyl-L-arginine (L-NMMA, 30 mg). Under constant pressure, L-NAME blunted increases in CBF by HC (274 +/- 32 vs. 113 +/- 24%) and ACh (400 +/- 43 vs. 68 +/- 17%), whereas increases in CBF by SNP were not significantly affected (207 +/- 34 vs. 186 +/- 18%). Results with L-NMMA were similar. Under constant flow, L-NAME attenuated decreases in CPP by HC and ACh, whereas it had no significant effect on decreases in CPP by SNP. In conclusion, HC elicits release of NO from coronary vascular endothelium via a direct effect rather than secondary to an increased flow rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7530920

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

    PubMed

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

    2013-01-01

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

  2. A novel heterozygous mutation in the ATP6V0A4 gene encoding the V-ATPase a4 subunit in an adult patient with incomplete distal renal tubular acidosis.

    PubMed

    Imai, Eri; Kaneko, Shuzo; Mori, Takayasu; Okado, Tomokazu; Uchida, Shinichi; Tsukamoto, Yusuke

    2016-06-01

    A 40-year-old Japanese man who had a medical history of hypokalemic periodic paralysis 4 months prior was hospitalized to undergo a cholecystectomy. Hypokalemia, nephrocalcinosis and alkaluria suggesting distal renal tubular acidosis (dRTA) were detected, but metabolic acidosis was not evident. An ammonium chloride/furosemide-fludrocortisone/bicarbonate loading test demonstrated a remarkable disability in urinary H(+) excretion. A novel heterozygous mutation in the ATP6V0A4 gene encoding the vacuolar H(+)-ATPase (V-ATPase) a4 subunit p.S544L was detected. Among cases of V-ATPase a4 mutations, this is the first case in which a heterozygous mutation developed to an incomplete or latent form of dRTA. PMID:27274828

  3. A novel heterozygous mutation in the ATP6V0A4 gene encoding the V-ATPase a4 subunit in an adult patient with incomplete distal renal tubular acidosis

    PubMed Central

    Imai, Eri; Kaneko, Shuzo; Mori, Takayasu; Okado, Tomokazu; Uchida, Shinichi; Tsukamoto, Yusuke

    2016-01-01

    A 40-year-old Japanese man who had a medical history of hypokalemic periodic paralysis 4 months prior was hospitalized to undergo a cholecystectomy. Hypokalemia, nephrocalcinosis and alkaluria suggesting distal renal tubular acidosis (dRTA) were detected, but metabolic acidosis was not evident. An ammonium chloride/furosemide–fludrocortisone/bicarbonate loading test demonstrated a remarkable disability in urinary H+ excretion. A novel heterozygous mutation in the ATP6V0A4 gene encoding the vacuolar H+-ATPase (V-ATPase) a4 subunit p.S544L was detected. Among cases of V-ATPase a4 mutations, this is the first case in which a heterozygous mutation developed to an incomplete or latent form of dRTA. PMID:27274828

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

    PubMed

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

    2000-12-01

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

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

    PubMed

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

    2013-12-15

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

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

    PubMed Central

    2010-01-01

    Introduction The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism. Methods In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 μl/min, collecting samples at 60 minute intervals. Occult metabolic alterations were determined by calculating the lactate- pyruvate (L/P), lactate- glucose (L/Glc), and lactate- glutamate (L/Glu) ratios. Results Brain glucose was influenced by arterial blood glucose. Elevated L/P and L/Glc were significantly reduced at brain glucose above 1 mM, reaching lowest values at blood and brain glucose levels between 6-9 mM (P < 0.001). Lowest cerebral glutamate was measured at brain glucose 3-5 mM with a significant increase at brain glucose below 3 mM and above 6 mM. While L/Glu was significantly increased at low brain glucose levels, it was significantly decreased at brain glucose above 5 mM (P < 0.001). Insulin administration increased brain glutamate at low brain glucose, but prevented increase in L/Glu. Conclusions Arterial blood glucose levels appear to be optimal at 6-9 mM. While low brain glucose levels below 1 mM are detrimental, elevated brain glucose are to be targeted despite increased brain glutamate at brain glucose >5 mM. Pathogenity of elevated glutamate appears to be relativized by L/Glu and suggests to exclude insulin- induced brain injury. PMID:20141631

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  9. Seasonal influence over serum and urine metabolic markers in submariners during prolonged patrols

    PubMed Central

    Holy, Xavier; Bégot, Laurent; Renault, Sylvie; Butigieg, Xavier; André, Catherine; Bonneau, Dominique; Savourey, Gustave; Collombet, Jean-Marc

    2015-01-01

    Within the framework of earlier publications, we have consistently dedicated our investigations to eliciting the effects of both seasonal vitamin D deficiency and submarine-induced hypercapnia on serum parameters for acid–base balance and bone metabolism in submariners over a 2-month winter (WP) or summer (SP) patrols. The latest findings reported herein, contribute further evidence with regard to overall physiological regulations in the same submariner populations that underwent past scrutiny. Hence, urine and blood samples were collected in WP and SP submariners at control prepatrol time as well as on submarine patrol days 20, 41, and 58. Several urine and serum metabolic markers were quantified, namely, deoxypyridinoline (DPD), lactate, albumin, creatinine, nonesterified fatty acids (NEFA), and ionized sodium (Na+) or potassium (K+), with a view to assessing bone, muscle, liver, or kidney metabolisms. We evidenced bone metabolism alteration (urine DPD, calcium, and phosphorus) previously recorded in submarine crewmembers under prolonged patrols. We also highlighted transitory modifications in liver metabolism (serum albumin) occurring within the first 20 days of submersion. We further evidenced changes in submariners’ renal physiology (serum creatinine) throughout the entire patrol time span. Measurements of ionic homeostasis (serum Na+ and K+) displayed potential seasonal impact over active ionic pumps in submariners. Finally, there is some evidence that submersion provides beneficial conditions prone to fend off seasonal lactic acidosis (serum lactate) detected in WP submariners. PMID:26265754

  10. Blueberries and Metabolic Syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. Extracellular Acidosis Is a Novel Danger Signal Alerting Innate Immunity via the NLRP3 Inflammasome

    PubMed Central

    Rajamäki, Kristiina; Nordström, Tommy; Nurmi, Katariina; Åkerman, Karl E. O.; Kovanen, Petri T.; Öörni, Katariina; Eklund, Kari K.

    2013-01-01

    Local extracellular acidification has been demonstrated at sites of ischemia and inflammation. IL-1β is one of the key proinflammatory cytokines, and thus, its synthesis and secretion are tightly regulated. The NLRP3 (nucleotide-binding domain leucine-rich repeat containing family, pyrin domain containing 3) inflammasome complex, assembled in response to microbial components or endogenous danger signals, triggers caspase-1-mediated maturation and secretion of IL-1β. In this study, we explored whether acidic environment is sensed by immune cells as an inflammasome-activating danger signal. Human macrophages were exposed to custom cell culture media at pH 7.5–6.0. Acidic medium triggered pH-dependent secretion of IL-1β and activation of caspase-1 via a mechanism involving potassium efflux from the cells. Acidic extracellular pH caused rapid intracellular acidification, and the IL-1β-inducing effect of acidic medium could be mimicked by acidifying the cytosol with bafilomycin A1, a proton pump inhibitor. Knocking down the mRNA expression of NLRP3 receptor abolished IL-1β secretion at acidic pH. Remarkably, alkaline extracellular pH strongly inhibited the IL-1β response to several known NLRP3 activators, demonstrating bipartite regulatory potential of pH on the activity of this inflammasome. The data suggest that acidic environment represents a novel endogenous danger signal alerting the innate immunity. Low pH may thus contribute to inflammation in acidosis-associated pathologies such as atherosclerosis and post-ischemic inflammatory responses. PMID:23530046

  12. Epimural Indicator Phylotypes of Transiently-Induced Subacute Ruminal Acidosis in Dairy Cattle

    PubMed Central

    Wetzels, Stefanie U.; Mann, Evelyne; Metzler-Zebeli, Barbara U.; Pourazad, Poulad; Qumar, Muhammad; Klevenhusen, Fenja; Pinior, Beate; Wagner, Martin; Zebeli, Qendrim; Schmitz-Esser, Stephan

    2016-01-01

    The impact of a long-term subacute rumen acidosis (SARA) on the bovine epimural bacterial microbiome (BEBM) and its consequences for rumen health is poorly understood. This study aimed to investigate shifts in the BEBM during a long-term transient SARA model consisting of two concentrate-diet-induced SARA challenges separated by a 1-week challenge break. Eight cows were fed forage and varying concentrate amounts throughout the experiment. In total, 32 rumen papilla biopsies were taken for DNA isolation (4 sampling time points per cow: at the baseline before concentrate was fed, after the first SARA challenge, after the challenge break, and after the second SARA challenge). Ruminal pH was continuously monitored. The microbiome was determined using Illumina MiSeq sequencing of the 16S rRNA gene (V345 region). In total 1,215,618 sequences were obtained and clustered into 6833 operational taxonomic units (OTUs). Campylobacter and Kingella were the most abundant OTUs (16.5 and 7.1%). According to ruminal pH dynamics, the second challenge was more severe than the first challenge. Species diversity estimates and evenness increased during the challenge break compared to all other sampling time points (P < 0.05). During both SARA challenges, Kingella- and Azoarcus-OTUs decreased (0.5 and 0.4 fold-change) and a dominant Ruminobacter-OTU increased during the challenge break (18.9 fold-change; P < 0.05). qPCR confirmed SARA-related shifts. During the challenge break noticeably more OTUs increased compared to other sampling time points. Our results show that the BEBM re-establishes the baseline conditions slower after a SARA challenge than ruminal pH. Key phylotypes that were reduced during both challenges may help to establish a bacterial fingerprint to facilitate understanding effects of SARA conditions on the BEBM and their consequences for the ruminant host. PMID:26973642

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

    PubMed

    Schmitz, J P J; van Dijk, J P; Hilbers, P A J; Nicolay, K; Jeneson, J A L; Stegeman, D F

    2012-05-01

    Muscle fiber conduction velocity (MFCV) has often been shown to decrease during standardized fatiguing isometric contractions. However, several studies have indicated that the MFCV may remain constant during fatiguing dynamic exercise. It was investigated if these observations can be related to the absence of a large decrease in pH and if MFCV can be considered as a good indicator of acidosis, also during dynamic bicycle exercise. High-density surface electromyography (HDsEMG) was combined with read-outs of muscle energetics recorded by in vivo (31)P magnetic resonance spectroscopy (MRS). Measurements were performed during serial exhausting bouts of bicycle exercise at three different workloads. The HDsEMG recordings revealed a small and incoherent variation of MFCV during all high-intensity exercise bouts. (31)P MRS spectra revealed a moderate decrease in pH at the end of exercise (~0.3 units down to 6.8) and a rapid ancillary drop to pH 6.5 during recovery 30 s post-exercise. This additional degree of acidification caused a significant decrease in MFCV during cycling immediately after the rest period. From the data a significant correlation between MFCV and [H(+)] ([H(+)] = 10(-pH)) was calculated (p < 0.001, Pearson's R = -0.87). Our results confirmed the previous observations of MFCV remaining constant during fatiguing dynamic exercise. A constant MFCV is in line with a low degree of acidification, considering the presence of a correlation between pH and MFCV after further increasing acidification. PMID:21861110

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

    PubMed

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

    2013-08-15

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

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

    PubMed Central

    2014-01-01

    Context The last decades have provided insights into vitamin D physiology linked to glucose homeostasis. Uncertainties remain in obesity due to its intrinsic effects on vitamin D and glucose tolerance. Objectives To assess the relationship between vitamin D and glucose abnormalities in severely obese individuals previously unknown to suffer from abnormal glucose metabolism. Setting Tertiary care centre. Patients 524 obese patients (50.3 ± 14.9 yrs; BMI, 47.7 ± 7.3 kg/m2) screened by OGTT, HbA1c and the lipid profile. Vitamin D status was assessed by 25(OH)D3, PTH and electrolyte levels. 25(OH)D3 deficiency/insufficiency were set at 20 and 30 ng/ml, respectively. All comparative and regression analyses were controlled for age, BMI and gender. Results The prevalence of vitamin D deficiency/insufficiency and secondary hyperparathyroidism were 95% and 50.8%, respectively. Normal glucose tolerance (NGT), impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) were found in 37.8%, 40.5% and 21.7% of cases, respectively. Large variations in metabolic parameters were seen across categories of vitamin D status, but the only significant differences were found for C-peptide, tryglicerides, LDL- and HDL-cholesterol levels (p < 0.05 for all). The prevalence of vitamin D deficiency was documented to be slightly but significantly more frequent in glucose-intolerant patients (IFG + IGT + T2DM) compared to the -normotolerant counterpart (87% vs. 80%, p < 0.05). In partial correlation analyses, there was no association between vitamin D levels and glucose-related markers but for HbA1c (r = −0.091, p < 0.05), and both basal and OGTT-stimulated insulin levels (r = 0.097 and r = 0.099; p < 0.05 for all). Vitamin D levels were also correlated to HDL-cholesterol (r = 0.13, p = 0.002). Multivariate regression analysis inclusive of vitamin D, age, BMI, gender and fat mass as

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

    PubMed Central

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

    2012-01-01

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

  17. Primary gradient defect distal renal tubular acidosis presenting as hypokalaemic periodic paralysis.

    PubMed

    Koul, P A; Wahid, A; Bhat, F A

    2005-07-01

    A 45 year old man presented with recurrent hypokalaemic paralysis. Laboratory investigations revealed renal tubular acidosis as the cause of the hypokalaemia, and dynamic tubular studies suggested a gradient defect as the underlying cause. The patient had associated dextrocardia. To our knowledge, this is the first report of this condition. PMID:15983101

  18. Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin

    PubMed Central

    McAleer, Maeve A.; Pohler, Elizabeth; Smith, Frances J.D.; Wilson, Neil J.; Cole, Christian; MacGowan, Stuart; Koetsier, Jennifer L.; Godsel, Lisa M.; Harmon, Robert M.; Gruber, Robert; Crumrine, Debra; Elias, Peter M.; McDermott, Michael; Butler, Karina; Broderick, Annemarie; Sarig, Ofer; Sprecher, Eli; Green, Kathleen J.; McLean, W.H. Irwin; Irvine, Alan D.

    2015-01-01

    Background Severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 gene (DSG1). To date, only 3 families have been reported. Objective We studied a new case of SAM syndrome known to have no mutations in DSG1 to detail the clinical, histopathologic, immunofluorescent, and ultrastructural phenotype and to identify the underlying molecular mechanisms in this rare genodermatosis. Methods Histopathologic, electron microscopy, and immunofluorescent studies were performed. Whole-exome sequencing data were interrogated for mutations in desmosomal and other skin structural genes, followed by Sanger sequencing of candidate genes in the patient and his parents. Results No mutations were identified in DSG1; however, a novel de novo heterozygous missense c.1757A>C mutation in the desmoplakin gene (DSP) was identified in the patient, predicting the amino acid substitution p.His586Pro in the desmoplakin polypeptide. Conclusions SAM syndrome can be caused by mutations in both DSG1 and DSP. Knowledge of this genetic heterogeneity is important for both analysis of patients and genetic counseling of families. This condition and these observations reinforce the importance of heritable skin barrier defects, in this case desmosomal proteins, in the pathogenesis of atopic disease. PMID:26073755

  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. Spermatozoa: models for studying regulatory aspects of energy metabolism.

    PubMed

    Kamp, G; Büsselmann, G; Lauterwein, J

    1996-05-15

    Spermatozoa are highly specialized cells, and they offer advantages for studying several basic aspects of metabolic control such as the role of adenosine triphosphate-(ATP)-homeostasis for cell function, the mechanisms of fatigue and metabolic depression, the metabolic channelling through the cytoplasm and the organization and regulation of glycolytic enzymes. Spermatozoa of four species with different reproductive modes are introduced and the first results are presented: Spermatozoa of the marine worm Arenicola marina are well adapted to external fertilization in sea water with fluctuating oxygen tension: they are motile for several hours in oxygen-free sea water, even when the ATP level is dramatically reduced. Anaerobic ATP production occurs by alanine, acetate and propionate fermentation probably by the same pathways known from somatic cells of this species. Under aerobic conditions the phosphagen system might function like a shuttle for energy-rich phosphate from mitochondria to the dynein-ATPases. Storage of turkey and carp spermatozoa for several hours without exogenous substrates and oxygen results in the degradation of phosphocreatine and ATP to inorganic phosphate and adenosine monophosphate (AMP), respectively. Despite low energy charges, stored spermatozoa of both species are capable of progressive movements. In carp spermatozoa fatigue of motility is not accompanied by the dramatic acidosis one discusses as an important effect in muscle fatigue. Energy metabolism of boar spermatozoa is typically based on glycolysis consuming extracellular carbohydrates and producing lactate and protons. The sperm seem to tolerate low intracellular pH (< 6.5). The lack of a phosphagen system (no energy shuttle from mitochondria to the distal dynein-ATPases) is probably compensated by a high glycolytic ATP-production in the mitochondria-free piece of the flagellum. PMID:8641386

  1. [Distal renal tubular acidosis: report of 3 cases].

