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Metabolic acidosis  


Arterial blood gas Serum electrolytes Urine pH Arterial blood gas analysis or a serum electrolytes test (such as a basic metabolic panel) will confirm acidosis is present and determine ... test may be needed to determine the cause of the acidosis.


Metabolic Acidosis  

Microsoft Academic Search

\\u000a 1.?Normal acid–base balance is crucial for proper cell function and integrity.\\u000a \\u000a 2.?Metabolic acidosis is due to either the loss of blood buffers, or the gain of non-volatile strong acids.\\u000a \\u000a \\u000a 3.?An organized, step-wise approach (the “ABCDE toolkit”) is crucial in determining both the magnitude and the cause of a\\u000a metabolic acidosis and deciding upon appropriate therapy.\\u000a \\u000a \\u000a \\u000a 4.?Base excess is a measure

Howard E. Corey; Uri S. Alon


Unexpectedly severe metabolic acidosis associated with sodium thiosulfate therapy in a patient with calcific uremic arteriolopathy.  


Calcific uremic arteriolopathy, formerly known as calciphylaxis is a devastating condition that primarily affects patients with end-stage renal disease. The lesions can progress to massive ulcerations of the subcutaneous tissue that are associated with a high degree of morbidity and mortality, usually related to sepsis. Although the pathophysiology of this condition is poorly understood, it appears to be related to a derangement in calcium-phosphate metabolism. Thus, treatments have focused on the treatment of hyperparathyroidism albeit with poor results. More recently, sodium thiosulfate (STS) has emerged as a promising therapy following multiple case reports of marked disease regression following its use. As STS is a strong acid, metabolic acidosis has been described following its administration, although relatively mild in degree. We report a case of a patient with calciphylaxis who repeatedly developed a severe anion gap metabolic acidosis following each dose of STS requiring a significant reduction in the dose. PMID:21338397

Selk, Natalie; Rodby, Roger A


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

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.



Metabolic acidosis in toluene sniffing.  


ABSTRACTToluene sniffing, frequently described under the generic category of "glue sniffing," is a potential cause of normal anion gap metabolic acidosis due to distal renal tubular acidosis. Urine anion gap is used to diagnose metabolic acidosis of a normal anion gap variety; however, pitfalls exist when using urine anion gap in the setting of toluene sniffing. We present the case of a young woman who had a normal anion gap metabolic acidosis due to toluene sniffing and an unexpectedly low urine anion gap. In such a scenario, the urine anion gap will underestimate the rate of ammonia excretion when the conjugate bases of acids other than HCl are excreted in large quantities. Estimation of the urine osmolal gap will provide a more accurate ammonia excretion rate in these circumstances. The challenges in interpretation of the urine anion gap and ammonia excretion in the setting of distal renal tubular acidosis due to toluene toxicity are discussed. PMID:23778000

Tuchscherer, Jon; Rehman, Habib



Benzonatate toxicity in a teenager resulting in coma, seizures, and severe metabolic acidosis.  


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

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



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

PubMed Central

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

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



Fatal metabolic acidosis caused by thiamine deficiency.  


Acute thiamine deficiency, an uncommon cause of hemodynamic instability in Western countries, may be manifested by acute heart failure and neurological deficits. Severe metabolic acidosis is one of its least recognized features. We present a report of foreign workers who complained of weakness and lower limb edema and were found to have acute thiamine deficiency. One died of refractory metabolic acidosis and shock, and the diagnosis was reached post mortem. Thiamine deficiency should be considered in every case of severe lactic acidosis without an obvious cause, especially in high-risk populations (malnourished, alcoholics, Far-East workers, etc). Whenever it is suspected, empiric treatment with thiamine should be initiated immediately. Physicians who care for populations at risk should be familiar with the clinical spectrum of nutritional deficits, and monitor the nutritional habits of these patients carefully. The treatment is inexpensive and devoid of adverse effects. Moreover, delaying thiamine administration in patients with deficiency may cause severe life-threatening metabolic acidosis and affect recovery. The prophylactic use of thiamine in a high-risk population, even before blood levels are received, may be cost effective. PMID:15028327

Klein, Moti; Weksler, Natan; Gurman, Gabriel M



Metabolic acidosis and infant feeding.  

PubMed Central

Most cows' milk based formulae for infant feeding present a greater acid load to the infant than breast milk. To determine the effect of this difference the acid base state of 180 healthy term infants was measured on the sixth day of life and related to the type of feed. Those infants fed on cows' milk formula (SMA) had a mean pH of 7-34 +/- 0-05 and a base deficit of 8-8 +/- 3-1, while those fed on breast milk had a mean pH of 7-38 +/- 0-05 and a base deficit of 5-6 +/- 3-1. The difference between the two groups of infants was significant for both these measurements. Metabolic acidosis was defined as a base deficit greater than 10 mmol/l. Seventy-four per cent of the 34 infants who were acidotic at six days were bottle-fed. There was a significant correlation between the pH of the feed and the degree of acidosis in the infant as measured by the base deficit. The findings suggest that when breast milk is not available a pH-adjusted milk formula would be desirable for preventing and treating neonatal metabolic acidosis.

Moore, A; Ansell, C; Barrie, H



Metabolic Acidosis of Chronically Hemodialyzed Patients  

Microsoft Academic Search

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

Vedran Kovacic; Luka Roguljic; Vinko Kovacic



Metabolic acidosis: pathophysiology, diagnosis and management  

Microsoft Academic Search

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

Jeffrey A. Kraut; Nicolaos E. Madias



An Unusual Case of Refractory Metabolic Acidosis  

PubMed Central

Homeopathy is one of the most frequently used systems of complementary and alternative medicine. The patients who seek homeopathic treatment are primarily those suffering from long-standing, chronic diseases. These medicines may have considerable risk of severe side effects. Some homeopathic medicinal preparations use alcohol as a base and are frequently prescribed for common conditions. We hereby report an unusual case of refractory metabolic acidosis after homeopathic medicinal treatment.

Sawlani, Kamal Kumar; Chaudhary, Shyam Chand; Patil, Malagouda Rajagouda; Yathish, Besthanahalli Errapa; Chandra, Amit



Pharmacologically-induced metabolic acidosis: a review.  


Metabolic acidosis may occasionally develop in the course of treatment with drugs used in everyday clinical practice, as well as with the exposure to certain chemicals. Drug-induced metabolic acidosis, although usually mild, may well be life-threatening, as in cases of lactic acidosis complicating antiretroviral therapy or treatment with biguanides. Therefore, a detailed medical history, with special attention to the recent use of culprit medications, is essential in patients with acid-base derangements. Effective clinical management can be handled through awareness of the adverse effect of certain pharmaceutical compounds on the acid-base status. In this review, we evaluate relevant literature with regard to metabolic acidosis associated with specific drug treatment, and discuss the clinical setting and underlying pathophysiological mechanisms. These mechanisms involve renal inability to excrete the dietary H+ load (including types I and IV renal tubular acidoses), metabolic acidosis owing to increased H+ load (including lactic acidosis, ketoacidosis, ingestion of various substances, administration of hyperalimentation solutions and massive rhabdomyolysis) and metabolic acidosis due to HCO3- loss (including gastrointestinal loss and type II renal tubular acidosis). Determinations of arterial blood gases, the serum anion gap and, in some circumstances, the serum osmolar gap are helpful in delineating the pathogenesis of the acid-base disorder. In all cases of drug-related metabolic acidosis, discontinuation of the culprit medications and avoidance of readministration is advised. PMID:20397738

Liamis, George; Milionis, Haralampos J; Elisaf, Moses



Metabolic acidosis during treatment of mushroom poisoning: a diagnostic pitfall.  


Metabolic acidosis is a frequently encountered acid-base disturbance in hospitalized patients that occasionally develops in the course of treatment with medications used in everyday clinical practice, including propylene glycol-containing drugs (lorazepam, diazepam, etomidate, pentobarbital). Disruption of enterohepatic circulation with activated charcoal is a common practice for several intoxications, including mushroom poisoning. Herein, we present a patient who was hospitalized due to mushroom intoxication and developed severe metabolic acidosis as a treatment side effect rather than from the mushroom poisoning. To the best of our knowledge, this is the first report on propylene glycol-containing activated charcoal-induced metabolic acidosis. PMID:22576391

Gatselis, Nikolaos K; Liamis, George; Makaritsis, Konstantinos P; Dalekos, George N



Metabolic acidosis of chronically hemodialyzed patients.  


Metabolic acidosis is a condition that is commonly encountered in both chronic renal failure and in end-stage renal disease. Metabolic acidosis is associated with many adverse effects: negative nitrogen balance, increased protein decomposition, anorexia, fatigue, bone lesions, impaired function of the cardiovascular system, impaired function of the gastrointestinal system, hormonal disturbances, insulin resistance, hyperkalemia, altered gluconeogenesis and triglyceride metabolism, increased progression of chronic renal failure, and growth retardation in children. Even 'minor' degrees of metabolic acidosis are deleterious. Metabolic acidosis of end-stage renal patients could be successfully corrected with bicarbonate hemodialysis and with peroral bicarbonate-containing phosphate binders, i.e. calcium carbonate. Bicarbonate powder compared with bicarbonate solutions has some advantages and enables a stabile composition of electrolytes. 'High' dialysate bicarbonate (40- 42 mmol/l) is a safe, well-tolerated and useful tool for better correction of the metabolic acidosis and must become a standard of hemodialysis treatment. Measured postdialysis blood bicarbonate concentration should be obtained at least every month and correction of metabolic acidosis by maintaining serum bicarbonate >or=22 mmol/l should be a goal of the management of patients undergoing chronic hemodialysis. PMID:12649614

Kovacic, Vedran; Roguljic, Luka; Kovacic, Vinko



Metabolic acidosis of CKD: diagnosis, clinical characteristics, and treatment.  


Metabolic acidosis is noted in the majority of patients with chronic kidney disease (CKD) when glomerular filtration rate (GFR) decreases to less than 20% to 25% of normal, although as many as 20% of individuals can have acid-base parameters close to or within the normal range. Acidosis generally is mild to moderate in degree, with plasma bicarbonate concentrations ranging from 12 to 22 mEq/L (mmol/L), and it is rare to see values less than 12 mEq/L (mmol/L) in the absence of an increased acid load. Degree of acidosis approximately correlates with severity of renal failure and usually is more severe at a lower GFR. The metabolic acidosis can be of the high-anion-gap variety, although anion gap can be normal or only moderately increased even with stage 4 to 5 CKD. Several adverse consequences have been associated with metabolic acidosis, including muscle wasting, bone disease, impaired growth, abnormalities in growth hormone and thyroid hormone secretion, impaired insulin sensitivity, progression of renal failure, and exacerbation of beta 2 -microglobulin accumulation. Administration of base aimed at normalization of plasma bicarbonate concentration might be associated with certain complications, such as volume overload, exacerbation of hypertension, and facilitation of vascular calcifications. Whether normalization of plasma bicarbonate concentrations in all patients is desirable therefore requires additional study. In the present review, we describe clinical and laboratory characteristics of metabolic acidosis, discuss potential adverse effects, and address benefits and complications of therapy. PMID:15957126

Kraut, Jeffrey A; Kurtz, Ira



Hypokalemic metabolic acidosis attributed to cough mixture abuse  

Microsoft Academic Search

This report describes a patient with mixed normal anion gap hyperchloremic metabolic and respiratory acidosis associated with hypokalemia attributed to cough mixture abuse. Metabolic acidosis was likely related to an overdose of ammonium chloride, whereas respiratory acidosis was probably related to the effect of hypokalemia on respiratory muscles, causing hypoventilation. Hypokalemia was caused by a transcellular shift of potassium induced

Kim Ming Wong; Wai Leung Chak; Chi Yuen Cheung; Yiu Han Chan; Koon Shing Choi; Ka Foon Chau; Chun Sang Li



Acute kidney injury, hyperosmolality and metabolic acidosis associated with lorazepam  

Microsoft Academic Search

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

Irfan Yusufzai; Anna Sullivan; Charles Graeber; Tausif Zar



Severe, self-limiting lactic acidosis and rhabdomyolysis accompanying convulsions  

Microsoft Academic Search

A 26 year old man with no previous history of convulsions presented in status epilepticus and severe lactic acidosis. He regained consciousness and the acidosis resolved after several hours of conservative management without intravenous bicarbonate, but he developed severe myalgia associated with marked elevation of creatine kinase and moderate raised plasma creatinine levels which resolved spontaneously after 3 days. Severe

P. H. Winocour; A. Waise; G. Young; K. J. Moriarty



Lactic acidosis in children with acute exacerbation of severe asthma.  


This is a retrospective case series reporting lactic acidosis in four pediatric patients with acute severe asthma treated with nebulized beta2-agonists in a pediatric intensive care unit of a tertiary care teaching facility. During treatment with beta2-agonists, these patients developed lactic acidosis with a peak concentration of 5.2 to 13 mmol/l. Lactic acidosis improved within 24 h after discontinuation or decrease in the dosage of beta2-agonists. We conclude that the intensive use of beta2-agonists for acute severe asthma in children may be the primary and significant cause of lactic acidosis. PMID:17198331

Koul, Pulin B; Minarik, Milan; Totapally, Balagangadhar R



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

PubMed Central

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

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



Metabolic acidosis inhibits soft tissue calcification in uremic rats.  


Metabolic acidosis is common in patients with chronic kidney disease, which is known to affect bone metabolism. We examined the effect of metabolic acidosis on the development of vascular and other soft-tissue calcifications in uremic rats treated with calcitriol. Extraskeletal calcification was measured in vivo, in control rats and rats with a remnant kidney model of uremia with or without ammonium chloride-induced acidosis. Soft-tissue calcification was assessed histologically, by measurement of the expression of the sodium-dependent phosphate cotransporter Pit-1 and by quantification of tissue calcium and phosphorus. Calcitriol administration to uremic rats resulted in significant deposition of material positive for von Kossa stain in the aorta, stomach, and kidney, elevated aortic calcium and phosphorus, increased aortic Pit-1 expression, and high mortality. Calcitriol-treated uremic rats with acidosis did not develop aortic or soft-tissue calcification, did not increase aortic Pit-1 expression, and had significantly lower mortality. Additionally, an acidotic environment prevented calcification of vascular smooth muscle cells in vitro. Our study shows that metabolic acidosis inhibits extraskeletal calcification. PMID:17989650

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



Metabolic Factors Influencing Myocardial Recovery from Acidosis (CiC3).  

National Technical Information Service (NTIS)

The mechanisms involved in cardiac dysfunction during acidosis were explored in an isolated heart model. Metabolic acidosis was observed to cause marked functional and energy metabolic derangement consistent with a primary impairment of energy production....

J. I. Shapiro J. Doers R. F. Kucera M. McCormick N. Elkins



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


Background: Pathophysiologic changes after brain death can lead to acid-base disturbances. The primary aim of this study was to clarify the acid-base state and its source in brain dead donors using Stewart's approach. Additionally, we investigated whether the presence of metabolic acidosis affected the number of organs retrieved from donors. Methods: A retrospective review of electronic medical records was performed for brain dead donors who had undergone organ harvesting during the past 5 years in a tertiary medical center. The parameters related to acid-base disturbance and the number of organs retrieved from the donors was assessed. Results: Sixty one brain dead donors were evaluated in this study. Twenty three (37.7%) of these patients had metabolic acidosis at the initial diagnosis of brain death. Metabolic acidosis resulted from hyperchloremia and a large strong ion gap. The severity of metabolic acidosis was masked by hypernatremia and hypoalbuminemia. In addition, donors without metabolic acidosis also showed mixed acid-base disturbances in which metabolic acidosis induced by significant hyperchloremia was combined with metabolic alkalosis caused by hypoalbuminemia and hypernatremia. Although more organs were retrieved from the donors without metabolic acidosis than those with metabolic acidosis (P=0.012), serum albumin level (P=0.010) and donor age (P<0.001), rather than metabolic acid-base disturbances, significantly correlated with the number of organs retrieved in multivariate regression analysis. Conclusion: Most brain dead donors exhibited metabolic acid-base disturbances. However, rather than metabolic acidosis, serum albumin level and donor age were well correlated with the number of organs retrieved. PMID:24042153

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



Evidence for an independent role of metabolic acidosis on nutritional status in haemodialysis patients  

Microsoft Academic Search

considered with caution as an estimate of the dietary protein intake in HD patients in the presence of Background. Malnutrition in haemodialysis (HD) patients has been referred to underdialysis with low metabolic acidosis. protein intake, and to acidosis. However, the separate Key words: acidosis; haemodialysis; nutrition; PCRn; eVects of underdialysis and acidosis on nutrition have Kt\\/V; serum albumin not been

Ezio Movilli; Nicola Bossini; Battista F. Viola; Corrado Camerini; Giovanni C. Cancarini; Paolo Feller; Achille Strada; Rosario Maiorca


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

Microsoft Academic Search

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

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



Arterial oxygen saturation in relation to metabolic acidosis in fetal lambs  

Microsoft Academic Search

OBJECTIVE: We studied the relationship between preductal arterial oxygen saturation and metabolic acidosis in 18 chronically instrumented fetal lambs (gestational age 119 to 133 days) in two experimental designs. In the first group the onset of metabolic acidosis was determined. In the second group the progression of metabolic acidosis was studied as was the cardiovascular and hormonal changes resulting from

Roel Nijland; Henk W. Jongsma; Jan G. Nijhuis; Paul P. van den Berg; Berend Oeseburg



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

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/or increased serum 1,25-(OH)2D concentrations.

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



Chronic metabolic acidosis alters osteoblast differentiation from human mesenchymal stem cells  

Microsoft Academic Search

Bone histology of distal renal tubular acidosis patients showed decreased bone formation with impaired bone matrix mineralization that is not entirely explained by an alteration in the mineral balance. Data from in vitro studies suggests a direct inhibitory effect of metabolic acidosis on osteoblast function. We investigated the effects of chronic metabolic acidosis on osteoblast differentiation from mesenchymal stem cells

S Disthabanchong; P Radinahamed; W Stitchantrakul; S Hongeng; R Rajatanavin



Chronic Low-Grade Metabolic Acidosis in Normal Adult Humans: Pathophysiology and Consequences  

Microsoft Academic Search

Normal adult humans eating modern-day diets have a chronic low-grade metabolic acidosis whose severity is determined in part\\u000a by the net rate of endogenous acid production (NEAP). NEAP varies mainly with diet composition. The greater the quantity of\\u000a organic and sulfuric acids produced from metabolism of animal foods, and the lower the amounts of potassium salts metabolizable\\u000a to bicarbonate, which

Lynda Frassetto; R. Curtis Morris; Karen Todd; Anthony Sebastian


Metabolic acidosis and the importance of balanced equations  

Microsoft Academic Search

Balancing biochemical equations for both mass and charge in metabolic networks is critical but unfortunately ignored too often.\\u000a Failure to do so, for example, results in a common misconception about the origin of protons during lactic fermentation. \\u000a Lactate, rather than lactic acid, is produced by glycolysis, and its production is a mechanism for alleviating intracellular\\u000a acidosis due to glycolysis. This

Teresa W.-M. Fan; Richard M. Higashi



Acidosis-induced osteomalacia: metabolic studies and skeletal histomorphometry.  


The pathogenesis of osteomalacia was investigated in three patients with chronic metabolic acidosis. Serum levels of parathyroid hormone and vitamin D metabolites were measured, and bone biopsy specimens were analyzed after double tetracycline labeling. Parathyroid hormone concentrations were normal in patients 1 and 3 and slightly elevated in patient 2. Vitamin D metabolism was undisturbed. Static indicators of bone remodeling substantiated the diagnosis of osteomalacia in each case. In patient 1 fluorescent microscopy revealed no evidence of tetracycline uptake. In patients 2 and 3 active mineralization was evident at all osteoid seams, but because double labels were rare, the mineral apposition rate appears to have been substantially reduced in most bone-forming units. Our results indicate that acidosis-induced osteomalacia, unlike that due to vitamin D deficiency, may be associated with mineral deposition at every possible site. Nevertheless, like other causes of osteomalacia, metabolic acidosis prevents mineral apposition at a normal rate even if mineral deposition is ubiquitous. We suggest that titration of newly deposited phosphate causes the observed impairment of mineral apposition and ultimately leads to osteomalacia. PMID:3768194

Phelps, K R; Einhorn, T A; Vigorita, V J; Lieberman, R L; Uribarri, J



Regulation of renal amino acid transporters during metabolic acidosis.  


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

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



Effect of acute and chronic metabolic acidosis on serum immunoreactive parathyroid hormone in man  

Microsoft Academic Search

Effect of acute and chronic metabolic acidosis on serum immunoreactive parathyroid hormone in man. The effects of acute and chronic metabolic acidosis on serum immunoreactive parathyroid hormone (iPTH) were studied. Acute metabolic acidosis induced by administration of ammonium chloride (NH4Cl) produced a barely detectable increase in serum iPTH. Chronic NH4Cl administration produced a marked elevation of serum iPTH that was

Fredric L Coe; John J Firpo; Don L Hollandsworth; Laurence Segil; Janet M Canterbury; Eric Reiss; Frederic L Coe



Acute metabolic acidosis enhances circulating parathyroid hormone, which contributes to the renal response against acidosis in the rat.  

PubMed Central

Acute PTH administration enhances final urine acidification in the rat. HCl was infused during 3 h in rats to determine the parathyroid and renal responses to acute metabolic acidosis. Serum immunoreactive PTH (iPTH) concentration significantly increased and nephrogenous adenosine 3H,5H-cyclic monophosphate tended to increase during HCl loading in intact and adrenalectomized (ADX) rats despite significant increments in plasma ionized calcium. Strong linear relationships existed between serum iPTH concentration and arterial bicarbonate or proton concentration (P less than 0.0001). Serum iPth concentration and NcAMP remained stable in intact time-control rats and decreased in CaCl2-infused, nonacidotic animals. Urinary acidification was markedly reduced in parathyroidectomized (PTX) as compared with intact rats during both basal and acidosis states; human PTH-(1-34) infusion in PTX rats restored in a dose-dependent manner the ability of the kidney to acidify the urine and excrete net acid. Acidosis-induced increase in urinary net acid excretion was observed in intact, PTX, and ADX, but not in ADX-thyroparathyroidectomized rats. We conclude that (a) acute metabolic acidosis enhances circulating PTH activity, and (b) PTH markedly contributes to the renal response against acute metabolic acidosis by enhancing urinary acidification.

Bichara, M; Mercier, O; Borensztein, P; Paillard, M



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

Microsoft Academic Search

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

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



The clinical spectrum of chronic metabolic acidosis: Homeostatic mechanisms produce significant morbidity  

Microsoft Academic Search

Chronic metabolic acidosis is a process whereby an excess nonvolatile acid load is chronically placed on the body due to excess acid generation or diminished acid removal by normal homeostatic mechanisms. Two common, often-overlooked clinical conditions associated with chronic metabolic acidosis are aging and excessive meat ingestion. Because the body's homeostatic response to these pathologic processes is very efficient, the

Robert J. Alpern; Khashayar Sakhaee



Addisonian crisis and severe acidosis in a cat: a case of feline hypoadrenocorticism.  


A 4-year-old female neutered British Shorthair cat was presented as an emergency owing to progressive apathy, anorexia, adipsia, weight loss and weakness. Clinical findings showed severe weakness, collapse, weak pulse, bradycardia, hypovolaemia and hypothermia. Blood examinations revealed marked metabolic acidosis, hyponatraemia, hyperkalaemia, hyperphosphataemia, hypercalcaemia, hypochloraemia and azotaemia. The diagnosis of feline hypoadrenocorticism was based on low cortisol and aldosterone plasma levels before and after synthetic adrenocorticotropic hormone administration. Initial treatment consisted of intravenous fluid therapy. After stabilisation a combination of fludrocortisone and prednisolone was given orally. One year after diagnosis the cat is free of clinical signs and in good condition. PMID:23482253

Sicken, Julia; Neiger, Reto



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

Microsoft Academic Search

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

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



Effects of Metabolic Acidosis on Zinc and Calcium Metabolism in Rats  

Microsoft Academic Search

To delineate the potential role of renal acidosis on zinc and calcium metabolism, 24 male Charles River rats, with a mean weight of 154 g, were assigned to four groups of 6 rats each. Three groups of rats were given ammonium chloride for 5 days by stomach tube at dosages of 4, 8, 16 mEq\\/kg\\/day, respectively. The control group received

Mary Jacob; James C. M. Chan



25-Hydroxycholecalciferol to 1,25Dihydroxycholecalciferol: Conversion Impaired by Systemic Metabolic Acidosis  

Microsoft Academic Search

An acute systemic acidosis in vitamin D depleted rats that was induced by ammonium chloride feeding resulted in defective biological hydroxylation of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol. Impaired enzymatic hydroxylation occurred despite the presence of either hypophosphatemia or hypocalcemia. The data suggest that acidosis interferes with the adaptive enzymatic control of 25-hydroxycholecalciferol metabolism in the vitamin D depleted state.

Sook Won Lee; Jean Russell; Louis V. Avioli



Circulating anions usually associated with the Krebs cycle in patients with metabolic acidosis  

Microsoft Academic Search

INTRODUCTION: Acute metabolic acidosis of non-renal origin is usually a result of either lactic or ketoacidosis, both of which are associated with a high anion gap. There is increasing recognition, however, of a group of acidotic patients who have a large anion gap that is not explained by either keto- or lactic acidosis nor, in most cases, is inappropriate fluid

Lui G Forni; William McKinnon; Gwyn A Lord; David F Treacher; Jean-Marie R Peron; Philip J Hilton



AcidBase, Calcium, Potassium and Aldosterone Metabolism in Renal Tubular Acidosis  

Microsoft Academic Search

Classic renal tubular acidosis is characterized by a primary defect in establishment of a large hydrogen ion gradient across the distal renal tubule. Thus the development of hyperchlorenic metabolic acidosis follows. In addition, hypokalemia results from renal potassium wasting and secondary hyperaldosteronism from sodium wasting and contraction of the extracellular fluid. The presenting signs and symptoms are growth retardation, fatigue,

James C. M. Chan



Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients  

PubMed Central

Introduction Acid–base abnormalities are common in the intensive care unit (ICU). Differences in outcome exist between respiratory and metabolic acidosis in similar pH ranges. Some forms of metabolic acidosis (for example, lactate) seem to have worse outcomes than others (for example, chloride). The relative incidence of each type of disorder is unknown. We therefore designed this study to determine the nature and clinical significance of metabolic acidosis in critically ill patients. Methods An observational, cohort study of critically ill patients was performed in a tertiary care hospital. Critically ill patients were selected on the clinical suspicion of the presence of lactic acidosis. The inpatient mortality of the entire group was 14%, with a length of stay in hospital of 12 days and a length of stay in the ICU of 5.8 days. Results We reviewed records of 9,799 patients admitted to the ICUs at our institution between 1 January 2001 and 30 June 2002. We selected a cohort in which clinicians caring for patients ordered a measurement of arterial lactate level. We excluded patients in which any necessary variable required to characterize an acid–base disorder was absent. A total of 851 patients (9% of ICU admissions) met our criteria. Of these, 548 patients (64%) had a metabolic acidosis (standard base excess < -2 mEq/l) and these patients had a 45% mortality, compared with 25% for those with no metabolic acidosis (p < 0.001). We then subclassified metabolic acidosis cases on the basis of the predominant anion present (lactate, chloride, or all other anions). The mortality rate was highest for lactic acidosis (56%); for strong ion gap (SIG) acidosis it was 39% and for hyperchloremic acidosis 29% (p < 0.001). A stepwise logistic regression model identified serum lactate, SIG, phosphate, and age as independent predictors of mortality. Conclusion In critically ill patients in which a measurement of lactate level was ordered, lactate and SIG were strong independent predictors of mortality when they were the major source of metabolic acidosis. Overall, patients with metabolic acidosis were nearly twice as likely to die as patients without metabolic acidosis.

Gunnerson, Kyle J; Saul, Melissa; He, Shui; Kellum, John A



Factors related to post-operative metabolic acidosis following major abdominal surgery.  


BACKGROUND: Metabolic acidosis is frequently observed in perioperative patients, especially those who undergo major surgery. The aim of this study was to evaluate the factors related to post-operative metabolic acidosis and to attempt to identify the clinical effect of metabolic acidosis following major abdominal surgery. METHODS: We included 172 patients admitted to a surgical intensive care unit (ICU) following major abdominal surgery. All cases were divided into either the acidosis or the normal group using immediate post-operative standard base excess (SBE). The following clinical data were retrospectively obtained from the chart and ICU database: basic clinical characteristics, operative data, type and volume of fluid infused during the operation, post-operative arterial blood gas analysis, lactate, and central venous oxygen saturation. RESULTS: The predominant intraoperative fluid was either 0.9% saline or lactated Ringer's solution. The operation length, estimated blood loss, total fluid infused, total saline infused, lactate and corrected chloride were significantly higher in the acidosis group; however, central venous oxygen saturation was lower in the normal group. Among these factors, total infused saline and lactate level were independent factors related to metabolic acidosis. The comparison between the types of fluid revealed that the saline group had a significantly lower SBE, strong ion difference and higher corrected chloride. SBE was significantly correlated with lactate and total infused saline. ICU and hospital length of stay were significantly longer in the acidosis group. CONCLUSIONS: Post-operative metabolic acidosis following major abdominal surgery was closely related to both hyperchloremic acidosis associated with large saline infusion and lactic acidosis caused by lactataemia. PMID:22985420

Park, Chi-Min; Chun, Ho-Kyung; Jeon, Kyeongman; Suh, Gee Young; Choi, Dong Wook; Kim, Sung



Metabolic Acidosis Treatment as Part of a Strategy to Curb Inflammation  

PubMed Central

Abnormalities in systemic acid-base balance may induce significant changes in the immune response, and they may play a significant role in the development or maintenance of immune dysfunction. Different forms of acidosis (metabolic and respiratory) and even different types of metabolic acidosis (hyperchloremic and lactic) may produce different effects on immune function. If alkalization has, or not, some effect on inflammation control is still a matter of speculation. Studies concerning these subjects are limited justifying this paper.

de Nadai, Tales Rubens; de Nadai, Mariane Nunes; Albuquerque, Agnes Afrodite Sumarelli; de Carvalho, Marco Tulio Menezes; Celotto, Andrea Carla; Evora, Paulo Roberto Barbosa



Newborn complications after intrapartum asphyxia with metabolic acidosis in the preterm fetus  

Microsoft Academic Search

OBJECTIVE: Our purpose was to determine the nature of the complications in preterm newborns after intrapartum fetal asphyxia with metabolic acidosis at delivery.STUDY DESIGN: Thirty-seven preterm fetuses with metabolic acidosis were matched with 37 preterm fetuses with normal blood gas measurements at delivery. A complication score expressed the magnitude of newborn complications during the 10 days after delivery.RESULTS: The mean

James A. Low; Constadina Panagiotopoulos; E. Jane Derrick



Atrioventricular conduction abnormality and hyperchloremic metabolic acidosis in toluene sniffing.  


Toluene is an aromatic hydrocarbon with widespread industrial use as an organic solvent. As a result of the euphoric effect and availability of these substances, inhalation of toluene-based products is popular among young adults and children. Chronic or acute exposure is known to cause acid-base and electrolyte disorders, and to be toxic to the nervous and hematopoietic systems. We report a 38-year-old man who suffered from general muscular weakness of all extremities after toluene sniffing, which was complicated with hypokalemic paralysis, atrioventricular conduction abnormality, and normal anion gap hyperchloremic metabolic acidosis. Renal function, serum potassium and acid-base status normalized within 3 days after aggressive potassium chloride and intravenous fluid replacement. Electrocardiography showed regression of first-degree atrioventricular block. Exposure to toluene can lead to cardiac arrhythmias and sudden sniffing death syndrome. Tachyarrhythmia is the classical manifestation of toluene cardiotoxicity. Atrioventricular conduction abnormalities have been rarely mentioned in the literature. Knowledge of the toxicology and medical complications associated with toluene sniffing is essential for clinical management of these patients. PMID:21982470

Tsao, Jian-Hsiung; Hu, Yu-Hui; How, Chorng-Kuang; Chern, Chii-Hwa; Hung-Tsang Yen, David; Huang, Chun-I



Chronic metabolic acidosis in azotemic rats on a high-phosphate diet halts the progression of renal disease  

Microsoft Academic Search

Chronic metabolic acidosis in azotemic rats on a high-phosphate diet halts the progression of renal disease.BackgroundHyperphosphatemia and metabolic acidosis are general features of advanced chronic renal failure (RF), and each may affect mineral metabolism. The goal of the present study was to evaluate the effect of chronic metabolic acidosis on the development of hyperparathyroidism and bone disease in normal and

Aquiles Jara; Arnold J Felsenfeld; Jordi Bover; Charles R Kleeman



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

PubMed Central

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

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



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

PubMed Central

In a crossover study, 5 calves were made acidotic by intermittent intravenous infusion of isotonic hydrochloric acid (HCl) over approximately 24 h. This was followed by rapid (4 h) or slow (24 h) correction of blood pH with isotonic sodium bicarbonate (NaHCO3) to determine if rapid correction of acidemia produced paradoxical cerebrospinal fluid (CSF) acidosis. Infusion of HCl produced a marked metabolic acidosis with respiratory compensation. Venous blood pH (mean ± Sx) was 7.362 ± 0.021 and 7.116 ± 0.032, partial pressure of carbon dioxide (Pco2, torr) 48.8 ± 1.3 and 34.8 ± 1.4, and bicarbonate (mmol/L), 27.2 ± 1.27 and 11 ± 0.96; CSF pH was 7.344 ± 0.031 and 7.240 ± 0.039, Pco2 42.8 ± 2.9 and 34.5 ± 1.4, and bicarbonate 23.5 ± 0.91 and 14.2 ± 1.09 for the period before the infusion of hydrochloric acid and immediately before the start of sodium bicarbonate correction, respectively. In calves treated with rapid infusion of sodium bicarbonate, correction of venous acidemia was significantly more rapid and increases in Pco2 and bicarbonate in CSF were also more rapid. However, there was no significant difference in CSF pH. After 4 h of correction, CSF pH was 7.238 ± 0.040 and 7.256 ± 0.050, Pco2 44.4 ± 2.2 and 34.2 ± 2.1, and bicarbonate 17.8 ± 1.02 and 14.6 ± 1.4 for rapid and slow correction, respectively. Under the conditions of this experiment, rapid correction of acidemia did not provoke paradoxical CSF acidosis.

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



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

Microsoft Academic Search

Dietary-induced metabolic acidosis (DIMA) has been implicated as a significant confounder in the development of osteoporosis. Twenty-four mature ewes were randomly assigned to four groups of six sheep. Group 1 consumed a control diet (ND); group 2 consumed a normal diet (ND) and had ovariectomy (OVX), group 3 consumed a diet that induced metabolic acidosis (MA), without OVX, and group

Jennifer M. MacLeay; Jerry D. Olson; A. Simon Turner



Grocery store baking soda. A source of sodium bicarbonate in the management of chronic metabolic acidosis.  


