• 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.

• Clinical and Experimental Pediatrics
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• 제50권10호
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• pp.948-953
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• 2007

Acute renal failure is the generic term for an abrupt and sustained decrease in renal function resulting in retention of nitrogenous and non nitrogenous waste product. This may results in life threatening consequences including volume overload, hyperkalemia, and metabolic acidosis. Acute renal failure is both common and carries high mortality rate, but as it is often preventable, identification of patients at risk and and appropriate management are crucial. This review summarized the most recent information on definition, epidemiology, clinical causes and management of acute renal failure in pediatric patients.

• 대한임상독성학회지
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• 제20권2호
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• pp.39-44
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• 2022

N-Acetylcysteine (NAC) is the standard antidote treatment for preventing hepatotoxicity caused by acetaminophen (AAP) poisoning. This review summarizes the recent evidence for the treatment of AAP poisoning. Several alternative intravenous regimens of NAC have been suggested to improve patient safety by reducing adverse drug reactions and medication errors. A two-bag NAC infusion regimen (200 mg/kg over 4 h, followed by 100 mg/kg over 16 h) is reported to have similar efficacy with significantly reduced adverse reactions compared to the traditional 3-bag regimen. Massive AAP poisoning due to high concentrations (more than 300-lines in the nomogram) needs to be managed with an increased maintenance dose of NAC. In addition to NAC, the combination therapy of hemodialysis and fomepizole is advocated for severe AAP poisoning cases. In the case of a patient presenting with an altered mental status, metabolic acidosis, elevated lactate, and an AAP concentration greater than 900 mg/L, hemodialysis is recommended even if NAC is used. Fomepizole decreases the generation of toxic metabolites by inhibiting CYP2E1 and may be considered an off-label use by experienced clinicians. Since the nomogram cannot be applied to sustained-release AAP formulations, all potentially toxic sustained-release AAP overdoses should receive a full course of NAC regimen. In case of ingesting less than the toxic dose, the AAP concentration is tested twice at an interval of 4 h or more; NAC should be administered if either value is above the 150-line of the nomogram.

• Tuberculosis and Respiratory Diseases
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• 제44권5호
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• pp.1040-1050
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• 1997

연구배경 : 만성폐쇄성폐질환 환자의 치료에 널리 적용되고 호흡재활치료는 폐기능을 호전시키지는 못하지만 호흡곤란 등의 증상과 운동능력을 호전시키는 것으로 알려져 있다. 그러나 이런 운동능력 개선의 기전은 여러 각도에서 해석되고 있다. 저자들은 $^{31}P$ MRS를 이용하여 만성 폐질환 환자들을 호흡재활치료 전후 전박근의 대사 변화를 관찰함으로써, 호흡재활치료 후 운동능력호전에 골격근 대사개선을 기여할 가능성을 조사하였다. 방 법 : 총 9명의 만성 폐질환을 갖고 있는 남자 환지들을 대상으로 하였고 이들의 평균 연령은 $58{\pm}11$세였으며, 이들의 기저 질환은 만성폐쇄성폐질환 8예 및 폐유육종증 1예였다. 호흡재활치료는 근육강화운동, 답차운동(treadmill walking), 자전거 운동(stationary bicycle riding) 및 상지 운동력측정계(arm ergometer)를 이용한 상지운동으로 구성했으며, 호흡재활치료 전후로 폐기능 검사, 운동부하 검사, 상하지의 지구력 측정 및 6분 보행거리 검사를 실시하였다. $^{31}P$ MRS검사를 치료 전후 전박근을 대상으로 안정시, 운동시 및 20분간의 회복시에 시행하여 세포내 산소성 인산화 능력을 반영하는 Pi/PCr의 비와 pHi(intracellular pH)를 구하여 비교하였다. 결 과 : 호흡재활치료 후 환자의 폐기능과 가스 교환의 호전은 없었으나, 운동지구력 및 보행능력은 현저한 호전을 보였으며 최대산소섭취량은 증가하는 경향을 보였고, 동 운동량에서의 분당환기량은 감소하는 경향을 나타내었다. $^{31}P$ MRS를 이용하여 재활치료 전후의 골격근 대사를 비교해 본 결과, 치료 후 운동시 및 극심한 피로상태에서의 pHi는 유의하게 높았고 산소성 인산화 과정을 반영하는 지표인 Pi/PCr는 감소하는 경향을 보였으나 안정시 및 회복기의 골격근 대사과정은 변화가 없었다. 결 론 : 이상으로 만성 폐질환 환자에서 6주간의 호흡재활치료는 운동지구력 및 보행 호전시켰으며 이러한 운동능력 호전에는 골격근 대사의 개선으로 초래된 골격근 세포내의 산성화 지연으로 인한 환기량의 감소가 기여할 사료되었다.