    PubMed

    Guibaud, P; Parchoux, B; Langue, J; Bouissou, F; Barthe, P; Larbre, F

    1979-06-01

    Three observations of R.T.A. with nerve deafness are reported. Case 1 and 2 concern consanguinous brothers whose parents are not affected, which confirm the syndrom as an autosomal recessive entity. The third, sporadic, case relates to a 13-year-old non consanguinous girl. Metabolic abnormalities and renal evolution with nephrocalcinosis was such as in Albright disease. However a progressive nerve deafness makes distinction. The authors underline the importance of this sometimes difficult distinction for genetic counseling. PMID:541679

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

    PubMed Central

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

    2012-01-01

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

  3. Severe systemic intoxication following triclopyr-TEA ingestion.

    PubMed

    Kyong, Yeon Y; Lee, Kyoung U; Choi, Kyoung H

    2010-11-01

    We report a case of triclopyr ingestion, a herbicide that acts via the auxin system in plants. It is classified as low-toxicity herbicide. The patient ingested this product and developed metabolic acidosis and coma with cardiovascular impairment. Echocardiography and elevated Troponin T and CK MB with prolongation of QTc suggested direct myocardial toxicity. The patient was extubated 57 h after ingestion, and he recovered completely. This case illustrates the potential acute toxicity of this agent in humans. PMID:21171852

  4. [A case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) with progressive cytochrome c oxidase deficiency].

    PubMed

    Sumi, K; Nagaura, T; Itagaki, Y; Inui, K; Abe, J

    1989-07-01

    We report a 9 year-old boy with MELAS. High dosed oral thiamine administration and high fat diet induced remarkable neurological and biochemical improvement. His mother had episodic headaches and hemiplegia, probably MELAS. He complained muscle weakness and repeated episodes of vomiting started from 2 years of age. High levels of serum lactate and pyruvate were recognized, but with no metabolic acidosis. He developed generalized muscle weakness, growth retardation, generalized convulsions and stroke-like episodes at 5 years old. Optic nerve atrophy and mental retardation gradually appeared. A muscle biopsy at 5 years old revealed numerous ragged-red fibers with excess accumulation of lipid droplets and glycogen particles. Scattered fibers had no cytochrome c oxidase (CCO) activity representing focal CCO deficiency. An electron microscopy showed markedly increased number of giant mitochondria filled with markedly proliferated complicated cristae. Pyruvate dehydrogenase complex level in the fibroblasts was within normal ranges. Serum carnitine level was normal. With oral administration of thiamine hydrochloride (1000 mg) and high fat diet (60-70%), muscle weakness improved, and lactate and pyruvate levels in the serum reduced to normal ranges, whereas the mental deterioration, muscle atrophy, pes cavus progressed very slowly. He died from cardiac and renal failures at 9 years old. Autopsied muscles showed a marked decrease in cytochrome c oxidase activity (biochemically 12.8% of the normal level), and almost all muscle fibers had no cytochrome c oxidase activity histochemically. The progression of the MELAS was probably in parallel with the decrease in CCO activity. PMID:2553313

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic?

    PubMed Central

    de Lima, Lúcio Flávio Peixoto

    2016-01-01

    Despite the advances made in monitoring and treatment of sepsis and septic shock, many septic patients ultimately develop multiple organ dysfunction (MODS) and die, suggesting that other players are involved in the pathophysiology of this syndrome. Mitochondrial dysfunction occurs early in sepsis and has a central role in MODS development. MODS severity and recovery of mitochondrial function have been associated with survival. In recent clinical and experimental investigations, mitochondrion-target therapy for sepsis and septic shock has been suggested to reduce MODS severity and mortality. This intervention, which might be named “metabolic resuscitation”, would lead to improved mitochondrial activity afforded by pharmacological and nutritional agents. Of particular interest in this therapeutic strategy is thiamine, a water-soluble vitamin that plays an essential role in cellular energy metabolism. Critical illness associated with hypermetabolic states may predispose susceptible individuals to the development of thiamine deficiency, which is not usually identified by clinicians as a source of lactic acidosis. The protective effects of thiamine on mitochondrial function may justify supplementation in septic patients at risk of deficiency. Perspectives of supplementation with other micronutrients (ascorbic acid, tocopherol, selenium and zinc) and potential metabolic resuscitators [coenzyme Q10 (CoQ10), cytochrome oxidase (CytOx), L-carnitine, melatonin] to target sepsis-induced mitochondrial dysfunction are also emerging. Metabolic resuscitation may probably be a safe and effective strategy in the treatment of septic shock in the future. However, until then, preliminary investigations should be replicated in further researches for confirmation. Better identification of groups of patients presumed to benefit clinically by a certain intervention directed to “mitochondrial resuscitation” are expected to increase driven by genomics and metabolomics. PMID:27501325

  8. Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic?

    PubMed

    Leite, Heitor Pons; de Lima, Lúcio Flávio Peixoto

    2016-07-01

    Despite the advances made in monitoring and treatment of sepsis and septic shock, many septic patients ultimately develop multiple organ dysfunction (MODS) and die, suggesting that other players are involved in the pathophysiology of this syndrome. Mitochondrial dysfunction occurs early in sepsis and has a central role in MODS development. MODS severity and recovery of mitochondrial function have been associated with survival. In recent clinical and experimental investigations, mitochondrion-target therapy for sepsis and septic shock has been suggested to reduce MODS severity and mortality. This intervention, which might be named "metabolic resuscitation", would lead to improved mitochondrial activity afforded by pharmacological and nutritional agents. Of particular interest in this therapeutic strategy is thiamine, a water-soluble vitamin that plays an essential role in cellular energy metabolism. Critical illness associated with hypermetabolic states may predispose susceptible individuals to the development of thiamine deficiency, which is not usually identified by clinicians as a source of lactic acidosis. The protective effects of thiamine on mitochondrial function may justify supplementation in septic patients at risk of deficiency. Perspectives of supplementation with other micronutrients (ascorbic acid, tocopherol, selenium and zinc) and potential metabolic resuscitators [coenzyme Q10 (CoQ10), cytochrome oxidase (CytOx), L-carnitine, melatonin] to target sepsis-induced mitochondrial dysfunction are also emerging. Metabolic resuscitation may probably be a safe and effective strategy in the treatment of septic shock in the future. However, until then, preliminary investigations should be replicated in further researches for confirmation. Better identification of groups of patients presumed to benefit clinically by a certain intervention directed to "mitochondrial resuscitation" are expected to increase driven by genomics and metabolomics. PMID:27501325

  9. Prevalence and severity of disordered mineral metabolism in patients with chronic kidney disease: A study from a tertiary care hospital in India

    PubMed Central

    Vikrant, Sanjay; Parashar, Anupam

    2016-01-01

    Background: Disordered mineral metabolism is common complications of chronic kidney disease (CKD). However, there are limited data on the pattern of these disturbances in Indian CKD population. Materials and Methods: This was a prospective observational study of CKD-mineral and bone disorder (CKD-MBD) over a period of 3 years. The biochemical markers of CKD-MBD, namely, calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone (iPTH), and 25-hydoxyvitamin Vitamin D3 (25OHD), were measured in newly diagnosed CKD Stage 3–5 and prevalent CKD Stage 5D adult patients. Results: A total of 462 patients of CKD Stage 3–5D were studied. The frequency of various biochemical abnormalities was hypocalcemia (23.8%), hypercalcemia (5.4%), hypophosphatemia (2.8%), hyperphosphatemia (55.4%), raised alkaline phosphatase (56.9%), secondary hyperparathyroidism (82.7%), and hypoparathyroidism (1.5%). 25OHD was done in 335 (72.5%) patients and 90.4% were found to have Vitamin D deficiency. About 70.6% of the patients had iPTH levels were above kidney disease outcomes quality initiative (KDOQI) target range. Nondiabetic CKD as compared to diabetic CKD had a higher alkaline phosphatase (P = 0.016), a higher iPTH (P = 0.001) a higher proportion of patients with iPTH above KDOQI target range (P = 0.09), and an elevated alkaline phosphatase (P = 0.004). The 25OHD levels were suggestive of severe Vitamin D deficiency in 33.7%, Vitamin D deficiency in 45.4%, and Vitamin D insufficiency in 11.3% patients. There was a significant positive correlation between iPTH with alkaline phosphatase (r = 0.572, P = 0.001), creatinine (r = 0.424, P = 0.001), and phosphorus (r = 0.241, P = 0.001) and a significant negative correlation with hemoglobin (r = −0.325, 0.001), age (r = −0.169, P = 0.002), and 25OHD (r = −0.126, P = 0.021). On multivariate logistic regression analysis, an elevated alkaline phosphatase was a significant predictor of hyperparathyroidism (odds ratio 9.7, 95

  10. 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

  11. A triad of linezolid toxicity: hypoglycemia, lactic acidosis, and acute pancreatitis

    PubMed Central

    Johnson, P. Connor; Phillips, Kristy M.; O'Donnell, Walter J.

    2015-01-01

    We present a case of suspected linezolid toxicity in a 34-year-old man with sickle cell disease and line-related vancomycin-resistant enterococcal bacteremia and tricuspid valve endocarditis. The patient developed sudden-onset hypoglycemia, lactic acidosis, and acute pancreatitis 11 days after initiation of linezolid. All adverse effects quickly resolved with drug cessation. The pathophysiology underlying this triad of linezolid toxicity is unclear, but may be related to mitochondrial dysfunction. PMID:26424943

  12. Chronic acidosis in the tumour microenvironment selects for overexpression of LAMP2 in the plasma membrane

    PubMed Central

    Damaghi, Mehdi; Tafreshi, Narges K.; Lloyd, Mark C.; Sprung, Robert; Estrella, Veronica; Wojtkowiak, Jonathan W.; Morse, David L.; Koomen, John M.; Bui, Marilyn M.; Gatenby, Robert A; Gillies, Robert J

    2015-01-01

    Early cancers are avascular and hence, profoundly acidic. Pre-malignant cells must adapt to acidosis to thrive in this hostile microenvironment. Here, we investigate MCF-7 cells that are adapted to grow in acidic conditions using SILAC proteomics and we reveal a significant upregulation of lysosomal proteins. Prominent among these is LAMP2 that functions to protect lysosomal membranes from acid proteolysis. LAMP2 upregulation by acidosis is confirmed both in vitro and in vivo. Furthermore, we show that the depletion of LAMP2 is sufficient to increase acidosis-mediated toxicity. In breast cancer patient samples, there is a high correlation of LAMP2 mRNA and protein expression with progression. We also observe that LAMP2 is located at the plasma membrane in clinical samples and this redistribution is acid-induced in vitro. Our findings suggest a potential adaptive mechanism, wherein cells chronically exposed to an acidic environment translocate lysosomal proteins to their surface, thus protecting the plasmalemma from acid-induced hydrolysis. PMID:26658462

  13. Diabetes Stimulates Osteoclastogenesis by Acidosis-Induced Activation of Transient Receptor Potential Cation Channels.

    PubMed

    Reni, Carlotta; Mangialardi, Giuseppe; Meloni, Marco; Madeddu, Paolo

    2016-01-01

    Patients with type 1 diabetes have lower bone mineral density and higher risk of fractures. The role of osteoblasts in diabetes-related osteoporosis is well acknowledged whereas the role of osteoclasts (OCLs) is still unclear. We hypothesize that OCLs participate in pathological bone remodeling. We conducted studies in animals (streptozotocin-induced type 1 diabetic mice) and cellular models to investigate canonical and non-canonical mechanisms underlying excessive OCL activation. Diabetic mice show an increased number of active OCLs. In vitro studies demonstrate the involvement of acidosis in OCL activation and the implication of transient receptor potential cation channel subfamily V member 1 (TRPV1). In vivo studies confirm the establishment of local acidosis in the diabetic bone marrow (BM) as well as the ineffectiveness of insulin in correcting the pH variation and osteoclast activation. Conversely, treatment with TRPV1 receptor antagonists re-establishes a physiological OCL availability. These data suggest that diabetes causes local acidosis in the BM that in turn increases osteoclast activation through the modulation of TRPV1. The use of clinically available TRPV1 antagonists may provide a new means to combat bone problems associated with diabetes. PMID:27468810

  14. Diabetes Stimulates Osteoclastogenesis by Acidosis-Induced Activation of Transient Receptor Potential Cation Channels

    PubMed Central

    Reni, Carlotta; Mangialardi, Giuseppe; Meloni, Marco; Madeddu, Paolo

    2016-01-01

    Patients with type 1 diabetes have lower bone mineral density and higher risk of fractures. The role of osteoblasts in diabetes-related osteoporosis is well acknowledged whereas the role of osteoclasts (OCLs) is still unclear. We hypothesize that OCLs participate in pathological bone remodeling. We conducted studies in animals (streptozotocin-induced type 1 diabetic mice) and cellular models to investigate canonical and non-canonical mechanisms underlying excessive OCL activation. Diabetic mice show an increased number of active OCLs. In vitro studies demonstrate the involvement of acidosis in OCL activation and the implication of transient receptor potential cation channel subfamily V member 1 (TRPV1). In vivo studies confirm the establishment of local acidosis in the diabetic bone marrow (BM) as well as the ineffectiveness of insulin in correcting the pH variation and osteoclast activation. Conversely, treatment with TRPV1 receptor antagonists re-establishes a physiological OCL availability. These data suggest that diabetes causes local acidosis in the BM that in turn increases osteoclast activation through the modulation of TRPV1. The use of clinically available TRPV1 antagonists may provide a new means to combat bone problems associated with diabetes. PMID:27468810

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

    PubMed Central

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

    2012-01-01

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

  16. Diffuse large B-cell lymphoma: A metabolic disorder?

    PubMed Central

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

    2013-01-01

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

  17. Mind the gap: a case of severe methanol intoxication.

    PubMed

    Nazir, Salik; Melnick, Stephen; Ansari, Shabana; Kanneh, Haitham T

    2016-01-01

    We report a case of a 37-year-old woman with non-insulin-dependent diabetes on sitagliptin, an alcohol abuser who was brought unresponsive to the emergency department of our hospital. On arrival, the patient was intubated and mechanically ventilated due to a low Glasgow Coma score of 3/15. Initial laboratory testing identified profound high anion gap metabolic acidosis. Owing to the dubious circumstances and the depth of acidosis, methanol and ethylene glycol intoxication was suspected. Further evaluation revealed a significantly increased serum osmolal gap. Pending volatile compound screen, fomepizole was started and urgent haemodialysis undertaken. Subsequent brain MRI identified changes in putamen of bilateral basal ganglia, suggestive of methanol intoxication. The patient was later found to have an initial methanol level of 237 mg/dL. She was successfully extubated on day 2 of hospitalisation, with residual cognitive and visual deficits. PMID:26917798

  18. Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis

    PubMed Central

    Karet, F. E.; Gainza, F. J.; Györy, A. Z.; Unwin, R. J.; Wrong, O.; Tanner, M. J. A.; Nayir, A.; Alpay, H.; Santos, F.; Hulton, S. A.; Bakkaloglu, A.; Ozen, S.; Cunningham, M. J.; di Pietro, A.; Walker, W. G.; Lifton, R. P.