Oral sodium bicarbonate is used to treat metabolic acidosis in patients with renal tubular acidosis. Since infants and young children are unable to swallow tablets, those affected must ingest sodium bicarbonate in a powder or liquid form. Pharmacy-weighed sodium bicarbonate is expensive and inconvenient to obtain; some pharmacists are reluctant to provide it. We determined that the sodium bicarbonate contained in 8-oz boxes of Arm and Hammer Baking Soda was sufficiently constant in weight that, dissolved in water to a given volume, it yielded a quantitatively acceptable therapeutic solution of sodium bicarbonate at a cost of approximately 3 percent of that of pharmacy-weighed sodium bicarbonate. Grocery store baking soda can be a safe, economical, and convenient source of sodium bicarbonate for the treatment of chronic metabolic acidosis in infants and young children. PMID:6319065

Booth, B E; Gates, J; Morris, R C



Respiratory Adaptation to Acute Metabolic Acidosis in Goats with Ablated Carotid Bodies.  

National Technical Information Service (NTIS)

In awake goats before and after ablation of carotid bodies (CBx) we studied the effect of acute metabolic acidosis (AMA) produced by intravenous infusion of HC1 on resting pulmonary ventilation, on composition of arterial blood and CSF, and on ventilatory...

R. A. Steinbrook S. Havaheri R. A. Gabel J. C. Donovan D. E. Leith



The magnitude of metabolic acidosis is dependent on differences in bicarbonate assays  

Microsoft Academic Search

Metabolic acidosis has been recently recognized as an important comorbid event in the high mortality rates seen in patients with end-stage renal disease. The recognition of hypobicarbonatemia is dependent on a reliable assay for total carbon dioxide (TCO2). It is common practice for dialysis facilities to send blood samples for testing to remote laboratories, which may assay bicarbonate differently than

Susan H. Bray; Ru-Lin Tung; Edward R. Jones



Infantile rickets with severe proximal renal tubular acidosis, responsive to vitamin D  

PubMed Central

A variant of the Fanconi syndrome is reported in an infant with rickets, hypophosphataemia, severe `proximal' renal tubular acidosis, and generalized hyperaminoaciduria. Noteworthy was the absence of glycosuria and cystinosis. Large doses of dihydrotachysterol (DHT) and of alkali controlled all of these abnormalities. Renal function tests including glomerular filtration rate, renal blood flow, ammonia secretion, titratable acidity, and bicarbonate handling were normal when the child was receiving DHT. At age 4½ years total relapse followed the cessation of therapy, and at this time serum parathyroid hormone levels were not raised. Now DHT alone (without alkali supplement) reversed all of the biochemical abnormalities including the acidosis. This child thus has an apparently vitamin D-dependent `proximal' tubular acidosis, which is not due to secondary hyperparathyroidism. ImagesFIG. 1FIG. 2

Huguenin, M.; Schacht, R.; David, R.



Sodium nitroprusside is not associated with metabolic acidosis during intraoperative infusion in children  

PubMed Central

Background Sodium nitroprusside (SNP) is a potent vasodilator that has been used to induce deliberate hypotension in children during surgery involving significant blood loss, including craniofacial and spinal fusion procedures. SNP metabolism liberates cyanide, which may cause interference with cellular energy metabolism, leading to metabolic acidosis and central nervous system injury. We performed a retrospective, case–control study to determine whether the short-term intra-operative use of SNP for deliberate hypotension is associated with metabolic acidosis in children undergoing surgical procedures for craniofacial or spinal anomalies. Cyanide and thiocyanate concentrations were also recorded in patients who received SNP. Methods Data from 166 children undergoing craniofacial and spinal fusion surgery between 2005 and 2010 at Lucile Packard Children's Hospital (LPCH) at Stanford were analyzed. Records from 60 patients who received SNP (SNP group) as part of a multicenter, randomized, double-blind study were compared with records from 106 eligible patients who had blood pressure reduction using anesthetic agents and did not receive SNP (control group). Metabolic acidosis was defined as serum bicarbonate (HCO3) < 18.5 mEq/L. Whole blood CN, plasma thiocyanate and urinary thiocyanate concentrations were measured in patients in the SNP group. Differences in metabolic acidosis rates between the SNP and control groups were assessed through a test of noninferiority in the rate for the SNP group with a noninferiority threshold of 0.2. A z-test was used to test the null hypothesis. The alternative hypothesis was that the difference in these rates was less than 0.2. The same noninferiority threshold of 0.2 was also used to perform separate, secondary tests for noninferiority in the proportion of patients with HCO3 levels below 18.5 mEq/L and the proportion of patients who required HCO3 administration. Results Fewer patients in the SNP group experienced metabolic acidosis compared to the control group (31.7% vs. 36.8%, respectively; p < .001). No whole blood CN levels above the lower limit of quantification were detected in any of the 51 patients with validated CN data. Plasma and urinary thiocyanate levels were also low. Conclusions Our findings suggest that SNP, when used for short-term deliberate hypotension, does not cause an increased incidence of metabolic acidosis compared with the use of anesthetic agents alone. Trial registration Trial registration number: NCT00135668



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

SciTech Connect

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.

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



Effects of tight versus non tight control of metabolic acidosis on early renal function after kidney transplantation  

PubMed Central

Background Recently, several studies have been conducted to determine the optimal strategy for intra-operative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetate)that indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods 120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE) measurements to achieve the normal values of BE (?5 to +5?mEq/L). In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE????15?mEq/L or bicarbonate???10?mEq/L or PH???7.15). Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24?h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.



[Changes in the levels of various substrates of nitrogen metabolism and tricarboxylic acid cycle during experimental acidosis in calves].  


The effect of experimental metabolic acidosis and its correction for nitrogen and energy metabolism was studied in new-born calves. It was discovered that a change in the acid-base balance towards acidosis causes a sharp increase in "ammoniogenesis", urea formation and inhibition of the tricarboxylic acid cycle, which is also observed in calves suffering from dyspepsia with symptoms of acute diarrhea. Alongside with the use of therapeutic measures for treating dyspepsia of new-born calves, it is necessary to control the acid-base balance of blood in the calves and in case of revealing the acidosis state to use means of its correction. PMID:3037745

Mel'nichuk, D A; Liubetskaia, T V; Makarenko, O N


Metabolic Acidosis in Restraint-associated Cardiac ArrestA Case Series  

Microsoft Academic Search

The mechanism of death in patients struggling against restraints remains a topic of de- bate. This article presents a series of five patients with restraint-associated cardiac arrest and profound metabolic acidosis. The lowest recorded pH was 6.25; this patient and three others died despite aggressive resuscitation. The survivor's pH was 6.46; this pa- tient subsequently made a good recovery. Struggling

John L. Hick; Stephen W. Smith; Michael T. Lynch



Mortality and the nature of metabolic acidosis in children with shock  

Microsoft Academic Search

Hypothesis.. Mortality in children with shock is more closely related to the nature, rather than the magnitude (base deficit\\/excess), of a metabolic acidosis. Objective.. To examine the relationship between base excess (BE), hyperlactataemia, hyperchloraemia, 'unmeasured' strong anions, and mortality. Design.. Prospective observational study set in a multi-disciplinary Paediatric Intensive Care Unit (PICU). Patients.. Forty-six children, median age 6 months (1.5-14.4),

Mark Hatherill; Zainab Waggie; Langley Purves; Louis Reynolds; Andrew Argent



Effect of ammonium-chloride-induced metabolic acidosis on renal electrolyte handling in human neonates  

Microsoft Academic Search

The present study was undertaken to determine the relative contribution of altered glomerular and tubular functions to the metabolic-acidosis-induced increase of renal electrolyte excretion in healthy preterm and full-term neonates and in older infants. Studies were performed in 10 premature infants (mean birth weight 1618 g, gestational age 30.8 weeks) weekly for 6 consecutive weeks, in 11 full-term neonates (mean

E. Sulyokl; J.-P. Guignard



Effect of metabolic acidosis on renal tubular sodium handling in rats as determined by lithium clearance.  


Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH4Cl-induced metabolic acidosis on the renal handling of Na+ in male Wistar-Hannover rats (200-250 g). Chronic acidosis (pH 7.16 +/- 0.13) caused a sustained increase in renal fractional Na+ excretion (267.9 +/- 36.4%), accompanied by an increase in fractional proximal (113.3 +/- 3.6%) and post-proximal (179.7 +/- 20.2%) Na+ and urinary K+ (163.4 +/- 5.6%) excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na+ filtered load. A lower final body weight was observed in the acidotic (232 +/- 4.6 g) and pair-fed (225 +/- 3.6 g) rats compared to the controls (258 +/- 3.7 g). In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 +/- 0.05 g) compared to the other experimental groups (control, 1.46 +/- 0.05 g; pair-fed, 1.4 +/- 0.05 g). We suggest that altered renal Na+ and K+ handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport. PMID:9876297

Menegon, L F; Figueiredo, J F; Gontijo, J A



Stimulation of rat-liver branched-chain alpha-keto acid dehydrogenase activity by chronic metabolic acidosis.  


During chronic metabolic acidosis, the degradation of protein and amino acids reportedly increases. Branched-chain alpha-keto acid dehydrogenase complex (BCKDH) relates amino-acid catabolism and mitochondrial-energy metabolism. This study was designed to evaluate the effect of acidosis on the activity of liver BCKDH, the key regulatory enzyme in the catabolism of branched-chain amino acids. Experimental acidosis was induced in rats by ingestion of 0.28 M ammonium chloride solution for 10 days. We made two different liver-mitochondrial extracts to assay independently the active form of BCKDH and the total BCKDH activity. Acidosis significantly increased both active and total BCKDH specific activities (P < 0.05). The mean value for the active form of the BCKDH complex was 9.27 +/- 1.10 (S.E.M., n = 7) mU/mg of mitochondrial protein in acidotic rats and 5.18 +/- 0.84 (n = 7) for the control rats. The value of the total complex was 16.10 +/- 1.22 (n = 7) for the acidosis and 11.51 +/- 0.58 (n = 7) for the control. No significant changes were found in the activity state of the complex. Citrate synthase activity did not show significant variations between treatments. The stimulation of liver BCKDH activities by the acidosis may contribute to maintaining the level of intermediates of the tricarboxylic-acid cycle in this metabolic situation in which the net release of glutamine are produced. PMID:9675886

Rodríguez-Bayona, B; Peragón, J



Both L- and D-lactate contribute to metabolic acidosis in diarrheic calves.  


Diarrhea in neonates is often complicated by metabolic acidosis. We used blood gas analysis and HPLC to determine whether bacterial fermentation might contribute to acidosis in diarrheic calves. Diarrheic calves (n = 21) had significantly lower pH, PCO(2), HCO(3)(-) and a higher anion gap than healthy calves (n = 21). Serum concentrations (mean +/- SD, mmol/L) of DL-, L- and D-lactate were also significantly higher in diarrheic (8.9 +/- 5.1, 4.1 +/- 3.4 and 5.2 +/- 5.7) than in healthy calves (1.7 +/- 1.2, 2.0 +/- 1.1 and too low to quantify). D- and L-lactate accounted for 64% anion gap increase in diarrheic calves. Fecal D- and L-lactate concentrations were also significantly higher in diarrheic calves (9.4 +/- 3.0 and 11.9 +/- 2.7 mmol/L) than healthy calves (1.1 +/- 0.1 and 1.6 +/- 0.1 mmol/L). The elevated concentrations of serum and fecal D-lactate suggest gut bacterial fermentation contributes to the development of acidosis in diarrhea. PMID:11481406

Omole, O O; Nappert, G; Naylor, J M; Zello, G A



[Alcoholic ketoacidosis: not rare cause of metabolic acidosis].  


Alcoholic ketoacidosis is an often overlooked disorder, which affects chronic ethanol abusers who have usually had a binge culminating in severe vomiting with resulting hypovolemia, acute starvation and then a beta-hydroxybutyrate dominated ketoacidosis (due to the conjonction of enhanced Glucagon/Insuline and NADH/NAD ratios). Although the pathophysiology is complex, the syndrome is quickly reversible with the administration of saline and glucose solutions along with the correction of electrolyte disturbances, often unmasked during the treatment. Insuline and bicarbonates are not indicated. The prognosis, which is excellent, depends mainly on the coexisting acute disorders, which should be purchased and treated appropriately. PMID:16238232

Sibaï, K; Eggimann, P



Coma, metabolic acidosis, and methemoglobinemia in a patient with acetaminophen toxicity.  


We present a case of early coma, metabolic acidosis and methemoglobinemia after substantial acetaminophen toxicity in the absence of hepatic failure. A 77-year-old female presented to the emergency department with a decreased level of consciousness. She was found unresponsive by a family member in her bed, and was reported to be acting normally when she was last seen eight hours earlier. Laboratory results on arrival were: pH 7.19, sodium 139 mmol/L, chloride 106 mmol/L, potassium 3.3 mmol/L, CO2 8 mmol/L, and an anion gap of 25. Both venous lactate (10.2 mmol/L) and methemoglobin (9.4 %) were elevated. The patient's acetaminophen concentration was markedly elevated at 7138 µmol/L (1078 µg/ml). Hepatic enzymes and coagulation tests were normal [alanine transaminase (ALT) 8 U/L, international normalized ratio (INR) 1.0]. Intravenous N-acetylcysteine (NAC) was initiated at a dose of 150 mg/kg over 15 minutes, followed by 50 mg/kg over the next four hours, followed by 100 mg/kg over the next 16 hours. Twenty-four hours after admission, the anion gap metabolic acidosis had resolved, and the methemoglobin was 2.1%. Aminotransferases peaked at 44 U/L and INR peaked at 1.9. A urine 5-oxoproline assay performed five days after admission was negative, suggesting no evidence of a 5-oxoprolinase deficiency. We describe the pathophysiology and discuss the literature on acetaminophen-induced coma and metabolic acidosis in the absence of hepatic injury; and propose mechanisms for associated methemoglobinemia.  PMID:24077426

Kanji, Hussein D; Mithani, Shazma; Boucher, Paul; Dias, Valerian C; Yarema, Mark C



Effects of aminophylline and salbutamol on diaphragmatic force during compensated metabolic acidosis.  


We investigated the effects of aminophylline and salbutamol on tetanic force generated by the diaphragm during compensated metabolic acidosis in dogs. Anesthetized, mechanically ventilated animals were prepared with an open thorax. A cast was placed around the abdomen to maintain length and geometry of the diaphragm during contractions. A thin-walled latex balloon was positioned beneath the diaphragm to measure transdiaphragmatic pressure (Pdi). Pdi served as the index of diaphragmatic force of contraction. We measured Pdi during supramaximal phrenic stimulation at low and high frequencies and also during spontaneous inspiratory efforts for a constant diaphragmatic EMG activity. Compensated metabolic acidosis significantly reduced Pdi at all stimulation frequencies (p less than 0.05). The mean percent decrease at low frequencies was greater than at high (p less than 0.05). Pdi was decreased during spontaneous contractions as well (p less than 0.05). Administration of aminophylline significantly improved Pdi at all frequencies of phrenic stimulation (p less than 0.05) and during spontaneous inspiratory efforts (p less than 0.05). Infusion of salbutamol did not have a significant effect on Pdi at any frequency of stimulation but did produce a small potentiating effect during spontaneous contractions (p less than 0.05). We also recorded and analyzed the Pdi response to a single supramaximal impulse to the phrenic nerve, referred to as a twitch, to gain insight into possible cellular mechanisms underlying alterations in tetanic force of contraction. Compensated metabolic acidosis led to a significant reduction in peak twitch tension (PTT) (p less than 0.05) and half relaxation time (1/2RT) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3082263

Howell, S; Fitzgerald, R S; Roussos, C



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


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

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



Alkali therapy versus sodium chloride supplement in low birthweight infants with incipient late metabolic acidosis.  


Two hundred and eighty-two patients with birthweights below 2.0 kg were routinely screened for spontaneous development of maximum renal acid stimulation (urine-pH < 5.4). Sixty episodes in 53 patients of incipient late metabolic acidosis (urine pH < 5.4 on 2 consecutive days) were randomly allocated to oral therapy with 2 mmol/kg/day of either NaHCO3 or NaCl for 7 days. All 27 patients on NaHCO3 therapy, but only 15 from 26 patients on NaCl therapy, showed an increase in urine pH values, combined with a relatively high gain in body weight and a tendency to increased N-assimilation. Eleven patients on NaCl therapy showed persistent maximal renal acid stimulation on all 7 days with possibly lower weight gain and no clear change in N-assimilation. Thus, in patients with incipient late metabolic acidosis, NaCl therapy is not as beneficial as NaHCO3 therapy. PMID:9116434

Kalhoff, H; Diekmann, L; Kunz, C; Stock, G J; Manz, F



Severe hypertension, hyperkalemia, and renal tubular acidosis responding to dietary sodium restriction.  


A 13-year-old girl with severe hypertension (240/140 mm Hg), short stature, marked hyperkalemia (8.6 mEq/liter), and renal tubular acidosis was studied. Renal parenchymal and renovascular diseases as well as endocrinologic causes of hypertension were ruled out by appropriate studies. The hypertension was associated with sodium retention, increased plasma volume, suppressed plasma renin activity, and decreased urinary excretion of aldosterone. Impaired renal excretion of potassium was demonstrated by sodium sulfate infusion when the patient was fed a high-sodium diet but a significant kaliuresis occurred when the test was performed on a low-sodium diet suggesting that renal sodium retention may play a role in the defect in potassium excretion. The renal tubular acidosis was associated with normal distal acidification but a low bicarbonate threshold (19 mmoles/liter) and marked suppression of urinary ammonium excretion. The hypertension, hyporeninemia, and hypoaldosteronism as well as the hyperkalemia and acid-base abnormalities were completely reversed by dietary sodium restriction or the administration of thiazides or furosemide. It is concluded that an unusual avidity for sodium chloride reabsorption by the renal tubules leading to extracellular volume expansion and renin-aldosterone suppression plays a significant pathogenic role in this syndrome and may explain the hypertension and biochemical abnormalities discussed. PMID:7063287

Sanjad, S A; Mansour, F M; Hernandez, R H; Hill, L L



What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?  


Abstract Context. Paracetamol (acetaminophen) ingestion is the most frequent pharmaceutical overdose in the developed world. Metabolic acidosis sometimes occurs, but the acidosis is infrequently persistent or severe. A growing number of case reports and case series describe high anion gap metabolic acidosis (HAGMA) following paracetamol exposure with subsequent detection or measurement of 5-oxoproline (also called pyroglutamic acid) in blood, urine, or both. Typically 5-oxoprolinuria or 5-oxoprolinemia occurs in the setting of inborn genetic errors in glutathione metabolism. It is unknown whether 5-oxoprolinemia in the setting of paracetamol exposure reflects an acquired or transient derangement of glutathione metabolism or previously unrecognized genetic defects. Objective. We reviewed the published cases of 5-oxoprolinemia or 5-oxoprolinuria among patients with HAGMA in the setting of paracetamol exposure. Our goal was to identify any consistent features that might increase our understanding of the pathophysiology, diagnosis, and treatment of similar cases. Methods. We searched the medical literature using PUBMED and EMBASE from inception to 28 August 2013 applying search terms ("oxoproline" OR "pyroglutamic acid" AND "paracetamol" OR "acetaminophen"). The intersection of these two searches returned 77 articles, of which 64 involved human subjects and were in English. Two articles, one each in Spanish and Dutch, were reviewed. An additional Google Scholar search was done with the same terms. We manually searched the reference lists of retrieved articles to identify additional four relevant articles. We focused on articles including measured 5-oxoproline concentrations in urine or blood. Results. Twenty-two articles included quantified 5-oxoproline concentrations. Several additional articles mentioned only qualitative detection of 5-oxoproline in urine or blood without concentrations being reported. Our manual reference search yielded four additional articles for a total of 24 articles describing 43 patients with quantified 5-oxoproline concentrations. The cases varied widely in paracetamol dose, duration and circumstances of paracetamol exposure, presence, and degree of elevation in transaminase activities, and when reported observed blood, serum, or urine 5-oxoproline concentrations. Concomitant use of flucloxacillin, another medication associated with oxoprolinemia or oxoprolinuria, confounded several of the cases. No clear dose-response relationship existed between the quantity of paracetamol ingested and the observed concentrations of 5-oxoproline. Clinical outcomes, including mortality, varied with no clear relationship to 5-oxoproline concentrations. Conclusions. In rare cases, HAGMA in the setting of paracetamol exposure is attributable to 5-oxoprolinemia. Clinicians should first exclude commoner and treatable causes of HAGMA, such as lactic acidosis, co-ingested drug administration, and ketoacidosis. It is likely that the propensity for HAGMA following paracetamol exposure may be genetically determined. The effects of acetylcysteine on 5-oxoproline concentrations or clinical outcome are unknown. When HAGMA is diagnosed, the 5-oxoproline concentration and the glutathione synthetase activity should be measured. PMID:24111553

Liss, D B; Paden, M S; Schwarz, E S; Mullins, M E



Influence of mild metabolic acidosis on cardiac contractility and isoprenaline response in isolated ovine myocardium.  


The postoperative course after major surgical procedures such as cardiothoracic operations is often accompanied by acute metabolic abnormalities due to large volume and temperature shifts. In general, those intervention-induced trauma might cause the use of catecholamines to stabilize hemodynamics. Within the cardiac community, there are still controversial discussions about standardized medical therapy to treat postoperative acidosis, for example, buffering versus nonbuffering for improving catecholaminergic response of myocardial contractility. The aim of this study was to investigate the influence of mild (and thus clinically relevant) acidosis on myocardial contractility and catecholamine response in explanted trabeculae of ovine hearts. Intact trabeculae (n = 24) were isolated from the right ventricle of healthy sheep hearts. Two different groups (group 1: pH = 7.40, n = 9 and group 2: pH = 7.20, n = 13) were investigated, and force amplitudes were measured at frequencies between 30 and 180 beats per minute and increasing catecholamine concentrations (isoprenaline 0-3 × 10(-6) mM). Force-frequency relation experiments in the presence of a physiological and/or mild acidotic pH solution showed no significant differences. Mean force amplitudes normalized to the lowest frequency showing no significant differences in force development between 0.5 and 3 Hz (n = 9 vs. 13, P = n.s.) (0.5 Hz absolute values 3.1 ± 2.6 for pH = 7.40 vs. 3.8 ± 2.6 mN/mm(2) for pH = 7.20, P = n.s.). Moreover, there was no significant difference in relaxation kinetics between the two groups. Furthermore, the experiments showed similar catecholamine responses in both groups. Force amplitudes normalized to baseline and maximum force showed no significant differences in force development between baseline and maximum isoprenaline concentrations (n = 6 vs. 9, P = n.s.) (baseline absolute values 4.3 ± 4.0 for pH = 7.40 vs. 3.9 ± 1.2 mN/mm(2) for pH = 7.20, P = n.s.). Additionally, relaxation kinetics did not show differences after catecholamine stimulation. The presented experiments revealed no significant negative inotropic effects on isometrically contracting ovine trabeculae with mild metabolic acidosis (pH = 7.2) compared with physiological pH (7.4). Additionally, similar catecholamine responses were seen in both groups. Further investigations (e.g., in vivo and/or in failing hearts with reduced compensatory reserves) will be necessary to examine optimal medical treatment for metabolic abnormalities after cardiac surgery. PMID:22097981

Schotola, Hanna; Sossalla, Samuel; Rajab, Taufiek K; Toischer, Karl; Quintel, Michael; Bauer, Martin; Schmitto, Jan D



Bone histology and bone mineral density after correction of acidosis in distal renal tubular acidosis  

Microsoft Academic Search

Bone histology and bone mineral density after correction of acidosis in distal renal tubular acidosis.BackgroundThe association between chronic metabolic acidosis and alterations in bone cell functions has been demonstrated in vitro and in animal studies. However, the causal role of acidosis and the effects of alkaline therapy on bone histology and bone mineral density in chronic metabolic acidosis have never

Somnuek Domrongkitchaiporn; Cholatip Pongskul; Vorachai Sirikulchayanonta; Wasana Stitchantrakul; Virut Leeprasert; Boonsong Ongphiphadhanakul; Piyanuch Radinahamed; Rajata Rajatanavin



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


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

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



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

PubMed Central

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

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



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

Microsoft Academic Search

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

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



Effect of chronic metabolic acidosis on the growth hormone/IGF-1 endocrine axis: new cause of growth hormone insensitivity in humans.  


The effects of metabolic acidosis on growth hormone and IGF-1 are poorly understood. We investigated the effects of chronic metabolic acidosis (induced by administration on NH4Cl, 4.2 mmol/kg body wt/day) on the growth hormone/IGF-1 endocrine axis in 6 normal male volunteers during metabolic balance conditions. NH4Cl administration resulted in hyperchloremic metabolic acidosis with plasma bicarbonate decreasing from 25 +/- 0.4 to 15.5 +/- 0.9 mmol/liter (P < 0.001). Metabolic acidosis significantly decreased serum IGF-1 concentration from 45 +/- 6 to 33 +/- 6 nmol/liter (P = 0.002), while serum IGF binding protein 3 concentration was not affected significantly. The growth hormone response to growth hormone releasing factor administration (1 microgram per kg body wt, intravenous bolus) was enhanced significantly during acidosis. The IGF-1 response to growth hormone administration (0.1 U kg body wt subcutaneously, every 12 hr for 48 hr) was blunted significantly during acidosis. Apparent endogenous serum half-life and metabolic clearance rates of growth hormone were not altered significantly by acidosis. Metabolic acidosis in humans results in a significant decrease in serum IGF-1 concentration without a demonstrable effect on IGF binding protein 3, and is related to a resistance to the hepatocellular action of growth hormone. The primary defect in the growth hormone/IGF-1 axis occurs via an impaired IGF-1 response to circulating growth hormone with consequent diminution of normal negative feedback inhibition of IGF-1 on growth hormone, as evidenced by the exaggerated growth hormone response to growth hormone releasing factor administration. PMID:8995736

Brüngger, M; Hulter, H N; Krapf, R



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


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

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



The relationship between rumen acidosis resistance and expression of genes involved in regulation of intracellular pH and butyrate metabolism of ruminal epithelial cells in steers.  


Past research has focused on the prevention and management of subacute rumen acidosis by manipulating the ration; however, the severity of acidosis varies even among animals fed a common high-grain diet. The objectives of this study were to compare the ruminal volatile fatty acid (VFA) profile and expression of genes involved in the metabolism of butyrate, the VFA most extensively metabolized by the ruminal epithelium, and intracellular pH regulation in ruminal epithelial cells between acidosis-resistant (AR) and acidosis-susceptible (AS) steers. Acidosis indexes (area per day under pH 5.8 divided by dry matter intake) were measured for 17 steers fed a common high-grain diet, and the 3 steers with the lowest (1.4 ± 1.2 pH?min/kg) and the 3 with the highest values (23.9 ± 7.4 pH?min/kg) were classified as AR and AS, respectively, and used in the subsequent study. The steers were force-fed a diet containing 85% grain at 60% of the expected daily intake (5.8 ± 0.8 and 5.6 ± 0.6 kg for AR and AS, respectively) within 30 min. Mean ruminal pH over the postprandial 6-h period was higher for AR compared with AS (6.02 vs. 5.55), and mean total VFA concentration was 74% for AR compared with AS (122 vs. 164 mM). Molar proportion of butyrate in the ruminal fluid was 139% higher for AR compared with AS (17.5 vs. 7.33 mol/100 mol of VFA). Expression of monocarboxylate cotransporter isoform 1, sodium hydrogen exchanger isoforms 1 and 2, and anion exchangers (downregulated in adenoma and putative anion exchanger, isoform 1) did not differ between AR and AS steers. However, expression of sodium hydrogen exchanger isoform 3, which imports Na(+) to the epithelial cell and exports H(+) to the rumen, was 176% higher in AR steers than in AS steers. Higher ruminal pH for AR might be partly due to a faster rate of VFA absorption, lower VFA production, or both. PMID:22863095

Schlau, N; Guan, L L; Oba, M



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

Microsoft Academic Search

We present the case of a 19-year-old female with nasopharyngeal carcinoma, who received two courses of chemotherapy with 5-fluorouracil (5-FU) in combination with folic acid and cisplatin. Upon developing esophageal strictures in the course of her radiotherapy, she required total parenteral nutrition. In the course of therapy, the patient developed severe multisystem failure with encephalopathy, lactic acidosis, vegetative instability and

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



Proximal renal tubular acidosis  


... will become too acidic. This can lead to electrolyte imbalances in the blood. Your kidneys help control ... and blood chemistries may suggest metabolic acidosis and electrolyte imbalances, most often low levels of potassium or ...


Distal renal tubular acidosis  


... will become too acidic. This can lead to electrolyte imbalances in the blood. Your kidneys normally help ... and blood chemistries may suggest metabolic acidosis or electrolyte imbalances, most often low levels of potassium or ...


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

PubMed Central

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.

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



The effects of metabolic acidosis on renal function of fetal sheep.  

PubMed Central

1. The effects of I.V. infusions of 6.7-19.3 mmol hydrochloric acid/kg on fetal renal function were studied in fourteen chronically catheterized fetal sheep aged 121-143 days. Infusion of acid caused arterial pH and plasma bicarbonate levels to fall (P less than 0.0005, P less than 0.001). These remained low for the next 3 h. Plasma chloride levels increased (P less than 0.0005). There were no other changes in plasma electrolytes nor in plasma osmolality. 2. Fetal glomerular filtration rate did not change; the fractional reabsorptions of sodium, chloride and phosphate all decreased (P less than 0.005). Initially urine volume did not change but urinary osmolality increased (P less than 0.0005). Fetal urinary pH fell abruptly, titratable acid excretion increased, urinary ammonium excretion increased (P less than 0.0005) but urinary bicarbonate excretion remained unchanged. Thus, net acid excretion increased significantly (P less than 0.0005). 3. Twenty-six hours after infusion of acid, fetal arterial pH, bicarbonate levels, urinary pH, titratable acid and ammonium excretion were no different from control. Net acid excretion was still increased (P less than 0.05), urine flow rate was less (P less than 0.01) and urinary osmolality still increased (P less than 0.05). 4. There were no differences in arterial blood gases nor in pH of four fetuses which died during or shortly after infusion of acid. However, prior to acid infusion they were already excreting significantly greater amounts of phosphate (P less than 0.01), ammonium and titratable acid (P less than 0.02). Thus the fetal kidney responds to a metabolic acidosis by excreting more acid and by generating more bicarbonate, but this response is limited.

Kesby, G J; Lumbers, E R



D-Lactic acidosis in calves.  


Metabolic acidosis has long been known as a frequent and potentially severe complication of neonatal calf diarrhoea. It has also been described in 'acidosis-without-dehydration' syndrome in calves and was suspected to occur during ruminal drinking. Clinical signs of central nervous impairment, particularly changes in behaviour and posture, progressing to coma and recumbency, were originally attributed to this metabolic disturbance. The loss of bicarbonate in the faeces was regarded as the main cause of acidosis in this context. During the past decade, however, evidence has accumulated that d-lactic acidosis is a more common occurrence in calves with neonatal diarrhoea. The most probable source of D-lactataemia is bacterial fermentation of undigested substrate that reaches the large intestine due to damage to small intestinal mucosal epithelium. Recent research has shown that most of the clinical signs that were formerly attributed to acidosis were in fact due to elevated blood levels of D-lactate. The aim of this review is to provide a current overview of d-lactic acidosis. PMID:17933565

Lorenz, Ingrid



Bench-to-bedside review: Severe lactic acidosis in HIV patients treated with nucleoside analogue reverse transcriptase inhibitors  

PubMed Central

Nucleoside reverse transcriptase inhibitors (NRTIs) are effective antiretroviral therapy for the treatment of HIV-infected patients. NRTIs can induce mitochondrial impairment that leads to a number of adverse events, including symptomatic lactic acidosis. In the present review, we describe the underlying mechanism of NRTI-induced toxicity and the main clinical features of this infrequent, but severe, emerging complication. We also summarise experimental data and clinical observations that support the use of L-carnitine supplementation to reverse NRTI-induced mitochondrial impairment.

Claessens, Yann-Erick; Chiche, Jean-Daniel; Mira, Jean-Paul; Cariou, Alain



Perinatal brain damage: predictive value of metabolic acidosis and the Apgar score  

Microsoft Academic Search

To assess the predictive value for perinatal brain damage of acidosis at birth, alone or in combination with the Apgar score at 5 minutes, a cohort of 982 liveborn infants delivered over two months was studied prospectively. The umbilical cord was double clamped, and arterial acid-base values were successfully determined in 964 infants and lactate concentration in 931. Reference values

V. J. Ruth; K. O. Raivio



The acute reversal of a diet-induced metabolic acidosis does not restore endurance capacity during high-intensity exercise in man  

Microsoft Academic Search

The present experiment was designed to investigate whether a diet-induced metabolic acidosis was a major factor in the earlier onset of fatigue during high-intensity exercise. Six healthy males cycled to exhaustion at a workload equivalent to 95% of maximum oxygen uptake on four separate occasions. Exercise tests were performed after an overnight fast and each test was preceded by one

D. Ball; P. L. Greenhaff; R. J. Maughan



Fetal exposure to magnesium chloride-adenosine triphosphate (MgCl2-ATP) results in alterations in cerebral blood flow and a metabolic acidosis.  


OBJECTIVE: Magnesium chloride-adenosine triphosphate (MgCl(2)-ATP), advocated as an adjunct treatment in shock resuscitation, might be useful for pregnant women who develop hypovolemia secondary to conditions such as placental abruption. The effects of this treatment on the fetus, however, have never been investigated. This study determined the direct, acute effects of MgCl(2)-ATP on fetal organ blood flow, hemodynamic measurements, and metabolic parameters before and after maternal hemorrhage. DESIGN: Experimental, randomized, nonblinded, control study. SETTING: Animal laboratory at a university research facility. SUBJECTS: This study was performed on 11 chronically instrumented, 123-day gestational age, pregnant ewes (term = 147 days) and their fetuses. INTERVENTIONS: Ewes were randomly allocated to either experimental (Expt, n = 5) or control (Cntl, n = 6) groups. After a 60-min baseline period, Expt fetuses received a 60-min iv infusion of MgCl(2)-ATP (150 &mgr;mole/hr each of MgCl(2) and ATP; at 3 mL/hr), and Cntl fetuses received an equivalent volume of 0.9% NaCl. After this infusion-only period, the infusion was continued, and ewes were intermittently bled over 1 hr for a total blood loss of 20 mL/kg (hemorrhage-plus-infusion period). After this, the infusions were continued, and ewes and fetuses were monitored for 1 additional hr (posthemorrhage period). Measurements: At the end of all periods, fetal and maternal blood pressures, blood gases, oxygen saturation, hemoglobin, serum electrolytes, and serum glucose concentrations were measured. At the end of the baseline, infusion-only, and hemorrhage-plus-infusion periods, fetal organ blood flows were determined using a fluorescent microsphere technique. Nonparametric statistics were used for comparisons (2-tailed, p metabolic acidosis developed during the hemorrhage period and it continued through the posthemorrhage period. This metabolic acidosis was more severe in the Expt fetuses and appeared to have started during the infusion-only period. There were no fetal deaths in either group. In the Cntl fetuses, there were increases from baseline after the hemorrhage-plus-infusion period in fetal adrenal (71%), brain (89%), and thymus (18%) blood flow and a decrease in muscle (-28%) blood flow. In the Expt fetuses, there were increases during the infusion-only period in adrenal (332%), myocardial (142%), and pancreatic (219%) blood flow and decreases in kidney (-25%) and skin (-75%) blood flow. These changes persisted during the hemorrhage-plus-infusion period. Most strikingly, regional cerebral blood flow in the Expt fetuses did not increase from baseline in any of the 10 brain areas sampled during the infusion-only period or following maternal hemorrhage. In Cntl fetuses, however, there was increase in blood flow in all 10 brain areas sampled following maternal hemorrhage. CONCLUSIONS: In healthy fetuses, direct MgCl(2)-ATP exposure caused metabolic acidosis and a redistribution of cardiac output to different organs. When the MgCl(2)-ATP fetuses were then subject to the effects of maternal hemorrhage, the expected increase in cerebral blood flow was not observed. Although an earlier study suggests that ATP may be beneficial to stressed fetuses when administered to mothers in labor, the direct effect of MgCl(2)-ATP appears to be potentially harmful by producing an acidosis and altering the normal fetal cerebral blood flow response to maternal hemorrhage. PMID:12797893

Moon, Paula F.; Ramsay, Margaret M.; Fecci, Peter E.; Nathanielsz, Peter W.



