• Biomolecules & Therapeutics
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• 제25권6호
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• pp.593-598
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• 2017

The $Na^+/H^+$ exchanger-1 (NHE-1) is a ubiquitously expressed pH-regulatory membrane protein that functions in the brain, heart, and other organs. It is increased by intracellular acidosis through the interaction of intracellular $H^+$ with an allosteric modifier site in the transport domain. In the previous study, we reported that glutamate-induced NHE-1 phosphorylation mediated by activation of protein kinase C-${\beta}$ (PKC-${\beta}$) in cultured neuron cells via extracellular signal-regulated kinases (ERK)/p90 ribosomal s6 kinases (p90RSK) pathway results in NHE-1 activation. However, whether glutamate stimulates NHE-1 activity solely by the allosteric mechanism remains elusive. Cultured primary cortical neuronal cells were subjected to intracellular acidosis by exposure to $100{\mu}M$ glutamate or 20 mM $NH_4Cl$. After the desired duration of intracellular acidosis, the phosphorylation and activation of PKC-${\beta}$, ERK1/2 and p90RSK were determined by Western blotting. We investigated whether the duration of intracellular acidosis is controlled by glutamate exposure time. The NHE-1 activation increased while intracellular acidosis sustained for >3 min. To determine if sustained intracellular acidosis induced NHE-1 phosphorylation, we examined phosphorylation of NHE-1 induced by intracellular acidosis by transient exposure to $NH_4Cl$. Sustained intracellular acidosis led to activation and phosphorylation of NHE-1. In addition, sustained intracellular acidosis also activated the PKC-${\beta}$, ERK1/2, and p90RSK in neuronal cells. We conclude that glutamate stimulates NHE-1 activity through sustained intracellular acidosis, which mediates NHE-1 phosphorylation regulated by PKC-${\beta}$/ERK1/2/p90RSK pathway in neuronal cells.

• Journal of Trauma and Injury
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• 제32권4호
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• pp.238-242
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• 2019

Extreme acidosis is a life-threatening physiological state that causes disturbances in the cardiovascular, pulmonary, immune, and hematological systems. Trauma patients commonly present to the operating room (OR) in hypovolemic shock, leading to tissue hypoperfusion and the development of acute metabolic acidosis with or without a respiratory component. It is often believed that trauma patients presenting to the OR in severe metabolic acidosis (pH <7.0) will have a nearly universal mortality rate despite aggressive resuscitation and damage control. The current literature does not include reports of successful resuscitations from a lower pH, which may lead providers to assume that a good outcome is not possible. However, here we describe a case of successful resuscitation from an initial pH of 6.5 with survival to discharge home 95 days after admission with almost full recovery. We describe the effects of acute acidosis on the respiratory and cardiovascular systems and hemostasis. Finally, we discuss the pillars of management in patients with extreme acute acidosis due to hemorrhage: transfusion, treatment of hyperkalemia, and consideration of buffering acidosis with bicarbonate and hyperventilation.

• The Korean Journal of Physiology
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• 제26권1호
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• pp.89-97
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• 1992

In hypoxic tissue conditions, pyruvate can not enter the Krebs cycle and lactic acid, produced from pyruvate, accumulates to induce lactic acidosis. Pyruvate, However, can also be converted to alanine by glutamate pyruvate transaminase, that could be enhanced by glutamate. Therefore, it would be a fundamental measure to treat the lactic acidosis in tissue hypoxic conditions when one can convert the accumulated lactic acid, through pyruvate, to alanine. To test the above hypothesis, we induced a lactic acidosis in cats and the effect of glutamate on recovery of acid base state and removal of the lactic acid from blood were assessed and the results were compared with those of bicarbonate administration, which is one of the most frequently used conventional measure for correction of the acid base state during lactic acidosis. The results were that glutamate and combined glutamate bicarbonate solutions not only restored the acid base status completely from the lactic acidosis in an hour or two, but also restored the blood level of lactate partially. We concluded that administration of glutamate solution to convert pyruvate into alanine is effective in preventing lactic acid accumulation and treating lactic acidosis.

• Neonatal Medicine
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• 제17권2호
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• pp.155-160
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• 2010

Metabolic acidosis is commonly encountered issues in the management of critically ill neonates and especially of preterm infants during early neonatal days. In extremely premature infants, low glomerular filtration rate and immaturity of renal tubules to produce new bicarbonate causes renal bicarbonate loss. Higher intake of amino acids, relatively greater contribution of protein to the energy metabolism and mineralization process in growing bones are also responsible for higher acid load in premature infant than in adult. Despite widespread use of sodium bicarbonate in the management of severe metabolic acidosis, use of sodium bicarbonate in premature infants should be restricted to a reasonable but unproven exception such as ongoing renal loss. Despite concern about the low pH value (<7.2) which can compromise cellular metabolic function, no treatment guideline has been established regarding the management of metabolic acidosis in premature infants. Appropriately powered randomized controlled trials of base therapy to treat metabolic acidosis in critically ill newborn infants are demanding.