    1998-01-01

    Primary distal renal tubular acidosis (dRTA) is characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Kindreds showing either autosomal dominant or recessive transmission are described. Mutations in the chloride-bicarbonate exchanger AE1 have recently been reported in four autosomal dominant dRTA kindreds, three of these altering codon Arg589. We have screened 26 kindreds with primary dRTA for mutations in AE1. Inheritance was autosomal recessive in seventeen kindreds, autosomal dominant in one, and uncertain due to unknown parental phenotype or sporadic disease in eight kindreds. No mutations in AE1 were detected in any of the autosomal recessive kindreds, and analysis of linkage showed no evidence of linkage of recessive dRTA to AE1. In contrast, heterozygous mutations in AE1 were identified in the one known dominant dRTA kindred, in one sporadic case, and one kindred with two affected brothers. In the dominant kindred, the mutation Arg-589/Ser cosegregated with dRTA in the extended pedigree. An Arg-589/His mutation in the sporadic case proved to be a de novo mutation. In the third kindred, affected brothers both have an intragenic 13-bp duplication resulting in deletion of the last 11 amino acids of AE1. These mutations were not detected in 80 alleles from unrelated normal individuals. These findings underscore the key role of Arg-589 and the C terminus in normal AE1 function, and indicate that while mutations in AE1 cause autosomal dominant dRTA, defects in this gene are not responsible for recessive disease. PMID:9600966

  19. Severe malaria in children: A descriptive report from Kinshasa, the Democratic Republic of Congo.

    PubMed

    Kunuanunua, Thomas S; Nsibu, Célestin N; Bodi, Joseph M; Tshibola, Thérèse K; Makusi Bura, Mimy; Magoga, Kumbundu; Ekila, Mathilde B; Situakibanza, Hypolite T; Aloni, Michel N

    2015-08-01

    The decline of susceptibility of Plasmodium falciparum to chloroquine and sulfadoxine-pyrimethamine resulted in the change of drug policy. This policy has probably changed the facies of the severe form of malaria. A prospective study was conducted in Kinshasa, the Democratic Republic of Congo. Data on children aged ≤13 years, diagnosed with severe malaria were analyzed. In total, 378 children were included with an overall median age of 8 years (age range: 1-13 years). Dark urine was seen in 25.1% of cases. Metabolic acidosis (85.2%), hypoglycemia (62.2%) and hemoglobin ≤5 g/dl (39.1%) were the common laboratories features. Severe malaria anemia, cerebral malaria and Blackwater fever (BWF) were found in 39.1, 30.1 and 25.4%, respectively. Mortality rate was 4%. BWF emerges as a frequent form of severe malaria in our midst. Availing artemisin-based combination treatments in the health care system is a priority to reduce the incidence of BWF in our environment. PMID:25957436

  20. 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 (τm5U) 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

  1. An in vitro analysis of the effect of acidosis on coagulation in chronic disease states - a thromboelastograph study.

    PubMed

    White, Hayden; Bird, Robert; Sosnowski, Kellie; Jones, Mark

    2016-06-01

    Thrombosis is a complication of many chronic illnesses. Chronic obstructive pulmonary disease (COPD) and diabetes mellitus are common medical conditions frequently associated with a hypercoagulable state. Acidaemia has been shown to reduce coagulation. COPD and diabetes mellitus during acute deterioration can present with a severe acidaemia. The impact of this acidaemia on coagulation is poorly studied. Patients presenting with a diagnosis of diabetic ketoacidosis or type II respiratory failure from COPD and a pH of less than 7.2 were included in our study. A coagulation screen and a thromboelastograph (TEG) were performed on admission and 24 hours later. The mean pH on admission was 7.07 and mean base excess was -16.3. The activated partial thromboplastin time was associated with pH change but remained within the normal range (26-41 s). All other coagulation and TEG parameters failed to show evidence of association (p>0.05). In the two models of non-haemorrhagic acidosis investigated, coagulation was not altered by the changes in pH. More work is needed to understand the complex relationship between factors affecting coagulation in individual disease processes. PMID:27251911

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

    PubMed

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

    1998-12-15

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

  3. Thiamine Deficiency in Tropical Pediatrics: New Insights into a Neglected but Vital Metabolic Challenge

    PubMed Central

    Hiffler, Laurent; Rakotoambinina, Benjamin; Lafferty, Nadia; Martinez Garcia, Daniel

    2016-01-01

    In humans, thiamine is a micronutrient prone to depletion that may result in severe clinical abnormalities. This narrative review summarizes current knowledge on thiamine deficiency (TD) and bridges the gap between pathophysiology and clinical presentation by integrating thiamine metabolism at subcellular level with its function to vital organs. The broad clinical spectrum of TD is outlined, with emphasis on conditions encountered in tropical pediatric practice. In particular, TD is associated with type B lactic acidosis and classic forms of beriberi in children, but it is often unrecognized. Other severe acute conditions are associated with hypermetabolism, inducing a functional TD. The crucial role of thiamine in infant cognitive development is also highlighted in this review, along with analysis of the potential impact of TD in refeeding syndrome during severe acute malnutrition (SAM). This review aims to increase clinical awareness of TD in tropical settings where access to diagnostic tests is poor, and advocates for an early therapeutic thiamine challenge in resource-limited settings. Moreover, it provides evidence for thiamine as treatment in critical conditions requiring metabolic resuscitation, and gives rationale to the consideration of increased thiamine supplementation in therapeutic foods for malnourished children. PMID:27379239

  4. Thiamine Deficiency in Tropical Pediatrics: New Insights into a Neglected but Vital Metabolic Challenge.

    PubMed

    Hiffler, Laurent; Rakotoambinina, Benjamin; Lafferty, Nadia; Martinez Garcia, Daniel

    2016-01-01

    In humans, thiamine is a micronutrient prone to depletion that may result in severe clinical abnormalities. This narrative review summarizes current knowledge on thiamine deficiency (TD) and bridges the gap between pathophysiology and clinical presentation by integrating thiamine metabolism at subcellular level with its function to vital organs. The broad clinical spectrum of TD is outlined, with emphasis on conditions encountered in tropical pediatric practice. In particular, TD is associated with type B lactic acidosis and classic forms of beriberi in children, but it is often unrecognized. Other severe acute conditions are associated with hypermetabolism, inducing a functional TD. The crucial role of thiamine in infant cognitive development is also highlighted in this review, along with analysis of the potential impact of TD in refeeding syndrome during severe acute malnutrition (SAM). This review aims to increase clinical awareness of TD in tropical settings where access to diagnostic tests is poor, and advocates for an early therapeutic thiamine challenge in resource-limited settings. Moreover, it provides evidence for thiamine as treatment in critical conditions requiring metabolic resuscitation, and gives rationale to the consideration of increased thiamine supplementation in therapeutic foods for malnourished children. PMID:27379239

  5. The importance of hyporheic sediment respiration in several mid-order Michigan rivers: Comparison between methods in estimates of lotic metabolism

    USGS Publications Warehouse

    Uzarski, D.G.; Stricker, C.A.; Burton, T.M.; King, D. K.; Steinman, A.D.

    2004-01-01

    Metabolism was measured in four Michigan streams, comparing estimates made using a flow-through chamber designed to include the hyporheic zone to a 20 cm depth and a traditional closed chamber that enclosed to a 5 cm depth. Mean levels of gross primary productivity and community respiration were consistently greater in the flow-through chamber than the closed chamber in all streams. Ratios of productivity to respiration (P/R) were consistently greater in the closed chambers than the flow-through chambers. P/R ratios were consistently <1 in all streams when estimated with flow-through chambers, suggesting heterotrophic conditions. Maintenance of stream ecosystem structure and function therefore is dependent on subsidies either from the adjacent terrestrial system or upstream sources. Our results suggest that stream metabolism studies that rely on extrapolation of closed chambers to the whole reach will most likely underestimate gross primary productivity and community respiration.

  6. Cadmium toxicity in diazotrophic Anabaena spp. adjudged by hasty up-accumulation of transporter and signaling and severe down-accumulation of nitrogen metabolism proteins.

    PubMed

    Singh, Prashant Kumar; Shrivastava, Alok Kumar; Chatterjee, Antra; Pandey, Sarita; Rai, Snigdha; Singh, Shilpi; Rai, L C

    2015-09-01

    Present study demonstrates interspecies variation in proteome and survival strategy of three Anabaena species i.e., Anabaena L31, Anabaena sp. PCC 7120 and Anabaena doliolum subjected to respective LC50 doses of Cd at 0, 1, 3, 5 and 7day intervals. The proteome coverage with 452 differentially accumulated proteins unveiled species and time specific expression and interaction network of proteins involved in important cellular functions. Statistical analysis of protein abundance across Cd-treated proteomes clustered their co-expression pattern into four groups viz., (i) early (days 1 and 3) accumulated proteins, (ii) proteins up-accumulated for longer duration, (iii) late (days 5 and 7) accumulated proteins, and (iv) mostly down-accumulated proteins. Appreciable growth of Cd treated A L31 over other two species may be ascribed to proteins contained in the first and second groups (belonging to energy and carbohydrate metabolism (TK, G6-PI, PGD, FBA, PPA, ATP synthase)), sulfur metabolism (GR, GST, PGDH, PAPS reductase, GDC-P, and SAM synthetase), fatty acid metabolism (AspD, PspA, SQD-1), phosphorous metabolism (PhoD, PstB and SQD1), molecular chaperones (Gro-EL, FKBP-type peptidylprolyl isomerase), and antioxidative defense enzymes (SOD-A, catalase). Anabaena sp. PCC 7120 harboring proteins largely from the third group qualified as a late accumulator and A. doliolum housing majority of proteins from the fourth group emerged as the most sensitive species. Thus early up-accumulation of transporter and signaling category proteins and drastic reduction of nitrogen assimilation proteins could be taken as a vital indicator of cadmium toxicity in Anabaena spp. This article is part of a Special Issue entitled: Proteomics in India. PMID:26021478

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

    SciTech Connect

    Conde, Vanessa R.; Oliveira, Pedro F.; 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. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression.

  8. Dynamic scenario of metabolic pathway adaptation in tumors and therapeutic approach.

    PubMed

    Peppicelli, Silvia; Bianchini, Francesca; Calorini, Lido

    2015-01-01

    Cancer cells need to regulate their metabolic program to fuel several activities, including unlimited proliferation, resistance to cell death, invasion and metastasis. The aim of this work is to revise this complex scenario. Starting from proliferating cancer cells located in well-oxygenated regions, they may express the so-called "Warburg effect" or aerobic glycolysis, meaning that although a plenty of oxygen is available, cancer cells choose glycolysis, the sole pathway that allows a biomass formation and DNA duplication, needed for cell division. Although oxygen does not represent the primary font of energy, diffusion rate reduces oxygen tension and the emerging hypoxia promotes "anaerobic glycolysis" through the hypoxia inducible factor-1α-dependent up-regulation. The acquired hypoxic phenotype is endowed with high resistance to cell death and high migration capacities, although these cells are less proliferating. Cells using aerobic or anaerobic glycolysis survive only in case they extrude acidic metabolites acidifying the extracellular space. Acidosis drives cancer cells from glycolysis to OxPhos, and OxPhos transforms the available alternative substrates into energy used to fuel migration and distant organ colonization. Thus, metabolic adaptations sustain different energy-requiring ability of cancer cells, but render them responsive to perturbations by anti-metabolic agents, such as inhibitors of glycolysis and/or OxPhos. PMID:25897425

  9. Dynamic scenario of metabolic pathway adaptation in tumors and therapeutic approach

    PubMed Central

    Peppicelli, Silvia; Bianchini, Francesca; Calorini, Lido

    2015-01-01

    Cancer cells need to regulate their metabolic program to fuel several activities, including unlimited proliferation, resistance to cell death, invasion and metastasis. The aim of this work is to revise this complex scenario. Starting from proliferating cancer cells located in well-oxygenated regions, they may express the so-called “Warburg effect” or aerobic glycolysis, meaning that although a plenty of oxygen is available, cancer cells choose glycolysis, the sole pathway that allows a biomass formation and DNA duplication, needed for cell division. Although oxygen does not represent the primary font of energy, diffusion rate reduces oxygen tension and the emerging hypoxia promotes “anaerobic glycolysis” through the hypoxia inducible factor-1α-dependent up-regulation. The acquired hypoxic phenotype is endowed with high resistance to cell death and high migration capacities, although these cells are less proliferating. Cells using aerobic or anaerobic glycolysis survive only in case they extrude acidic metabolites acidifying the extracellular space. Acidosis drives cancer cells from glycolysis to OxPhos, and OxPhos transforms the available alternative substrates into energy used to fuel migration and distant organ colonization. Thus, metabolic adaptations sustain different energy-requiring ability of cancer cells, but render them responsive to perturbations by anti-metabolic agents, such as inhibitors of glycolysis and/or OxPhos. PMID:25897425

  10. Important Role of FTO in the Survival of Rare Panresistant Triple-Negative Inflammatory Breast Cancer Cells Facing a Severe Metabolic Challenge

    PubMed Central

    Singh, Balraj; Kinne, Hannah E.; Milligan, Ryan D.; Washburn, Laura J.; Olsen, Mark; Lucci, Anthony

    2016-01-01

    We have previously shown that only 0.01% cells survive a metabolic challenge involving lack of glutamine in culture medium of SUM149 triple-negative Inflammatory Breast Cancer cell line. These cells, designated as SUM149-MA for metabolic adaptability, are resistant to chemotherapeutic drugs, and they efficiently metastasize to multiple organs in nude mice. We hypothesized that obesity-related molecular networks, which normally help in cellular and organismal survival under metabolic challenges, may help in the survival of MA cells. The fat mass and obesity-associated protein FTO is overexpressed in MA cells. Obesity-associated cis-acting elements in non-coding region of FTO regulate the expression of IRX3 gene, thus activating obesity networks. Here we found that IRX3 protein is significantly overexpressed in MA cells (5 to 6-fold) as compared to the parental SUM149 cell line, supporting our hypothesis. We also obtained evidence that additional key regulators of energy balance such as ARID5B, IRX5, and CUX1 P200 repressor could potentially help progenitor-like TNBC cells survive in glutamine-free medium. MO-I-500, a pharmacological inhibitor of FTO, significantly (>90%) inhibited survival and/or colony formation of SUM149-MA cells as compared to untreated cells or those treated with a control compound MO-I-100. Curiously, MO-I-500 treatment also led to decreased levels of FTO and IRX3 proteins in the SUM149 cells initially surviving in glutamine-free medium as compared to MO-I-100 treatment. Interestingly, MO-I-500 treatment had a relatively little effect on cell growth of either the SUM149 or SUM149-MA cell line when added to a complete medium containing glutamine that does not pose a metabolic challenge. Importantly, once selected and cultured in glutamine-free medium, SUM149-MA cells were no longer affected by MO-I-500 even in Gln-free medium. We conclude that panresistant MA cells contain interconnected molecular networks that govern developmental status and

  11. Important Role of FTO in the Survival of Rare Panresistant Triple-Negative Inflammatory Breast Cancer Cells Facing a Severe Metabolic Challenge.

    PubMed

    Singh, Balraj; Kinne, Hannah E; Milligan, Ryan D; Washburn, Laura J; Olsen, Mark; Lucci, Anthony

    2016-01-01

    We have previously shown that only 0.01% cells survive a metabolic challenge involving lack of glutamine in culture medium of SUM149 triple-negative Inflammatory Breast Cancer cell line. These cells, designated as SUM149-MA for metabolic adaptability, are resistant to chemotherapeutic drugs, and they efficiently metastasize to multiple organs in nude mice. We hypothesized that obesity-related molecular networks, which normally help in cellular and organismal survival under metabolic challenges, may help in the survival of MA cells. The fat mass and obesity-associated protein FTO is overexpressed in MA cells. Obesity-associated cis-acting elements in non-coding region of FTO regulate the expression of IRX3 gene, thus activating obesity networks. Here we found that IRX3 protein is significantly overexpressed in MA cells (5 to 6-fold) as compared to the parental SUM149 cell line, supporting our hypothesis. We also obtained evidence that additional key regulators of energy balance such as ARID5B, IRX5, and CUX1 P200 repressor could potentially help progenitor-like TNBC cells survive in glutamine-free medium. MO-I-500, a pharmacological inhibitor of FTO, significantly (>90%) inhibited survival and/or colony formation of SUM149-MA cells as compared to untreated cells or those treated with a control compound MO-I-100. Curiously, MO-I-500 treatment also led to decreased levels of FTO and IRX3 proteins in the SUM149 cells initially surviving in glutamine-free medium as compared to MO-I-100 treatment. Interestingly, MO-I-500 treatment had a relatively little effect on cell growth of either the SUM149 or SUM149-MA cell line when added to a complete medium containing glutamine that does not pose a metabolic challenge. Importantly, once selected and cultured in glutamine-free medium, SUM149-MA cells were no longer affected by MO-I-500 even in Gln-free medium. We conclude that panresistant MA cells contain interconnected molecular networks that govern developmental status and

  12. [A 38 years old female with inflammatory myofibroblastic tumor and lactic acidosis].