Molecular Pathophysiology of Renal Tubular Acidosis  

Microsoft Academic Search

Renal tubular acidosis (RTA) is characterized by metabolic acidosis due to renal impaired acid excretion. Hy- perchloremic acidosis with normal anion gap and normal or minimally affected glomerular filtration rate defines this dis- order. RTA can also present with hypokalemia, medullary nephrocalcinosis and nephrolitiasis, as well as growth retarda- tion and rickets in children, or short stature and osteomalacia in

P. C. B. Pereira; D. M. Miranda; E. A. Oliveira; A. C. Simoes e Silva



Autism and lactic acidosis  

Microsoft Academic Search

Four patients are described who have two coexistent syndromes: the behavioral syndrome of autism and the biochemical syndrome of lactic acidosis. One of the four patients also had hyperuricemia and hyperuricosuria. These patients raise the possibility that one subgroup of the autism syndrome may be associated with inborn errors of carbohydrate metabolism.

Mary Coleman; John P. Blass



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


The physiological response to the onset of metabolic acidosis requires pronounced changes in renal gene expression. Adaptations within the proximal convoluted tubule support the increased extraction of plasma glutamine and the increased synthesis and transport of glucose and of NH(4)(+) and HCO(3)(-) ions. Many of these adaptations involve proteins associated with the apical membrane. To quantify the temporal changes in these proteins, proteomic profiling was performed using brush-border membrane vesicles isolated from proximal convoluted tubules (BBMV(PCT)) that were purified from normal and acidotic rats. This preparation is essentially free of contaminating apical membranes from other renal cortical cells. The analysis identified 298 proteins, 26% of which contained one or more transmembrane domains. Spectral counts were used to assess changes in protein abundance. The onset of acidosis produced a twofold, but transient, increase in the Na(+)-dependent glucose transporter and a more gradual, but sustained, increase (3-fold) in the Na(+)-dependent lactate transporter. These changes were associated with the loss of glycolytic and gluconeogenic enzymes that are contained in the BBMV(PCT) isolated from normal rats. In addition, the levels of ?-glutamyltranspeptidase increased twofold, while transporters that participate in the uptake of neutral amino acids, including glutamine, were decreased. These changes could facilitate the deamidation of glutamine within the tubular lumen. Finally, pronounced increases were also observed in the levels of DAB2 (3-fold) and myosin 9 (7-fold), proteins that may participate in endocytosis of apical membrane proteins. Western blot analysis and accurate mass and time analyses were used to validate the spectral counting. PMID:22357915

Walmsley, Scott J; Freund, Dana M; Curthoys, Norman P



Severe encephalopathy, lactic acidosis, vegetative instability and neuropathy with 5-Fluorouracil treatment - pyrimidine degradation defect or beriberi?  


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

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



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

PubMed Central

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

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



Acidosis, not azotemia, stimulates branched-chain, amino acid catabolism in uremic rats  

Microsoft Academic Search

Acidosis, not azotemia, stimulates branched-chain, amino acid catabolism in uremic rats. To investigate branched-chain, amino acid metabolism (BCAA) in muscle in chronic renal failure (CRF), we studied rats with moderately severe uremia (PUN 110 ˜ mg\\/dl) and spontaneous metabolic acidosis (bicarbonate, 19 ± 1 mEq\\/liter). Plasma BCAA levels in CRF compared to pair-fed control rats were ˜ 15% lower and

Yoko Hara; Robert C May; Ralph A Kelly; William E Mitch



Severe hereditary spherocytosis and distal renal tubular acidosis associated with the total absence of band 3  

Microsoft Academic Search

Absence of band 3, associated with the mutation Coimbra (V488M) in the homozy- gous state, caused severe hereditary spherocytosis in a young child. Although prenatal testing was made available to the parents, it was declined. Because the fetus stopped moving near term, an emer- gency cesarean section was performed and a severely anemic, hydropic female baby was delivered. She was

Maria Leticia Ribeiro; Nicole Alloisio; Helena Almeida; Clara Gomes; Pascale Texier; Carlos Lemos; Gabriela Mimoso; Laurette Morle; Faiza Bey-Cabet; Jean Delaunay; Gabriel Tamagnini


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

Microsoft Academic Search

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

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



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

PubMed Central

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



Acidosis activates complement system in vitro.  

PubMed Central

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

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



Dialysis Disequilibrium Syndrome: Brain death following hemodialysis for metabolic acidosis and acute renal failure - A case report  

PubMed Central

Background Dialysis disequilibrium syndrome (DDS) is the clinical phenomenon of acute neurologic symptoms attributed to cerebral edema that occurs during or following intermittent hemodialysis (HD). We describe a case of DDS-induced cerebral edema that resulted in irreversible brain injury and death following acute HD and review the relevant literature of the association of DDS and HD. Case Presentation A 22-year-old male with obstructive uropathy presented to hospital with severe sepsis syndrome secondary to pneumonia. Laboratory investigations included a pH of 6.95, PaCO2 10 mmHg, HCO3 2 mmol/L, serum sodium 132 mmol/L, serum osmolality 330 mosmol/kg, and urea 130 mg/dL (46.7 mmol/L). Diagnostic imaging demonstrated multifocal pneumonia, bilateral hydronephrosis and bladder wall thickening. During HD the patient became progressively obtunded. Repeat laboratory investigations showed pH 7.36, HCO3 19 mmol/L, potassium 1.8 mmol/L, and urea 38.4 mg/dL (13.7 mmol/L) (urea-reduction-ratio 71%). Following HD, spontaneous movements were absent with no pupillary or brainstem reflexes. Head CT-scan showed diffuse cerebral edema with effacement of basal cisterns and generalized loss of gray-white differentiation. Brain death was declared. Conclusions Death is a rare consequence of DDS in adults following HD. Several features may have predisposed this patient to DDS including: central nervous system adaptations from chronic kidney disease with efficient serum urea removal and correction of serum hyperosmolality; severe cerebral intracellular acidosis; relative hypercapnea; and post-HD hemodynamic instability with compounded cerebral ischemia.

Bagshaw, Sean M; Peets, Adam D; Hameed, Morad; Boiteau, Paul JE; Laupland, Kevin B; Doig, Christopher J



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

Microsoft Academic Search

Autosomal recessive distal renal tubular acidosis (rdRTA) is characterised by severe hyperchloraemic metabolic acidosis in childhood, hypokalaemia, decreased urinary calcium solubility, and impaired bone physiology and growth. Two types of rdRTA have been differentiated by the presence or absence of sensorineural hearing loss, but appear otherwise clinically similar. Recently, we identified mutations in genes encoding two different subunits of the

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



Effect of Sodium Bicarbonate Administration on Mortality in Patients with Lactic Acidosis: A Retrospective Analysis  

PubMed Central

Background Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death. Methods We conducted a single center analysis from May 2011 through April 2012. We retrospectively analyzed 103 patients with lactic acidosis among 207 patients with metabolic acidosis. We used SOFA and APACHE II as severity scores to estimate illness severity. Multivariate logistic regression analysis and Cox regression analysis models were used to identify factors that affect mortality. Results Of the 103 patients with a mean age of 66.1±11.4 years, eighty-three patients (80.6%) died from sepsis (61.4%), hepatic failure, cardiogenic shock and other causes. The percentage of sodium bicarbonate administration (p?=?0.006), catecholamine use, ventilator care and male gender were higher in the non-survival group than the survival group. The non-survival group had significantly higher initial and follow-up lactic acid levels, lower initial albumin, higher SOFA scores and APACHE II scores than the survival group. The mortality rate was significantly higher in patients who received sodium bicarbonate. Sodium bicarbonate administration (p?=?0.016) was associated with higher mortality. Independent factors that affected mortality were SOFA score (Exp (B)?=?1.72, 95% CI?=?1.12–2.63, p?=?0.013) and sodium bicarbonate administration (Exp (B)?=?6.27, 95% CI?=?1.10–35.78, p?=?0.039). Conclusions Lactic acidosis, which has a high mortality rate, should be evaluated in patients with metabolic acidosis. In addition, sodium bicarbonate should be prescribed with caution in the case of lactic acidosis because sodium bicarbonate administration may affect mortality.

Kim, Hyun Jeong; Son, Young Ki; An, Won Suk



Secondary renal tubular acidosis in a Hereford calf.  


A 3-month-old Hereford heifer calf was presented for lethargy. Blood gas analysis and plasma biochemical testing revealed severe metabolic acidosis, azotemia, hyponatremia, hyperchloremia, and normal anion gap. Results of a urinalysis were consistent with acute tubular necrosis with inadequate acidification of urine based on the degree of acidemia. Salmonella enterica serovar agona was cultured from both urine and feces. The calf was treated with intravenous polyionic fluids, bicarbonate, and antimicrobials. Acidosis and azotemia resolved, and 4 months following initial presentation the heifer was clinically normal. PMID:21554363

Hardefeldt, Laura Y; Poulsen, Keith P; Darien, Benjamin J



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

PubMed Central

Background Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Case Presentation Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of which was pre-renal due to profound volume depletion. Renal failure was associated with marked hypochloremic metabolic alkalosis which only responded to high volume repletion and high dose blockade of gastric hypersecretion. Intestinal failure with stomal fluid losses of up to 5.7 litres per day required port implantation to commence parenteral nutrition. Fluid and electrolyte replacement rapidly improved renal function and acid base homeostasis. Conclusions This case highlights the important role of gastrointestinal function to maintain acid base status in patients with Crohn's disease.



Incomplete Renal Tubular Acidosis in ‘Primary’ Osteoporosis  

Microsoft Academic Search

:   Chronic metabolic acidosis may increase alkali mobilization from bone and thus promote the development of osteoporosis. While\\u000a it is undisputed that overt metabolic acidosis is associated with metabolic bone disease, renal acidification in patients\\u000a with idiopathic osteoporosis has not been studied systematically. The purpose of this study was to investigate the prevalence\\u000a of renal acidification defects in patients with

M. Weger; H. Deutschmann; W. Weger; P. Kotanko; F. Skrabal



Atypical presentation of distal renal tubular acidosis in two siblings.  


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

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



Metabolic Management of Severe Acute Pancreatitis  

Microsoft Academic Search

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

John A. Windsor; Hisham Hammodat



[D-Lactic acidosis secondary to short bowel syndrome].  


The short bowel syndrome appears for the reduction of intestinal absorptive surface due to functional or anatomical loss of part of the small bowel. We present the case of a 35-year-old woman with severe short bowel syndrome secondary to acute intestinal ischemia in adults, who presented at 5 years of evolution episodes of dizziness with gait instability and loss of strength in hands. The diagnosis was D-lactic acidosis. D-lactic acidosis is a rare complication, but important for their symptoms, of this syndrome. It is due to a change in intestinal flora secondary to an overgrowth of lactic acid bacteria that produce D-lactate. D-lactic acidosis should be looked for in cases of metabolic acidosis in which the identity of acidosis is not apparent, neurological manifestations without focality and the patient has short bowel syndrome or patients who have had jejunoileal bypass surgery. Appropriate treatment usually results in resolution of neurologic symptoms and prevents or reduces further recurrences. PMID:21336448

Tapia Guerrero, M J; Olveira, G; Bravo Utrera, M; Colomo Rodríguez, N; Fernández García, J C


Renal tubular acidosis.  


In the past decade major advances in our understanding of renal tubular hydrogen ion secretion and bicarbonate reabsorption have provided new insight into the pathophysiology of renal tubular acidosis. Thus "fragment to fragment clings" and the number of disorders categorized within the syndrome grows, until we have come to know and name four types, with many subtypes. We hope this new perspective provides a basis for the physician to recognize renal tubular acidosis in its several forms so that an informed decision may be arrived at in choosing the best therapy. The physician may also be prepared to reasonably project the prognosis for each patient. We also hope that our detailed examination of renal acidification will provide a reference for delineation of new clinical expressions of acid-base disorders and kidney malfunction certain to be described in the years ahead. PMID:6402574

Chan, J C



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

Microsoft Academic Search

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

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



Severe metabolic alkalosis due to the combination of unmeasured cations and hypochloraemia in a patient with gastroparesia and frequent emesis  

PubMed Central

This report describes a patient with gastroparesia and frequent emesis admitted with severe metabolic alkalaemia, hyperlactataemia and acute renal failure. Metabolic alkalaemia was not only due to hypochloraemia but also due to unmeasured cations. These cations were found to be present by calculating anion gap and strong ion gap (both were negative, which is rare). After massive gastric bleeding the patient had a cardiac arrest; following cardiopulmonary resuscitation and infusion of a large volume of normal saline, new blood tests revealed improvement in chloraemia but also a significant increase in the anion gap, suggesting that unmeasured anions rapidly overcame unmeasured cations. The patient died after sequential episodes of cardiac arrest. Anion gap and strong ion gap were useful in the diagnosis of this “hidden” unusual cause of metabolic alkalosis and also in the diagnosis of metabolic acidosis after cardiac arrest, even with normal/high values of base excess and bicarbonate.

Maciel, Alexandre Toledo



The Genomic Analysis of Lactic Acidosis and Acidosis Response in Human Cancers  

PubMed Central

The tumor microenvironment has a significant impact on tumor development. Two important determinants in this environment are hypoxia and lactic acidosis. Although lactic acidosis has long been recognized as an important factor in cancer, relatively little is known about how cells respond to lactic acidosis and how that response relates to cancer phenotypes. We develop genome-scale gene expression studies to dissect transcriptional responses of primary human mammary epithelial cells to lactic acidosis and hypoxia in vitro and to explore how they are linked to clinical tumor phenotypes in vivo. The resulting experimental signatures of responses to lactic acidosis and hypoxia are evaluated in a heterogeneous set of breast cancer datasets. A strong lactic acidosis response signature identifies a subgroup of low-risk breast cancer patients having distinct metabolic profiles suggestive of a preference for aerobic respiration. The association of lactic acidosis response with good survival outcomes may relate to the role of lactic acidosis in directing energy generation toward aerobic respiration and utilization of other energy sources via inhibition of glycolysis. This “inhibition of glycolysis” phenotype in tumors is likely caused by the repression of glycolysis gene expression and Akt inhibition. Our study presents a genomic evaluation of the prognostic information of a lactic acidosis response independent of the hypoxic response. Our results identify causal roles of lactic acidosis in metabolic reprogramming, and the direct functional consequence of lactic acidosis pathway activity on cellular responses and tumor development. The study also demonstrates the utility of genomic analysis that maps expression-based findings from in vitro experiments to human samples to assess links to in vivo clinical phenotypes.

Chen, Julia Ling-Yu; Lucas, Joseph E.; Schroeder, Thies; Mori, Seiichi; Wu, Jianli; Nevins, Joseph; Dewhirst, Mark; West, Mike; Chi, Jen-Tsan



Acid and mineral balances and bone in familial proximal renal tubular acidosis  

Microsoft Academic Search

Acid and mineral balances and bone in familial proximal renal tubular acidosis.BackgroundMetabolic acidosis caused by increased rates of fixed acid production is associated with increased urinary excretion of Ca and negative Ca balances. Metabolic acidosis caused by a reduced capacity of the kidneys to excrete acid contributes to the development of bone disease in the course of chronic renal failure

Jacob Lemann; Nancy D Adams; Donald R Wilz; Luis G Brenes



The acute reversal of a diet-induced metabolic acidosis does not restore endurance capacity during high-intensity exercise in man.  


The present experiment was designed to investigate whether a diet-induced metabolic acidosis was a major factor in the earlier onset of fatigue during high-intensity exercise. Six healthy males cycled to exhaustion at a workload equivalent to 95 percent of maximum oxygen uptake on four separate occasions. Exercise tests were performed after an overnight fast and each test was preceded by one of four experimental conditions. Two experimental diets were designed, either to replicate each subject's own normal diet [N diet, mean (SD) daily energy intake (E) = 13 (0.7) MJ, 14.5 (0.8) percent protein (Pro), 37.5 (2.2) percent fat (Fat) and 47.5 (2.1) percent carbohydrate (CHO)], or a low-carbohydrate diet [E = 12.6 (0.8) MJ, 33.6 (1.3) percent Pro, 64.4 (1.5) percent Fat and 2.2 (0.4) percent CHO]. These diets were prepared and consumed within the department over a 3-day period. Over a 3-period prior to the exercise trial subjects ingested either NaHCO(3) or CaCO(3) (3.6 and 3.0 mmol*kg body mass), thus giving four experimental conditions: N diet and treatment, N diet and placebo, low-CHO diet and treatment and low-CHO diet and placebo. Treatments were assigned using a randomised protocol. Arterialised venous blood samples were taken for the determination of acid-base status and metabolite concentrations at rest prior to exercise and at intervals for 30 min following exhaustion. Consumption of the low-CHO diet induced a mild metabolic acidosis which was reversed by the ingestion of NaHCO(3). Blood pH, bicarbonate (HCO-(3)) and base excess (BE) were higher following NaHCO(3) ingestion after the normal diet than all of the other experimental conditions (P <0.01). Exercise time following the low-CHO diet was less than on the normal diet conditions (P <0.05): bicarbonate ingestion had no effect on exercise time on either of the diet conditions. Post-exercise blood pH, HCO-(3); and BE were higher following the ingestion of NaHCO(3) irrespective of the pre-exercise diet (P <0.05). Blood lactate concentration was higher 2 min after exercise following the N diet with NaHCO(3) when compared to the low-CHO diets with either NaHCO(3) or placebo (P <0.05). Plasma ammonia accumulation was not significantly different between experimental conditions. These data confirm previous data showing that the ingestion of a low-CHO diet reduces the capacity to perform high-intensity exercise, but it appears that the metabolic acidosis induced by the low-CHO diet is not the cause of the reduced exercise capacity observed during high-intensity exercise under these conditions. PMID:8861677

Ball, D; Greenhaff, P L; Maughan, R J



Bone mineral density and histology in distal renal tubular acidosis  

Microsoft Academic Search

Bone mineral density and histology in distal renal tubular acidosis.BackgroundChronic metabolic acidosis in distal renal tubular acidosis (RTA) has been implicated in the pathogenesis of enhanced bone resorption and osteopenia, resulting in a loss of bone mineral content. However, histomorphometric and bone densitometric studies of patients who suffered from long-standing distal RTA have rarely been done.MethodsA cross-sectional study to determine

Somnuek Domrongkitchaiporn; Chonlatrip Pongsakul; Wasana Stitchantrakul; Vorachai Sirikulchayanonta; Boonsong Ongphiphadhanakul; Piyanuch Radinahamed; Patcharee Karnsombut; Narin Kunkitti; Chatuporn Ruang-Raksa; Rajata Rajatanavin



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


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

Y?lmaz, Hakk?; Kaya, Mustafa; Özbek, Mustafa; ÜUreten, Kemal; Safa Y?ld?r?m, ?



Sj?gren syndrome presenting with hypopotassemic periodic paralysis due to renal tubular acidosis  

PubMed Central

Summary Background: Sjögren syndrome (SS) is an autoimmune-lymphoproliferative disorder characterized by mononuclear cell infiltration of exocrine glands. Clinically, Sjögren syndrome (SS) has a wide spectrum, varying from autoimmune exocrinopathy to systemic involvement. There have been few cases reporting that primary SS developed with distal renal tubular acidosis clinically. Case Report: Here, we present a case with primary Sjögren syndrome accompanied by hypopotassemic paralysis due to renal tubular acidosis. Severe hypopotassemia, hyperchloremic metabolic acidosis, alkaline urine and disorder in urinary acidification test were observed in the biochemical examination of the 16-year-old female patient, who had applied to our clinic for extreme loss of muscle force. After the examinations it was determined that the patient had developed Type 1 RTA (distal RTA) due to primary Sjögren syndrome. Potassium and alkaline replacement was made and an immediate total recovery was achieved. Conclusions: Hypopotassemic paralysis due to primary Sjögren syndrome is a rare but severe disorder that could lead to death if not detected early and cured appropriately. Thus, effective treatment should be immediately initiated in cases where severe hypopotassemia is accompanied by metabolic acidosis, and the cases should also be examined for extraglandular involvement of SS.

Ataoglu, Esra Hayriye; Demir, Betul; Tuna, Mazhar; Cavus, Bilger; Cetin, Faik; Temiz, Levent Umit; Ozturk, Savas; Yenigun, Mustafa



Lactic acidosis and mitochondrial disorders.  


Characterization of the biochemical basis of various inherited disorders associated with lactic acidosis has increased dramatically in recent years. These include defects of enzymes of gluconeogenesis, pyruvate oxidation, and electron transport. Clinical manifestations of these disorders show great variation and overlap, frequently involving the central nervous system as well as skeletal and cardiac muscle. Several of these enzymes are large complexes of subunits encoded by multiple genes; the electron transport chain complexes include subunits encoded by both nuclear and mitochondrial genes. This great complexity complicates analysis of specific mutations, despite considerable progress in defining the primary structure of component proteins and their genes. With few exceptions, treatment of disorders associated with congenital lactic acidosis remains unsatisfactory. PMID:1959224

Kerr, D S



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...


Increased Red Cell Osmotic Fragility and Hematocrit After Hyperbaric O2 E xposure are Related to acidosis.  

National Technical Information Service (NTIS)

Exposure to hyperbaric O2 (0.6 MPo) until convulsion occurred resulted in increased red blood cell osmotic fragility, increased hematocrit, and acidosis. Correction of the mixed metabolic and respiratory acidosis in arterial blood samples completely resto...

J. C. Braisted A. L. Harabin



Severe illness caused by the products of bacterial metabolism in a child with a short gut  

Microsoft Academic Search

An 8-year-old boy with a short gut had six episodes of metabolic acidosis and neurological dysfunction over a 1 month period. The neurological features consisted of a depressed conscious state, confusion, aggressive behaviour, slurred speech and ataxia. The organic acid profile of urine demonstrated increased amounts of lactic, 3-hydroxypropionic, 3-hydroxyisobutyric, 2-hydroxyisocaproic, phenyllactic, 4-hydroxyphenylacetic and 4-hydroxyphenyllactic acids. Of the lactic acid

E. Haan; G. Brown; A. Bankier; D. Mitchell; S. Hunt; J. Blakey; G. Barnes



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

PubMed Central

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



A Review of metabolic staging in severely injured patients  

PubMed Central

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



Perinatal Acidosis and Hypoxic-Ischemic Encephalopathy in Preterm Infants of 33 to 35 Weeks' Gestation  

PubMed Central

Objectives To determine the frequency of hypoxic-ischemic encephalopathy (HIE) in preterm infants of 33 to 35 weeks’ gestational age on the basis of physiological screening for perinatal acidosis and neurological assessment of encephalopathy and to correlate neurodevelopmental outcomes with brain magnetic resonance imaging findings. Study design This retrospective cohort study included all inborn infants of 33 to 35 weeks’ gestation admitted to the neonatal intensive care unit at Parkland Memorial Hospital with perinatal acidosis from October 2005 to September 2008. Their medical records were reviewed, and pertinent data were recorded. Results Of 1305 newborns, 2.5% (n = 33) had perinatal acidosis, and 27% (n = 9) of these had HIE (2, mild; 4, moderate; 3, severe). Persistence of metabolic acidosis on the first arterial blood gas obtained in the first hour of age was significantly associated with HIE (P < .005). Magnetic resonance imaging results were abnormal in 3 of 4 infants with moderate HIE and in both survivors with severe HIE. Death or disability occurred in no infants with mild or moderate HIE, but in all infants with severe HIE. Conclusion Screening criteria for HIE that use biochemical and neurological assessments as performed in term newborns can be applied to preterm infants of 33 to 35 weeks’ gestation.

Chalak, Lina F.; Rollins, Nancy; Morriss, Michael C.; Brion, Luc P.; Heyne, Roy; Sanchez, Pablo J.



A case of PDH-E1? mosaicism in a male patient with severe metabolic lactic acidosis  

Microsoft Academic Search

We have characterized a novel mutation in a male patient that affects the coding sequence of PDH-E1a gene and changes arginine-141 to a leucine. This nucleotide substitution was found in about 75% of the studied DNA (fibroblasts, liver and muscle), a scenario that would indicate a case of E1a mosaicism in a male patient. When the mutant E1a protein was

A. Seyda; K. Chun; S. Packman; B. H. Robinson



A Review of metabolic staging in severely injured patients  

Microsoft Academic Search

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

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



The syndrome of irreversible acidosis after prolonged propofol infusion  

Microsoft Academic Search

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

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



Systemic acidosis after controlled hypotension activates catechol activity in the vasomotor center.  


Activation of the catechol metabolism, assessed with in vivo voltammetry, in the vasopressor area of the vasomotor center was investigated during systemic acidosis occurring after controlled hypotension. Rats anesthetized with halothane were mechanically ventilated. Sodium nitroprusside lowered mean arterial pressure to 55 mmHg for > or = 20 min. Arterial blood gases allowed us to group rats according to whether they showed symptoms of metabolic acidosis (pH < or = 7.34) immediately after controlled hypotension. To assess the effect of systemic acidosis independently of the progressive decline in pressure observed during the recovery period after controlled hypotension, we used phenylephrine infusion to maintain mean arterial pressure at baseline pressure during the recovery period after controlled hypotension in two groups of animals. Systemic acidosis increased the catechol signal in a prolonged manner [nitroprusside with acidosis (n = 7) vs. nitroprusside without acidosis (n = 5); P < 0.0001]. This catechol activation was greater when pressure was restored after hypotension [nitroprusside with acidosis plus phenylephrine (n = 5) vs. nitroprusside with acidosis over the whole interval (from -30 to +150 min); P < 0.05]. When the nitroprusside with acidosis group and nitroprusside with acidosis plus phenylephrine group were compared, hypercapnia had an involvement in the larger increase of the catechol signal observed in the nitroprusside with acidosis plus phenylephrine group [arterial PCO2: nitroprusside with acidosis vs. nitroprusside with acidosis plus phenylephrine over the whole interval (from -30 to +150 min) and at +30 and +60 min; all P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7928888

Bruandet, N; Quintin, L



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


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

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




Technology Transfer Automated Retrieval System (TEKTRAN)

Although the main focus in ruminal acidosis has been on the rumen, it might be more accurate to consider this nutritional disorder as a syndrome that can affect systems beyond the rumen and outside of the gastrointestinal tract. Notwithstanding that ruminal acidosis is by definition related to low r...


The Treatment of Acidosis in Acute Lung Injury with Tris-Hydroxymethyl Aminomethane (THAM)  

Microsoft Academic Search

Mechanical hyperventilation of acidemic patients with acute lung injury (ALI) requires the use of high volumes and pressures that may worsen lung injury. However, permissive hypercapnia in the presence of shock, metabolic acidosis, and multi-organ system dysfunction may compromise normal cellular function. Tris-hy- droxymethyl aminomethane (THAM) may be an effective method to control acidosis in this circumstance. Protonated THAM is




Renal tubular acidosis during therapy for diabetic ketoacidosis.  

PubMed Central

A young woman presented with typical diabetic ketoacidosis. Five hours after insulin had been given hyperchloremic metabolic acidosis developed. This could not be attributed to gastrointestinal loss of bacarbonate, ingestion of HCI or carbonic anhydrase inhibitor, or the administered fluids and electrolytes. The combination of hyperchloremic metabolic acidosis and a urine pH of 5.6 during acidemia prompted specific studies that established the presence of disorders of renal acidification. A transient defect of hydrogen ion secretion in the distal nephron was suggested by the decrease in urine-blood Pco-2 gradient after administration of sodium bicarbonate. Proximal renal tubular acidosis was indicated by the reduced bicarbonate threshold that persisted for approximately 7 weeks.

Giammarco, R.; Goldstein, M. B.; Halperin, M. L.; Stinebaugh, B. J.



Severe pulmonary hypertension: The role of metabolic and endocrine disorders.  


Pulmonary arterial hypertension (PAH) is a multi-factorial condition and the underlying pulmonary vascular disease is shaped by the combined action of genetic, epigenetic and immune-related factors. Whether and how gender, obesity and the metabolic syndrome modify PAH and associated right heart failure is under intense investigation. Estrogens may enhance the process of pulmonary angioproliferation, but may also protect the right ventricle under pressure. Obesity may affect the pulmonary circulation via interactions with inflammatory cells and mediators, or via alterations in endocrine signaling. Obesity is a major risk factor for pulmonary hypertension in patients with elevated pulmonary venous pressure and preserved LV ejection fraction. Given the overlap between PAH and autoimmune diseases, hypothyroidism in patients with PAH is commonly considered a consequence of an autoimmune thyroiditis. In the clinical setting of hyperthyroidism, severe pulmonary hypertension may develop due to a hyperdynamic circulation, but a more complex situation presents itself when hyperthyroidism is associated with PAH. We recently showed in a relevant animal model of severe PAH that thyroid hormone, via its endothelial cell-proliferative action, can be permissive and drive angioproliferation. Signaling via the integrin ?v?3 and FGF receptors may participate in the formation of the lung vascular lesions in this model of PAH. Whether thyroid hormones in euthyroid PAH patients play a pathobiologically important role is unknown- as we also do not know whether the commonly diagnosed hypothyroidism in patients with severe PAH is cardioprotective. This brief review highlights some recent insights into the role of metabolic and endocrine disorders in PAH. PMID:22837855

Bogaard, Harm J; Al Husseini, Aysar; Farkas, Laszlo; Farkas, Daniela; Gomez-Arroyo, Jose; Abbate, Antonio; Voelkel, Norbert F


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

PubMed Central

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

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



Examining the relationship between diet-induced acidosis and cancer  

PubMed Central

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



Hyperkalemia in neonatal diarrheic calves depends on the degree of dehydration and the cause of the metabolic acidosis but does not require the presence of acidemia.  


Hyperkalemia is a clinically important electrolyte imbalance in neonatal diarrheic calves that has previously been associated with skeletal muscle weakness and life-threatening cardiac arrhythmias. The aim of the present retrospective analysis was to identify risk factors for hyperkalemia in a convenience sample of 832 calves (?21d of age) with a clinical diagnosis of diarrhea admitted to a veterinary teaching hospital. Plasma potassium concentrations were most closely associated with parameters of dehydration and renal function such as serum creatinine [Spearman correlation (rs)=0.61], urea (rs=0.51), and inorganic phosphorus concentrations (rs=0.64). Plasma potassium concentrations were weakly associated with venous blood pH (rs=-0.21). Although venous blood pH was not predictive in a multivariate linear regression analysis, the odds of having hyperkalemia (>5.8mmol/L) in acidemic calves was found to be 8.6 times as high as in nonacidemic calves [95% confidence interval (CI): 4.8-15.4]. However, the presence of hyperkalemia depended on the nature of an existing acidosis, and the odds for the presence of hyperkalemia in acidemic calves with hyper-d-lactatemia (>3.96mmol/L) were only 0.15 times as high as in acidemic calves with normal d-lactate concentrations (95% CI, 0.11-0.22). Acidemia in hyperkalemic diarrheic calves was associated with hyponatremia and increased concentrations of inorganic phosphorus, l-lactate, and unidentified strong anions that presumably included uremic anions such as sulfate. We conclude that hyper-d-lactatemia in neonatal diarrheic calves is not usually associated with elevated plasma potassium concentrations. Application of the simplified strong ion acid-base model indicated that dehydration is an important contributor to the pathogenesis of hyperkalemia and acidemia in neonatal calves with diarrhea. PMID:24011947

Trefz, F M; Constable, P D; Sauter-Louis, C; Lorch, A; Knubben-Schweizer, G; Lorenz, I



Tumor growth inhibition by ammonium chloride-induced acidosis.  


Ammonium chloride-induced metabolic acidosis decreases the growth of various experimental tumors. Spleen exhibits the same effects. There is a sex factor which seems to affect the growth of both tumor and spleen. The observed tumor inhibition appears to be related to a systemic impairment of the anabolic mechanisms. The decrease in tumor calcium suggests that this element may play a role in the tissue growth. The possible implication of cell membrane changes and of a block in glycolysis in the acidosis effects are discussed. PMID:51839

Anghileri, L J



[Bronchial asthma attack with lactic acidosis and hypokalemia in a case receiving high dose inhalation of procaterol hydrochloride].  


We report a case of bronchial asthma attack with lactic acidosis and hypokalemia in a patient receiving high-dose inhalation of procaterol hydrochloride. A 28-year-old man was transferred to our hospital because of adynamia, nausea and dyspnea. He had used inhaled procaterol hydrochloride with a pressurized metered dose inhaler about 20 times before admission. On admission, there were no signs of shock state or hypoxemia and laboratory data showed hypokalemia, hyperglycemia and metabolic acidosis with elevated anion gap. Lactic acidosis was identified as the reason for the metabolic acidosis with elevated anion gap. Lactic acidosis improved after 12 hours. Lactic acidosis due to high dose inhalation of procaterol hydrochloride was suggested. PMID:17491317

Noma, Satoshi; Kubota, Shingo; Matsukizono, Kazuya; Tanoue, Asako; Kumamoto, Tomohiro; Taira, Tetsuhiko; Mitsuyama, Hideo; Kawabata, Toshihumi; Suetsugu, Takayuki; Iwakaw, Jun; Koreed, Yoshimizu; Matsuyama, Wataru; Mizuno, Keiko; Higashimoto, Ikkou; Osame, Mitsuhiro; Arimura, Kimiyoshi



A distal (type 1) renal tubular acidosis case that mimic coronary ischemia.  