• Childhood Kidney Diseases
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• 제14권2호
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• pp.120-131
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• 2010

Renal tubular acidosis (RTA) is a metabolic acidosis due to impaired excretion of hydrogen ion, or reabsorption of bicarbonate, or both by the kidney. These renal tubular abnormalities can occur as an inherited disease or can result from other disorders or toxins that affect the renal tubules. Disorders of bicarbonate reclamation by the proximal tubule are classified as proximal RTA, whereas disorders resulting from a primary defect in distal tubular net hydrogen secretion or from a reduced buffer trapping in the tubular lumen are called distal RTA. Hyperkalemic RTA may occur as a result of aldosterone deficiency or tubular insensitivity to its effects. The clinical classification of renal tubular acidosis has been correlated with our current physiological model of how the nephron excretes acid, and this has facilitated genetic studies that have identified mutations in several genes encoding acid and base ion transporters. Growth retardation is a consistent feature of RTA in infants. Identification and correction of acidosis are important in preventing symptoms and guide approved genetic counseling and testing.

• Journal of Korean Neurosurgical Society
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• 제56권2호
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• pp.135-140
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• 2014

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

• Journal of Chest Surgery
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• 제12권4호
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• pp.395-402
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• 1979

Intracellular pH was determined by distribution of 5.5-dimethyl-2,4-oxazolidlnedione [DMO]in the skeletal muscle of dogs before and after lactic acidosis induced by intravenous infusion of lactic acid solution. After infusion of lactic acid solution arterial pH decreased from 7.40 to around 7.12 [P<0.001]and metabolic acidosis was induced. However, dose-pH change response was not proportional as in the case of hydrochloric acid infusion. During lactic acidosis, intracellular pH changed very little except when venous blood $pCO_2$ increased significantly. The decrease of intracellular pH in lactic acidosis might be due primarily to the increase of intracellular $pCO_2$. And during lactic acidosis, change of extracellular pH was larger than that of intracellular pH, and this was also the case of change In hydrogen Ion concentration in extracellular and intracellular fluid. The fact was estimated that exogenous lactic acid transported into the cell does not contribute to pH change by the participation in the metabolism. Change in plasma potassium Ion concentration was not eminent as metabolic acid-base disturbances by other origin, and changing pattern of Hi/He ratio was not same as Ki/Ke ratio. In spite of no changes in extracellular potassium ion concentration after exogenous lactic acidosis total amount of potassium ion in extracellular fluid increased from 12.62mEg to 18.26mEg [P< 0.05].

• 대한약리학회지
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• 제31권1호
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• pp.75-84
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• 1995

NO의 위산분비에 대한 작용을 규명하기 위하여 분리한 토끼위선세포에서 hypoxia/reoxygenation과 acidosis후 위산분비와 NO synthase 활성을 측정하였다. 분리한 위선세포에 30분의 hypoxia와 1시간의 reoxygenation을 주었으며, acidosis를 위하여 배지의 pH를 6.0과 4.0으로 변화시켜 실험하였다. 위산분비는 위선세포 내와 외의 $[^{14}C]-aminopyrine$ 축적비율로 측정하였으며, NO synthase 활성은 NO의 전구물질인 $[^{14}C]L-arginine$으로부터 $[^{14}C]-citrulline$으로의 전환율로 결정하였다. 결과로서 dibutyryl cAMP는 농도 의존적으로 위산분비를 촉진시켰으나 NO synthase 활성엔 영향을 주지 않았다. Hypoxia/reoxygenation은 기초 및 자극 위산분비를 억제하였으며 acidosis에 의해 위산분비억제는 더욱 심화되었다. Constitutive NO synthase 활성 역시 hypoxia/reoxygenation과 acidosis에 의해 억제되었다. 결론적으로 hypoxia/reoxygenation과 acidosis 같은 위점막의 병적상태는 위산분비와 NO 유리를 모두 억제하나, 기초상태의 위선에서 dibutyryl cAMP에 의한 위산분비 촉진에 대한 NO의 직접적인 작용은 확인되지 않았다.

• 한국응용과학기술학회지
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• 제35권4호
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• pp.1433-1441
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• 2018

고강도 운동 시 산성화의 과정은 수소이온의 방출과 젖산 나트륨염을 형성하는 젖산의 생산 증가에 따른 것이라 설명되어져 왔다. 이 설명에 의하면, 젖산의 생산 비율이 세포내의 수소이온 완충능력을 초과하였을 때 세포의 수소이온 농도는 증가한다고 한다. 이러한 생화학적 과정을 젖산의 산성화라 한다. 이 이론에 따라 고강도 운동 시 젖산의 생산이 대사적 산성화와 피로의 원인이 되는 것으로 해석되어져 왔다. 그러나, 본 고찰에서는 젖산의 생산이 산성화와 피로의 원인이라는 어떠한 생화학적 근거가 없음을 명확히 제시하고 있다. 오히려 젖산의 생산은 해당과정에서 필요한 $NAD^+$의 지속적인 공급을 위해 필수적이며 수소이온을 소비하는 대사과정이다. 젖산의 축적은 세포와 혈중의 수소이온 농도의 증가를 알려주는 좋은 지표가 될 수는 있지만 그것이 산성화의 직접적인 원인은 아니다.

• 대한임상독성학회지
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• 제6권1호
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• pp.42-44
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• 2008

Metformin which is an oral hypoglycemic agents, acts by enhancing insulin sensitivity, decreasing hepatic glucose production and increasing peripheral utilization of glucose. Deliberate self poisoning with oral hypoglycemic agents is rare. The lactic acidosis associated with metformin toxicity is well described in the medical literature. Metformin overdose even in otherwise healthy patients may produce a profound and life threatening lactic acidosis. We report a case of massive metformin ingestion(75g) in a patient presenting with lactic acidosis and hypotension. She died 24h after presenting to our emergency department despite bicarbonate treatment and hemofiltration therapy.