    PubMed

    Gorham, J; Liberale, G; Haydar, H Nasser; De Saint Aubain, N; Meert, A P

    2016-01-01

    Inflammatory myofibroblastic tumors (IMT) are rare tumors. They were originally described in the lung, but they have been now observed in many others locations, mainly abdominal and pelvic. These tumors are usually benign but their recurrent nature and the presence of an abnormality of chromosome band 2p23 in some of them, suggest that some lesions form a true tumor entity. Surgical excision as complete as possible is the gold standard treatment. We report the case of a 38 years old female, who presented a recurrent metastasizing inflammatory myofibroblastic tumor causing lactic acidosis and other biological abnormalities such as hypercalcemia, hypoalbuminemia, hypoglycemia, disseminated intravascular coagulation and inflammatory syndrome. PMID:27487696

  13. Primary Sjö-gren's syndrome presenting with distal, renal tubular acidosis and rhabdomyolysis.

    PubMed

    Prakash, E B S; Fernando, M E; Sathiyasekaran, Malathi; Bhoopathy, R M; Jayanth, J J; Samuel, J

    2006-12-01

    Primary Sjögren's syndrome (PSS) is rare in India. Clinically manifest renal disease in PSS is uncommon and is usually an autoimmune tubulointerstitial nephritis presenting with distal renal tubular acidosis (dRTA) or a urinary concentrating defect. Hypokalemic paralysis due to dRTA in PSS is rare but well documented in medical literature. Rhabdomyolysis as a consequence of hypokalemia in PSS is exceptional. We report a case of PSS with dRTA and rhabdomyolysis causing prolonged respiratory failure and quadriparesis. PMID:17334013

  14. Draft Genome Sequence of Lactobacillus delbrueckii Strain #22 Isolated from a Patient with Short Bowel Syndrome and Previous d-Lactic Acidosis and Encephalopathy.

    PubMed

    Domann, Eugen; Fischer, Florence; Glowatzki, Fabian; Fritzenwanker, Moritz; Hain, Torsten; Zechel-Gran, Silke; Giffhorn-Katz, Susanne; Neubauer, Bernd A

    2016-01-01

    d-Lactic acidosis with associated encephalopathy caused by overgrowth of intestinal lactic acid bacteria is a rarely diagnosed neurological complication of patients with short bowel syndrome. Here, we report the draft genome sequence of Lactobacillus delbrueckii strain #22 isolated from a patient with short bowel syndrome and previous d-lactic acidosis/encephalopathy. PMID:27469967

  15. Draft Genome Sequence of Lactobacillus delbrueckii Strain #22 Isolated from a Patient with Short Bowel Syndrome and Previous d-Lactic Acidosis and Encephalopathy

    PubMed Central

    Fischer, Florence; Glowatzki, Fabian; Fritzenwanker, Moritz; Hain, Torsten; Zechel-Gran, Silke; Giffhorn-Katz, Susanne; Neubauer, Bernd A.

    2016-01-01

    d-Lactic acidosis with associated encephalopathy caused by overgrowth of intestinal lactic acid bacteria is a rarely diagnosed neurological complication of patients with short bowel syndrome. Here, we report the draft genome sequence of Lactobacillus delbrueckii strain #22 isolated from a patient with short bowel syndrome and previous d-lactic acidosis/encephalopathy. PMID:27469967

  16. 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

  17. [Higher Brain Dysfunction in Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS)].

    PubMed

    Ichikawa, Hiroo

    2016-02-01

    Stroke-like episodes are one of the cardinal features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and occur in 84-99% of the patients. The affected areas detected on neuroimaging do not have classical vascular distribution, and involve predominantly the temporal, parietal and occipital lobes. Thus, the neurological symptoms including higher brain dysfunction correlate with this topographical distribution. In association with the occipital lobe involvement, the most frequent symptom is cortical blindness. Other symptoms have been occasionally reported in case reports: visual agnosia, prosopagnosia, cortical deafness, auditory agnosia, topographical disorientation, various types of aphasia, hemispatial neglect, and so on. On the other hand, cognitive decline associated with more diffuse brain impairment rather than with focal stroke-like lesions has been postulated. This condition is also known as mitochondrial dementia. Domains of cognitive dysfunction include abstract reasoning, verbal memory, visual memory, language (naming and fluency), executive or constructive functions, attention, and visuospatial function. Cognitive functions and intellectual abilities may decline from initially minimal cognitive impairment to dementia. To date, the neuropsychological and neurologic impairment has been reported to be associated with cerebral lactic acidosis as estimated by ventricular spectroscopic lactate levels. PMID:26873235

  18. 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

  19. Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions.

    PubMed

    Mashima, T; Sato, S; Sugimoto, Y; Tsuruo, T; Seimiya, H

    2009-01-01

    Extracellular acidosis (low pH) is a tumor microenvironmental stressor that has a critical function in the malignant progression and metastatic dissemination of tumors. To survive under stress conditions, tumor cells must evolve resistance to stress-induced toxicity. Acyl-CoA synthetase 5 (ACSL5) is a member of the ACS family, which converts fatty acid to acyl-CoA. ACSL5 is frequently overexpressed in malignant glioma, whereas its functional significance is still unknown. Using retrovirus-mediated stable gene transfer (gain of function) and small interfering RNA-mediated gene silencing (loss of function), we show here that ACSL5 selectively promotes human glioma cell survival under extracellular acidosis. ACSL5 enhanced cell survival through its ACS catalytic activity. To clarify the genome-wide changes in cell signaling pathways by ACSL5, we performed cDNA microarray analysis and identified an ACSL5-dependent gene expression signature. The analysis revealed that ACSL5 was critical to the expression of tumor-related factors including midkine (MDK), a heparin-binding growth factor frequently overexpressed in cancer. Knockdown of MDK expression significantly attenuated ACSL5-mediated survival under acidic state. These results indicate that ACSL5 is a critical factor for survival of glioma cells under acidic tumor microenvironment, thus providing novel molecular basis for cancer therapy. PMID:18806831

  20. Lactic acidosis

    MedlinePlus

    ... of Family Medicine, UW Medicine, School of Medicine, University of Washington, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, ... Injuries Browse the Encyclopedia A.D.A.M., ...

  1. Planned reoperation for severe trauma.

    PubMed Central

    Hirshberg, A; Mattox, K L

    1995-01-01

    OBJECTIVE: The authors review the physiologic basis, indications, techniques, and results of the planned reoperation approach to severe trauma. SUMMARY BACKGROUND DATA: Multivisceral trauma and exsanguinating hemorrhage lead to hypothermia, coagulopathy, and acidosis. Formal resections and reconstructions in these unstable patients often result in irreversible physiologic insult. A new surgical strategy addresses these physiologic concerns by staged control and repair of the injuries. METHOD: The authors review the literature. RESULTS: Indications for planned reoperation include avoidance of irreversible physiologic insult and inability to obtain direct hemostasis or formal abdominal closure. The three phases of the strategy include initial control, stabilization, and delayed reconstruction. Various techniques are used to obtain rapid temporary control of bleeding and hollow visceral spillage. Hypothermia, coagulopathy, and the abdominal compartment syndrome are major postoperative concerns. Definitive repair of the injuries is undertaken after stabilization. CONCLUSION: Planned reoperation offers a simple and effective alternative to the traditional surgical management of complex or multiple injuries in critically wounded patients. PMID:7618965

  2. Traumatic rhabdomyolysis from severe beating--experience of volume diuresis in 200 patients.

    PubMed

    Knottenbelt, J D

    1994-08-01

    Fluid loading with balanced salt solution (BSS) was carried out in 200 patients with extensive soft tissue injuries from severe beatings. Urinary volume and dipstick specific gravity testing were used to monitor renal function with administration of furosemide for persistent oliguria. Acute intrinsic renal failure (AIRF) occurred in 21 patients (10.5%) and five patients died (2.5%); two of hyperkalemia, two of sepsis and one of multiple organ failure. Significantly increased rates of AIRF and death were associated with injury-admission intervals of more than 12 hours, severe metabolic acidosis, low initial hemoglobin, heavy pigmenturia, and high serum creatine kinase (CK) levels. An increased serum creatinine/BUN ratio was noted in four of the five patients who died. An average of 7.5 L fluids was needed in non-AIRF patients to achieve adequate diuresis with a mean positive fluid balance of 4.7 L. No patient without pigmenturia developed AIRF. Balanced salt solution volume diuresis supplemented with furosemide as necessary appears to be safe and effective in preventing AIRF in soft tissue injuries sustained in beatings. PMID:8064919

  3. The Role of Plasma and Urine Metabolomics in Identifying New Biomarkers in Severe Newborn Asphyxia: A Study of Asphyxiated Newborn Pigs following Cardiopulmonary Resuscitation

    PubMed Central

    Sachse, Daniel; Solevåg, Anne Lee; Berg, Jens Petter; Nakstad, Britt

    2016-01-01

    Background Optimizing resuscitation is important to prevent morbidity and mortality from perinatal asphyxia. The metabolism of cells and tissues is severely disturbed during asphyxia and resuscitation, and metabolomic analyses provide a snapshot of many small molecular weight metabolites in body fluids or tissues. In this study metabolomics profiles were studied in newborn pigs that were asphyxiated and resuscitated using different protocols to identify biomarkers for subject characterization, intervention effects and possibly prognosis. Methods A total of 125 newborn Noroc pigs were anesthetized, mechanically ventilated and inflicted progressive asphyxia until asystole. Pigs were randomized to resuscitation with a FiO2 0.21 or 1.0, different duration of ventilation before initiation of chest compressions (CC), and different CC to ventilation ratios. Plasma and urine samples were obtained at baseline, and 2 h and 4 h after return of spontaneous circulation (ROSC, heart rate > = 100 bpm). Metabolomics profiles of the samples were analyzed by nuclear magnetic resonance spectroscopy. Results Plasma and urine showed severe metabolic alterations consistent with hypoxia and acidosis 2 h and 4 h after ROSC. Baseline plasma hypoxanthine and lipoprotein concentrations were inversely correlated to the duration of hypoxia sustained before asystole occurred, but there was no evidence for a differential metabolic response to the different resuscitation protocols or in terms of survival. Conclusions Metabolic profiles of asphyxiated newborn pigs showed severe metabolic alterations. Consistent with previously published reports, we found no evidence of differences between established and alternative resuscitation protocols. Lactate and pyruvate may have a prognostic value, but have to be independently confirmed. PMID:27529347

  4. 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

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

    PubMed

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

    2014-11-01

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

  6. Oral rehydration therapy: efficacy of sodium citrate equals to sodium bicarbonate for correction of acidosis in diarrhoea.

    PubMed Central

    Islam, M R; Samadi, A R; Ahmed, S M; Bardhan, P K; Ali, A

    1984-01-01

    Forty patients with moderate degrees of dehydration and acidosis because of acute watery diarrhoea were successfully treated randomly with either WHO recommended oral rehydration solution containing 2.5 g sodium bicarbonate or an oral solution containing 2.94 g sodium citrate in place of sodium bicarbonate per litre of oral rehydration rehydration solution. Efficacies were compared by measuring oral fluid intake, stool and vomitus output, change in body weight, hydration status, and rate of correction of acidosis during a period of 48 hours. Seventy five per cent (21 cases) in the citrate group and 83% (19 cases) in the bicarbonate group were successfully rehydrated (p greater than 0.05). There were no significant differences in intake, output, gain in body weight, fall in haematocrit and plasma specific gravity, and correction of acidosis between the two groups of patients within 48 hours after initiation of therapy. The solution with sodium citrate base was as effective as WHO-oral rehydration solution for management of diarrhoea. This study shows the efficacy, safety, and acceptability of citrate containing oral rehydration solution for rehydration and correction of acidosis in diarrhoea. PMID:6086466

  7. 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...

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

    PubMed

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

    2015-01-01

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

  9. 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. PMID:26106600

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  12. Systemic lupus erythematosus with distal renal tubular acidosis presenting as hypokalemic paralysis with respiratory failure.

    PubMed

    Koul, Parvaiz Ahmad; Wahid, Abdul; Shah, Bashir Ahmad

    2003-01-01

    An eighteen-year-old woman presented with hypokalemic respiratory failure. She was found to have distal renal tubular acidosis (dRTA) as the underlying cause for hypokalemia. This was treated successfully, and no apparent etiology for the dRTA was discovered. Three years later she presented with full-blown picture of systemic lupus erythematosus (SLE) together with features of persistent dRTA complicated, this time, with bilateral renal calculi and nephrocalcinosis. It is very likely that the dRTA was an early feature that preceded the other markers of SLE. The moral of this case is that patients with dRTA should be followed-up carefully as a primary cause for the dRTA may show up in-due-course and to monitor the treatment so as to prevent long-term complications of the RTA. PMID:18209445

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-08-01

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

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

    PubMed

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

    2014-02-01

    The regulation of intracellular pH (pHi) is a fundamental aspect of cell physiology that has received little attention in studies of the phylum Cnidaria, which includes ecologically important sea anemones and reef-building corals. Like all organisms, cnidarians must maintain pH homeostasis to counterbalance reductions in pHi, which can arise because of changes in either intrinsic or extrinsic parameters. Corals and sea anemones face natural daily changes in internal fluids, where the extracellular pH can range from 8.9 during the day to 7.4 at night. Furthermore, cnidarians are likely to experience future CO₂-driven declines in seawater pH, a process known as ocean acidification. Here, we carried out the first mechanistic investigation to determine how cnidarian pHi regulation responds to decreases in extracellular and intracellular pH. Using the anemone Anemonia viridis, we employed confocal live cell imaging and a pH-sensitive dye to track the dynamics of pHi after intracellular acidosis induced by acute exposure to decreases in seawater pH and NH₄Cl prepulses. The investigation was conducted on cells that contained intracellular symbiotic algae (Symbiodinium sp.) and on symbiont-free endoderm cells. Experiments using inhibitors and Na⁺-free seawater indicate a potential role of Na⁺/H⁺ plasma membrane exchangers (NHEs) in mediating pHi recovery following intracellular acidosis in both cell types. We also measured the buffering capacity of cells, and obtained values between 20.8 and 43.8 mM per pH unit, which are comparable to those in other invertebrates. Our findings provide the first steps towards a better understanding of acid-base regulation in these basal metazoans, for which information on cell physiology is extremely limited. PMID:24256552

  16. Ruminal lipopolysaccharide concentration and inflammatory response during grain-induced subacute ruminal acidosis in dairy cows.

    PubMed

    Gozho, G N; Krause, D O; Plaizier, J C

    2007-02-01

    The effects of grain-induced subacute ruminal acidosis (SARA) in lactating dairy cows on free ruminal lipopolysaccharide (LPS) and indicators of inflammation were determined. Four mid lactation dairy cows were divided into 2 groups of 2 cows and used in a repeated switchover design. During each period, SARA was induced in 2 animals for 5 subsequent days by replacing 25% of their total mixed ration (dry matter basis) with a concentrate made of 50% wheat and 50% barley. The other 2 cows acted as controls and were fed a total mixed ration diet in which 44% of dry matter was concentrate. On average, inducing SARA did not affect milk composition, increased the duration of rumen pH below 5.6 from 187 to 309 min/d, and increased free ruminal LPS concentration from 24,547 endotoxin units (EU)/mL to 128,825 EU/mL. Averaged across treatments, milk fat yield and milk protein yield were 0.66 and 1.00 kg/d, respectively. Rumen pH and milk fat data suggest that control cows also experienced ruminal acidosis, albeit a milder form of this disease than SARA cows. Serum LPS concentration in both control and SARA cows was less than the detection limit of <0.01 EU/mL for the assay. Induction of SARA elevated serum amyloid A concentration from 286.8 to 498.8 mug/mL, but did not affect other markers of inflammation including haptoglobin, fibrinogen, serum copper, or white blood cells. These results suggest that grain-induced SARA in mid lactation dairy cows increases the lysis of gram-negative bacteria and activates an inflammatory response. PMID:17235162

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. Re-engineering Cytochrome P450 2B11dH for Enhanced Metabolism of Several Substrates Including the Anti-cancer Prodrugs Cyclophosphamide and Ifosfamide

    PubMed Central

    Sun, Ling; Chen, Chong S.; Waxman, David J.; Liu, Hong; Halpert, James R.; Kumar, Santosh

    2007-01-01

    Based on recent directed evolution of P450 2B1, six P450 2B11 mutants at three positions were created in an N-terminal modified construct termed P450 2B11dH and characterized for enzyme catalysis using five substrates. Mutant I209A demonstrated a 3.2-fold enhanced kcat/Km for 7-ethoxy-4-trifluoromethylcourmarin O-deethylation, largely due to a dramatic decrease in Km (0.72 vs. 18 μM). I209A also demonstrated enhanced selectivity for testosterone 16β-hydroxylation over 16α-hydroxylation. In contrast, V183L showed a 4-fold increased kcat for 7-benzyloxyresorufin debenzylation and a 4.7-fold increased kcat/Km for testosterone 16α-hydroxylation. V183L also displayed a 1.7-fold higher kcat/Km than P450 2B11dH with the anti-cancer prodrugs cyclophosphamide and ifosfamide, resulting from a ~4-fold decrease in Km. Introduction of the V183L mutation into full-length P450 2B11 did not enhance the kcat/Km. Overall, the re-engineered P450 2B11dH enzymes exhibited enhanced catalytic efficiency with several substrates including the anti-cancer prodrugs. PMID:17254539

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

    SciTech Connect

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

    1988-12-01

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

  20. [3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency as a cause of severe neurological damage].