Abstract Introduction: Type 1 (distal) renal tubular acidosis (RTA) is a rare clinical condition characterized with defect of urinary acidification in distal tubulus. If diagnosis delays, RTA may cause metabolic and clinical complications and comorbidities. We describe here a type 1 distal RTA case with symptoms mimicking coronary ischemia. Case report: A 46-year-old woman admitted with complaints of chest pain, palpitation, walking disability, fatigue and nausea. On physical examination muscles were weaken 3/5 in four extremities. An electrocardiogram revealed supraventricular tachycardia and ST depression on precordial V2-6 derivations. An acute coronary syndrome diagnosis made based on anginal symptoms, supraventricular tachycardia, ST depression on V2-6 derivations and elevated cardiac enzymes. Urgent coronary angiography was normal except a 30% narrowing in LAD. She had recurrent nephrolithiasis and had operated because of hydronephrosis. She had two episodes of fatigue and walking disability previously. Hyperchloremic metabolic acidosis with normal anion gap determined in blood gas analyze. Patient diagnosed with type I RTA with the signs and symptoms of recurrent nephrolithiasis, fatigue, severe hypokalemia (1.8?mmol/L), hyperchloremic metabolic acidosis with normal anionic gap, alkaline urine (pH 8) and positive urinary anionic gap (13.7?mmol/L). Sodium bicarbonate infusion and potassium replacement therapy administered. Clinical and laboratory signs of the patient dissolved during treatment. Conclusion: Type 1 RTA should be considered in acidotic patients admitted with hypokalemia and coronary symptoms. Urinary and blood gas analyses should be done beside cardiac tests initially. Therefore, a precise diagnosis may be possible without the possible complications of unnecessary coronary interventions. PMID:23906332

Tekçe, Hikmet; Akta?, Gülali; Oztürk, Serkan



Hypokalemic periodic paralysis associated with thyrotoxicosis, renal tubular acidosis and nephrogenic diabetes insipidus.  


A 19-year-old girl presented at our emergency room with hypokalemic periodic paralysis. She had a thyrotoxic goiter and had experienced three paralytic attacks during the previous 2 years on occasions when she stopped taking antithyroid drugs. In addition to thyrotoxic periodic paralysis (TPP), she had metabolic acidosis, urinary potassium loss, polyuria and polydipsia. Her reduced ability to acidify urine during spontaneous metabolic acidosis was confirmed by detection of coexisting distal renal tubular acidosis (RTA). The polyuria and polydipsia were caused by nephrogenic diabetes insipidus, which was diagnosed using the water deprivation test and vasopressin administration. Her recurrent and frequent paralytic attacks may have been the combined effects of thyrotoxicosis and RTA. Although the paralytic attack did not recur after improving the thyroid function, mild acidosis and nephrogenic DI have been remained subsequently. Patients with TPP, especially females with atypical metabolic features, should be investigated for possible precipitating factors. PMID:20150720

Im, Eun Joo; Lee, Jung Min; Kim, Ji Hyun; Chang, Sang Ah; Moon, Sung Dae; Ahn, Yu Bae; Son, Hyun Shik; Cha, Bong Yun; Lee, Kwang Woo; Son, Ho Young



[Ruminal acidosis complex--new observations and experiences (2). A review].  


By "Rumen acidosis" until recently only the acute indigestion with intoxication caused by excessive production of lactic acid was understood. Meanwhile, however, it has become evident that further pathologic changes can take place in the acid-base status of the rumen contents which may also be referred to as "Rumen acidosis". Basing on new literature and own experiences the paper gives a review of that "Rumen acidosis complex": Fundamentals of the regulation of pH in the rumen; chronic latent rumen acidosis (hyper- and parakeratosis, chronic hyperplastic rumenitis, rumenitis-liver abscess complex, hyperlipodeposition, low milk fat syndrome, atypical ketosis, chronic laminitis, cerebrocortical necrosis, acid-base metabolism); acute lactic acidosis (etiology, pathogenesis, therapy, prophylaxis). PMID:2872733

Dirksen, G



[The rumen acidosis complex--recent knowledge and experiences (1). A review].  


By "Rumen acidosis" until recently only the acute indigestion with intoxication caused by excessive production of lactic acid was understood. Meanwhile, however, it has become evident that further pathologic changes can take place in the acid-base status of the rumen contents which may also be referred to as "Rumen acidosis". Basing on new literature and own experiences the paper gives a review of that "Rumen acidosis complex": Fundamentals of the regulation of pH in the rumen; chronic latent rumen acidosis (hyper-and parakeratosis, chronic hyperplastic rumenitis, rumenitis-liver abscess complex, hyperlipodeposition, low milk fat syndrome, atypical ketosis, chronic laminitis, cerebrocortical necrosis, acid-base metabolism); acute lactic acidosis (etiology, pathogenesis, therapy, prophylaxis). PMID:3834644

Dirksen, G



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

PubMed Central

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



Acidosis in Cattle: A Review1  

Microsoft Academic Search

Acute and chronic acidosis, conditions that follow ingestion of excessive amounts of readily fermented carbohydrate, are prominent production problems for ruminants fed diets rich in concentrate. Often occurring during adaptation to concentrate-rich diets in feedyards, chronic acidosis may continue during the feeding period. With acute acidosis, rumi- nal acidity and osmolality increase markedly as acids and glucose accumulate; these can

F. N. Owens; D. S. Secrist; W. J. Hill; D. R. Gill



Acidosis in muscle tissue distal to vascular contusion despite unchanged global blood flow in rats: An uncoupling of microvascular blood flow and metabolism?  

Microsoft Academic Search

Studies using a contusion trauma model have shown that the femoral artery of the rat remains patent in 85% despite a severe vessel injury. A significant increase in tissue oxygenation (PtO2) has been found despite only a minor effect on blood flow (<20% decrease) on the muscle surface distal to the injury indicating a disturbed relationship between microvascular blood flow

L. E. Karlander; J. Henriksson; F. Sjöberg



Lactate Metabolism Following Severe Hemorrhage in the Conscious Dog.  

National Technical Information Service (NTIS)

The kinetics of lactate metabolism before and after hemorrhage of over 50% of the blood volume was studied in six conscious dogs given lactate-UC(14) by the primed infusion technique. In association with the marked rise in arterial Lactate concentration d...

R. Wiener J. J. Spitzer



Bovine Acidosis: Implications on Laminitis  

Microsoft Academic Search

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

James E. Nocek



Bicarbonate therapy improves growth in children with incomplete distal renal tubular acidosis  

Microsoft Academic Search

Incomplete distal renal tubular acidosis (idRTA) has recently been associated with osteoporosis and growth retardation, attributed\\u000a to the mild persistent metabolic acidosis. We hypothesized a therapeutic benefit from bicarbonate therapy on growth parameters\\u000a in children with idRTA. In a study group of 40 surgically treated patients with posterior urethral valve (PUV) and normal\\u000a estimated glomerular filtration rate, we evaluated the

Ajay P. Sharma; Ram N. Singh; Connie Yang; Raj K. Sharma; Rakesh Kapoor; Guido Filler



A case report of acute lymphoblastic leukemia complicated by lactic acidosis  

Microsoft Academic Search

Type B lactic acidosis (LA) is a distinct form of metabolic acidosis characterized by low blood pH (?7.35) accompanied by\\u000a accumulation of lactate (blood concentration ? 5 mmol\\/L) (Luft et al. in Am J Clin Pathol 80:484–489, 1983). There are two types of LA that are caused by different mechanisms. Type A is more common, and is caused by the lack of

Hong Chang; Xiao Shuai; Hong-Bing Ma; Ting Liu



Severe Obesity: Evidence for a Deranged Metabolic Program in Skeletal Muscle?  

PubMed Central

Severe obesity is increasing at a disproportionate rate compared to milder grade obesity. Our research group has obtained evidence indicative of an “obesity metabolic program” in the skeletal muscle of severely obese individuals which may be genetically or epigenetically determined. We believe this represents a paradigm shift in thinking about metabolic regulation in obesity.

Houmard, Joseph A; Pories, Walter J; Dohm, G Lynis



Severe obesity: evidence for a deranged metabolic program in skeletal muscle?  


Severe obesity is increasing at a disproportionate rate compared with milder grade obesity. Our research group has obtained evidence indicative of an "obesity metabolic program" in skeletal muscles of severely obese individuals, which may be determined genetically or epigenetically. We believe that this represents a paradigm shift in thinking about metabolic regulation in obesity. PMID:22710702

Houmard, Joseph A; Pories, Walter J; Dohm, G Lynis



[Liver function in cattle in experimental rumen acidosis].  


The investigations were performed on 6 Friesian-Holstein heifers, weighing 410-504 kg, in which acid indigestion was induced by intraruminal administration of saccharose in a dose of 12 g/kg body weight. The animals were observed for 9 days after the treatment. Functional state of the liver was evaluated on the basis of bromosulphthalein clearance, total bilirubin level and aspartate amino-transferase (AspAT) activity in serum, concentration of blood glucose, total serum protein and protein fractions. Within the first 24 hours, all heifers developed acute symptoms of rumen acidosis which persisted for 3 days after saccharose administration. Afterwards, a phase of gradual spontaneous recovery was observed. In the course of rumen acidosis a reduction in bromosulphthalein clearance, an increase in bilirubin level and AspAT activity, a decrease and then an increase in glucose concentration and a reduction in albumin content and, as a consequence, in albumin/globulin ratio were found. The results indicate that experimental rumen acidosis produced disturbances in excretory and metabolic functions of the liver in the examined heifers. Changes in biochemical parameters were preceded by an increase in AspAT activity and were most remarkable between 48 and 144 hours after saccharose administration. Liver dysfunction was of a various degree in individual animals and recovered within a relatively short period following the disappearance of rumen acidosis symptoms. PMID:7301626

Bieniek, K



Purpura associated with hypergammaglobulinemia, renal tubular acidosis and osteomalacia.  

PubMed Central

Two patients with hyperglobulinemia associated with purpura were studied. One had features of Sjögren's syndrome, while the other appeared to have a primary condition -- "chronic benign purpura". Both patients also had renal tubular acidosis, osteomalacia and renal calculi, with disturbed calcium metabolism and acid-base balance. Autoantibodies were detected in the serum of both patients, and mononuclear cell infiltrates were noted in skin and kidney biopsies from both. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4

Marquez-Julio, A.; Rapoport, A.; Wilansky, D. L.; Rabinovich, S.; Chamberlain, D.



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

PubMed Central

Background Base deficit (BD), anion gap (AG), and albumin corrected anion gap (ACAG) are used by clinicians to assess the presence or absence of hyperlactatemia (HL). We set out to determine if these tools can diagnose the presence of HL using cotemporaneous samples. Methods We conducted a chart review of ICU patients who had cotemporaneous arterial blood gas, serum chemistry, serum albumin (Alb) and lactate(Lac) levels measured from the same sample. We assessed the capacity of AG, BD, and ACAG to diagnose HL and severe hyperlactatemia (SHL). HL was defined as Lac > 2.5 mmol/L. SHL was defined as a Lac of > 4.0 mmol/L. Results From 143 patients we identified 497 series of lab values that met our study criteria. Mean age was 62.2 ± 15.7 years. Mean Lac was 2.11 ± 2.6 mmol/L, mean AG was 9.0 ± 5.1, mean ACAG was 14.1 ± 3.8, mean BD was 1.50 ± 5.4. The area under the curve for the ROC for BD, AG, and ACAG to diagnose HL were 0.79, 0.70, and 0.72, respectively. Conclusion AG and BD failed to reliably detect the presence of clinically significant hyperlactatemia. Under idealized conditions, ACAG has the capacity to rule out the presence of hyperlactatemia. Lac levels should be obtained routinely in all patients admitted to the ICU in whom the possibility of shock/hypoperfusion is being considered. If an AG assessment is required in the ICU, it must be corrected for albumin for there to be sufficient diagnostic utility.

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



[The role of lactate besides the lactic acidosis].  


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

Brucculeri, S; Urso, C; Caimi, G


Lactobacillus GG does not affect D-lactic acidosis in diarrheic calves, in a clinical setting.  


D-lactate, produced by gastrointestinal fermentation, is a major contributor to metabolic acidosis in diarrheic calves. Lactobacillus rhamnosus GG survives gastrointestinal transit in the neonatal calf and does not produce D-lactate. To determine whether this probiotic reduces gastrointestinal D-lactate production or severity of diarrhea or both, 48 calves (mean, 11 days old; range, 2-30 days) admitted to the clinic for treatment of diarrhea were randomly allocated to 2 groups. The experimental group was given Lactobacillus rhamnosus GG (1 x 10(11) cfu/d) PO, dissolved in milk or oral electrolyte solution, in addition to clinic treatment protocols; the other group served as a control. Serum and fecal samples were obtained at admission and at 24 and 48 hours after initial administration of Lactobacillus rhamnosus GG. All samples were analyzed for D- and L-lactate by using high-pressure liquid chromatography. Feces were also analyzed for pathogens, Lactobacillus rhamnosus GG recovery, and dry matter. D-lactic acidemia (>3 mmol/L) was present in 37/48 calves at admission. Lactobacillus rhamnosus GG was recovered in the feces of 13 experimental calves and 0 control calves 24 hours after administration. No difference in serum or fecal D- or L-lactate between the groups was detected at any time point. After therapy, D-lactic acidosis was absent at 48 hours in all but 1 calf. No relation between fecal pathogen (viral, bacterial, or protozoal) and degree of D-lactic acidosis was observed. The reduction in mortality and greater fecal dry matter in Lactobacillus rhamnosus GG-treated calves was not statistically significant. PMID:16734098

Ewaschuk, Julia B; Zello, Gordon A; Naylor, Jonathan M


Anaerobic metabolism in the leech ( Hirudo medicinalis L.): direct and indirect calorimetry during severe hypoxia  

Microsoft Academic Search

Anaerobic metabolism in the limnic annelid Hirudo medicinalis L. was investigated by direct and indirect calorimetry. During long-term severe hypoxia, the rate of heat dissipation was reduced up to 13% of the aerobic rate. At the same time, the rate of ATP turnover was reduced to about 30% of the aerobic rate, indicating that metabolic depression is an important mechanism

H. Schmidt; A. Wichmann; I. Lamprecht; I. Zerbst-Boroffka



Enteral glutamine spares endogenous glutamine in chronic acidosis.  


Metabolic acidosis associated with the catabolic state mobilizes muscle nitrogen and releases it into blood as glutamine (GLN) targeted for renal consumption and base generation. Because GLN removed by the kidneys during acidosis is a major drain on the GLN available to other sites, subsequent deprivation may lead to impaired organ function. Conversely, GLN supplementation may spare endogenous supplies and restore organ function. To test this, Sprague-Dawley rats weighing between 250 and 350 g were pair-fed elemental diets supplemented with GLN 4.9 g/L (GLN-ED) or an equivalent mixture of neutral amino acids substituted for GLN (ED). Acid loading was effected by adding hydrochloric acid to the liquid diet (110 mmol/L). Animals were studied in metabolic cages for five consecutive 24-hour urine collection periods and then anesthetized for short-term studies of interorgan fluxes and tissue GLN content. Acidosis effected an increase in ammonium nitrogen excretion (fivefold) and a reciprocal decrease (24%) in urea nitrogen excretion. Enteral GLN had no effect on the acidosis-effected ammonium (2170 +/- 71 vs 2059 +/- 361 mumol/100 g, ED vs GLN-ED, respectively) or urea excretion (5522 +/- 95 vs 5915 +/- 984 mumol/100 g, ED vs GLN-ED, respectively). Although arterial blood GLN was not increased in the GLN-ED group (531 +/- 58 vs 438 +/- 51 nmol/mL, p = .10), both liver and muscle GLN were elevated (11,650 +/- 1137 nmol/g vs 7063 +/- 578 and 5503 +/- 489 and 4742 +/- 333 nmol/g, respectively, each p < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7914940

Welbourne, T C; Joshi, S


Seizure Termination by Acidosis Depends on ASIC1a  

PubMed Central

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

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



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

PubMed Central

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

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



Pseudohypoaldosteronism Type II: Proximal Renal Tubular Acidosis and dDAVP-Sensitive Renal Hyperkalemia  

Microsoft Academic Search

The mechanisms of metabolic acidosis and hyperkalemia were investigated in a patient with chronic mineralocorticoid-resistant renal hyperkalemia (5.3–6.9 mmol\\/l), metabolic acidosis (arterial blood pH 7.27, total CO2 17 mmol\\/l), arterial hypertension, undetectable plasma renin activity ( < 0.10 ng\\/ml\\/h), high plasma aldosterone level (32–100 ng\\/dl), and normal glomerular filtration rate (131 ml\\/min\\/1.73 m2). During the hyperkalemic period, urine was highly

Hervé Nahum; Michel Paillard; Alain Prigent; Françoise Leviel; Maurice Bichara; Jean-Paul Gardin; Jean-Marie Idatte



Disorders of pyruvate metabolism.  


Pyruvate dehydrogenase and pyruvate carboxylase deficiency are the most common disorders in pyruvate metabolism. Diagnosis is made by enzymatic and DNA analysis after basic biochemical tests in plasma, urine, and CSF. Pyruvate dehydrogenase has three main subunits, an additional E3-binding protein and two complex regulatory enzymes. Most frequent are deficiencies in PDH-E1?. There is a spectrum of clinical presentations in E1? deficiency, ranging in boys from severe neonatal lactic acidosis, Leigh encephalopathy, to later onset of neurological disease such as intermittent ataxia or dystonia. Females tend to have a more uniform presentation resembling nonprogressive cerebral palsy. Neuroradiological abnormalities such as corpus callosum agenesis are seen more frequently in girls, basal ganglia and midbrain disturbances in boys. Deficiencies in the other subunits have also been described, but in a smaller number of patients. Pyruvate carboxylase deficiency has three clinical phenotypes. The infantile type is characterized mainly by severe developmental delay, failure to thrive, and seizures. The second type is characterized by neonatal onset of severe lactic acidosis with rigidity and hypokinesia. A third form is rarer with intermittent episodes of lactic acidosis and ketoacidosis. Neuroradiological findings such as cystic periventricular leukomalacia have been described. PMID:23622387

Meirleir, Linda De



Recurrent metabolic alkalosis and elevated troponins after crack cocaine use in a hemodialysis patient  

Microsoft Academic Search

When acid-base disorders have been described after cocaine use, they are usually metabolic acidosis. We report a case of recurrent\\u000a crack cocaine use associated with severe metabolic alkalosis on two successive admissions, in a patient in renal failure on\\u000a hemodialysis and with minimal urine output, despite no history of vomiting or alkali ingestion. The metabolic alkalosis did\\u000a not recur after

Charles J. Diskin; Thomas J. Stokes; Linda M. Dansby; Lautrec Radcliff; Thomas B. Carter




Technology Transfer Automated Retrieval System (TEKTRAN)

Ruminal acidosis is a major diet-related health disorder of dairy cattle. Although the main focus of research on ruminal acidosis has been on the rumen, there is ample evidence that the disorder is not strictly centered in the rumen, and that it may involve other gastrointestinal compartments. To ...


Ruminal Acidosis in Milk-fed Calves  

Microsoft Academic Search

Ruminal acidosis in pre-ruminant calves is caused primarily by the inefficient function of the esophageal groove, producing an abnormal accumulation of fermentable liquid in the rumen. This issue of Large Animal Veterinary Rounds describes the most important factors that induce esophageal groove dysfunction and the etiological, pathogenic, and clinical aspects of ruminal acidosis in milk-fed calves. This issue will also

Arcangelo Gentile; Jonathan M. Naylor; Charles S. Rhodes; David G. Wilson; Ken Armstrong; Emeritus Sue Ashburner; Jeremy Bailey



Successful treatment of thyroid crisis accompanied by hypoglycemia, lactic acidosis, and multiple organ failure.  


We describe a case of thyroid crisis with hypoglycemia, lactic acidosis, multiple organ failure, and disseminated intravascular coagulation--rare but severe complications of thyroid crisis. The patient was a 59-year-old Chinese woman who presented with evidence of heart failure and atrial fibrillation. Analysis of a blood sample yielded astonishing results: her blood glucose was 1.7 mmol/L, and lactate greater than 15 mmol/L with the arterial pH as 6.94. Liver enzymes (alanine aminotransferase, 1846 U/L; aspartate aminotransferase, 6242 U/L) and bilirubin elevated rapidly and dramatically. Prompt treatments such as mechanical ventilation, plasma exchange, and continuous venovenous hemofiltration were preformed, along with antithyroid medication. The patient finally survived after 3 weeks of intensive care. We herein discuss the possible mechanisms of these metabolic disorders in thyroid crisis and possible therapeutic measures that could be used to reduce mortality. PMID:22386356

Deng, Yongmei; Zheng, Weiwei; Zhu, Jihong



Metabolic and cardiovascular improvements after biliopancreatic diversion in a severely obese patient  

Microsoft Academic Search

BACKGROUND: Severe obesity is associated with important morbidity and increased mortality. The successes of lifestyle modifications and drug therapy have been partial and mostly unsustained in reducing obesity and its comorbidities. Bariatric surgery, particularly biliopancreatic diversion with duodenal switch reduces efficiently excess body weight and improves metabolic and cardiovascular functions. CASE PRESENTATION: A 56-year-old man with severe clinical obesity underwent

Philippe Woods; Carmen Paquette; Julie Martin; Jean-Gaston Dumesnil; Picard Marceau; Simon Marceau; Simon Biron; Frédéric Hould; Odette Lescelleur; Stéphane Lebel; Paul Poirier



Cerebral energy metabolism during transient hyperglycemia in patients with severe brain trauma  

Microsoft Academic Search

Objective. To study whether transient hyperglycemia adversely affects cerebral energy metabolism in patients with severe traumatic brain lesions. Design and setting. Prospective, nonrandomized study in the neurosurgical intensive care unit of a university hospital. Patients. 108 patients treated for severe traumatic brain lesions. Interventions. All patients were treated according to neurosurgical intensive care routine including monitoring of intracranial pressure. One

Pedro Diaz-Parejo; Nils Ståhl; Wangbin Xu; Peter Reinstrup; Urban Ungerstedt; Carl-Henrik Nordström



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

Microsoft Academic Search

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

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



The Relationship of Omental and Subcutaneous Adipocyte Size to Metabolic Disease in Severe Obesity  

Microsoft Academic Search

ObjectiveSeveral studies have reported the existence of a subgroup of obese individuals with normal metabolic profiles. It remains unclear what factors are responsible for this phenomenon. We proposed that adipocyte size might be a key factor in the protection of metabolically healthy obese (MHO) individuals from the adverse effects of obesity.SubjectsThirty-five patients undergoing bariatric surgery were classified as MHO (n

Jean OConnell; Lydia Lynch; Tom J. Cawood; Anna Kwasnik; Niamh Nolan; Justin Geoghegan; Aiden McCormick; Cliona OFarrelly; Donal OShea



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

PubMed Central

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

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



Acidosis induced by lactate, pyruvate, or HCl increases blood viscosity  

Microsoft Academic Search

Purpose: Serum lactate correlates with the severity of disease and the mortality in shock. It is not clear if lactate is only a marker or a mediator of disease. We tested the hypothesis that acidosis induced by lactate and pyruvate affects blood flow properties. Materials and Methods: Human blood was incubated with additional lactate (0-50 mmol\\/L) or pyruvate (0-25 mmol\\/L)

Walter H. Reinhart; Roman Gaudenz; Roland Walter



Mutations in the gene encoding B1 subunit of H+ATPase cause renal tubular acidosis with sensorineural deafness  

Microsoft Academic Search

H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations

Fiona E. Karet; Karin E. Finberg; Raoul D. Nelson; Ahmet Nayir; Hilal Mocan; Sami A. Sanjad; Juan Rodriguez-Soriano; Fernando Santos; Cor W. R. J. Cremers; Antonio Di Pietro; Barry I. Hoffbrand; Jacek Winiarski; Aysin Bakkaloglu; Seza Ozen; Ruhan Dusunsel; Paul Goodyer; Sally A. Hulton; Doris K. Wu; Anne B. Skvorak; Cynthia C. Morton; Michael J. Cunningham; Vivekanand Jha; Richard P. Lifton



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


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

Lau, Emily; Mazer, Jeffrey; Carino, Gerardo



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

Microsoft Academic Search

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

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



How to Achieve Optimal Correction of Acidosis in End-Stage Renal Failure Patients  

Microsoft Academic Search

Metabolic acidosis appears to be responsible for a variety of detrimental clinical and biological effects in uremic subjects, making its correction with dialysis mandatory. By utilizing the kinetic approach, pre- and post-dialysis target levels to be achieved by dialysis can be defined. Although a clear-cut bicarbonate concentration threshold, below which deleterious effects appear, has not yet been defined, it seems

Pietro Zucchelli; Antonio Santoro



Intracellular potential and K + activity in rat kidney proximal tubular cells in acidosis and K + depletion  

Microsoft Academic Search

Summary Techniques were developed for the measurement of intracellular potentials and potassium activities in rat proximal tubule cells using double barreled K+ liquid-ion-exchanger microelectrodes. After obtaining measurements of stable and reliable control values, the effects of K+ depletion and metabolic and respiratory acidosis on the intracellular potential and K+ activity in rat kidney proximal tubular cells were determined. At a

D. Cemeriki?; C. S. Wilcox; G. Giebisch



Cerebral perfusion and metabolism in resuscitated patients with severe post-hypoxic encephalopathy  

Microsoft Academic Search

Positron emission tomography (PET) was used for the study of regional cerebral perfusion and metabolism in eight patients with severe post-hypoxic encephalopathy, caused by cardiac arrest and resulting in a coma lasting for at least 24 h. Using this method, we aimed to identify regional vulnerability, which was hypothesized to provide (i) insight in pathogenic mechanisms and (ii) early prognostic

A Schaafsma; B. M de Jong; J. L Bams; H Haaxma-Reiche; J Pruim; J. G Zijlstra



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

Microsoft Academic Search

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

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



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

Microsoft Academic Search

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

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



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


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

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



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


Groups of male rats were exposed to acute doses of oxygen, ozone, or paraquat which produced equivalent mortality (25-30%) over a 28 day post-exposure period. Quantitative evaluation of morphological changes indicated the primary response to be edema and inflammation with only slight fibrosis being apparent by the end of the observation period. Aerobic pulmonary metabolism was inhibited in lungs from animals exposed to oxygen and ozone as evidenced by decreased oxygen consumption; however, this was transient and O2 consumption returned to normal within 24 hours after removal from the exposure chamber. Conversely, treatment with paraquat caused an immediate, transient stimulation of O2 consumption. Glucose metabolism was unaltered by the gas exposures and, as previously reported, was initially stimulated by paraquat treatment. In vitro, only paraquat altered both O2 consumption and glucose metabolism when added to lung slice preparations; ozone had no effect. Oxygen did not alter O2 consumption but caused a slight biphasic response in glucose metabolism. Aerobic metabolism is relatively unchanged by these doses of oxygen and ozone which result in the death of 25-30% of all treated animals. Even though paraquat produces similar morphologic changes, it may represent a more severe metabolic insult than "equivalent" doses of oxygen or ozone. Also, if interstitial pulmonary fibrosis is a desired result of experimental exposure, rats may not be a suitable model for oxidant induced lung injury. PMID:3795010

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


Acidosis and Correction of Acidosis Does Not Affect rFVIIa Function in Swine.  

National Technical Information Service (NTIS)

Background: Hemorrhagic shock and trauma are associated with acidosis and altered coagulation. A fall in pH has been reported to attenuate the activity of recombinant activated Factor VII (rFVIIa) in vitro. However, it is not known if acidosis induced by ...

B. S. Kheirabadi D. N. Darlington M. A. Dubick M. R. Scherer W. Z. Martini



Anaerobic metabolism in the leech (Hirudo medicinalis L.): direct and indirect calorimetry during severe hypoxia.  


Anaerobic metabolism in the limnic annelid Hirudo medicinalis L. was investigated by direct and indirect calorimetry. During long-term severe hypoxia, the rate of heat dissipation was reduced up to 13% of the aerobic rate. At the same time, the rate of ATP turnover was reduced to about 30% of the aerobic rate, indicating that metabolic depression is an important mechanism to ensure survival of the leech during environmental anaerobiosis. Heat dissipation during hypoxia was monitored under two experimental conditions, favouring either concomitant hypocapnia (continuous N2 bubbling) or hypercapnia (self-induced hypoxia). The reduction in heat dissipation during hypocapnic hypoxia was less pronounced than during hypercapnic hypoxia, indicating that the different experimental conditions may influence anaerobic metabolism and the extent of metabolic depression. Biochemical analysis of known anaerobic substrates and endproducts provided the basis for indirect calorimetry during self-induced hypoxia. From changes in metabolites, the expected heat dissipation was calculated for initial (0-8 ,h) and long-term severe hypoxia (8-72 h). During the initial period, the calculated heat dissipation fully accounted for direct calorimetric determination. During long-term hypoxia, only 71% of the measured heat production could be explained from biochemical analysis of metabolites. Therefore, an additional unknown endproduct cannot be excluded, especially when anaerobic ammonia production and analysis of the carbohydrate balance are considered. PMID:8765666

Schmidt, H; Wichmann, A; Lamprecht, I; Zerbst-Boroffka, I



The Relationship of Omental and Subcutaneous Adipocyte Size to Metabolic Disease in Severe Obesity  

PubMed Central

Objective Several studies have reported the existence of a subgroup of obese individuals with normal metabolic profiles. It remains unclear what factors are responsible for this phenomenon. We proposed that adipocyte size might be a key factor in the protection of metabolically healthy obese (MHO) individuals from the adverse effects of obesity. Subjects Thirty-five patients undergoing bariatric surgery were classified as MHO (n?=?15) or metabolically unhealthy obese (MUO, n?=?20) according to cut-off points adapted from the International Diabetes Federation definition of the metabolic syndrome. Median body mass index (BMI) was 48 (range 40–71). Results There was a moderate correlation between omental adipocyte size and subcutaneous adipocyte size (r?=?0.59, p<0.05). The MHO group had significantly lower mean omental adipocyte size (80.9±10.9 µm) when compared with metabolically unhealthy patients (100.0±7.6 µm, p<0.0001). Mean subcutaneous adipocyte size was similar between the two groups (104.1±8.5 µm versus 107.9±7.1 µm). Omental, but not subcutaneous adipocyte size, correlated with the degree of insulin resistance as measured by HOMA-IR (r?=?0.73, p<0.0005), as well as other metabolic parameters including triglyceride/HDL-cholesterol ratio and HbA1c. Twenty-eight patients consented to liver biopsy. Of these, 46% had steatohepatitis and fibrosis. Fifty percent (including all the MHO patients) had steatosis only. Both omental and subcutaneous adipocyte size were significantly associated with the degree of steatosis (r?=?0.66, p<0.0001 and r?=?0.63, p<0.005 respectively). However, only omental adipocyte size was an independent predictor of the presence or absence of fibrosis. Conclusion Metabolically healthy individuals are a distinct subgroup of the severely obese. Both subcutaneous and omental adipocyte size correlated positively with the degree of fatty liver, but only omental adipocyte size was related to metabolic health, and possibly progression from hepatic steatosis to fibrosis.

O'Connell, Jean; Lynch, Lydia; Cawood, Tom J.; Kwasnik, Anna; Nolan, Niamh; Geoghegan, Justin; McCormick, Aiden; O'Farrelly, Cliona; O'Shea, Donal



Growth hormone action is blunted by acidosis in experimental uremia or acid load.  


The effects of rhGH (H) daily injection (2 IU/d) and of vehicle (V) during two weeks were studied in young (60 g) growing rats. Experiment I was performed in uremic rats (mean plasma creatinine: 65-71 mumol/l) either acidotic (mean HCO3-:11.5 mmol/l: UAH, n = 20; UAV, n = 18), or with corrected acidosis by addition of NaHCO3 in the diet (mean HCO3-:26 mmol/l: UBH, n = 25; UBV, n = 23). Experiment II used rats with normal renal function (plasma creatinine: 25 mumol/l), either non-acidotic but food restricted to the dietary intake of uremic rats (CRH: n = 18, CRV: n = 18), or rendered acidotic by NH4Cl (CAH: n = 16, CAV: n = 16). GH induced an augmentation of body weight and length gains in non-acidotic uremic rats (+33% and +41%: p < 0.01), and in non-acidotic food restricted rats (+13% and 42%: p < 0.05 and p < 0.0001). This was associated with increased protein synthesis rate in muscle and with little change of food intake as well as of plasma IGF 1. Plasma IGF 1 kept the same relationship to food intake, regardless of treatment, but length gain for each level of plasma IGF 1 was enhanced by GH in GH responding groups. In both acidotic rat groups, GH altered none of the parameters studied. Thus: 1) the presence of severe metabolic acidosis blunts the response to GH in uremic and non-uremic rats. 2) The increment of growth rate does not depend on a rise of plasma IGF 1. PMID:8832158

Maniar, S; Kleinknecht, C; Zhou, X; Motel, V; Yvert, J P; Dechaux, M



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


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

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



Feeling blue with metformin-associated lactic acidosis.  


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

Plumb, Benjamin; Parker, Alex; Wong, Paul




Microsoft Academic Search

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

T. L. Huber


Effect of acarbose on acute acidosis.  


A challenge model was used to evaluate a new approach to controlling acute acidosis. Acute acidosis reduces performance in both dairy and beef cattle and most often occurs as a consequence of ingestion of large amounts of readily fermentable starch, resulting in increased production of volatile fatty acids (VFA) and lactic acid and a reduction in ruminal pH. Acarbose is an alpha-amylase and glucosidase inhibitor that slows the rate of degradation of starch to glucose, thereby reducing the rate of VFA production and maintaining rumen pH at a more stable level. It is commercially available (Glucobay, Bayer, Wuppertal, Germany) and indicated for the control of blood glucose in diabetic patients. The ability of acarbose to reduce the incidence of acidosis and the comparative efficacies of acarbose, sodium bicarbonate, and monensin were tested in 3 acute acidosis challenge experiments in cattle. Rumen-cannulated Holstein steers were challenged with a mixture of 48.4% cornstarch, 48.4% ground corn, 2.1% sodium caseinate, and 1.1% urea with or without test substance. The challenge was administered at a rate of 12.5 g/kg of body weight (BW) as a slurry through the cannula directly into the rumen. Ruminal pH was monitored at 10-min intervals throughout the study. Animals were removed from study and rumen contents replaced if they exhibited acute acidosis as defined as pH <4.5. If acidosis was not observed within 24 h, animals were subjected to a second challenge. Ruminal fluid samples were taken for measurement of VFA and lactate concentrations at various intervals after the challenge. In experiment 1, the carbohydrate challenge induced acidosis in 4 of 4 control animals and 0 of 4 animals treated with 2.14 or 21.4 mg of acarbose/kg of BW in the challenge based on the criterion of pH <4.5. In experiment 2, the carbohydrate challenge induced acidosis in 4 of 7 control animals and 1 of 7 animals when 1.07 mg of acarbose/kg of BW was included in the challenge. In experiment 3, acidosis was induced in 7 of 7 animals in the control, 1% sodium bicarbonate, and 12 mg of monensin/kg of dry matter intake groups and in 3 of 8 steers administered 1.07 mg of acarbose/kg of BW in the challenge. Increases in lactate concentrations and decreases in total VFA associated with acute acidosis were mitigated by acarbose. Thus, acarbose, an amylase and glucosidase inhibitor, prevented or reduced the incidence of acidosis in an acute challenge model in steers and was more effective than monensin or sodium bicarbonate. PMID:19448010

McLaughlin, C L; Thompson, A; Greenwood, K; Sherington, J; Bruce, C



A Rare Case of Type I RenalTubular Acidosis with Membranous Nephropathy Presenting as Hypokalemic Paralysis.  