    PubMed

    Dodelson de Kremer, R; Kelley, R I; Depetris de Boldini, C; Paschini de Capra, A; Corbella, L; Givogri, I; Giner de Ayala, A; Albarenque, M

    1992-01-01

    This paper describes the first Argentine case of 3-hydroxy-3-methylglutaric aciduria, a genetic defect of ketogenesis and leucine catabolism step. At the age of 4 months, the patient presented a life-threatening episode of hypoglucemia, metabolic acidosis and hyperammonemia resembling Reye syndrome. The lack of urinary ketone bodies, normal levels of plasma aminoacids and normal urinary excretion of p-hydroxyphenolic acids, led us to look for a ketogenic defect. An abnormal profile of urinary organic acids detected by thin layer chromatography and later characterized and quantified by gas chromatography-mass spectrometry (Figs. 1, 2; Table 1), showed a marked increase in the acidic metabolites typical of the 3-hydroxy-3-methylglutaric aciduria: 3-hydroxy-3-methylglutaric, 3-methylglutaconic, 3-methylglutaric and 3-hydroxyisovaleric acids. The activity of 3-hydroxy-3-methylglutaryl coenzyme A lyase was absent in white cell pellets and between 2-5% of the control values in skin fibroblasts (Table 2). Treatment of the disorder, mainly restricted leucine or low-protein diet and addition of L-carnitine had no significant effect on the severe neurological injuries present since the first illness. MRI of the brain, at the age of 1 year and 8 months, showed images in T1 suggestive of marked cerebral atrophy and in T2 hyperintensive images predominating in the right frontal and posterior parietal areas and of the punctiform lesions in the basal ganglia, particularly in the heads of both caudate nuclei.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1302289

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

    PubMed

    Kasapkara, Ciğdem Seher; Akar, Melek; Yürük Yıldırım, Zeynep Nagehan; Tüzün, Heybet; Kanar, Berat; Ozbek, Mehmet Nuri

    2014-04-01

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

  2. Coagulopathy after severe pediatric trauma.

    PubMed

    Christiaans, Sarah C; Duhachek-Stapelman, Amy L; Russell, Robert T; Lisco, Steven J; Kerby, Jeffrey D; Pittet, Jean-François

    2014-06-01

    Trauma remains the leading cause of morbidity and mortality in the United States among children aged 1 to 21 years. The most common cause of lethality in pediatric trauma is traumatic brain injury. 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 include hypothermia, acidosis, hemodilution, and consumption of coagulation factors secondary to local activation of the coagulation system after severe traumatic injury. Furthermore, there is also recent evidence for a distinct mechanism of trauma-induced coagulopathy 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

  3. Elevated Carboxyhaemoglobin Concentrations by Pulse CO-Oximetry is Associated with Severe Aluminium Phosphide Poisoning.

    PubMed

    Mashayekhian, Mohammad; Hassanian-Moghaddam, Hossein; Rahimi, Mitra; Zamani, Nasim; Aghabiklooei, Abbas; Shadnia, Shahin

    2016-09-01

    In pulse CO-oximetry of aluminium phosphide (ALP)-poisoned patients, we discovered that carboxyhaemoglobin (CO-Hb) level was elevated. We aimed to determine whether a higher CO level was detected in patients with severe ALP poisoning and if this could be used as a prognostic factor in these patients. In a prospective case-control study, 96 suspected cases of ALP poisoning were evaluated. In the ALP-poisoned group, demographic characteristics, gastric and exhalation silver nitrate test results, average CO-Hb saturation, methaemoglobin saturation, and blood pressure and blood gas analysis until death/discharge were recorded. Severely poisoned patients were defined as those with systolic blood pressure ≤80 mmHg, pH ≤7.2, or HCO3 ≤15 meq/L or those who died, while patients with minor poisoning were those without any of these signs/symptoms. A control group (37 patients) was taken from other medically ill patients to detect probable effects of hypotension and metabolic acidosis on CO-Hb and methaemoglobin saturations. Of 96 patients, 27 died and 37 fulfilled the criteria for severe poisoning. All patients with carbon monoxide saturation >18% met the criteria to be included in the severe poisoning group and all with a SpCO >25% died. Concerning all significant variables in univariate analysis of severe ALP toxicity, the only significant variable which could independently predict death was carbon monoxide saturation. Due to high mortality rate and need for intensive care support, early prediction of outcome is vital for choosing an appropriate setting (ICU or ordinary ward). CO-oximetry is a good diagnostic and prognostic factor in patients with ALP poisoning even before any clinical evidence of toxicity will develop. PMID:26899262

  4. 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

  5. 17β-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex Difference in Acidosis-Induced Nociception.

    PubMed

    Qu, Zu-Wei; Liu, Ting-Ting; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Ren, Ping; Rao, Zhiguo; Hu, Wang-Ping

    2015-12-01

    Sex differences have been reported in a number of pain conditions. Women are more sensitive to most types of painful stimuli than men, and estrogen plays a key role in the sex differences in pain perception. However, it is unclear whether there is a sex difference in acidosis-evoked pain. We report here that both male and female rats exhibit nociceptive behaviors in response to acetic acid, with females being more sensitive than males. Local application of exogenous 17β-estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2 and estrogen receptor (ER)-α agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, but not ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile, replacement also reversed attenuation of the acetic acid-induced nociceptive response in ovariectomized females. Moreover, E2 can exert a rapid potentiating effect on the functional activity of acid-sensing ion channels (ASICs), which mediated the acidosis-induced events. E2 dose dependently increased the amplitude of ASIC currents with a 42.8 ± 1.6 nM of EC50. E2 shifted the concentration-response curve for proton upward with a 50.1% ± 6.2% increase of the maximal current response to proton. E2 potentiated ASIC currents via an ERα and ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability of dorsal root ganglia neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acidic stimuli. E2 potentiation of the functional activity of ASICs revealed a peripheral mechanism underlying this sex difference in acetic acid-induced nociception. PMID:26441237

  6. Acidosis decreases c-Myc oncogene expression in human lymphoma cells: a role for the proton-sensing G protein-coupled receptor TDAG8.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  8. Cellular metabolism and disease: what do metabolic outliers teach us?

    PubMed Central

    DeBerardinis, Ralph J.; Thompson, Craig B.

    2012-01-01

    An understanding of metabolic pathways based solely on biochemistry textbooks would underestimate the pervasive role of metabolism in essentially every aspect of biology. It is evident from recent work that many human diseases involve abnormal metabolic states – often genetically programmed – that perturb normal physiology and lead to severe tissue dysfunction. Understanding these metabolic outliers is now a crucial frontier in disease-oriented research. This review discusses the broad impact of metabolism in cellular function, how modern concepts of metabolism can inform our understanding of common diseases like cancer, and considers the prospects of developing new metabolic approaches to disease treatment. PMID:22424225

  9. A stand-alone synbiotic treatment for the prevention of D-lactic acidosis in short bowel syndrome.

    PubMed

    Takahashi, Kazuhiro; Terashima, Hideo; Kohno, Keisuke; Ohkohchi, Nobuhiro

    2013-01-01

    Synbiotics are combinations of probiotics and prebiotics that have recently been used in the context of various gastrointestinal diseases, including infectious enteritis, inflammatory bowel disease, and bowel obstruction. We encountered a patient with recurrent D-lactic acidosis who was treated successfully for long periods using synbiotics. The patient was diagnosed as having short bowel syndrome and had recurrent episodes of neurologic dysfunction due to D-lactic acidosis. In addition to fasting, the patient had been treated with antibiotics to eliminate D-lactate-producing bacteria. After the failure of antibiotic treatment, a stand-alone synbiotic treatment was started, specifically Bifidobacterium breve Yakult and Lactobacillus casei Shirota as probiotics, and galacto-oligosaccharide as a prebiotic. Serum D-lactate levels declined, and the patient has been recurrence-free for 3 years without dietary restriction. Synbiotics allowed the reduction in colonic absorption of D-lactate by both prevention of D-lactate-producing bacterial overgrowth and stimulation of intestinal motility, leading to remission of D-lactate acidosis. PMID:23701144

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

    PubMed Central

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

    2014-01-01

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

  11. 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

  12. Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven®)

    PubMed Central

    Viuff, D.; Lauritzen, B.; Pusateri, A. E.; Andersen, S.; Rojkjaer, R.; Johansson, P. I.

    2008-01-01

    Background A range of plasma volume expanders is used clinically, often in settings where haemostasis may already be impaired. The haemostatic agent, recombinant activated factor VII (rFVIIa, NovoSeven®), may be used to improve haemostasis but potential interactions with different volume expanders are poorly understood. Methods Clot formation was measured by thromboelastography (TEG) using blood from healthy volunteers. In vitro effects of rFVIIa with haemodilution, acidosis, and hypothermia were examined. Conditions were induced by dilution with NaCl (0.9%), lactated Ringer's solution, albumin 5%, or hydroxyethyl starch (HES) solutions [MW (molecular weight) 130–670 kDa]; by adjusting pH to 6.8 with 1 M HEPES (N-2-hydroxyethylpiperazine-N′-2-ethanesulphonic acid) buffer; or by reducing temperature to 32°C. We also studied the effect of low vs high MW HES (MW 200 vs 600 kDa) and rFVIIa on in vivo bleeding time (BT) in rabbits. Results Haemodilution progressively altered TEG parameters. rFVIIa improved TEG parameters in the presence of acidosis, hypothermia or 20% haemodilution (P<0.05). At 40% haemodilution, the rFVIIa effect was diminished particularly with high MW HES. In vivo, rFVIIa shortened the BT (P<0.05) with low but not high MW HES. Conclusions Efficacy of rFVIIa was affected by the degree of haemodilution and type of volume expander, but not by acidosis or hypothermia. PMID:18565966

  13. Metabolism of meperidine in several animal species.

    PubMed

    Yeh, S Y

    1984-12-01

    Four new meperidine metabolites were identified by GC-MS in the urine of rats, guinea pigs, rabbits, cats, and dogs. In addition to known meperidine metabolites, 4-ethoxycarbonyl-4-phenyl-1,2,3,4-tetrapyridine (dehydronormeperidine; IV, the N-hydroxydehydro derivative of normeperidine (X), the dihydroxy derivative of meperidine (XII), and the dihydroxy derivative of normeperidine (XIII) were identified. The possible role of the N-hydroxy derivative of normeperidine (IX) in the pharmacological interaction of meperidine (I) with MAO inhibitors, seen selectively in the rabbit (and humans), is discussed. Following the administration of the p-hydroxy derivative of meperidine (VII), the major metabolite was conjugated VII. Trace amounts of the p-hydroxy derivative of normeperidine (VIII), the methoxy hydroxy derivative of meperidine (XI), XII, and XIII also were detected as metabolites of VII. The degree of N-demethylation of VII, both in vitro and in vivo, was small. PMID:6527256

  14. 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 (β-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-1α 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-1α 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-1α 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

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

    PubMed

    Abou Ziki, Maen D; Verjee, Mohamud A

    2015-01-01

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

  16. Hypercapnic acidosis impairs plasma membrane wound resealing in ventilator-injured lungs.

    PubMed

    Doerr, Clinton H; Gajic, Ognjen; Berrios, Jorge C; Caples, Sean; Abdel, Matthew; Lymp, James F; Hubmayr, Rolf D

    2005-06-15

    The objective of this study was to assess the effects of hypercapnic acidosis on lung cell injury and repair by confocal microscopy in a model of ventilator-induced lung injury. Three groups of normocapnic, hypocapnic, and hypercapnic rat lungs were perfused ex vivo, either during or after injurious ventilation, with a solution containing the membrane-impermeant label propidium iodide. In lungs labeled during injurious ventilation, propidium iodide fluorescence identifies all cells with plasma membrane wounds, both permanent and transient, whereas in lungs labeled after injurious ventilation propidium iodide fluorescence identifies only cells with permanent plasma membrane wounds. Hypercapnia minimized the adverse effects of high-volume ventilation on vascular barrier function, whereas hypocapnia had the opposite effect. Despite CO2-dependent differences in lung mechanics and edema the number of injured subpleural cells per alveolus was similar in the three groups (0.48 +/- 0.34 versus 0.51 +/- 0.19 versus 0.43 +/- 0.20 for hypocapnia, normocapnia, and hypercapnia, respectively). However, compared with normocapnia the probability of wound repair was significantly reduced in hypercapnic lungs (63 versus 38%; p < 0.02). This finding was subsequently confirmed in alveolar epithelial cell scratch models. The potential relevance of these observations for lung inflammation and remodeling after mechanical injury is discussed. PMID:15695495

  17. Extracellular Spermine Exacerbates Ischemic Neuronal Injury through Sensitization of ASIC1a Channels to Extracellular Acidosis

    PubMed Central

    Duan, Bo; Wang, Yi-Zhi; Yang, Tao; Chu, Xiang-Ping; Yu, Ye; Huang, Yu; Cao, Hui; Hansen, Jillian; Simon, Roger P.; Zhu, Michael X.; Xiong, Zhi-Gang; Xu, Tian-Le

    2011-01-01

    Ischemic brain injury is a major problem associated with stroke. It has been increasingly recognized that acid-sensing ion channels (ASICs) contribute significantly to ischemic neuronal damage, but the underlying mechanism has remained elusive. Here, we show that extracellular spermine, one of the endogenous polyamines, exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis. Pharmacological blockade of ASIC1a or deletion of the ASIC1 gene greatly reduces the enhancing effect of spermine in ischemic neuronal damage both in cultures of dissociated neurons and in a mouse model of focal ischemia. Mechanistically, spermine profoundly reduces desensitization of ASIC1a by slowing down desensitization in the open state, shifting steady-state desensitization to more acidic pH, and accelerating recovery between repeated periods of acid stimulation. Spermine-mediated potentiation of ASIC1a activity is occluded by PcTX1 (psalmotoxin 1), a specific ASIC1a inhibitor binding to its extracellular domain. Functionally, the enhanced channel activity is accompanied by increased acid-induced neuronal membrane depolarization and cytoplasmic Ca2+ overload, which may partially explain the exacerbated neuronal damage caused by spermine. More importantly, blocking endogenous spermine synthesis significantly attenuates ischemic brain injury mediated by ASIC1a but not that by NMDA receptors. Thus, extracellular spermine contributes significantly to ischemic neuronal injury through enhancing ASIC1a activity. Our data suggest new neuroprotective strategies for stroke patients via inhibition of polyamine synthesis and subsequent spermine–ASIC interaction. PMID:21307247

  18. 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

  19. UPLC/ESI-MS/MS-based determination of metabolism of several new illicit drugs, ADB-FUBINACA, AB-FUBINACA, AB-PINACA, QUPIC, 5F-QUPIC and α-PVT, by human liver microsome.

    PubMed

    Takayama, Takahiro; Suzuki, Mayu; Todoroki, Kenichiro; Inoue, Koichi; Min, Jun Zhe; Kikura-Hanajiri, Ruri; Goda, Yukihiro; Toyo'oka, Toshimasa

    2014-06-01

    The metabolism by human liver microsomes of several new illicit drugs, that is, N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3- carboxamide (ADB-FUBINACA), N-(1-amino-3-methyl-1-oxobutan-2-yl)-1- (4-fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA), N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA), quinolin-8-yl 1-pentyl-(1H-indole)-3-carboxylate (QUPIC), quinolin-8-yl 1-(5-fluoropentyl)-(1H-indole)-3-carboxylate (5 F-QUPIC) and α-pyrrolidinovalerothiophenone (α-PVT), which have indole, indazole, quinolinol ester and thiophene structures, was investigated using reversed-phase chromatography and mass spectrometry. The present method is based upon the oxidation by cytochrome p450 superfamily enzymes in the microsomes. The oxidation of ADB-FUBINACA and AB-FUBINACA mainly occurred on the N-(1-amino-alkyl-1-oxobutan) moiety. However, the oxidation of AB-PINACA seemed to occur on the 1-pentyl moiety. On the other hand, QUPIC and 5 F-QUPIC, which have a quinolinol ester structure, predominantly underwent a cleavage reaction to produce indoleacetic acid type metabolites. In contrast, the metabolism reaction of α-PVT was different from that of the other tested drugs, and various oxidation products were observed on the chromatograms. The obtained metabolites are not in conflict with the results predicted by MetaboLynx software. However, the exact structures of the metabolites, except for 1-pentyl-1H-indole-3-carboxylic acid (QUPIC metabolite) and 1-(5-fluoropentyl)-1H-indole-3-carboxylic acid (5 F-QUPIC metabolite), are currently not proven, because we have no authentic compounds for comparison. The proposed approach using human liver microsome seems to provide a new technology for the prediction of possible metabolites occuring in humans. PMID:24861751

  20. Targeting the Metabolic Microenvironment of Tumors

    PubMed Central

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

    2013-01-01

    The observation of aerobic glycolysis by tumor cells in 1924 by Otto Warburg, and subsequent innovation of imaging glucose uptake by tumors in patients with PET-CT has incited a renewed interest in the altered metabolism of tumors. As tumors grow in situ, a fraction of it is further away from their blood supply, leading to decreased oxygen concentrations (hypoxia), which induces the hypoxia response pathways of HIF1α, mTOR and UPR. In normal tissues, these responses mitigate hypoxic stress and induce neo-angiogenesis. In tumors, these pathways are dysregulated and lead to decreased perfusion and exacerbation of hypoxia as a result of immature and chaotic blood vessels. Hypoxia selects for a glycolytic phenotype and resultant acidification of the tumor microenvironment, facilitated by upregulation of proton transporters. Acidification selects for enhanced metastatic potential and reduced drug efficacy through ion trapping. In this review, we provide a comprehensive summary of pre-clinical and clinical drugs under development for targeting aerobic glycolysis, acidosis, hypoxia and hypoxia-response pathways. Hypoxia and acidosis can be manipulated, providing further therapeutic benefit for cancers that feature these common phenotypes. PMID:22959024

  1. Sustained metabolic scope.

    PubMed Central

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

    1990-01-01

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

  2. 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 for ...

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

    PubMed

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

    2014-02-01

    , irrespective of its viability, in reducing the severity of SARA. However, further studies are required to evaluate the importance of yeast viability for other dietary conditions, particularly when the risk of acidosis is high. PMID:24398831

  4. Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

    PubMed Central

    Wang, Ying-Xin; Le, Wei-Dong

    2015-01-01

    Objective: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a progressive, multisystem affected mitochondrial disease associated with a number of disease-related defective genes. MELAS has unpredictable presentations and clinical course, and it can be commonly misdiagnosed as encephalitis, cerebral infarction, or brain neoplasms. This review aimed to update the diagnosis progress in MELAS, which may provide better understanding of the disease nature and help make the right diagnosis as well. Data Sources: The data used in this review came from published peer review articles from October 1984 to October 2014, which were obtained from PubMed. The search term is “MELAS”. Study Selection: Information selected from those reported studies is mainly based on the progress on clinical features, blood biochemistry, neuroimaging, muscle biopsy, and genetics in diagnosing MELAS. Results: MELAS has a wide heterogeneity in genetics and clinical manifestations. The relationship between mutations and phenotypes remains unclear. Advanced serial functional magnetic resonance imaging (MRI) can provide directional information on this disease. Muscle biopsy has meaningful value in diagnosing MELAS, which shows the presence of ragged red fibers and mosaic appearance of cytochrome oxidase negative fibers. Genetic studies have reported that approximately 80% of MELAS cases are caused by the mutation m.3243A>G of the mitochondrial transfer RNA (Leu (UUR)) gene (MT-TL1). Conclusions: MELAS involves multiple systems with variable clinical symptoms and recurrent episodes. The prognosis of MELAS patients depends on timely diagnosis. Therefore, overall diagnosis of MELAS should be based on the maternal inheritance family history, clinical manifestation, and findings from serial MRI, muscle biopsy, and genetics. PMID:26112726

  5. Molecular Investigation of Distal Renal Tubular Acidosis in Tunisia, Evidence for Founder Mutations

    PubMed Central

    Voskarides, Konstantinos; Nouira, Sonia; Ben Halim, Nizar; Kefi, Rym; Aloulou, Hajer; Romdhane, Lilia; Ben Abdallah, Rim; Ben Rhouma, Faten; Aissa, Khaoula; Boughamoura, Lamia; Kammoun, Thouraya; Azzouz, Hatem; Abroug, Saoussen; Ben Turkia, Hathemi; Ayadi, Abdelkarim; Mrad, Ridha; Chabchoub, Imen; Hachicha, Mongia; Chemli, Jalel; Deltas, Constantinos; Abdelhak, Sonia

    2014-01-01

    Background: Distal renal tubular acidosis (dRTA) is a rare genetic disease caused by mutations in different genes involved in the secretion of H+ ions in the intercalated cells of the collecting duct. Both autosomal dominant and recessive forms have been described; the latter is also associated with sensorineural hearing loss. Methods: Twenty-two Tunisian families were analyzed for mutations in the ATP6V1B1 and ATP6V0A4 genes by direct sequencing. Dating of the founder mutations was performed. Results: Two founder mutations in the ATP6V1B1 gene were found in 16/27 dRTA cases. The p.Ile386Hisfs*56 founder mutation was estimated to be older than 2400 years and no correlations were found with deafness. For the remaining patients, two mutations in the ATP6V0A4 gene, one of them being novel, were found in three Tunisian cases. The presence of a heterozygous missense mutation p.T30I, of the ATP6V1B1 gene, was identified in six patients, while no mutations of the second gene were detected. No deleterious mutations of either ATP6V1B1 or ATP6V0A were found for the two probands. Conclusion: Our study gives evidence of phenotypic and genotypic heterogeneity of dRTA in the Tunisian population. Five different mutations were found, two of them were due to a founder effect, and screening of these mutations could provide a rapid and valuable tool for diagnosis of dRTA. PMID:25285676

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

    PubMed Central

    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 α-tocopherol analogues, trolox and butylated hydroxytoluene (BHT), and the spin trapping molecule α-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

  7. Non-specific inhibition of ischemia- and acidosis-induced intracellular calcium elevations and membrane currents by α-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 α-tocopherol analogues, trolox and butylated hydroxytoluene (BHT), and the spin trapping molecule α-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

  8. Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review

    PubMed Central

    Dell'Orto, Valentina G; Belotti, Eva A; Goeggel-Simonetti, Barbara; Simonetti, Giacomo D; Ramelli, Gian Paolo; Bianchetti, Mario G; Lava, Sebastiano A G

    2014-01-01

    Aims The use of topiramate, which is prescribed for the management of epilepsy, for migraine headache prophylaxis and as a weight-loss agent, has been associated with the development of metabolic acidosis, hypokalaemia and renal stone disease. We systematically reviewed all the literature. Methods The systematic review of the literature was realized using the principles underlying the UK Economic and Social Research Council guidance on the conduct of narrative synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results Fourty-seven reports published between 1996 and 2013 were retained for the final analysis. Five case–control studies and six longitudinal studies addressed the effect of topiramate on acid–base and potassium balance. A significant tendency towards mild-to-moderate hyperchloraemic metabolic acidosis (with bicarbonate ≤21.0 mmol l−1 in approximately every third case) and mild hypokalaemia (with potassium ≤3.5 mmol l−1 in 10% of the cases) was noted on treatment with topiramate, which was similar in children and adults. A single study observed that topiramate causes mild hyperuricaemia in male adults. A tendency towards hypocitraturia, a recognized promoter of renal stone formation, was noted in all patients on topiramate. Conclusions Increasing evidence supports the use of topiramate. Topiramate is generally well tolerated, and serious adverse events are rare. Nonetheless, the present systematic review of the literature indicates that its use is linked with the development of acidosis, hypokalaemia, hyperuricaemia and hypocitraturia. PMID:24219102

  9. Comparison of lidocaine and bupivacaine depression of sinoatrial nodal activity during hypoxia and acidosis in adult and neonatal guinea pigs.

    PubMed

    Bosnjak, Z J; Stowe, D F; Kampine, J P

    1986-09-01

    High blood concentrations of local anesthetics are cardiotoxic. The aim of this study was to compare the effects of lidocaine and bupivacaine on the intrinsic pacemaker activity of in vitro sinoatrial nodal cells of the adult and neonatal guinea pig in the presence and absence of hypoxia and acidosis. Fifteen pairs of adult (greater than 80 days old) and neonatal (0-3 days old) hearts were isolated. Nodal tissues were suffused with Krebs-Ringer solution at 37 degrees C and exposed to increasing concentrations of either lidocaine (0.05-0.8 mM) or bupivacaine (0.01-0.4 mM). The suffusate was equilibrated either with 5% CO2, 95% O2 (pH 7.40, PO2 482 torr) or with 12% CO2, 88% N2 (pH 7.01, PO2 58 torr). Transmembrane action potentials were recorded from sinoatrial nodal cells and impulse intervals were converted to rates. We found that hypoxia and acidosis alone reduced rates in both adults and neonates, and that the reduction was additive to the effects of local anesthetics. Bupivacaine was 4-5 times more potent in decreasing rates than was lidocaine in both age groups. Lidocaine was about twice as effective in depressing neonatal rates as adult rates, and bupivacaine caused cessation of pacemaker activity in a greater percentage of nodes than did lidocaine. Our results demonstrate, in vitro, that the neonatal sinoatrial node is more sensitive to lidocaine and bupivacaine than is the adult node, that bupivacaine is more potent in depressing and stopping nodal activity, and that hypoxia and acidosis enhance pacemaker depression caused by these agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3740490

  10. Inhibition of the oxygen sensor PHD2 in the liver improves survival in lactic acidosis by activating the Cori cycle

    PubMed Central

    Suhara, Tomohiro; Hishiki, Takako; Kasahara, Masataka; Hayakawa, Noriyo; Oyaizu, Tomoko; Nakanishi, Tsuyoshi; Kubo, Akiko; Morisaki, Hiroshi; Kaelin, William G.; Suematsu, Makoto; Minamishima, Yoji Andrew

    2015-01-01

    Loss of prolyl hydroxylase 2 (PHD2) activates the hypoxia-inducible factor-dependent hypoxic response, including anaerobic glycolysis, which causes large amounts of lactate to be released from cells into the circulation. We found that Phd2-null mouse embryonic fibroblasts (MEFs) produced more lactate than wild-type MEFs, as expected, whereas systemic inactivation of PHD2 in mice did not cause hyperlacticacidemia. This unexpected observation led us to hypothesize that the hypoxic response activated in the liver enhances the Cori cycle, a lactate–glucose carbon recycling system between muscle and liver, and thereby decreases circulating lactate. Consistent with this hypothesis, blood lactate levels measured after a treadmill or lactate tolerance test were significantly lower in Phd2-liver-specific knockout (Phd2-LKO) mice than in control mice. An in vivo 13C-labeled lactate incorporation assay revealed that the livers of Phd2-LKO mice produce significantly more glucose derived from 13C-labeled lactate than control mice, suggesting that blockade of PHD2 in the liver ameliorates lactic acidosis by activating gluconeogenesis from lactate. Phd2-LKO mice were resistant to lactic acidosis induced by injection of a lethal dose of lactate, displaying a significant elongation of survival. Moreover, oral administration of a PHD inhibitor improved survival in an endotoxin shock mice model. These data suggest that PHD2 is a potentially novel drug target for the treatment of lactic acidosis, which is a serious and often fatal complication observed in some critically ill patients. PMID:26324945

  11. 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

  12. Inhalational sevoflurane in severe bronchial obstruction unresponsive to multipharmacologic therapy: a case report

    PubMed Central

    Weber, Thomas

    2012-01-01

    Introduction: Bronchial asthma with respiratory failure is a challenge for the intensivist as mechanical ventilation is often difficult due to bronchoconstriction and air-trapping. We describe a case of severe asthma with respiratory acidosis in a 10-year-old patient unresponsive to multipharmacologic broncholytic therapy. Only the initiation of sevoflurane inhalation resolved severe bronchoconstriction and dynamic hyperinflation, leading to complete recovery. Case presentation: A 10-year-old Caucasian boy was intubated and mechanically ventilated due to an asthmatic attack. Bronchoconstriction and dynamic hyperinflation were severe while multipharmacological broncholytic therapy was unsuccessful. Inhalation with sevoflurane via an anaesthesia machine was the key intervention leading to gradual resolving of severe hypercapnia and respiratory acidosis. Furthermore bilateral pupil dilation occurred during hypercapnia, but no intracranial pathology could be detected. The patient made an uneventful recovery. To our knowledge this is the first case where hypercapnia and respiratory acidosis were so profound and long lasting yet the patient survived without any damage. Conclusions: Inhalational anaesthetics must be considered as an early treatment option in ventilated asthmatic patients with bronchial obstruction unresponsive to conventional therapy even though their administration in intensive care units may be difficult. PMID:24358829

  13. Acute renal failure and type B lactic acidosis as first manifestation of extranodal T-cell lymphoblastic lymphoma

    PubMed Central

    Yun, Seongseok; Walker, Courtney N; Vincelette, Nicole D; Anwer, Faiz

    2014-01-01

    We describe a rare case of a 19-year-old male patient with a history of epilepsy and developmental delay who presented with acute renal failure (ARF) and lactic acidosis (LA) as the first manifestation of T-cell lymphoblastic lymphoma. Renal ultrasound and CT of the abdomen showed renal parenchymal infiltration, and renal biopsy demonstrated T-cell lymphoblastic lymphoma. LA, ARF and electrolyte abnormalities were refractory to the initial treatment of bicarbonate infusion and hydration. However, these abnormalities rapidly normalised after the initiation of chemotherapy, suggesting that the LA and ARF were secondary to lymphomatous renal infiltration. PMID:24913086

  14. Acidosis Is a key regulator of osteoblast ecto‐nucleotidase pyrophosphatase/phosphodiesterase 1 (NPP1) expression and activity

    PubMed Central

    Key, Michelle L.; Hajjawi, Mark O.R.; Millán, José L.; Arnett, Timothy R.

    2015-01-01

    Previous work has shown that acidosis prevents bone nodule formation by osteoblasts in vitro by inhibiting mineralisation of the collagenous matrix. The ratio of phosphate (Pi) to pyrophosphate (PPi) in the bone microenvironment is a fundamental regulator of bone mineralisation. Both Pi and PPi, a potent inhibitor of mineralisation, are generated from extracellular nucleotides by the actions of ecto‐nucleotidases. This study investigated the expression and activity of ecto‐nucleotidases by osteoblasts under normal and acid conditions. We found that osteoblasts express mRNA for a number of ecto‐nucleotidases including NTPdase 1–6 (ecto‐nucleoside triphosphate diphosphohydrolase) and NPP1‐3 (ecto‐nucleotide pyrophosphatase/phosphodiesterase). The rank order of mRNA expression in differentiating rat osteoblasts (day 7) was Enpp1 > NTPdase 4 > NTPdase 6 > NTPdase 5 > alkaline phosphatase > ecto‐5‐nucleotidase > Enpp3 > NTPdase 1 > NTPdase 3 > Enpp2 > NTPdase 2. Acidosis (pH 6.9) upregulated NPP1 mRNA (2.8‐fold) and protein expression at all stages of osteoblast differentiation compared to physiological pH (pH 7.4); expression of other ecto‐nucleotidases was unaffected. Furthermore, total NPP activity was increased up to 53% in osteoblasts cultured in acid conditions (P < 0.001). Release of ATP, one of the key substrates for NPP1, from osteoblasts, was unaffected by acidosis. Further studies showed that mineralised bone formation by osteoblasts cultured from NPP1 knockout mice was increased compared with wildtypes (2.5‐fold, P < 0.001) and was partially resistant to the inhibitory effect of acidosis. These results indicate that increased NPP1 expression and activity might contribute to the decreased mineralisation observed when osteoblasts are exposed to acid conditions. J. Cell. Physiol. 230: 3049–3056, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc

  15. Severe Weather

    ERIC Educational Resources Information Center

    Forde, Evan B.

    2004-01-01

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

  16. Severe Weather

    ERIC Educational Resources Information Center

    Forde, Evan B.

    2004-01-01

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

  17. Disorders of Carbohydrate Metabolism

    MedlinePlus

    ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism Carbohydrates are sugars. ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism NOTE: This is ...

  18. Standardized treatment of severe methanol poisoning with ethanol and hemodialysis

    SciTech Connect

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

    1985-03-01

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

  19. A primary Sjögren's syndrome patient with distal renal tubular acidosis, who presented with symptoms of hypokalemic periodic paralysis: Report of a case study and review of the literature.

    PubMed

    Soy, Mehmet; Pamuk, Omer Nuri; Gerenli, Murat; Celik, Yahya

    2005-11-01

    Although renal tubular acidosis (RTA), secondary to autoimmune interstitial nephritis, develops in a large proportion of patients with Sjögren's syndrome (SS), most of the subjects are asymptomatic. Here, we shall present a 39-year-old female patient who came to us with hypokalemic periodic paralysis (HPP), and who was later diagnosed with distal RTA. The patient, who had xerostomia and xerophthalmia for a long period of time, was diagnosed with primary SS from serologic and histologic findings. The patient recovered by being prescribed potassium replacement therapy. Although renal biopsy was not performed, corticosteroids were administered because HPP indicated severe interstitial nephritis. HPP did not reoccur during a 2-year follow-up period. We also review cases with SS-related distal RTA and HPP. PMID:15690142

  20. Clinical Features and Outcome in Children with Severe Plasmodium falciparum Malaria: A Meta-Analysis

    PubMed Central

    Manning, Laurens; Laman, Moses; Davis, Wendy A.; Davis, Timothy M. E.