Type 1 renal tubular acidosis (RTA), or distal RTA (dRTA), is a disorder of renal tubular acidification, which is generally asymptomatic but may rarely present as hypokalemic paralysis. Here, we report the case of a young male who presented with sudden onset weakness of all 4 limbs and a 2-month history of swelling of the legs. An investigation revealed hypokalemia, metabolic acidosis, and nephrotic syndrome. Additional analyses revealed normal anion gap metabolic acidosis with a positive urine anion gap and dRTA. Renal biopsy showed evidence of membranous nephropathy (MN). The patient's weakness improved with potassium supplements. Normalization of the serum potassium level and disappearance of proteinuria were established with an ACE inhibitor and potassium supplementation. This case is an unusual combination of dRTA with MN coupled with the rare presenting symptoms of hypokalemic paralysis and medullary nephrocalcinosis. PMID:23898345

Sunder, Sham; Sathi, Satyanand; Venkataramanan, K; Verma, Himanshu; Bhardwaj, Minakshi; Rajesh, J; Mahapatra, Himanshu



A Rare Case of Type I RenalTubular Acidosis with Membranous Nephropathy Presenting as Hypokalemic Paralysis  

PubMed Central

Type 1 renal tubular acidosis (RTA), or distal RTA (dRTA), is a disorder of renal tubular acidification, which is generally asymptomatic but may rarely present as hypokalemic paralysis. Here, we report the case of a young male who presented with sudden onset weakness of all 4 limbs and a 2-month history of swelling of the legs. An investigation revealed hypokalemia, metabolic acidosis, and nephrotic syndrome. Additional analyses revealed normal anion gap metabolic acidosis with a positive urine anion gap and dRTA. Renal biopsy showed evidence of membranous nephropathy (MN). The patient's weakness improved with potassium supplements. Normalization of the serum potassium level and disappearance of proteinuria were established with an ACE inhibitor and potassium supplementation. This case is an unusual combination of dRTA with MN coupled with the rare presenting symptoms of hypokalemic paralysis and medullary nephrocalcinosis.

Sunder, Sham; Sathi, Satyanand; Venkataramanan, K.; Verma, Himanshu; Bhardwaj, Minakshi; Rajesh, J.; Mahapatra, Himanshu



Metabolic and cardiovascular improvements after biliopancreatic diversion in a severely obese patient  

PubMed Central

Background Severe obesity is associated with important morbidity and increased mortality. The successes of lifestyle modifications and drug therapy have been partial and mostly unsustained in reducing obesity and its comorbidities. Bariatric surgery, particularly biliopancreatic diversion with duodenal switch reduces efficiently excess body weight and improves metabolic and cardiovascular functions. Case presentation A 56-year-old man with severe clinical obesity underwent a biliopancreatic diversion with a duodenal switch after unsuccessful treatment with weight loss pharmacotherapy. He had diabetes, hypertension and sleep apnea syndrome and was on three medications for hypertension and two hypoglycemic agents in addition to > 200 insulin units daily. Eleven months after the surgery, he had lost 40% of his body weight. The lipid profile showed great improvement and the hypertension and diabetes were more easily controlled with no more insulin needed. The pseudonormalized pattern of left ventricular diastolic function improved and ventricular walls showed decreased thickness. Conclusion Biliopancreatic diversion may bring metabolic and cardiovascular benefits in severely obese patients from a cardiovascular perspective.

Woods, Philippe; Paquette, Carmen; Martin, Julie; Dumesnil, Jean-Gaston; Marceau, Picard; Marceau, Simon; Biron, Simon; Hould, Frederic; Lescelleur, Odette; Lebel, Stephane; Poirier, Paul



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

Microsoft Academic Search

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

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



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

SciTech Connect

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

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



Acquired distal renal tubular acidosis in man  

Microsoft Academic Search

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

O. S. Better



Metformin-associated lactic acidosis in an intensive care unit  

PubMed Central

Introduction Metformin-associated lactic acidosis (MALA) is a classic side effect of metformin and is known to be a severe disease with a high mortality rate. The treatment of MALA with dialysis is controversial and is the subject of many case reports in the literature. We aimed to assess the prevalence of MALA in a 16-bed, university-affiliated, intensive care unit (ICU), and the effect of dialysis on patient outcome. Methods Over a five-year period, we retrospectively identified all patients who were either admitted to the ICU with metformin as a usual medication, or who attempted suicide by metformin ingestion. Within this population, we selected patients presenting with lactic acidosis, thus defining MALA, and described their clinical and biological features. Results MALA accounted for 0.84% of all admissions during the study period (30 MALA admissions over five years) and was associated with a 30% mortality rate. The only factors associated with a fatal outcome were the reason for admission in the ICU and the initial prothrombin time. Although patients who went on to haemodialysis had higher illness severity scores, as compared with those who were not dialysed, the mortality rates were similar between the two groups (31.3% versus 28.6%). Conclusions MALA can be encountered in the ICU several times a year and still remains a life-threatening condition. Treatment is restricted mostly to supportive measures, although haemodialysis may possess a protective effect.

Peters, Nicolas; Jay, Nicolas; Barraud, Damien; Cravoisy, Aurelie; Nace, Lionel; Bollaert, Pierre-Edouard; Gibot, Sebastien



Enduring effects of severe developmental adversity, including nutritional deprivation, on cortisol metabolism in aging Holocaust survivors  

PubMed Central

Objective In animal models, early life exposure to major environmental challenges such as malnutrition and stress results in persisting cardiometabolic, neuroendocrine and affective effects. While such effects have been associated with pathogenesis, the widespread occurrence of ‘developmental programming’ suggests it has adaptive function. Glucocorticoids may mediate ‘programming’ and their metabolism is known to be affected by early life events in rodents. To examine these relationships in humans, cortisol metabolism and cardiometabolic disease manifestations were examined in Holocaust survivors in relation to age at exposure and affective dysfunction, notably lifetime posttraumatic stress disorder (PTSD). Methods 51 Holocaust survivors and 22 controls without Axis I disorder collected 24-hr urine samples and were evaluated for psychiatric disorders and cardiometabolic diagnoses. Corticosteroids and their metabolites were assayed by gas chromatography mass spectroscopy (GCMS); cortisol was also measured by radioimmunoassay (RIA). Results Holocaust survivors showed reduced cortisol by RIA, and decreased levels of 5?-tetrahydrocortisol (5?-THF) and total glucocorticoid production by GCMS. The latter was associated with lower cortisol metabolism by 5?-reductase and 11?-hydroxysteroid dehydrogenase (11?-HSD) type-2. The greatest decrements were associated with earliest age of Holocaust exposure and less severe PTSD symptomatology. Cardiometabolic manifestations were associated with decreased 11?-HSD-2 activity. In contrast to the relationship in Holocaust survivors, in controls, 5?-reductase was positively associated with trauma-related symptoms. Conclusion Extreme malnutrition and related stress during development is associated with long-lived alterations in specific pathways of glucocorticoid metabolism. These effects may be adaptive and link with lower risks of cardiometabolic and stress-related disorders in later life.

Yehuda, Rachel; Bierer, Linda M.; Andrew, Ruth; Schmeidler, James; Seckl, Jonathan R.



Effects of intravenous hyperosmotic sodium bicarbonate on arterial and cerebrospinal fluid acid-base status and cardiovascular function in calves with experimentally induced respiratory and strong ion acidosis.  


The objectives of this study were to determine the effects of hyperosmotic sodium bicarbonate (HSB) administration on arterial and cerebrospinal fluid (CSF) acid-base balance and cardiovascular function in calves with experimentally induced respiratory and strong ion (metabolic) acidosis. Ten healthy male Holstein calves (30-47 kg body weight) were instrumented under halothane anesthesia to permit cardiovascular monitoring and collection of blood samples and CSE Respiratory acidosis was induced by allowing the calves to spontaneously ventilate, and strong ion acidosis was subsequently induced by i.v. administration of L-lactic acid. Calves were then randomly assigned to receive either HSB (8.4% NaHCO3; 5 ml/kg over 5 minutes, i.v.; n=5) or no treatment (controls, n=5) and monitored for 1 hour. Mixed respiratory and strong ion acidosis was accompanied by increased heart rate, cardiac index, mean arterial pressure, cardiac contractility (maximal rate of change of left ventricular pressure), and mean pulmonary artery pressure. Rapid administration of HSB immediately corrected the strong ion acidosis, transiently increased arterial partial pressure of carbon dioxide (P(CO2)), and expanded the plasma volume. The transient increase in arterial P(CO2) did not alter CSF P(CO2) or induce paradoxical CSF acidosis. Compared to untreated control calves, HSB-treated calves had higher cardiac index and contractility and a faster rate of left ventricular relaxation for 1 hour after treatment, indicating that HSB administration improved myocardial systolic function. We conclude that rapid i.v. administration of HSB provided an effective and safe method for treating strong ion acidosis in normovolemic halothane-anesthetized calves with experimentally induced respiratory and strong ion acidosis. Fear of inducing paradoxical CSF acidosis is not a valid reason for withholding HSB administration in calves with mixed respiratory and strong ion acidosis. PMID:15822570

Berchtold, Joachim F; Constable, Peter D; Smith, Geoffrey W; Mathur, Sheerin M; Morin, Dawn E; Tranquilli, William J


Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid resuscitation  

PubMed Central

Base deficit is a parameter often used to guide further treatment in acidotic children and is taken as a measure of how "sick" they are. Five children with septic shock are presented who had persisting base deficit after large volume resuscitation with 0.9% saline. Stewart's strong ion theory of acid-base balance is able to quantify the causes of metabolic acidosis and is used to show that our patients had a hyperchloraemic metabolic acidosis. We show how the chloride content of the saline loads given to our patients caused this hyperchloraemia. It is concluded that 0.9% saline and other chloride rich fluids may not be ideal resuscitation fluids; if used, clinicians must be aware of their potential to cause a persistent base deficit.??

Skellett, S; Mayer, A; Durward, A; Tibby, S; Murdoch, I



Comparative study of the effects of acebutolol, atenolol, d-propranolol and dl,-propranolol on the alterations in energy metabolism caused by ischemia and reperfusion: A 31P NMR study on the isolated rat heart  

Microsoft Academic Search

31-P NMR spectroscopy data recorded for the isolated heart were analyzed, in conjunction with functional and biochemical variables, in order to investigate the effect observed for several different beta-adrenoceptor antagonists on the alterations provoked by global partial ischemia (37°C, 24 minutes, 1% residual coronary flow) and reperfusion in the metabolism of the myocardium. During ischemia: intracellular acidosis, adenosine triphosphate (ATP)

N. Lavanchy; J. Martin; A. Rossi



Brain lactic acidosis and ischemic cell damage: Quantitative ultrastructural changes in capillaries of rat cerebral cortex  

Microsoft Academic Search

Excessive tissue lactic acidosis has earlier been shown to aggravate structural damage of both neurons and glial cells in the rat cerebral cortex. To study the reactions of cortical capillaries, light- and electronmicroscopic morphometry was used. Rats were subjected to severe incomplete ischemia (cerebral blood flow below 5% of normal) for 30 min by clamping their carotid arteries and by

L. Palfiirvi; S. Rehncrona; B. Söderfeldt; Y. Olsson; H. Kalimo



A pig hemorrhagic shock model: oxygen debt and metabolic acidemia as indicators of severity.  


"Uncontrolled bleeding," "a controlled prefixed bleeding volume," or "controlled decrements in blood pressure" are traditional models of experimental hemorrhagic shock. They are influenced by compensatory mechanisms and do not adequately reflect the severity of the cellular insult as a major target for therapeutic strategies. The aim of this study was to develop an animal model that uses oxygen debt (OD) and metabolic acidemia as indicators of hemorrhage severity. Twenty-five female pigs (mean weight: 23.8 kg) were anesthesized and randomized to 1 of 5 groups of increasing OD (<50 through >120 mL/kg). The predetermined OD was accrued by hemorrhage uniformly over 60 min and followed by retransfusion. The animals were allowed to recover under anesthesia for 200 min and were then observed for 3 days. The extent of metabolic derangements were quantified by arterial base excess (BE) and plasma lactate (LAC) measurements. OD, BE, and LAC were shown to be superior as predictors of outcome in comparison with traditional variables ("bleeding volume," "blood pressure," "cardiac output") in correlation and regression. Of the analyzed predictors of outcome, BE and LAC showed the highest correlation to levels of OD (r = -0.78, 0.8 respectively; P < 0.0001), and regression models were developed. The LD50 for OD was 95.0 mL/kg, for BE -15.3 mmol/L and for LAC 7.7 mmol/L. By using the developed regression models, it is possible to estimate accurately the actual level of OD from BE and LAC values obtained during hemorrhagic shock. OD, BE, and LAC appear to be optimal indicators of severity for a pig hemorrhagic shock model. PMID:11531028

Rixen, D; Raum, M; Holzgraefe, B; Sauerland, S; Nagelschmidt, M; Neugebauer, E A



Earlier Onset and Greater Severity of Disordered Mineral Metabolism in Diabetic Patients With Chronic Kidney Disease  

PubMed Central

OBJECTIVE Disordered mineral metabolism is a common complication of chronic kidney disease (CKD) and a novel risk factor for CKD progression, cardiovascular disease, and mortality. Although diabetes is the leading cause of CKD and is associated with worse clinical outcomes than other etiologies, few studies have evaluated mineral metabolism in CKD according to diabetes status. RESEARCH DESIGN AND METHODS Using the Chronic Renal Insufficiency Cohort Study, we tested the hypothesis that diabetes is independently associated with lower serum calcium and higher serum phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23). RESULTS Compared with participants without diabetes (n = 1,936), those with diabetes (n = 1,820) were more likely to have lower estimated glomerular filtration rate (eGFR), lower serum albumin, and higher urinary protein excretion (all P < 0.001). Unadjusted serum phosphate, PTH, and FGF23 levels were higher and calcium was lower among those with compared with those without diabetes (all P < 0.001). After multivariate adjustment, diabetes remained a significant predictor of serum phosphate, PTH, and FGF23 but not calcium. The eGFR cut point at which 50% of participants met criteria for secondary hyperparathyroidism or elevated FGF23 was higher in participants with diabetes compared with those without (PTH: eGFR 30–39 vs. 20–29, P < 0.001; FGF23: eGFR 50–59 vs. 40–49, P < 0.001). CONCLUSIONS Disordered mineral metabolism begins earlier in the course of CKD and is more severe among CKD patients with compared with those without diabetes. Future studies should explore mechanisms for these differences and whether they contribute to excess risks of adverse clinical outcomes among diabetic patients with CKD.

Wahl, Patricia; Xie, Huiliang; Scialla, Julia; Anderson, Cheryl A.M.; Bellovich, Keith; Brecklin, Carolyn; Chen, Jing; Feldman, Harold; Gutierrez, Orlando M.; Lash, Jim; Leonard, Mary B.; Negrea, Lavinia; Rosas, Sylvia E.; Anderson, Amanda Hyre; Townsend, Raymond R.; Wolf, Myles; Isakova, Tamara



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

Microsoft Academic Search

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

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



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


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

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




Microsoft Academic Search

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

Leonard L. Slyter



Distal renal tubular acidosis with hereditary spherocytosis.  


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

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



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


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

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



Extracellular acidosis modulates the endocytosis and maturation of macrophages.  


Extracellular acidosis is involved in various pathological situations of central nervous system and the effects are largely mediated by acid sensing ion channels (ASICs). However, it remains unclear whether extracellular acidosis affects immune cells. Macrophages are immune cells that play important role in immune reactions. In this study we investigated the impact of extracellular acidosis on the function of bone marrow derived macrophages (BMMs). The results showed that extracellular acidosis upregulated the endocytosis, surface molecular expression and interleukin-10 secretion of BMMs, in which the expression of ASIC1 and ASIC3 was detected. Notably, extracellular acidosis stimulated endocytosis and upregulation of surface molecules expression in BMMs could be abolished by amiloride, a blocker of ASICs, and nonsteroid anti-inflammatory drugs. Our findings provide new insight into the role of extracellular acidosis in the regulation of immune function and suggest ASICs as new targets for the modulation of immune response. PMID:23435349

Kong, Xiaoling; Tang, Xianying; Du, Wenjiao; Tong, Jing; Yan, Yutao; Zheng, Fang; Fang, Min; Gong, Feili; Tan, Zheng



Seizure termination by acidosis depends on ASIC1a  

Microsoft Academic Search

Most seizures stop spontaneously; however, the molecular mechanisms that terminate seizures remain unknown. Observations that seizures reduced brain pH and that acidosis inhibited seizures indicate that acidosis halts epileptic activity. Because acid-sensing ion channel 1a (ASIC1a) is exquisitely sensitive to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a, which would terminate seizures. Disrupting mouse ASIC1a

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



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

Microsoft Academic Search

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

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



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


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

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



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

Microsoft Academic Search

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

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



Fatal lactic acidosis associated with coadministration of didanosine and tenofovir disoproxil fumarate.  


Lactic acidosis is an uncommon but potentially life-threatening adverse effect of didanosine. When given concomitantly with tenofovir disoproxil fumarate (DF), the area under the concentration-time curve of didanosine is increased by 48-60%. A 63-year-old man with human immunodeficiency virus (HIV) infection tolerated several didanosine-containing antiretroviral regimens. He developed generalized weakness, loss of appetite, weight loss, nausea, and vomiting 1.5 years after tenofovir DF was added to his didanosine-containing regimen. He was diagnosed with lactic acidosis and died after a 13-day hospital stay, when his lactate level increased to 189.7 mg/dl and his arterial blood gas pH value fell to 6.75. Health care providers should maintain a high index of suspicion for lactic acidosis in patients with HIV infection who receive didanosine and tenofovir DF concurrently. For patients receiving antiretroviral regimens containing this drug combination, it would be prudent to monitor lactate levels periodically. This is especially important when patients experience symptoms suggestive of lactic acidosis, such as weakness, abdominal pain, weight loss, nausea and vomiting, and shortness of breath. PMID:15338857

Guo, Yi; Fung, Horatio B




Technology Transfer Automated Retrieval System (TEKTRAN)

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


The Influence of Vasoconstriction and Acidosis on Disseminated Intravascular Coagulation.  

National Technical Information Service (NTIS)

CONCLUSIONS: (1) Acute hemorrhage produces an immediate venous acidosis which is shortly followed by arterial acidosis if blood volume is not replaced. (2) Vasodilators bring about an immediate improvement in both arterial and venous pH. (3) Acid pH's in ...

W. R. Brewster R. M. Hardaway M. J. Elovitz



Optimal correction of acidosis changes progression of dialysis osteodystrophy  

Microsoft Academic Search

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

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



Contribution of respiratory acidosis to diaphragmatic fatigue at exercise  

Microsoft Academic Search

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

S. Jonville; N. Delpech; A. Denjean



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

PubMed Central

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

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



Holocarboxylase synthetase deficiency: a treatable metabolic disorder masquerading as cerebral palsy.  


A 20-month-old boy of Jewish-Turkish origin presented with severe metabolic acidosis. He was born prematurely and had bacteremia during the neonatal period. Scaly skin eruption, developmental delay, generalized muscular hypertonia, and mild ventriculomegaly were noted during the 1st year. Holocarboxylase synthetase deficiency was diagnosed, and biotin and carnitine were administered. The skin rash and the organic aciduria resolved within several days, and at 30 months, his psychomotor development was appropriate for age. Metabolic evaluation should be performed in patients with combined neurologic and dermatologic symptoms even when medical history suggests a nonmetabolic etiology. PMID:8006369

Livne, M; Gibson, K M; Amir, N; Eshel, G; Elpeleg, O N



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

Microsoft Academic Search

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

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



A case of mitochondrial myopathy, lactic acidosis and complex I deficiency  

Microsoft Academic Search

A 34-year-old man affected by exercise intolerance, mild proximal weakness and severe lactic acidosis is described. Muscle biopsy revealed mitochondrial abnormalities and an increase of cytochrome c oxidase histochemical reaction. Biochemical investigations on isolated muscle mitochondria as well as polarographic studies revealed a mitochondrial NADH-CoQ reductase (complex I) deficiency. Mitochondrial dysfunction was confirmed by 31P nuclear magnetic resonance spectroscopy. Immunological

L. Bet; N. Bresolin; M. Moggio; G. Meola; A. Prelle; A. H. Schapira; T. Binzoni; A. Chomyn; F. Fortunato; P. Cerretelli; G. Scarlato



[Fatal lactic acidosis in a patient with acquired immunodeficiency syndrome treated with highly active antiretroviral therapy. Report of a case].  


Type B lactic acidosis occurs without any evidence of cellular hypoxia and is associated with the use of drugs or toxins. We report a 36 years old woman with acquired immunodeficiency syndrome that was admitted to the hospital with a severe lactic acidosis. She had been treated with didanosine, stavudine and efavirenz for four months prior to admission. Despite the use of high bicarbonate doses and vasoactive drugs, the patient had a catastrophic evolution and died in shock and multiple organ failure, 68 hours after admission. (Rev Méd Chile 2000; 128: 1139-43). PMID:11349514

Lasso, M; Pérez, J; Noriega, L M; Northland, R



The role of chronic anion gap and/or nonanion gap acidosis in the osteodystrophy of chronic renal failure in the predialysis era: a minority report.  


Chronic renal failure (CRF) due to (1) glomerulopathies, vascular and tubulointerstitial disorders, and (2) chronic nonazotemic renal tubular disorders creates sustained acidosis in the untreated state. Number 1 represents a mixture of anion and nonanion gap acidosis and number 2 a pure nonanion gap acidosis. There remains significant uncertainty as to the role of the acidosis (CRF) in the associated osteodystrophy. In general, little attention has been given to this subject in recent monographs. It is the purpose of this review ('minority report') to 'reexamine' the information available on this subject in humans and animals. The author has concluded that the chronic metabolic acidosis of CRF may well contribute to the development and maintenance of the osteodystrophy, and that its treatment should be included along with the other modalities of therapy. The subject is not a 'dead issue' but one definitely deserving further investigation. The response of the skeleton to acid loads clearly represents another 'trade-off' in ion metabolism in CRF. PMID:8202057

Kleeman, C R



[Metabolic efficiency of carbostimulin in therapy of acidosis with diabetes].  


The total content of ketoacids, ketonic bodies and state of acid-base balance in blood of sugar diabetes patients was studied as affected by 10-day complex therapy with application of carbostimulin. It is established that carbostimulin lowers the content of ketonic bodies, increases the total content of ketoacids, concentration of buffer bases, CO2, HCO3-. Application of the complex therapy without the preparation causes only a tendency to study the mentioned indexes for the same period of the treatment. PMID:6770524

Shcherbak, A B; Dzvonkevich, N D


Daily exercise enhances fat utilization and maintains metabolic rate during severe energy restriction in humans  

Microsoft Academic Search

Whether daily exercise initiated with dieting can increase resting energy expenditure and fat utlization while minimizing loss of lean tissue is equivocal. Therefore, the effect of a 4?week program of food restriction and daily exercise on resting metabolic rate (RMR) and body composition was studied and compared with the effect of the same diet program without exercise on moderately obese

Paul A. Molé



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

Microsoft Academic Search

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

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



Effect of Severe Water Stress on Aspects of Crassulacean Acid Metabolism in Xerosicyos  

Microsoft Academic Search

Xerosicyos danguyi H. Humb. (Cucurbitaceae) is a Crassulacean acid metabolism (CAM) species native to Madagascar. Previously, it was shown that when grown under good water conditions, it is a typical CAM plant, but when water stressed, it shifts to a damp- ened form of CAM, termed CAM-idling, in which stomata are closed day and night but with a continued, low

Brigitte Bastide; Deborah Sipes; Janet Hann; P. Ting


Dilutional acidosis: where do the protons come from?  

Microsoft Academic Search

Purpose  To investigate the mechanism of acidosis developing after saline infusion (dilutional acidosis or hyperchloremic acidosis).\\u000a \\u000a \\u000a \\u000a Methods  We simulated normal extracellular fluid dilution by infusing distilled water, normal saline and lactated Ringer’s solution.\\u000a Simulations were performed either in a closed system or in a system open to alveolar gases using software based on the standard\\u000a laws of mass action and mass conservation.

Luciano Gattinoni; E. Carlesso; G. Maiocchi; F. Polli; P. Cadringher



Exercise training with weight loss and either a high or low glycemic diet reduces metabolic syndrome severity in older adults  

PubMed Central

Background The efficacy of combining carbohydrate quality with exercise on metabolic syndrome risk is unclear. Thus, we determined the effects of exercise training with a low or high glycemic diet on metabolic syndrome severity (Z-score). Methods Twenty-one adults (66.2 ± 1.1 yr; BMI = 35.3 ± 0.9 kg/m2) with metabolic syndrome were randomized to 12 weeks of exercise (60 minutes/d for 5 d/week at ~85% HRmax) and provided a low-glycemic (n=11; LoGIx) or high glycemic (n=10; HiGIx) diet. Z-scores were determined from: blood pressure, triglycerides (TG), high-density lipoproteins (HDL), fasting plasma glucose (FPG), and waist circumference (WC) before and after the intervention. Body composition, aerobic fitness, insulin resistance, and non-esterfied fatty acid (NEFA) suppression were also assessed. Results LoGIx and HiGIx decreased body mass and insulin resistance and increased aerobic fitness comparably (p < 0.05). LoGIx and HiGIx decreased the Z-score similarly, as each intervention decreased blood pressure, TG, FPG, and WC (p < 0.05). HiGIx tended to suppress NEFA during insulin stimulation compared to LoGIx (p = 0.06). Conclusions Our findings highlight that exercise with weight loss reduces metabolic syndrome severity whether individuals were randomized to a high or low glycemic index diet.

Malin, Steven K.; Niemi, Nicole; Solomon, Thomas P.J.; Haus, Jacob M.; Kelly, Karen R.; Filion, Julianne; Rocco, Michael; Kashyap, Sangeeta R.; Barkoukis, Hope; Kirwan, John P.





Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Elsas LJ II. Approach to inborn errors of metabolism. In: Goldman L, Schafer AI, eds. Cecil Medicine . ...


Renal hypoprostaglandism, hypertension, and type IV renal tubular acidosis reversed by furosemide.  


A 13-year-old white girl with severe hypertension and type IV renal tubular acidosis had decreased renal chloride clearance and exaggerated sodium chloride reabsorption by the ascending limb of Henle during hypotonic saline diuresis. Urinary prostaglandin E2 excretion was markedly diminished and often undetectable (0 to 37 ng/24 h). Treatment with oral furosemide completely reversed the hypertension and hyperkalemic acidosis, and effected a 20-fold rise in urinary prostaglandin E2. Sodium chloride reabsorption by the thick ascending limb of Henle decreased from 93.5% to 79.3%. Renal hypoprostaglandism may have a pathogenic role in this syndrome by enhancing chloride reabsorption in the ascending limb of Henle leading to extracellular fluid volume expansion, hypertension, and suppression of the renin-angiotensin-aldosterone axis. The therapeutic effects of furosemide may be partially mediated by enhancing the biosynthesis of renal prostaglandins or inhibiting their breakdown. PMID:6579876

Sanjad, S A; Keenan, B S; Hill, L L



The Expression of Omental 11?-HSD1 Is Not Increased in Severely Obese Women with Metabolic Syndrome  

Microsoft Academic Search

Objective: Plasma cortisol in obese subjects does not differ from that in normoweight subjects. Extra-adrenal cortisol production by 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) can result in local hypercortisolemia. The aim of the present study was to examine the role of visceral hypercortisolemia in the development of metabolic syndrome in severe obesity. Methods: Eight lean women during hysterectomy (controls) and 19

Marina Michalaki; Venetsana Kyriazopoulou; Anna Antonacopoulou; Vasiliki Koika; Marinos Nikolaou; Athanasios Tsoukas; Fotis Kalfarentzos; Apostolos G. Vagenakis; Georgia Voukelatou; Athanasios G. Papavassiliou



Changes in work tolerance associated with metabolic and physiological adjustment to moderate and severe iron deficiency anemia?4  

Microsoft Academic Search

The time course of metabolic and physiological adjustment to moderate iron deficiency anemia (MIDA, 8 g Hb\\/dl) and to severe iron deficiency anemia (SIDA, 4 g Hb\\/dI) was studied in adult, male Sprague-Dawley rats at 3, 7, 14, 30, 60, 90, 150, and 360 days and 30 days, respectively. Our previous studies using the same rats used in the present

Brian J Koziol; V Reggie Edgerton; Donald R Simpson


A Phanerochaete chrysosporium mutant defective in lignin degradation as well as several other secondary metabolic functions  

Microsoft Academic Search

A pleiotropic mutant of Phanerochaete chrysosporium 104-2 lacking phenol oxidase and unable to form fruit bodies and a revertant strain 424-2 were isolated after UV mutagenesis. Strains 104-2 and 424-2 had no apparent dysfunction in primary metabolism with glucose as a carbon source. Unlike the wild type strain and strain 424-2, strain 104-2 was unable to evolve 14CO2 from 14C

Michael H. Gold; Mary B. Mayfield; Therese M. Cheng; Kanit Krisnangkura; Mikio Shimada; Akio Enoki; Jeffrey K. Glenn



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

PubMed Central

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

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



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


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

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



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


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

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



Alterations in Coagulation Induced by Hypothermia and Acidosis in Swine.  

National Technical Information Service (NTIS)

Although clinical coagulopathy is associated with acidosis and hypothermia, the underlying mechanisms by which these factors alter the coagulation process remains unclear. The primary purpose of this study was to investigate the contributory effects of ac...

W. Z. Martini J. B. Holcomb J. M. Uscilowicz A. V. Delgado A. E. Pusateri



Lactic Acidosis: From Sour Milk to Septic Shock  

Microsoft Academic Search

Lactic acidosis is frequently encountered in the intensive care unit. It occurs when there is an imbalance between production and clearance of lactate. Although lactic acidosis is often associated with a high anion gap and is generally defined as a lactate level >5 mmol\\/L and a serum pH <7.35, the presence of hypoalbuminemia may mask the anion gap and concomitant

Pamela J. Fall; Harold M. Szerlip



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

PubMed Central

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



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

PubMed Central

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

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



Relationship between rickets and incomplete distal renal tubular acidosis in children  

PubMed Central

Background In the Sub Saharan Africa Rickets has now been established to be due primarily to calcium deficiency and sometimes in combination with vitamin D deficiency. The main thrust of management is calcium supplementation with or without vitamin D. An observation was made that some children with nutritional rickets do not respond to this management modality. The recently reported high prevalence of Incomplete Distal Renal Tubular Acidosis (idRTA) in adults with osteoporosis as brought to fore the possibility of this being a possible cause of calcium wastage and therefore the poor response in these group of children with rickets. Aim To determine the prevalence of idRTA amongst a cohort of subjects with rickets To show a relationship between rickets and incomplete distal renal acidosis To determine the response of children with rickets and idRTA to addition of Shohl's solution to therapy Methodology Two separate cohorts of children with rickets performed the ammonium chloride loading test to detect those with incomplete renal tubular acidosis. Following identification for idRTA, Shohl's solution was added to therapy of calcium and vitamin D supplementation and their response compared to those without idRTA on calcium and vitamin D supplementation solely. Results 50 children with rickets aged from two to six years of age and composed of 29 females and 21males were investigated. Incomplete renal tubular acidosis was found in 38% of them. Prevalence of idRTA was highest amongst those aged 3-6 years of age. Those with idRTA had worse limb deformities, biochemical and radiological parameters than those who hadn't. Rate of response on those with idRTA treated with Shohl's solution was at par with those without idRTA. Conclusion Incomplete idRTA exist amongst children with rickets and should be looked out for in severe rickets and older children. Treatment of idRTA will lead to optimal response and healing of rickets.



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

PubMed Central

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.

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



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

PubMed Central

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



Expression and activities of several drug-metabolizing enzymes in LLC-PK1 cells.  


LLC-PK1 cells are frequently used in toxicology research, but little information is available concerning the capacity of these cells to metabolize xenobiotics. We examined the expression and activities of cytochromes P450 (P450) 1A1/1A2 (CYP 1A1/1A2), 2E1 (CYP 2E1), flavin monooxygenase (FMO), 5-lipoxygenase (5-LO) and prostaglandin H synthase (PHS)-associated cyclooxygenase-1 (COX-1). We prepared S9 fractions from LLC-PK1 cells, rat liver, and rat kidney, and measured enzyme activities using ethoxyresorufin O-deethylation (EROD) for CYP 1A1/1A2 and ethoxycoumarin O-deethylation (ECOD) for CYP 2E1, benzydamine N-oxidation (BNO) for FMO, leukotriene B(4) (LTB(4)) formation for 5-LO, and thromboxane B(2) (TXB(2)) formation for COX-1 activities. To assure that product formation was due to enzymatic activity, we used the following inhibitors: 1-aminobenzotriazole (ABT) for P450, methimazole for FMO, caffeic acid for 5-LO and acetylsalicylic acid (ASA) for COX-1. We also performed Western blot analysis to confirm our observations. All five enzyme activities were demonstrable in rat liver at much greater levels than in rat kidney S9 fractions. Activities in LLC-PK1 cells were significantly lower than activities in rat liver S9 fraction and generally less than activities in rat kidney S9 fraction. Enzyme inhibitors decreased product formation in all three tissues and Western blot analysis supported our observations of low enzyme activity in LLC-PK1 cells. These results indicate that LLC-PK1 cells have very low content of relevant drug-metabolizing enzyme activities. PMID:15465656

Gonzalez, Raymond J; Tarloff, Joan B



Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness.  


H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease. PMID:9916796

Karet, F E; Finberg, K E; Nelson, R D; Nayir, A; Mocan, H; Sanjad, S A; Rodriguez-Soriano, J; Santos, F; Cremers, C W; Di Pietro, A; Hoffbrand, B I; Winiarski, J; Bakkaloglu, A; Ozen, S; Dusunsel, R; Goodyer, P; Hulton, S A; Wu, D K; Skvorak, A B; Morton, C C; Cunningham, M J; Jha, V; Lifton, R P



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

SciTech Connect

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

Peek, K.E.H.