    2014-01-01

    Background Although global malaria mortality is declining, estimates may not reflect better inpatient management of severe malaria (SM) where reported case fatality rates (CFRs) vary from 1–25%. Methods A meta-analysis of prospective studies of SM was conducted to examine i) whether hypothesized differences between clinical features and outcome in Melanesian compared with African or Asian children really exist, and ii) to explore temporal changes in overall and complication-specific CFRs. The proportions of different SM complications and, overall and complication-specific CFRs were incorporated into the meta-analysis. Adjustments were made for study-level covariates including geographic region, SM definition, artemisinin treatment, median age of participants and time period. Findings Sixty-five studies were included. Substantial heterogeneity (I2>80%) was demonstrated for most outcomes. SM definition contributed to between-study heterogeneity in proportions of cerebral malaria (CM), metabolic acidosis (MA), severe anemia and overall CFR, whilst geographic region was a significant moderator in for CM and hypoglycemia (HG) rates. Compared with their African counterparts, Melanesian children had lower rates of HG (10% [CI95 7–13%] versus 1% [0–3%], P<0.05), lower overall CFR (2% [0–4%] versus 7% [6–9%], P<0.05) and lower CM-specific CFR (8% [0–17%] versus 19% [16–21%], P<0.05). There was no temporal trend for overall CFR and CM-specific CFR but declining HG- and MA- specific CFRs were observed. Interpretation These data highlight that recent estimates of declining global malaria mortality are not replicated by improved outcomes for children hospitalized with SM. Significant geographic differences in the complication rates and subsequent CFRs exist and provide the first robust confirmation of lower CFRs in Melanesian children, perhaps due to less frequent HG. PMID:24516538

  1. Adult nephron-specific MR-deficient mice develop a severe renal PHA-1 phenotype.

    PubMed

    Canonica, Jérémie; Sergi, Chloé; Maillard, Marc; Klusonova, Petra; Odermatt, Alex; Koesters, Robert; Loffing-Cueni, Dominique; Loffing, Johannes; Rossier, Bernard; Frateschi, Simona; Hummler, Edith

    2016-05-01

    Aldosterone is the main mineralocorticoid hormone controlling sodium balance, fluid homeostasis, and blood pressure by regulating sodium reabsorption in the aldosterone-sensitive distal nephron (ASDN). Germline loss-of-function mutations of the mineralocorticoid receptor (MR) in humans and in mice lead to the "renal" form of type 1 pseudohypoaldosteronism (PHA-1), a case of aldosterone resistance characterized by salt wasting, dehydration, failure to thrive, hyperkalemia, and metabolic acidosis. To investigate the importance of MR in adult epithelial cells, we generated nephron-specific MR knockout mice (MR(Pax8/LC1)) using a doxycycline-inducible system. Under standard diet, MR(Pax8/LC1) mice exhibit inability to gain weight and significant weight loss compared to control mice. Interestingly, despite failure to thrive, MR(Pax8/LC1) mice survive but develop a severe PHA-1 phenotype with higher urinary Na(+) levels, decreased plasma Na(+), hyperkalemia, and higher levels of plasma aldosterone. This phenotype further worsens and becomes lethal under a sodium-deficient diet. Na(+)/Cl(-) co-transporter (NCC) protein expression and its phosphorylated form are downregulated in the MR(Pax8/LC1) knockouts, as well as the αENaC protein expression level, whereas the expression of glucocorticoid receptor (GR) is increased. A diet rich in Na(+) and low in K(+) does not restore plasma aldosterone to control levels but is sufficient to restore body weight, plasma, and urinary electrolytes. In conclusion, MR deletion along the nephron fully recapitulates the features of severe human PHA-1. ENaC protein expression is dependent on MR activity. Suppression of NCC under hyperkalemia predominates in a hypovolemic state. PMID:26762397

  2. Distal renal tubular acidosis, hypokalemic paralysis, nephrocalcinosis, primary hypothyroidism, growth retardation, osteomalacia and osteoporosis leading to pathological fracture: a case report.

    PubMed

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

    2011-07-01

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

  3. Induction of Subacute Ruminal Acidosis Affects the Ruminal Microbiome and Epithelium

    PubMed Central

    McCann, Joshua C.; Luan, Shaoyu; Cardoso, Felipe C.; Derakhshani, Hooman; Khafipour, Ehsan; Loor, Juan J.

    2016-01-01

    Subacute ruminal acidosis (SARA) negatively impacts the dairy industry by decreasing dry matter intake, milk production, profitability, and increasing culling rate and death loss. Six ruminally cannulated, lactating Holstein cows were used in a replicated incomplete Latin square design to determine the effects of SARA induction on the ruminal microbiome and epithelium. Experimental periods were 10 days with days 1–3 for ad libitum intake of control diet, followed by 50% feed restriction on day 4, and ad libitum access on day 5 to the basal diet or the basal diet with an additional 10% of a 50:50 wheat/barley pellet. Based on subsequent ruminal pH, cows were grouped (SARA grouping; SG) as Non-SARA or SARA based on time <5.6 pH (0 and 3.4 h, respectively). Ruminal samples were collected on days 1 and 6 of each period prior to feeding and separated into liquid and solid fractions. Microbial DNA was extracted for bacterial analysis using 16S rRNA gene paired-end sequencing on the MiSeq Illumina platform and quantitative PCR (qPCR). Ruminal epithelium biopsies were taken on days 1 and 6 before feeding. Quantitative RT-PCR was used to determine gene expression in rumen epithelium. Bray–Curtis similarity indicated samples within the liquid fraction separated by day and coincided with an increased relative abundance of genera Prevotella, Ruminococcus, Streptococcus, and Lactobacillus on day 6 (P < 0.06). Although Firmicutes was the predominant phyla in the solid fraction, a SG × day interaction (P < 0.01) indicated a decrease on day 6 for SARA cows. In contrast, phylum Bacteroidetes increased on day 6 (P < 0.01) for SARA cows driven by greater genera Prevotella and YRC22 (P < 0.01). Streptococcus bovis and Succinivibrio dextrinosolvens populations tended to increase on day 6 but were not affected by SG. In ruminal epithelium, CLDN1 and CLDN4 expression increased on day 6 (P < 0.03) 24 h after SARA induction and a tendency for a SG × day interaction (P < 0.10) was

  4. Induction of Subacute Ruminal Acidosis Affects the Ruminal Microbiome and Epithelium.

    PubMed

    McCann, Joshua C; Luan, Shaoyu; Cardoso, Felipe C; Derakhshani, Hooman; Khafipour, Ehsan; Loor, Juan J

    2016-01-01

    Subacute ruminal acidosis (SARA) negatively impacts the dairy industry by decreasing dry matter intake, milk production, profitability, and increasing culling rate and death loss. Six ruminally cannulated, lactating Holstein cows were used in a replicated incomplete Latin square design to determine the effects of SARA induction on the ruminal microbiome and epithelium. Experimental periods were 10 days with days 1-3 for ad libitum intake of control diet, followed by 50% feed restriction on day 4, and ad libitum access on day 5 to the basal diet or the basal diet with an additional 10% of a 50:50 wheat/barley pellet. Based on subsequent ruminal pH, cows were grouped (SARA grouping; SG) as Non-SARA or SARA based on time <5.6 pH (0 and 3.4 h, respectively). Ruminal samples were collected on days 1 and 6 of each period prior to feeding and separated into liquid and solid fractions. Microbial DNA was extracted for bacterial analysis using 16S rRNA gene paired-end sequencing on the MiSeq Illumina platform and quantitative PCR (qPCR). Ruminal epithelium biopsies were taken on days 1 and 6 before feeding. Quantitative RT-PCR was used to determine gene expression in rumen epithelium. Bray-Curtis similarity indicated samples within the liquid fraction separated by day and coincided with an increased relative abundance of genera Prevotella, Ruminococcus, Streptococcus, and Lactobacillus on day 6 (P < 0.06). Although Firmicutes was the predominant phyla in the solid fraction, a SG × day interaction (P < 0.01) indicated a decrease on day 6 for SARA cows. In contrast, phylum Bacteroidetes increased on day 6 (P < 0.01) for SARA cows driven by greater genera Prevotella and YRC22 (P < 0.01). Streptococcus bovis and Succinivibrio dextrinosolvens populations tended to increase on day 6 but were not affected by SG. In ruminal epithelium, CLDN1 and CLDN4 expression increased on day 6 (P < 0.03) 24 h after SARA induction and a tendency for a SG × day interaction (P < 0.10) was

  5. A single mild episode of subacute ruminal acidosis does not affect ruminal barrier function in the short term.

    PubMed

    Penner, G B; Oba, M; Gäbel, G; Aschenbach, J R

    2010-10-01

    Twenty-four German Merino sheep (72.3±10.1 kg of body weight) were fed an all-hay diet and assigned to either the subacute ruminal acidosis (SARA) treatment (n=17) or sham treatment (n=7). The SARA sheep were orally dosed with a 2.2 M glucose solution to supply 5 g of glucose/kg of body weight, whereas sham sheep received an equal volume of water. Ruminal pH was measured for 48 h before and 3 h after the oral dose. Sheep were then killed and ruminal epithelia from the ventral sac were mounted in Ussing chambers. The serosal-to-mucosal flux rate of partially (3)H-labeled mannitol (J(mannitol-SM)), an indicator of barrier function, was measured while epithelia were exposed to 3 sequential in vitro measurement periods lasting 1 h each. The measurement periods consisted of baseline, challenge, and recovery periods and were interspersed by 30-min periods for treatment equilibration. Baseline conditions were pH 6.1 (mucosal solution) and pH 7.4 (serosal solution) with a bilateral osmolarity of 293 mOsm/L. During the challenge period, the mucosal side of the epithelia was exposed to either an acidotic challenge (pH 5.2, osmolarity 293 mOsm/L) or an osmotic challenge (pH 6.1, osmolarity 450 mOsm/L); a third group served as control (pH 6.1, osmolarity 293 mOsm/L). The mucosal buffer solution was replaced for the recovery period. In vivo, sheep on the SARA treatment had lower mean (5.77 vs. 6.67) and nadir (5.48 vs. 6.47) ruminal pH for the 3h following the oral drench compared with sham sheep, indicating the successful induction of SARA with the oral glucose dose. Despite the marked reduction in pH in vivo, induction of SARA had no detectable effects on the baseline measurements of J(mannitol-SM), tissue conductance (G(t)), and short-circuit current (I(sc)) in vitro. However, reducing mucosal pH to 5.2 in vitro had negative effects on epithelial barrier function in the recovery period, including increased J(mannitol-SM), increased G(t), and decreased I(sc). The osmotic

  6. Quiescence in Artemia franciscana embryos: reversible arrest of metabolism and gene expression at low oxygen levels.

    PubMed

    Hand, S C

    1998-04-01

    Depression of the production and consumption of cellular energy appears to be a prerequisite for the survival of prolonged bouts of anoxia. A correlation exists between the degree of metabolic depression under anoxia and the duration of anoxia tolerance. In the case of brine shrimp (Artemia franciscana) embryos, oxygen deprivation induces a reversible quiescent state that can be tolerated for several years with substantial survivorship. A global arrest of cytoplasmic translation accompanies the transition into anoxia, and rates of protein synthesis in mitochondria from these embryos appears to be markedly reduced in response to anoxia. Previous evidence suggests that the acute acidification of intracellular pH (pHi) by over 1.0 unit during the transition into anoxia contributes to the depression of biosynthesis, but message limitation does not appear to play a role in the down-regulation in either cellular compartment. The ontogenetic increase in mRNA levels for a mitochondrial-encoded subunit of cytochrome c oxidase (COX I) and for nuclear-encoded actin is blocked by anoxia and aerobic acidosis (artificial quiescence imposed by intracellular acidification under aerobic conditions). Further, the levels of COX I and actin mRNA do not decline appreciably during 6 h bouts of quiescence, even though protein synthesis is acutely arrested across this same period. Thus, the constancy of mRNA levels during quiescence indicates that reduced protein synthesis is not caused by message limitation but, instead, is probably controlled at the translational level. This apparent stabilization of mRNA under anoxia is mirrored in an extension of protein half-life. The ubiquitin-dependent pathway for protein degradation is depressed under anoxia and aerobic acidosis, as judged by the acute drop in levels of ubiquitin-conjugated proteins. Mitochondrial protein synthesis is responsive to both acidification of pHi and removal of oxygen per se. Matrix pH declines in parallel with pHi, and

  7. Metabolic Disorders

    MedlinePlus

    ... as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body ... that produce the energy. You can develop a metabolic disorder when some organs, such as your liver or ...

  8. Sever's Disease

    MedlinePlus

    ... Tests How do I know if my child's heel pain is caused by Sever's disease? In Sever's disease, heel pain can be in one or both heels. It ... cut down or stop any activity that causes heel pain. Apply ice to the injured heel for 20 ...

  9. 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

  10. Severe Sarcoidosis.

    PubMed

    Kouranos, Vasileios; Jacob, Joe; Wells, Athol U

    2015-12-01

    In sarcoidosis, reduction in mortality and the prevention of disability due to major organ involvement are treatment goals. Thus, it is important to recognize severe disease and identify patients at higher risk of progression to severe disease. In this article, fibrotic lung disease and cardiac sarcoidosis are reviewed as the major contributors to sarcoidosis mortality and morbidity. In the absence of a standardized definition of severe pulmonary disease, a multidisciplinary approach to clinical staging is suggested, based on symptoms, pulmonary function tests, and imaging findings at presentation, integrated with the duration of disease and longitudinal disease behavior during early follow-up. PMID:26593144

  11. Sever's Disease

    MedlinePlus

    ... Are Reading Upsetting News Reports? What to Say Vaccines: Which Ones & When? Smart School Lunches Emmy-Nominated Video "Cerebral Palsy: Shannon's Story" 5 Things to Know About Zika & Pregnancy Sever's Disease KidsHealth > ...

  12. 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

  13. Cryoamputation as a temporizing measure in severe burn injury.

    PubMed

    Pennington, J Daniel; Wall, Anji E; Schlesinger, Joseph J; Higdon, Kent K; Weavind, Liza

    2014-01-01

    Cryoamputation, or physiologic amputation, is a well-described procedure typically used to amputate gangrenous lower extremities. In such cases the patient is too unstable for transport to the operating room, so cryoamputation using dry ice or other refrigerant allows for immediate bedside intervention and later operative amputation when the patient is more stable. In this study the authors describe the use of cryoamputation to stabilize a burn patient with a nonviable upper extremity considered to be contributing significantly to his metabolic acidosis. This experience suggests that cryoamputation may be a reasonable technique to consider when a burn patient presents with a nonviable extremity but is too unstable for immediate operative amputation. PMID:24978024

  14. 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

    2014-01-01

    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

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

    PubMed

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

    2014-12-01

    The objective of the study was to determine the effect of active dry Saccharomyces cerevisiae (ADSC) supplementation on dry matter intake, milk yield, milk components, ruminal pH, and microbial community during a dietary regimen that leads to subacute ruminal acidosis (SARA). Sixteen multiparous, rumen-cannulated lactating Holstein cows were randomly assigned to 1 of 2 dietary treatments that included ADSC (Biomate; AB Vista, Marlborough, UK; 8 × 10(10) cfu/head per day) or control. During wk 1 to 6, all cows received a high-forage (HF) diet (77:23, forage:concentrate). Cows were then abruptly switched during wk 7 to a high-grain (HG) diet (49:51, forage:concentrate) and remained on the HG until the end of wk 10. Feed intake and milk yields were recorded daily. Ruminal pH was recorded continuously using an indwelling system for 1 to 2 d per week during the pre-experimental phase, and wk 6, 7, and 10. Ruminal digesta samples were collected at the end of the experiment and analyzed for relative change in microbial communities using real-time quantitative PCR. Cows were considered to have SARA if the duration below pH 5.6 was ≥300 min/d. Ruminal pH during wk 6 (HF plateau) was not different across treatments (15 ± 46 min/d at pH <5.6). The dietary regimen successfully induced SARA during wk 7 (transition from HF to HG diet), and ruminal pH (551 ± 46 min/d at pH <5.6) was not different across treatments. However, cows receiving ADSC had an improved ruminal pH (122 ± 57 vs. 321 ± 53 min/d at pH <5.6) during wk 10 (HG plateau) compared with control. Additionally, cows receiving ADSC had a better dry matter intake (23.3 ± 0.66 vs. 21.6 ± 0.61 kg/d) and 4% fat-corrected milk yield (29.6 ± 1.2 vs. 26.5 ± 1.2 kg/d) than control cows during the HG phase (wk 8 to 10). During HG feeding, cows receiving ADSC had greater total volatile fatty acid and propionate concentrations (175 ± 7.5 vs. 154 ± 7.5 and 117 ± 6.1 vs. 94 ± 5.7 mM for ADSC and control, respectively

  16. A grain-based subacute ruminal acidosis challenge causes translocation of lipopolysaccharide and triggers inflammation.