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


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

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



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

SciTech Connect

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

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



Ten-week lifestyle changing program reduces several indicators for metabolic syndrome in overweight adults  

PubMed Central

We aim to investigate the effectiveness of a 10-week lifestyle intervention focusing on physical activity and high fiber intake for reducing indicators for metabolic syndrome in overweight-obese individuals. A prospective study of 50 overweight (OW) adults (22 in the general educational group - G1; 28 in the high fiber nutrition group - G2) was performed. Both groups were offered dietary counseling and supervised exercise. Clinical, anthropometric, dietary and plasma biochemical tests were performed at baseline - time 0 (T0) and after 10 weeks - time 1 (T1). Both groups improved their dietary quality, but only G2 presented higher intake of fruit and vegetables (servings/day), higher plasma ?-carotene levels and a 24% reduction of MetS incidence. Additionally G2 showed greater reductions in body fat (4%), and waist circumference (7%), obesity class III (2%) and obesity class II (14%) rate. Lifestyle intervention, including a high dietary fiber intake, improved healthy eating index and decreased body fat composition and plasma lipid concentrations leading to MetS incidence reduction.



Cerebrospinal fluid lactic acidosis in bacterial meningitis.  

PubMed Central

A rapid, microenzymatic method was used to measure cerebrospinal fluid lactate levels in 205 children with suspected bacterial meningitis. Fifty children with normal CSF containing fewer than 0.005 X 10(9)/l WBC, no segmented neutrophils, glucose 3.4 +/- 0.8 mmol/l (61.2 +/- 14.4 mg/100 ml), and a protein of less than 0.30 g/l had CSF lactate levels below 2.0 mmol/l (18 mg/100 ml) (mean and standard deviation 1.3 +/- 0.3 mmol/l (11.8 +/- 2.7 mg/100 ml)). In 31 cases of proved viral meningitis as with 58 cases of clinically diagnosed viral meningitis, levels were below 3.8 mmol/l (34.5 mg/100 ml), being 2.3 +/- 0.6 mmol/l (20.9 +/- 5.4 mg/100 ml), and 2.1 +/- 0.7 mmol/l (19.1 +/- 6.4 mg/100 ml) respectively. Sixty-six cases of bacterial meningitis had CSF lactate levels ranging from 3.9 mmol/l (35.4 mg/100 ml) to greater than 10.0 mmol/l (90.0 mg/100 ml). Longitudinal studies in 7 children with bacterial meningitis showed that cerebrospinal fluid lactate levels differentiated bacterial from viral meningitis up to 4 days after starting treatment with antibiotics. Use of CSF lactate measurement for monitoring the efficacy of treatment is illustrated in a case of bacterial meningitis due to Pseudomonas aeruginosa. The origin of the cerebrospinal fluid lactate acidosis and the role of lactate in the pathophysiological cycle leading to intensification of brain tissue hypoxia and cellular damage is discussed with respect to the short-term prognosis and the long-term neurological sequelae.

Eross, J; Silink, M; Dorman, D



Subacute ruminal acidosis (SARA): a review.  


Subacute ruminal acidosis (SARA) is likely to arise when an easily palatable, high-energy diet meets a ruminal environment not adapted to this type of substrate. Increase of short-chained fatty acids (SCFA) will occur. Eventually, this may result in a transient nadir of ruminal pH below 5.5. Two situations are likely to represent the risk of SARA. First, fresh lactating cows are confronted with a diet considerably differing from that in the dry-period. A diet change carried out too rapidly or without proper transition management will put the animals at risk. Secondly, further in lactation, inaccurate calculation of dry-matter-intake (DMI) leading to wrong roughage/concentrate ratio, an inadequate content of structure within the diet or mistakes in preparing of total mixed rations may produce SARA. The consequences of SARA are diverse and complex. Laminitis is regularly connected to SARA and the negative impact of organic acids on the ruminal wall may lead to parakeratosis enabling translocation of pathogens into the bloodstream provoking inflammation and abscessation throughout the ruminant body. Moreover, milk-fat depression (MFD) can be related to SARA. In order to achieve a proper diagnosis, SARA has to be understood as a herd-management problem. A screening of the herd for SARA by means of a rumenocentesis, performed on a sample-group, preferably 12 individuals, may reveal the presence of SARA. The herd screening should include the risk group suspected, preferably. The prevention of SARA applies to the principles of ruminant feeding. Careful transition management from the dry to the lactation period and control of fibre-content and ration quality should be more yielding than the use of buffers or antibiotic drugs. PMID:14633219

Kleen, J L; Hooijer, G A; Rehage, J; Noordhuizen, J P T M



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

Microsoft Academic Search

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

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



Traditional Anthropometric Parameters Still Predict Metabolic Disorders in Women With Severe Obesity  

Microsoft Academic Search

It is well established that fat distribution rather than the total quantity of fat is the major determinant of cardiovascular risk in overweight subjects. However, it is not known whether the concept of fat distribution still makes sense in severely obese subjects. Particularly, the role of visceral fat accumulation and\\/or of adipocyte hypertrophy in insulin resistance (IR) has not been

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



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...


Acidosis, acid-sensing ion channels, and neuronal cell death.  


Acidosis is a common feature of many neuronal diseases and often accompanied with adverse consequences such as pain and neuronal injury. Before the discovery of acid-sensing ion channels (ASICs), protons were usually considered as a modulator of other ion channels, such as voltage-gated calcium channels, N-methyl-D-aspartate, and ?-amino butyric acid(A) receptor channels. Accordingly, the functional effects of acidosis were considered as consequences of modulations of these channels. Since the first cloning of ASICs in 1997, the conventional view on acidosis-mediated pain and cell injury has been dramatically changed. To date, ASICs, which are directly activated by extracellular protons, are shown to mediate most of the acidosis-associated physiological and pathological functions. For example, ASIC1a channels are reported to mediate acidosis-induced ischemic neuronal death. In this article, we will review the possible mechanisms that underlie ASIC1a channel-mediated neuronal death and discuss ASIC1a channel modulators involved in this process. PMID:21932071

Wang, Yi-Zhi; Xu, Tian-Le



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

PubMed Central

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?severity of illness, hematologic indices, length of stay or mechanical ventilation duration. Conclusions In sepsis, the early stress-metabolic pattern is characterized by a high (nCD64, glucose, TG) - low (TC, HDL, LDL) combination in contrast to the moderate pattern of TBI in which only glucose increases combined with a moderate cholesterol - lipoprotein decrease. These early metabolic patterns persist the first 3?days of acute illness and are associated with the acute phase CD64 expression on neutrophils.



Successful treatment of uterine torsion in a cat with severe metabolic and haemostatic complications.  


A peri-parturient fifteen-month-old female Maine Coon cat was presented with extreme weakness and depression, profound hypovolaemia and hypothermia. Severe hyperkalaemia, hyponatraemia and anaemia were detected. Disseminated intravascular coagulation was suspected due to marked prolongation of activated partial thromboplastin time. Uterine torsion was diagnosed at exploratory laparotomy. The cat made a full recovery following ovariohysterectomy and intensive supportive therapy. PMID:11716604

Ridyard, A E; Welsh, E A; Gunn-Moore, D A



Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease.  


Nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular and liver-related mortality. NAFLD is characterized by both triglyceride and free cholesterol (FC) accumulation without a corresponding increment in cholesterol esters. The aim of this study was to evaluate the expression of cholesterol metabolic genes in NAFLD and relate these to disease phenotype. NAFLD was associated with increased SREBP-2 maturation, HMG CoA reductase (HMGCR) expression and decreased phosphorylation of HMGCR. Cholesterol synthesis was increased as measured by the circulating desmosterol:cholesterol ratio. miR-34a, a microRNA increased in NAFLD, inhibited sirtuin-1 with downstream dephosphorylation of AMP kinase and HMGCR. Cholesterol ester hydrolase was increased while ACAT-2 remained unchanged. LDL receptor expression was significantly decreased and similar in NAFLD subjects on or off statins. HMGCR expression was correlated with FC, histologic severity of NAFLD and LDL-cholesterol. These data demonstrate dysregulated cholesterol metabolism in NAFLD which may contribute to disease severity and cardiovascular risks. PMID:22560219

Min, Hae-Ki; Kapoor, Ashwani; Fuchs, Michael; Mirshahi, Faridoddin; Zhou, Huiping; Maher, James; Kellum, John; Warnick, Russell; Contos, Melissa J; Sanyal, Arun J




PubMed Central

SUMMARY Nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular and liver-related mortality. NAFLD is characterized by both triglyceride and free cholesterol (FC) accumulation without a corresponding increment in cholesterol esters. The aim of this study was to evaluate the expression of cholesterol metabolic genes in NAFLD and relate these to disease phenotype. NAFLD was associated with increased SREBP-2 maturation, HMG CoA reductase (HMGCR) expression and decreased phosphorylation of HMGCR. Cholesterol synthesis was increased as measured by the circulating desmosterol:cholesterol ratio. miR-34a, a microRNA increased in NAFLD, inhibited sirtuin-1 with downstream dephosphorylation of AMP kinase and HMGCR. Cholesterol ester hydrolase was increased while ACAT-2 remained unchanged. LDL receptor expression was significantly decreased and similar in NAFLD subjects on or off statins. HMGCR expression was correlated with FC, histologic severity of NAFLD and LDL-cholesterol. These data demonstrate dysregulated cholesterol metabolism in NAFLD which may contribute to disease severity and cardiovascular risks.

Min, Hae-Ki; Kapoor, Ashwani; Fuchs, Michael; Mirshahi, Faridoddin; Zhou, Huiping; Maher, James; Kellum, John; Warnick, Russell; Contos, Melissa J; Sanyal, Arun J.



5-Aminosalicylic Acid-Associated Renal Tubular Acidosis with Decreased Renal Function in Crohn’s Disease  

Microsoft Academic Search

The use of 5-aminosalicylic acid (5-ASA, mesalazine) in Crohn’s disease is usually well tolerated. Nevertheless, the occasional occurrence of nephrotoxic side effects has been described in several case reports. We present the case of a 34-year-old female in whom chronic use of 5-ASA may have caused renal damage which manifested with tubular acidosis, severe weight loss, shortness of breath and

Jens Hämling; Andreas Raedler; Udo Helmchen; Stefan Schreiber



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

PubMed Central

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 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.

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



Intracellular Acidosis Enhances the Excitability of Working Muscle  

NASA Astrophysics Data System (ADS)

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

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



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

SciTech Connect

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

Swenson, E.R.



Investigation of enzyme defects in children with lactic acidosis  

Microsoft Academic Search

Summary Screening for enzyme deficiencies was carried out in cultured skin fibroblasts and leukocytes of 19 patients with lactic acidosis and neurological problems. Pyruvate carboxylase deficiency was demonstrated in three cases. Reduced pyruvate oxidation was found in seven cultures; six showed no significant stimulation of the oxidation rate by methylene blue and in three a decreased pyruvate dehydrogenase complex activity

B. Merinero; C. Pérez-Cerda; M. Ugarte



Renal Tubular Acidosis: A New Look at an Old Problem  

Microsoft Academic Search

Although the definition of renal tubular acidosis (RTA) is simple, understanding the physiologic basis underlying the various types of this clinical entity is much more difficult. The pathophysiology of this disorder is reviewed using the normal acid-base functions of the involved segments of the nephron as a guide to understanding. Clinical and laboratory features of the subtypes of RTA are

Karl S. Roth; James C. M. Chan




Microsoft Academic Search

Summary Fistulated bull calves that were given ground wheat intraruminally at 40 g\\/kg body weight developed both ruminal and systemic lactic acidosis. Rumen lactate increased from less than 1 to over 100 jumoles\\/ml by 6 hr after wheat administration. Plasma lactate increased and blood base excess decreased after elevation of rumen lactate, with calves dying when plasma lactate and blood

Larry A. Muir; Eric L. Rickes; Paul F. Duquette; Gary E. Smith


The spectrum of renal tubular acidosis in paediatric Sjogren syndrome  

Microsoft Academic Search

Objectives. Renal tubular acidosis (RTA) is a well-recognized extraglandular complication of adult Sjogren syndrome (SS) but has been reported only rarely in paediatric SS. We wished to describe the natural history of RTA in paediatric SS. Methods. We performed a chart and literature review. Inclusion criteria were primary or secondary SS with onset before 18 yr of age, complicated by

F. Pessler; H. Emery; L. Dai; Y.-M. Wu; B. Monash; R. Q. Cron; M. Pradhan




Microsoft Academic Search

ABSTRACT A study was conducted to determine whether feeding sodium,bicarbonate (SB) reduces the risk of subacute acidosis (SARA) in cattle receiving high concentrate diets. Twelve Hereford cross heifers (Exp.1) and six ruminally cannulated animals (Exp. 2; three Jersey steers and three Holstein cows), previously adapted to a high concentrate diet, were used in 3 _ 3 Latin square designs to




Sodium Bicarbonate for the Treatment of Lactic Acidosis  

Microsoft Academic Search

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

Sean M. Forsythe; Gregory A. Schmidt


Acidosis, magnesium and acetylsalicylic acid: Effects on thrombin  

NASA Astrophysics Data System (ADS)

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

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



How well does reflectance pulse oximetry reflect intrapartum fetal acidosis?  

Microsoft Academic Search

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

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



Acidosis leads to neurological disorders through overexciting cortical pyramidal neurons  

Microsoft Academic Search

The patients suffering from acidosis usually sign psychological deficits. The cerebral dysfunction is reportedly caused by an acid-induced functional impairment of GABAergic neurons; however, the role of pyramidal neurons in this process remains unclear. By using electrophysiological method and changing extracellular pH, we investigated the influence of acidic environment on pyramidal neurons in the cortical slices, such as their ability

Hong Zhao; Yan Cai; Zichao Yang; Dandan He; Baozhong Shen


Acute Renal Response to Rapid Onset Respiratory Acidosis  

PubMed Central

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

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



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

Microsoft Academic Search

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

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



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

PubMed Central

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

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.



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

Microsoft Academic Search

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

Dieter Rixen; John H Siegel



The presence of metabolic syndrome is independently associated with elevated serum CD40 ligand and disease severity in patients with symptomatic coronary artery disease  

Microsoft Academic Search

Nontraditional atherosclerotic risk factors have become the focus of attention in recent years. In addition, metabolic syndrome is gaining recognition as another multiplex cardiovascular risk factor. However, to date, no studies have investigated the effect of metabolic syndrome on circulating soluble CD40 ligand (sCD40L), monocyte chemoattractant protein 1, cellular adhesion molecules, and disease severity in patients with symptomatic coronary artery

Wen-Lieng Lee; Wen-Jane Lee; Ying-Tsung Chen; Tsun-Jui Liu; Kae-Woei Liang; Chih-Tai Ting; Wayne Huey-Herng Sheu



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


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

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



The effects of different types of acidosis and extracellular calcium on the mechanical activity of turtle atria  

Microsoft Academic Search

The effects of acidosis and extracellular calcium were examined at 20°C in the isolated spontaneously contracting atria of the freshwater turtle (Chrysemys picta bellii). The atria were subjected to treatments of lactic acidosis, hypercapnic acidosis or chloride acidosis in the presence of both normal (2.0 mM) and high (10.0 mM) calcium, which simulated levels of acidosis and calcium observed in

Hal F. Yee; Donald C. Jackson



Impact of Clinical Characteristics of Individual Metabolic Syndrome on the Severity of Insulin Resistance in Chinese Adults  

PubMed Central

The impact the metabolic syndrome (MetS) components on the severity of insulin resistance (IR) has not been reported. We enrolled 564 subjects with MetS and they were divided into quartiles according to the level of each component; and an insulin suppression test was performed to measure IR. In males, steady state plasma glucose (SSPG) levels in the highest quartiles, corresponding to body mass index (BMI) and fasting plasma glucose (FPG), were higher than the other three quartiles and the highest quartiles, corresponding to the diastolic blood pressure and triglycerides, were higher than in the lowest two quartiles. In females, SSPG levels in the highest quartiles, corresponding to the BMI and triglycerides, were higher than in all other quartiles. No significant differences existed between genders, other than the mean SSPG levels in males were greater in the highest quartile corresponding to BMI than that in the highest quartile corresponding to HDL-cholesterol levels. The factor analysis identified two underlying factors (IR and blood pressure factors) among the MetS variables. The clustering of the SSPG, BMI, triglyceride and HDL-cholesterol was noted. Our data suggest that adiposity, higher FPG and triglyceride levels have stronger correlation with IR and subjects with the highest BMI have the highest IR.

Hsieh, Chang-Hsun; Hung, Yi-Jen; Wu, Du-An; Kuo, Shi-Wen; Lee, Chien-Hsing; Sheu, Wayne Huey-Herng; Li, Jer-Chuan; Yeh, Kuan-Hung; Chen, Cheng-Yu



Pneumoperitoneum and acidosis during arthroscopy with CO2.  


Two cases of knee arthroscopy are reported in which the patient sustained both pneumoperitoneum and acidosis. In each case, a pump was used to maintain a set intraarticular pressure of CO2. In neither case was the pneumatic tourniquet inflated. The conclusion is drawn that, to avoid these two complications, arthroscopists should routinely exsanguinate the extremity and inflate the pneumatic tourniquet when using this type of pump. PMID:3118897

Lotman, D B



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


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 eIF2? 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

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



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

PubMed Central

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

Rixen, Dieter; Siegel, John H



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


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

Rixen, Dieter; Siegel, John H



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


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

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



Tumor cell metabolism  

PubMed Central

Cancer is a genetic disease that is caused by mutations in oncogenes, tumor suppressor genes and stability genes. The fact that the metabolism of tumor cells is altered has been known for many years. However, the mechanisms and consequences of metabolic reprogramming have just begun to be understood. In this review, an integral view of tumor cell metabolism is presented, showing how metabolic pathways are reprogrammed to satisfy tumor cell proliferation and survival requirements. In tumor cells, glycolysis is strongly enhanced to fulfill the high ATP demands of these cells; glucose carbons are the main building blocks in fatty acid and nucleotide biosynthesis. Glutaminolysis is also increased to satisfy NADPH regeneration, whereas glutamine carbons replenish the Krebs cycle, which produces metabolites that are constantly used for macromolecular biosynthesis. A characteristic feature of the tumor microenvironment is acidosis, which results from the local increase in lactic acid production by tumor cells. This phenomenon is attributed to the carbons from glutamine and glucose, which are also used for lactic acid production. Lactic acidosis also directs the metabolic reprogramming of tumor cells and serves as an additional selective pressure. Finally, we also discuss the role of mitochondria in supporting tumor cell metabolism.

Romero-Garcia, Susana; Lopez-Gonzalez, Jose Sullivan; B?ez-Viveros, Jose Luis; Aguilar-Cazares, Dolores



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


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

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



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

Microsoft Academic Search

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

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



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

Microsoft Academic Search

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

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



Metabolic abnormalities associated with HIV infection and antiretroviral therapy  

Microsoft Academic Search

Although noted early in the HIV epidemic, metabolic abnormalities came to prominence when potent combination antiretroviral\\u000a therapy was introduced. Complications associated with HIV infection and antiretroviral therapy include cardiovascular disease,\\u000a lipid disorders, glucose metabolism disorders, adipose tissue disorders, bone metabolism disorders, and lactic acidosis. Metabolic\\u000a complications have driven the discovery of new agents and classes of antiretrovirals, and have shaped

Carl J. Fichtenbaum



Zidovudine-induced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion  

Microsoft Academic Search

Zidovudine is known to be responsible for a mitochondrial myopathy with ragged-red fibres and mitochondrial DNA depletion in muscle. Lactic acidosis alone or associated with hepatic abnormalities has also been reported. A single report mentioned the concomitant occurrence of muscular and hepatic disturbances and lactic acidosis in a patient receiving zidovudine, but muscle and liver tissues were not studied. A

Patrick Chariot; Irène Drogou; Isabelle de Lacroix-Szmania; Marie-Christine Eliezer-Vanerot; Bénédicte Chazaud; Anne Lombès; Annette Schaeffer; Elie Serge Zafrani



Hyperkalemic distal renal tubular acidosis and selective aldosterone deficiency. Combination in a patient with lead nephropathy.  


A patient with chronic renal failure, a strong history of moonshine abuse, and excessive urinary lead excretion had clinical and laboratory measurements compatible with combined hyperkalemic distal renal tubular acidosis and the syndrome of selective aldosterone deficiency. Extended treatment with fludrocortisone acetate, 0.1 to 0.2 mg/day, did not ameliorate acidosis or restore potassium excretion. PMID:4015282

Ashouri, O S



The Definition of Acidosis in Dairy Herds Predominantly Fed on Pasture and Concentrates1  

Microsoft Academic Search

This cross-sectional survey examined the prevalence of ruminal acidosis and the effects of acidosis on the production of dairy cattle. Eight fresh cows, 3 primipa- rous and 5 multiparous (<100 d in milk), were selected randomly from each of 100 dairy herds in 5 regions of Australia. Rumen fluid was obtained from each cow by rumenocentesis and a stomach tube,

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



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

PubMed Central

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



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

Microsoft Academic Search

IntroductionFunctional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron

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



[Effect of nootropic agents on the brain bioelectrical activity and on the indices of neuromediator metabolism in the acute period of severe craniocerebral trauma].  


Clinico-biochemical examination and EEG were conducted in 39 patients with severe craniocerebral trauma who were given nootropic agents in a complex of intensive therapy measures. Four types of changes of monoamine metabolism in treatment with piracetam were revealed which were combined with two types of EEG changes. The authors recommend the time for beginning piracetam therapy depending on the level of traumatic injury to the brain. PMID:2572097

Madorski?, S V; Potapov, A A; Piasetskaia, M V; Shapova, E V; Il'icheva, R F


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

SciTech Connect

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

Leitz, T.



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

Microsoft Academic Search

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

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



Metabolic programming of obesity by energy restriction during the perinatal period: different outcomes depending on gender and period, type and severity of restriction  

PubMed Central

Epidemiological studies in humans and controlled intervention studies in animals have shown that nutritional programming in early periods of life is a phenomenon that affects metabolic and physiological functions throughout life. The phenotypes of health or disease are hence the result of the interaction between genetic and environmental factors, starting right from conception. In this sense, gestation and lactation are disclosed as critical periods. Continuous food restriction during these stages may lead to permanent adaptations with lasting effects on the metabolism of the offspring and may influence the propensity to develop different chronic diseases associated with obesity. However, the different outcomes of these adaptations on later health may depend on factors such as the type, duration, period, and severity of the exposure to energy restriction conditions, and they are, in part, gender specific. A better understanding of the factors and mechanisms involved in metabolic programming, and their effects, may contribute significantly to the prevention of obesity, which is considered to be one of the major health concerns of our time. Here, the different outcomes of maternal food restriction during gestation and lactation in the metabolic health of offspring, as well as potential mechanisms underlying these effects are reviewed.

Pico, Catalina; Palou, Mariona; Priego, Teresa; Sanchez, Juana; Palou, Andreu



Cerebral blood flow and metabolism in children with severe head injury. Part 1: Relation to age, Glasgow coma score, outcome, intracranial pressure, and time after injury.  

PubMed Central

Understanding the pathophysiology of paediatric head trauma is essential for rational acute management. It has been proposed that the response to severe head injury in children differs from that in adults, with increased cerebral blood flow (cerebral hyperaemia) representing the most common cause of raised intracranial pressure, but this has recently been disputed. The relation between the pathophysiological response and time after injury has not been defined in children. This paper describes 151 serial measurements of cerebral blood flow, arteriojugular venous oxygen difference (AJVDO2), and cerebral metabolic rate for oxygen (CMRO2) that were performed in 21 children with severe head injury, mean age 8 (range 2-16) years, Glasgow coma score < or = 8. Absolute cerebral hyperaemia was uncommon, only 10 (7%) of the 151 cerebral blood flow values being at or above the upper limit of the range published in normal children. There was an inverse correlation between cerebral blood flow and intracranial pressure. (r = -0.24, p = 0.009). Contrary to the widespread assumption that cerebral metabolic rate in patients with head injury is always low, CMRO2 was initially within the normal range in 17/21 (81%) children. Both CMRO2 and AJVDO2 fell significantly between the first and third days after injury. There was a non-significant rise in cerebral blood flow over time. These data represent the first evidence that the temporal change in cerebral metabolic rate reported in experimental models of traumatic brain injury also occurs in patients with head injury. The changes in the pathophysiological response over time suggest that the management may need to be modified accordingly. If cerebral metabolic rate and cerebral oxygen extraction are maximal shortly after injury in children with severe head injury then the children are most likely to sustain secondary damage during this period. Images

Sharples, P M; Stuart, A G; Matthews, D S; Aynsley-Green, A; Eyre, J A



Absence of adrenergic red cell pH and oxygen content regulation in American eel ( Anguilla rostrata ) during hypercapnic acidosis in vivo and in vitro  

Microsoft Academic Search

American eels (Anguilla rostrata) were exposed to acute (30 min) external hypercapnia (1% CO2 or 5% CO2 in air) in order to assess the involvement of circulating catecholamines in regulating red blood cell (RBC) pH and oxygen content during whole blood acidosis. Plasma adrenaline levels increased approximately 5-fold during severe hypercapnia yet absolute levels remained below 1.0 nM; plasma noradrenaline

D. A. Hyde; S. F. Perry



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


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

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



Respiratory muscle acidosis stimulates endogenous opioids during inspiratory loading.  


Activation of endogenous opioid pathways during intense inspiratory flow-resistive loading (IRL) results in greater inhibition of EMG activity in the external oblique (EMGeo) relative to the diaphragm (EMGdi). Dichloroacetate (DCA) abolishes opioid-mediated inhibitory influences upon these muscles, suggesting a causal relationship between respiratory muscle lactic acidosis and activation of endogenous opioid pathways, during IRL. We tested the hypothesis that a more intense acidosis of the external oblique relative to the diaphragm may be the signal that determines the differential inhibitory opioid-mediated effect upon the respiratory muscles during IRL. Unanesthetized goats were exposed to IRL (50 cm H2O/1/s) for 120 min, before and after intravenous pretreatment with DCA (50 mg/kg) or saline. We measured peak phasic EMGdi and EMGeo, and respective muscle interstitial pH (pHdi, pHeo) using flexible pH probes. After 120 min IRL with saline, pHdi, and pHeo declined by -0.12 +/- 0.03 (mean +/- SEM) and -0.20 +/- 0.04 units, respectively (p < 0.05, pHdi versus pHeo). Naloxone (NLX), 0.3 mg/kg given intravenously at this time, increased EMGdi by 26.5 +/- 6.1%, but EMGeo by 81.9 +/- 13.3% (p < 0.05, EMGdi versus EMGeo). DCA blunted both the change in pHdi and pHeo during IRL (to -0.01 +/- 0.01 and -0.08 +/- 0.03 units, respectively) (p < 0.05, DCA versus saline) and the increase in EMGdi and EMGeo with NLX (to -1.0 +/- 2.6% and 5.7 +/- 5.8%, respectively) (p < 0.05, DCA versus saline).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8442594

Petrozzino, J J; Scardella, A T; Edelman, N H; Santiago, T V



Venous diethylene glycol poisoning in patients with preexisting severe liver disease in China  

PubMed Central

AIM: To analyze the clinical presentation of venous diethylene glycol (DEG) poisoning in patients with preexisting severe liver disease and factors that correlate with DEG poisoning. METHODS: Retrospective chart review was performed to analyze the epidemiology, clinical presentation, hepatorenal functions, hemodynamics and pathological characteristics of 64 patients with severe liver disease who received intravenous armillarisin-A, the solvent of which was DEG. Comparative analyses of correlating factors and causes for poisoning were based on the presence or absence of poisoning. RESULTS: Of the 64 patients who received armillarisin-A, 15 were found to have DEG poisoning. Twelve poisoned patients died. After a mean of 5 d, the poisoned patients displayed acute renal failure. Metabolic acidosis occurred in 13 cases. BUN, Cr, and CO2 values were significantly elevated and exacerbation of digestive tract symptoms and/or symptom was noted in 11 cases. Neurological system impairment was observed in 10 cases after 2 wk. Compared to the 49 non-poisoned patients, the poisoned patients exhibited significantly lower RBC and Hb values and higher WBC count. Renal biopsy from the poisoned patients revealed acute tubular necrosis and interstitial nephritis. Significant differences in preexisting severe hepatitis, ascites, renal disease, and diuretic therapy were found between groups. Prior to diethylene glycol injections, the mean values for neutral granular cells, BUN, Cr, calcium and phosphorous ions differed significantly between groups. CONCLUSION: Venous diethylene glycol poisoning is characterized by oliguric acute renal failure, metabolic acidosis, digestive symptoms, nervous system impairment, and a high probability of anemia and WBC proliferation. Mortality is high. Correlative factors include preexisting severe liver disease, renal disease, and infection.

Lin, Bing-Liang; Zhao, Zhi-Xin; Chong, Yu-Tian; Li, Jian-Guo; Zuo, Xing; Tao, Yu; Lou, Tan-Qi; Gao, Zhi-Liang



Twenty-four hour metabolic rate measurements utilized as a reference to evaluate several prediction equations for calculating energy requirements in healthy infants  

PubMed Central

Background To date, only short-duration metabolic rate measurements of less than four hours have been used to evaluate prediction equations for calculating energy requirements in healthy infants. Therefore, the objective of this analysis was to utilize direct 24-hour metabolic rate measurements from a prior study to evaluate the accuracy of several currently used prediction equations for calculating energy expenditure (EE) in healthy infants. Methods Data from 24-hour EE, resting (RMR) and sleeping (SMR) metabolic rates obtained from 10 healthy infants, served as a reference to evaluate 11 length-weight (LWT) and weight (WT) based prediction equations. Six prediction equations have been previously derived from 50 short-term EE measurements in the Enhanced Metabolic Testing Activity Chamber (EMTAC) for assessing 24-hour EE, (EMTACEE-LWT and EMTACEE-WT), RMR (EMTACRMR-LWT and EMTACRMR-WT) and SMR (EMTACSMR-LWT and EMTACSMR-WT). The last five additional prediction equations for calculating RMR consisted of the World Health Organization (WHO), the Schofield (SCH-LWT and SCH-WT) and the Oxford (OXFORD-LWT and OXFORD-WT). Paired t-tests and the Bland & Altman limit analysis were both applied to evaluate the performance of each equation in comparison to the reference data. Results 24-hour EE, RMR and SMR calculated with the EMTACEE-WT, EMTACRMR-WT and both the EMTACSMR-LWT and EMTACSMR-WT prediction equations were similar, p = NS, to that obtained from the reference measurements. However, RMR calculated using the WHO, SCH-LWT, SCH-WT, OXFORD-LWT and OXFORD-WT prediction equations were not comparable to the direct 24-hour metabolic measurements (p < 0.05) obtained in the 10 reference infants. Moreover, the EMTACEE-LWT and EMTACRMR-LWT were also not similar (p < 0.05) to direct 24-hour metabolic measurements. Conclusions Weight based prediction equations, derived from short-duration EE measurements in the EMTAC, were accurate for calculating EE, RMR and SMR in healthy infants.



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

SciTech Connect

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

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



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


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

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



Localization of a gene for autosomal recessive distal renal tubular acidosis with normal hearing (rdRTA2) to 7q33-34.  


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

Karet, F E; Finberg, K E; Nayir, A; Bakkaloglu, A; Ozen, S; Hulton, S A; Sanjad, S A; Al-Sabban, E A; Medina, J F; Lifton, R P



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

PubMed Central

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.

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.



DUSP1 Gene Polymorphisms Are Associated with Obesity-Related Metabolic Complications among Severely Obese Patients and Impact on Gene Methylation and Expression  

PubMed Central

The DUSP1 gene encodes a member of the dual-specificity phosphatase family previously identified as being differentially expressed in visceral adipose tissue (VAT) of severely obese men with versus without the metabolic syndrome. Objective. To test the association between DUSP1 polymorphisms, obesity-related metabolic complications, gene methylation, and expression levels in VAT. Methods. The DUSP1 locus and promoter region were sequenced in 25 individuals. SNPs were tested for association with obesity-related complications in a cohort of more than 1900 severely obese individuals. The impact of SNPs on methylation levels of 36 CpG sites and correlations between DNA methylation and gene expression levels in VAT were computed in a subset of 14 samples. Results. Heterozygotes for rs881150 had lower HDL-cholesterol levels (HDL-C; P = 0.01), and homozygotes for the minor allele of rs13184134 and rs7702178 had increased fasting glucose levels (P = 0.04 and 0.01, resp.). rs881150 was associated with methylation levels of CpG sites located ~1250?bp upstream the transcription start site. Methylation levels of 4 CpG sites were inversely correlated with DUSP1 gene expression. Conclusion. These results suggest that DUSP1 polymorphisms modulate plasma glucose and HDL-C levels in obese patients possibly through alterations of DNA methylation and gene expression levels.

Guenard, F.; Bouchard, L.; Tchernof, A.; Deshaies, Y.; Hould, F. S.; Lebel, S.; Marceau, P.; Perusse, L.; Vohl, M. C.



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

Microsoft Academic Search

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

Markus Rehm; Udilo Finsterer



The anion gap does not accurately screen for lactic acidosis in emergency department patients  

PubMed Central

Introduction Lactic acidosis portends a poor prognosis in trauma, sepsis, and other shock states and is useful for triaging and resuscitating emergency department (ED) patients. The authors sought to determine whether the AG is a reliable screen for lactic acidosis when applied specifically in the ED setting. Methods The authors performed a retrospective cohort study over a seven month period. Subjects were all ED patients that had a serum lactate obtained. Sensitivity analyses of the AG for detecting presence of lactic acidosis were calculated for the traditional AG normal value (AG <12) and for the lower AG normal value when using newer ion selective electrode assays (AG <6). Results Serum lactate levels were ordered in the ED on 440 occasions. 137 samples were excluded by protocol. Using an AG cutoff of 12, the sensitivity for detecting lactic acidosis was 58.2%, specificity was 81.0%, and the negative predictive value was 89.7%. Using the AG cutoff of 6, the sensitivity was 93.2%, the specificity was 17.3%, and the negative predictive value was 91.8%. Conclusions The traditional definition of AG >12 was insensitive for the presence of lactic acidosis. Using the revised AG of >6 is more sensitive but non?specific for lactic acidosis. The authors conclude that employing the AG as a screen for LA may be inappropriate in ED patients. Instead, they recommend ordering a serum lactate immediately upon suspicion of a shock state. A prospective study to confirm these findings is needed.

Adams, B D; Bonzani, T A; Hunter, C J



Nonsense mutation in pseudouridylate synthase 1 (PUS1) in two brothers affected by myopathy, lactic acidosis and sideroblastic anaemia (MLASA)  

PubMed Central

Myopathy, lactic acidosis and sideroblastic anaemia (MLASA) is a rare condition that combines early-onset myopathy with lactic acidosis and sideroblastic anaemia. MLASA has been associated with a missense mutation in pseudouridylate synthase 1 (PUS1), an enzyme located in both nucleus and mitochondria, which converts uridine into pseudouridine in several cytosolic and mitochondrial tRNA positions and increases the efficiency of protein synthesis in both compartments. We examined two Italian brothers with MLSA and sequenced the PUS1 gene. We found combined defects in mitochondrial respiratory chain complexes in muscle and fibroblast homogenates of both patients, and low levels of mtDNA translation products in fibroblast mitochondria. A novel, homozygous stop mutation was present in PUS1 (E220X). The stop mutation in PUS1 is likely to determine the loss of function of the protein, since it predicts the synthesis of a protein missing 208/427 amino acid residues on the C terminus, and was associated with low mtDNA translation.

Fernandez-Vizarra, Erika; Berardinelli, Angela; Valente, Lucia; Tiranti, Valeria; Zeviani, Massimo



Sporadic intragenic inversion of the mitochondrial DNA MTND1 gene causing fatal infantile lactic acidosis.  


Mutations of mitochondrial DNA (mtDNA) are an important cause of genetic disease, yet rarely present in the neonatal period. Here we report the clinical, biochemical, and molecular genetic findings of an infant who died at the age of 1 mo with marked biventricular hypertrophy, aortic coarctation, and severe lactic acidosis due to a previously described but unusual mtDNA mutation, a 7-bp intragenic inversion within the mitochondrial gene encoding ND1 protein of complex I (MTND1). In direct contrast to the previous case, an adult with exercise intolerance who only harbored the mutation in muscle, the MTND1 inversion in our patient was present at high levels in several tissues including the heart, muscle, liver, and cultured skin fibroblasts. There was no evidence of the mutation or respiratory complex I defect in a muscle biopsy from the patient's mother. Transmitochondrial cytoplasmic hybrids (cybrids) containing high mutant loads of the inversion expressed the biochemical defect but apparently normal levels of the assembled complex. Our report highlights the enormous phenotypic diversity that exists among pathogenic mtDNA mutations and reemphasizes the need for appropriate genetic counseling for families affected by mtDNA disease. PMID:16492986

Blakely, Emma L; Rennie, Katherine J; Jones, Linda; Elstner, Mattias; Chrzanowska-Lightowlers, Zofia M A; White, Christopher B; Shield, Julian P H; Pilz, Daniela T; Turnbull, Douglass M; Poulton, Joanna; Taylor, Robert W



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


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

Kondo, Naoki; Yoda, Takuya



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

PubMed Central

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

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



Effects of Glucagon-like Peptide 1 (GLP-1) on Glycemia Control and Its Metabolic Consequence after Severe Thermal Injury - Studies in an Animal Model  

PubMed Central

Background Hyperglycemia with insulin resistance is commonly seen in severely burned patients and tight glycemia control with insulin (TGCI) may be beneficial in this condition. The most potent insulinotropic hormone GLP-1 stimulates insulin secretion in a glucose dependent manner. Since infusion of GLP-1 never reduces glucose levels to below ~70mg/dl, the risk of hypoglycemia associated with TGCI is reduced. In this study we investigated the metabolic effects of GLP-1 infusion after burn injury (BI) in an animal model. Methods Male CD rats were divided in 3 groups: BI with saline (B), BI with GLP-1 treatment (B+GLP) and sham burn (SB). BI was full thickness 40% TBSA. The B+GLP group received GLP-1 infusion via osmotic pump. Fasting blood glucose (FG), plasma insulin and plasma GLP-1 levels were measured during intraperitoneal glucose tolerance tests (IGTT). Expressions of caspase 3 and bcl-2 were evaluated in pancreatic islets. In a sub-set of animals, protein metabolism and total energy expenditure (TEE) were measured. Results Fasting GLP was reduced in B compared to SB or B+GLP. B+GLP showed reduced FG, improved IGTT, with increased plasma insulin and GLP-1 responses to glucose. GLP-1 reduced protein breakdown and TEE in B+GLP versus B, with improved protein balance. Increased expression of caspase 3 and decreased expression of bcl-2 in islet cells by BI were ameliorated by GLP-1. Conclusions BI reduced plasma GLP-1 in association with insulin resistance. GLP-1 infusion improved glucose tolerance and showed anabolic effects on protein metabolism and reduced TEE after BI, possibly via insulinotropic and non-insulintripic mechanisms.

Shen, Chuan-an; Fagan, Shawn; Fischman, Alan J.; Carter, Edward E.; Chai, Jia-Ke; Lu, Xiao-Ming; Yu, Yong-Ming; Tompkins, Ronald G.



Ethanol metabolism, cirrhosis and alcoholism.  


Alcohol-induced tissue damage results from associated nutritional deficiencies as well as some direct toxic effects, which have now been linked to the metabolism of ethanol. The main pathway involves liver alcohol dehydrogenase which catalyzes the oxidation of ethanol to acetaldehyde, with a shift to a more reduced state, and results in metabolic disturbances, such as hyperlactacidemia, acidosis, hyperglycemia, hyperuricemia and fatty liver. More severe toxic manifestations are produced by an accessory pathway, the microsomal ethanol oxidizing system involving an ethanol-inducible cytochrome P450 (2E1). After chronic ethanol consumption, there is a 4- to 10-fold induction of 2E1, associated not only with increased acetaldehyde generation but also with production of oxygen radicals that promote lipid peroxidation. Most importantly, 2E1 activates many xenobiotics to toxic metabolites. These include solvents commonly used in industry, anaesthetic agents, medications such as isoniazid, over the counter analgesics (acetaminophen), illicit drugs (cocaine), chemical carcinogens, and even vitamin A and its precursor beta-carotene. Furthermore, enhanced microsomal degradation of retinoids (together with increased hepatic mobilization) promotes their depletion and associated pathology. Induction of 2E1 also yields increased acetaldehyde generation, with formation of protein adducts, resulting in antibody production, enzyme inactivation, decreased DNA repair, impaired utilization of oxygen, glutathione depletion, free radical-mediated toxicity, lipid peroxidation, and increased collagen synthesis. New therapies include adenosyl-L-methionine which, in baboons, replenishes glutathione, and attenuates mitochondrial lesions. In addition, polyenylphosphatidylcholine (PPC) fully prevents ethanol-induced septal fibrosis and cirrhosis, opposes ethanol-induced hepatic phospholipid depletion, decreased phosphatidylethanolamine methyltransferase activity and activation of hepatic lipocytes, whereas its dilinoleoyl species increases collagenase activity. Current clinical trials with PPC are targeted on susceptible populations, namely heavy drinkers at precirrhotic stages. PMID:9028626

Lieber, C S



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


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

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



Effect of furosemide on urinary acidification in distal renal tubular acidosis.  


Furosemide stimulates urinary acidification in normal humans probably by increasing distal Na delivery and transport, thus creating a favorable electric gradient for H+ and K secretion. Therefore, furosemide should stimulate urinary acidification in patients with distal renal tubular acidosis, provided the distal nephron is capable of transporting Na and the H+ pumps can respond to the favorable electric gradient. We examined the effect of short-term furosemide administration on urinary acidification in five normal participants and 12 patients with normokalemic, hypokalemic, or hyperkalemic distal renal tubular acidosis. In controls, furosemide decreased urine pH and increased net acid and K excretion. In six of eight patients with normokalemic or hypokalemic renal tubular acidosis, furosemide decreased urine pH and increased net acid and K excretion to levels not significantly different from control values. The patients that had normal responses were interpreted as having a rate-dependent or gradient distal renal tubular acidosis, and thus increased distal Na delivery created a favorable electric gradient for H+ and K secretion. The normokalemic patients who did not have a response were considered to have a defect in the pumps (secretory defect). Of the four hyperkalemic patients, two had a voltage-dependent defect and the other two had aldosterone deficiency. The patients with selective aldosterone deficiency had low baseline urine pH values that did not change with furosemide administration, but net acid and K excretion did increase significantly. The patients with voltage-dependent defect did not lower urine pH or increase net acid and K excretion. Our data demonstrate that administration of furosemide enhances urinary acidification in certain patients with distal renal tubular acidosis. We suggest that furosemide administration may be useful in the characterization of the mechanism responsible for distal renal tubular acidosis and in the treatment of distal renal tubular acidosis in selected patients. PMID:6747443

Rastogi, S P; Crawford, C; Wheeler, R; Flanigan, W; Arruda, J A



Direct activation of cloned K(atp) channels by intracellular acidosis.  


ATP-sensitive K(+) (K(ATP)) channels may be regulated by protons in addition to ATP, phospholipids, and other nucleotides. Such regulation allows a control of cellular excitability in conditions when pH is low but ATP concentration is normal. However, whether the K(ATP) changes its activity with pH alterations remains uncertain. In this study we showed that the reconstituted K(ATP) was strongly activated during hypercapnia and intracellular acidosis using whole-cell recordings. Further characterizations in excised patches indicated that channel activity increased with a moderate drop in intracellular pH and decreased with strong acidification. The channel activation was produced by a direct action of protons on the Kir6 subunit and relied on a histidine residue that is conserved in all K(ATP). The inhibition appeared to be a result of channel rundown and was not seen in whole-cell recordings. The biphasic response may explain the contradictory pH sensitivity observed in cell-endogenous K(ATP) in excised patches. Site-specific mutations of two residues showed that pH and ATP sensitivities were independent of each other. Thus, these results demonstrate that the proton is a potent activator of the K(ATP). The pH-dependent activation may enable the K(ATP) to control vascular tones, insulin secretion, and neuronal excitability in several pathophysiologic conditions. PMID:11278532

Xu, H; Cui, N; Yang, Z; Wu, J; Giwa, L R; Abdulkadir, L; Sharma, P; Jiang, C



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

PubMed Central

Modern ventilation strategies for patients with acute lung injury and acute respiratory distress syndrome frequently result in hypercapnic acidosis (HCA), which is regarded as an acceptable side effect ('permissive hypercapnia'). Multiple experimental studies have demonstrated advantageous effects of HCA in several lung injury models. To date, however, human trials studying the effect of carbon dioxide per se on outcome in patients with lung injury have not been performed. While significant concerns regarding HCA remain, in particular the possible unfavorable effects on bacterial killing and the inhibition of pulmonary epithelial wound repair, the potential for HCA in attenuating lung injury is promising. The underlying mechanisms by which HCA exerts its protective effects are complex, but dampening of the inflammatory response seems to play a pivotal role. After briefly summarizing the physiological effects of HCA, a critical analysis of the available evidence on the potential beneficial effects of therapeutic HCA from in vitro, ex vivo and in vivo lung injury models and from human studies will be reviewed. In addition, the potential concerns in the clinical setting will be outlined.



Ruminal acidosis challenge impact on ruminal temperature in feedlot cattle.  


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

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



Contribution of nitric oxide to coronary vasodilation during hypercapnic acidosis.  


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

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



Does high-dose metformin cause lactic acidosis in type 2 diabetic patients after CABG surgery? A double blind randomized clinical trial  

PubMed Central

Metformin is a dimethyl biguanide oral anti-hyperglycemic agent. Lactic acidosis due to metformin is a fatal metabolic condition that limits its use in patients in poor clinical condition, consequently reducing the number of patients who benefit from this medication. In a double blind randomized clinical trial, we investigated 200 type 2 diabetic patients after coronary artery bypass surgery in the open heart ICU of the Mazandaran Heart Center, and randomly assigned them to equal intervention and control groups. The intervention group received regular insulin infusion along with 2 metformin 500 mg tablets every twelve hours, while the control group received only intravenous insulin with 2 placebo tablets every twelve hours. Lactate level, pH, base excess, blood glucose and serum creatinine were measured over five 12 h periods, with data averaged for each period. The primary outcome in this study was high lactate levels. Comparison between the 2 groups was made by independent Student’s t-test. To compare changes in multiple measures in each group and analysis of group interaction, a repeated measurement ANOVA test was used. There was no significant difference between the 2 groups regarding pH, base excess, or bicarbonate intake (P>0.05). No patient showed lactic acidosis in either group. Lactate levels were 23.0 vs 23.4 in the insulin-metformin and insulin only groups when the study was started, respectively. At the end of the study, those levels were 18.7 vs 18.9, respectively. In addition, the ANOVA repeated measurement test did not show a significant difference in terms of changes in the amount of lactate level between the 2 groups during the five measurement tests of the study period (P>0.05). High-dose metformin (1,000 mg twice daily with insulin) does not cause lactic acidosis in type 2 diabetic patients after coronary artery bypass surgery.

Baradari, Afshin Gholipour; Habibi, Mohammad Reza; Khezri, Hadi Darvishi; Aarabi, Mohsen; Khademloo, Mohammad; Jalali, Zahra; Ghafari, Rahman



Co-expressed immune and metabolic genes in visceral and subcutaneous adipose tissue from severely obese individuals are associated with plasma HDL and glucose levels: a microarray study  

PubMed Central

Background Excessive accumulation of body fat, in particular in the visceral fat depot, is a major risk factor to develop a variety of diseases such as type 2 diabetes. The mechanisms underlying the increased risk of obese individuals to develop co-morbid diseases are largely unclear. We aimed to identify genes expressed in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) that are related to blood parameters involved in obesity co-morbidity, such as plasma lipid and glucose levels, and to compare gene expression between the fat depots. Methods Whole-transcriptome SAT and VAT gene expression levels were determined in 75 individuals with a BMI >35 kg/m2. Modules of co-expressed genes likely to be functionally related were identified and correlated with BMI, plasma levels of glucose, insulin, HbA1c, triglycerides, non-esterified fatty acids, ALAT, ASAT, C-reactive protein, and LDL- and HDL cholesterol. Results Of the approximately 70 modules identified in SAT and VAT, three SAT modules were inversely associated with plasma HDL-cholesterol levels, and a fourth module was inversely associated with both plasma glucose and plasma triglyceride levels (p < 5.33 × 10-5). These modules were markedly enriched in immune and metabolic genes. In VAT, one module was associated with both BMI and insulin, and another with plasma glucose (p < 4.64 × 10-5). This module was also enriched in inflammatory genes and showed a marked overlap in gene content with the SAT modules related to HDL. Several genes differentially expressed in SAT and VAT were identified. Conclusions In obese subjects, groups of co-expressed genes were identified that correlated with lipid and glucose metabolism parameters; they were enriched with immune genes. A number of genes were identified of which the expression in SAT correlated with plasma HDL cholesterol, while their expression in VAT correlated with plasma glucose. This underlines both the singular importance of these genes for lipid and glucose metabolism and the specific roles of these two fat depots in this respect.



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


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

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



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

PubMed Central

Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O2) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH4Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH4Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening, and enhances pulmonary vascular responsiveness to vasoconstrictor and vasodilator stimuli. Together with our finding that acidosis decreases VSMC proliferation, the results are consistent with the possibility that nonhypercapnic acidosis promotes differentiation of pulmonary VSMCs to a more contractile phenotype, which may enhance the effectiveness of vasodilator therapies in PH.

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



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

PubMed Central

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

Chaudhry, Neera; Patidar, Yogesh; Puri, Vinod



ATP6V1B1 mutations in distal renal tubular acidosis and sensorineural hearing loss: clinical and genetic spectrum of five families.  


Abstract Distal renal tubular acidosis (DRTA) is characterized by tubular defects in urinary acidification and hyperchloremic metabolic acidosis, hypokalemia, hypercalciuria, hypocitraturia, nephrocalcinosis and nephrolithiasis. Mutations in ATP6V1B1 cause DRTA associated with sensorineural hearing loss. The objective of this multicenter study is to screen DRTA patients with sensorineural hearing loss for ATP6V1B1 gene mutations and present genotype/phenotype correlation. Clinical data in five unrelated consanguineous families with DRTA and hearing loss were obtained in Turkey. For mutation screening, all coding exons of ATP6V1B1 were PCR-amplified and sequenced from genomic DNA. In our cohort of five families, there were four different homozygous ATP6V1B1 mutations in affected individuals: c.91C>T (p.R31X), c.232G>A (p.G78R), c.497delC (p.T166RfsX9) and c.1155dupC (p.I386HfsX56). Our study shows that rare and family-specific variants in ATP6V1B1 are responsible for DRTA and sensorineural hearing loss syndrome in Turkey. While firm genotype-phenotype correlations are not available, detailed clinical and molecular analyses provide data to be used in genetic counseling. PMID:23923981

Subasioglu Uzak, Asli; Cakar, Nilgun; Comak, Elif; Yalcinkaya, Fatos; Tekin, Mustafa



Opioid Metabolism  

PubMed Central

Clinicians understand that individual patients differ in their response to specific opioid analgesics and that patients may require trials of several opioids before finding an agent that provides effective analgesia with acceptable tolerability. Reasons for this variability include factors that are not clearly understood, such as allelic variants that dictate the complement of opioid receptors and subtle differences in the receptor-binding profiles of opioids. However, altered opioid metabolism may also influence response in terms of efficacy and tolerability, and several factors contributing to this metabolic variability have been identified. For example, the risk of drug interactions with an opioid is determined largely by which enzyme systems metabolize the opioid. The rate and pathways of opioid metabolism may also be influenced by genetic factors, race, and medical conditions (most notably liver or kidney disease). This review describes the basics of opioid metabolism as well as the factors influencing it and provides recommendations for addressing metabolic issues that may compromise effective pain management. Articles cited in this review were identified via a search of MEDLINE, EMBASE, and PubMed. Articles selected for inclusion discussed general physiologic aspects of opioid metabolism, metabolic characteristics of specific opioids, patient-specific factors influencing drug metabolism, drug interactions, and adverse events.

Smith, Howard S.



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

Microsoft Academic Search

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

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



Response to Metabolic (Ammonium Chloride) Acidosis at Sea Level and at High Altitude  

Microsoft Academic Search

Summary Ammonium chloride was intravenously infused in a group of sea-leve. residents and in a group of high-altitude natives living at 4300 m above sea level. Blood pH, and buffer base; plasma bicarbonate, chloride, sodium and potassium; and urine pH, ammonium and titratable acidity were determined before and after the ammonium infusion. Blood pH, pCO2 blood buffer base, serum bicarbonate

R. Lozano; C. Torres; C. Marchena; J. Whittembury; C. C. Monge



A Case Study of Chronic Metabolic Acidosis, Neuropathies and Other Injuries Due to Solvent Exposure  

Microsoft Academic Search

A 61 year old male worker (Mr. T) previously employed on a lacquer coating line of a custom printing and packaging manufacturer contacted WorkCover during 2009 seeking help, as he was unable to work due to his injuries. More correctly, the pain, in combination with the amount and type of analgesic medication (including morphine patches, Vicodin, Gabapentin, etc) he was

Phillip C Cantrell


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

Microsoft Academic Search

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

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



Influence of alkaline buffers on cytoplasmic pH in myocardial cells exposed to metabolic acidosis  

Microsoft Academic Search

The influence of different clinically used alkaline buffers on cytoplasmic pH in normal as well as acidotic rat myocardial cells was investigated in this study by means of the fluorescent intracellular probe 2?,7?-bis-(carboxyethyl)-5,6-carboxyfluorescein acetoxymethyl ester (BCECF-AM). It was shown that both sodium bicarbonate and Tris buffer mixture (Tribonat®) caused a significant and dose-dependent acidification of the cytoplasm of suspended myocardial

Yu-Cai Li; Lars Wiklund; Pekka Tarkkila; Gunnel Bjerneroth



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

Microsoft Academic Search

Systemic acidosis has detrimental effects on the skeleton, and local acidosis coincides with bone destruction in inflammatory and metastatic diseases. Acidification dramatically enhances osteoclastic resorption, although the underlying mechanism has remained elusive. We investigated the effect of acidosis on the osteoclastogenic transcription factor NFATc1, which upon dephosphorylation translocates from the cytoplasm to nuclei. Lowering extracellular pH dramatically increased accumulation of

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



Activation of GPR4 by acidosis increases endothelial cell adhesion through the cAMP/Epac pathway.  


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 G(i) signaling inhibitor increases HUVEC adhesiveness, suggesting a role of the G(s)/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 G(s)/cAMP/Epac pathway and may play a role in the inflammatory response of vascular endothelial cells. PMID:22110680

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



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

PubMed Central

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

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



Severe carbon monoxide poisoning complicated by hypothermia: a case report.  


It is proposed that the significant elevation of interleukin-6 (>400 pg/mL) in cerebrospinal fluid during the early phase of carbon monoxide poisoning may be a predictive biomarker for the development of delayed encephalopathy. A 52-year-old man presented to the emergency department with severe carbon monoxide poisoning. On arrival, the patient was comatose with decorticate rigidity (Glasgow Coma Scale, E1V1M3). His core body temperature, measured in the urinary bladder, was 32.4°C. Laboratory blood analysis revealed elevated CO-Hb (36.0%) and metabolic acidosis with elevated lactate (pH 7.081; base excess [BE], -19.2 mmol/L; HCO3, -9.8 mmol/L; lactate, 168.8 mg/dL). After treatment with hyperbaric oxygen and several different rewarming techniques, he became alert and his core body temperature increased to normal. Interleukin-6 in cerebrospinal fluid at 5.5 hours after his last exposure to carbon monoxide was significantly elevated (752 pg/mL). However, he did not develop delayed encephalopathy. In this case, hypothermia in the range of therapeutic hypothermia (32°C to 34°C) may have suppressed formation of reactive oxygen species and subsequent lipid peroxydation, preventing the development of delayed encephalopathy. Therapeutic hypothermia initiated soon after the last exposure to carbon monoxide may be an effective prophylactic method for preventing the development of delayed encephalopathy. PMID:20674229

Kamijo, Yoshito; Ide, Toshimitsu; Ide, Ayako; Soma, Kazui



[Impact of lactic acid fermentation in the large intestine on acute lactic acidosis in cattle].  


Microbial and fermentation changes in the ingesta of the large intestine and their influence on the pathogenesis of acute lactic acidosis were studied in 4 cows fitted with permanent cannulas in the ileum and cecum. Feed mixture containing 65% of maize was infused into the cecum for several days in amounts of 2 and 4 kg per day. The daily amount was divided in 8 equal portions and given with 3 l of warm physiologic saline solution. During the period of ad libitum feeding of hay, the pH values in cecal digesta were 7.4 to 7.6 and the amount of total volatile fatty acids 40-60 mmol/kg with high molar percentage (87-90 mol%) of acetic acid. As to lactic acid only the L(+) lactic isomer was found in a concentration of about 0.4 mmol/kg. Infusion of low amounts of starch induced mild lactic acid fermentation in the cecum associated with a pronounced increase in the concentration of L(+) and D (-) lactic acid to peak levels of 80 +/- 10 mmol/kg and 7 +/- 1 mmol/kg, respectively. Lactic acid fermentation ceased within 2 to 3 days indicating that the gut microflora had adapted to the starch infusion. Slight decreases of blood pH and bicarbonates in blood as well as a moderate increase of netto acid-base excretion in urine indicated mild changes of acid-base balance, but clinically no pathological symptoms were observed. Higher amounts of infused starch caused pronounced lactic acid production in the large intestine which persisted throughout the experiment. Peak L(+) and D(-) lactic acid concentration in cecal digesta reached on the average 137 +/- 16 mmol/kg and 45 +/- 7 mmol/kg respectively. Significant decreases of blood pH values from 7.41 +/- 0.02 to 7.18 +/- 0.08 (P < 0.001), actual bicarbonate from 28.2 +/- 3.2 to 11.0 +/- 2.6 mmol/l (P < 0.001) and base excess from 3.9 +/- 3.6 to -15.2 +/- 3.8 mmol/l (P < 0.001) were observed. D (-) lactic acid concentration in blood increased to 3.2 +/- 0.4 mmol/l, but L(+) lactic acid values remained unchanged under 1 mmol/l. Clear clinical symptoms of indigestion and intoxication characterized by severe inappetence, ruminal stasis and general weakness were also observed. Typical clinical symptoms of disease as well as blood and urine changes in acid-base balance indicated that lactic acid fermentation in the large intestine contributes considerably to the pathogenesis of acute ruminant lactic acidosis. PMID:11471493

Zust, J; Pestevsek, U; Vengust, A



Tumor cell metabolism: an integral view.  


Cancer is a genetic disease that is caused by mutations in oncogenes, tumor suppressor genes and stability genes. The fact that the metabolism of tumor cells is altered has been known for many years. However, the mechanisms and consequences of metabolic reprogramming have just begun to be understood. In this review, an integral view of tumor cell metabolism is presented, showing how metabolic pathways are reprogrammed to satisfy tumor cell proliferation and survival requirements. In tumor cells, glycolysis is strongly enhanced to fulfill the high ATP demands of these cells; glucose carbons are the main building blocks in fatty acid and nucleotide biosynthesis. Glutaminolysis is also increased to satisfy NADPH regeneration, whereas glutamine carbons replenish the Krebs cycle, which produces metabolites that are constantly used for macromolecular biosynthesis. A characteristic feature of the tumor microenvironment is acidosis, which results from the local increase in lactic acid production by tumor cells. This phenomenon is attributed to the carbons from glutamine and glucose, which are also used for lactic acid production. Lactic acidosis also directs the metabolic reprogramming of tumor cells and serves as an additional selective pressure. Finally, we also discuss the role of mitochondria in supporting tumor cell metabolism. PMID:22057267

Romero-Garcia, Susana; Lopez-Gonzalez, Jose Sullivan; Báez-Viveros, José Luis; Aguilar-Cazares, Dolores; Prado-Garcia, Heriberto



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


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

Schmitz, J P J; van Dijk, J P; Hilbers, P A J; Nicolay, K; Jeneson, J A L; Stegeman, D F



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


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

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



Exercise acidosis as cause of electrolyte changes in femoral venous blood of trained and untrained man  

Microsoft Academic Search

Relations among exercise acidosis and various electrolyte concentrations in plasma of femoral venous blood were investigated during bicycling. At equal work rates the changes in endurance trained athletes were compared with the changes in non-athletes. The increase of [Ca++] and [Mg++] could be explained by hemoconcentration. In untrained [H+], [K+], [orthophosphate] (Pi), [lactate] (Lac) and [protein] (Prot) increased significantly more

Ulrich Tibes; Bernd Hemmer; Ursula Schweigart; Dieter Böning; Dorin Fotescu



Effects of Hypoxia, Hypotension, and Acidosis on the Electrolyte Composition of Rat Kidneys  

Microsoft Academic Search

Summary The effect of prolonged hypoxia, transient and prolonged hypotension, and of acidosis on rat kidney and muscle water, sodium, potassium, magnesium, and phosphate composition was investigated. A significant increase in kidney tissue water was found in all experimental groups. Prolonged hypotension produced a decrease in kidney potassium and magnesium content and an increase in sodium content. Hypoxia produced an

P. R. Uldall; W. J. Schorr; J. R. Osmun; D. A. Ogden; J. H. Holmes



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

Microsoft Academic Search

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

W. C. Stone



Correction of Acidosis by Hemodialysis: Proposal of a Correlation with Urea Kinetics  

Microsoft Academic Search

Background\\/Aims: We examined the effect of hemodialysis (HD) on acid-base status and its relation to urea kinetics in clinically stable renal HD patients. The purpose of this study was to design a practical approach to monitoring the correction of acidosis, as it can be assisted by routine parameters of adequacy. Methods: Blood samples were drawn immediately before and after HD

Maurilo Leite Jr.; Ethel Leal; Lúcio R. Cardoso



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

Microsoft Academic Search

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

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



[Acidosis inhibits oxidative phosphorylation in intrasynaptosomal mitochondria by releasing calcium from cytoplasmic store].  


The origin of calcium responsible for earlier observed acidosis-induced decrease in ATP content and inhibition of respiration in rat brain synaptosomes was studied. Acidosis (pH 6.0) inhibits both basal and potassium-stimulated 45Ca2+ uptake (60 mM KCl). Calcium channel blockers verapamil (100 microM) and 45Ca2+ (100 microM) have no effect on the level of ATP and respiration rate at pH 6.0. Theophylline (10 mM) releasing calcium from intracellular stores lowered ATP and O2 consumption rate at pH 7.4 but not at pH 6.0 being effective only in calcium-containing medium. Inhibitor of calcium transport in mitochondria ruthenium red (10 microM) prevented acidosis-induced ATP decrease. It is suggested that acidosis inhibits oxidative phosphorylation by releasing calcium from cytoplasmic stores with its subsequent transport into intrasynaptosomal mitochondria. PMID:9591106

Aksentsev, S L; Levko, A V; Fedorovich, S V; Orlov, S N; Konev, S V


Knockdown of ASIC2a subunit aggravates injury of rat C6 glioma cells in acidosis.  


Acid-sensing ion channel 1a (ASIC1a) and 2a (ASIC2a) subunits are widely expressed throughout mammalian central nervous system. Activation of Ca²?-permeable ASIC1a homomultimers is largely responsible for acidosis-mediated, glutamate receptorindependent, ischemic neuronal injury. The function of ASIC2a in brain ischemia is less known except that transient global ischemia induces ASIC2a protein expression up-regulation in neurons that survived ischemia. Acidosis is assumed to play a critical role in brain ischemia injury. In the present experiment, rat C6 neuroglioma cells were used to explore the function of ASIC2a. MTT and relative LDH release assay revealed that knockdown of ASIC2a could aggravate the acidosis-induced injury of C6 cells. Through changing extracellular Ca²? concentration and measuring intracellular calcium fluorescence intensity, it was found that aggravated damage was due to toxic Ca²? overload via ASICs mechanisms. The current results indicated that, different from ASIC1a, ASIC2a probably played a protective role against the injury induced by extracellular acidosis in C6 cells. PMID:21061195

Liu, Xiao-Yan; Zhang, Shu-Zhuo; Ma, Xiao-Yun; Wang, Hui; Wu, Bao-Hong; Sun, Hong-Liang; Li, Xin; Wei, Xiao-Li; Zheng, Jian-Quan



Genetic Metabolic Disease  

Microsoft Academic Search

The terms inborn errors of metabolism, genetic metabolic disease, disorders of intermediary metabolism, and inherited metabolic disease are used interchangeably. For the sake of clarity, inborn errors of metabolism (IEMs) is used in this chapter. The common\\u000a feature of these disorders is a genetically determined interruption in one (or several related) metabolic pathway. This results\\u000a in clinical symptoms caused by

David R. FitzPatrick


Inherited metabolic disorders and cerebral infarction.  


The association of genetic factors and cerebral infarction (CI) has long been established. A positive family history alone is a recognized risk factor for CI and vascular events in general. However, there are certain inherited conditions that further increase the risk of stroke. These conditions are generally metabolic and mitochondrial genetic defects that have variable modes of inheritance. This article reviews major inherited metabolic disorders that predispose an individual to CI. Ten main conditions will be discussed: Fabry's disease, cerebrotendinous xanthomatosis, tangier disease, familial hypercholesterolemia, homocystinuria, methylmalonic acidemia, glutaric aciduria type I, propionic acidemia, ornithine transcarbamylase deficiency and mitochondrial encephalopathy, lactic acidosis and stroke-like phenomenon. PMID:18986243

Kalidas, Kavita; Behrouz, Réza



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

PubMed Central

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



Testosterone protects female embryonic heart H9c2 cells against severe metabolic stress by activating estrogen receptors and up-regulating IES SUR2B.  


A recent clinical study demonstrated that a testosterone supplementation improves functional capacity in elderly female patients suffering from heart failure. These findings prompted us to consider possible mechanisms of testosterone-induced cardioprotection in females. To address this question we have used a pure female population of rat heart embryonic H9c2 cells. Pre-treatment of cells with testosterone for 24h significantly increased survival of H9c2 cells exposed to 2,4-dinitrophenol (DNP), an inhibitor of oxidative phosphorylation. These cells expressed low level of androgen receptors and the effect of testosterone was not modified by hydroxyflutamide, an antagonist of androgen receptor. In contrast, cyclohexamide, an inhibitor of protein biosynthesis, and tamoxifene, a partial agonist of estrogen receptors, abolished cardioprotection afforded by testosterone. In addition, finasteride, an inhibitor of 5?-reductase, and anastrazole, an inhibitor of ?-aromatase, also blocked testosterone-induced cytoprotection. Real time RT-PCR revealed that testosterone did not regulate the expression of nine subunits and accessory proteins of sarcolemmal ATP-sensitive K(+) (K(ATP)) channels. On the other hand, testosterone, as well as 17?-estradiol, up-regulated a putative mitochondrial K(ATP) channel subunit, mitochondrial sulfonylurea receptor 2B intraexonics splice variant (IES SUR2B), without affecting expression of IES SUR2A. Tamoxifene inhibited testosterone-induced up-regulation of IES SUR2B without affecting IES SUR2A. In conclusion, this study has shown that testosterone protect female embryonic heart H9c2 cells against severe metabolic stress by its conversion into metabolites that activate estrogen receptors and up-regulate IES SUR2B. PMID:23085378

Ballantyne, Thomas; Du, Qingyou; Jovanovi?, Sofija; Neemo, Andrew; Holmes, Robert; Sinha, Sharabh; Jovanovi?, Aleksandar



Hypercapnia and Acidosis During Open and Thoracoscopic Repair of Congenital Diaphragmatic Hernia and Esophageal Atresia: Results of a Pilot Randomized Controlled Trial.  


OBJECTIVE:: We aimed to evaluate the effect of thoracoscopy in neonates on intraoperative arterial blood gases, compared with open surgery. BACKGROUND:: Congenital diaphragmatic hernia (CDH) and esophageal atresia with tracheoesophageal fistula (EA/TEF) can be repaired thoracoscopically, but this may cause hypercapnia and acidosis, which are potentially harmful. METHODS:: This was a pilot randomized controlled trial. The target number of 20 neonates (weight > 1.6 kg) were randomized to either open (5 CDH, 5 EA/TEF) or thoracoscopic (5 CDH, 5 EA/TEF) repair. Arterial blood gases were measured every 30 minutes intraoperatively, and compared by multilevel modeling, presented as mean and difference (95% confidence interval) from these predictions. RESULTS:: Overall, the intraoperative PaCO2 was 61 mm Hg in open and 83 mm Hg [difference 22 mm Hg (2 to 42); P = 0.036] in thoracoscopy and the pH was 7.24 in open and 7.13 [difference -0.11 (-0.20 to -0.01); P = 0.025] in thoracoscopy. The duration of hypercapnia and acidosis was longer in thoracoscopy compared with that in open. For patients with CDH, thoracoscopy was associated with a significant increase in intraoperative hypercapnia [open 68 mm Hg; thoracoscopy 96 mm Hg; difference 28 mm Hg (8 to 48); P = 0.008] and severe acidosis [open 7.21; thoracoscopy 7.08; difference -0.13 (-0.24 to -0.02); P = 0.018]. No significant difference in PaCO2, pH, or PaO2 was observed in patients undergoing thoracoscopic repair of EA/TEF. CONCLUSIONS:: This pilot randomized controlled trial shows that thoracoscopic repair of CDH is associated with prolonged and severe intraoperative hypercapnia and acidosis, compared with open surgery. These findings do not support the use of thoracoscopy with CO2 insufflation and conventional ventilation for the repair of CDH, calling into question the safety of this practice. The effect of thoracoscopy on blood gases during repair of EA/TEF in neonates requires further evaluation. ( Identifier: NCT01467245). PMID:23604057

Bishay, Mark; Giacomello, Luca; Retrosi, Giuseppe; Thyoka, Mandela; Garriboli, Massimo; Brierley, Joe; Harding, Louise; Scuplak, Stephen; Cross, Kate M; Curry, Joe I; Kiely, Edward M; De Coppi, Paolo; Eaton, Simon; Pierro, Agostino



Severe hyperkalemia requiring hospitalization: predictors of mortality  

PubMed Central

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




Microsoft Academic Search

Summary White muscle and arterial blood plasma were sampled at rest and during 4 h of recovery from exhaustive exercise in rainbow trout. A compound respiratory and metabolic acidosis in the blood was accompanied by increases in plasma lactate (in excess of the metabolic acid load), pyruvate, glucose, ammonia and inorganic phosphate levels, large elevations in haemoglobin concentration and haematocrit,



Blood pH level modulates organ metabolism of lactate in septic shock in dogs  

Microsoft Academic Search

Objective: Lactic acidosis is an important complication of septic shock. Alkali treatment such as sodium bicarbonate is often used to treat the low pH level that develops in sepsis. The effect of this treatment on lactate (Lac) clearance is not clear. In the present study, the objective was to examine whether blood pH level alters Lac metabolism in sepsis. Measurements

Carla Chrusch; Edgar Bautista; Hans K. Jacobs; R. Bruce Light; Deepak Bose; Krika Duke; Steven N. Mink



A practical and direct comparison of intrinsic metabolic clearance of several non-CYP enzyme substrates in freshly isolated and cryopreserved hepatocytes.  