    PubMed

    Khafipour, E; Krause, D O; Plaizier, J C

    2009-03-01

    The effects of a grain-based subacute ruminal acidosis (SARA) challenge on translocation of lipopolysaccharide (LPS) into the peripheral circulation, acute phase proteins in blood and milk, feed intake, milk production and composition, and blood metabolites were determined in 8 lactating Holstein cows. Between wk 1 and 5 of 2 successive 6-wk periods, cows received a total mixed ration ad libitum with a forage to concentrate (F:C) ratio of 50:50. In wk 6 of both periods, the SARA challenge was conducted by replacing 21% of the dry matter of the total mixed ration with pellets containing 50% wheat and 50% barley. Rumen pH was monitored continuously using indwelling pH probes in 4 rumen cannulated cows. Rumen fluid samples were collected 15 min before feed delivery and at 2, 4, 6, 12, 14, 16, 18, and 24 h after feed delivery for 2 d during wk 5 (control) and wk 6 (SARA). Peripheral blood samples were collected using jugular catheters 15 min before feeding and at 6 and 12 h after feeding at the same days of the rumen fluid collections. The SARA challenge significantly reduced average daily pH from 6.17 to 5.97 and increased the duration of rumen pH below pH 5.6 from 118 to 279 min/d. The challenge reduced dry matter intake (16.5 vs. 19 kg/d), milk yield (28.3 vs. 31.6 kg/d), and milk fat (2.93 vs. 3.30%, 0.85 vs. 0.97 kg/d), and tended to increase milk protein percentage (3.42 vs. 3.29%), without affecting milk protein yield (1.00 vs. 0.98 kg/d). The challenge also increased the concentration of free LPS in rumen fluid from 28,184 to 107,152 endotoxin units (EU)/mL. This was accompanied by an increase in LPS in peripheral blood plasma (0.52 vs. <0.05 EU/mL) with a peak at 12 h after feeding (0.81 EU/mL). Concentrations of the acute phase proteins serum amyloid A, haptoglobin, and LPS-binding protein (LBP) in peripheral blood as well as LBP concentration in milk increased (438.5 vs. 167.4, 475.6 vs. 0, 53.1 vs. 18.2, and 6.94 vs. 3.02 microg/mL, respectively) during

  17. Dysregulated metabolism contributes to oncogenesis.

    PubMed

    Hirschey, Matthew D; DeBerardinis, Ralph J; Diehl, Anna Mae E; Drew, Janice E; Frezza, Christian; Green, Michelle F; Jones, Lee W; Ko, Young H; Le, Anne; Lea, Michael A; Locasale, Jason W; Longo, Valter D; Lyssiotis, Costas A; McDonnell, Eoin; Mehrmohamadi, Mahya; Michelotti, Gregory; Muralidhar, Vinayak; Murphy, Michael P; Pedersen, Peter L; Poore, Brad; Raffaghello, Lizzia; Rathmell, Jeffrey C; Sivanand, Sharanya; Vander Heiden, Matthew G; Wellen, Kathryn E

    2015-12-01

    Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review "Hallmarks of Cancer", where dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results demonstrate that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it. PMID:26454069

  18. Characteristics of metabolism during prolonged water immersion.

    PubMed

    Tigranyan, R A

    1975-01-01

    The effect on the organism of a 12-day stay in a water immersion medium (head on the water surface) was studied on 10 subjects. The condition of the metabolic processes in the subjects was judged from the investigation of the parameters of protein and carbohydrate metabolism, acid-base equilibrium, the activity of a number of enzymes and steroid hormones. The venous blood and diurnal urine served as the material for conducting the corresponding biochemical determinations. The stay in an immersion medium is accompanied by a significant increase in the content of residual nitrogen in the blood, by a reduction of the creatinine content in the blood and by an increase of the creatine content of the blood with the simultaneous increase of the excretion of creatinine and creatine with the urine, by a significant increase of the glucose and lactate content in the blood, by the development of acidosis of a respiratory and metabolic character, as well as by a significant increase of the activity of creatine phosphokinase and the isoenzyme fraction of lactate dehydrogenase3. In all the subjects, an expressed intensification of the glucocorticoid and androgenic functions of the adrenal cortex is noted during the experimental period. PMID:11887912

  19. 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 α-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 μm, 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

  20. The Effects of Lung Protective Ventilation or Hypercapnic Acidosis on Gas Exchange and Lung Injury in Surfactant Deficient Rabbits

    PubMed Central

    Hummler, Helmut D.; Banke, Katharina; Wolfson, Marla R.; Buonocore, Giuseppe; Ebsen, Michael; Bernhard, Wolfgang; Tsikas, Dimitrios; Fuchs, Hans

    2016-01-01

    Background Permissive hypercapnia has been shown to reduce lung injury in subjects with surfactant deficiency. Experimental studies suggest that hypercapnic acidosis by itself rather than decreased tidal volume may be a key protective factor. Objectives To study the differential effects of a lung protective ventilatory strategy or hypercapnic acidosis on gas exchange, hemodynamics and lung injury in an animal model of surfactant deficiency. Methods 30 anesthetized, surfactant-depleted rabbits were mechanically ventilated (FiO2 = 0.8, PEEP = 7cmH2O) and randomized into three groups: Normoventilation-Normocapnia (NN)-group: tidal volume (Vt) = 7.5 ml/kg, target PaCO2 = 40 mmHg; Normoventilation-Hypercapnia (NH)-group: Vt = 7.5 ml/kg, target PaCO2 = 80 mmHg by increasing FiCO2; and a Hypoventilation-Hypercapnia (HH)-group: Vt = 4.5 ml/kg, target PaCO2 = 80 mmHg. Plasma lactate and interleukin (IL)-8 were measured every 2 h. Animals were sacrificed after 6 h to perform bronchoalveolar lavage (BAL), to measure lung wet-to-dry weight, lung tissue IL-8, and to obtain lung histology. Results PaO2 was significantly higher in the HH-group compared to the NN-group (p<0.05), with values of the NH-group between the HH- and NN-groups. Other markers of lung injury (wet-dry-weight, BAL-Protein, histology-score, plasma-IL-8 and lung tissue IL-8) resulted in significantly lower values for the HH-group compared to the NN-group and trends for the NH-group towards lower values compared to the NN-group. Lactate was significantly lower in both hypercapnia groups compared to the NN-group. Conclusion Whereas hypercapnic acidosis may have some beneficial effects, a significant effect on lung injury and systemic inflammatory response is dependent upon a lower tidal volume rather than resultant arterial CO2 tensions and pH alone. PMID:26840779

  1. Effects of grain, fructose, and histidine on ruminal pH and fermentation products during an induced subacute acidosis protocol.

    PubMed

    Golder, H M; Celi, P; Rabiee, A R; Heuer, C; Bramley, E; Miller, D W; King, R; Lean, I J

    2012-04-01

    The effects of grain, fructose, and histidine on ruminal pH and fermentation products were studied in dairy cattle during an induced subacute acidosis protocol. Thirty Holstein heifers were randomly allocated to 5 treatment groups: (1) control (no grain); (2) grain [fed at a crushed triticale dry matter intake (DMI) of 1.2% of body weight (BW)]; (3) grain (0.8% of BW DMI)+fructose (0.4% of BW DMI); (4) grain (1.2% of BW DMI)+histidine (6 g/head); and (5) grain (0.8% of BW DMI)+fructose (0.4% of BW DMI)+histidine (6 g/head) in a partial factorial arrangement. Heifers were fed 1 kg of grain daily with ad libitum access to ryegrass silage and alfalfa hay for 10 d. Feed was withheld for 14 h before challenge day, on which heifers were fed 200 g of alfalfa hay and then the treatment diets immediately thereafter. Rumen samples were collected 5 min after diet ingestion, 60 min later, and at 3 subsequent 50-min intervals. Grain decreased ruminal pH and increased ammonia, total volatile fatty acid (VFA), acetate, butyrate, propionate, and valerate concentrations compared with controls. The addition of grain had no effect on ruminal D- and L-lactate concentrations. Fructose markedly decreased ruminal pH and markedly increased D- and L-lactate concentrations. Fructose increased total VFA and butyrate and decreased valerate concentrations. Although histidine did not have a marked effect on ruminal fermentation, increased concentrations of histamine were observed following feeding. This study demonstrates that the substitution of some grain for fructose can lower ruminal pH and increase VFA and lactate concentrations, warranting further investigation into the role of sugars on the risk of acidosis in dairy cattle. PMID:22459843

  2. Intracellular acidosis modulates the stretch-induced changes in E-C coupling of the rat atrium.

    PubMed

    Tavi, P; Han, C; Weckström, M

    1999-11-01

    By inducing a small reduction of the intracellular pH (0.18 units) with 20 mmol L-1 propionate we demonstrated that acidification changed the responses of isolated rat atria to stretch. Stretch (increase of the intra-atrial pressure) in normal pH increased the Ca2+ transients' amplitude (Indo-1 fluorescence) from 0.26 +/- 0.09 in 1 mmHg to 0.36 +/- 0.13 in 4 mmHg (P < 0.05, n=6), without affecting the diastolic [Ca2+]i level (n.s. n=6). The changes in Ca2+ balance during stretch were accompanied by a biphasic increase in the contraction force. Five minutes of continuous stretch increased the action potential duration (APD90%, P < 0.01, n=13) and decreased the APD15% (P < 0.001, n=13). During acidosis, the stretch-induced increase of the Ca2+ transient amplitude (0.4 +/- 0. 13 vs. 0.3 +/- 0.08, P < 0.05, n=6) was accompanied by the increase of the diastolic [Ca2+]i (1.16 +/- 0.07, P < 0.05, n=6) compared with non-acidotic control (1.06 +/- 0.06, n=6). Acidic intracellular pH also inhibited the stretch-induced changes in the action potentials (n=10) and slowed down the development of the contractile force during stretch. The results showed that acidosis modulates the mechanotransduction. It does this by interfering with the intracellular Ca2+ balance, inhibiting the Ca2+ extrusion mechanisms and reducing the Ca2+-buffering power of the cells. The physiological and pathological processes associated with stretch are therefore modulated by intracellular pH owing to its concerted effects on intracellular Ca2+ handling caused by a competitive inhibition of various Ca2+-binding molecules. PMID:10606822

  3. Fully Balanced Fluids do not Improve Microvascular Oxygenation, Acidosis and Renal Function in a Rat Model of Endotoxemia.

    PubMed

    Ergin, Bulent; Zafrani, Lara; Kandil, Asli; Baasner, Silke; Lupp, Corinna; Demirci, Cihan; Westphal, Martin; Ince, Can

    2016-07-01

    The expectation of fluid therapy in patients with septic shock is that it corrects hypovolemia, with the aim of restoring tissue perfusion and oxygenation and organ function. This study investigated whether different types of resuscitation fluids were effective in improving renal microcirculatory oxygenation, acidosis, oxidative stress, and renal function in a rat model of endotoxemic shock. Five groups of rats were used: a sham group, a lipopolysaccharide (LPS) group, and three LPS groups that received 30 mL/kg/h of 0.9% sodium chloride (0.9% NaCl), a new bicarbonate buffered crystalloid solution closely resembling the composition of plasma (FB-Cxt) or a hydroxyethyl starch-ringer acetate solution. Systemic hemodynamic variables, renal blood flow, microvascular oxygenation, oxidative/nitrosative stress, and renal function were measured. LPS-induced shock was only partially resolved by fluid administration. Animals became arterially hypotensive despite adequate central venous pressure. Hydroxyethyl starch-ringer acetate was more effective at improving arterial pressures and renal blood flow than 0.9% NaCl or FB-Cxt. Fluids had marginal effects on pH and HCO3 levels irrespective of the buffer, or on renal μPO2 and dysfunction. Colloids increased the markers of renal oxidative stress (P < 0.001), whereas unbalanced crystalloids increased the markers of nitrosative stress during sepsis (P < 0.01). Endotoxemia-induced acidosis and decreases in renal μPO2 or renal injury were not corrected solely by fluid resuscitation, irrespective of the buffer of the fluid. Our study supported the idea that fluids must be supplemented by other compounds that specifically correct renal inflammation and oxygenation to be effective in resolving septic shock-induced renal failure. PMID:26825634

  4. 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.

  5. 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

  6. Oxygen-deficient metabolism and corneal edema.

    PubMed

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

    2011-11-01

    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

  7. Metabolic ecology.

    PubMed

    Humphries, Murray M; McCann, Kevin S

    2014-01-01

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

  8. Niche metabolism in parasitic protozoa

    PubMed Central

    Ginger, Michael L

    2005-01-01

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

  9. [Severe asthma].

    PubMed

    González, Claudio D

    2016-01-01

    The objectives of this work were to investigate the frequency of severe asthma (SA) according to WHO definition and to compare SA patients' characteristics with those of non-severe asthma (NSA); secondly, to investigate the level of control reached throughout a period of regular treatment. Between 1-1-2005 and 12-31-2014, 471 medical records from patients with bronchial asthma assisted in Buenos Aires City were analyzed. SA frequency was 40.1% (189/471), being significantly higher among patients from the public health system (47.7%, 108/226 vs. 33%, 81/245, p = 0.001). SA patients were older than NSA ones (51.3 ± 17.4 vs. 42.6 ± 17.1 years, p = 0.000), presented longer time since onset of the disease (median 30 vs. 20 years, p = 0.000), lower educational levels (secondary level or higher 41.7% vs. 58.1%, p = 0.000), lower frequency of rhinitis (47% vs. 60.6%, p = 0.004), more severe levels of airway obstruction (FEV% 50.2 ± 13.7 vs. 77.7 ± 12.4, p = 0.000), more frequent antecedents of Near Fatal Asthma (11.1% vs. 2.8%, p = 0.000), higher levels of serum IgE (median of 410 vs. 279 UI/l, p = 0.01) and higher demand of systemic steroids requirements and hospitalizations (68.7% vs. 50.7%, p = 0.000 and 37.5% vs. 15.9%, p = 0.000, respectively). A 30.6% of SA patients (58/189) reached a follow-up period of 12 months, 13 (22.5%) of whom reached the controlled asthma level. The frequency of SA found seems to be considerable. Multicenter studies to investigate the levels of control reached by SA patients with access to proper treatment are recommended. PMID:26826988

  10. A severe case of vasoplegic shock following metformin overdose successfully treated with methylene blue as a last line therapy.

    PubMed

    Graham, Rachel Erin; Cartner, Michaela; Winearls, James

    2015-01-01

    A 44-year-old man presented to hospital 24 h after an intentional overdose of metformin and gliclazide. He had a critical metabolic acidosis on presentation with a pH of 6.88, and very rapidly deteriorated into distributive shock refractory to large volume fluid resuscitation and massive doses of vasopressors. We introduced a methylene blue infusion as a rescue therapy in an attempt to improve the patient's haemodynamics, which was successful. The patient made a full recovery with no long-term sequelae. PMID:26150642

  11. Simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro

    PubMed Central

    Sørensen, Brita Singers; Busk, Morten; Overgaard, Jens; Horsman, Michael R.; Alsner, Jan

    2015-01-01

    Background The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect), which weakens the spatial linkage between hypoxia and acidosis. Methods Five different human squamous cell carcinoma cell lines (SiHa, FaDuDD, UTSCC5, UTSCC14 and UTSCC15) were treated with hypoxia, acidosis (pH 6.3), or a combination, and gene expression analyzed using microarray. SiHa and FaDuDD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of 35S-labelled methionine and cysteine into protein. Results Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pHe), genes induced at low oxygen at both normal and low pHe, and genes induced at low pHe independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2), and Ribosomal protein L37 (RPL37). Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa) and protein synthesis (both cell lines) was observed when hypoxia and low pHe were combined. Conclusions We demonstrate here that the influence of hypoxia and acidosis causes different responses, both

  12. Metabolic and Cardiovascular Implications of a Metabolically Healthy Obesity Phenotype

    PubMed Central

    Seo, Mi Hae

    2014-01-01

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

  13. Mammalian Sirtuins and Energy Metabolism

    PubMed Central

    Li, Xiaoling; Kazgan, Nevzat

    2011-01-01

    Sirtuins are highly conserved NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies. The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response. Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals. This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes. PMID:21614150

  14. Gut Microbiota and Metabolic Disorders.

    PubMed

    Hur, Kyu Yeon; Lee, Myung-Shik

    2015-06-01

    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. PMID:26124989

  15. 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