Human hepatocytes are a physiologically relevant tool useful in evaluating liver-related pharmacokinetics, including non-cytochrome P-450 (CYP) metabolism, due to their broad spectrum of metabolic enzyme activity. To verify the usefulness of human hepatocytes in evaluating non-CYP metabolism for drug discovery, we compared intrinsic clearance values (CL(int)) in freshly isolated and cryopreserved hepatocytes using 14 compounds primarily metabolized by non-CYP enzymes, including UDP-glucuronosyltransferase, carbonyl/aldo-keto reductase, aldehyde oxidase, flavin-containing monooxygenase, and monoamineoxidase. Cryopreservation resulted in a >20% reduction (maximum: 50%) in CL(int) in 7/14 compounds (statistically significant for 5 compounds) on comparing CL(int) values in freshly isolated and cryopreserved hepatocytes from the same donors (n = 4). However, the number of compounds with >20% CL(int) reduction decreased to 3 on comparing average of CL(int) values including un-matched donors (dolasetron: -27%, naltorexone: -32%, and phthalazine: -48%; statistically significant for phthalazine, n = 6-11). These findings suggest that fresh hepatocytes are useful in evaluating intact non-CYP enzyme activities. However, we must note that the reduction in CL(int) by cryopreservation could be rendered negligible if high-activity lots are selected for assay. We therefore recommend using cryopreserved hepatocytes for large-scale screening for non-CYP metabolism in drug discovery research considering the advantages in usability with cryopreserved hepatocytes. PMID:22027494

Akabane, Takafumi; Gerst, Nicolas; Naritomi, Yoichi; Masters, Jeffrey N; Tamura, Kouichi



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

PubMed Central

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



Renal tubular acidosis, hypokalemic paralysis, rhabdomyolysis, and acute renal failure--a rare presentation of Chinese herbal nephropathy.  


We encountered a 66-year-old Chinese man presented with hypokalemic paralysis, rhabdomyolysis and acute renal failure after administration of mixed Chinese herbs. Proximal renal tubular acidosis and selective glucosuria were the main tubular dysfunctions. The renal failure recovered smoothly and rapidly after resuscitation and the tubular function abnormalities regained spontaneously after medicine withdrawal. It should be recognized that renal tubular acidosis with hypokalemic paralysis, rhabdomyolysis and subsequent acute renal failure may develop after taking Chinese mixed herbal medicine. PMID:10088184

Lee, C T; Wu, M S; Lu, K; Hsu, K T



Energy metabolism in cardiac remodeling and heart failure.  


Fatty acids are the main substrates used by mitochondria to provide myocardial energy under normal conditions. During heart remodeling, however, the fuel preference switches to glucose. In the earlier stages of cardiac remodeling, changes in energy metabolism are considered crucial to protect the heart from irreversible damage. Furthermore, low fatty acid oxidation and the stimulus for glycolytic pathway lead to lipotoxicity, acidosis, and low adenosine triphosphate production. While myocardial function is directly associated with energy metabolism, the metabolic pathways could be potential targets for therapy in heart failure. PMID:22990373

Azevedo, Paula S; Minicucci, Marcos F; Santos, Priscila P; Paiva, Sergio A R; Zornoff, Leonardo A M


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

Microsoft Academic Search

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

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



The importance of hyporheic sediment respiration in several mid-order Michigan rivers: comparison between methods in estimates of lotic metabolism  

Microsoft Academic Search

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.

D. G. Uzarski; C. A. Stricker; T. M. Burton; D. K. King; A. D. Steinman



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

Microsoft Academic Search

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

Tuty Asmawaty Abdul Kadir; Ahmad A Mannan; Andrzej M Kierzek; Johnjoe McFadden; Kazuyuki Shimizu



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

Microsoft Academic Search

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



Sheep Fed Grain Prefer Foods and Solutions That Attenuate Acidosis1  

Microsoft Academic Search

We conducted experiments to deter- mine whether lambs fed grain prefer foods and solutions containing sodium bicarbonate (NaHCO3) and lasalocid, compounds capable of attenuating acidosis. In Exp. 1, we determined whether lambs fed barley preferred flavored rabbit pellets (RP) contain- ing NaHCO3 and lasalocid. Lambs in two groups (n = 10\\/group) were fed increasing amounts of barley on d 1

Timothy S. Phy; Frederick D. Provenza



Effect of acute hypoxia and hypercapnic acidosis on the development of acetylstrophanthidin-induced arrhythmias  

PubMed Central

The effect of acutely induced hypoxia, hypercapnic acidosis, and the combination of the two on the amount of acetylstrophanthidin (AS) required to produce cardiac arrhythmias was determined in anesthetized dogs. Each animal was studied during ventilation with room air and again during ventilation with gas mixtures of appropriate concentrations; 24 hr separated the study periods. AS was infused intravenously at a rate of 5 ?g/kg per min. Significantly less AS was required to produce arrhythmias during hypoxia and hypercapnic acidosis together than during the period with normal arterial Po2, Pco2, and pH (10 animals). Included in this group were two animals which had undergone previous bilateral adrenalectomy and four animals in which heart rate was maintained at the same frequency during both study periods. A significant reduction in the toxic dose of AS also was demonstrated in eight animals, two with constant heart rate, during hypoxia with normal arterial Pco2 and pH. Hypercapnic acidosis alone (eight animals) did not significantly alter the toxic dose of AS. After the administration of propranolol (six animals) or hexamethionium (six animals), no significant difference was observed between the toxic dose of AS during hypoxia and that during ventilation with room air. Thus although hypoxia and hypercapnic acidosis together do reduce the amount of AS required to produce arrhythmias, it is the hypoxia which exerts the predominant effect on the development of this increased sensitivity to AS. Furthermore, this effect of hypoxia occurs primarily as a result of reflexly augmented sympathetic stimulation of the heart.

Williams, John F.; Boyd, Daniel L.; Border, John F.



?-Alanine supplementation reduces acidosis but not oxygen uptake response during high-intensity cycling exercise  

Microsoft Academic Search

The oral ingestion of ?-alanine, the rate-limiting precursor in carnosine synthesis, has been shown to elevate the muscle\\u000a carnosine content. Carnosine is thought to act as a physiologically relevant pH buffer during exercise but direct evidence\\u000a is lacking. Acidosis has been hypothesised to influence oxygen uptake kinetics during high-intensity exercise. The present\\u000a study aimed to investigate whether oral ?-alanine supplementation

Audrey Baguet; Katrien Koppo; Andries Pottier; Wim Derave



Anion exchanger 1 mutations associated with distal renal tubular acidosis in the Thai population  

Microsoft Academic Search

We have previously demonstrated that compound heterozygous (SAO\\/G701D) and homozygous (G701D\\/G701D) mutations of the anion exchanger 1 ( AE1) gene, encoding erythroid and kidney AE1 proteins, cause autosomal recessive distal renal tubular acidosis (AR dRTA) in Thai patients. It is thus of interest to examine the prevalence of these mutations in the Thai population. The SAO and G701D mutations were examined

Pa-thai Yenchitsomanus; Nunghathai Sawasdee; Atchara Paemanee; Thitima Keskanokwong; Somkiat Vasuvattakul; Sasitorn Bejrachandra; Warunee Kunachiwa; Supan Fucharoen; Prapaporn Jittphakdee; Wanwimon Yindee; Charupon Promwong



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

Microsoft Academic Search

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

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



Subacute Ruminal Acidosis and Evaluation of Blood Gas Analysis in Dairy Cow  

PubMed Central

Subacute Ruminal Acidosis (SARA) corresponds to an imbalance between lactate-producing bacteria and lactate-using bacteria, which results in a change in ruminal pH associated with a prevalent consumption of rapidly fermentable carbohydrates. In our study, 216 primiparus and multiparus dairy cows were selected from 20 Italian intensive dairy herds and were divided into three groups based on the risk of SARA. All the dairy cows had high average milk production. After blood sampling, a complete blood gas analysis was performed. One-way ANOVA was performed to compare the three groups. O2 Cont, PCO2, blood pH, O2Hb, urinary pH, and rumen pH were significantly lower in cows with rumen pH < 5.5. These results indicate that blood gas analysis is a valuable tool to diagnose acidosis in dairy cows because it provides good assessment of acidosis while being less invasive than rumen pH analysis.

Gianesella, Matteo; Morgante, Massimo; Cannizzo, Chiara; Stefani, Annalisa; Dalvit, Paolo; Messina, Vanessa; Giudice, Elisabetta



Acid-sensing ion channels in acidosis-induced injury of human brain neurons  

PubMed Central

Acidosis is a common feature of the human brain during ischemic stroke and is known to cause neuronal injury. However, the mechanism underlying acidosis-mediated injury of the human brain remains elusive. We show that a decrease in the extracellular pH evoked inward currents characteristic of acid-sensing ion channels (ASICs) and increased intracellular Ca2+ in cultured human cortical neurons. Acid-sensing ion channels in human cortical neurons show electrophysiological and pharmacological properties distinct from those in neurons of the rodent brain. Reverse transcriptase-PCR and western blot detected a high level of the ASIC1a subunit with little or no expression of other ASIC subunits. Treatment of human cortical neurons with acidic solution induced substantial cell injury, which was attenuated by the ASIC1a blockade. Thus, functional homomeric ASIC1a channels are predominantly expressed in neurons from the human brain. Activation of these channels has an important role in acidosis-mediated injury of human brain neurons.

Li, Minghua; Inoue, Koichi; Branigan, Deborah; Kratzer, Eric; Hansen, Jillian C; Chen, Jeff W; Simon, Roger P; Xiong, Zhi-Gang



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

PubMed Central

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

Vengust, Modest



[Remarks on the metabolic evaluation of renal lithiasis].  


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

Thomas, J



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


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

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



Metabolic dysfunction and relationship in human frontoparietal cortex in severe traumatic brain injury: single-voxel (1)H magnetic resonance spectroscopy study.  


(1)H-magnetic resonance spectroscopy revealed that apparently normal (from the data of magnetic resonance imaging) human brain frontoparietal cortex in the subacute stage of traumatic brain injury is characterized by decreased level of N-acetylaspartate (NAA) and increase in levels of myoinositol, choline-containing compounds (Cho), and creatine/phosphocreatine (Cr). Correlations between Cr, Cho, and NAA were established. We propose a scheme of neuronal metabolic processes that joins these substances. PMID:22809158

Semenova, N A; Akhadov, T A; Petryaykin, A V; Sidorin, S S; Lukovenkov, A V; Varfolomeev, S D



Experimental feed induction of ruminal lactic, propionic, or butyric acidosis in sheep.  


A study was conducted to determine the feasibility to induce rumen acidosis with propionate, butyrate, or lactate as the major fermentation end products. Three rumen-cannulated Texel wethers were used in a 3 x 3 Latin square design. Each period consisted of 11 d of adaptation where wethers were daily fed at 90% of ad libitum intake a hay and wheat-based concentrate diet (4:1 ratio on a DM basis) in 2 equal portions followed by 3 d of acidosis induction. During the challenge, the morning feeding was replaced by an intraruminal supply of wheat (readily fermentable starch), corn (slowly fermentable starch), or beet pulp (easily digestible fiber), dosed at 1.2% of BW. Ruminal liquid samples were taken daily 1 h before (-1) and 1, 3, 5, and 6 h after intraruminal feed supply to measure pH, VFA, and lactic acid concentration. The differences between treatments accentuated throughout the 3-d challenge, being maximal and significant on d 3. Indeed, 6 h after the third day of the challenge, mean ruminal pH was less for wheat (4.85) than for corn (5.61; P = 0.008) and beet pulp (6.09; P = 0.001), and total VFA tended to be less for wheat (48.7 mM) than for corn and beet pulp (84.7 mM on average; P = 0.08). At the same time, the proportion of acetate was greater for wheat than for corn (75.5 and 62.2%, respectively; P = 0.005) but did not differ from beet pulp challenge (69.0%). The proportion of propionate was greatest for beet pulp compared with corn and wheat (21.0, 17.3, and 12.1%, respectively; P = 0.03), whereas the butyrate proportion was greatest for corn, intermediate for wheat, and least for beet pulp (16.3, 10.8, and 8.3%, respectively; P = 0.05). Lactate concentration was greatest for wheat (45.5 mM) compared with corn and beet pulp (8.3 mM on average; P = 0.01). Under our experimental conditions, ruminal lactic acidosis was successfully induced by wheat, whereas butyric and propionic subacute ruminal acidosis were respectively provoked by corn and beet pulp. We developed an original model that promoted differentiated fermentation pathways in the rumen of sheep. It will be used to study the ruminal microbiome changes involved in different acidosis situations. PMID:20495125

Lettat, A; Nozière, P; Silberberg, M; Morgavi, D P; Berger, C; Martin, C



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


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

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



Mineral metabolism and bone abnormalities in children with chronic renal failure  

Microsoft Academic Search

Abnormalities in mineral metabolism and changes in skeletal histology may contribute to growth impairment in children with\\u000a chronic renal failure. Hyperphosphatemia, hypocalcemia, metabolic acidosis, alterations in vitamin D and IGF synthesis and\\u000a parathyroid gland dysfunction play significant roles in the development of secondary hyperparathyroidism and subsequently,\\u000a bone disease in renal failure. The recent KDIGO conference has made recommendations to consider

Cheryl P. Sanchez



Effects of exercise-induced intracellular acidosis on the phosphocreatine recovery kinetics: a (31) P MRS study in three muscle groups in humans.  


Little is known about the metabolic differences that exist among different muscle groups within the same subjects. Therefore, we used (31) P-magnetic resonance spectroscopy ((31) P-MRS) to investigate muscle oxidative capacity and the potential effects of pH on PCr recovery kinetics between muscles of different phenotypes (quadriceps (Q), finger (FF) and plantar flexors (PF)) in the same cohort of 16 untrained adults. The estimated muscle oxidative capacity was lower in Q (29?±?12 mM min(-1) , CVinter-subject ?=?42%) as compared with PF (46?±?20 mM min(-1) , CVinter-subject ?=?44%) and tended to be higher in FF (43?±?35 mM min(-1) , CVinter-subject ?=?80%). The coefficient of variation (CV) of oxidative capacity between muscles within the group was 59?±?24%. PCr recovery time constant was correlated with end-exercise pH in Q (p?acidosis and PCr recovery kinetics in FF compared with either PF or Q muscles. Overall, this study supports the concept of skeletal muscle heterogeneity by revealing a comparable inter- and intra-individual variability in oxidative capacity across three skeletal muscles in untrained individuals. These findings also indicate that the sensitivity of mitochondrial respiration to the inhibition associated with cytosolic acidosis is greater in the finger flexor muscles compared with locomotor muscles, which might be related to differences in permeability in the mitochondrial membrane and, to some extent, to proton efflux rates. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23703831

Layec, Gwenael; Malucelli, Emil; Le Fur, Y; Manners, David; Yashiro, Kazuya; Testa, Claudia; Cozzone, Patrick J; Iotti, Stefano; Bendahan, David



Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis  

PubMed Central

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.

Karet, F. E.; Gainza, F. J.; Gyory, 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.



Carbon Dioxide Pneumoamnios Causes Acidosis in Fetal Lamb  

Microsoft Academic Search

Recently developed techniques of video-endoscopic surgery may offer new hope for the future of fetal surgery. To allow this approach, the amniotic cavity has to be temporarily enlarged, either by carbon dioxide (CO2) insufflation or by amnioinfusion. In 6 anesthetized ewes, CO2 insufflation of the amniotic cavity produced severe fetal hypercapnia (from 57.6 ± 1.6 to 87.0 ± 7.0 torr)

Francois I. Luks; Jan Deprest; Marco Marcus; Kamiel Vandenberghe; Jan D. Vertommen; Toni Lerut; Ivo Brosens



Metabolic Surgery Profoundly Influences Gut Microbial-Host Metabolic Crosstalk  

PubMed Central

Background and Aims Bariatric surgery is increasingly performed worldwide to treat morbid obesity and is also known as metabolic surgery to reflect its beneficial metabolic effects especially with respect to improvement in type 2 diabetes. Understanding surgical weight loss mechanisms and metabolic modulation is required to enhance patient benefits and operative outcomes. Methods We apply a parallel and statistically integrated metagenomic and metabonomic approach to characterize Roux-en-Y gastric bypass (RYGB) effects in a rat model. Results We show substantial shifts of the main gut phyla towards higher levels of Proteobacteria (52-fold) specifically Enterobacter hormaechei. We also find low levels of Firmicutes (4.5-fold) and Bacteroidetes (2-fold) in comparison to sham-operated rats. Faecal extraction studies reveal a decrease in faecal bile acids and a shift from protein degradation to putrefaction through decreased faecal tyrosine with concomitant increases in faecal putrescine and diamnoethane. We find decreased urinary amines and cresols and demonstrate indices of modulated energy metabolism post-RYGB including decreased urinary succinate, 2-oxoglutarate, citrate and fumarate. These changes could also indicate renal tubular acidosis, which associates with increased flux of mitochondrial tricarboxylic acid cycle intermediates. A surgically-induced effect on the gut-brain-liver metabolic axis is inferred by increased neurotropic compounds; faecal ?-aminobutyric acid (GABA) and glutamate. Conclusion This profound co-dependence of mammalian and microbial metabolism, which is systematically altered following RYGB surgery, suggests that RYGB exerts local and global metabolic activities. The effect of RYGB surgery on the host metabolic-microbial crosstalk augments our understanding of the metabolic phenotype of bariatric procedures and can facilitate enhanced treatments for obesity-related diseases.

Li, Jia V.; Ashrafian, Hutan; Bueter, Marco; Kinross, James; Sands, Caroline; le Roux, Carel W; Bloom, Stephen R.; Darzi, Ara; Athanasiou, Thanos; Marchesi, Julian R.; Nicholson, Jeremy K.; Holmes, Elaine



Fibrinogen metabolic responses to trauma  

PubMed Central

Coagulation complications are significant contributors to morbidity and mortality in trauma patients. Although the lethal triad of hypothermia, acidosis and coagulopathy has been recognized for over a decade, the underlying mechanisms related to the development of coagulopathy remain unclear. Recent data suggest that decreased fibrinogen levels contribute to the development of coagulation disorders. Thus, regulation of fibrinogen availability, not fully understood at present, may play an important role in survival of trauma patients. This review summarizes the recent findings of the studies that have explored mechanisms related to changes in fibrinogen availability following trauma-related events. Trauma alters fibrinogen metabolism in a variety of ways: hemorrhage – accelerated fibrinogen breakdown; hypothermia – inhibited fibrinogen synthesis; and, acidosis – accelerated fibrinogen breakdown. However, hemorrhage, hypothermia andcidosis all result in a consistent outcome of fibrinogen availability deficit, supporting the notion of fibrinogen supplementation in trauma patients with coagulation defects. Future prospective clinical trials are needed to confirm the beneficial effects of fibrinogen supplementation in trauma patients with bleeding complications.

Martini, Wenjun Zhou



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


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

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



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


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

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



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

PubMed Central

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

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



The effect of induced alkalosis and acidosis on plasma lactate and work output in elite oarsmen  

Microsoft Academic Search

Summary  In order to test the effect of artificially induced alkalosis and acidosis on the appearance of plasma lactate and work production,\\u000a six well-trained oarsmen (age=23.8±2.5 years; mass=82.0±7.5 kg) were tested on three separate occasions after ingestion of\\u000a 0.3 g·kg?1. NH4Cl (acidotic), NaHCO3 (alkalotic) or a placebo (control). Blood was taken from a forearm vein immediately prior to exercise for determination

Donald M. Brien; Donald C. McKenzie



The intensity of acidosis differentially alters the pathways of ammoniagenesis in LLC-PK1 cells  

Microsoft Academic Search

The intensity of acidosis differentially alters the pathways of ammoniagenesis in LLC-PK1 cells. Utilizing [5-15N] and [2-15N]-labeled glutamine and gas chromatography mass spectrometry methodology, we examined the pathways of ammoniagenesis under basal and acute acidotic conditions of pH 7.0 and pH 6.8, respectively. LLC-PK1 cultures were incubated for one hour with gentle rocking in a bicarbonate buffer of pH 7.4,

Itzhak Nissim; Atul Sahai; Rose S Sandler; Richard L Tannen



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


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

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



One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen administration  

Microsoft Academic Search

BACKGROUNDNon-invasive ventilation (NIV) reduces mortality and intubation rates in patients with chronic obstructive pulmonary disease (COPD) admitted to hospital with respiratory acidosis. This study aimed to determine the prevalence of respiratory acidosis in patients admitted with COPD, to draw inferences about oxygen therapy, and to determine the need for NIV services for acute COPD in typical UK hospitals.METHODSThis one year

P K Plant; J L Owen; M W Elliott



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


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

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



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

PubMed Central

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

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



Profiling Genetic Variation along the Androgen Biosynthesis and Metabolism Pathways Implicates Several Single Nucleotide Polymorphisms and Their Combinations as Prostate Cancer Risk Factors  

Microsoft Academic Search

Several candidate genes along androgen pathway have been suggested to affect prostate cancer risk but no single gene seems to be overwhelmingly important for a large fraction of the patients. In this study, we first screened for variants in candidate genes and then chose to explore the association between 18 variants and prostate cancer risk by genotyping DNA samples from

Nina Mononen; Eija H. Seppala; Priya Duggal; Ville Autio; Tarja Ikonen; Pekka Ellonen; Juha Saharinen; Janna Saarela; Mauno Vihinen; Teuvo L. J. Tammela; Olli Kallioniemi; Joan E. Bailey-Wilson; Johanna Schleutker


Correction of renal tubular acidosis in carbonic anhydrase II-deficient mice with gene therapy.  

PubMed Central

Carbonic anhydrase II (CAII) deficiency in humans is associated with a syndrome of renal tubular acidosis, osteopetrosis, and cerebral calcification. A strain of mice of CAII deficiency due to a point mutation also manifests renal tubular acidosis. We report here that retrograde injection of cationic liposome complexed with a CAII chimeric gene, using a cytomegalovirus (CMV) promoter/enhancer as an expression cassette to drive human CAII cDNA, into the renal pelvis of CAII-deficient mice results in expression of CAII in the kidney. The levels of both the CAII gene and its corresponding mRNA were highest by day 3 after treatment, diminishing thereafter, but remaining detectable by 1 mo. After gene therapy, CAII-deficient mice restored the ability to acidify urine after oral administration of ammonium chloride. The ability to acidify urine was maintained at 3 wk after gene therapy, and was eventually lost by 6 wk. Immunohistochemistry studies using anti-CAII antibodies showed that CAII was expressed in tubular cells of the outer medulla and corticomedullary junction. The gene therapy was not associated with nephrotoxicity as assessed by blood urea nitrogen levels and renal histology. To our knowledge, this is the first successful gene therapy of a genetic renal disease. Our results demonstrate the potential of gene therapy as a novel treatment for hereditary renal tubular defects.

Lai, L W; Chan, D M; Erickson, R P; Hsu, S J; Lien, Y H



Diagnosis of subacute ruminal acidosis (SARA) by continuous reticular pH measurements in cows.  


The objective of this study was to determine whether subacute ruminal acidosis (SARA) could be diagnosed by continuous measurements of the reticular pH, as compared with the ruminal pH, using healthy cows fed a control diet and SARA cows fed a rumen acidosis-inducing diet. The reticular and ruminal pH were measured simultaneously by a radio transmission pH measurement system. The mean reticular pH at 1-h intervals decreased gradually from the morning feeding to the next feeding time in both healthy and SARA cows, though the decrease in the ruminal pH was observed to be more drastic as compared with that observed in the reticular pH. The threshold of the 1-h mean pH in the reticulum for a diagnosis of SARA was considered to be 6.3, and a significant positive correlation was observed between the reticular and ruminal pH. No differences in the concentrations of lactic acid, ammonia nitrogen, and volatile fatty acids were noted between the reticular and ruminal fluids in SARA cows. These results demonstrate that the reticular pH can be used to detect SARA in cows, as opposed to using the ruminal pH. PMID:22773224

Sato, Shigeru; Ikeda, Aya; Tsuchiya, Yoshiyuki; Ikuta, Kentaro; Murayama, Isao; Kanehira, Masahiro; Okada, Keiji; Mizuguchi, Hitoshi



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

PubMed Central

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

Sherwood, Thomas W.; Askwith, Candice C



Magnetic Resonance Imaging Detects Placental Hypoxia and Acidosis in Mouse Models of Perturbed Pregnancies  

PubMed Central

Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T2 (spin-spin or transverse) relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds.

Bobek, Gabriele; Stait-Gardner, Tim; Surmon, Laura; Makris, Angela; Lind, Joanne M.; Price, William S.; Hennessy, Annemarie



Hepatic 11 beta-hydroxysteroid dehydrogenase 1 involvement in alterations of glucose metabolism produced by acidotic stress in rat  

Microsoft Academic Search

11 beta-hydroxysteroid dehydrogenase (HSDs) enzymes regulate the activity of glucocorticoids in target organs. HSD1, one of\\u000a the two existing isoforms, locates mainly in CNS, liver and adipose tissue. HSD1 is involved in the pathogenesis of diseases\\u000a such as obesity, insulin resistance, arterial hypertension and the Metabolic Syndrome. The stress produced by HCl overload\\u000a triggers metabolic acidosis and increases liver HSD1

M. E. Altuna; M. B. Mazzetti; L. F. Rago; L. C. San Martín de Viale; M. C. Damasco



Intima-Media Thickness in Severe Obesity: Links with BMI and metabolic status but not with systemic or adipose tissue inflammation.  


OBJECTIVE Obesity is associated with cardiovascular risk and a low-grade inflammatory state in both blood and adipose tissue (AT). Whether inflammation contributes to vascular alteration remains an open question. To test this hypothesis, we measured arterial intima-media thickness (IMT), which reflects subclinical atherosclerosis, in severely obese subjects and explored associations with systemic inflammation and AT inflammation. RESEARCH DESIGN AND METHODS IMT of the carotid artery (C-IMT) and IMT of the femoral artery (F-IMT) were measured in 132 nonobese (control) subjects (BMI 22.3 kg/m(2); mean age 44.8 years) and 232 subjects who were severely obese without diabetes (OB/ND; n = 146; BMI 48.3 kg/m(2); age 38.2 years) or severely obese with type 2 diabetes (OB/D; n = 86; BMI 47.0; age 49.4 years). In 57 OB/ND subjects, circulating soluble E-selectin, matrix metalloproteinase 9, myeloperoxidase, soluble intracellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, tissue plasminogen activator inhibitor 1, cystatin C, cathepsin S, and soluble CD14 were measured in serum. AT macrophages were quantified by CD68 immunochemistry. RESULTS Both C-IMT and F-IMT increased in OB/ND and OB/D patients. In OB/ND patients, age was the sole independent determinant of IMT. No significant association was found with circulating inflammation-related molecules, number of CD68(+) cells, or the presence of crown-like structures in visceral or subcutaneous AT of OB/ND patients. CONCLUSIONS IMT increased with severe obesity but was not influenced by the degree of systemic inflammation or AT macrophage accumulation. PMID:24062328

Dalmas, Elise; Kahn, Jean-François; Giral, Philippe; Abdennour, Meriem; Bouillot, Jean-Luc; Fellahi, Soraya; Oppert, Jean-Michel; Clément, Karine; Guerre-Millo, Michèle; Poitou, Christine



Lactic Acidosis.  

National Technical Information Service (NTIS)

Many assumptions and compromises must be made in order to establish blood lactate as a reliable parameter of tissue oxygenation. One must think not only of reactions and cells as having oxidation-reduction potentials, but the concept of the Redox potentia...

A. H. Harken



Carbon dioxide pneumoperitoneum causes severe peritoneal acidosis, unaltered by heating, humidification, or bicarbonate in a porcine model  

Microsoft Academic Search

Background: Carbon dioxide (CO2) is the most common gas used for insufflation in laparoscopy, but its effects on peritoneal physiology are poorly understood. This study looks at the changes in peritoneal and bowel serosal pH during CO2 pneumoperitoneum, and whether heating and humidification with or without bicarbonate alters the outcomes. Methods: Twenty-one pigs divided into four groups as follows: (1)

Y. T. Wong; P. C. Shah; D. H. Birkett; D. M. Brams



Effect of moderate and high-dose simvastatin on asymmetric dimethylarginine-homocysteine metabolic pathways in patients with newly detected severe hypercholesterolemia.  


The assumption that statin therapy can decrease asymmetric dimethylarginine through lowering low-density lipoprotein cholesterol levels seems logical and yet arises some controversy. The aim of the present study is to compare the effects of moderate (40 mg) to high (80 mg) simvastatin doses on asymmetric dimethylarginine and total homocysteine levels in patients with newly detected severe hypercholesterolemia (after target LDL-C levels, ?2.6 mmol/L, are reached). The study included 120 adult patients with newly detected severe hypercholesterolemia (total cholesterol ?7.5 mmol/L and low-density lipoprotein cholesterol ?4.9 mmol/L). Asymmetric dimethylarginine levels were determined by enzyme-linked immunosorbent assay, total homocysteine-by a high-performance liquid chromatographic method. There was a statistically significant decrease in total cholesterol, triglycerides, low-density lipoprotein cholesterol, and apolipoprotein-B levels as well as in the apolipoprotein-B/apolipoprotein-A1 index after a 1-month therapy with 40 mg simvastatin (P <0.001). Asymmetric dimethylarginine and total homocysteine levels were also decreased but the difference did not reach statistical significance (P= 0.571; P= 0.569). A dose-dependent effect was established, comparing the influence of moderate (40 mg) to high (80 mg) simvastatin doses on the tested atherogenic biomarkers (lipid profile, apolipoprotein-A1, and apolipoprotein-B). Asymmetric dimethylarginine and total homocysteine levels were lowered significantly with 80 mg simvastatin (P <0.001; P= 0.038). In conclusion, optimizing the target values of low-density lipoprotein cholesterol, a moderate dose (40 mg) of simvastatin has no effect on asymmetric dimethylarginine and total homocysteine in contrast to a high dose (80 mg) after target LDL-C levels are reached (?2.6 mmol/L) in patients with newly detected severe hypercholesterolemia. PMID:20345493

Vladimirova-Kitova, Lyudmila G; Deneva, Tania I; Marinov, B



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

Microsoft Academic Search

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

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



Topological Location and Structural Importance of the NBCe1-A Residues Mutated in Proximal Renal Tubular Acidosis*  

PubMed Central

NBCe1-A electrogenically cotransports Na+ and HCO3? across the basolateral membrane of renal proximal tubule cells. Eight missense mutations and 3 nonsense mutations in NBCe1-A cause severe proximal renal tubular acidosis (pRTA). In this study, the topologic properties and structural importance of the 8 endogenous residues mutated in pRTA and the in situ topology of NBCe1-A were examined by the substituted cysteine accessibility method. Of the 55 analyzed individually introduced cysteines, 8 were labeled with both membrane permeant (biotin maleimide (BM)) and impermeant (2-((5(6)-tetramethylrhodamine)carboxylamino)ethyl methanethiosulfonate (MTS-TAMRA)) sulfhydryl reagents, 4 with only BM, and 3 with only MTS-TAMRA. The location of the labeled and unlabeled introduced cysteines clearly indicates that the transmembrane region of NBCe1-A contains 14 transmembrane segments (TMs). In this in situ based NBCe1-A topology, residues mutated in pRTA (pRTA residues) are assigned as: Ser427, TM1; Thr485 and Gly486, TM3; Arg510 and Leu522, TM4; Ala799, TM10; and Arg881, TM12. Substitution of pRTA residues with cysteines impaired the membrane trafficking of R510C and R881C, the remaining membrane-processed constructs had various impaired transport function. Surprisingly, none of the membrane-processed constructs was accessible to labeling with BM and MTS-TAMRA, nor were they functionally sensitive to the inhibition by (2-aminoethyl)methanethiosulfonate. Functional analysis of Thr485 with different amino acid substitutions indicated it resides in a unique region important for NBCe1-A function. Our findings demonstrate that the pRTA residues in NBCe1-A are buried in the protein complex/lipid bilayer where they perform important structural roles.

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



Human H+ATPase a4 subunit mutations causing renal tubular acidosis reveal a role for interaction with phosphofructokinase-1.  


The vacuolar-type ATPase (H+ATPase) is a ubiquitously expressed multisubunit pump whose regulation is poorly understood. Its membrane-integral a-subunit is involved in proton translocation and in humans has four forms, a1-a4. This study investigated two naturally occurring point mutations in a4's COOH terminus that cause recessive distal renal tubular acidosis (dRTA), R807Q and G820R. Both lie within a domain that binds the glycolytic enzyme phosphofructokinase-1 (PFK-1). We recreated these disease mutations in yeast to investigate effects on protein expression, H+ATPase assembly, targeting and activity, and performed in vitro PFK-1 binding and activity studies of mammalian proteins. Mammalian studies revealed complete loss of binding between the COOH terminus of a4 containing the G-to-R mutant and PFK-1, without affecting PFK-1's catalytic activity. In yeast expression studies, protein levels, H+ATPase assembly, and targeting of this mutant were all preserved. However, severe (78%) loss of proton transport but less decrease in ATPase activity (36%) were observed in mutant vacuoles, suggesting a requirement for the a-subunit/PFK-1 binding to couple these two functions. This role for PFK in H+ATPase function was supported by similar functional losses and uncoupling ratio between the two proton pump domains observed in vacuoles from a PFK-null strain, which was also unable to grow at alkaline pH. In contrast, the R-to-Q mutation dramatically reduced a-subunit production, abolishing H+ATPase function completely. Thus in the context of dRTA, stability and function of the metabolon composed of H+ATPase and glycolytic components can be compromised by either loss of required PFK-1 binding (G820R) or loss of pump protein (R807Q). PMID:18632794

Su, Ya; Blake-Palmer, Katherine G; Sorrell, Sara; Javid, Babak; Bowers, Katherine; Zhou, Aiwu; Chang, Simon H; Qamar, Seema; Karet, Fiona E